[Impact of VA-ECMO combined with IABP and timing on outcome of patients with acute myocardial infarction complicated with cardiogenic shock].

Objective: To investigate the impact of combined use and timing of arterial-venous extracorporeal membrane oxygenation (VA-ECMO) with intra-aortic balloon pump (IABP) on the prognosis of patients with acute myocardial infarction complicated with cardiogenic shock (AMICS). Methods: This was a prospective cohort study, patients with acute myocardial infarction and cardiogenic shock who received VA-ECMO support from the Heart Center of Lanzhou University First Hospital from March 2019 to March 2022 in the registration database of the Chinese Society for Extracorporeal Life Support were enrolled. According to combination with IABP and time point, patients were divided into VA-ECMO alone group, VA-ECMO+IABP concurrent group and VA-ECMO+IABP non-concurrent group. Data from 3 groups of patients were collected, including the demographic characteristics, risk factors, ECG and echocardiographic examination results, critical illness characteristics, coronary intervention results, VA-ECMO related parameters and complications were compared among the three groups. The primary clinical endpoint was all-cause death, and the safety indicators of mechanical circulatory support included a decrease in hemoglobin greater than 50 g/L, gastrointestinal bleeding, bacteremia, lower extremity ischemia, lower extremity thrombosis, acute kidney injury, pulmonary edema and stroke. Kaplan-Meier survival curves were used to analyze the survival outcomes of patients within 30 days of follow-up. Using VA-ECMO+IABP concurrent group as reference, multivariate Cox regression model was used to evaluate the effect of the combination of VA-ECMO+IABP at different time points on the prognosis of AMICS patients within 30 days. Results: The study included 68 AMICS patients who were supported by VA-ECMO, average age was (59.8±10.8) years, there were 12 female patients (17.6%), 19 cases were in VA-ECMO alone group, 34 cases in VA-ECMO+IABP concurrent group and 15 cases in VA-ECMO+IABP non-concurrent group. The success rate of ECMO weaning in the VA-ECMO+IABP concurrent group was significantly higher than that in the VA-ECMO alone group and the VA-ECMO+IABP non-concurrent group (all P<0.05). Compared with the ECMO+IABP non-concurrent group, the other two groups had shorter ECMO support time, lower rates of acute kidney injury complications (all P<0.05), and lower rates of pulmonary edema complications in the ECMO alone group (P<0.05). In-hospital survival rate was significantly higher in the VA-ECMO+IABP concurrent group (28 patients (82.4%)) than in the VA-ECMO alone group (9 patients) and VA-ECMO+IABP non-concurrent group (7 patients) (all P<0.05). The survival rate up to 30 days of follow-up was also significantly higher surviving patients within were in the ECMO+IABP concurrent group (26 cases) than in VA-ECMO alone group (9 patients) and VA-ECMO+IABP non-concurrent group (4 patients) (all P<0.05). Multivariate Cox regression analysis showed that compared with the concurrent use of VA-ECMO+IABP, the use of VA-ECMO alone and non-concurrent use of VA-ECMO+IABP were associated with increased 30-day mortality in AMICS patients (HR=2.801, P=0.036; HR=2.985, P=0.033, respectively). Conclusions: When VA-ECMO is indicated for AMICS patients, combined use with IABP at the same time can improve the ECMO weaning rate, in-hospital survival and survival at 30 days post discharge, and which does not increase additional complications.

[Safety and efficacy of regional transport combined with PCI model in patients with STEMI after thrombolysis in northwest China].

Objective: To investigate the safety and efficacy of regional transport to percutaneous coronary intervention(PCI) hospitals from non-PCI hospitals after thrombolysis in patients with acute ST-segment elevation myocardial infarction(STEMI) in northwest China. Methods: In this retrospective study, 1 062 STEMI patients who were transferred from non-PCI hospitals within 24 hours from symptom onset, during January 2015 and January 2019 in the First Hospital of Lanzhou University, were included. According to the treatment strategy, they were divided into two groups, namely intravenous thrombolysis combined with PCI group(n=240), and primary PCI group(n=822). Observation endpoint were in-hospital adverse cardiovascular and cerebrovascular events and bleeding events, Including all-cause death, ischemic stroke, malignant arrhythmia, intracranial hemorrhage and hemorrhage with hemoglobin decrease≥50 g/L. Results: A total of 1 062 STEMI patients were included(age was (61±12) years old), with 905 males (85.2%). The proportion of grade 0 TIMI blood flow in the primary PCI group before operation was significantly higher than that in the thrombolysis combined with PCI group(63.0%(518/822) vs. 36.3%(87/240)， P<0.001). Compared with primary PCI group, the time from symptom onset to first medical contact(2.11(1.00, 4.00)hours vs.3.00(1.13, 7.07)hours, P<0.001) and reperfusion in thrombolysis combined with PCI group(3.07(1.83, 4.87)hours vs. 6.92(4.07, 11.15) hours, P<0.001) were significantly shorter. The proportion of all-cause death was significantly higher in the primary PCI group than that in the thrombolysis combined with PCI group (1.8%(15/822) vs. 0, P=0.03). There was no significant difference in hemorrhage, ischemic stroke and malignant arrhythmia between the two groups(all P>0.05). Conclusions: For STEMI patients initially hospitalized in non-PCI hospitals, regional transport combined with PCI is feasible and effective. It does not significantly increase the risk of bleeding and cardiovascular and cerebrovascular events, with shorter time from symptom onset to myocardial reperfusion.

MiR-99a suppresses cell migration and invasion by regulating IGF1R in gastric cancer.

OBJECTIVE: Gastric cancer is a common kind of gastrointestinal malignancies. Increasing evidence indicates dysregulation of microRNA-99a (miR-99a) in gastric cancer, and has been extensively investigated in terms of cancer formation, progression, diagnosis, therapy, and prognosis. The purpose of this study is to explore how miR-99a worked in gastric cancer on migration and invasion. PATIENTS AND METHODS: The mRNA and protein levels of miR-99a and insulin-like growth factor 1 receptor (IGF1R) in gastric cancer were measured by quantitative Real Time-Polymerase Chain Reaction (qRT-PCR) and Western blot. Transwell assay was employed to analyze the migratory and invasive capacities. The Dual-Luciferase reporter assay was performed to confirm miR-99a mediated the expression of IGF1R by directly targeting its mRNA 3'-untranslated regions (3'-UTR) in gastric cancer cells. RESULTS: MiR-99a was discovered to be significantly downregulated while IGF1R was upregulated in gastric cancer tissues and cell lines. The expression of miR-99a had a negative correlation with the IGF1R expression in gastric cancer tissues. Moreover, miR-99a was low expressed in gastric cancer cells HGC-27 and MGC-803 compared to the normal cell line. MiR-99a suppressed the migration and invasion through directly binding to the 3'-UTR of IGF1R mRNA in HGC-27 cells. In addition, IGF1R could reverse partial roles of miR-99a on migration and invasion in gastric cancer. CONCLUSIONS: MiR-99a inhibited the migratory and invasive abilities by regulating the expression of IGF1R. MiR-99a was downregulated while IGF1R was upregulated in gastric cancer cell lines. The newly identified miR-99a/IGF1R axis provides novel insight into the pathogenesis of gastric cancer.

Telomerase reverse transcriptase expression protects transformed human cells against DNA-damaging agents, and increases tolerance to chromosomal instability.

Reactivation of telomerase reverse transcriptase (TERT) expression is found in more than 85% of human cancers. The remaining cancers rely on the alternative lengthening of telomeres (ALT), a recombination-based mechanism for telomere-length maintenance. Prevalence of TERT reactivation over the ALT mechanism was linked to secondary TERT function unrelated to telomere length maintenance. To characterize this non-canonical function, we created a panel of ALT cells with recombinant expression of TERT and TERT variants: TERT-positive ALT cells showed higher tolerance to genotoxic insults compared with their TERT-negative counterparts. We identified telomere synthesis-defective TERT variants that bestowed similar genotoxic stress tolerance, indicating that telomere synthesis activity is dispensable for this survival phenotype. TERT expression improved the kinetics of double-strand chromosome break repair and reduced DNA damage-related nuclear division abnormalities, a phenotype associated with ALT tumors. Despite this reduction in cytological abnormalities, surviving TERT-positive ALT cells were found to have gross chromosomal instabilities. We sorted TERT-positive cells with cytogenetic changes and followed their growth. We found that the chromosome-number changes persisted, and TERT-positive ALT cells surviving genotoxic events propagated through subsequent generations with new chromosome numbers. Our data confirm that telomerase expression protects against double-strand DNA (dsDNA)-damaging events, and show that this protective function is uncoupled from its role in telomere synthesis. TERT expression promotes oncogene-transformed cell growth by reducing the inhibitory effects of cell-intrinsic (telomere attrition) and cell-extrinsic (chemical- or metabolism-induced genotoxic stress) challenges. These data provide the impetus to develop new therapeutic interventions for telomerase-positive cancers through simultaneous targeting of multiple telomerase activities.

Proper placement of the Escherichia coli division site requires two functions that are associated with different domains of the MinE protein.

The proper placement of the Escherichia coli division septum requires the MinE protein. MinE accomplishes this by imparting topological specificity to a division inhibitor coded by the minC and minD genes. As a result, the division inhibitor prevents septation at potential division sites that exist at the cell poles but permits septation at the normal division site at midcell. In this paper, we define two functions of MinE that are required for this effect and present evidence that different domains within the 88-amino acid MinE protein are responsible for each of these two functions. The first domain, responsible for the ability of MinE to counteract the activity of the MinCD division inhibitor, is located in a small region near the N terminus of the protein. The second domain, required for the topological specificity of MinE function, is located in the more distal region of the protein and affects the site specificity of placement of the division septum even when separated from the domain responsible for suppression of the activity of the division inhibitor.

Safety and immunogenicity study of the auxotrophic Shigella flexneri 2a vaccine SFL1070 with a deleted aroD gene in adult Swedish volunteers.

The live auxotrophic Shigella flexneri 2a vaccine strain SFL1070 with a deleted aroD gene was given orally to 37 adult Swedish volunteers who received three doses within 5 days. Each dose comprised 1 x 10(5) (n = 9), 1 x 10(7) (n = 10), 1 x 10(8) (n = 9) or 1 x 10(9) (n = 9) c.f.u. S. flexneri SFL1070. One volunteer vaccinated with 1 x 10(7) and three vaccinated with 1 x 10(8) c.f.u. reported mild gastrointestinal symptoms after the first dose. Vaccination with 1 x 10(9) c.f.u. caused abdominal pain and watery diarrhoea in four volunteers who all recovered spontaneously within 72 h. S. flexneri SFL1070 was not recovered from volunteers given 1 x 10(5) c.f.u., but was shed in faeces by six volunteers vaccinated with 1 x 10(7), by all nine vaccinated with 1 x 10(8), and by seven volunteers vaccinated with 1 x 10(9) c.f.u. The mean excretion time was 2.6 (range 0-4) days in the 1 x 10(8) and the 1 x 10(9) groups. Serum antibody responses against either S. flexneri 2a and Y lipopolysaccharides (LPSs) or Shigella invasion plasmid antigens (Ipa) were seen in eight volunteers vaccinated with 1 x 10(9) (p < 0.01 to p < 0.05 for mean relative titres of IgA and IgG against S. flexneri 2a and Y LPSs), in four vaccinated with 1 x 10(8), and in two and one volunteers each vaccinated with 1 x 10(7) and 1 x 10(5) c.f.u. of S. flexneri SFL1070. Intestinal sIgA responses to the same antigens were elicited in all volunteers in the 1 x 10(9) and the 1 x 10(8) groups, and in six and one volunteers vaccinated with 1 x 10(7) and 1 x 10(5) c.f.u., respectively. The sIgA responses against S. flexneri 2a and Y LPSs were significant in all but the 1 x 10(5) group (p < 0.01 to p < 0.05). Significant antibody-secreting cell (ASC) responses specific to S. flexneri 2a LPS were seen in peripheral blood from eight volunteers each in the 1 x 10(9) and 1 x 10(8) groups and from five volunteers vaccinated with 1 x 10(7) c.f.u. (p < 0.01 to p < 0.05). The number of volunteers showing anti-Shigella Ipa ASC responses in these groups were five (p < 0.01 to p < 0.05), three and one, respectively.(ABSTRACT TRUNCATED AT 400 WORDS)

Serum IgG antibody responses to Shigella invasion plasmid-coded antigens detected by immunoblot.

Serum IgG antibody responses to Shigella invasion plasmid-coded antigens (Ipa) from 58 Shigella flexneri, S. sonnei, and S. dysenteriae infected Swedish patients were investigated by immunoblot technique. Intense responses to most components of Ipa (Ipas A, B, C, D, and VirG-virulence determinant on SalI fragment G of the plasmid) were evident in sera from S. flexneri infected patients. The strongest response was to Ipa B and the weakest, to Ipa D. In contrast, there were weaker responses to Ipas A, B, C, and VirG but none at all to Ipa D in sera from S. sonnei infected patients. After absorption of the Ipa-positive sera by Ipa expressing strains of S. flexneri and S. sonnei, most IgG antibodies to components of Ipa were removed in sera absorbed by S. flexneri, but IgG antibodies to Ipas--especially to Ipa D--were only slightly reduced in sera absorbed by S. sonnei, suggesting that Ipa D in S. sonnei may not be exposed on the S. sonnei cell surface.

Specificity of monoclonal antibodies binding to the polysaccharide antigens (Vi, O9) of Salmonella typhi.

A panel of monoclonal antibodies were generated against the surface polysaccharide antigens of the cell envelope of Salmonella typhi. Four clones (IgM) were specific for the capsular Vi polysaccharide, and one clone (IgG3) reacted selectively with the S. typhi lipopolysaccharide in enzyme immunoassay. On the basis of their reactivity pattern and binding affinity, MATy-V7 (IgM) and MATy-O9 (IgG3) antibodies were selected for further characterization of their antigenic specificity. In an inhibition enzyme immunoassay with rabbit factor-specific anti-Salmonella antibodies as the competing agents, the reactivity of MATy-V7 and MATy-O9 were significantly inhibited by the anti-Vi and anti-O9 antisera, respectively. Moreover, both the Vi- and O9-specific monoclonal antibodies were shown to be useful serotyping agents by correct identification in slide agglutination tests of 32 clinical isolates of all the S. typhi and other serogroup D salmonellae among a total of 140 bacterial isolates representing eight different Enterobacteriaceae genera tested.