Role of Extracellular Vesicles in Placental Inflammation and Local Immune Balance.

BACKGROUND: Pregnancy maintenance depends on the formation of normal placentas accompanied by trophoblast invasion and vascular remodeling. Various types of cells, such as trophoblasts, endothelial cells, immune cells, mesenchymal stem cells (MSCs), and adipocytes, mediate cell-to-cell interactions through soluble factors to maintain normal placental development. Extracellular vesicles (EVs) are diverse nanosized to microsized membrane-bound particles released from various cells. EVs contain tens to thousands of different RNA, proteins, small molecules, DNA fragments, and bioactive lipids. EV-derived microRNAs (miRNAs) and proteins regulate inflammation and trophoblast invasion in the placental microenvironment. Maternal-fetal communication through EV can regulate the key signaling pathways involved in pregnancy maintenance, from implantation to immune regulation. Therefore, EVs and the encapsulating factors play important roles in pregnancy, some of which might be potential biomarkers. CONCLUSION: In this review, we have summarized published studies about the EVs in the placentation and pregnancy-related diseases. By summarizing the role of EVs and their delivering active molecules in pregnancy-related diseases, it provides novel insight into the diagnosis and treatment of diseases.

MiR-6869-5p Induces M2 Polarization by Regulating PTPRO in Gestational Diabetes Mellitus.

The role of microRNA (miRNA) in gestational diabetes mellitus has been widely investigated during the last decade. However, the altering effect of miR-6869-5p on immunity and placental microenvironment in gestational diabetes mellitus is largely unknown. In our study, the expression of miR-6869-5p was documented to be significantly decreased in placenta-derived mononuclear macrophages, which was also negatively related to PTPRO. Besides, PTPRO was negatively regulated by miR-6869-5p in placenta-derived mononuclear macrophages. In vitro, miR-6869-5p inhibited macrophage proliferation demonstrated by EdU and CCK-8 experiments. The inflammatory response in macrophages was also significantly inhibited by miR-6869-5p, which could regulate PTPRO as a target documented by luciferase reporter assay. Moreover, miR-6869-5p promoted M2 macrophage polarization and thus restrain inflammation. Accordingly, miR-6869-5p is involved in maintaining placental microenvironment balance by preventing from inflammation and inducing M2 macrophages in gestational diabetes mellitus.

MiR-6803-5p Promotes Cancer Cell Proliferation and Invasion via PTPRO/NF-κB Axis in Colorectal Cancer.

Accumulated studies have implicated microRNAs (miRNAs) exert modifying effects on colorectal cancer (CRC). Protein tyrosine phosphatase, receptor type O (PTPRO) has been identified as a tumor suppressor in several kinds of cancer, including CRC. Previously, we have found that exosome-encapsulated miR-6803-5p is increased in CRC. However, the mechanism of miR-6803-5p in CRC is not clear yet. This study is aimed at elucidating the effect of miR-6803-5p in colorectal carcinogenesis. Expression of miR-6803-5p and PTPRO mRNA in peripheral blood mononuclear cells of CRC patients is estimated by real-time PCR. PTPRO protein in CRC cells is detected by western blot. To verify the association of miR-6803-5p with PTPRO, luciferase reporter assay is performed. CCK-8 and EdU assays are conducted to assess cell proliferation. Real-time PCR and ELISA are applied to detect cytokine expression in CRC cells. Cell invasion and migration assays are evaluated by transwell and scratch tests. Immunofluorescence is carried out to determine the activation of NF-κB in HCT116 cells. Negative correlation is demonstrated between miR-6803-5p and PTPRO in CRC. PTPRO is demonstrated to be a direct target of miR-6803-5p. miR-6803-5p can promote cancer cell proliferation and invasion and enhance inflammation through PTPRO/NF-κB axis in CRC, which serves as a useful target for CRC.

MiRNA-548c-5p downregulates inflammatory response in preeclampsia via targeting PTPRO.

Preeclampsia is a serious complication of pregnancy and leads to maternal hypertension and proteinuria. It remains a major health problem for mothers and babies across the world due to high maternal and fetal morbidity and mortality. Accumulated data have implicated the critical role of microRNA in preeclampsia. However, to date, the role of miR-548c-5p in preeclampsia remains vaguely understood. In this study, we first elucidate the role of miR-548c-5p and its underlying molecular mechanism in preeclampsia. Compared with healthy controls, miR-548c-5p was obviously downregulated in serum exosomes and placental mononuclear cells in patients with preeclampsia. Nonetheless, PTPRO was significantly upregulated and negatively associated with miR-548c-5p in placental mononuclear cells in patients with preeclampsia. PTPRO was a target of miR-548c-5p. PTPRO was downregulated in the miR-548c-5p-overexpressed macrophages. In addition, miR-548c-5p could inhibit the proliferation and activation of LPS-stimulated macrophages, as evidenced by decreased levels of inflammatory cytokines (IL-12 and TNF-α) and less nuclear translocation of pNF-κB in pTHP1 cells. MiR-548c-5p acts as an anti-inflammatory factor in preeclampsia. The axis of miR-548c-5p/PTPRO/NF-κB may provide novel targets for the diagnosis and treatment of preeclampsia.

Dysregulation of microRNA-657 influences inflammatory response via targeting interleukin-37 in gestational diabetes mellitus.

A number of studies have implicated that microRNAs (miRNAs) play a critical role in the development of gestational diabetes mellitus (GDM). However, the role of miR-657 in GDM remains vague up to date. We aim to investigate the modifying effect of miR-657 on GDM, which will provide new insight into the pathogenesis of GDM and may help to identify new diagnostic or therapeutic targets for GDM. Increased expression of miR-657 but decreased expression of interleukin-37 (IL-37) was observed in patients with GDM. Besides, negative association between miR-657 and IL-37 was demonstrated in this study. miR-657 could targetedly regulate IL-37 and enhance the proliferation of mononuclear macrophages. Moreover, miR-657 promoted the generation of inflammatory cytokines (IL-6 and tumor necrosis factor-α [TNF-α]) and activation of nuclear factor κB (NF-κB) in lipopolysaccharide-induced mononuclear macrophages, while its effect was significantly inhibited when exogenous recombinant IL-37 was administrated into cells. Accordingly, dysregulation of miR-657 contributes to the pathogenesis of GDM via IL-37/NF-κB signaling axis.

miR-657 Promotes Macrophage Polarization toward M1 by Targeting FAM46C in Gestational Diabetes Mellitus.

MicroRNA (miRNA) has been widely suggested to play a vital role of in the pathogenesis of gestational diabetes mellitus (GDM). We have previously demonstrated that miR-657 can regulate macrophage inflammatory response in GDM. However, the role of miR-657 on M1/M2 macrophage polarization in GDM pathogenesis is not clear yet. This study is aimed at elucidating this issue and identifying novel potential GDM therapeutic targets based on miRNA network. miR-657 is found to be upregulated in placental macrophages demonstrated by real-time PCR, which can enhance macrophage proliferation and migration in vitro. Luciferase reporter assay shows the evidence that FAM46C is a target of miR-657. In addition, miR-657 can promote macrophage polarization toward the M1 phenotype by downregulating FAM46C in macrophages. The present study strongly suggests miR-657 is involved in GDM pathogenesis by regulating macrophage proliferation, migration, and polarization via targeting FAM46C. miR-657/FAM46C may serve as promising targets for GDM diagnosis and treatment.

MicroRNA-6869-5p acts as a tumor suppressor via targeting TLR4/NF-κB signaling pathway in colorectal cancer.

Many studies have implicated that microRNAs (miRNAs), as non-coding RNAs, play important roles in the development and progression of colorectal cancer (CRC). However, little is known about the role of a newly identified miRNA, miR-6869-5p, in CRC. We aim to investigate the modifying effects and underlying mechanisms of miR-6869-5 in colorectal carcinogenesis and progression. Significantly reduced levels of miR-6869-5p were observed in both serum exosomes tumor tissue samples from patients with CRC. The prediction of targets of miR-6869-5p in databases of targetscan, microRNA. ORG and miRDBA revealed that toll-like receptor 4 (TLR4) is a potential target for this miRNA. MiR-6869-5p could inhibit cell proliferation and the production of inflammatory cytokines (TNF-α and IL-6) in CRC cells via directly targeting TLR4. The protective effect of miR-6869-5p from colorectal carcinogenesis was dependent on TLR4/NF-κB signaling pathway. In addition, the 3-year survival was poor among CRC patients with decreased levels of miR-6869-5p in serum exosomes. Thus, miR-6869-5p may serve as a tumor suppressor in CRC, and serum exosomal miR-6869-5p is a promising circulating biomarker for the prediction of CRC prognosis.

Expression of ERO1L in gastric cancer and its association with patient prognosis.

The present study aimed to assess the expression of endoplasmic reticulum oxidoreductin-1-like (ERO1L) in gastric cancer and determine its association with patient prognosis. A total of 105 patients with gastric cancer undergoing radical gastrectomy were selected for the current study. Gastric cancer tissues (the observation group) and normal gastric tissue adjacent to the carcinoma (the control group) were resected from patients. Levels of ERO1L mRNA and protein in tumor tissues and adjacent tissues were detected using reverse transcription-quantitative polymerase chain reaction, western blotting and immunohistochemistry. Patients were divided into two groups: A positive group and negative group, according to the expression of ERO1. The expression of ERO1L in gastric cancer and its association with patient prognosis was analyzed. Levels of ERO1 mRNA and protein in gastric cancer were significantly higher than those of adjacent tissues (P<0.05). Immunohistochemical analysis demonstrated that there were 22 patients exhibiting negative expression of ERO1L and 83 patients exhibiting positive expression of ERO1L. The cumulative recurrence rates over 3 years in patients with positive expression of ERO1L were significantly higher than in patients with negative expression of ERO1L (P<0.05); the cumulative survival rates over 3 years in patients with positive expression of ERO1L were significantly lower than those of patients with negative expression of ERO1L (P<0.05). Thus, the current study determined that ERO1L was highly expressed in gastric cancer tissue. The high expression of ERO1L was associated with adverse prognoses in patients with gastric cancer. ERO1L may therefore be a therapeutic target for the prevention of gastric cancer.

Exosome-encapsulated microRNAs as circulating biomarkers for colorectal cancer.

Currently available studies have suggested that a number of exosome-encapsulated microRNAs (miRNAs) are recognized as stable biomarkers for cancers. However, little is known about the effect of exosomal miRNAs on colorectal cancer (CRC). The aim of study is to identify specific miRNAs in serum exosomes, which may serve as potential diagnostic and prognostic biomarkers and therapeutic targets for CRC. Microarray analyses of miRNAs in serum exosomes from 3 primary CRC patients and 3 healthy controls were performed. Those differentially expressed exosome-encapsulated miRNAs were verified in exosome-enriched serum samples from 77 CRC patients and 20 healthy controls by quantitative real-time PCR (qRT-PCR). A total of 39 aberrantly expressed miRNAs in serum exosomes were identified by microarray analysis. After confirmation by qRT-PCR, we found that 5 exosome-encapsulated miRNAs (miR-638, miR-5787, miR-8075, miR-6869-5p and miR-548c-5p) were significantly down-regulated, while 2 exosome-encapsulated miRNAs (miR-486-5p and miR-3180-5p) were significantly up-regulated in serum. Decreased levels of miR-638 in serum exosomes were associated with increased risk of liver metastasis and later TNM stage of CRC. Networks analyses revealed that 5 aberrantly expressed miRNAs (miR-638, miR-5787, miR-8075, miR-6869-5p, and miR-548c-5p) might be involved in the process of glucose metabolism in CRC. The present study shows the specific serum profile of exosome-encapsulated miRNAs in CRC. Those specific miRNAs in serum exosomes may serve as disease biomarkers and novel therapeutic targets for CRC.

Hypertensive disorders during pregnancy and risk of type 2 diabetes in later life: a systematic review and meta-analysis.

Many studies assessed the association between hypertensive disorders during pregnancy and risk of type 2 diabetes mellitus in later life, but contradictory findings were reported. A systemic review and meta-analysis was carried out to elucidate type 2 diabetes mellitus risk in women with hypertensive disorders during pregnancy. Pubmed, Embase, and Web of Science were searched for cohort or case-control studies on the association between hypertensive disorders during pregnancy and subsequent type 2 diabetes mellitus. Random-effect model was used to pool risk estimates. Bayesian meta-analysis was carried out to further estimate the type 2 diabetes mellitus risk associated with hypertensive disorders during pregnancy. Seventeen cohort or prospective matched case-control studies were finally included. Those 17 studies involved 2,984,634 women and 46,732 type 2 diabetes mellitus cases. Overall, hypertensive disorders during pregnancy were significantly correlated with type 2 diabetes mellitus risk (relative risk = 1.56, 95 % confidence interval 1.21-2.01, P = 0.001). Preeclampsia was significantly and independently correlated with type 2 diabetes mellitus risk (relative risk = 2.25, 95 % confidence interval 1.73-2.90, P < 0.001). In addition, gestational hypertension was also significantly and independently correlated with subsequent type 2 diabetes mellitus risk (relative risk = 2.06, 95 % confidence interval 1.57-2.69, P < 0.001). The pooled estimates were not significantly altered in the subgroup analyses of studies on preeclampsia or gestational hypertension. Bayesian meta-analysis showed the relative risks of type 2 diabetes mellitus risk for individuals with hypertensive disorders during pregnancy, preeclampsia, and gestational hypertension were 1.59 (95 % credibility interval: 1.11-2.32), 2.27 (95 % credibility interval: 1.67-2.97), and 2.06 (95 % credibility interval: 1.41-2.84), respectively. Publication bias was not evident in the meta-analysis. Preeclampsia and gestational hypertension are independently associated with substantially elevated risk of type 2 diabetes mellitus in later life.

Expression of GOLPH3 protein in colon cancer tissues and its association with the prognosis of patients.

The present study aimed to investigate the expression of Golgi phosphoprotein-3 (GOLPH3) protein in colon cancer tissues and the association with the prognosis of patients. In total, 98 patients with colon cancer admitted to The First Affiliated Hospital of Henan University of Science and Technology for surgery between June 2011 and June 2013 were taken as the observation group. In addition, 15 healthy individuals, determined by enteroscopy, were taken as the control group. The expressions of GOLPH3 mRNA and protein were detected by reverse transcription-polymerase chain reaction and immunohistochemistry, respectively. The patients were divided into GOLPH3-positive and GOLPH3-negative groups according to the expression of GOLPH3. The expression of GOLPH3 in colon cancer and its association with the prognosis of patients was analyzed. The expression of GOLPH3 mRNA and protein in colon cancer tissues was significantly increased compared with normal colon mucosa (P<0.05); among the tissues, GOLPH3 was not expressed in 29 patients and positively expressed in 69 patients. The expression of GOLPH3 was negatively associated with the tumor differentiation degree, and positively associated with tumor invasion depth, lymph node metastasis and clinical stages in GOLPH3-positive patients. The cumulative recurrence rates at 1, 2 and 3 years were significantly lower in GOLPH3-negative patients (P<0.05). The survival rates at 1, 2 and 3 years in the GOLPH3-positive group were significantly higher than that of the GOLPH3-negative patients (P<0.05). In conclusion, the positive expression of GOLPH3 mRNA and protein in colon cancer tissue was significantly increased compared with the control group. GOLPH3 expression was closely associated with the pathological features, consisting of tissue typing, clinical stage, degree of tumor invasion and lymph node metastasis, and GOLPH3 expression. Patients with GOLPH3 overexpression also had a poor prognosis.

Glutathione S-transferase M1 null genotype related to poor prognosis of colorectal cancer.

Published studies showed controversial findings about the relationship between glutathione S-transferase M1 (GSTM1) null genotype and clinical outcomes of patients with colorectal cancer. We performed a meta-analysis to quantitatively assess the association between GSTM1 null genotype and prognosis of patients with colorectal cancer. We systematically searched Pubmed, Embase, and Web of Science to identify prospective or retrospective cohort studies assessing the association of GSTM1 null genotype with overall survival (OS) or disease-free survival (DFS) in colorectal cancer. The hazard ratios (HRs) and 95 % confidence intervals (95 % CIs) were used to assess the association of GSTM1 null genotype with OS or DFS. Finally, 15 studies from 14 publications with 4326 colorectal cancer patients were included into the meta-analysis. There was no heterogeneity in the meta-analysis relating OS (I (2) = 0 %) and DFS (I (2) = 0 %). Overall, GSTM1 null genotype was significantly associated with poor OS in patients with colorectal cancer (HR = 1.18, 95 % CI 1.07-1.30, P = 0.001). In addition, GSTM1 null genotype was also significantly associated with poor DFS in patients with colorectal cancer (HR = 1.15, 95 % CI 1.03-1.28, P = 0.015). No obvious risk of publication bias was observed. GSTM1 null genotype is significantly associated with poor OS and DFS in patients with colorectal cancer, which suggests that GSTM1 null genotype confers poor effect on the prognosis of colorectal cancer.

Maternal Thyroxine Levels During Pregnancy and Outcomes of Cognitive Development in Children.

Though there were many studies assessing the relationship between maternal thyroxine levels during pregnancy and cognitive development in children, there was still lack of evidence for the association from a comprehensive assessment of published data. To get a more comprehensive estimate of the influence of low maternal thyroxine levels on cognitive function, a meta-analysis of prospective cohort studies was performed. Two electronic databases, MEDLINE and EMBASE, were searched for relevant prospective cohort studies. Relative risks (RR) with 95% confidence intervals (95% CI) were pooled using random-effect model of meta-analysis to assess the risk of delayed cognitive development in children. Seven prospective cohort studies with a total of 8273 mother-child pairs were included into the meta-analysis. There was obvious between-study heterogeneity in the meta-analysis (I(2) = 69.6%). Meta-analysis of using random-effect model showed that low maternal thyroxine level was significantly associated with a threefold risk of delayed cognitive development in children (random RR = 3.08, 95% CI 1.83-5.18, P < 0.001). When excluding the study with largest weight, there was no obvious between-study heterogeneity in the left studies (I(2) = 47.6%), and meta-analysis using random-effect model showed that low maternal thyroxine level was still significantly associated with increased risk of delayed cognitive development in children (random RR = 3.76, 95% CI 2.14-6.58, P < 0.001). Sensitivity analysis by omitting other studies by turns showed that there was no obvious change in the pooled risk estimates, and all pooled RRs were statistically significant. Therefore, the findings from the meta-analysis provide strong evidence for the association between maternal thyroxine levels during pregnancy and cognitive development in children. Low maternal thyroxine level is significantly associated with a threefold risk of delayed cognitive development in children.

The diagnosis value of promoter methylation of UCHL1 in the serum for progression of gastric cancer.

BACKGROUND: Aberrant promoter methylation has been considered as a potential molecular marker for gastric cancer (GC). However, the role of methylation of FLNC, THBS1, and UCHL1 in the development and progression of GC has not been explored. METHODS: The promoter methylation status of UCHL1, FLNC, THBS1, and DLEC1 was assessed by quantitative methylation-specific PCR (QMSP) in the serum of 82 GC patients, 46 chronic atrophic gastritis (CAG) subjects, and 40 healthy controls. RESULTS: All four genes had significantly higher methylation levels in GC patients than in CAG and control subjects. However, only UCHL1 methylation was significantly correlated with the tumor stage and lymph node metastasis. While THBS1 methylation was altered in an age-dependent manner, FLNC methylation was correlated with differentiation and Helicobacter pylori infection. DLEC1 methylation was only associated with tumor size. Moreover, methylated UCHL1 with or without THBS1 in the serum was found to be significantly associated with a poor prognosis. CONCLUSION: The promoter methylation degree of FLNC, THBS1, UCHL1, and DLEC1 in serum could tell the existence of GC and only UCHL1 in the serum was also associated with poor prognosis of GC.

Risk factors for the Long-Term Efficacy, Recurrence, and Metastasis in Small Hepatocellular Carcinomas.

We tried to determine the risk factors for the long-term efficacy, recurrence, and metastasis of small hepatocellular carcinoma (HCC, diameter <5 cm). One hundred sixty-eight small liver cancer patients received percutaneous cryoablation therapy by argon-helium superconducting surgery system under the ultrasound guidance. Clinical parameter and the efficacy were analyzed after follow-up. After cryoablation treatment, the median follow-up time for the 168 patients was 36 (7-41) months. Liver functions were impaired as indicated by increased alanine aminotransferase, total bilirubin, total protein, albumin, and prothrombin activity. The difference of VEGF expression in liver cancer and the surrounding tissue is significant. 1-, 2-, and 3-year overall survival were 92.9, 83.9, and 65.5 %, respectively. Relapse-free survival was 76.8, 53.0, and 41.1 %. Less tumor number, higher tumor differentiation, and low VEGF expression predict higher metastasis-free and relapse-free survival rate. Lower Child-Pugh classification is correlated with the higher overall survival after cryoablation. There was no statistical significance in in situ intrahepatic recurrence patients, but VEGF changes were statistically significant for metastasis in other parts of liver or extrahepatic metastasis. Tumor number, differentiation, VEGF expression, large vessel invasion, lymph node, and extrahepatic metastasis all affect the overall and relapse-free survival. VEGF expression can be a predictable factor for liver cancer recurrence and metastasis.

Serum CA242, CA199, CA125, CEA, and TSGF are Biomarkers for the Efficacy and Prognosis of Cryoablation in Pancreatic Cancer Patients.

This study aimed to compare the changes and determine the clinical significance of carbohydrate antigens CA242, CA199, CA125, carcinoembryonic antigen (CEA), and tumor-specific growth factor (TSGF) before and after cryoablation by Cryocare system. Thirty-one pancreatic cancer patients were selected to receive cryoablation by Cryocare system. The serum expression levels of CA242, CA199, CA125, CEA, and TSGF before and 1 month after treatment were determined. Meanwhile, the serum level of these factors was also determined in 31 healthy volunteers. The parameter changes were analyzed with the clinical pathological data. The serum levels of CA242, CA199, CA125, CEA, and TSGF in the pancreatic cancer group were significantly higher than those of the control group both before and after the cryoablation treatment (P < 0.05). The serum CA199, CEA, and TSGF dramatically decreased 1 month after the treatment, which were statistically different (P < 0.05). The positive rates of serum CA242, CA199, CA125, and CEA in the pancreatic cancer group were much higher than those in the control group both before and after treatment (P < 0.05), and the positive rate of TSGF was significantly higher than that of the control group before the treatment (P < 0.05). The positive rate of CA199, CEA, and TSGF after the treatment was significantly lower than that before the treatment (P < 0.05). Serum level of CA242 was correlated with the tumor diameter, clinical staging, tumor differentiation, lymph node, and liver metastasis (P < 0.05). Except gender, CA199 was correlated with all the other clinical pathological parameters (P < 0.05). The serum levels of CA125 and CEA were correlated with all the other clinical pathological parameters (P < 0.05). The serum level of TSGF was only correlated with tumor differentiation (P < 0.05). Cryoablation treatment by Cryocare system can decrease the serum levels of CA199, CEA, TSGF, and the positive rate. Serum CA199, CEA, and TSGF can be important index for pancreatic cancer treatment assessment. Serum levels of CA242, CA199, CA125, and CEA are of great clinical value for metastasis assessment and prognosis in pancreatic cancer patients.

High leptin level is an independent risk factor of endometrial cancer: a meta-analysis.

BACKGROUND/AIMS: Previous studies suggested that high leptin level might increase risk of endometrial cancer, but available data were conflicting and whether high leptin level was an independent risk factor of endometrial cancer was still unclear. Therefore, a meta-analysis was performed to assess whether high leptin level was an independent risk factor of endometrial cancer. METHODS: PubMed, Web of Science, and Embase databases were searched for epidemiological studies published up to June 26, 2014. The pooled risk ratio (RR) with 95% confidence interval (95%CI) was used to assess the association between leptin level and risk of endometrial cancer. RESULTS: Six studies with a total of 3136 individuals were finally included into the meta-analysis. Meta-analysis of total 6 studies showed that high leptin level was associated with increased risk of endometrial cancer (RR = 2.55, 95%CI 1.91-3.41, P < 0.001). After adjusting for confounding factors, high leptin level was also associated with increased risk of endometrial cancer (RR =1.59, 95%CI 1.27-1.98, P < 0.001). Sensitivity analysis proved the stability of the pooled estimates. The RR of endometrial cancer was 1.10 (95%CI, 1.03-1.18, P = 0.005) per 5 ng/mL increment in leptin levels. There was no obvious risk of publication bias (P Egger = 0.54). CONCLUSION: Our findings suggest that high leptin level is an independent risk factor of endometrial cancer. More prospective studies are needed to further confirm the association in the future.

[Two types of digestive tract reconstruction after proximal gastrectomy for early gastroesophageal junction adenocarcinoma: a randomized controlled study].

OBJECTIVE: To investigate the better method of digestive tract reconstruction in proximal gastrectomy for early gastroesophageal junction adenocarcinoma. METHODS: A total of 153 cases of early gastroesophageal junction adenocarcinoma who were planned to receive radical proximal gastrectomy from January 2003 to December 2011 were prospectively enrolled and randomly divided into two groups by table of random number according to methods of digestive tract reconstruction, including 3S anastomosis group (80 cases, 3S jejunal interposition) and traditional anastomosis group (73 cases, esophageal remnant gastric posterior wall anastomosis). Postoperative complications, operative time, mortality, nutritional parameters and postoperative quality of life were compared between these two groups. RESULTS: There were no significant differences between two groups in postoperative complications, operative time and mortality (all P>0.05). 3S anastomosis group was better in nutritional parameters than traditional group six months after operation (P<0.05). As compared to traditional group, incidence of reflux esophagitis decreased [20.0%(16/80) vs. 46.6%(34/73), P<0.01] and gastric emptying time prolonged obviously [(160.8±8.1) min vs. (61.1±10.8) min, P<0.01] in 3S anastomosis group 18 months after operation. Postoperative QLQ-C30 rating scale revealed quality of life was significantly higher in 3S anastomosis group as compared to traditional group. CONCLUSION: Jejunal interposition is a better method of digestive tract reconstruction in proximal gastrectomy for early gastroesophageal junction carcinoma.

[Promotion of postoperative recovery with fast track surgery for gastric cancer patients undergoing gastrectomy: a prospective randomized controlled study].

OBJECTIVE: To study the safety and feasibility of fast track surgery (FTS) in the promotion of postoperative recovery for gastric cancer patients undergoing gastrectomy. METHODS: From January to December in 2013, 71 gastric cancer patients were prospectively enrolled and randomized into the FTS group and the control group. Patient in the FTS group received FTS management and those in the control group received routine management. The postoperative recovery and stress were compared between the two groups. RESULTS: FTS was associated with shorter time to bowel function return [(67.8±19.7) h vs. (90.0±20.6) h, P<0.01], shorter hospital stay [(13.5±3.0) d vs. (17.8±7.3) d, P=0.01], lower hospital cost [(23.8±3.7) thousand Yuan vs. (27.8±6.1) thousand Yuan, P<0.05], and less stress response (lower pain score, WBC count, C-reactive protein, all P<0.01). The postoperative complications including ileus, infection, anastomotic leakage were similar (all P>0.05). CONCLUSION: Fast track surgery decreases postoperative stress response and promotes recovery.

The eosinophil surface receptor epidermal growth factor-like module containing mucin-like hormone receptor 1 (EMR1): a novel therapeutic target for eosinophilic disorders.

BACKGROUND: Although several novel agents are currently in clinical trials for eosinophilic disorders, none has demonstrated efficacy in reducing blood and tissue eosinophilia in all subjects. Additional approaches are clearly needed. OBJECTIVE: We sought to explore the potential of the human eosinophil surface receptor epidermal growth factor-like module containing mucin-like hormone receptor 1 (EMR1) as a therapeutic target for eosinophilic disorders. METHODS: EMR1 expression was assessed in blood and bone marrow specimens from eosinophilic and healthy subjects, cell lines, CD34(+) cells differentiated in vitro, and tissue biopsy specimens by using flow cytometry, quantitative PCR, and immunostaining. Eosinophil targeting by a novel, humanized, afucosylated anti-EMR1 IgG1 was evaluated in vitro by using a natural killer cell-mediated killing assay and in vivo in cynomolgus monkeys. RESULTS: Analysis of blood and bone marrow cells from healthy and eosinophilic donors and in vitro-differentiated CD34(+) cells confirmed restriction of human EMR1 surface and mRNA expression to mature eosinophils. Tissue eosinophils also expressed EMR1. Although EMR1 was highly expressed on eosinophils from all subjects, surface expression was negatively correlated with absolute eosinophil counts (r = -0.46, P < .001), and soluble plasma levels correlated positively with absolute eosinophil counts (r = 0.69, P < .001), suggesting modulation of EMR1 in vivo. Nevertheless, afucosylated anti-EMR1 mAb dramatically enhanced natural killer cell-mediated killing of eosinophils from healthy and eosinophilic donors and induced a rapid and sustained depletion of eosinophils in monkeys. CONCLUSION: EMR1 expression is restricted to mature blood and tissue eosinophils. Targeting of eosinophils with afucosylated anti-EMR1 antibody shows promise as a treatment for eosinophilic disorders.