Long-term Outcomes of Endoscopic Resection for Gastric Subepithelial Tumors.

OBJECTIVE: The purpose of the current study was to analyze the safety and efficacy of endoscopic resection for gastric subepithelial tumors (SETs) using long-term patient outcome data. PATIENTS AND METHODS: A retrospective analysis of 73 consecutive patients with gastric SETs was performed from June 2014 to December 2016. The treatment methods included submucosal dissection, submucosal excavation or endoscopic full-thickness resection (EFTR). In addition to epidemiological data (sex and age), tumor size, surgical parameters, length of stay, complications, costs, and endoscopic, clinicopathologic, and follow-up data were analyzed to compare treatments. RESULTS: The complete resection rate was 97.3% (71/73). Three patients experienced complications (4.1%), including 2 with delayed perforation and 1 with perioperative infection. The median postoperative feeding time was 3 days, and the median postoperative hospital stay was 5 days. The median follow-up period was 19 months, with no patient death or tumor recurrence. Among the 38 patients with gastrointestinal stromal tumors, the complete resection rate was 97.4% (37/38). The complete resection and complication rates between the endoscopic submucosal excavation (ESE) group and the EFTR group were not statistically significant. There was no recurrence or metastasis detected among either group; however, the ESE group had earlier postoperative feeding, a shorter postoperative hospital stay, and less hospitalization expenses. CONCLUSIONS: Endoscopic resection for gastric SETs (<3 cm) is safe and feasible concerning medium-term and long-term effects. Compared with the EFTR group, the ESE group had earlier postoperative feeding, a shorter postoperative hospital stay, and less hospitalization expenses. Even so, gastric SETs with malignant potential are at risk of recurrence. Larger prospective multicenter studies are warranted.

The nuclear hormone receptor E75A regulates vitellogenin gene (Al-Vg) expression in the mirid bug Apolygus lucorum.

Apolygus lucorum is the predominant pest of Bacillus thuringiensis (Bt) cotton in China. 20-hydroxyecdysone (20E) plays a key role in the reproduction of this insect. To better understand the mechanism underlying 20E-regulated reproduction, the nuclear hormone receptor E75 isoform-A of Ap. lucorum (Al-E75A) was cloned and its expression analysed. A 2241-bp sequence of Al-E75A cDNA encoded an open reading frame of a polypeptide with a predicted molecular mass of 69.04 kDa. Al-E75A mRNA was detected in female adult stages of Ap. lucorum with peak expression in 7-day-old animals. Al-E75A was also expressed in several tissues, particularly in the fat body and ovary. A 3.2 kb Al-E75A mRNA was detected in all tissues by Northern blot. The fecundity and longevity were significantly decreased in female adults treated with Al-E75A small interfering RNA. The rates of egg incubation rates were considerably lower in the RNA interference-treated animals compared to the untreated controls. In order to investigate the molecular mechanism underlying the effects described above, vitellogenin (Al-Vg) was selected for further investigation. The expression pattern of Al-Vg was similar to that of Al-E75A and was up-regulated by 20E. After knockdown of Al-E75A, the expression profile of Al-Vg and the protein levels were down-regulated. These findings suggest that Al-E75A plays a crucial role in the regulation of Al-Vg expression in Ap. lucorum.

Virulence and serological studies of recombinant infectious hematopoietic necrosis virus (IHNV) in rainbow trout.

Infectious hematopoietic necrosis virus is a highly contagious disease of juvenile salmonid species. From the IHNV HLJ-09 isolated in China, two recombinant viruses were generated by reverse genetics using the RNA polymerase II transcription system. The recombinant viruses were confirmed by RT-PCR, indirect immunofluorescence assay and electron microscopy. They were referred to as rIHNV HLJ-09 and rIHNV-EGFP. rIHNV HLJ-09 and rIHNV-EGFP could stably replicate in EPC cell lines and had the same cellular tropism as wtIHNV HLJ-09. But the titer of rIHNV-EGFP was significantly lower than rIHNV HLJ-09 and wtIHNV HLJ-09. rIHNV-EGFP strain could express EGFP stably at least in 20 passages, and the fluorescence could be observed clearly. To assess the virulence and pathogenicity of the recombinant viruses in vivo, juvenile rainbow trout were challenged by intraperitoneal injection with 20µl of rIHNV HLJ-09, rIHNV-EGFP or wtIHNV HLJ-09 (1×10(6)pfuml(-1)). Fish challenged with rIHNV HLJ-09 and wtIHNV HLJ-09 exhibited clinical signs typical of IHN disease and both produced 90% cumulative percent mortality, whlie rIHNV-EGFP produced only 5%. Pathological sectioning results showed that the tissues (liver, kidney, heart muscle, back muscle) of the fish infected with rIHNV HLJ-09 exhibited pathological changes, with the exception of cerebral neurons and the cheek. However, no lesions of liver, kidney, heart, muscle, brain in rainbow trout of rIHNV-EGFP or the control group were observed. Indirect ELISA results showed that a high level of serum antibody was detected in the experimental fish challenged with rIHNV HLJ-09, just as the same as wtIHNV HLJ-09, while a lower titer was detecred in the fish infected with rIHNV-EGFP. This indicated that the recombinant viruses could induce humoral immune response in the experimental fish. The recombinant viruses had unique genetic tags and could be used for genetic engineering, laying new ground for further investigation of IHNV pathopoiesis molecular mechanism, host tropism and the development of novel vaccines against IHN.

Analysis of the genome sequence of infectious hematopoietic necrosis virus HLJ-09 in China.

Infectious hematopoietic necrosis virus (IHNV) is a highly contagious disease of juvenile salmonid fish. Six genome target fragments of the complete genome sequence of IHNV HLJ-09 were amplified by RT-PCR, and the 3'-terminal and 5'-terminal region of the genomic RNA were amplified using the RACE method. The complete genome sequence of HLJ-09 comprises 11,132 nucleotides (nt) (Accession number JX649101) and is different from that of other IHNV strains published in GenBank. Homology comparison and phylogenetic analysis of six ORF sequences were carried out using HLJ-09 and other IHNV strains published in GenBank. From phylogenetic tree analysis, the N gene, M gene, and P gene had the closest genetic relationship to IHNV-PRT from Korea. Phylogenetic analysis for the full length of the G gene showed that the HLJ-09 strain exhibited very close homology to the ChYa07, RtNag96, RtUi02, and RtGu01 strains from Korea and Japan, indicating that the HLJ-09 strain belonged to the genotype JRt. Ultimately, the Chinese IHNV HLJ-09 strain may have originated in Korea and Japan.

Maternal obesity during pregnancy is negatively associated with maternal and neonatal iron status.

BACKGROUND/OBJECTIVES: Obesity among pregnant women may adversely affect both maternal iron status throughout pregnancy and placental transfer of iron. The objective of this study was to determine the association of maternal body mass index (BMI) with (1) maternal iron status and inflammation in mid and late pregnancy, (2) the change in maternal iron status throughout pregnancy and (3) neonatal iron status. SUBJECTS/METHODS: We examined longitudinal data from 1613 participants in a pregnancy iron supplementation trial in rural China. Women with uncomplicated singleton pregnancies were enrolled in the early second trimester of pregnancy and followed through parturition. Maternal blood samples obtained at enrollment and in the third trimester and cord blood samples were analyzed for a range of hematological and iron biomarkers. RESULTS: There was a negative association between maternal BMI and iron status at enrollment (transferrin receptor (sTfR): r=0.20, P<0.001; body iron (BI): r=-0.05; P=0.03). This association was markedly stronger among obese women. Maternal BMI was positively associated with maternal inflammation (C-reactive protein: r=0.33, P<0.001). In multiple linear regression models, maternal BMI was negatively associated with neonatal iron status (cord serum ferritin: -0.01, P=0.008; BI: -0.06, P=0.006) and associated with a lower decrease in iron status throughout pregnancy (sTfR: -4.6, P<0.001; BI: 1.1, P=0.004). CONCLUSIONS: Maternal obesity during pregnancy may adversely affect both maternal and neonatal iron status, potentially through inflammatory pathways.

Studying the growth of cervical carcinoma nests and angiogenesis by immunostaining, quantitation and three-dimensional structural analysis.

OBJECTIVE: To analyze the relationship and mutual effect of the growth of cervical carcinoma nests and angiogenesis. STUDY DESIGN: Serial paraffin sections of cervical squamous carcinoma were stained in repeated order with hematoxylin-eosin (HE), immunostain for factor VIII-related antigen, type IV collagen and proliferating cell nuclear antigen (PCNA). Three-dimensional reconstructions were made, and the volumes of carcinoma nests, necrosis and microvessels were measured. RESULTS: Two types of cervical carcinoma nests were distinguished on the basis of their growth characteristics and vascularity (groups I and II). Group I nests: The carcinoma cells were proliferating actively, as determined by their morphology and PCNA staining. There were abundant microvessels. Some endothelial sprouts and cords penetrated the nests and then formed networks and new vessels. The volume ratio of microvessels, including sprouts and cords, to the nests was 0.6282:1. Group II nests: The center of these nests underwent necrosis. The peripheral cells were rather small, with no mitosis. The PCNA index was rather low; these nests grew very slowly. There were only a few surrounding microvessels with no endothelial sprouts or cords. The volume ratio of vessels to nest was 0.0657:1. CONCLUSION: Two types of cervical carcinoma nests show a close relationship and mutual effect of the growth of carcinoma nest and angiogenesis. Group I nests grow and develop well, with abundant microvessels. Thus, many tumor cells may be angiogenic and induce angiogenesis; growth of the nests seemed dependent on adequate neovascularization. Group II nests grow slowly, with a few microvessels; the center of the nests undergoes necrosis. The inadequate blood supply must be one of the important causes of necrosis. Considering that there must have been abundant neovascularization during their growth in the past, most of the microvessels must have been obliterated and then reabsorbed to make the remaining vessels so few.

A death-domain-containing receptor that mediates apoptosis.

The cell-killing effects of the cytokines TNF-alpha and FasL are mediated by the distinct cell-surface receptors TNFR1, TNFR2 and Fas (also known as CD95/APO-1), which are all members of a receptor superfamily that is important for regulating cell survival. The cytoplasmic regions of TNFR1 and Fas contain a conserved 'death' domain which is an essential component of the signal pathway that triggers apoptosis and activation of the transcription factor NF-kappaB (refs 5,6). Here we report the isolation of a 54K receptor that is a new member of the TNFR superfamily, using the death domain of TNFR1 in a yeast two-hybrid system. This protein, WSL-1, is most similar to TNFR1 itself, particularly in the death-domain region. The gene wsl-1 is capable of inducing apoptosis when transfected into 3T3 and 293 cells, and can also activate NF-kappaB in 293 cells. Like TNFR1, WSL-1 will homodimerize in yeast. WSL-1 also interacts specifically with the TNFR1-associated molecule TRADD. The tissue distribution is very restricted and significantly different from that of Fas and TNFR1.

[Protective effects of ginsenoside on myocardiac ischemic and reperfusion injuries].

Thirty mitral valvular surgical patients were randomly divided into three groups for study of protective effects of Ginsenoside on myocardiac ischemic and reperfusion injuries. In GI, 11 patients (controls), no Ginsenoside was used, in GII, 11, Ginsenoside in total was added into the cardioplegic solusion made in our hospital, and in GIII, 8, instead of Ginsenoside in total Ginsenoside Rb was added. During operation comparative studies were made of pre- and postoperative cardiac functions with intraoperative transesophageal echocardiography and ultrastructures of myocardiac cells with electromicroscopy. We conclude that both Ginsenoside in total and Ginsenoside Rb have protective effects on myocardiac ischemic and reperfusion injuries in open heart surgery, and the effect of Ginsenoside in total is even better than that of Ginsenoside Rb.

Domain 3 of kininogens contains a cell-binding site and a site that modifies thrombin activation of platelets.

High and low molecular weight kininogens (HK and LK) are able to bind to platelets to inhibit thrombin binding to and activation of platelets. The heavy chain domain on the kininogens that contains these functions has been determined. Domain 3 (D3) but not domains 1 or 2, completely inhibited 125I-HK binding to platelets (Ki = 24 +/- 7 nM, n = 4). 125I-D3 specifically bound to unstimulated platelets and human umbilical vein endothelial cells. On platelets, it was blocked by unlabeled D3 and HK but not prekallikrein, factor XII, C1s, or C1 inhibitor. Further, one monoclonal antibody (HKH13) directed to kininogens' D3 blocked 125I-HK and 125I-D3 binding to platelets. The binding of 125I-D3 to platelets was fully reversible by addition of 35 molar excess of unlabeled D3. D3 binding to platelets was saturable with an apparent Kd of 39 +/- 8 nM (n = 4) and 1227 +/- 404 binding sites/platelet. D3, like HK and LK, inhibited thrombin-induced platelet activation by preventing thrombin binding to platelets. Another monoclonal antibody (HKH12), directed to D3, which did not block HK binding to platelets, reduced HK's ability to inhibit 125I-alpha-thrombin binding. This result suggests that the region on D3 that inhibits 125I-alpha-thrombin binding to platelets is different from that which directly binds to platelets. These studies indicate that D3 of the kininogens contains both a binding region for platelets and endothelial cells and another region that inhibits thrombin-induced platelet activation.

Characterization of cell binding and thrombin inhibitory regions on kininogens' heavy chain.

Investigations have been performed to determine the domain(s) on kininogens' heavy chain that binds to platelets and contains thrombin inhibitory region Domain 3, but not domains 1 or 2, completely inhibited 125I-HK binding to platelets (Ki = 24 nM +/- 7, n = 4). D3 binding to platelets was saturable with an apparent Kd of 39 nM +/- 8 (n = 4) and 1227 +/- 404 binding sites/platelet. D3 inhibited 125I-thrombin binding to platelets which prevented thrombin-induced platelet aggregation and secretion. These studies indicate that D3 on kininogens' heavy chain contains a cell binding region and another region which inhibits thrombin binding and activation of platelets.

Cells secreting anti-MAG antibody occur in cerebrospinal fluid and bone marrow in patients with polyneuropathy associated with M component.

Occurrence and distribution of cells secreting antibodies against myelin associated glycoprotein (MAG) were studied in 9 patients with polyneuropathy associated with the monoclonal (M) component in serum. Utilizing an immunospot assay, we found that 4 of 7 patients with polyneuropathy associated with an IgM M component had cells secreting anti-MAG IgM antibody in cerebrospinal fluid (CSF) numbering between 1 per 212 and 1 per 3333 mononuclear cells. All 7 patients had cells secreting anti-MAG IgM antibody in bone marrow (median value 1 per 2000 cells). In contrast, peripheral blood from only 2 of these patients contained low numbers of such cells. One patient with polyneuropathy associated with an IgA M component had cells secreting anti-MAG IgA antibody in CSF, and 1 with an IgG M component had cells secreting anti-MAG IgG antibody in CSF; both patients also had anti-MAG IgM antibodies detectable in CSF only by ELISA. These 2 patients may thus have concurrent intrathecal production of antibodies of 2 different isotypes which are directed against the same or different epitopes of MAG. The production of antibodies directed against a component of myelin occurring in the immediate vicinity of the peripheral nervous system might be involved in the pathogenesis of the polyneuropathy.