A BEST classification system of large to giant congenital melanocytic nevi based on expert consensus and distribution characteristics.

BACKGROUND: Large to giant congenital melanocytic nevi (LGCMN) significantly decrease patients' quality of life, but the inaccuracy of current classification system makes their clinical management challenging. OBJECTIVES: To improve and extend the existing LGCMN 6B/7B classification systems by developing a novel LGCMN classification system based on a new phenotypic approach to clinical tool development. METHODS: Three hundred and sixty-one LGCMN cases were categorized into four subtypes based on anatomic site: bonce (25.48%), extremity (17.73%), shawl (19.67%) and trunks (37.12%) LGCMN. A 'BEST' classification system of LGCMN was established and validated by a support vector machine classifier combined with the 7B system. RESULTS: The most common LGCMN distributions were on bonce and trunks (bathing trunk), whereas breast/belly and body LGCMN were exceptionally rare. Sexual dimorphism characterized distribution, with females showing a wider range of lesions in the genital area. Nearly half of the patients with bathing trunk LGCMN exhibited a butterfly-like distribution. Approximately half of the LGCMN with chest involvement did not have nipple-areola complex involvement. Abdomen, back and buttock involvement was associated with the presence of satellite nevi (r = 0.558), and back and buttock involvement was associated with the presence of nodules (r = 0.364). CONCLUSIONS: The effective quantification of a standardized anatomical site provides data support for the accuracy of the 6B/7B classification systems. The simplified BEST classification system can help establish a LGCMN clinical database for exploration of LGCMN aetiology, disease management and prognosis prediction.

Rare Earth Single-Atom Catalysis for High-Performance Li-S Full Battery with Ultrahigh Capacity.

Lithium-sulfur (Li-S) batteries have many advantages but still face problems such as retarded polysulfides redox kinetics and Li dendrite growth. Most reported single atom catalysts (SACs) for Li-S batteries are based on d-band transition metals whose d orbital constitutes active valence band, which is inclined to occur catalyst passivation. SACs based on 4f inner valence orbital of rare earth metals are challenging for their great difficulty to be activated. In this work, we design and synthesize the first rare earth metal Sm SACs which has electron-rich 4f inner orbital to promote catalytic conversion of polysulfides and uniform deposition of Li. Sm SACs enhance the catalysis by the activated 4f orbital through an f-d-p orbital hybridization. Using Sm-N3C3 modified separators, the half cells deliver a high capacity over 600 mAh g-1 and a retention rate of 84.3 % after 2000 cycles. The fabricated Sm-N3C3-Li|Sm-N3C3@PP|S/CNTs full batteries can provide an ultra-stable cycling performance of a retention rate of 80.6 % at 0.2 C after 100 cycles, one of the best full Li-S batteries. This work provides a new perspective for the development of rare earth metal single atom catalysis in electrochemical reactions of Li-S batteries and other electrochemical systems for next-generation energy storage.

Protective effect of cinnamaldehyde on channel catfish infected by drug-resistant Aeromonas hydrophila.

The protective effect of cinnamaldehyde on channel catfish infected by drug-resistant Aeromonas hydrophila CW strain was explored by observing the clinical signs and histopathology, measuring the cumulative mortality, serum biochemical and non-specific immune indicators, and intestinal microbiota in this study. The cumulative survival rate of the cinnamaldehyde within 14 days was significantly higher than that of the challenge group, which was 70% and 20%, respectively. Compared with the challenge group, the activities of lysozyme, superoxide dismutase, and glutathione peroxidase in the treatment group were increased, while there was no significant difference in catalase activity. Compared with the challenge group, the histopathology results showed that the injury of liver, spleen, and kidney was significantly alleviated after cinnamaldehyde treatment. The results of intestinal microbiota showed that the proportion of Proteobacteria in the challenge group was significantly increased, and the proportion of Aeromonas sp. reached 30% based on the analysis of species classification level. The composition of dominant species in the treatment group was similar to the control group. In conclusion, cinnamaldehyde increased the cumulative survival rate of channel catfish infected by A. hydrophila. It could protect channel catfish through improving the non-specific immune function of channel catfish, alleviating the pathological lesions of liver, spleen, kidney, and intestine, and maintaining the relative balance of the intestinal microbiota. Therefore, cinnamaldehyde could be a candidate drug for the treatment of A. hydrophila infection.

Culprit Lesion Characteristics in Young Patients with Hyperhomocysteinemia.

BACKGROUND The relationships between culprit coronary plaque characteristics and hyperhomocysteinemia (HHcy) are not fully understood in young patients. In this study we investigated the relationship between culprit atherosclerotic plaque phenotype assessed by optical coherence tomography (OCT) and hyperhomocysteinemia (HHcy) in young patients. MATERIAL AND METHODS We investigated the OCT imaging and HHcy of 123 lesions in 123 young patients (≤45 years of age). According to OCT images, culprit lesions were classified as thin-cap fiber atheroma (TCFA), thrombus, and other. The 123 patients were grouped as: HHcy group (53 cases, HHcy ≥15.5 µmol/l) and control group (70 cases, HHcy <15.5 µmol/l). RESULTS Compared with the control group, the HHcy group had a higher proportion of OCT-TCFA (p=0.03), OCT-vasa vasorum (p=0.013), and OCT-thrombus (p=0.012), and a larger lipid arc (p=0.002). HHcy (P=0.037) and metabolic syndrome (MetS) (P=0.016) remained independent predictors of TCFAs. HHcy (P=0.026) and smoking (P=0.005) remained independent determinants of thrombus. CONCLUSIONS HHcy and MetS are associated with TCFAs, and HHcy and smoking are associated with thrombus in young patients with coronary artery disease.

Systems Biology Approaches-based Biomarkers Discovery for Acute Aortic Dissection.

Acute aortic dissection (AAD) faces great challenges in early diagnosis and effective drug treatment. Recent developments in systems biology approaches allow high-throughput screening of novel diagnostic biomarkers and potential therapeutic targets. In this review, we summarize the currently available AAD biomarkers identified in the context of genomic, transcriptomic, proteomic, and metabolic profiles, and highlight the benefits of using a combination of these findings for a better understanding of the molecular nature of this life-threatening disease. This review also provides a reference for future studies that employ a comprehensive, multiple-level approach at the single-cell level to decipher the underlying molecular pathophysiology of AAD.

MiR-27a modulates radiosensitivity of triple-negative breast cancer (TNBC) cells by targeting CDC27.

BACKGROUND: MiR-27a is significantly overexpressed in triple-negative breast cancer (TNBC). However, the exact biological function of MiR-27a in TNBC is not fully understood. In this study, we verified miR-27a expression in TNBC cells and explored how its overexpression modulates radiosensitivity of the cells. MATERIAL/METHODS: qRT-PCR analysis was performed to study miR-27a expression in TNBC lines MDA-MB-435 and MDA-MB-231 and in normal human breast epithelial cell line MCF10A. Dual luciferase assay was performed to verify a putative downstream target of miR-27a, CDC27. CCK-8 assay was used to assess the influence of miR-27a-CDC27 axis on cell proliferation under irradiation (IR) treatment. RESULTS: We confirmed significantly higher miR-27a expression in 2 TNBC cell lines--MDA-MB-435 and MDA-MB-231--than in human breast epithelial cell line MCF10A. miR-27a could modulate proliferation and radiosensitivity of TNBC cells. CDC-27 is a direct target of miR-27a and its downregulation conferred increased radioresistance of the cells. CONCLUSIONS: The miR-27a-CDC27 axis might play an important role in modulating response to radiotherapy in TNBC cells. Testing miR-27a expression might be a useful way to identify a subgroup of patients who will benefit from an IR-based therapeutic approach.

Correlations between serum trypsinogen-2 and pancreatic cancer.

BACKGROUND/AIMS: To investigate associations be- tween serum trypsinogen-2, pancreatitis and pancreatic cancer (PC) and determine cutoff values for PC diagnosis. METHODOLOGY: We recruited 88 patients from Internal Medicine/Surgical Departments of General Military Hospital of Beijing PLA between 12/2009 and 6/2010. Serum samples were collected preoperatively from 23 PC patients, 30 pancreatitis patients and 35 healthy controls. Enzyme-linked immunosorbent assay was used to detect trypsinogen-2 semiquantitatively. RESULTS: Serum trypsinogen-2 levels of PC and pancreatitis patients were significantly higher than those of controls (51.2 ± 80.3, 107.7 ± 98.1 vs. 1.0 ± 0.5, p = 0.03, p < 0.001) and significantly higher in pancreatitis vs. PC patients (107.7 ± 98.1 vs. 51.2 ± 80.3, p = 0.01). Higher Balthazar CT grades correlated with higher trypsinogen-2 in pancreatitis group. ROC curves for trypsinogen-2 revealed optimal cutoff value 1.8 as lower PC detection limit with 95.7% sensitivity and 91.4% specificity, and optimal cutoff value 19.9 for upper PC detection limit with 87.0% sensitivity and 97.1% specificity. Trypsinogen-2 levels correlated with pancreatic injury level. An AUC of 0.73 (95% Cl: 0.59-0.84, p = 0.002) distinguished PC from pancreatitis. CONCLUSION: Serum trypsinogen-2 is associated with PC and pancreatitis. Levels between 1.8 µg/L and 19.9 µg/L strongly suggest PC. Detection of serum trypsinogen-2 may provide simple, sensitive, specific non-invasive initial screening for early PC diagnosis.

Liposculpture and fat grafting for aesthetic correction of the gluteal concave deformity associated with multiple intragluteal injection of penicillin in childhood.

BACKGROUND: The gluteal concave deformity, a complication of repeated intragluteal injections in childhood, is a relatively common complaint of many young women in China. This issue could be addressed by lipofilling, as the method could produce aesthetically acceptable results in correcting soft tissue contour defects. METHODS: Twelve patients with bilateral gluteal concave deformities associated with repeated intragluteal injections were operated on from June 2006 to June 2010. The deformities were classified as major or minor. Overall satisfaction with body appearance after gluteal fat grafting and liposculpture was rated on a scale of 1 (poor), 2 (fair), 3 (good), 4 (very good), and 5 (excellent). The evaluation was performed at 3-44 months after surgery. RESULTS: The average volume of fat injected was 196.9 ± 41.4 ml. No serious adverse events occurred. One patient with major deformity had one additional fat grafting procedure. One patient developed cellulitis in the feet and lower legs, upon which the grafted areas were incised and drained on suspicion of infection but with negative cultures. The patient recovered uneventfully with intravenous antibiotic application for 7 days. At the office visit nine cases judged that their appearance after the operation as "very good" (4) to "excellent" (5) and three cases responded that their contour was "good." Improvement in skin texture and alleviation of the pigmentation in the concave area were observed in all cases during the 3-44-month follow-up intervals after the fat grafting, and softening of the hypertrophic scar was also observed as early as 1 month after the fat grafting and continuously improved during the 12-month follow-up. CONCLUSION: Autologous lipografting for gluteal concave deformity, combining a liposculpture procedure adjacent to the defects, accomplishes good aesthetic results with high patient satisfaction. The key to success is complete release of fibrosis adhesion, meticulous manipulation of fat grafts, and multitunnel and multiplane injections to ensure maximum take of the grafts. LEVEL OF EVIDENCE IV: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Spring Viremia of Carp Virus Infection Induces Carp IL-10 Expression, Both In Vitro and In Vivo.

Interleukin-10 (IL-10) is a pleiotropic cytokine with both immune enhancement and immunosuppression activities, but the main role is immunosuppression and anti-inflammatory ability. In order to use the immunosuppressive function of IL-10, many viruses, such as SARS-CoV-2, hepatitis B virus and EB virus, can evade the host's immune surveillance and clearance by increasing the expression of host IL-10. However, it has not been reported whether the aquatic animal infection virus can upregulate the expression of host IL-10 and the mechanisms are still unknown. Spring viremia of carp (SVC) is a fatal viral disease for many fish species and is caused by spring viremia of carp virus (SVCV). This disease has caused significant economic losses in the aquaculture industry worldwide. In this study, the expression of carp IL-10 with or without infection of SVCV in epithelioma papulosum cyprinid (EPC) cells, carp head kidney (cHK) primary cells and common carp tissues were analyzed using RT-PCR and ELISA. The results show that SVCV infection induced carp IL-10 mRNA and protein expression, both in vitro and in vivo. However, the upregulation of carp IL-10 by SVCV was hindered by specific inhibitors of the JAK inhibitor (CP-690550), STAT3 inhibitor (STA-21), NF-κB inhibitor (BAY11-7082) and p38 MAPK (mitogen-activated protein kinase) inhibitor (SB202190), but not JNK inhibitor (SP600125). Furthermore, the results demonstrated that JAK1, JAK2, JAK3, TYK2 and STAT5 played important roles in carp IL-10 production induced by SVCV infection. Taken together, SVCV infection significantly induced carp IL-10 expression and the upregulation trigged in JAK-STAT, NF-κB and p38MAPK pathways. To our knowledge, this is the first time that a fish infection virus upregulated the host IL-10 expression through the JAK-STAT, NF-κB and p38MAPK pathways. Altogether, fish viruses may have a similar mechanism as human or other mammalian viruses to escape host immune surveillance and clearance.

Characteristics of pathology and transcriptome profiling reveal features of immune response of acutely infected and asymptomatic infected of carp edema virus in Koi.

Koi sleepy disease (KSD) is a high mortality and infection viral disease caused by carp edema virus (CEV), which was a serious threat to aquaculture of common carp and export trade of Koi worldwide. Asymptomatic infection is an important cause of the difficulty in preventing KSD and its worldwide spread, because asymptomatic infection can be activated under appropriate condition. However, the understanding of the molecular correlates of these infections is still unknown. The purpose of this study was to compare the pathology change, enzyme activity, immunoglobulin activity, host and viral gene expression differences in acutely infected and cohabiting asymptomatic Koi infected with CEV. Healthy Koi were used as a control. The gross pathology, histopathology and ultrastructural pathology showed the difference and characteristics damage to the tissues of Koi under different infection conditions. Periodic Acid-Schiff stain (PAS), enzyme activity and immunoglobulin activity revealed changes in the immune response of gill tissue between acutely infected, asymptomatic infected and healthy Koi. A total of 111 and 2484 upregulated genes and 257 and 4940 downregulated genes were founded in healthy Koi vs asymptomatic infected Koi and healthy Koi vs acutely infected Koi, respectively. Additionally, 878 upregulated genes and 1089 downregulated genes were identified in asymptomatic vs. acutely infected Koi. Immune gene categories and their corresponding genes in different comparison groups were revealed. A total of 3, 59 and 28 immune-related genes were identified in the group of healthy Koi vs asymptomatic infected Koi, healthy Koi vs acutely infected Koi and asymptomatic infected Koi vs acutely infected Koi, respectively. Nineteen immune-related genes have the same expression manner both in healthy Koi vs acutely infected Koi and asymptomatic Koi vs acutely infected Koi, while 9 immune-related genes were differentially expressed only in asymptomatic Koi vs acutely infected Koi, which may play a role in viral reactivation. In addition, 8 differentially expressed genes (DEGs) were validated by quantitative reverse transcription PCR (RT-qPCR), and the results were consistent with the RNA-Seq results. In conclusion, the data obtained in this study provide new evidence for further elucidating CEV-host interactions and the CEV infection mechanism and will facilitate the implementation of integrated strategies for controlling CEV infection and spread.

Numerical Simulation on the Effect of Burner Bias Angles on the Performance of a Two-Stage Entrained-Flow Gasifier.

A 2000 t/day HNCERI (Huaneng Clean Energy Research Institute) entrained-flow pulverized coal gasifier suffers from the problem of a high ash-slag ratio. An appropriate bias angle of the burners is the key to solve this issue for the gasifier with a specific structure. A random pore model considering bulk and pore diffusion effects was extended by user-defined function to describe the gasification reactions. The simulation of the gas flow and char gasification characteristics under different bias angles (0, 1.5, 2.5, 3.5, and 4.5°) of the four burners in the first stage was conducted. The simulation results showed favorable agreement with the industrial data. The evaporation, devolatilization, and char oxidation mainly occurred in the first-stage jet zone, and the upflow and downflow zones are dominated by the gasification reactions. The bias angles of the burners mainly affect the scale of gasification reaction zones. As the bias angles increased from 0 to 4.5°, the gas temperature at the slag tap hole decreased from 1880 to 1500 K. The carbon conversion efficiency of the first stage decreases and that of the second stage increases with the bias angle increasing. An optimal bias angle of 2.5° is recommended for the HNCERI gasifier with a total carbon conversion efficiency of 98.16%.

The Antibacterial Activity of Thymol Against Drug-Resistant Streptococcus iniae and Its Protective Effect on Channel Catfish (Ictalurus punctatus).

Streptococcus iniae is a zoonotic pathogen, which seriously threatens aquaculture and human health worldwide. Antibiotics are the preferred way to treat S. iniae infection. However, the unreasonable use of antibiotics leads to the enhancement of bacterial resistance, which is not conducive to the prevention and treatment of this disease. Therefore, it is urgent to find new efficient and environmentally friendly antibacterial agents to replace traditional antibiotics. In this study, the antibacterial activity and potential mechanism of thymol against S. iniae were evaluated by electron microscopy, lactate dehydrogenase, DNA and protein leakage and transcriptomic analysis. Thymol exhibited potent antibacterial activity against S. iniae in vitro, and the MIC and MBC were 128 and 256µg/mL, respectively. SEM and TEM images showed that the cell membrane and cell wall were damaged, and the cells were abnormally enlarged and divided. 2MIC thymol disrupted the integrity of cell walls and membranes, resulting in the release of intracellular macromolecules including nucleotides, proteins and inorganic ions. The results of transcriptomic analysis indicated that thymol interfered with energy metabolism and membrane transport, affected DNA replication, repair and transcription in S. iniae. In vivo studies showed that thymol had a protective effect on experimental S. iniae infection in channel catfish. It could reduce the cumulative mortality of channel catfish and the number of S. iniae colonization in tissues, and increase the activities of non-specific immune enzymes in serum, including catalase, superoxide dismutase, lysozyme and acid phosphatase. Taken together, these findings suggested that thymol may be a candidate plant agent to replace traditional antibiotics for the prevention and treatment of S. iniae infection.

Coulomb forces on DNA polymers in charged fluidic nanoslits.

We investigate the repulsive electrostatic interactions between a DNA polyelectrolyte and the charged walls of a fluidic nanoslit. The scaling of the DNA coil size with the physical slit height revealed electrostatic depletion regions that reduced the effective slit height. These regions exceeded the Debye screening length of the buffer, λ(D)(buffer), and saturated at ≈ 50 nm when λ(D)(buffer) reached 10 nm. We explain these results by modeling a semiflexible charged rod near a charged wall and the electrostatic screening by the polyelectrolyte. These results demonstrate the surprisingly long range over which a nanofluidic device can exert field-effect control over confined molecules.

[Reduced left ventricular systolic atrioventricular plane displacement in heart failure patients with preserved ejection fraction].

OBJECTIVE: To determine whether patients with suspected heart failure but preserved left ventricular ejection fraction (LVEF) have systolic dysfunction in left ventricular long axis detected by left ventricular systolic atrioventricular plane displacement (AVPD). METHODS: The data of 96 patients with heart failure who admitted to our hospital between August 2007 and October 2008 were collected. Heart failure with preserved LVEF was diagnosed in 48 patients and heart failure with reduced LVEF was diagnosed in another 48 patients. Fifty age-matched healthy subjects served as the control group. The NYHA classification, etiology of heart failure, AVPD and plasma NT-proBNP concentration were compared among the 3 groups. RESULTS: There was no difference in terms of NYHA classification between patients with preserved LVEF and reduced LVEF. Hypertension and coronary heart disease were often diagnosed in heart failure patients with preserved LVEF. The degree of AVPD decrease was more significant in heart failure patients with reduced LVEF than those with preserved LVEF. In all subjects, the AVPD was negatively correlated with the NT-proBNP concentration (r = -0.35, P < 0.05). CONCLUSION: Left ventricular systolic atrioventricular plane displacement was decreased in heart failure patients with preserved LVEF, therefore, besides "diastolic heart failure", systolic dysfunction was also impaired in these patients.

Knockdown of GC binding factor 2 by RNA interference inhibits invasion and migration of vascular smooth muscle cells.

GC binding factor 2 (GCF2) is a transcriptional repressor that inhibits the transcription of GC­rich promoters, thereby regulating biological processes, including proliferation. However, the role of GCF2 in vascular smooth muscle cells (VSMCs) remains unclear. The level of α­smooth muscle (α­SM) actin was determined by immunofluorescence. Cell viability, migration and invasion were analyzed using Cell Counting Kit­8, wound healing and Transwell assays, respectively. Apoptosis and cell cycle progression were determined using flow cytometry. The expressions of Bcl­2, Bax, cleaved caspase­3, cyclin E, CDK2 and the CDK inhibitor p21 were determined by reverse transcription­quantitative (RT­q)PCR and western blot analysis. RT­qPCR was performed to analyze the levels of GCF2 and western blot analysis was conducted to determine the phosphorylation levels of PI3K and AKT. α­SM actin was found to be expressed in VSMCs. Cell viability, migration and invasion were inhibited by small interfering (si)RNA targeting GCF2. Changes in the expression levels of Bcl­2, Bax and cleaved caspase­3 showed that the pro­apoptotic capacity of the cells was increased by siGCF2. Cell cycle arrest in the G0/G1 phase was induced by siGCF2, which was accompanied by changes in the levels of cyclin E, CDK2 and p21. Furthermore, phosphorylation of PI3K and AKT was suppressed by siGCF2. However, the inhibitory effects of siGCF2 on cell viability, migration and invasion were increased by insulin­like growth factor 1, which is a specific agonist of AKT. The anti­proliferative activity of siGCF2 may be associated with the PI3K/AKT pathway in VSMCs.

Efficacy and safety of combined neprilysin and RAS inhibition in heart failure: A meta-analysis of randomized controlled trials.

OBJECTIVES: Concerns about safety make physicians reluctant to prescribe neprilysin-renin-angiotensin system (RAS) inhibitors. This meta-analysis was performed to assess the efficacy and safety of combined neprilysin and RAS inhibition in heart failure. BACKGROUND: Combined inhibitors of neprilysin and RAS reduced heart failure hospitalization and cardiovascular death. While adverse events of neprilysin-RAS inhibitors in clinical trials are still controversial. METHODS: Medline, the Cochrane Library and Clinicaltrials.gov were searched for randomized controlled trials (RCTs). Twelve studies covering 21,212 patients were eligible for inclusion. RESULTS: Compared with RAS inhibition, neprilysin-RAS inhibition had a significant decrease in the mortality of heart failure [Odds Ratio (OR) 0.84; 95% Confidence Interval (CI) 0.78-0.91; P < 0.05], cardiovascular death (OR 0.78; 95% CI 0.69-0.88; P < 0.05), all-cause death (OR 0.86; 95% CI 0.79-0.93; P < 0.05) and the occurrence of renal dysfunction (OR 0.78; 95% CI 0.63-0.96; P < 0.05). The incidence of hypotension (OR 1.44; 95% CI 1.15-1.80; P < 0.05) and dizziness (OR 1.46; 95% CI 1.32-1.62; P < 0.05) was obviously increased in neprilysin-RAS inhibition compared with RAS inhibition. There were no significant differences in any adverse events, serious adverse events, myocardial ischemia, angioedema, hyperkalemia, fatigure, cough, gastrointestinal disorders and infections compared neprilysin-RAS inhibition with RAS inhibition alone. CONCLUSIONS: The available evidence are supportive of the use of combined neprilysin and RAS inhibition in heart failure with close observation of blood pressure.

P4HA3 is Epigenetically Activated by Slug in Gastric Cancer and its Deregulation is Associated With Enhanced Metastasis and Poor Survival.

Prolyl 4-hydroxylase alpha subunit is the enzymic active site of prolyl 4-hydroxylase, which is a critical enzyme to maintain the stability of newly synthesized collagens. The expression profile and functional role of P4HA3 in gastric cancer have not been explored. In the Cancer Genome Atlas-Stomach Cancer, P4HA3 RNA is significantly upregulated in gastric cancer than in normal stomach tissues. In the Human Protein Atlas, Prolyl 4-hydroxylase alpha subunit is not detectable by immunohistochemistry staining in normal stomach tissues, but it has weak staining in 7 of 12 gastric cancer tissues. Further study showed that SNAI2 (encoding Slug) is highly coexpressed with P4HA3 (Pearson r = 0.70) in Cancer Genome Atlas-Stomach Cancer. In vitro cell assay showed that Slug could efficiently bind to the P4HA3 promoter and increase its transcription. P4HA3 exon array data in Cancer Genome Atlas-Stomach Cancer revealed that 2 exons are significantly upregulated in M1 (N = 27) cases than in M0 (N = 367) cases. In MKN-45 and AGS cells, P4HA3 upregulation could enhance cell motility and invasiveness. In Cancer Genome Atlas-Stomach Cancer, high P4HA3 exon expression is associated with significantly worse 5-year and 10-year overall survival ( P = .007 and .009, respectively). Data mining in Kaplan-Meier plotter also showed that high P4HA3 expression is related to unfavorable overall survival (hazard ratio: 1.54, 95% confidence interval: 1.23-1.93, P < .001) and first progression-free survival (hazard ratio: 1.64, 95% confidence interval: 1.29-2.1, P < .001). Based on findings above, we infer that P4HA3 is epigenetically activated by Slug, and its deregulation is associated with enhanced metastasis and poor survival of gastric cancer.

WBP2 modulates G1/S transition in ER+ breast cancer cells and is a direct target of miR-206.

PURPOSE: The mechanisms underlying the oncogenic properties of WW domain binding protein 2 (WBP2) in breast cancer have not been fully understood. In this study, we explored the role of WBP2 in cell cycle regulation in ER+ breast cancer cells and how it is regulated in the cancer cells. METHODS: The association between WBP2 expression and prognosis in ER+ breast cancer was assessed by data mining in Breast Cancer Gene-Expression Miner v4.0. Cell cycle was assessed by PI staining and flow cytometry. EdU staining was applied to visualize cells in S phase. The binding between miR-206 and WBP2 were verified by dual luciferase assay. CCK-8 assay and flow cytometric analysis were applied to assess the functional role of WBP2 and miR-206 in the cancer cells. RESULTS: High WBP2 expression correlates with higher risk of any events (AE) and metastatic relapse (MR) and also indicates shorter AE-free survival and MR-free survival in ER+ breast cancer patients. In both MCF-7 and BT474 cells, WBP can influence the expression of G1/S-related cell cycle proteins, including p21, CDK4, and cyclin D1. In addition, WBP2 overexpression resulted in facilitated G1/S transition, while WBP2 knockdown impaired the transition. The 3'UTR of WBP2 has a conserved miR-206 binding site. Functionally, miR-206 knockdown decreased tamoxifen sensitivity in tamoxifen-sensitive (TamS) MCF-7 cells, while miR-206 overexpression and WBP2 knockdown enhanced the sensitivity in tamoxifen-resistant (TamR) MCF-7 cells. CONCLUSION: Based on these findings, we infer that the miR-206/WBP2 axis can modulate tamoxifen sensitivity via regulating G1/S progression in ER+ breast cancer.

[Efficacy Analysis of Arsenic Trioxide Combined with All Trans Retinoic Acid for Acute Promyelocytic Leukemia].

OBJECTIVE: To investigate the efficacy of arsenic trioxide combined with all trans retinoic acid (ATRA) for patients with acute promyelocytic leukemia (APL). METHODS: A total of 159 cases of APL were selected from January 2011 to December 2014 in our hospital, among them 75 cases were treated by As2O3combined with ATRA, 43 cases were treated with As2O3alone, 41 cases were treated with ATRA alone. The cardiac enzymes level, lever function index change, death rate, complate remission (CR) rate, time of reaching CR and complicatiens were compared in 3 groups. RESULTS: After treatment of 8 courses, ALT and AST levels in As2O3+ ATRA group were significantly higher than those in As2O3and ATRA alone groups; the CK-MB and TnI-UI index increased in As2O3group (P < 0.05); as compared with As2O3group, the mortality and CR rate in As2O3+ ATRA group were no significant different, but the time of reaching CR was significantly shortened. For relapsed patients, the CR rate in As2O3+ ATRA group was no significantly different from that in As2O3group, while was significantly higher than that in ATRA group. The ratio of liver function damage in As2O3+ ATRA group was increased, moreover the incidence of leukocytosis and headache in ATRA group was significantly higher than that in As2O3+ ATRA and As2O3group (P < 0.05). CONCLUSIONS: The efficacy of As2O3conbined with ATRA for inducing remission is better than that of single drug treatment, moreover the adverse reactions occur less.

TROP-1/Ep-CAM and CD24 are potential candidates for ovarian cancer therapy.

To clarify the possible roles of epithelial cell adhesion molecule (TROP-1/Ep-CAM) and CD24 molecule (CD24) in ovarian tumorigenesis, and explore the possible mechanism underlying this disease. Recombinant eukaryotic expression vectors pCIneo-TROP-1/Ep-CAM and pCIneo-CD24 were transfected into human normal ovarian surface epithelia cell line IOSE-80 respectively, with IOSE-80 cells transfected with the empty vector pCIneo as control. MRNA and protein expression of TROP-1/Ep-CAM and CD24 were detected by RT-PCR and Western blotting, respectively. Cell migration was assayed by trans-well inserts; cell proliferation and adhesion were analyzed by CCK-8 Cell Counting kit; cell cycle and cell apoptosis analysis were performed by flow cytometer. The expressions of TROP-1/Ep-CAM and CD24 were obviously up-regulated in TROP-1/Ep-CAM group and CD24 group compared to that in control group (P<0.01). Cells of TROP-1/Ep-CAM group and CD24 group was significantly promoted migratory and proliferation abilities, but inhibited cell apoptosis and adhesive than that of control group (P<0.05). Besides, the number of the cells in G1 and G2 stages was significantly lower in two disease groups than that in control group (P<0.05). TROP-1/Ep-CAM and CD24 may play key roles in the progression of ovarian cancer through promoting migration, proliferation, inhibiting cell apoptosis and adhesion, and disturbing cell cycle. They may be used as specific therapeutic targets in the treatment of ovarian cancer. However, further experiments are still needed to confirm our results.