Manipulated overlapping reactivation of multiple memories promotes explicit gist abstraction.

Sleep is considered to promote gist abstraction on the basis of spontaneous memory reactivation. As speculated in the theory of 'information overlap to abstract (iOtA)', 'overlap' between reactivated memories, beyond reactivation, is crucial to gist abstraction. Yet so far, empirical research has not tested this theory by manipulating the factor of 'overlap'. In the current study, 'overlap' itself was manipulated by targeted memory reactivation (TMR), through simultaneously reactivating multiple memories that either contain or do not contain spatially overlapped gist information, to investigate the effect of overlapping reactivation on gist abstraction. This study had a factorial design of 2 factors with 2 levels respectively (spatial overlap/no spatial overlap, TMR/no-TMR). Accordingly, 82 healthy college students (aged 19 âˆ¼ 25, 57 females) were randomized into four groups. After learning 16 pictures, paired with 4 auditory cues (4 pictures - 1 cue) according to the grouping, participants were given a 90-minute nap opportunity. Then TMR cueing was conducted during N2 and slow wave sleep of the nap. Performance in memory task was used to measure gist abstraction. The results showed a significant main effect of TMR on both implicit and explicit gist abstraction, and a marginally significant interaction effect on explicit gist abstraction. Further analyses showed that explicit gist abstraction in the spatial overlap & TMR group was significantly better than in the control group. Moreover, explicit gist abstraction was positively correlated with spindle density. The current study thus indicates that TMR facilitates gist abstraction, and explicit gist abstraction may benefit more from overlapping reactivation.

[Discussion on reference sample research of traditional Chinese medicine compound preparations developed from catalogued ancient classical prescriptions].

The concept of reference sample was put forward in the Guidance on CMC of Traditional Chinese Medicine Compound Preparations Developed from Catalogued Ancient Classical Prescriptions(Interim). The research on reference sample is a key link in the research and development of traditional Chinese medicine(TCM) compound prescriptions from catalogued ancient classical prescriptions(known as Category 3.1 TCM). This paper discusses the content of research on reference sample by analyzing the characteristics of Category 3.1 TCM and the purpose of research on reference sample. Furthermore, suggestions on the research of reference sample are proposed according to the development and evaluation practice of Category 3.1 TCM and research achievements of TCM regulatory science, aiming to provide reference for colleagues in this industry.

Quercetin inhibits the NOX2/ROS-mediated NF-κB/TXNIP signaling pathway to ameliorate pyroptosis of cardiomyocytes to relieve sepsis-induced cardiomyopathy.

Sepsis-induced cardiomyopathy (SIC) has high morbidity and mortality. Quercetin (QUE) has been used to treat many inflammatory diseases related to pyroptosis. However, its effect on SIC has not been reported before. We aimed to explore the therapeutic mechanism of QUE on SIC. We found that the expression levels of NOX2, markers of myocardial injury and inflammatory factors related to pyroptosis were upregulated in the serum of SIC patients. QUE improved the viability and reduced the death rate of LPS-treated H9C2 cells. It could downregulate the expression level of NOX2 and alleviate NOX2-induced mitochondrial damage to inhibit the ROS-mediated NF-κB/TXNIP pathway thus ameliorating cell pyroptosis. Overexpression of NOX2 partially attenuated the anti-pyroptotic effects of QUE on LPS-treated H9C2 cells in vitro. Besides, the results of animal experiments reported that the mitochondrial damage was reduced by QUE treatment, which subsequently inhibited the ROS-mediated NF-κB/TXNIP pathway to ameliorate cell pyroptosis to further alleviate myocardial injury in CLP-induced rats in vivo. To conclude, QUE suppressed the NOX2/ROS-mediated NF-κB/TXNIP signaling pathway to ameliorate pyroptosis of cardiomyocytes to relieve SIC.

The effect of (H2O)n (n = 1-3) clusters on the reaction of HONO with HCl: a mechanistic and kinetic study.

The reaction between HONO and HCl is a possible pathway for the generation of ClNO, which is prone to photolyze, produce chlorine radicals, and accelerate the oxidation of tropospheric VOCs. Current experimental and theoretical studies have significant differences in rate constants under similar conditions. This study aims to examine the reasons for this difference. In this study, the effects of a single water molecule, water dimer, water trimer, excess HCl and excess HONO on the reaction mechanism of HONO + HCl were studied at the CCSD(T)/aug-cc-pVTZ//M06-2X/6-311+G(2df,2p) level and the rate constants of each reaction channel were calculated. Our results showed that the reaction potential barrier of HONO with HCl was the lowest only when the water dimer was present, and the reaction rate constants were close to the experimental results, and both the cis-HONO⋯(H2O)2 + HCl and the trans-HONO⋯(H2O)2 + HCl reaction paths are likely to occur. We think that the reason for the inconsistency between experimental and theoretical results is that the water dimer is involved in the reaction in experiments.

Off-label uses of ustekinumab.

Ustekinumab (brand name Stelara®) is a human interleukin-12 and -23 antagonist and has been indicated for the treatments of moderate to severe plaque psoriasis, psoriatic arthritis, Crohn's disease and ulcerative colitis. This review aims to synthesize and interpret the literature evaluating the off-label uses of ustekinumab. We performed searches in PubMed and ClinicalTrials.gov for clinical trials, observational studies, case series, and case reports evaluating label uses of ustekinumab. Studies evaluated the efficacy of ustekinumab for the following conditions: other types of psoriasis (expect plaque psoriasis and psoriatic arthritis), pityriasis rubra pilaris, hidradenitis suppurativa, atopic dermatitis, pyoderma gangrenosum, et al. Based on the available literature, ustekinumab appears to be a potential treatment choice for many other diseases. However, more clinical trials data are needed to adequately assess the safety and efficacy of ustekinumab for the treatment of these conditions.

Aggressive disseminated Rhizomucor pusillus infection in a Ph-like acute lymphoblastic leukemia patient: Early detection by cell-free DNA next-generation sequencing.

Disseminated Rhizomucor pusillus infection is a very rare but fatal complication in immunocompromised patients, because of aggressive clinical process with delayed diagnosis by routine laboratory tests. Recently, cell-free DNA next-generation sequencing (cfDNA NGS) has been used for the timely detection of infectious pathogens including mucormycosis. Herein, we described an 18-year-old male with Philadelphia-like acute lymphoblastic leukemia who received a timely diagnosis of R. pusillus infection by cell-free DNA next-generation sequencing, and confirmed by silver staining and qPCR on biopsy tissue. To the best of our knowledge, this was the first case of disseminated R. pusillus infection detected by cfDNA NGS and confirmed by histology in an adult leukemia patient. In addition, this case was supposed to be the most extensive R. pusillus infection diagnosed, involving the lung, skin, liver, kidney, spleen and brain, and the only one case who survived the infection had a favorable outcome through treatment with liposome amphotericin B sequential posaconazole. This case suggested that cfDNA NGS could be used to successfully detect rare pathogen infections, and this was especially important for R. pusillus because timely diagnosis and effective treatment could improve the prognosis of this kind of patient.

The Two-Steps Reaction Fluorescent Probe for the Selective Detection of Cysteine and Its Applications.

We reported the specific fluorescent probe (MC-BOD-XDS) with two-steps reaction based on monosulfanyl-coumarin-BODIPY for selective detection of cysteine, high activity sulfanyl-coumarin as the multiple reaction group instead of a group internal standard fluorophore. The reaction mechanism of MC-BOD-XDS for detecting cysteine was different from the reported probes about the nucleophilic aromatic substitution reaction (SNAr) of chlorinated BODIPY. The fluorescent color of MC-BOD-XDS changed from yellow to red, and then to orange. The linear calibration diagram showed that it can potentially be used for quantitatively detection of Cys. Its potential applications were demonstrated by employing it for detection of Cys in artificial urine and in fluorescent imaging in HeLa cells.

Virulence of "white-gray-opaque" tri-stable transformation in clinical Candida albicans in vitro and in vivo.

The study aimed to induce the white-opaque-gray tri-stable transformation in clinical C. albicans and to explore their potential pathogenicity. Sixty-four clinical strains were used to induce the white, opaque and gray cells of C. albicans. Secreted aspartyl proteinases (Sap) activity of the three phenotypes was then measured, and a vulvovaginal candidiasis (VVC) animal model was constructed. Of the 64 clinical strains, only 3 strains successfully underwent white-gray-opaque tri-stable transformation, and the three strains all belonged to MTL homozygous strains. Pz values in white, opaque and gray phenotypes were 0.834 ± 0.012, 0.707 ± 0.036, and 0.628 ± 0.002, respectively, which indicated that the cells with gray phenotype had higher Sap activity. After inoculation of different fungal suspension, the fungal colony count in descending order was as follows: gray phenotype, opaque phenotype and white phenotype. After treated with fluconazole for 3 days or 10 days, the fungal colony counts were significantly decreased compared with that before treatment (P < 0.05). The Sap activity and pathogenicity of gray cells in C. albicans were the strongest, followed by opaque cells and white cells. Additionally, white, gray and opaque phenotypic cells were all susceptible to fluconazole.

Advances in understanding the role of adiponectin in renal fibrosis.

Renal fibrosis is characterized by the proliferation of renal intrinsic cells, activation of renal interstitial fibroblasts and deposition of extracellular matrix (ECM), processes that lead to the progressive loss of renal function. Renal fibrosis is characterized by the proliferation of renal intrinsic cells, activation of renal interstitial fibroblasts, and septal fibrosis is recognized as a marker for the progression of chronic kidney disease, a condition that is associated with high morbidity and mortality and is a significant public health burden. Despite extensive studies, there are no effective treatments for renal fibrosis. Adiponectin (APN) is a protein mainly produced by adipocytes that has anti-inflammatory and anti-atherosclerotic effects, improves insulin resistance and provides other salutary effects. Recent studies found that APN can inhibit ECM deposition by inhibiting inflammation and oxidative stress, and by regulating the TGF-ß, AMPK, MCP-1 and other signalling pathways. Many recent studies have examined the roles of these pathways in the pathogenesis of renal fibrosis. In this article, we review the pathogenic mechanism of APN in renal fibrosis and provide a theoretical basis for delaying and blocking renal fibrosis by alteration of APN activity.

[Analysis of innovative drug category 1.2 in traditional Chinese medicine and considerations on quality control of extracts].

In this article, the essence of innovative drug category 1.2 extracts and preparations in the new version of the New Drug Registration Category of traditional Chinese medicines(TCM) was analyzed by combing through the history of provisions on drug registration and comparing with other categories of drugs. After analyzing the characteristics of this type of preparations, the author concluded that the quality control objectives of category 1.2 extract should focus on ensuring the quality consistency of the active ingredients/components in batches, so as to guarantee the consistency of drug quality and efficacy. With reference to the relevant technical requirements for herbal medicinal products in European Medicines Agency(EMA) and botanicals in Food and Drug Administration(FDA),the key points in quality control of the extract should include the content and composition of the therapeutic constituents, the type and content of the concomitants, and the influence of exogenous contaminants on drug safety.

Composition and function of soil fungal community during the establishment of Quercus acutissima (Carruth.) seedlings in a Cd-contaminated soil.

This study was designed to explore the functions of soil fungal communities in the Cd tolerance of Q. acutissima seedling. Three Cd levels of 15, 30, and 40 mg kg-1 were set up using the soils collected from Q. acutissima forests. The benomyl was applied to inhibit the fungal communities in the soil. Following a 100-day pot cultivation of Q. acutissima seedlings, the plant growth, Cd content, N uptake, and fungal communities were evaluated. The results showed that the root dry weights were significantly reduced after the benomyl addition at the Cd concentrations of 30 and 40 mg kg-1. Root fungi colonization was enhanced under higher Cd concentrations when soil fungi are present (without the benomyl treatment). The fungi associated with root increased the Cd accumulation in the roots while decreased the Cd transfer to the shoot at 40 mg Cd kg-1. The 15N enrichment in root tip was positively correlated with enzyme activities of soil catalase and urease. And the activities of acid phosphatase, catalase, and urease were inhibited at each Cd level. The abundance of the dominant fungal genus differed in their response to Cd contamination. The ectomycorrhizal fungi of Tomentella and Cortinarius were identified under the higher Cd levels (40 mg kg-1). Our results implied Tomentella and Cortinarius could be applied to enhance the capacity of Quercus acutissima in the bioremediation of Cd polluted soil.

[Therapeutic experience of type â ¢-b congenital intestinal atresia].

OBJECTIVE: To summarize the clinical characteristics and treatment of type Ⅲ-b congenital intestinal atresia (CIA). METHODS: The clinical data of 12 type Ⅲ-b CIA treated in the Children's Hospital of Zhejiang University School of Medicine from January 2015 to December 2017 were analyzed retrospectively. RESULTS: Of the 12 patients diagnosed as type Ⅲ-b CIA in operation, treatment was refused during operation by their parents in 2 cases. For one child, only the proximal intestine was partly resected in the first operation, dilatation and dysplasia of the duodenum was diagnosed and total duodenum was resected and sutured in the second operation, as the child had postoperative intestinal obstruction. For one child, due to the long distal normal intestine, distal apple-peel like intestine was partly resected without mesenteric reformation. For the rest 8 children total duodenum resection and mesenteric reformation were performed. During the postoperative follow-up, one case was early rejected for further treatment by parents, one case died from complex congenital heart disease, 5 cases had the complication of short bowel syndrome. All 8 survival children received parenteral nutrition support after operation, 5 of whom received parenteral nutrition support for more than 42 days, and they were followed up for 1-3 years after discharge. The short-time efficacy was satisfactory. CONCLUSIONS: For children with type Ⅲ-b CIA, the distal apple-peel like intestine should be preserved as much as possible, the mesenteric reformation should be performed and the proximal dilated bowel should be partly resected and sutured. Postoperative nutritional support and early intestinal rehabilitation contribute to the compensation for rest intestines.

[Screening and identification of antagonistic Bacillus against Astragalus membranaceus root rot and its effect on microorganism community in root zone soil].

The Astragalus membranaceus root rot disease,a soil-borne disease,has become increasingly severe in Shanxi province.This study was aimed at getting antagonistic Bacillus with excellent bio-control effects,and determining its effects on bacterial communities in root zone soil. With Fusarium solani and F. acuminatum as the target,antagonistic Bacillus was selected through such tests as living body dual culture,antifungal effect of bacteria-free filtrate,mycelia growth inhibition in vitro and control effect in detached roots,and identified with morphology,physio-biochemical characteristics and 16 S r DNA sequence analysis. The results showed that the Bacillus strain SXKF16-1 had obvious antifungal effect. The diameter of inhibition zone of its bacteria-free filtrate to F. solani and F. acuminatum was( 25. 90±1. 18) mm and( 25. 86±1. 85) mm respectively,and showed a lasting inhibition effect to mycelia growth. The disease index of the protective treatment and that of the cure treatment in detached roots test to F. solani and F. acuminatum were( 37. 50±8. 58),( 41. 67±4. 90) and( 25. 00±8. 33),( 38. 89±9. 62) respectively,both being significantly different( P<0. 05) from that of the control. The strain SXKF16-1 was identified as Bacillus atrophaeus. The B. atrophaeus SXKF16-1 showed significantly inhibition effect to pathogen causing root rot and could increase the bacterial diversity in root zone soil. It has potential to be developed as a special biocontrol agent.

Identification of EGFR in pearl oyster (Pinctada fucata martensii) and correlation analysis of its expression and growth traits.

Marine pearl production is directly influenced by the growth speed of Pinctada fucata martensii. However, the slow growth rate of this organism remains the main challenge in aquaculture production. Epidermal growth factor receptor (EGFR), an important receptor of tyrosine kinases in animals, plays versatile functions in development, growth and tissue regeneration. In this study, we described the characteristic and function of an EGFR gene identified from P. f. martensii (PmEGFR). PmEGFR possesses a typical EGFR structure and is expressed in all studied tissues, with the highest expression level in adductor muscle. PmEGFR expression level is significantly higher in the fast-growing group than that in the slow-growing one. Correlation analysis represents that shell height and shell weight show positive correlation with PmEGFR expression (p < 0.05), and total weight and tissue weight exhibit positive correlation with it (p < 0.01). This study indicates that PmEGFR is a valuable functional gene associated with growth traits.

Alisol B 23-Acetate Inhibits IgE/Ag-Mediated Mast Cell Activation and Allergic Reaction.

Alisol B 23-acetate (AB23A), a natural triterpenoid, has been reported to exert hepatoprotective and antitumor activities. Aiming to investigate the anti-inflammatory activity, this study examined the effect of AB23A on mast cells and allergic reaction. AB23A inhibited the degranulation of mast cells stimulated by immunoglobulin E/antigen (IgE/Ag), and also decreased the synthesis of leukotriene C4 (LTC4), production of interlukin-6 (IL-6), and expression of cyclooxygenase-2 (COX-2) in a concentration-dependent manner with no significant cytotoxicity in bone marrow-derived mast cells (BMMCs). AB23A inhibited spleen tyrosine kinase (Syk) and the downstream signaling molecules including phospholipase Cγ (PLCγ), serine-threonine protein kinase/inhibitor of nuclear factor kappa-B kinase/nuclear factor kappa-B (Akt/IKK/NF-κB), and mitogen-activated protein kinases/cytosolic phospholipase A2 (MAPK/cPLA2). Furthermore, AB23A blocked mobilization of Ca2+. Similar results were obtained in other mast cell lines Rat basophilic leukemia (RBL)-2H3 cells and a human mast cell line (HMC-1). In addition, AB23A attenuated allergic responses in an acute allergy animal model, passive cutaneous anaphylaxis (PCA). Taken together, this study suggests that AB23A inhibits the activation of mast cells and ameliorates allergic reaction, and may become a lead compound for the treatment of mast cell-mediated allergic diseases.

[Transumbilical single-site laparoscopic surgery for congenital duodenal obstruction in neonates].

OBJECTIVE: To evaluate the efficacy and safety of transumbilical single-site laparoscopic surgery for congenital duodenal obstruction (CDO) in neonates. METHODS: A retrospective analysis of clinical data of 15 patients with CDO undergoing transumbilical single-site laparoscopic treatment during November 2017 and January 2018 (single-site group), and 20 patients with CDO undergoing conventional three-hole laparoscopic treatment during August 2017 and October 2017 (three-hole group) was performed. All patients were from the Children's Hospital, Zhejiang University School of Medicine. The operation time, time of initial feeding, time of adequate feeding, length of hospital stay after operation and postoperative complications were compared between two groups. RESULTS: The operations were completed in all patients. No patient converted to laparotomy, and no massive hemorrhage was observed during operation. The operation time of single-site group was (90±10) min for patients with duodenal diamond-shaped anastomosis and (81±15) min for patients with Ladd operation, while those of three-hole group were (85±9) min and (72±11) min, respectively. Postoperative initial feeding time of single-site group was (5.0±1.0) d, and that of the three-hole group was (4.8±0.8) d. The adequate feeding time was (9.0±1.2) d in the single-site group, and (9.3±0.8) d in the three-hole group. The length of hospital stay after operation was (11.2±2.5) d in the single-site group, and (11.5±2.8) d in the three-hole group. There was no significant difference in operation time, postoperative initial feeding time, adequate feeding time and length of hospital stay after operation between two groups (all P>0.05). CONCLUSIONS: Transumbilical single-site laparoscopic surgery for CDO in neonates is safe and effective, and the postoperative abdominal scar is more hidden.

[Complications after laparoscopic Ladd operation for intestinal malrotation in neonates].

OBJECTIVE: To analyze complications after laparoscopic Ladd operation for intestinal malrotation, related causes and possible solutions. METHODS: Clinical data of 81 neonates who underwent laparoscopic Ladd operations for intestinal malrotation in the Children's Hospital, Zhejiang University School of Medicine between January 2015 and January 2018 were reviewed. The abdominal complications and findings during operation and reoperation were analyzed. RESULTS: Operations were successfully completed in all patients, and there was no patient converted to open surgery. The annular pancreas in 6 cases and duodenal diaphragm in 4 cases were confirmed during the operation. The recurrent volvulus developed in 3 patients (3.7%), of whom 2 cases were confirmed to have midgut necrosis during open surgery 1 week and 3 months after laparoscopic Ladd operation, and both finally died; 1 case was corrected by second laparoscopic operation. Cecal perforation occurred in 1 patient (1.2%), which was caused by intensive high frequency coagulation of the appendiceal stump. One patient (1.2%) developed chylous ascites and improved after conservative treatment. Adhesive small bowel obstruction was observed in 3 cases (3.7%), and all relieved after conservative treatment. CONCLUSIONS: Laparoscopic Ladd operation for intestinal malrotation in neonates was effective, and the incidence of abdominal complications may be minimized by experienced skills and strict perioperative management.

[Comparison and review on specifications of fermented Cordyceps sinensis products].

There are five kinds of fermented Cordyceps crude drug and their preparations that have been approved as medicine on the market. Since the initial strains of the crude drug were all isolated from natural Cordyceps sinensis， they have similar names， chemical components and even clinical applications. However， because of the different strain species and fermentation processes， there was significant difference in quality. As a result， they should be clearly distinguished in clinical use. Most of the products were researched and developed during the 1980s and 1990s， so there was difference in quality standards for different products， and their quality control levels of some products were not perfect. At present， some of the products are approved as Chinese medicine， others are approved as chemical drugs， with a confusion in products name， management and clinical application. In this paper， the approval numbers， quality standards and clinical applications， and current problems of these products were summarized and compared; some suggestions were put forward， such as standardizing the product name， unifying the management of approval number category， and increasing the specific quality control attributes， in order to provide reference for standard implementation， quality control and drug regulation for fermented Cordyceps crude drugs and their preparations.

[Correlation of TLR2 and TLR4 gene polymorphisms with the susceptibility and recurrence of condyloma acuminatum].

OBJECTIVE: To explore the correlation of the gene polymorphisms of Toll-like receptor 2 ( TLR2) and TLR4 with the susceptibility and recurrence of condyloma acuminatum (CA). METHODS: Using Snapshot, we detected the gene polymorphisms of TLR2 597(T/C), 1350(T/C), 15607(A/G), and 2258(G/A) and TLR4 896(A/G) and 1196(C/T) in the peripheral blood of 140 CA patients and 105 HPV-negative controls. We made comparisons between the CA patients and controls as well as between the cases of recurrent CA and those of non-recurrence at 6 months after treatment. RESULTS: There were 72, 48, and 20 cases of genotype TT, TC, and CC of TLR2 597 (T/C), respectively, in the CA patients, as compared with 71, 31, and 3 cases in the controls. The gene frequency of mutant C was 31. 43% in the patients, significantly higher than 17.62% in the controls (χ2 = 12.04, P < 0.01), and it was 38.68% in the recurrent cases, remarkably higher than 27.01% in the non-recurrent cases (χ2 = 4.16, P < 0.05). There were 74, 49, and 17 cases of genotype TT, TC, and CC of TLR2 1350( T/C), respectively, in the CA patients, as compared with 73, 29, and 3 cases in the controls. The gene frequency of mutant C was 29. 64% in the patients, significantly higher than 16. 67% in the controls (χ2 =11.05, P < 0.01), and it was 36.79% in the recurrent cases, markedly higher than 25. 29% in the non-recurrent cases (χ2 = 4.18, P < 0.05). There were 44, 66, and 30 cases of genotype AA, AG, and GG of TLR2 15607(A/G), respectively, in the CA patients, as compared with 26, 58, and 21 cases in the controls. There was no significant difference in the gene frequencies of mutant G between the two groups (χ2 = 0.33, P > 0.05). No mutant genes of TLR2 2508 (G/A) or TLR4 896(A/G) and 1196(C/ T) were detected in either the CA patients or the controls. Linkage disequilibrium analysis showed a tight linkage between TLR2 597 (T/C) and 1350(T/C) (D' = 1, r2 = 0.93). CONCLUSION: TLR2 597(T/C) is tightly linked to 1350(T/C), which is correlated with both the susceptibility and the recurrence of condyloma acuminatum.