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For the reason of rapid evolution of antibiotic resistance in Staphylococcus aureus, antivirulence therapy may be a promising alternative for effective control of spread of resistant pathogens. The Chinese Materia Medica has been widely used for treatment of disease and production of health food, and it remains a valuable resource for discovery of compounds possessing antivirule nce activity.Through a Caenorhabditis elegans infection model, EtOAc-soluble fraction of 80% EtOH extract of Salvia miltiorrhiza Bunge (SMEA) was found to possess potential anti-infective activity against S. aureus. Then, several in vitro assays indicated that SMEA had robust antivirulence activity at the dose of 400 μg/mL, reducing hemolytic activity and α-hemolysin expression in S. aureus. Furthermore, at 100 mg/kg, SMEA reduced abscess formation in the main organs of mice challenged with S. aureus. In order to identify the bioactive components of SMEA and investigate the mechanisms underlying the antivirulence activity, SMEA was separated using bioassay-guided fractionation. As a result, eight compounds were identified in SMEA. Among them, tanshinone IIB (TNB) showed strong antivirulence activity both in vitro and in vivo. Furthermore, at 24 μg/mL, TNB significantly reduced the expression of RNAIII and psmα, indicating that the mechanism underlying TNB activity was related to the accessory gene regulator quorum sensing system. Collectively, the antivirulence effect of TNB making it a promising candidate for the development of drugs used against S. aureus infections.

A type III polyketide synthase (SfuPKS1) from the edible seaweed Sargassum fusiforme was molecularly cloned and biochemically characterized. The recombinant SfuPKS1 catalyzed the condensation of fatty acyl-CoA with two or three malonyl-CoA using lactone-type intramolecular cyclization to produce tri- and/or tetraketides. Moreover, it can also utilize phenylpropanoyl-CoA to synthesize phloroglucinol derivatives through Claisen-type cyclization, exhibiting broad substrate and catalysis specificity. Furthermore, the catalytic efficiency (kcat/KM) for acetyl-CoA was 11.8-fold higher than that for 4-coumaroyl-CoA. A pathway for the synthesis of naringenin involving SfuPKS1 was also constructed in Escherichia coli by recombinant means, resulting in 4.9 mg of naringenin per liter.

The potential advantage of laparoscopic gastrectomy (LG) compared with open gastrectomy (OG) for serosa-invasive (pT4a) Siewert type II and III adenocarcinoma of the esophagogastric junction (AEG) remains uncertain. Thus, the purpose of this study was to investigate the short- and long-term outcomes of LG compared to OG for pT4a Siewert type II/III AEG cancers. We retrospectively evaluated 283 patients with pathological confirmed T4a Siewert type II and type III AEG who underwent LG or OG in our center between January 2004 and September 2015. The short- and long-term outcomes were compared between the groups using a 1:1 matched propensity score matching method (PSM). The LG group had a longer operation time, less estimated blood loss, less time to first flatus, less time to start liquid diet, less time to first ambulation, and shorter length of incision than the OG group. The conversion rates were 5.4% in the LG groups. There was no significant difference in the overall complication rate between the LG and OG groups. The 5-year overall survival (OS) and the 5-year disease-free survival (DFS) were comparable between the LG and OG groups (35.4% vs 32.1%, p = 0.541; 34.1% vs 31.0%, p = 0.523, respectively). There was no significant difference in the recurrence rate and pattern between the LG and OG groups. Laparoscopic gastrectomy is associated with better short-term outcomes and similar long-term outcomes for pT4a Siewert type II/III AEG. This study reveals that LG could be a safe and feasible option for pT4a Siewert type II/III AEG compared to OG.

Comorbid chronic pain and depression are increasingly becoming a concerning public problem, but the underlying mechanisms remain unclear. Here, we demonstrate that pain-related depression-like behaviors are induced in a rat model of chronic constriction injury (CCI). Using this model, we found that chronic neuropathic pain decreased the activity and expression of sirtuin 1 (SIRT1, an NAD+-dependent deacetylase) in the central nucleus of the amygdala (CeA). In addition, the pharmacologic activation of SIRT1 in the CeA could alleviate the depression-like behaviors associated with chronic pain while relieving sensory pain. Accordingly, adeno-associated virus (AAV)-mediated SIRT1 overexpression in the CeA produced a positive effect on the easement of chronic pain and comorbid depression. Taken together, these findings highlight the role of SIRT1 in the CeA in chronic pain and depression states and reveal that the upregulation of SIRT1 may be a potential therapy for the treatment of pain-depression comorbidities.

The presence of the blood-brain barrier (BBB) remains a challenge in the treatment of central nervous system (CNS) diseases, as it hinders the infiltration of many therapeutic drugs into the brain parenchyma. Therefore, developing efficacious pharmacological agents that can traverse the BBB is crucial for optimal treatment of diseases of the CNS such as neurodegenerative conditions and brain tumors. Adeno-associated virus (AAV), one of the most promising gene therapy vectors, has been shown to cross the BBB safely and is non-pathogenic in nature and therefore has been utilized for numerous diseases of the CNS. Along with the development of protein engineering techniques such as directed evolution including DNA shuffling, a great number of BBB-crossing AAVs have been developed, that could be systemically injected for therapeutic benefit. In this review, we discuss several feasible approaches to improve transportation of therapeutic agents to the CNS. We also discuss the advantages of using BBB-crossing AAVs, their role as a gene delivery agent and highlight the different types of BBB-AAV vectors that have been developed in order to provide a greater insight into how they can be used in diseases of the CNS.

Anesthesia of neonates with propofol induces persistent behavioral abnormalities in adulthood. Although propofol-triggered apoptosis of neurons in the developing brain may contribute to the development of cognitive deficits, the mechanism of neurotoxicity induced by neonatal exposure to propofol remains unclear. In this study, the effects of neonatal propofol anesthesia on synaptic plasticity and neurocognitive function were investigated. Postnatal day 7 (PND-7) Sprague-Dawley rats were intraperitoneally injected with fat emulsion or 20, 40 or 60 mg/kg propofol for three consecutive days. The expression of brain-derived neurotrophic factor (BDNF), tropomyosin-related kinase B (TrkB) and postsynaptic density protein 95 (PSD-95) in the rat hippocampus at PND-10 and PND-12 was measured by Western blotting. The number of dendritic branches, total dendritic length and dendritic spine density were observed by Golgi-Cox staining 24 h and 72 h after the last propofol administration. Long-term potentiation (LTP) was measured electrophysiologically in hippocampus of PND-60 rats to evaluate the synaptic function. The learning and memory abilities of rats were evaluated by Morris water maze (MWM) experiments, Novel object recognition test (NORT) and Object location test (OLT) at PND-60. Our results showed that neonatal exposure to propofol significantly inhibited the expression of BDNF, TrkB and PSD-95 in the rat hippocampus. The number of dendritic branches, total dendritic length and dendritic spine density of neurons in the rat hippocampus were markedly reduced after neonatal propofol anesthesia. LTP was significantly diminished in hippocampus of PND-60 rats after repeated exposure to propofol in the neonatal period. Morris water maze experiments showed that repeated neonatal exposure to propofol significantly prolonged the escape latency and decreased the time spent in the target quadrant and the number of platform crossings. NORT and OLT showed that repeated neonatal exposure to propofol markedly reduced the Investigation Time for novel object or location. All of the results above indicate that repeated exposure to propofol in the neonatal period can impair hippocampal synaptic plasticity and the recognition function of rats in adulthood.

Group 2 innate lymphoid cells (ILC2s), characterized by secretion of type 2 cytokines, regulate multiple immune responses. ILC2s are found in different tumor tissues, and ILC2-derived interleukin (IL)-4, IL-5, and IL-13 act on the cells in tumor microenvironment to participate in tumor progression. ILC2s are abundant in colorectal cancer (CRC) tissue, but the role of ILC2s in CRC remains unclear. In this study, we found that the percentage of ILC2s was higher in CRC tissue than in the adjacent normal tissue and that these ILC2s were the dominant IL-9-secreting cell-subsets in CRC tissue, as shown by flow cytometry analysis. ILC2s-derived IL-9 could activate CD8+ T cells to inhibit tumor growth, while anti-IL-9 reversed this effect. In vivo experiments showed that neutralizing ILC2s promoted tumor growth, while tumor inhibition occurred by intravenous injection of IL-9. In conclusion, our results demonstrated that ILC2-derived IL-9 could activate CD8+ T cells to promote anti-tumor effects in CRC.

Lev/MSNs/n-HA/PU has been proved to be a novel scaffold material to treat bone defect caused by chronic osteomyelitis. We have previously identified that this material can effectively treat chronic osteomyelitis caused by Staphylococcus aureus in vivo. However, the potential mechanisms of antibacterial and osteogenic induction properties remain unclear. Thus, for osteogenesis property, immunohistochemistry, PCR, and Western blot were performed to detect the expression of osteogenic markers. Furthermore, flow cytometry and TUNEL were applied to analyze MC3T3-E1 proliferation and apoptosis. For antibacterial property, the material was co-cultivated with bacteria, bacterial colony forming units was counted and the release time of the effective levofloxacin was assayed by agar disc-diffusion test. Moreover, scanning electron microscope was applied to observe adhesion of bacteria. In terms of osteogenic induction, we found BMSCs adherently grew more prominently on Lev/MSNs/n-HA/PU. Lev/MSNs/n-HA/PU also enhanced the expression of osteogenic markers including OCN and COL1α1, as well as effectively promoted the transition from G1 phase to G2 phase. Furthermore, Lev/MSNs/n-HA/PU could reduce apoptosis of MC3T3-E1. Besides, both Lev/MSNs/n-HA/PU and n-HA/PU materials could inhibit bacterial colonies, while Lev/MSNs/n-HA/PU possessed a stronger antibacterial activities, and lower bacterial adhesion than n-HA/PU. These results illustrated that Lev/MSNs/n-HA/PU composite scaffold possess favorable compatibility in vitro, which induce osteogenic differentiation of MSCs, promote proliferation and differentiation of MC3T3-E1, and inhibit apoptosis. Moreover, clear in vitro antibacterial effect of Lev/MSNs/n-HA/PU was also observed. In summary, this study replenishes the potential of Lev/MSNs/n-HA/PU composite scaffold possess dual functions of anti-infection and enhanced osteogenesis for future clinical application.

Abstract Interleukin (IL)-9 belongs to the IL-2Rγc chain family and is a multifunctional cytokine that can regulate the function of many kinds of cells. It was originally identified as a growth factor of T cells and mast cells. In previous studies, IL-9 was mainly involved in the development of allergic diseases, autoimmune diseases and parasite infections. Recently, IL-9, as a double-edged sword in the development of cancers, has attracted extensive attention. Since T-helper 9 (Th9) cell-derived IL-9 was verified to play a powerful antitumor role in solid tumors, an increasing number of researchers have started to pay attention to the role of IL-9-skewed CD8+ T (Tc9) cells, mast cells and Vδ2 T cell-derived IL-9 in tumor immunity. Here, we review recent studies on IL-9 and several kinds of IL-9-producing cells in tumor immunity to provide useful insight into tumorigenesis and treatment. Graphical abstract

BackgroundMacrophages are heterogenous phagocytic cells with an important role in the innate immunity. They are, also, significant contributors in the adaptive immune system. Macrophages are the most abundant immune cells in the lung during allergic asthma, which is the most common chronic respiratory disease of both adults and children. Macrophages activated by Th1 cells are known as M1 macrophages while those activated by IL-4 and IL-13 are called alternatively activated macrophages (AAM) or M2 cells. AAM are subdivided into four distinct subtypes (M2a, M2b, M2c and M2d), depending on the nature of inducing agent and the expressed markers.BodyIL-4 is the major effector cytokine in both alternative activation of macrophages and pathogenesis of asthma. Thus, the role of M2a macrophages in asthma is a major concern. However, this is controversial. Therefore, further studies are required to improve our knowledge about the role of IL-4-induced macrophages in allergic asthma, through precisive elucidation of the roles of specific M2a proteins in the pathogenesis of asthma. In the current review, we try to illustrate the different functions of M2a macrophages (protective and pathogenic roles) in the pathogenesis of asthma, including explanation of how different M2a proteins and markers act during the pathogenesis of allergic asthma. These include surface markers, enzymes, secreted proteins, chemokines, cytokines, signal transduction proteins and transcription factors.ConclusionsAAM is considered a double-edged sword in allergic asthma. Finally, we recommend further studies that focus on increased selective expression or suppression of protective and pathogenic M2a markers.

IL-10-producing B Cells (B10) is a functionally defined regulatory B-cell subset. It plays an important role in the control of inflammation and autoimmune diseases, although it is present at low numbers in peripheral blood. Graves' disease is an autoimmune disease characterized by the production of autoantibodies such as TRAb. ILC2s maintains Th2 polarization state by producing type-II cytokines. It is not clear whether the level of autoantibody is related to ILC2s and B10 cells in Graves' disease. In this study, we analyzed the frequencies of B10, Treg cells and ILC2s, as well as the expression of related cytokines in peripheral blood from patients with Graves' disease and evaluated the correlation between B10 cell numbers and autoantibodies level. Our data showed that the frequency of B10 or Treg cells was significantly decreased in peripheral blood mononuclear cells from Graves' disease patients, while the percentage of ILC2s cells was increased; the levels of cytokine IL-5, IL-13 and related transcription factor RORα were up-regulated. Autoantibodies analysis also showed that high level of TRAb was accompanied by low rates of B10 cells in patients, there was a negative correlation trend. In addition, the analytical data from mouse disease models also showed similar results. It indicates that B10 cells may affect the production of TRAb by negative regulation of Th2 cells, while ILC2s can promote the production of autoantibodies such as TRAb by maintaining the dominant response state of Th2 cells.

Type 2 innate lymphoid cells (ILC2s) have multiple functions that can respond to allergic diseases, parasite infection, metabolic homeostasis, tissue repair, and adipose metabolism homeostasis. In these diseases, ILC2s can be activated by various inflammatory cytokines released by damaged cells. Activated ILC2s produce different type 2 cytokines, including interleukin (IL)-4, IL-5, IL-9, and IL-13, which involved in the pathogenesis of many diseases. In recent years, the relationship between ILC2s and tumor diseases has attracted more and more attention. The role of ILC2s in tumor immunity depends on its surface molecules and cytokine context. This review aims to conclude tumorigenic and antitumorigenic roles of ILC2s, and the characters of ILC2s-related cytokines in tumor diseases to provide a comprehensive overview of the impact of ILC2s in tumor immunity.

Bronchial asthma is one of the most chronic pulmonary diseases and major public health problems. In general, asthma prevails in developed countries than developing countries, and its prevalence is increasing in the latter. For instance, the hygiene hypothesis demonstrated that this phenomenon resulted from higher household hygienic standards that decreased the chances of infections, which would subsequently increase the occurrence of allergy. In this review, we attempted to integrate our knowledge with the hygiene hypothesis into beneficial preventive approaches for allergic asthma. Therefore, we highlighted the studies that investigated the correlation between allergic asthma and the two different types of infections that induce the two major antagonizing arms of T cells. This elucidation reflects the association between various types of natural infections and the immune system, which is predicted to support the main objective of the current research on investigating of the benefits of natural infections, regardless their immune pathways for the prevention of allergic asthma. We demonstrated that natural infection with Mycobacterium tuberculosis (Mtb) prevents the development of allergic asthma, thus Bacille Calmette-Guérin (BCG) vaccine is suggested at early age to mediate the same prevention particularly with increasing its efficiency through genetic engineering-based modifications. Likewise, natural helminth infections might inhabit the allergic asthma development. Therefore, helminth-derived proteins at early age are good candidates for designing vaccines for allergic asthma and it requires further investigation. Finally, we recommend imitation of natural infections as a general strategy for preventing allergic asthma that increased dramatically over the past decades.

IntroductionChronic heart failure (CHF) is a common disease worldwide, and imposes a substantial burden to the healthcare system. In CHF, limited exercise capacity and affected mental well-being leads to a reduced quality of life (QOL). How to improve the QOL and exercise endurance is critical for patients with CHF. Exercise therapy, such as some traditional Asian exercises (TAEs) including Taichi, Baduanjin and Yoga, plays an important role in the rehabilitation of patients with CHF. TAE is suitable for the rehabilitation of patients with CHF because of its soft movements and can relax the body and mind. Studies have shown that TAE can regulate the overall health status of the body and exercise tolerance, improve QOL and reduce rehospitalisation rate in patients with CHF. However, the difference in efficacy of TAE in patients with CHF is not yet clear. The main purpose of this study is to conduct a network meta-analysis (NMA) of randomised trials to determine the impact of TAE on patients with CHF of different types, different causes and different New York Heart Association (NYHA) heart function classifications and to provide references for different types of patients with CHF to choose appropriate exercise rehabilitation therapy.Methods and analysisThe literature search will be retrieved from PubMed, the Cochrane Library, Embase, Web of Science, Chinese National Knowledge Infrastructure, Wanfang database, Chinese biomedical literature service system (SinoMed) and Chinese Scientific Journals Database (VIP) from the date of their inception until 1 August 2021. All randomised controlled trials that evaluated the effects of three different TAE therapies (Taichi, Baduanjin and Yoga) on patients with CHF will be included. The primary outcomes are peak oxygen uptake (peak VO2), exercise capacity (6-min walking distance) and QOL tested with the Minnesota Living with Heart Failure Questionnaire. Secondary outcomes include the levels of N-terminal pro brain natriuretic peptide, left ventricular ejection fraction, systolic blood pressure and diastolic blood pressure. For included articles, two reviewers will independently extract the data, and Cochrane Collaboration’s tool will be used to assess risk of bias. We will perform the Bayesian NMA to pool all treatment effects. The ranking probabilities for the optimal intervention of various treatments (Taichi, Baduanjin or Yoga) will be estimated by the mean ranks and surface under the cumulative ranking curve. Subgroup analysis for different types, different causes and different NYHA heart function classifications of CHF will be performed. We will use the Grading of Recommendations Assessment, Development and Evaluation system to assess the quality of evidence contributing to each network estimate.Ethics and disseminationThe results will be disseminated through peer-reviewed publications. They will provide useful information to inform clinicians on the potential functions of TAE in CHF, and to provide consolidated evidence for clinical practice and further research of TAE.PROSPERO registration numberCRD42020179304.

Background/purpose: Gold metal technology improves flexibility and the resistance to cyclic fatigue of the endodontic mechanical files. This study compared the performance of ProTaper Gold (PTG) multiple file system and WaveOne Gold (WOG) single file system in simulated S-shaped root canals, which represents one of the most challenging root canal morphology. Materials and methods: Forty S-shaped canals (n = 20 canals/per group) in resin blocks were instrumented to an apical size of 0.25 mm using PTG and WOG Primary, respectively. The total amount of resin removal, canal transportation, centering ratio, and the degree of canal straightening were measured in Photoshop CS6 software. Statistical analysis was performed by using Mann–Whitney U-test (α = .05). Results: None of the files fractured during the instrumentation. The WOG group removed significantly less amount of resin at 0, 3, 6, 7 and 9 mm from the apex (P .05). Conclusion: The WOG Primary file has a less aggressive dentin cutting and more centered apical preparation. The PTG system is more advantageous in shaping the coronal curvature of S-shaped canal.

Even without formal training, humans experience a wide range of emotions in response to changes in musical features, such as tonality and rhythm, during music listening. While many studies have investigated how isolated elements of tonal and rhythmic properties are processed in the human brain, it remains unclear whether these findings with such controlled stimuli are generalizable to complex stimuli in the real world. In the current study, we present an analytical framework of a linearized encoding analysis based on a set of music information retrieval features to investigate the rapid cortical encoding of tonal and rhythmic hierarchies in natural music. We applied this framework to a public domain EEG dataset (OpenMIIR) to deconvolve overlapping EEG responses to various musical features in continuous music. In particular, the proposed framework investigated the EEG encoding of the following features: tonal stability, key clarity, beat, and meter. This analysis revealed a differential spatiotemporal neural encoding of beat and meter, but not of tonal stability and key clarity. The results demonstrate that this framework can uncover associations of ongoing brain activity with relevant musical features, which could be further extended to other relevant measures such as time-resolved emotional responses in future studies.

Background There is limited literature on conventional US to assess bone age. Purpose To determine the diagnostic performance of US in the assessment of abnormal bone age in Chinese children. Materials and Methods In this prospective study, children and young adults aged between birth and 19 years from a large provincial teaching hospital were enrolled from January to November 2020. Children without clinical diseases potentially affecting skeletal growth were included in the normal-value group. Children with clinically suspected growth disturbances who were undergoing bone age evaluation were included in the validation group. Ossification ratios (ie, the ratio of the height of the epiphyseal ossification center to the entire epiphysis, including the cartilaginous component) of the radius, ulna, and femur from all the children were measured using US. Ultrasonic skeletal maturity scores (ie, the summation of ossification ratios of the radius, ulna, and femur multiplied by 100) collected from children in the normal-value group were used for score-for-age curve fitting through Box-Cox power exponential distribution. Test performance characteristics for the ability of US to help diagnose abnormal bone age were determined using radiographic bone age as a reference standard. Statistically significant difference between groups was determined by using a paired-sample t test. Results A total of 1089 children (median age, 9 years [interquartile range, 3-14 years]; 578 boys) were enrolled, including 929 children (mean age, 8 years [interquartile range, 4-12 years]; 515 boys) in the normal-value group and 160 children (mean age, 9 years [interquartile range, 7-11 years]; 63 boys) in the validation group. Ultrasonic bone ages in the validation group were evaluated with use of the lists of normal score-for-age values. With radiographic bone age as a reference standard, US could help diagnose abnormal bone age with high sensitivity (93% [14 of 15 participants; 95% CI: 66, 100] for boys, 100% [14 of 14 participants; 95% CI: 73, 100] for girls) and specificity (98% [47 of 48 participants; 95% CI: 88, 100] for boys, 98% [81 of 83 participants; 95% CI: 91, 100] for girls). Conclusion The US scoring system established can be used to evaluate bone age with high sensitivity and specificity. Clinical trial registration no. ChiCTR1900027917 © RSNA, 2021 Online supplemental material is available for this article.

Background The herbal pairing of Dangshen (DS) [Codonopsis pilosula (Franch.) Nannf.] and Huangqi (HQ) [Astragalus membranaceus (Fisch.) Bge.] (DHP) is a traditional Chinese herbal medicine that is frequently used to treat chronic heart failure (CHF) in China. However, the pharmacological mechanism of DHP has not been fully elucidated. This is the first study aimed to reveal the active mechanism of DHP in the treatment of CHF by using network pharmacology methods. Methods The active ingredients of DHP were obtained from the TCMSP database, and the potential targets of DHP were predicted using the SwissTargetPrediction database. CHF-related targets were searched by the DisGeNET and GeneCards databases. The common targets between the disease and herbs were obtained using a Venn diagram. The STRING database was utilized to obtain the protein-protein interaction data. Next, we used Cytoscape 3.7.2 software to construct and analyze the herb-ingredient-potential targets-disease network. Topology analysis was used to identify the key ingredients and hub genes. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed using the Metascape database to reveal the mechanism. Furthermore, molecular docking simulation was performed using AutoDock Vina software to assess the affinity of the key ingredients and hub genes. Results Five key ingredients and six hub genes were screened. The six hub genes were closely related to PI3K /AKT or ERK1/2 pathways. The KEGG pathways mainly involved the TNF signaling pathway, calcium signaling pathway, and cancer-related pathways. The GO enrichment analysis results showed that DHP might act on biological processes including positive regulation of kinase activity and cellular response to nitrogen compound via the three above-mentioned pathways in the treatment of CHF. Finally, the molecular docking results showed that the five key ingredients exhibited strong affinities to the six hub genes. Conclusions This study revealed the molecular mechanism that the flavonoids in DHP may alleviate endothelial dysfunction and cardiac hypertrophy via regulation of the TNF pathway and its downstream PI3K/Akt or ERK1/2 signaling pathways, or improve excitation-contraction coupling by regulating calcium signaling pathway, thereby improving CHF. These results provide insights for further experimentation on its pharmacological effects.

Background/purpose: Calcium hydroxide [Ca(OH)2], a wildly used intracanal medicament, should be completely removed from the root canal before obturation to avoid negative effects on the treatment. This study evaluated the effectiveness of conventional needle irrigation (CNI), passive ultrasonic activation (PUI), photon-induced photoacoustic streaming (PIPS), XP-endo Finisher (XP) and EDDY for the removal of Ca(OH)2 from S-shaped root canal. Materials and methods: Eighty-four S-shaped root canals in resin blocks were prepared using Protaper Gold up to size #25/0.08 and filled with Ca(OH)2. Five groups were established according to the removal techniques (n = 16): CNI, PUI, PIPS, XP and EDDY group. The positive and negative control group (n = 2) were also established. Sodium hypochlorite 3% was used as the irrigant. Digital radiographs were used to measure the remaining Ca(OH)2. Statistical analysis of the data was performed by using the Kruskal–Wallis test, followed by Dunn's post hoc test with Bonferroni correction (α = 0.05). Results: All the tested techniques completely removed Ca(OH)2 from the straight portion and coronal curve of the S-shaped root canal in 100% of cases. Regarding the apical curve, PUI, EDDY, PIPS and XP removed significantly more Ca(OH)2 than CNI (P 0.05). The complete clearance of Ca(OH)2 from the apical curve was observed in 75%, 62.5%, 56.3%, 43.8% and 0% of cases of PUI, EDDY, PIPS, XP and CNI group, respectively. Conclusion: Irrigant activation enhanced Ca(OH)2 removal from the apical region of the S-shaped root canal. CNI was significantly less effective than all activation techniques.

Objective: Myocardial ischemia/reperfusion (I/R) injury is one of the causes of most cardiomyocyte injuries and deaths. Berberine (BBR) has been suggested a potential to exert protective effects against myocardial I/R injury. This systematic review aims to determine the intrinsic mechanisms of BBR's protective effects in myocardial I/R injury.Methods: Seven databases were searched for studies performed from inception to July 2020. Methodological quality was assessed by SYRCLE's-RoB tool.Results: Ten studies including a total of 270 animals were included in this study. The methodology quality scores of the included studies ranged from 5 to 7 points. The meta-analysis we conducted demonstrated that BBR significantly reduced myocardial infarct size and the incidence of ventricular arrhythmia, compared to control groups (P < 0.00001). Cardiac function of animals in the BBR treatment group was also markedly increased (P < 0.00001). The index of myocardial apoptosis and the levels of biomarkers of myocardial infarction (LDH and CK) were also decreased in the BBR treatment groups compared to the control groups (P < 0.00001).Conclusions: The pre-clinical evidence, according to our study, showed that BBR is a promising therapeutic agent for myocardial I/R injury. However, this conclusion should be further investigated in clinical studies.

Chemoresistance is the primary obstacle in the treatment of locally advanced and metastatic nasopharyngeal carcinoma (NPC). Recent evidence suggests that the transcription factor forkhead box M1 (FoxM1) is involved in chemoresistance. Our group previously confirmed that FoxM1 is overexpressed in NPC. In this study, we investigated the role of FoxM1 in cisplatin resistance of the cell lines 5-8F and HONE-1 and explored its possible mechanism. Our results showed that FoxM1 and NBS1 were both overexpressed in NPC tissues based on data from the GSE cohort (GSE12452). Then, we measured FoxM1 levels in NPC cells and found FoxM1 was overexpressed in NPC cell lines and could be stimulated by cisplatin. MTT and clonogenic assays, flow cytometry, γH2AX immunofluorescence, qRT-PCR, and western blotting revealed that downregulation of FoxM1 sensitized NPC cells to cisplatin and reduced the repair of cisplatin-induced DNA double-strand breaks via inhibition of the MRN (MRE11-RAD50-NBS1)-ATM axis, which might be related to the ability of FoxM1 to regulate NBS1. Subsequently, we demonstrated that enhanced sensitivity of FoxM1 knockdown cells could be reduced by overexpression of NBS1. Taken together, our data demonstrate that downregulation of FoxM1 could improve the sensitivity of NPC cells to cisplatin through inhibition of MRN-ATM-mediated DNA repair, which could be related to FoxM1-dependent regulation of NBS1. [BMB Reports 2019; 52(3): 208-213].

Objective: To investigate the relationship between early intervention timing and complications of acute Stanford type B aortic dissection. Methods: The clinical data of 146 patients with acute stanford type B aortic dissection treated with transseptal stent for aortic endovascular repair (TEVAR) from January 2012 to October 2017 in Xiaogan Central Hospital were analyzed. The time was divided into 3 groups, including the onset to TEVAR time ≤ 48 h group (41 cases in group A), the onset to TEVAR time 48 h - 7 d group (56 cases in group B), the onset to TEVAR time 7 d - 14 d group (49 cases in group C)). The clinical baseline data, the incidence of different complications during perioperative period, and the mortality rate at 30 days were compared between the three groups. Results: There were no significant differences in age, gender and comorbidities between the three groups (all P > 0.05). Group A had a clearer indication of immediate intervention compared with group B and group C (P 0.05). Conclusion: Early intervention of acute TBAD may increase the risk of serious complications after surgery, and the incidence of serious complications will gradually decrease over time; the reduction of severe complications after early grouping is not accompanied by Early mortality and reoperation rates were significantly reduced, and TEVAR treatment in some patients with dissection did not prevent dissection progression and rupture.

Both Gram-Positive and Gram-Negative bacteria can secrete outer membrane vesicles (OMVs) in their growth and metabolism process. Originally, OMVs were considered as a by-product of bacterial merisis. However, many scientists have reported the important role of OMVs in many fields recently. In this review, we briefly introduce OMVs biological functions and then summarize the findings about the OMVs interactions with host cells. At last, we will make an expectation about the prospects of the application of OMVs as vaccines.

Objective: To identify the high risk factors associated with postpartum hemorrhage (PPH) after selective cesarean delivery of twins. Methods: This retrospective cohort study included all women with twin gestations who choosed an elective cesarean delivery after 28 weeks of gestation at Women's Hospital of Zhejiang University School of m from September 2014 to April 2019. The Women with an intrauterine fetal demise one or both of twins were excluded.A total of 532 wemen were analysed,they were classified as PPH group(n=70) and No PPH group(n=462). Estimated blood loss greater than or equal to 1000 ml was defined as Postpartum hemorrhage(PPH).Univariate and multivariate logistic regression analysis were performed to assess the independent risk factors.Results: Of the 532 twin pregnant women, PPH occurred in 13.2% (n=70). There were statistically signifcant diferences in preeclampsia (P=0.005), premature rupture of membranes(Pp < 0.05), premature rupture of membranes (OR17.9, P < 0.05), placental adhesion (OR5.71, p < 0.05) and placenta previa (OR10, p < 0.05). Conclusions: preeclampsia , premature rupture of membranes , placental adhesion and placenta previa were risk factors for postpartum hemorrhage after elective cesarean section for twin pregnancy. Risk factor identification and prevention should be a priority.

As the age profile of many societies continues to increase, supporting health, both mental and physical, is of increasing importance if independent living is to be maintained. Sensing and, ultimately, recognising activities of daily living has been perceived as a prerequisite for detecting tasks that people avoid or find increasingly difficult to perform, as well as being indicators of certain illnesses. To date, extensive research efforts have been made in activity monitoring, recognition and assistance in indoor scenarios, frequently through smart home initiatives. Moreover, certain behaviours and activities may indicate certain disease especially for elderly people, such as sleep disorder. Thus this paper advocates a need for platforms that enable activity monitoring, in particularly, this sleep disorder, in home environment, thereby enabling the construction of more complex yet realistic activity models and behaviours patterns.