Iron overload enhances TBI-induced cardiac dysfunction by promoting ferroptosis and cardiac inflammation.

Previous studies have proved that cardiac dysfunction and myocardial damage can be found in TBI patients, but the underlying mechanisms of myocardial damage induced by TBI can't be illustrated. We want to investigate the function of ferroptosis in myocardial damage after TBI and determine if inhibiting iron overload might lessen myocardial injury after TBI due to the involvement of iron overload in the process of ferroptosis and inflammation. We detect the expression of ferroptosis-related proteins in cardiac tissue at different time points after TBI, indicating that TBI can cause ferroptosis in the heart in vivo. The echocardiography and myocardial enzymes results showed that ferroptosis can aggravate TBI-induced cardiac dysfunction. The result of DHE staining and 4-HNE expression showed that inhibition of ferroptosis can reduce ROS production and lipid peroxidation in myocardial tissue. In further experiments, DFO intervention was used to explore the effect of iron overload inhibition on myocardial ferroptosis after TBI, the production of ROS, expression of p38 MAPK and NF-κB was detected to explore the effect of iron overload on myocardial inflammation after TBI. The results above show that TBI can cause heart ferroptosis in vivo. Inhibition of iron overload can alleviate myocardial injury after TBI by reducing ferroptosis and inflammatory response induced by TBI.

Brain-derived extracellular vesicles mediate traumatic brain injury associated multi-organ damage.

Traumatic brain injury (TBI) can negatively impact systemic organs, which can lead to more death and disability. However, the mechanism underlying the effect of TBI on systemic organs remains unclear. In previous work, we found that brain-derived extracellular vesicles (BDEVs) released from the injured brain can induce systemic coagulation with a widespread fibrin deposition in the microvasculature of the lungs, kidney, and heart in a mouse model of TBI. In this study, we investigated whether BDEVs can induce heart, lung, liver, and kidney injury in TBI mice. The results of pathological staining and related biomarkers indicated that BDEVs can induce histological damage and systematic dysfunction. In vivo imaging system demonstrated that BDEVs can gather in systemic organs. We also found that BDEVs could induce cell apoptosis in the lung, liver, heart, and kidney. Furthermore, we discovered that BDEVs could cause multi-organ endothelial cell damage. Finally, this secondary multi-organ damage could be relieved by removing circulating BDEVs. Our research provides a novel perspective and potential mechanism of TBI-associated multi-organ damage.

NCOA4-mediated ferritinophagy aggravate intestinal oxidative stress and ferroptosis after traumatic brain injury.

Intestinal injury caused by traumatic brain injury (TBI) seriously affects patient prognosis; however, the underlying mechanisms are unknown. Recent studies have demonstrated that ferritinophagy-mediated ferroptosis is involved in several intestinal disorders. However, uncertainty persists regarding the role of ferritinophagy-mediated ferroptosis in the intestinal damage caused by TBI. High-throughput transcriptional sequencing was used to identify the genes that were differentially expressed in the intestine after TBI. The intestinal tissues were harvested for hematoxylin and eosin staining (HE), immunofluorescence, and western blot (WB). Lipid peroxide markers and iron content in the intestines were determined using the corresponding kits. High throughput sequencing revealed that the ferroptosis signaling pathway was enriched, demonstrating that intestinal damage caused by TBI may include ferroptosis. Chiu's score, tight junction proteins, and lipid peroxide indicators demonstrated that TBI caused an intestinal mucosal injury that persisted for several days. The ferroptosis pathway-related proteins, ferritin heavy polypeptide 1 (Fth1) and glutathione peroxidase 4 (GPX4), exhibited dynamic changes. The results indicated that lipid peroxide products were markedly increased, whereas antioxidant enzymes were markedly decreased. WB analysis demonstrated that the expression levels of nuclear receptor coactivator 4 (NCOA4), LC3II/LC3I, and p62 were markedly upregulated, whereas those of GPX4 and Fth1 were markedly downregulated. In addition, ferrostatin-1 attenuates intestinal ferroptosis and injury post-TBI in vivo. Intriguingly, 3-methyladenine (3-MA) reduces intestinal ferritin decomposition, iron accumulation, and ferroptosis after TBI. Moreover, 3-MA markedly reduced intestinal apoptosis. In conclusion, NCOA4 mediated ferritinophagy and ferroptosis play roles in intestinal oxidative stress injury post-TBI. This study provides a deeper understanding of the mechanisms underlying intestinal damage following TBI.

Prognostic value of Hematoxylin and eosin staining tumor-infiltrating lymphocytes (H&E-TILs) in patients with esophageal squamous cell carcinoma treated with chemoradiotherapy.

BACKGROUND: Tumor-infiltrating lymphocytes (TILs) by routine hematoxylin and eosin staining (H&E-TILs) are a robust prognostic biomarker in various cancers. However, the role of H&E-TILs in esophageal squamous cell carcinoma (ESCC) treated with concurrent chemoradiotherapy (CCRT) has not been reported. The purpose of this study was to assess the prognostic value of H&E-TILs in ESCC treated with CCRT. METHODS: The clinical data of 160 patients with ESCC treated with CCRT in our center between Jan. 2014 and Dec. 2021 were collected and retrospectively reviewed, and propensity score matching (PSM) analyses were performed. The H&E-TILs sections before CCRT were reassessed by two experienced pathologists independently. The H&E-TILs sections were classified into a positive group (+, > 10%) and a negative group (-, ≤ 10%) using 10% as the cutoff. The effects of H&E-TILs on overall survival (OS), progression-free survival (PFS), distant metastasis-free survival (DMFS), and locoregional recurrence-free survival (LRFS) were explored using the Kaplan‒Meier method, and the log-rank test was used to test the differences. Multivariable analysis was performed using the Cox proportion hazards model. RESULTS: The short-term response to CCRT and the OS (P < 0.001), DMFS (P = 0.001), and LRFS (P < 0.001) rates were significantly different between the H&E-TILs (+) and H&E-TILs (-) groups. Subgroup analysis showed that H&E-TILs(+) with CR + PR group had a longer survival than H&E-TILs(-) with CR + PR, H&E-TILs(+) with SD + PD and H&E-TILs(-) with SD + PD group, respectively(P < 0.001). Furthermore, based on TCGA data, patients in the high TILs group had a better prognosis than those in the low TILs group. Multivariate analyses indicated that H&E-TILs and the short-term response to CCRT were the only two independent factors affecting OS, PFS, DMFS, and LRFS simultaneously, and H&E-TILs expression was associated with an even better prognosis for those patients with CR + PR. CONCLUSIONS: H&E-TILs may be an effective and beneficial prognostic biomarker for ESCC patients treated with CCRT. Patients with H&E-TILs (+) with PR + CR would achieve excellent survival. Further prospective studies are required to validate the conclusions.

Collagen-related gene expression level predicts the prognosis and immune therapy response.

BACKGROUND: Gastric cancer patients responded differently to the same treatment strategy and had various prognoses for the lack of biomarkers to guide the therapy choice. METHODS: RNA data of a local gastric cancer cohort with 103 patients were processed and used to explore potential treatment guiding factors. Cluster analysis was performed by non-negative matrix factorization. The expression level of collagen-related genes was evaluated by ssGSEA named collagen score (CS). Data from TCGA, ACRG, and an immune therapy cohort were utilized to explore prognosis and efficacy. Prognostic predictive power of CS was assessed using the nomogram. RESULTS: In our study, local RNA data were processed by cluster analysis, and it was found that cluster 2 contained a worse tumor infiltration status. The GSEA result showed that collagen-related pathways were differentially activated in two clusters. In TCGA and ACRG cohorts, the CS can be used as an independent prognostic factor (TCGA OS: p = 0.018, HR = 3.5; ACRG OS: p = 0.014, HR = 4.88). An immunotherapy cohort showed that the patients with higher CS had a significantly worse ORR (p = 0.0025). The high CS group contained several cell death pathways down-regulated and contained the worse tumor microenvironment. The nomogram demonstrated the survival prediction capability of collagen score. CONCLUSION: CS was verified as an independent prognostic factor and potentially reflected the therapeutic effect of immunotherapy. The CS could provide a new way to evaluate the clinical prognosis and response information helping develop the collagen-targeted treatment.

Recombinant Human Annexin A5 Alleviated Traumatic-Brain-Injury Induced Intestinal Injury by Regulating the Nrf2/HO-1/HMGB1 Pathway.

Aims: Annexin A5 (ANXA5) exhibited potent antithrombotic, antiapoptotic, and anti-inflammatory properties in a previous study. The role of ANXA5 in traumatic brain injury (TBI)-induced intestinal injury is not fully known. Main methods: Recombinant human ANXA5 (50 µg/kg) or vehicle (PBS) was administered to mice via the tail vein 30 min after TBI. Mouse intestine tissue was gathered for hematoxylin and eosin staining 0.5 d, 1 d, 2 d, and 7 d after modeling. Intestinal Western blotting, immunofluorescence, TdT-mediated dUTP nick-end labeling staining, and enzyme-linked immunosorbent assays were performed 2 days after TBI. A series of kits were used to assess lipid peroxide indicators such as malonaldehyde, superoxide dismutase activity, and catalase activity. Key findings: ANXA5 treatment improved the TBI-induced intestinal mucosa injury at different timepoints and significantly increased the body weight. It significantly reduced apoptosis and matrix metalloproteinase-9 and inhibited the degradation of tight-junction-associated protein in the small intestine. ANXA5 treatment improved intestinal inflammation by regulating inflammation-associated factors. It also mitigated the lipid peroxidation products 4-HNE, 8-OHDG, and malonaldehyde, and enhanced the activity of the antioxidant enzymes, superoxide dismutase and catalase. Lastly, ANXA5 significantly enhanced nuclear factor E2-related factor 2 (Nrf2) and hemeoxygenase-1, and decreased high mobility group box 1 (HMGB1). Significance: Collectively, the results suggest that ANXA5 inhibits TBI-induced intestinal injury by restraining oxidative stress and inflammatory responses. The mechanisms involved sparking the Nrf2/hemeoxygenase-1-induced antioxidant system and suppressing the HMGB1 pathway. ANXA5 may be an attractive therapeutic candidate for protecting against TBI-induced intestinal injury.

Endoscopic endoclip papilloplasty preserves sphincter of oddi function.

BACKGROUND: Endoscopic sphincterotomy (EST) can destroy sphincter of Oddi (SO) structure and function. The purpose of this study was to assess the feasibility of endoscopic endoclip papilloplasty (EEPP) in restoring SO function after EST. METHODS: Seven 26-week-old domestic pigs were divided into control and EEPP groups. Necropsy and haematoxylin-eosin staining plus anti-α-smooth muscle actin (α-SMA) staining of papilla and sphincter of Oddi manometry (SOM) were conducted in animals at three independent time points. RESULTS: EST and EEPP were safely performed in all 7 pigs without serious adverse events. For primary outcome, compared to the controls, EEPP generated smaller dilation and less inflammation. Fibrous repair of the papilla was observed at 24 weeks after EEPP. For secondary outcome, in the control group, SO basal pressure (17.25 ± 18.14 to 5.50 ± 0.71 mmHg), SO contraction amplitude (46.00 ± 19.20 to 34.50 ± 48.79 mmHg), peak (4.50 ± 4.04 to 1.50 ± 2.12) and frequency (3.05 ± 3.29 to 1.41 ± 2.19/min) were reduced after EST. Further reductions to almost 0 of these SOM parameters were observed 3 weeks later, including common bile duct pressure and SO contraction period. In contrast, in the EEPP group, these manometric data were recovered to pre-EST levels, including CBD pressure (11.5 ± 7.31 vs 11 ± 2.16 mmHg), SO pressure (17.50 ± 17.75 vs 18.20 ± 21.39 mmHg) and SO contraction amplitude (53.67 ± 21.54 vs 60.00 ± 36.08 mmHg). However, no significant differences were observed between control and EEPP groups by Student t test. CONCLUSIONS: In this porcine study, EEPP accelerated and improved papillary healing after EST, further preserved SO function.

Endoclip papillaplasty restores sphincter of Oddi function: Pilot study.

OBJECTIVES: Endoscopic sphincterotomy (EST) damaged the sphincter of Oddi (SO) function. This study aimed to explore the feasibility and efficacy of endoclip papillaplasty in restoring SO function. METHODS: This prospective pilot study included consecutive patients with choledocholithiasis (stone size ≥10 mm) who underwent large-EST for stone removal, followed by endoclip papillaplasty, between May 2018 and March 2019. RESULTS: Thirty patients were enrolled in this trail. Overall, 80% of the patients had a SO basal pressure of >10 mmHg after endoclip papillaplasty. Manometric parameters, including SO basal pressure, phasic wave contraction amplitude, phasic waves per minute, recovered after endoclip papillaplasty (P > 0.05). There were no significant differences in the manometric parameters of SO between healing grades A and B. Six patients developed mild post-endoscopic retrograde cholangiopancreatography pancreatitis, including three that had pancreatic stenting. Bile duct stone recurrence developed in 3.3% of the patients (1/30) during an 18-month follow-up. CONCLUSIONS: Endoclip papillaplasty might restore SO function and possibly prevented biliary stone and cholangitis recurrence.

Comparison of Short-Term Efficacy Between Endoscopic Submucosal Tunnel Dissection and Endoscopic Submucosal Dissection in Treatment of Wide Esophageal Squamous Cell Carcinoma of Early Stage.

GOAL: The goal of this study was to compare the efficacy and safety of endoscopic submucosal tunnel dissection (ESTD) with endoscopic submucosal dissection (ESD) for the removal of early-stage esophageal squamous cancer wider than or equal to one half the circumference of the esophagus. BACKGROUND: Although ESD has been successfully applied for resection of early-stage esophageal cancer, there are still technical challenges and postoperative stenosis when it is applied to treat large lesions. PATIENTS AND METHODS: A total of 40 patients with early-stage esophageal cancer wider than or equal to one half its circumference were enrolled in this study and randomly assigned to an ESTD or ESD group for treatment of esophageal superficial squamous cell carcinoma. All of the patients received oral steroids after endoscopic dissection. We then compared the 2 groups in terms of average operating time, dissection speed, en bloc resection rate, R0 resection rate, and complications during a 1-year follow-up period. RESULTS: The dissection speed in the ESTD group was significantly faster than that in the ESD group (P=0.047). There were no significant differences in operating time, en bloc resection rates, or R0 resection rates between the ESTD and ESD group (P=0.319, 1.000, 1.000, respectively). There were also no significant differences in perforation, bleeding, or stenosis rates between the ESTD and ESD group (P=1.000, 0.748, 1.000, respectively). CONCLUSION: Both ESTD and ESD are safe and effective therapies for early-stage esophageal cancer wider than or equal to one half the esophageal circumference. The dissection speed of ESTD is faster than that of ESD.

The Significance of a Pale Area Via Flexible Spectral Imaging Color Enhancement in the Diagnosis of Esophageal Precancerous Lesions and Early-stage Squamous Cancer.

GOALS: The main aim of this study was to investigate the significance of a pale area via flexible spectral imaging color enhancement (FICE) in the diagnosis of esophageal dysplasia and cancer. BACKGROUND: The early diagnosis of esophageal squamous cancer is challenging, and the indication of Lugol's chromoendoscopy has not yet been well established. STUDY: The esophageal mucosa of patients at our endoscopic center were sequentially evaluated with white-light endoscopy and FICE during insertion of the endoscope, followed by staining with Lugol's solution during withdrawal. Patients were divided into 2 groups depending on whether esophageal leukoplakia was detected by white-light endoscopy and 2 groups depending on whether a pale area was detected by FICE. We compared cases of patients with abnormal iodine staining, and cases of dysplasia or cancer in esophageal leukoplakia-or pale area-positive and negative groups. RESULTS: Cases of abnormal staining in the esophageal leukoplakia-or pale area-positive group were far more numerous than cases without esophageal leukoplakia or pale area, respectively (P=0.000). Cases of esophageal dysplasia and cancer in the esophageal leukoplakia-or pale area-positive group were far more numerous than cases without esophageal leukoplakia or pale area, respectively (P=0.000). CONCLUSIONS: Iodine staining should be performed in patients with esophageal leukoplakia or pale areas. Esophageal dysplasia and early-stage cancer were more easily detected in those with esophageal leukoplakia or pale areas.

CMTM4 inhibits cell proliferation and migration via AKT, ERK1/2, and STAT3 pathway in colorectal cancer.

CMTM4 (CKLF-like MARVEL transmembrane domain containing 4), a potential tumor suppressor gene, is involved in several types of malignancies. It has been reported to be downregulated and exhibit anti-tumorigenic activities by regulating cell growth and cell cycle in clear cell renal cell carcinoma. It has also been identified as a tumor suppressor in hepatocellular carcinoma (HCC), and its negative expression is a risk factor for poor prognosis of HCC patients. In the present study, an integrated bioinformatics analysis based on The Cancer Genome Atlas (TCGA) database showed that CMTM4 was frequently reduced in colorectal cancer (CRC) and high expression of CMTM4 was associated with increased overall survival rates. Based on these findings, we adopted gain-of-function and lost-of-function strategies using SW480 and HT29 CRC cell lines which have relatively low and high endogenous CMTM4 levels, respectively. We observed impeded cell proliferation and migration upon overexpression of CMTM4 in SW480 cells, and the opposite effects were observed upon knockdown of CMTM4 in HT-29 cells. Cell signaling pathways essential for CRC progression were then examined, and the phosphorylation levels of AKT, ERK1/2, and STAT3 were found to be decreased by CMTM4 overexpression in SW480 cells and elevated by CMTM4 silencing in HT29 cells. Their inhibitors were used to validate that the three signaling pathways contributed to the inhibitory effects of CMTM4 on CRC cells. Taken together, our results suggest that CMTM4 plays a tumor suppressive role in CRC.

Clinicopathological features of duodenal bulb biopsies and their relationship with upper gastrointestinal diseases.

AIM: To assess the prevalence of the lesions in duodenal bulb mucosa and the relationship between duodenal lesions and upper gastrointestinal diseases, including helicobacter pylori infection. METHODS: Clinical, endoscopic and pathological data of the cases with duodenal bulb and gastric mucosal biopsy from January 2005 to May 2017 were analyzed retrospectively. RESULTS: A total of 3540 patients were enrolled. The biopsy from protuberant lesions with endoscopic morphology are mostly duodenal gastric heterotopia or adenoma. The biopsy from duodenal ulcers are often observed in inflammatory changes and gastric metaplasia. Patients with gastric heterotopia had a significantly lower prevalence of chronic atrophic gastritis, intestinal metaplasia, and gastric ulcer; and much higher prevalence of gastroesophageal reflux disease and gastric fundic polyps. Patients with gastric metaplasia had been positively associated with gastroesophageal reflux disease, and negatively associated with gastric fundic polyps. There were positive correlation between helicobacter pylori infection and duodenal active inflammation, Brunner gland hyperplasia, gastric metaplasia and duodenal ulcer. However, Patients with gastric heterotopia in bulb had been negatively associated with helicobacter pylori infection. CONCLUSIONS: The mucosa lesions in duodenal bulb were associated with concurrent gastric fundic gland polyps, gastroesophageal reflux disease, duodenal ulcer, and helicobacter pylori infection.

Prediction of three lipid derivatives for postoperative gastric cancer mortality: the Fujian prospective investigation of cancer (FIESTA) study.

BACKGROUND: As we previously reported, the presence of preoperative metabolic syndrome can predict the significant risk of gastric cancer mortality. As a further extension, we evaluated the prediction of three lipid derivatives generated from triglycerides (TG), total cholesterol (TC), high- and low-density lipoprotein cholesterol (HDLC and LDLC) at baseline for postoperative gastric cancer mortality by prospectively analysing 3012 patients. The three lipid derivatives included the ratio of TC minus HDLC to HDLC known as atherogenic index (AI), the ratio of TG to HDLC abbreviated as THR and the ratio of LDLC to HDLC abbreviated as LHR. METHODS: Gastric cancer patients who received gastrectomy between January 2000 and December 2010 were consecutively recruited from Fujian Cancer Hospital. Follow-up assessment was implemented annually before December 2015. RESULTS: Finally, there were 1331 deaths from gastric cancer and 1681 survivors, with a median follow-up time of 44.05 months. 3012 patients were evenly randomized into the derivation group and the validation group, and both groups were well balanced at baseline. Overall adjusted estimates in the derivation group were statistically significant for three lipid derivatives (hazard ratio [HR]: 1.20, 1.17 and 1.19 for AI, THR and LHR, respectively, all P < 0.001), and were reproducible in the validation group. The risk prediction of three lipid derivatives was more obvious in males than females, in patients with tumor-node-metastasis stage I-II than stage III-IV, in patients with intestinal-type than diffuse-type gastric cancer, in patients with normal weight than obesity, and in patients without hypertension than with hypertension, especially for AI and LHR, and all results were reproducible. Calibration and discrimination statistics showed good reclassification performance and predictive accuracy when separately adding three lipid derivatives to baseline risk model. A prognostic nomogram was accordingly built based on significant attributes to facilitate risk assessment, with a good prediction capability. CONCLUSIONS: Our results indicate that preoperative lipid derivatives, especially AI and LHR, are powerful predictors of postoperative gastric cancer mortality, with more obvious prediction in patients of male gender or with tumor-node-metastasis stage I-II or intestinal-type gastric cancer, and in the absence of obesity or hypertension before gastrectomy.

Hyperplastic polyps arising in autoimmune metaplastic atrophic gastritis patients: is this a distinct clinicopathological entity?

OBJECTIVES: Gastric hyperplastic polyp (GHP) commonly arises in the abnormal surrounding mucosa, including autoimmune metaplastic atrophic gastritis (AMAG). We aimed to compare clinicopathological features in patients with GHPs associated with AMAG with those in patients with GHPs associated with non-AMAG. PATIENTS AND METHODS: A total of 1170 patients with GHP(s) were enrolled, and their clinical and pathological data were analyzed, retrospectively. RESULTS: The GHP patients were divided into 181 A-GHP (type A GHP, AMAG-associated GHP) participants, 312 B-GHP (type B GHP, Helicobacter pylori infection-associated GHP) participants, and 677 other GHP participants (non-A-GHP and non-B-GHP) based on pathological status of the surrounding non-polypoid mucosa. The A-GHP patients were older and predominantly female (p < .05). Gastroscopically, A-GHPs showed less distal and more multiple-region distribution in the stomach (p < .001). In addition, the A-GHPs were observed to be usually numerous (55.8%), larger (mean maximum diameter 12.3 mm), and more pedunculated or sub-pedunculated (45.3%) (p < .001). Histopathologically, the intestinal metaplasia, intraepithelial neoplasia, and carcinomatous transformation within GHPs were present in 24.3%, 9.9%, and 2.8% of AMAG patients, respectively, which were significantly higher than those in the B-GHPs and other GHPs (p < .05). However, the differences of intraepithelial neoplasia and adenocarcinoma in surrounding non-polypoid mucosa did not reach statistical significance (p > .05). CONCLUSIONS: The GHP(s) arising in AMAG patients is a distinct subgroup of GHP(s) and was an important precancerous lesion. The biopsy from surrounding non-polypoid mucosa was essential to evaluate the underlying etiology of the GHPs, and endoscopists should pay attention to these.

Endoscopic molecular imaging of early gastric cancer using fluorescently labeled human H-ferritin nanoparticle.

Optical imaging technologies improve clinical diagnostic accuracy of early gastric cancer (EGC). However, there was a lack of imaging agents exhibiting molecular specificity for EGCs. Here, we employed the dye labeled human heavy-chain ferritin (HFn) as imaging nanoprobe, which recognizes tumor biomarker transferrin receptor 1 (TfR1), to enable specific EGC imaging using confocal laser endomicroscopy (CLE). TfR1 expression was initially examined in vitro in gastric tumor cells and in vivo through whole-body fluorescence and CLE imaging in tumor-bearing mice. Subsequently, dye labeled HFn was topically applied to resected human tissues for EGC detection. CLE analysis of TfR1-targeted fluorescence imaging allowed distinction of neoplastic from non-neoplastic tissues (P < 0.0001), and TfR1 expression level was found to correlate with EGC differentiation degrees (P < 0.0001). Notably, the CLE evaluation correlated well with the immunohistochemical findings (κ-coefficient: 0.8023). Our HFn-nanoprobe-based CLE increases the accuracy of EGC detection and enables visualization of tumor margins and endoscopic resection.

Autoimmune metaplastic atrophic gastritis in chinese: a study of 320 patients at a large tertiary medical center.

OBJECTIVES: Autoimmune metaplastic atrophic gastritis (AMAG) is an uncommon disease worldwide and may predispose to gastric carcinoid tumors or adenocarcinomas. The aims of this study were to outline the clinical characteristics of Chinese AMAG patients, including demographic pattern, hematologic features, and gastroscopic and histopathologic findings. PATIENTS AND METHODS: A total of 320 Chinese patients with AMAG, from January 2007 to December 2014, were reviewed in a regional hospital of China. RESULTS: Of the 320 AMAG patients, the mean age was 60.6 ± 12.3 years [range 26-86; 206 (64.4%) women]. The coarse annual detection rate was 0.9%. Anemia was present in only 19.3% patients (53/275) and 3.5% (11/315) AMAG patients also had primary biliary cirrhosis. One hundred and thirty-six had endoscopically identifiable lesions. These lesions consisted of 130 polypoid lesions (63 hyperplastic polyps, 2 oxyntic mucosa pseudopolyps, 2 intestinal-type gastric adenomas, 2 fundic gland polyps, 5 concurrent polyps, 14 well-differentiated neuroendocrine neoplasms, 7 submucosal tumors and 35 chronic gastritis), 6 adenocarcinomas. The detection rate of atrophy and intestinal metaplasia in antral mucosa were 47.2 and 37.5%, respectively. CONCLUSIONS: AMAG is more frequent than expected in China and display a female predominance, accompanied with other autoimmune disorders. AMAG should be paid more attention by clinicians through a multidisciplinary team approach.

Preoperative metabolic syndrome and prognosis after radical resection for colorectal cancer: The Fujian prospective investigation of cancer (FIESTA) study.

This prospective study sought to investigate the prediction of preoperative metabolic syndrome and its components for the risk of colorectal cancer (CRC) mortality by analyzing a subset of data from the ongoing Fujian prospective investigation of cancer (FIESTA) study. In total, 1,318 CRC patients who received radical resection were consecutively enrolled between January 2000 and December 2008. The median follow-up time was 58.6 months, with 412 deaths from CRC. The CRC patients with metabolic syndrome had significantly shorter median survival time (MST) than those without (50.9 vs. 170.3 months, p < 0.001). Among four components of metabolic syndrome, hyperglycemia was the strongest predictor and its presence was associated with shorter MST than its absence (44.4 vs. 170.3 months, p < 0.001). Moreover, the complication of metabolic syndrome in CRC patients was associated with a 2.98-fold increased risk of CRC mortality (hazard ratio [HR] = 2.98, 95% confidence interval [CI]: 2.40-3.69, p < 0.001) after adjusting for confounding factors. The magnitude of this association was especially potentiated in CRC patients with tumor-node-metastasis stage I/II (HR = 3.94, 95% CI: 2.65-5.85, p < 0.001), invasion depth T1/T2 (HR = 5.41, 95% CI: 2.54-11.50, p < 0.001), regional lymph node metastasis N0 (HR = 4.06, 95% CI: 2.85-5.80, p < 0.001) and negative distant metastasis (HR = 3.23, 95% CI: 2.53-4.12, p < 0.001). Further survival tree analysis reinforced the prognostic capability of fasting blood glucose in CRC survival. Our findings convincingly demonstrated that preoperative metabolic syndrome, especially hyperglycemia, was a robust predictor for CRC mortality, and the protection was more obvious in patients with Stage I/II.

[Analysis of clinical, endoscopic and pathological characteristics of gastric hyperplastic polyps].

OBJECTIVE: To investigate the clinical, endoscopic and pathologic characteristics of gastric hyperplastic polyps. METHODS: A total of 1 676 gastric hyperplastic polyps patients diagnosed by gastroscopy and pathology from January 2005 to October 2014 were enrolled and analyzed retrospectively. RESULTS: Among them, 1 030 patients (61.46%) were female, 1 014 patients (60.50%) aged ≥ 60 years old, 1 093 patients (65.21%) polyps distributed in the fundus and body of stomach. And the concurrent conditions included dysplasia in polyps tissue (n = 89, 5.31%), intestinal metaplasia (n = 94, 5.61%), focal carcinoma (n = 5, 0.30%). In the background gastric mucosa included Helicobacter pylori gastritis (n = 368, 21.96%), autoimmune gastritis (n = 238, 14.20%), intestinal metaplasia (n = 379, 22.61%), dysplasia (n = 110, 6.56%), adenocarcinoma (n = 13, 0.78%), carcinoid tumor (n = 3, 0.18%). CONCLUSIONS: Hyperplastic polyps are mainly distributed in the proximal stomach, and malignant transformation may be detected in hyperplastic polyps. Whereas, both precancerous lesions and malignant transformation are detected in background gastric mucosa. Therefore, the endoscopist should always pay attention to background gastric mucosa.

[Adult-onset generalized autoimmune enteropathy involving small intestine and colon: report of a case and review of literature].

OBJECTIVE: To investigate the clinicopathologic features of adult-onset autoimmune enteropathy (AIE). METHODS: A case of adult-onset AIE was described along with a literature review. RESULTS: A 41-year-old male patient was admitted for intractable diarrhea for more than three months despite of any dietary restriction or anti-inflammatory therapy. Fat globule was observed by stool examination and Sudan III staining of the stool was positive. Enteroclysis showed weak movement and few plica of small intestine, while colonoscopy appeared normal. Small bowel biopsies revealed villus atrophy and increased crypt apoptotic bodies and lymphocytic infiltration in deep crypt. Although without significant surface intro-epithelial lymphocytosis, there were a large number of monocytes, lymphocytes, plasmacytes and neutrophilic granulocytes infiltrating in the lamina propria. Morphologically, the colonic mucous was similar to the small intestine although cryptitis and crypt abscess were significant in the former. Serum IgG anti-goblet cell antibody was demonstrated by indirect immunofluorescence. Other causes of diarrhea were excluded on the base of medical history, histopathology and other accessory examinations before the diagnosis of AIE was made. The patient had a complete remission after steroid treatment without recurrence for eight months during the follow-up even after steroid withdrawal for five months. CONCLUSIONS: AIE is exceedingly rare and timely diagnosis is important for successful therapy. Histological differential diagnoses should include ulcerative colitis, celiac disease, lymphocytic colitis, etc. The final diagnosis should be based on histological examination combined with the patient history, clinical manifestation, endoscopy finding and serological testing.

Serum proteomic profiling of precancerous gastric lesions and early gastric cancer reveals signatures associated with systemic inflammatory response and metaplastic differentiation.

The noninvasive detection technique using serum for large-scale screening is useful for the early diagnosis of gastric cancer (GC). Herein, we employed liquid chromatography mass spectrometry to determine the serum proteome signatures and related pathways in individuals with gastric precancerous (pre-GC) lesions and GC and explore the effect of Helicobacter pylori (H. pylori) infection. Differentially expressed proteins in GC and pre-GC compared with non-atrophic gastritis (NAG) group were identified. APOA4, a protein associated with metaplastic differentiation, and COMP, an extracellular matrix protein, were increased in the serum of patients with pre-GC lesions and GC. In addition, several inflammation-associated proteins, such as component C3, were decreased in the GC and pre-GC groups, which highlight a tendency for the inflammatory response to converge at the gastric lesion site during the GC cascade. Moreover, the abundance of proteins associated with oxidant detoxification was higher in the GC group compared with that in the NAG group, and these proteins were also increased in the serum of the H. pylori-positive GC group compared with that in the H. pylori-negative GC patients, reflecting the importance of oxidative stress pathways in H. pylori infection. Collectively, the findings of this study highlight pathways that play important roles in GC progression, and may provide potential diagnostic biomarkers for the detection of pre-GC lesions.