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BACKGROUND A rapid detection system for multiple pathogens that combines loop-mediated isothermal amplification (LAMP) technology and microfluidic chip technology was established. METHODS Primers were designed for the specific conservative genes of the multiple pathogens. A rapid detection method for multiple pathogens based on LAMP technology was established using the primer screening and optimization of reaction conditions. The microfluidic chip was designed. manufactured, and combined with the LAMP method for detection pathogenic bacteria as detected by a chip detector. After this, the detection limit and anti-interference ability of the chip were evaluated, and the accuracy of chip was verified by clinical samples. RESULTS A rapid microfluidic detection system for Staphylococcus aureus, Escherichia coli, Pneumoniae klebsiella, Shigella, Methicillin-resistant Staphylococcus Aureus (MRSA) and Candida albicans was established. The detection limits of the 6 strains above were 6.95, 44.6, 3.89, 15.33, 16.45, and 463 pg/µL, respectively; there was no cross-reaction with the other 15 strains; analysis of ROC curve showed the best cut-off values for the 6 strains are 38.5, 21.25, 31.5, 36.5, 22.5 and 33.75 respectively and the area under the curve for the 6 strains was 0.91, 0.91, 0.83, 0.97, 0.96, and 0.9, respectively, as analyzed by receiver operating characteristic curve (ROC). A total of 278 clinical samples collected including blood, urine, sputum and drainage fluid were analyzed, and the total coincidence rates were 0.91, 0.83, 0.75, 0.99, 0.92 and 0.76, respectively. CONCLUSIONS The establishment of microfluidic detection chips for multiple pathogen types can be used for the rapid detection of bacteria and may be particularly useful in environments with the limited equipment and personnel, such as infection sites, grassroots hospitals, disaster area rescue, etc.

Safety and efficacy of allogeneic anti-CD19 chimeric antigen receptor T cells (CAR-T cells) in persons with CD19-positive B-cell acute lymphoblastic leukemia (B-ALL) relapsing after an allotransplant remain unclear. Forty-three subjects with B-ALL relapsing post allotransplant received CAR-T cells were analyzed. 34 (79%; 95% confidence interval [CI]: 66, 92%) achieved complete histological remission (CR). Cytokine release syndrome (CRS) occurred in 38 (88%; 78, 98%) and was ≥grade-3 in 7. Two subjects died from multiorgan failure and CRS. Nine subjects (21%; 8, 34%) developed ≤grade-2 immune effector cell-associated neurotoxicity syndrome (ICANS). Two subjects developed ≤grade-2 acute graft-versus-host disease (GvHD). 1-year event-free survival (EFS) and survival was 43% (25, 62%). In 32 subjects with a complete histological remission without a second transplant, 1-year cumulative incidence of relapse was 41% (25, 62%) and 1-year EFS and survival, 59% (37, 81%). Therapy of B-ALL subjects relapsing post transplant with donor-derived CAR-T cells is safe and effective but associated with a high rate of CRS. Outcomes seem comparable to those achieved with alternative therapies but data from a randomized trial are lacking.

Pegylated liposomal doxorubicin (Peg-Dox) treatment resulted in a good outcome for patients with lymphoma and multiple myeloma, with reduced cardiotoxicity and an improved pharmacokinetic profile when compared to those of conventional doxorubicin. However, the use of Peg-Dox in myeloid neoplasms remains poorly studied. In this study, we first tested the role of Peg-Dox in the killing of myeloid cell lines and of primary myeloid leukemia cells. Then, a Peg-Dox-based protocol was used to treat patients with myeloid neoplasms. The results showed that the Peg-Dox and Peg-Dox-based protocols had a similar killing ability in myeloid cell lines and in primary myeloid leukemia cells compared to that of conventional doxorubicin. The complete remission rate was 87.5% and 100% for patients with refractory/relapsed acute myeloid leukemia and myelodysplastic syndrome with excess blasts, respectively, after treatment with Peg-Dox. All patients developed grade 3 or 4 hematological toxicity and recovered approximately 2 weeks after completing chemotherapy. No deaths or other severe complications were reported. Our results showed that Peg-Dox can be used in the treatment of myeloid neoplasms with high rates of complete remission and with mild complications.

Background Polycystic ovary syndrome (PCOS) is the most common type of endocrine disorder, affecting 5–11% of women of reproductive age worldwide. microRNAs (miRNAs) stably exist in circulating blood encapsulated in extracellular vesicles such as exosomes; therefore, serum miRNAs have the potential to serve as novel PCOS biomarkers. Methods To identify miRNA biomarkers that are associated with PCOS, we performed a comprehensive sequence-based characterization of the PCOS serum miRNA landscape. The serum exosomes were successfully isolated and characterized in a variety of ways. Next, sequence-based analysis was performed on serum exosomes to screen the differentially expressed miRNAs in women with and without PCOS. Results The sequence data revealed that the levels of 54 miRNAs significantly differed between PCOS patients and normal controls. The levels of these miRNAs were detected by RT-qPCR. The results show that hsa-miR-1299, hsa-miR-6818-5p hsa-miR-192-5p, and hsa-miR-145-5p are significantly differentially expressed in PCOS patients serum exosomes and identify these microRNAs as potential biomarkers for PCOS. Furthermore, Gene Ontology (GO) analyses and KEGG pathway analyses of the miRNA targets further allowed to explore the potential implication of the miRNAs in PCOS. Conclusion Our findings suggest that serum exosomal miRNAs serve important roles in PCOS and may be used as novel molecular biomarkers for clinical diagnosis.

Hypoxia and high-fat diet (HFD) feeding are two factors commonly existing in aquaculture. However, their individual and combined effects on nutrient composition and flesh quality in fish have not been investigated. The present study evaluated the alterations of growth, nutrient composition and flesh quality in Nile tilapia (initially 7.0 ± 0.1 g and 5.6 ± 0.2 cm) fed with normal fat diet (5.95% fat) or HFD (11.8% fat) at two dissolved oxygen levels (1.1 ± 0.1 and 7.2 ± 0.1 mg/L) for 8 weeks. The results showed that hypoxia and HFD had similar effects in inducing lipid deposition, reducing flesh protein and amino acids content, pH values and water holding ability. Hypoxia had additional adverse effects in decreasing meat yield, flesh contents of n-3 PUFA and glycogen, increasing flesh fragmentation and causing liver damages. The combination of hypoxia and HFD significantly decreased feed intake, survival rate and muscle protein content, but didn’t affect flesh quality-related parameters.

With the advent of tyrosine kinase inhibitors (TKIs), the treatment of Philadelphia chromosome-positive (Ph+) acute lymphoblastic leukemia (ALL) has entered a new era. The efficacy of TKIs compared with other ALL treatment options is emphasized by a rapid increase in the number of TKI clinical trials. Subsequently, the use of traditional approaches, such as combined chemotherapy and even allogeneic hematopoietic stem cell transplantation (allo-HSCT), for the treatment of ALL is being challenged in the clinic. In light of the increased use of TKIs in the clinic, several questions have been raised. First, is it necessary to use intensive chemotherapy during the induction course of therapy to achieve a minimal residual disease (MRD)-negative status? Must a patient reach a complete molecular response/major molecular response before receiving allo-HSCT? Does MRD status affect long-term survival after allo-HSCT? Is auto-HSCT an appropriate alternative for allo-HSCT in those Ph+ ALL patients who lack suitable donors? Here, we review the recent literature in an attempt to summarize the current status of TKI usage in the clinic, including several new therapeutic approaches, provide answers for the above questions, and speculate on the future direction of TKI utilization for the treatment of Ph+ ALL patients.

Background Approximately 30% to 60% of patients with acute B-lymphocytic leukemia (B-ALL) show as refractory or relapsed, which is one of the major causes of death in patients with B-ALL, but the methods of the treatment for relapsed/refractory B-ALL (R/R B-ALL) are limited. The chimeric antigen receptors redirected T cells (CAR-T cells) have showed a strong anti-leukemia role for B-ALL. About 90% of patients with R/R B-ALL treated with CD19-CAR-T cells achieved complete remission. However, 60% to 70% of patients relapsed after CAR-T cells treatment, which may be related to target antigen reduction or escape. New products are urgently needed to prevent and treat antigenic escapes causing recurrence. Patients and Methods In this article, we retrospectively analyzed the immunophenotype of patients with B-ALL initially diagnosed in our center from January 2010 to December 2015 to determine whether aberrant antigen expression was associated with the prognosis of patients in order to find new targets for immunotherapy. Results The results show that disease-free and overall survival in patients without aberrant antigen expression were better than patients with aberrant antigen expression. The most common abnormal antigens were CD123, CD13, and CD56. Correlation analysis showed a negative correlation between aberrant CD123 expression and both disease-free and overall survival. Conclusion Therefore, in the construction of CAR-T cells in patients with R/R B-ALL, conventional CD19 can be combined with aberrant antigens such as CD123 to form CARs with bi-specific antigens or multi-specific antigens may achieve the purpose of improving efficacy. However, more clinical trials are needed.

On the basis of single-factor test, we conducted optimization study on the three major factors (material moisture content, cultivation time, temperature) that affect the production of purebred Monascus spores through orthogonal trial. The results show that, in the trial-level range, moisture content of materials and cultivation time have larger effect on the test results, while the cultivation temperature has little effect. The optimum conditions in preparation of purebred Monascus seed koji are: 60% moisture content of materials, 5 d cultivation time, 35°C cultivation temperature, 0.1 mL inoculation, 10 g filling and 0.2% lactic acid. To verify this test scheme, ultimately the number of spores produced by Monascus is 3.35×10^7/g.

Fetal liver tyrosine kinase 3 (FLT3)-internal tandem duplications (ITDs) has been used as a powerful adverse prognostic indicator for acute myeloid leukemia (AML) in any age group. Evidence is mixed regarding the effects of allogeneic transplantation (allo-HSCT) in first complete remission (CR) for patients with FLT3/ITD AML. To fill this gap, this study provides a systematic review and meta-analysis of patients with FLT3/ITD AML receiving HSCT. A search of PubMed, Embase, and OVID yielded 1706 abstracts, two researchers screening the trials based on inclusion and exclusion criteria, and assessed the methodology quality independently. Meta-analysis showed that compared with chemotherapy, both allo-HSCT and autologous hematopoietic cell transplantation (auto-HSCT) can reduce the relapse rate (p < 0.01) and improve both the OS (p < 0.01) and DFS (p < 0.01). But when compared allo-HSCT with auto-HSCT, the OS (p = 0.27) and DFS (p = 0.19) have no statistical significance, and only the relapse indicator has statistical significance, p < 0.01. Based on the results, we can conclude that allo-HSCT is an efficient therapy approach for patients with FLT3/ITD AML. Chemotherapy cannot change the poor prognosis. Auto-HSCT can improve OS and DFS, but it cannot reduce the relapse rate.

Effects of different airing way of fermented grains on the physical and chemical indicators, uniformity, of unfermented grain and pits fermentation of Luzhou-flavor liquor were studied in this study. The results indicated that as the way of mechanization airing, the machine airing way absolutely more meets the technology demand on the production of Luzhou-flavor liquor than the airing on-field and airing on-bed. Furthermore, it not only benefits for the stability and uniformity of fermented grains, fermenting, but raises productivity of liquor.

Airing on-field, airing on-bed and airing on-machine are the usual way on production of Luzhou-flavor liquor. The essay makes a brief introduction about the three airing ways, at the same time it researches the effect of different airing ways on fermented grains and pits fermentation. As the way of mechanization airing, the machine of airing absolutely meets the technology demand on the production of Luzhou-flavor liquor, moreover, it has saved labor. Furthermore, it not only benefits for the stability and uniformity of fermented grains, fermenting, but raises productivity of liquor.

Background The Chimeric Antigen Receptor T (CAR-T) cells with strong anti-leukemia role can treat relapsed/refractory CD19-positive acute lymphoblastic leukemia (CD19+-ALL) with good outcome. The allogeneic CAR-T cells receives activation signals from both T cell receptor (TCR) and CAR, which may possess stronger activity in anti-leukemia cells. However, the infusion of allogeneic CAR-T cells may cause graft-versus-host disease, which could limit its application after allogeneic hematopoietic stem cell transplantation (allo-HSCT). It is still unclear that the role of the donor-derived CAR-T cells in treating relapsed patients after allo-HSCT. In this study, the prospective study was performed to investigate the role of donor-derived CAR-T cells on relapsed patients after allo-HSCT. Methods From April 2016 to March 2019, relapsed patients after allo-HSCT with CD19+-ALL and a Karnofsky score greater than or equal to 60 were enrolled in this study. The donor underwent apheresis for mononuclear cells to construct the CAR-T cells. The bone marrow aspiration every month after CART- cells infusion was carried out for the assessment of disease status by follow cytometry. The chimerism was detected every month after CAR-T cells treatment. Results Eighteen patients enrolled in this study. The median number of infused CAR-T cells was 1.825Í106/Kg. Thirteen patients (13/18=72.22%) reached complete remission (CR) after CAR-T cells treatment. Four patients (4/18=22.22%) had ineffectiveness. One patient died from b uncontrolled bleeding because of low platelet. The patients with blast cells Conclusion Our results showed that the treatment by donor-derived CAR-T cells for relapsed patients after allo-HSCT is safe and effective. No second transplantation was needed for relapsed patients after allo-HSCT with the treatment of donor-derived CAR-T cells that with good chimerism and continual proliferation of CAR-T cells. However, further clinical trials should be performed to investigate this protocol with larger cases. Disclosures No relevant conflicts of interest to declare.

Rationale:Relapse is the main cause of death after allogeneic hematopoietic stem cell transplantation (allo-HSCT). Unfortunately, there are no efficient methods to prevent relapse after allo-HSCT. Chimeric antigen receptor T (CAR-T) cells have achieved favorable outcomes in the treatment of

The two acetyl monoxime colorimetric method was used to detect urea content. The yeast growth curve shows that a large amount of urea in the extracellular is secreted during the growth processing. And in the stable phase (cultured for 51 hours), urea concentration is up to 38.642 mg / L, but intracellular urea concentration (cultured for 27 hours) is only 6.043 mg / L. At same time, the extracellular urea amount secreted in the medium at initial pH3-4 is less than it at initial pH5 treatment. The urea secretion level is lower when yeast cultured in the medium with 12% of alcohol. The extracellular urea level decrease when the culture temperature increased from 28°C to 32°C.

Digital image watermarking techniques for copyright protection are in widespread use. Commercial SureSign watermark software is strongly robust. However, we analyze its frequency domain features and propose an effective method to remove the SureSign watermark. Experimental results show the quality of image is good after the watermark is removed.

To evaluate the possible relationship between subclinical hypothyroidism (SCH) and metabolic syndrome (MS) and the response to clomiphene citrate (CC) stimulation in women with polycystic ovary syndrome (PCOS).One hundred and ninety-six women with PCOS were divided into two groups: (1) the SCH group with 92 patients; (2) the euthyroid (EU) group with 104 patients. Physical characteristics and metabolic parameters as well as the reaction to CC stimulating test were compared between these two groups.(1) In the SCH group, significantly higher body mass index, Ferriman-Gallwey score, serum triglyceride, insulin and glucose of oral glucose tolerance test, homeostatic model assessment-insulin resistance (HOMA-IR) and significantly lower serum high-density lipoprotein cholesterol was observed in comparison with those in the EU group (p 0.05). (2) The prevalence of CC resistance (30.4%), IR (43.5%) and MS (34.8%) in the SCH group was significantly higher than that in the EU group (p0.05).SCH was found associated with IR, MS and CC resistance in women with PCOS. PCOS patients with SCH may have a poorer treatment response to ovulation induction with CC.

Most existing digital watermarking algorithms, which are based on the Discrete Wavelet Transform, are not robust to geometric distortions, even if for some special distortions, such as multiples of 90^o rotation of integers and image flipping, which change the location of pixels but have no effect on the value of the image. Therefore, to solve the problem, according to Haar wavelet transform theory, the redistributed invariant wavelet domain is constructed and proofed in this paper; a novel image watermarking algorithm, based on the invariant domain, is proposed to eliminate such distortions. The experimental results showed that the proposed algorithm not only can resist the common image processing operations, but also successfully resist the distortions that result from multiples of 90^o rotations of integers and image flipping.

OBJECTIVE To explore the anti-angiogenic effects of genistein on synovium in a rat model of type II collagen-induced arthritis (CIA). METHODS Forty SD rats were randomly divided into normal group, model group, genistein group, methotrexate (MTX) group and Gen plus MTX group with 8 rats in each group. Arthritis in rats was induced by subcutaneous injection of type II collagen combined with complete Freund's adjuvant (CFA). On the second day after the injection, 1 mL of suspension liquid of genistein (30 mg/kg body weight, once daily) and MTX (0.2 mg/kg body weight, once a week) were administered by oral gavage respectively. The rats in normal group and model group were administered with normal saline in the same volume. Synovium of knee joints and peripheral serum were collected from the CIA rats. Microvessel density in synovium (MVD) was detected by immunohistochemical method and serum vascular endothelial growth factor (VEGF) and matrix metallopeptidase (MMP)-1, 2 and 9 levels were detected by using Western blotting. RESULTS Arthritis index score, paw volume of rats in the model group were significantly higher than those in the normal group (P

The selection of keywords for bidding is a critical component of paid search advertising. When the number of possible keywords is enormous, it becomes difficult to choose the best keywords for advertising and then subsequently to assess their effect. To this end, we propose an ultrahigh dimensional keyword selection approach that not only reduces the dimension for selections, but also generates the top listed keywords for profits. An empirical analysis using a unique panel dataset from a large online clothes retailer that advertises on the largest search engine in China (i.e., Baidu) is presented to illustrate the usefulness of our approach.