Lysyl Oxidase 3 Is a Dual-Specificity Enzyme Involved in STAT3 Deacetylation and Deacetylimination Modulation.

In mammalian cells, histone deacetylase (HDAC) and Sirtuin (SIRT) are two families responsible for removing acetyl groups from acetylated proteins. Here, we describe protein deacetylation coupled with deacetylimination as a function of lysyl oxidase (LOX) family members. LOX-like 3 (Loxl3) associates with Stat3 in the nucleus to deacetylate and deacetyliminate Stat3 on multiple acetyl-lysine sites. Surprisingly, Loxl3 N-terminal scavenger receptor cysteine-rich (SRCR) repeats, rather than the C-terminal oxidase catalytic domain, represent the major deacetylase/deacetyliminase activity. Loxl3-mediated deacetylation/deacetylimination disrupts Stat3 dimerization, abolishes Stat3 transcription activity, and restricts cell proliferation. In Loxl3-/- mice, Stat3 is constitutively acetylated and naive CD4+ T cells are potentiated in Th17/Treg cell differentiation. When overexpressed, the SRCR repeats from other LOX family members can catalyze protein deacetylation/deacetylimination. Thus, our findings delineate a hitherto-unknown mechanism of protein deacetylation and deacetylimination catalyzed by lysyl oxidases.

Effect of Premedication With Pronase Before Upper Gastrointestinal Endoscopy: A Multicenter Prospective Randomized Controlled Study.

OBJECTIVES: This study aimed to confirm whether premedication with pronase before endoscopy improves mucosal visualization and increases precancerous lesion and cancer lesion detection rates. MATERIALS AND METHODS: From June 2018 to April 2019, out-patients scheduled for endoscopy from 13 hospitals were screened to be randomly allocated in a 2:1 ratio to premedication with pronase (group A) and water (group B). The primary endpoint was mucosal visibility scores, and the secondary endpoint was precancerous and cancer lesion detection rates. This trial was registered at Chinese Clinical Trial Registry, and the registration number was ChiCTR1800016853. RESULTS: Group A showed significantly lower mucosal visibility scores (better mucosal visibility) of esophagus, stomach, and duodenum than group B, with all P -values <0.001. The overall cancer detection rates between group A and group B were 0.83 and 1.08%, and overall detection rates of precancerous and cancer lesion were 4.4 and 4.9%, both without significant difference ( P =1.000 and 0.824). In addition, the flushing volume (milliliter) of group A (10.52±23.41) was less than group B (36.30±52.11) ( P <0.001), and the flushing frequency of group A (0.46±1.01) was fewer than group B (1.62±2.12) ( P <0.001). CONCLUSIONS: Premedication with pronase could achieve better mucosal visibility and decrease flushing frequency and volume, but may not increase lesion detection rates.

An evaluation of aging measures: from biomarkers to clocks.

With the increasing number of aged population and growing burden of healthy aging demands, a rational standard for evaluation aging is in urgent need. The advancement of medical testing technology and the prospering of artificial intelligence make it possible to evaluate the biological status of aging from a more comprehensive view. In this review, we introduced common aging biomarkers and concluded several famous aging clocks. Aging biomarkers reflect changes in the organism at a molecular or cellular level over time while aging clocks tend to be more of a generalization of the overall state of the organism. We expect to construct a framework for aging evaluation measurement from both micro and macro perspectives. Especially, population-specific aging clocks and multi-omics aging clocks may better fit the demands to evaluate aging in a comprehensive and multidimensional manner and make a detailed classification to represent different aging rates at tissue/organ levels. This framework will promisingly provide a crucial basis for disease diagnosis and intervention assessment in geroscience.

A Randomized Double-blind Clinical Trial of Weierkang Pills for the Treatment of Chronic Atrophic Gastritis.

BACKGROUND AND GOALS: There are currently no standard treatments for chronic atrophic gastritis and traditional Chinese medicine may be effective. This study aims to investigate the efficacy and safety of Weierkang pills in treating chronic atrophic gastritis. MATERIALS AND METHODS: There were 108 patients in our study. They were randomly assigned to 2 groups. In group A, patients received Weierkang pills and patients in group B received folic acid combined with teprenone. Symptoms, endoscopic scores, and biopsy specimens were compared at baseline and 3 months after treatment. Meanwhile, the expressions of vascular endothelial growth factor and trefoil factor 3 (TFF3) in biopsy specimens were also compared. RESULTS: Our study showed that the total effective rates of atrophy/intestinal metaplasia in group A reached the same level as group B (51.7% vs. 40.0%, P =0.419). Weierkang significantly improved the total effective rate of atrophy/intestinal metaplasia in gastric angle compared with group B (64.7% vs. 33.3%, P =0.024). Weierkang can significantly lower the total Kyoto risk score (2.6±1.1 vs. 3.3±1.0, P =0.002) and atrophy score (1.4±0.6 vs. 1.8±0.5, P =0.001) after treatment. In addition, Weierkang improves symptoms (1.3±1.3 vs. 2.3±1.8, P =0.003) and epigastric pain (0.2±0.4 vs. 0.5±0.6, P =0.041). The expression of TFF3 in gastric mucosa decreased significantly after treatment with Weierkang ( P =0.002). CONCLUSIONS: Weierkang can improve the endoscopic appearance and pathologic changes of chronic atrophic gastritis patients. Symptoms also improved. TFF3 may be involved the pathophysiology mechanism.

Premedication with reformulated simethicone and sodium bicarbonate improves mucosal visibility during upper gastrointestinal endoscopy: a double-blind, multicenter, randomized controlled trial.

BACKGROUND: The reformulated simethicone emulsion from Berlin Chemical AG might develop white flocculate precipitate covering the gastric mucosa when used before esophagogastroduodenoscopy (EGD). We aim to investigate whether combining the reformulated simethicone emulsion with 5% sodium bicarbonate solution could prevent the development of white precipitate and improve visibility during EGD. METHODS: Our clinical study involved 523 patients. They were randomly assigned to two groups. In Group A, patients received a warm solution containing 30 ml 5% sodium bicarbonate solution and 15 ml reformulated simethicone emulsion. In Group B, patients received 45 ml 40 °C lukewarm water. Visibility scores were recorded and analyzed. Flushes, volume of flush water, overall time taken for EGD and complications during or after the procedure were also recorded. RESULTS: We found that no white precipitate was observed during EGD in Group A. Moreover, visibility scores in Group A were significantly lower (P < 0.01). Patients in Group A had fewer flushes (P < 0.01) and smaller volume of flush water (P < 0.01). In addition, the overall time taken for the EGD procedure was significantly shorter in Group A (P < 0.01). The percentage of patients who had no adverse response was significantly higher in Group A than in Group B (P < 0.01). CONCLUSIONS: Premedication with a mixed solution of 15 ml reformulated simethicone emulsion and 30 ml 5% sodium bicarbonate solution can prevent the development of white precipitate, substantially enhancing mucosal visibility safely. TRIAL REGISTRATION: The registered name of the trial is "Efficacy of using premedication with reformulated simethicone emulsion during upper gastrointestinal endoscopy examination". Its Current Controlled Trials number is ChiCTR1900021689. Its date of registration is 11 September 2019. Retrospectively registered, http://www.medresman.org.cn/uc/sindex.aspx .

ATP13A2 Regulates Cellular α-Synuclein Multimerization, Membrane Association, and Externalization.

ATP13A2, a late endo-/lysosomal polyamine transporter, is implicated in a variety of neurodegenerative diseases, including Parkinson's disease and Kufor-Rakeb syndrome, an early-onset atypical form of parkinsonism. Loss-of-function mutations in ATP13A2 result in lysosomal deficiency as a consequence of impaired lysosomal export of the polyamines spermine/spermidine. Furthermore, accumulating evidence suggests the involvement of ATP13A2 in regulating the fate of α-synuclein, such as cytoplasmic accumulation and external release. However, no consensus has yet been reached on the mechanisms underlying these effects. Here, we aimed to gain more insight into how ATP13A2 is linked to α-synuclein biology in cell models with modified ATP13A2 activity. We found that loss of ATP13A2 impairs lysosomal membrane integrity and induces α-synuclein multimerization at the membrane, which is enhanced in conditions of oxidative stress or exposure to spermine. In contrast, overexpression of ATP13A2 wildtype (WT) had a protective effect on α-synuclein multimerization, which corresponded with reduced αsyn membrane association and stimulation of the ubiquitin-proteasome system. We also found that ATP13A2 promoted the secretion of α-synuclein through nanovesicles. Interestingly, the catalytically inactive ATP13A2 D508N mutant also affected polyubiquitination and externalization of α-synuclein multimers, suggesting a regulatory function independent of the ATPase and transport activity. In conclusion, our study demonstrates the impact of ATP13A2 on α-synuclein multimerization via polyamine transport dependent and independent functions.

Long Noncoding RNA GMAN, Up-regulated in Gastric Cancer Tissues, Is Associated With Metastasis in Patients and Promotes Translation of Ephrin A1 by Competitively Binding GMAN-AS.

BACKGROUND & AIMS: We aimed to identify long noncoding RNAs (lncRNAs) that are up-regulated in gastric cancer tissues from patients and study their function in gastric tumor metastasis. METHODS: We collected gastric tumor and nontumor tissues from patients in China and analyzed levels of lncRNAs by microarray analysis, proteins by immunohistochemistry, and RNAs by quantitative reverse-transcription polymerase chain reaction; we compared these with survival times of patients and tumor progression. RNA levels were knocked down or knocked out in BGC-823, SGC-7901, and MKN45 cell lines using small interfering or short hairpin RNAs or clustered regularly interspaced short palindromic repeats (ie, CRISPR)/CRISPR associated protein 9 (ie, Cas9) vectors. Genes were overexpressed from transfected plasmids in HGC-27 cells. Cells were analyzed by Northern blot and immunoblot, polysome profiling assay, and cell invasion assay. Cells were injected into the tail veins or spleens of nude mice or SCID mice; lung and liver tissues were collected, and metastases were counted. lncRNAs were cloned by using rapid amplification of complementary DNA ends. Their interactions with other genes were determined by RNA pulldown and mapping assays. RESULTS: In microarray analyses, we identified 151 lncRNAs expressed at significantly higher levels in gastric tumor vs nontumor tissues. Levels of an lncRNA that we called gastric cancer metastasis associated long noncoding RNA (GMAN) were increased in gastric tumor tissues, compared with nontumor tissues; its up-regulation was associated with tumor metastasis and shorter survival times of patients. The GMAN gene overlaps with the ephrin A1 gene (EFNA1) and was highly expressed in BGC-823 and MKN45 cells. Knockdown of GMAN in these cells did not affect proliferation, colony formation, or adhesion but did reduce their invasive activity in Transwell assays. Ectopic expression of GMAN increased the invasive activity of HGC-27 cells. BGC-823 and MKN45 cells with knockdown of GMAN formed fewer metastases after injection into tail veins of nude mice. Knockdown or knockout of GMAN also reduced levels of ephrin A1 protein in cells. We found that GMAN promoted translation of ephrin A1 messenger RNA into protein by binding to the antisense GMAN RNA (GMAN-AS)-this antisense sequence is also complementary to that of ephrin A1 mRNA. Levels of ephrin A1 protein were also increased in gastric tumors from patients with metastases than in those without metastases. Knockout of ephrin A1 in BGC-823 cells reduced their invasive activity in Transwell assays and ability to form metastases after injection into SCID mice. Ectopic expression of ephrin A1 in BGC-823 cells with knockdown or knockout of GMAN restored their invasive activities and ability form metastases in nude or SCID mice. A CRISPR/Cas9-based strategy to disrupt the GMAN gene significantly reduced the numbers of metastases formed from SGC-7901 cells in mice. CONCLUSIONS: We identified an lncRNA, which we call GMAN, that is increased in gastric tumors from patients and associated with survival and formation of metastases. It regulates translation of ephrin A1 mRNA by binding competitively to GMAN-AS. Knockdown or knockout of GMAN or ephrin A1 in gastric cancer cell lines reduces their invasive activity and ability to form metastases after injection into mice. These genes might be targeted to prevent or reduce gastric cancer metastasis.

HoxC6 Functions as an Oncogene and Isoform HoxC6-2 May Play the Primary Role in Gastric Carcinogenesis.

PURPOSE: Based on previous researches of HoxC6, this study aims to investigate the expression levels of isoforms HoxC6-1 and HoxC6-2 and to explore their roles in gastric carcinogenesis as well as the possible molecular mechanism. METHODS: We investigated expression levels of HoxC6, HoxC6-1, and HoxC6-2 in gastric cancer tissues, coupled with relevant data in TCGA dataset. In vitro, HoxC6, HoxC6-1, and HoxC6-2 knockdown by small interference RNA was carried for evaluating the changes of malignant biological behaviors of gastric cancer cells, such as proliferation, migration, invasion, apoptosis, and cell cycle alternation. Metastasis-related nucleotide lncRNA HOTAIR was selected by bioinformatics, and verification was carried out by in vitro researches. RESULTS: Data suggested HoxC6-1 and HoxC6-2 were considerably over-expressed with different folds in gastric cancerous tissues. Decreased expression of HoxC6-2 was detected in well-differentiated type of gastric cancer. In vitro, the conclusion that HoxC6 functions as a tumor oncogene illuminated by previous studies was verified again. Additionally, down-regulating of HoxC6-2 significantly inhibited SGC-7901 and BGC-823 cells from proliferation, migration, invasion, apoptosis, while quite slight results or none statistically significant results were observed when HoxC6-1 was knockdown. Besides, over-expression of HOTAIR, which is relevant with HoxC6 during gastric carcinogenesis, was detected in gastric cancerous tissues. Restored expression of HoxC6 partially reversed the decreased migration caused by down-regulating HOTAIR in gastric cancer cells. CONCLUSION: HoxC6 acts as an oncogene in gastric carcinogenesis and might be a promising therapeutic target. Isoform HoxC6-2 plays a primary carcinogenic role in gastric carcinogenesis. HOTAIR, over-expressed in gastric cancer, might regulate HoxC6 on the protein level in promoting migration of gastric cells.

Impact of preprocedure simethicone on adenoma detection rate during colonoscopy: a multicenter, endoscopist-blinded randomized controlled trial.

BACKGROUND AND STUDY AIMS: Ideal bowel preparation for colonoscopy requires complete removal of fluid and foam from the colon. Polyethylene glycol (PEG) is widely used for bowel preparation, with antifoaming agents such as simethicone commonly used in combination with PEG. Data on the effect of simethicone on the adenoma detection rate (ADR) were limited. This study therefore aimed to investigate whether preprocedure simethicone could increase the ADR. PATIENTS AND METHODS: This was a prospective, multicenter, endoscopist-blinded randomized controlled trial involving consecutive patients who underwent colonoscopy in six centers in China. Patients were randomly assigned to one of two groups: PEG plus simethicone or PEG alone. The primary outcome was ADR; secondary outcomes were quality of bowel preparation, measured by the Boston bowel preparation scale (BBPS) and bubble scores. RESULTS: 583 patients were included. More adenomas were detected in the PEG plus simethicone group than in the PEG alone group (ADR 21.0 % vs. 14.3 %, P = 0.04; advanced ADR 9.0 % vs. 7.0 %, P = 0.38). The mean number of adenomas detected was 2.20 ±â€Š1.36 vs. 1.63 ±â€Š0.89 (P = 0.02). Patients in the PEG plus simethicone group showed better bowel cleansing efficacy: BBPS ≥ 6 in 88.3 % vs. 75.2 % (P < 0.001) and bubble scores of 1.00 ±â€Š1.26 vs. 3.98 ±â€Š2.50 (P < 0.001). Abdominal bloating was reported less frequently in the PEG plus simethicone group (7.8 % vs. 19.7 %, P < 0.001) than in the PEG alone group. CONCLUSION: Combined use of PEG and simethicone is associated with a significantly increased ADR in a Chinese population.

Validation of the American Joint Committee on Cancer (AJCC) 8th edition stage system for gastric cancer patients: a population-based analysis.

BACKGROUND: Our aim was to validate the American Joint Committee on Cancer (AJCC) 8th edition stage system for gastric cancer in the Western world and to compare several modifications between the 7th and 8th edition systems. METHODS: Eligible patients having undergone surgical resection of gastric cancer during 2004-2011 from the Surveillance, Epidemiology, and End Results (SEER) database were included in the current study. Survival differences were assessed by Kaplan-Meier curve and log-rank tests. The discriminative power of the AJCC 8th and 7th editions was compared by Harrell's concordance index (c-index). RESULTS: Patients with pN3a and pN3b presented distinct survival outcomes, especially for cases in which more than 15 lymph nodes were examined. The overall (OS) and cancer-specific survival (CSS) c-indices for the 8th edition were largely comparable with c-indices for the 7th edition throughout the cohort. Notably, the new edition improved the power of discrimination slightly in OS and CSS (c-indices: 0.717, 0.744) compared with the 7th edition (c-indices: 0.712, 0.739) for patients for whom 15 or more lymph nodes were examined. The analysis of stage migration in the new edition revealed nonhomogeneous survival outcomes in stages IIIB and IIIC. CONCLUSION: The AJCC 8th stage system for gastric cancer performs as well as the AJCC 7th edition in the United States (USA). Importantly, when more than 15 lymph nodes are examined, the discriminatory performance of the new edition is improved.

HOTAIR induces the ubiquitination of Runx3 by interacting with Mex3b and enhances the invasion of gastric cancer cells.

BACKGROUND: Long non-coding RNAs (LncRNAs) exert their functions mainly by binding to their corresponding proteins. Runt-related transcription factor 3 (Runx3) is an important transcription factor that functions as a tumor suppressor in gastric cancer. Whether there is an interplay between LncRNAs and Runx3 remains unclear. METHODS: RPISeq was applied to screen the LncRNAs that potentially bind to Runx3. The interaction between LncRNA HOX antisense intergenic RNA (HOTAIR) and Runx3 was validated by RNA Immunoprecipitation and RNA pull-down assays. The role of Mex3b in the ubiquitination of Runx3 induced by HOTAIR was assessed by immunoprecipitation. Pearson's correlation between HOTAIR mRNA expression and Runx3 protein expression was analyzed. Cell migration and invasion were explored by transwell assays. RESULTS: We found that HOTAIR was bound to Runx3 protein and identified the fragment of HOTAIR spanning 1951-2100 bp as the specific binding site. In addition, mex-3 RNA binding family member B (Mex3b) was an E3 ligase involved in HOTAIR-induced ubiquitous degradation of Runx3. Silencing the expression of HOTAIR or Mex3b attenuated the degradation of Runx3. In human gastric cancer tissues, HOTAIR was negatively associated with the expression level of Runx3 protein (Pearson coefficient - 0.501, p = 0.025). Inhibition of HOTAIR significantly suppressed gastric cancer cell migration and invasion through upregulating claudin1, which could be reversed by co-deficiency of Runx3. CONCLUSIONS: These results uncovered the novel interaction between HOTAIR and Runx3, and provided potential therapeutic targets on the metastasis of gastric cancer.

1-Day or 5-Day Fecal Samples, Which One is More Beneficial to be Used for DNA-Based Gut Microbiota Study.

Fecal sample collection is an important influential factor for DNA-based gut microbiota study. It is controversial whether the microbiome detected in fecal sample collected at one random day could fully represent the gut microbial community. The aim of the study is to figure out whether the use of fecal sample mixture collected at consecutive 5 days could more accurately represent gut microbial community. 1- and 5-day fecal samples were collected from 8 healthy adults and analyzed by 16S rRNA sequence. Our results indicated that both 1-day fecal samples and 5-day samples exhibited relatively high repeatability. The relative abundance of majority of bacterial taxa did not changed between 1-day fecal samples and 5-day fecal samples. However, the alpha diversity of 5-day fecal samples was higher than that of 1-day fecal samples. When the aims of studies are to analyze the relative abundance of specific OTUs among subjects, fecal samples collected at one day could be used. When microbial diversity is one of essential factors to be analyzed, the use of 5-day fecal samples may be more recommended.

The mitochondrial protein BNIP3L is the substrate of PARK2 and mediates mitophagy in PINK1/PARK2 pathway.

Mitochondrial dysfunction plays important roles in Parkinson's disease (PD) and the degradation of the damaged mitochondria by the mitochondria quality control system is important for dopaminergic (DA) neuronal survival. BNIP3L/Nix is a mitochondrial outer membrane protein that is required for the selective clearance of mitochondria. Here, we found that the mitochondrial protein BNIP3L acts downstream of the PINK1/PARK2 pathway to induce mitophagy. BNIP3L is a substrate of PARK2 to drive PARK2-mediated mitophagy. The ubiquitination of BNIP3L by PARK2 recruits NBR1 to mitochondria, thereby targeting mitochondria for degradation. BNIP3L rescues mitochondrial defects in pink1 mutant Drosophila but not in park mutant Drosophila, indicating that the clearance of mitochondria induced by BNIP3L depends on the presence of PARK2. In cells intoxicated with mitochondrial complex I inhibitors rotenone, 6-OHDA or MPP(+), the disrupted mitochondria are not appropriately eliminated by mitophagy due to the improper degradation of BNIP3L. Thus, our study demonstrates that BNIP3L, as a substrate of PARK2, promotes mitophagy in the PINK1/PARK2 pathway associated with PD pathogenesis.

The tumor promoting roles of erythropoietin/erythropoietin receptor signaling pathway in gastric cancer.

Erythropoietin (EPO), binding with its receptor (EPOR), plays an important role in erythropoiesis. EPOR is reported to be expressed in various non-hematopoietic cancers, including gastric cancer. Although recombinant human EPO (rhEPO) has been widely used clinically in anemia patients, it remains controversial whether it would promote tumor progression. In this study, we used siRNA interference method to downregulate EPOR expression to investigate the function of EPO/EPOR pathway in human gastric cancer cells. We found EPOR expressed significantly higher in gastric cancer tissues, and also in most gastric cancer cell lines. RhEPO promoted gastric cancer cell proliferation, migration in AGS cells, and promoted cells from G0/G1 stage to G2/M stage, but had no regulation on AGS cell apoptosis. Downregulation of EPOR expression by siRNA interference in AGS cells resulted in no significant effects on proliferation and invasiveness of the cells, but induced apoptosis (p < 0.05). Xenografted gastric tumor model was used to explore the effect of EPOR-overexpression on gastric cancer cells in vivo. Our result showed that overexpression of EPOR enhanced tumor formation in nude mice (p < 0.01). Our results suggest that EPO/EPOR pathway promotes gastric cancer formation, proliferation, migration, and decreases apoptosis.

Comparing endoscopic mucosal resection with endoscopic submucosal dissection: the different endoscopic techniques for colorectal tumors.

BACKGROUND: Endoscopic mucosal resection (EMR) and endoscopic submucosal dissection (ESD) are used for the removal of colorectal tumors. There are no current guidelines or consensus on the optimal treatment strategy for these lesions. A meta-analysis was conducted to compare the effectiveness and safety of ESD and EMR for colorectal tumors. METHODS: For the years 1966 until October 2014, Medline, PubMed, Scopus, Web of Science, and Cochrane Central Register of Controlled Trials were searched for articles comparing the effectiveness and safety of ESD and EMR. STATA 11.0 and RevMan 5.0 were used for meta-analysis and publication bias. RESULTS: Seventeen articles were included in this meta-analysis. ESD was more effective than EMR in endoscopic complete resection rate (odds ratio [OR] = 2.81; 95% confidence interval [CI], 1.39-5.70; Z = 2.86; P = 0.004) and pathologic complete resection rate (OR = 2.81; 95% CI, 1.39-5.70; Z = 2.86; P = 0.004). ESD resulted in a higher perforation rate (OR = 5.27; 95% CI, 2.75-10.08; Z = 5.01; P < 0.00001) and a lower recurrence rate (OR = 0.14; 95% CI, 0.06-0.30; Z = 5.04; P < 0.00001). The tumor size was larger in the ESD group (OR = 3.09; 95% CI, 1.54-4.63; Z = 3.92; P < 0.0001), and the procedure time was longer in the ESD group (OR = 21.39; 95% CI, 10.33-32.46; Z = 3.79; P = 0.0002). But bleeding rate did not differ significantly (OR = 1.34; 95% CI, 0.81-2.20; Z = 1.14; P = 0.25). There was no publication bias analyzed by Begg test and Egger test. CONCLUSIONS: The study indicates that ESD is the better treatment for colorectal tumors for its higher complete resection rate despite the longer procedure time and higher perforation rate.

Small-bowel capsule endoscopy in patients with unexplained chronic abdominal pain: a systematic review.

BACKGROUND: Patients frequently consult primary care physicians and gastroenterologists when experiencing chronic abdominal pain. Although its diagnostic efficacy in these settings is uncertain, small-bowel capsule endoscopy (SBCE) has been used to evaluate the unexplained reasons for abdominal pain. OBJECTIVE: To evaluate the diagnostic yield of SBCE in patients with unexplained chronic abdominal pain. DESIGN: We performed a retrospective review of publications reporting the diagnostic yield of SBCE in patients with unexplained chronic abdominal pain and calculated the overall diagnostic yield. SETTING: Two investigators independently searched studies from databases and analyzed the results. PATIENTS: A total of 1520 patients from 21 studies were included. INTERVENTIONS: Small-bowel capsule endoscopy. MAIN OUTCOME MEASUREMENTS: Per-patient diagnostic yield, with 95% confidence intervals (CI), was evaluated by a random-effect model. Clear categorical analysis also was performed. RESULTS: The pooled diagnostic yield of SBCE in patients with unexplained chronic abdominal pain was 20.9% (95% CI, 15.9%-25.9%), with high heterogeneity (I(2) = 80.0%; P ＜ .001). Inflammatory lesions were the most common (78.3%) positive findings, followed by tumors (9.0%). LIMITATIONS: Heterogeneity among studies, retrospective design, variable chronicity of abdominal pain, and different previous examinations before SBCE. CONCLUSION: SBCE provides a noninvasive diagnostic tool for patients with unexplained chronic abdominal pain, but the diagnostic yield is limited (20.9%). Among patients with positive findings, inflammatory lesions are the most common.

Parkin represses 6-hydroxydopamine-induced apoptosis via stabilizing scaffold protein p62 in PC12 cells.

AIM: Parkin has been shown to exert protective effects against 6-hydroxydopamine (6-OHDA)-induced neurotoxicity in different models of Parkinson disease. In the present study we investigated the molecular mechanisms underlying the neuroprotective action of parkin in vitro. METHODS: HEK293, HeLa and PC12 cells were transfected with parkin, parkin mutants, p62 or si-p62. Protein expression and ubiquitination were assessed using immunoblot analysis. Immunoprecipitation assay was performed to identify the interaction between parkin and scaffold protein p62. PC12 and SH-SY5Y cells were treated with 6-OHDA (200 µmol/L), and cell apoptosis was detected using PI and Hoechst staining. RESULTS: In HEK293 cells co-transfected with parkin and p62, parkin was co-immunoprecipitated with p62, and parkin overexpression increased p62 protein levels. In parkin-deficient HeLa cells, transfection with wild-type pakin, but not with ligase activity-deficient pakin mutants, significantly increased p62 levels, suggesting that parkin stabilized p62 through its E3 ligase activity. Transfection with parkin or p62 significantly repressed ERK1/2 phosphorylation in HeLa cells, but transfection with parkin did not repress ERK1/2 phosphorylation in p62-knockdown HeLa cells, suggesting that p62 was involved in parkin-induced inhibition on ERK1/2 phosphorylation. Overexpression of parkin or p62 significantly repressed 6-OHDA-induced ERK1/2 phosphorylation in PC12 cells, and parkin overexpression inhibited 6-OHDA-induced apoptosis in PC12 and SH-SY5Y cells. CONCLUSION: Parkin protects PC12 cells against 6-OHDA-induced apoptosis via ubiquitinating and stabilizing scaffold protein p62, and repressing ERK1/2 activation.

Endoscopic submucosal dissection for early gastric cancer in elderly patients: a meta-analysis.

BACKGROUND: The effectiveness of endoscopic submucosal dissection (ESD) has been increasingly reported. However, studies addressing the safety and application value of ESD in elderly patients with early gastric cancer (EGC) were still lacking. This meta-analysis was intended to evaluate the feasibility and safety of ESD in elderly patients with EGC. METHODS: A systematic search was conducted in PubMed, EBSCO, Cochrane Library, EMBASE, and Web of Science. Studies were screened out if data of elderly and non-elderly gastric cancer patients were reported separately. The qualities of included studies were assessed using Newcastle-Ottawa Quality Assessment Scale. The pooled odd ratios (ORs) with 95 % confidence intervals (CIs) were calculated. Statistical analysis was conducted using the Review Manager 5.2 (Cochrane Collaboration, Oxford, UK). RESULTS: Nine studies (eight in Japan, one in China), including a total of 30,100 lesions, met the inclusion criteria. The "en bloc" and histological complete resection rates of the elderly and non-elderly groups were similar [OR, 0.98, 95 % CI, 0.56 to 1.71; P = 0.93 and OR, 0.79, 95 % CI, 0.58 to 1.07; P = 0.13, respectively]. As for procedure-related complications, similar perforation rates [OR, 1.19, 95 % CI, 0.94 to 1.51; P = 0.15], and bleeding rates [OR, 1.13, 95 % CI, 0.83 to 1.56); P = 0.43] between the elderly and non-elderly groups were observed. Whereas, the elderly patients had a higher procedure-related pneumonia rate compared with non-elderly ones [OR, 2.18, 95 % CI, 1.55 to 3.08; P < 0.01]. CONCLUSIONS: The ESD procedure appears to be a safe technique in elderly patients with EGC while appropriate approach should be taken to avoid procedure-related pneumonia.

[Searching for Rare Celestial Objects Automatically from Stellar Spectra of the Sloan Digital Sky Survey Data Release Eight].

There are many valuable rare and unusual objects in spectra dataset of Sloan Digital Sky Survey (SDSS) Data Release eight (DR8), such as special white dwarfs (DZ, DQ, DC), carbon stars, white dwarf main-sequence binaries (WDMS), cataclysmic variable (CV) stars and so on, so it is extremely significant to search for rare and unusual celestial objects from massive spectra dataset. A novel algorithm based on Kernel dense estimation and K-nearest neighborhoods (KNN) has been presented, and applied to search for rare and unusual celestial objects from 546 383 stellar spectra of SDSS DR8. Their densities are estimated using Gaussian kernel density estimation, the top 5 000 spectra in descend order by their densities are selected as rare objects, and the top 300 000 spectra in ascend order by their densities are selected as normal objects. Then, KNN were used to classify the rest objects, and simultaneously K nearest neighbors of the 5 000 rare spectra are also selected as rare objects. As a result, there are totally 21 193 spectra selected as initial rare spectra, which include error spectra caused by deletion, redden, bad calibration, spectra consisting of different physically irrelevant components, planetary nebulas, QSOs, special white dwarfs (DZ, DQ, DC), carbon stars, white dwarf main-sequence binaries (WDMS), cataclysmic variable (CV) stars and so on. By cross identification with SIMBAD, NED, ADS and major literature, it is found that three DZ white dwarfs, one WDMS, two CVs with company of G-type star, three CVs candidates, six DC white dwarfs, one DC white dwarf candidate and one BL Lacertae (BL lac) candidate are our new findings. We also have found one special DA white dwarf with emission lines of Ca II triple and Mg I, and one unknown object whose spectrum looks like a late M star with emission lines and its image looks like a galaxy or nebula.

ERK1/2 inhibition enhances apoptosis induced by JAK2 silencing in human gastric cancer SGC7901 cells.

Recent studies suggest JAK2 signaling may be a therapeutic target for treatment of gastric cancer (GC). However, the exact roles of JAK2 in gastric carcinogenesis are not very clear. Here, we have targeted JAK2 to be silenced by shRNA and investigated the biological functions and related mechanisms of JAK2 in GC cell SGC7901. In this study, JAK2 is commonly highly expressed in GC tissues as compared to their adjacent normal tissues (n = 75, p < 0.01). Specific down-regulation of JAK2 suppressed cell proliferation and colony-forming units, induced G2/M arrest in SGC7901 cells, but had no significant effect on cell apoptosis in vitro or tumor growth inhibition in vivo. Interestingly, JAK2 silencing-induced activation of ERK1/2, and inactivation of ERK1/2 using the specific ERK inhibitor PD98059 markedly enhanced JAK2 shRNA-induced cell proliferation inhibition, cell cycle arrest and apoptosis. Ultimately, combination of PD98059 and JAK2 shRNA significantly inhibited tumor growth in nude mice. Our results implicate JAK2 silencing-induced cell proliferation inhibition, cell cycle arrest, and ERK1/2 inhibition could enhance apoptosis induced by JAK2 silencing in SGC7901 cells.