A new combined technology: Macroporous adsorption resin and high speed counter current chromatography for hydroxytyrosol separation from olive leaf enzymatic hydrolysate.

Due to three free hydroxyl groups, hydroxytyrosol (HT) presents strong bioactivity and has broad food and drug application prospects. However, there is no good separation and purification technology. In this study, separation and purification technology of HT from the ethyl acetate extraction of enzymatic hydrolysate from olive leaf (EEEH) was investigated with macroporous adsorption resin (MAR) and high-speed counter-current chromatography (HSCCC) and the separation factors were optimized. First, the adsorption properties of eight MARs (AB-8, S-8, D-101, X-5, XAD-1, XAD-5, NKA-Ⅱ, H-103) for HT enrichment were studied. The results showed that H-103 macroporous resin was adsorbent, sample concentration was 1.5 mg/mL, eluent was 30 % ethanol solution, sample loading rate was 3.0 BV/h, elution velocity was 2.0 BV/h, and HT purity of EEEH was increased from 10.23 % to 40.78 %. Then, solvent systems were examined according to partition coefficients of target component and petroleum ether: ethyl acetate: methanol: water (4:6:4:6, v/v) system was chosen. The critical experimental parameters of HSCCC were optimized as following: revolution speed was 1200 rpm and flow rate was 3 mL/min. The HT purity of macroporous resin purified EEEH was increased from 40.78 % to 85.7 %. Therefore, MAR-HSCCC combined technology could be a very effective approach to separate and purify HT from EEEH.

Borderline personality disorder and thyroid diseases: a Mendelian randomization study.

Background: Previous studies have shown that there is a correlation between diseases of the thyroid gland and mental illnesses; however, any causal relationship between them remains unclear. This study aimed to evaluate the causal relationship between borderline personality disorder and four thyroid diseases. Methods: The causal relationship was inferred using double-sample Mendelian randomization analysis of appropriate instrumental variables from genome-wide association studies. We calculated the estimated value of the effect using various statistical methods. Results: Borderline personality disorder was a risk factor for non-toxic single thyroid nodules with each increase in standard deviation increasing the risk of a non-toxic single thyroid nodule by 1.13 times (odds ratio = 1.131; 95% confidence interval, 1.006-1.270; P=0.039). There was no evidence of a correlation between borderline personality disorder and hyperthyroidism/thyrotoxicosis, hypothyroidism, and autoimmune thyroiditis. Conclusion: This study showed that there is a positive causal correlation between borderline personality disorder and non-toxic single thyroid nodules but not with other thyroid diseases. This means that thyroid status should be monitored in patients with borderline personality disorder. However, the possibility of a causal relationship between other mental illnesses and thyroid diseases requires further research.

[Preparation and Application of Monoclonal Antibody Against Human von Willebrand Factor Propeptide].

OBJECTIVE: To develop monoclonal antibodies that can specifically recognize human von Willebrand factor (VWF) propeptide (VWFpp) in plasma, and establish a rapid and reliable method for the detection of VWFpp antigen in plasma by using the double-antibody sandwich ELISA with the obtained anti-VWFpp monoclonal antibody. METHODS: The recombinant human VWFpp (D1 and D2 regions) protein expressed in eukaryotic cells was used as immunogen to immunize BALB/c mice with routine method, so as to obtain clones of fusion cells. After screening and identification, hybridoma cell lines secreting monoclonal antibodies against VWFpp were selected, and then double-antibody sandwich ELISA assay was used to construct VWFpp antigen detection kit for the determination of VWFpp in human plasma. The levels of VWFpp antigen in plasma of 12 leukemia patients who underwent bone marrow transplantation were dynamically detected. RESULTS: Two hybridoma cell lines that can be subcultured continuously and secrete monoclonal antibodies against VWFpp were obtained and named SZ175 and SZ176 respectively. Identified by ELISA and Western blot, the antibodies could both specifically recognize VWFpp but couldn't recognize mature VWF (without propeptide). Based on the principle of double-antibody sandwich ELISA, monoclonal antibodies SZ175 and SZ176 were successfully made into a kit for detecting VWFpp antigen. The plasma VWFpp levels of leukemia patients before and after bone marrow transplantation were dynamically detected. The results showed that the plasma VWFpp levels of the patients after transplantation were significantly higher than those before transplantation. CONCLUSION: Two monoclonal antibodies against VWFpp were successfully prepared, and a double-antibody sandwich ELISA detection kit for VWFpp antigen was constructed, which provides a powerful tool for further study on the biological function of VWFpp, the clinical diagnosis and classification of von Willebrand disease (VWD), and the prognostic monitoring of endothelial injury-related diseases.

Higher efficacy of Etoposide + Cytarabine Plus Pegfilgrastim in poorly mobilizing Multiple Myeloma and lymphoma Patients.

BACKGROUND AIMS: An optimal strategy for mobilizing hematopoietic stem cells in poorly mobilizing patients with multiple myeloma (MM) and lymphoma has not yet been determined. METHODS: We retrospectively analyzed the efficacy and safety of etoposide combined with cytarabine (etoposide 75 mg/m2, daily d1∼2; Ara-C 300 mg/m2, every 12 h d1∼2), plus pegfilgrastim (6 mg d6) in 32 patients with MM or lymphoma, among whom 53.1% were defined as "proven poor mobilizers." RESULTS: This approach resulted in adequate mobilization (≥2.0 × 106 CD34+ cells/kg) in 93.8% of patients and optimal mobilization (≥5.0 × 106 CD34+ cells/kg) in 71.9% of patients. A total of 100% of patients with MM reached at least 5 × 106 CD34+ cells/kg collected, the amount required for double autologous stem cell transplant. In total, 88.2% of patients with lymphoma reached at least 2 × 106 CD34+ cells/kg collected, the amount required for a single autologous stem cell transplant. This was achieved with a single leukapheresis in 78.1% of cases. A median peak number of 42.0/µL circulating CD34+ cells and a median number of blood CD34+ cells counts in 6.7 × 106/L were collected among 30 successful mobilizers. Approximately 6.3% of patients required plerixafor rescue, which was successful. Nine (28.1%) of the 32 patients suffered grade 2∼3 infections, and 50% required platelet transfusions. CONCLUSIONS: We conclude that chemo-mobilization with etoposide, Ara-C and pegfilgrastim in poorly mobilizing patients with MM or lymphoma is very effective and has acceptable toxicity.

Loss of IRF8 inhibits the growth of acute myeloid leukemia cells.

The transcription factor interferon regulatory factor 8 (IRF8), as a member of the IRF family, is essential for myeloid cell differentiation. However, the precise role of IRF8 in the pathogenesis of acute myeloid leukemia (AML) remains unknown. By using multivariate analysis, we discovered that high IRF8 expression was an independent poor predictor of overall survival (OS) in AML patients from our clinical follow-up study. The proliferation of three AML cell lines was significantly inhibited by shRNA-mediated knockdown of IRF8, owing to cell cycle S-phase arrest. Furthermore, we demonstrated that knocking down IRF8 could suppress the expression of CyclinA and CyclinB1, resulting in a shift in cell cycle distribution. Loss of IRF8 in AML cells decreased the expression of STAT3 and phosphor-STAT3 (pSTAT3), which are key factors in JAK/STAT signal pathway and are important for AML progression. Using a xenograft mouse model, we discovered the antiproliferative effect of losing IRF8 in vivo. In conclusion, this study found that IRF8 may play a prognostic factor and therapeutic target in AML.

Enhanced antihypertensive potential of fermented pomegranate juice: The contribution of phenolic compounds biotransformation and the resultant angiotensin-I-converting enzyme inhibition mechanism.

Current research on plant food-derived phenolic compounds as angiotensin-I-converting enzyme (ACE) inhibitors has been well documented. Pomegranate juice (PJ) has been reported positively contributed to ACE inhibition. Microbial fermentation is a preferable technique to regulate the biotransformation of phenolic compounds and their bioaccessibility, therefore promoting the ACE inhibitory activity in plant food with antihypertension potential. In this study, the remarkable improvements of ACE inhibitory activity and antioxidant capacity in Lactobacillus plantarum fermented PJ were observed. A consecutive study of phenolic compounds biotransformation, ACE inhibition kinetics and structure-activity relationship were performed. This study firstly highlights the relationship between the enhanced ACE inhibitory activity in fermented PJ and the biotransformation of phenolic compounds, providing a new way to reinforce plant food ACE inhibition potential by microbial fermentation.

Hematopoiesis reconstitution and anti-tumor effectiveness of Pai-Neng-Da capsule in acute leukemia patients with haploidentical hematopoietic stem cell transplantation.

BACKGROUND: With the rapid development of haploidentical hematopoietic stem cell transplantation (haplo-HSCT), primary poor graft function (PGF) has become a life-threatening complication. Effective therapies for PGF are inconclusive. New Chinese patent medicine Pai-Neng-Da (PND) Capsule exerts dual effect in promoting hematopoiesis recovery and regulating immunity. Still, the application of PND capsule in hematopoietic stem cell transplantation, especially in the haplo-HSCT setting, has not yet been reported. AIM: To evaluate the role of PND capsule in acute leukemia patients with haplo-HSCT. METHODS: We retrospectively collected data of acute leukemia patients who underwent haplo-HSCT at the Affiliated People's Hospital of Ningbo University between April 1, 2015 and June 30, 2020. Twenty-nine consecutive patients received oral PND capsule from the sixth day to the first month after haplo-HSCT were included in the PND group. In addition, 31 patients who did not receive PND capsule during haplo-HSCT were included in the non-PND group. Subsequently, we compared the therapeutic efficacy according to the western medical evaluation indexes and Chinese medical symptom scores, and the survival between the PND group and the non-PND group, using the chi-square test, Fisher's exact test, and the Kaplan-Meier method. RESULTS: The duration of platelet engraftment was shorter in the PND group than in the non-PND group (P = 0.039). The PND group received a lower frequency of red blood cells and platelet transfusions than the non-PND group (P = 0.033 and P = 0.035, respectively). In addition, PND capsule marginally reduced the rate of PGF (P = 0.027) and relapse (P = 0.043). After 33 (range, 4-106) months of follow-up, the 3-year relapse-free survival (P = 0.046) and progression-free survival (P = 0.049) were improved in the PND group than in the non-PND group. Also, the therapeutic efficacy of the PND group according to Chinese medical symptom scores was significantly better than that of the non-PND group (P = 0.022). Moreover, the adverse events caused by PND capsule were mild. Nevertheless, there were no significant differences in the duration of neutrophil engraftment, the risk of infection within 100 days after haplo-HSCT, the acute graft-versus-host disease, or the 3-year overall survival between the two groups. CONCLUSION: PND capsule could promote hematopoiesis reconstitution, improve the therapeutic efficacy of Chinese medical symptom scores, present anti-tumor effectiveness, and prolong the survival of acute leukemia patients with haplo-HSCT.

Numerical solution for circular tunnel excavated in strain-softening rock masses considering damaged zone.

Despite the extensive investigation on the stress and displacement distributions in tunnels, few have considered the influences of the damaged zone around a tunnel on the strength and stiffness parameters of the surrounding rock, including the gradual variation in the damaged factor D and dimensionless damaged radius [Formula: see text], under the effect of excavation disturbance. In this paper, a numerical solution is presented for the stresses and displacement of a circular tunnel excavated in a Hoek-Brown rock mass considering the progressive destruction of the damaged zone. First, the results obtained using the proposed algorithm are compared with those obtained using other numerical solutions, demonstrating a high degree of accuracy through some examples. Second, the influences of the damaged factor [Formula: see text] and dimensionless damaged radius [Formula: see text] on the stresses, radial displacement, plastic radii, and ground response curve are investigated. The results show that, as the damaged factor D increases, the radial displacement and plastic radius increase, whereas the tangential stress decreases. Both the plastic radius and displacement decrease with decreasing [Formula: see text]. This shows that the damaged factor D has a significant effect on tunnel convergence.

Identification of blood-based key biomarker and immune infiltration in Immunoglobulin A nephropathy by comprehensive bioinformatics analysis and a cohort validation.

BACKGROUND: To identify the critical genes in the onset and progression of Immunoglobulin A nephropathy (IgAN) and to explore its immune cell infiltration feature. METHODS: Differentially expressed genes (DEGs) were firstly screened from 1 blood-derived dataset GSE73953 and a glomerulus derived dataset GSE93798 through limma analysis, overlap genes omitting and weighted gene correlation network analysis (WGCNA) and further reduced according to expression pattern and correlation with the clinical features: eGFR and proteinuria, followed by external validation using the GSE37460 dataset and an IgAN cohort. In addition, the CIBERSORT tool for immune cell infiltration analysis, ceRNA network construction and Connectivity Map (CMAP) were also performed. RESULTS: A total of 195 DEGs were found, and among them, 3 upregulated (ORMDL2, NRP1, and COL4A1) and 3 downregulated genes (ST13, HSPA8 and PKP4) are verified to correlate clinically, and finally ORMDL2, NRP1 and COL4A1 were validated in patient cohort and with the ability of IgAN discrimination (highest AUC was COL4A1: 97.14%). The immune cell infiltration results revealed that significant differences could be found on resting memory CD4 T cells, activated NK cells, and M2 macrophages between control and IgAN. CONCLUSIONS: Our results demonstrated here that significantly upregulated DEGs: ORMDL2, NRP1 and COL4A1, could be served as the diagnostic marker for IgAN, and dysregulated immune cell infiltration hinted possible the immune system intervention point in the setting of IgAN.

The first complete mitogenome of skin beetles Omorgus chinensis (Coleoptera: Trogidae) with the phylogenetic implications.

The first complete mitogenome of Trogidae, Omorgus chinensis (Coleoptera: Trogidae) is sequenced using the next generation sequencing. The genomic structure is a circular molecule with 18682 bp in length, comprising 13 protein-coding genes, 22 transfer RNA genes (tRNAs), 2 ribosomal RNAs (rRNAs) and a control region. The nucleotide composition is A (39.44%), C (13.82%), T (36.78%), and G (9.96%) with an AT content of 76.22%. The phylogenetic analysis of 18 insects in Scarabaeoidae show that Omorgus chinensis shares a close ancestry with Lucanidae and Geotrupidae.

Local symptoms of Hashimoto's thyroiditis: A systematic review.

Objective: Hashimoto's thyroiditis (HT) is the most common type of thyroid disease and can cause many different manifestations. The local symptoms of HT are an under-studied area of research. Therefore, the purpose of this study was to investigate the local symptoms of HT and their prevalence. Methods: A systematic review was performed to find articles in PubMed that discuss the local symptoms of HT. Relevant vocabulary terms and key terms included: autoimmune thyroid disease (AITD), hyperthyroidism, hypothyroidism, neck, throat, pharynx, airway, esophagus, breathe, swallow, globus, sleep apnea, symptoms, and quality of life. Two investigators independently screened the eligible studies. Results: A total of 54 articles fulfilled the inclusion criteria. Of these, 25 were clinical studies, 24 were case reports, and five were reviews. These clinical studies and case reports included a total of 2660 HT patients. There were eight local symptoms related to HT: neck pain (0.02%~16%), voice changes (7%~30%), throat discomfort (20%~43.7%), shortness of breath (28%~50%), dysphagia (29%), goiter-related symptoms (69.44%), sleep apnea, and generally defined compressive symptoms. Due to the use of different outcome measures among all the studies, a meta-analysis of the data could not be performed. Conclusion: Goiter symptoms, which are an item on the ThyPRO scales, are the most frequent local symptoms in HT patients, and include neck pain, voice changes, throat discomfort, and dysphagia. These local symptoms should be identified in the clinic and included in the early diagnosis and management of HT, as well as evaluated further to understand their relevance in the pathogenesis of HT.

Relationship between platelet/lymphocyte ratio and prognosis of patients with septic acute kidney injury: A pilot study.

BACKGROUND: To explore the potential role of the platelet/lymphocyte ratio (PLR) as a prognostic marker in septic patients with acute kidney injury (AKI) and to provide theoretical evidence for the epidemiological study of the prognosis of patients with septic AKI in its early stage. METHODS: A pilot study was conducted. A logistic regression analysis was conducted to screen the risk factors, and the selected factors were performed using multiple logistic regression analysis; a Receiver Operating Characteristic curve was used to determine the optimal cutoff value of the PLR and then to calculate the sensitivity and specificity of the PLR ratio. RESULTS: Mechanical ventilation, platelet count, PLR, and arterial blood lactate concentration have a correlation with sepsis (p < 0.05). An elevated PLR is significantly associated with a worse prognosis of sepsis-induced AKI (higher mortality). CONCLUSION: The PLR might be an effective factor in predicting a worse prognosis of septic AKI patients.

Transcriptome Analysis Reveals Key Pathways and Hormone Activities Involved in Early Microtuber Formation of Dioscorea opposita.

Chinese yam (Dioscorea opposita) is an important tuberous crop used for both food and medicine. Despite a long history of cultivation, the understanding of D. opposita genetics and molecular biology remains scant, which has limited its genetic improvement. This work presents a de novo transcriptome sequencing analysis of microtuber formation in D. opposita. We assembled cDNA libraries from different stages during the process of microtuber formation, designated as initial explants (EXP), axillary bud proliferation after three weeks (BUD), and microtuber visible after four weeks (MTV). More differentially expressed genes (DEGs) and pathways were identified between BUD vs. EXP than in MTV vs. BUD, indicating that proliferation of the axillary bud is the key stage of microtuber induction. Gene classification and pathway enrichment analysis showed that microtuber formation is tightly coordinated with primary metabolism, such as amino acid biosynthesis, ribosomal component biosynthesis, and starch and sucrose metabolism. The formation of the microtuber is regulated by a variety of plant hormones, including ABA. Combined with analysis of physiological data, we suggest that ABA positively regulates tuberization in D. opposita. This study will serve as an empirical foundation for future molecular studies and for the propagation of D. opposita germplasm in field crops.

Clinical utility of characterizing intestinal flora in septic kidney injury.

The incidence of septic acute kidney injury (AKI) is increasing, it has become a major threat to human health because of its acute onset, poor prognosis, and high hospital costs. The most common cause of AKI in critical-care units is sepsis. Septic AKI is a complex and multi-factorial process; its pathogenesis is not fully understood. In sepsis, the destruction of mucosal barriers, intestinal flora disorders, intestinal ischemia/reperfusion injury, use of antibiotics, and lack of intestinal nutrients lead to an inflammatory reactions that in turn affects the metabolism and immunity of the host. Such changes further influence the occurrence and development of AKI. New technology is enabling various detection methods for intestinal flora. Clinical application of these methods in septic renal injury is expected to clarify the relationship among pathogenesis, disease progression mechanism, and intestinal flora.

[Systematic review of ultrasound-guided fluid resuscitation vs. early goal-directed therapy in patients with septic shock].

OBJECTIVE: To systematically review the efficacy of ultrasound-guided fluid resuscitation and early goal-directed therapy (EGDT) in patients with septic shock. METHODS: Multiple databases including Wanfang, CNKI, SinoMed, VIP, PubMed, Embase, Cochrane Library and Web of Science were searched from initial to August 2019 for randomized controlled trial (RCT) studies about the comparison of ultrasound-guided fluid resuscitation and EGDT on resuscitation effect in patients with septic shock. Language, country and region were unlimited. Data extraction and quality evaluation were carried out by means of independent review and cross check results by two researchers. RESULTS: Finally, only two English RCT studies were enrolled. In the two RCT studies, the ultrasound groups used inferior vena cava collapse index (VCCI) and ultrasound score to guide fluid resuscitation, which resulted in clinical heterogeneity. Because the results could not be pooled, only systematic review, not meta-analysis, could be done. There were measurement bias and selection bias in the two RCT studies, and the literature quality level was B and C respectively. System review results showed that using ultrasound would reduce 7-day mortality (15.0% vs. 35.0%, P = 0.039) and prescribe less of 24-hour intravenous fluids (mL: 900 vs. 1 850, P < 0.01) for patients with septic shock as compared with EGDT. Ultrasound was easy to assess the reactive capacity and cardiac function of patients with septic shock, so as to decrease the incidence of pulmonary edema, which was significantly lower than EGDT (15.0% vs. 37.5%, P = 0.022). However, there was no statistically significant difference in 28-day mortality, duration of mechanical ventilation or length of intensive care unit (ICU) stay between the two groups. CONCLUSIONS: The ultrasound-guided fluid resuscitation may be useful and practical for septic shock patients within 7 days after admission as compared with EGDT, but it cannot reduce the 28-day mortality, duration of mechanical ventilation or length of ICU stay.

Visualization data on concentrating apple juice with a trinitarian crystallization suspension freeze concentrator.

This article contains visualization data on concentrating apple juice with a trinitarian suspension crystallization freeze concentrator, which integrates scraped-surface heat exchanger, suspension crystallizer and wash-column into one piece of equipment. The visualization data on ice accumulation, ice bed development and consolidation in the crystallizer/wash-column of the freeze concentrator are presented in a set of photographs in chronological order and videos attached as appendix materials. These data refer to the related research article entitled "Concentration of Apple Juice with an Intelligent Freeze Concentrator" Ding et al., 2019.

[Clinical value of non-coding RNA molecular markers for sepsis].

OBJECTIVE: Sepsis and septic shock are important clinical problems in critically ill patients, accounting for the first cause of death in intensive care unit (ICU). Therefore, early diagnosis and treatment are particularly important. Recently, genome-wide expression analysis of non-coding RNA in septic patients showed that more than 80% were differentially expressed compared with healthy individuals. These molecules play important roles in biological processes, including innate immunity, mitochondrial function and apoptosis. Therefore, a class of non-coding RNAs such as microRNA (miRNA), long-chain non-coding RNA (lncRNA) and circular non-coding RNA (circRNA) are increasingly recognized as a regulator of various signaling pathways. The potential of regulatory non-coding RNA target to treat sepsis was discussed by studying non-coding RNAs that might serve as molecular markers of sepsis, and its clinical value was evaluated.

Levosimendan does not reduce the mortality of critically ill adult patients with sepsis and septic shock: a meta-analysis.

BACKGROUND: Previous studies on whether or not levosimendan improved the prognosis of patients with sepsis and septic shock have been inconsistent. We aimed to provide an updated analysis of the therapeutic value of levosimendan in adult patients with sepsis and septic shock, in order to provide evidence-based medical evidence for its use. METHODS: PubMed, Embase, Cochrane Library, Wanfang Data, and CNKI were searched until August 2018 without language restriction. Randomized controlled studies of levosimendan with either inotropic drugs or placebo for the treatment of sepsis or septic shock were enrolled. The primary outcome was mortality, and cardiac index and serum lactate levels were the secondary outcomes. RESULTS: A total of 20 randomized controlled studies were included in this meta-analysis, including 1467 patients, with 738 patients in the experimental group (levosimendan group) and 729 patients in the control group (other inotropic drugs or placebo). There were no significant differences in mortality between the levosimendan and control groups (fixed-effect relative risk [RR] = 0.90, 95% confidence interval [CI] [0.79, 1.03], P = 0.13). Levosimendan increased the cardiac index (VMD [weighted mean difference] = 0.51, 95% CI [0.06, 0.95], P = 0.02); and serum lactate levels were lower (VMD = -1.04, 95% CI [-1.47, -0.60], P < 0.00001). CONCLUSIONS: Based on current clinical evidence, levosimendan does not reduce mortality in adult critically ill patients with sepsis and septic shock. Physicians should use levosimendan with caution in patients with sepsis and septic shock.