Objectives: To investigated the safety and efficacy of treating patients with acute non-ST-segment elevation myocardial infarction (NSTEMI) and elevated levels of N-terminal pro-hormone B-type natriuretic peptide (NT-proBNP) with levosimendan within 24 hours of first medical contact (FMC). Methods: This multicenter, open-label, block-randomized controlled trial (NCT03189901) investigated the safety and efficacy of levosimendan as an early management strategy of acute heart failure (EMS-AHF) for patients with NSTEMI and high NT-proBNP levels. This study included 255 patients with NSTEMI and elevated NT-proBNP levels, including 142 males and 113 females with a median age of 65 (58-70) years, and were admitted in the emergency or outpatient departments at 14 medical centers in China between October 2017 and October 2021. The patients were randomly divided into a levosimendan group (n=129) and a control group (n=126). The primary outcome measure was NT-proBNP levels on day 3 of treatment and changes in the NT-proBNP levels from baseline on day 5 after randomization. The secondary outcome measures included the proportion of patients with more than 30% reduction in NT-proBNP levels from baseline, major adverse cardiovascular events (MACE) during hospitalization and at 6 months after hospitalization, safety during the treatment, and health economics indices. The measurement data parameters between groups were compared using the t-test or the non-parametric test. The count data parameters were compared between groups using the χ² test. Results: On day 3, the NT-proBNP levels in the levosimendan group were lower than the control group but were statistically insignificant [866 (455, 1 960) vs. 1 118 (459, 2 417) ng/L, Z=-1.25,P=0.21]. However, on day 5, changes in the NT-proBNP levels from baseline in the levosimendan group were significantly higher than the control group [67.6% (33.8%,82.5%)vs.54.8% (7.3%,77.9%), Z=-2.14, P=0.03]. There were no significant differences in the proportion of patients with more than 30% reduction in the NT-proBNP levels on day 5 between the levosimendan and the control groups [77.5% (100/129) vs. 69.0% (87/126), χ²=2.34, P=0.13]. Furthermore, incidences of MACE did not show any significant differences between the two groups during hospitalization [4.7% (6/129) vs. 7.1% (9/126), χ²=0.72, P=0.40] and at 6 months [14.7% (19/129) vs. 12.7% (16/126), χ²=0.22, P=0.64]. Four cardiac deaths were reported in the control group during hospitalization [0 (0/129) vs. 3.2% (4/126), P=0.06]. However, 6-month survival rates were comparable between the two groups (log-rank test, P=0.18). Moreover, adverse events or serious adverse events such as shock, ventricular fibrillation, and ventricular tachycardia were not reported in both the groups during levosimendan treatment (days 0-1). The total cost of hospitalization [34 591.00(15 527.46,59 324.80) vs. 37 144.65(16 066.90,63 919.00)yuan, Z=-0.26, P=0.80] and the total length of hospitalization [9 (8, 12) vs. 10 (7, 13) days, Z=0.72, P=0.72] were lower for patients in the levosimendan group compared to those in the control group, but did not show statistically significant differences. Conclusions: Early administration of levosimendan reduced NT-proBNP levels in NSTEMI patients with elevated NT-proBNP and did not increase the total cost and length of hospitalization, but did not significantly improve MACE during hospitalization or at 6 months.
Male ; Female ; Humans ; Aged ; Natriuretic Peptide, Brain ; Simendan/therapeutic use* ; Non-ST Elevated Myocardial Infarction ; Heart Failure/drug therapy* ; Peptide Fragments ; Arrhythmias, Cardiac ; Biomarkers ; Prognosis

To give full play to the therapeutic advantages of traditional Chinese medicine （TCM） in sepsis， clarify the entry point of integrated TCM and western medicine， further standardize the clinical treatment of TCM， develop a recognized and integrated treatment protocol of TCM and western medicine， and improve the clinical efficacy on sepsis，the Chinese Association of Chinese Medicine organized TCM and western medicine experts specialized in sepsis treatment to conduct in-depth discussions on the advantages of TCM and integrated TCM and western medicine in the treatment of sepsis based on the TCM etiology and pathogenesis of sepsis， a representative acute and critical disease. They emphasized the pathogenesis characteristics of asthenia of healthy Qi and sthenia of pathogenic factors and summarized the roles of Chinese medicine in correcting the imbalance of inflammatory response， improving blood coagulation dysfunction， and relieving organ damage. Furthermore， they proposed the treatment protocol with integrated TCM and western medicine， which is expected to provide references for actual clinical treatment and scientific research.

Objective To characterize the species of invasive Pomacea snails that were discovered for the first time in Shandong Province. Methods Pomacea snails samples were collected in the field of Jining City, Shandong Province on October 2021 for morphological identification. Pomacea snails were randomly sampled and genomic DNA was extracted from foot muscle tissues of Pomacea snails for multiplex PCR amplification. The PCR amplification product was sequenced. Then, the sequence was aligned and a phylogenetic tree was created using the software MegAlign 7.1.0. In addition, Angiostongylus cantonensis infection was detected in Pomacea snails with the lung microscopy. Results A total of 104 living Pomacea snails were collected, and all were characterized as Pomacea spp. based on morphological features. Of 12 randomly selected adult Pomacea snails, multiplex PCR assay and sequencing identified eleven snails as P. canaliculata and one as P. maculata. No A. cantonensis infection was detected in 104 Pomacea snails. Conclusion This is the first report of invasive Pomacea snails in Shandong Province, where P. canaliculata and P. maculata are found.

Anaerobic Threshold ; Exercise Test ; Female ; Heart Rate ; Lactic Acid ; Lung ; Male

Anemia, Aplastic/drug therapy* ; Animals ; Antilymphocyte Serum ; Child ; Cyclosporine ; Humans ; Immunosuppressive Agents ; Swine ; Treatment Outcome

OBJECTIVETo explore clinical significance of monitoring the level of minimal residual disease (MRD) at different time point in the risk stratification and prognosis of Childhood B-lineage Acute Lymphoblastic Leukemia.

METHODSThree hundred and eighty cases of children's B-ALL from Augest 2008 to January 2013 in our hospital were enrolled in this study. MRD levels were detected at day 15, day 33 and week 12 after initial chemotherapy. The event-free survival(EFS) and overall survival (OS) were measured on the basis of MRD levels at different stages of chemotherapy and were compared by Kaplan Meier analyses.

RESULTSThe patient's age, initial white blood cell count, chromosome, MLL, BCR/ABL, pretreatment reaction, bone marrow MRD at days 33 were closely related with the 5-year EFS rate. Multiparameter flow cytometry showed the marked MRD and unmarked MRD were not significantly different between their 5-year EFS rate(P>0.05), and the every immune phenotype was also no significantly different between the 5-year EFS rate(P>0.05). The children with MRD≥10at day 15(P<0.01), MRD≥10at day 33 (P<0.01) and MRD≥10on week 12(P<0.01) have a decreased 5-year EFS rate and overall survival, which related with poor prognosis obviously. The 5-year EFS rates at the MRD<10(negative), 10-10, 10-10and ≥10at day 33 were 86.6±2.7%, 77.5±4.9%, 70.1±8.0%, and 44.8±9.9%(P<0.01) with significant difference respectively; the 5-year OS rate was 89.5±2.7%, 80±4.9%, 76.0±7.8%, and 53.2±10.1% with statistically significant difference(P<0. 01).

CONCLUSIONThe MRD≥10at day 33 is a high risk factor for significant reduction of the 5-year EFS rate and the 5-year OS rate of children with B-ALL. Thus, dynamic monitoring the MRD level can predict relapse of B-ALL after remission.

OBJECTIVETo explore the clinical features and prognostic factors of pediatric acute lymphoblastic leukemia (ALL) in high-risk (HR) group.

METHODSA total of 421 children with ALL in the Children's Hospital of Soochow University from August 2008 to March 2013 were diagnosed and treated according to the Chinese Children Leukemia Group (CCLG)-2008 Protocol. Among different risk-groups, 148 cases were stratified into the low-risk group and 191 cases were included in the moderate-risk group. Eight-two patients of the high-risk group were analyzed retrospectively for their clinical features, 5-year event-free survival (EFS) rate and overall survival (OS) rate.

RESULTSThe median follow-up times of 82 patients were 64 months(3.0-76.3 months), 55 patient achieved complete remission(CR) after 1 cycle of induction chemotherapy(CR rate 67.1%), 25 patients relapsed(30.5%) mainly in very early and early relapse phases, significantly different from the low-risk group (P=0.013), 27 pateitns died(32.9%). The 5-year pEFS and pOS were 57.20% and 58.5%, respectively. Phor BCR/ABLand MRD>10on the 33rd day in the high-risk group were 2 main factors influencing EFS and OS according to single factor analysis. Phor BCR/ABLwas an independent prognostic factor, however, the MRD value on the 33rd day was not statistically significant differente by virtue of COX regression analysis.

CONCLUSIONThe clinical feature of children with ALL in high risk group display low induction CR rate, high recurrence rate and the lower 5-year pEFS. Phor BCR/ABLis regarded as an independent factor of poor prognosis.

OBJECTIVETo study the molecular risk factors of lymph node metastasis in stage T1 and T2 colorectal cancers by tissue microarray and immunohistochemistry techniques.

METHODSTwo hundred and three patients with stage T1 and T2 colorectal carcinoma who underwent radical surgery from 1999 to 2010 in our department were included in this study. Their clinicopathological data were retrospectively analyzed. Expression of the following 14 molecular markers were selected and assayed by tissue microarray and immunohistochemistry: VEGFR-3, HER2, CD44v6, CXCR4, TIMP-1, EGFR, IGF-1R, IGF-2, IGFBP-1, ECAD, MMP-9, RKIP, CD133, MSI. Chi-squared test and logistic regression were used to evaluate the variables as potential risk factors for lymph node metastasis.

RESULTSThe positive expression rates of biomarkers were as following: VEGFR-3 (44.3%), EGFR (30.5%), HER-2 (28.1%), IGF-1R (63.5%), IGF-2 (44.8%), IGFBP-1 (70.9%), ECAD (45.8%), CD44v6 (51.2%), MMP-9 (44.3%), TIMP-1 (41.4%), RKIP (45.3%), CXCR4 (40.9%), and CD133 (49.8%). The positive rate of MSI expression was 22.2%. Both univariate and multivariate analyses showed that VEGFR-3, HER-2, and TIMP-1 were significant predictors of lymph node metastasis. Univariate analysis showed that CD44v6 and CXCR4 were significant significant predictors of lymph node metastasis.

CONCLUSIONSVEGFR-3, HER2 and TIMP-1 are independent factors for lymph node metastasis in stage T1 and T2 colorectal cancers.

Aged ; Biomarkers, Tumor ; metabolism ; Colonic Neoplasms ; metabolism ; pathology ; Female ; Humans ; Hyaluronan Receptors ; metabolism ; Immunohistochemistry ; Lymphatic Metastasis ; Male ; Microsatellite Instability ; Middle Aged ; Neoplasm Staging ; Oligonucleotide Array Sequence Analysis ; Receptor, ErbB-2 ; metabolism ; Receptors, CXCR4 ; metabolism ; Rectal Neoplasms ; metabolism ; pathology ; Retrospective Studies ; Tissue Inhibitor of Metalloproteinase-1 ; metabolism ; Vascular Endothelial Growth Factor Receptor-3 ; metabolism

OBJECTIVETo study the selective killing effects of adenovirus (Ad)-mediated double suicide gene system driven by KDR promoter (KDR-CdglyTK) on the human hepatic carcinoma cells and human umbilical vein endothelial cells (HUVECs).

METHODSKDR-expressing BEL-7402 and HUVECs and HepG2 cells that did not express KDR were infected by KDR-CdglyTK, and the infection efficiency and the expression of CdglyTK in the cells was detected by RT-PCR. The infected cells were treated with the the prodrugs 5-FC and GCV at different concentrations, and the cell-killing effects and bystander effects were evaluated by MTT method.

RESULTSAt the multiplicity of infection (MOI) of 100, the recombinant AdKDR-CDglyTK showed similar infection efficiency in the 3 cell lines. RT-PCR demonstrated CDglyTK expression in the recombinant adenovirus and the 3 infected cell lines. BEL-7402 and HUVECs infected by the KDR-CdglyTK, but not the HepG2 cells, were highly sensitive to the prodrugs (P<0.001). Bystander effects of the double suicide gene system were observed in the coculture of the infected and non-infected BEL-7402 and HUVECs.

CONCLUSIONThe double suicide gene system driven by KDR promoter has specific killing effect on KDR-expressing hepatocellular carcinoma cells and HUVECs.

Adenoviridae ; genetics ; Apoptosis ; genetics ; Cells, Cultured ; Cytosine Deaminase ; genetics ; metabolism ; Endothelial Cells ; cytology ; Genes, Transgenic, Suicide ; genetics ; Genetic Therapy ; Genetic Vectors ; Humans ; Liver Neoplasms ; pathology ; Promoter Regions, Genetic ; genetics ; Recombinant Fusion Proteins ; genetics ; metabolism ; Thymidine Kinase ; genetics ; metabolism ; Tumor Cells, Cultured ; Umbilical Veins ; cytology ; Vascular Endothelial Growth Factor Receptor-2 ; genetics ; metabolism

OBJECTIVETo evaluate the effect of adenovirus-mediated double suicide gene (CD/TK) for selective killing of breast cancer cells.

METHODSVascular endothelial growth factor (VEGF)-expressing MCF-7 cells and normal human mammary epithelial cells that did not express VEGF were infected with the adenovirus containing VEGFP-CD/TK-GFP genes. CD/TK gene expression in the infected cells was detected by RT-PCR. After treatment of the infected cells with GCV and/or 5-FC, the cell growth status was evaluated using MTT assay, and the cell cycle changes were detected with flow cytometry. In nude mice bearing human breast cancer, the recombinant adenovirus vector was injected directly into the tumor followed by intraperitoneal injection of the prodrugs GCV and/or 5-FC, and the subsequent tumor growth was observed.

RESULTSThe recombinant adenovirus achieved similar infection rates in MCF-7 and human mammary epithelial cells, and the rates increased gradually with the multiplicity of infection (MOI) of the virus. RT-PCR demonstrated the presence of CD/TK gene product in infected MCF-7 cells, but not in the infected mammary epithelial cells. The infected MCF-7 cells, but not the mammary epithelial cells, were highly sensitive to the pro-drugs. The CD/TK fusion gene system showed significantly greater efficiency than either of the single suicide gene in killing the target cells (P<0.01). At the MOI of 100, treatment of the infected cells with the pro-drugs resulted in increased cell percentage in G(0)-G(1) phase and decreased percentage in S phase. In nude mice bearing MCF-7 cell-derived subcutaneous tumor, treatment with the double suicide gene system significantly inhibited the tumor growth, showing much stronger effect than either of the single suicide gene (P<0.01).

CONCLUSIONThe adenovirus-mediated CD/TK double suicide gene driven by VEGF promoter combined with GCV and 5-FC treatment can be an effective therapy against experimental breast cancer, and produces much greater efficacy than the single suicide gene CD/TK combined with GCV or 5-FC.

Adenoviridae ; genetics ; Breast Neoplasms ; genetics ; metabolism ; pathology ; Cell Cycle ; drug effects ; Cell Line, Tumor ; Cell Proliferation ; drug effects ; Cell Survival ; drug effects ; Cytosine Deaminase ; genetics ; metabolism ; Female ; Flow Cytometry ; Flucytosine ; pharmacology ; Ganciclovir ; pharmacology ; Genes, Transgenic, Suicide ; genetics ; Genetic Therapy ; methods ; Genetic Vectors ; genetics ; Green Fluorescent Proteins ; genetics ; metabolism ; Humans ; Recombinant Fusion Proteins ; genetics ; metabolism ; Reverse Transcriptase Polymerase Chain Reaction ; Thymidine Kinase ; genetics ; metabolism ; Vascular Endothelial Growth Factor A ; genetics ; metabolism