Publications by authors named "Wei Xu"

4,391 Publications

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Association of Pharyngocutaneous Fistula With Cancer Outcomes in Patients After Laryngectomy: A Multicenter Collaborative Cohort Study.

JAMA Otolaryngol Head Neck Surg 2021 Jul 29. Epub 2021 Jul 29.

Princess Margaret Cancer Centre, University Health Network, Toronto, Ontario, Canada.

Importance: Pharyngocutaneous fistula (PCF) results in an inflammatory reaction, but its association with the rate of locoregional and distant control, disease-free survival, and overall survival in laryngeal cancer remains uncertain.

Objective: To determine if pharyngocutaneous fistula after salvage laryngectomy is associated with locoregional and distant control, disease-free survival, and/or overall survival.

Design, Setting, And Participants: A multicenter collaborative retrospective cohort study conducted at 5 centers in Canada and the US of 550 patients who underwent salvage laryngectomy for recurrent laryngeal cancer from January 1, 2000, to December 31, 2014. The median follow-up time was 5.7 years (range, 0-18 years).

Main Outcomes And Measures: Outcomes examined included locoregional and distant control, disease-free survival, and overall survival. Fine and Gray competing risk regression and Cox-proportional hazard regression models were used for outcomes. Competing risks and the Kaplan-Meier methods were used to estimate outcomes at 3 years and 5 years.

Results: In all, 550 patients (mean [SD] age, 64 [10.4] years; men, 465 [85%]) met inclusion criteria. Pharyngocutaneous fistula occurred in 127 patients (23%). The difference in locoregional control between the group of patients with PCF (75%) and the non-PCF (72%) group was 3% (95% CI, -6% to 12%). The difference in overall survival between the group with PCF (44%) and the non-PCF group (52%) was 8% (95% CI, -2% to 20%). The difference in disease-free survival between PCF and non-PCF groups was 6% (95% CI, -4% to 16%). In the multivariable model, patients with PCF were at a 2-fold higher rate of distant metastases (hazard ratio, 2.00; 95% CI, 1.22 to 3.27). Distant control was reduced in those with PCF, a 13% (95% CI, 3% to 21%) difference in 5-year distant control.

Conclusions And Relevance: This multicenter retrospective cohort study found that development of PCF after salvage laryngectomy is associated with an increased risk for the development of distant metastases.
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http://dx.doi.org/10.1001/jamaoto.2021.1545DOI Listing
July 2021

Ultra-Fast Label-Free Serum Metabolic Diagnosis of Coronary Heart Disease via a Deep Stabilizer.

Adv Sci (Weinh) 2021 Jul 29:e2101333. Epub 2021 Jul 29.

State Key Laboratory for Oncogenes and Related Genes, School of Biomedical Engineering, Institute of Medical Robotics and Med-X Research Institute, Shanghai Jiao Tong University, Shanghai, 200030, P. R. China.

Although mass spectrometry (MS) of metabolites has the potential to provide real-time monitoring of patient status for diagnostic purposes, the diagnostic application of MS is limited due to sample treatment and data quality/reproducibility. Here, the generation of a deep stabilizer for ultra-fast, label-free MS detection and the application of this method for serum metabolic diagnosis of coronary heart disease (CHD) are reported. Nanoparticle-assisted laser desorption/ionization-MS is used to achieve direct metabolic analysis of trace unprocessed serum in seconds. Furthermore, a deep stabilizer is constructed to map native MS results to high-quality results obtained by established methods. Finally, using the newly developed protocol and diagnosis variation characteristic surface to characterize sensitivity/specificity and variation, CHD is diagnosed with advanced accuracy in a high-throughput/speed manner. This work advances design of metabolic analysis tools for disease detection as it provides a direct label-free, ultra-fast, and stabilized platform for future protocol development in clinics.
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http://dx.doi.org/10.1002/advs.202101333DOI Listing
July 2021

Increased plasma and milk short-chain acylcarnitines concentrations reflect systemic LPS response in mid-lactation dairy cows.

Am J Physiol Regul Integr Comp Physiol 2021 07 28. Epub 2021 Jul 28.

Institute of Animal Science, University of Hohenheim, Stuttgart, Germany.

Lipopolysaccharides (LPS) challenge the metabolic integrity of high yielding dairy cows, activating the immune system and altering energy metabolism. Fatty acid oxidation, a major energy gaining pathway, can be improved by supplementary carnitine, facilitating the transport of fatty acids into mitochondria. The metabolic response to LPS challenge could alter both the plasma and the milk metabolome. Plasma and milk samples collected from cows treated with (n=27) or without (n=27) dietary carnitine, before and after intravenous administration of LPS, were subjected to a targeted metabolomics analysis. Multivariate statistical analyses revealed that both plasma and milk metabolome changed in response to the LPS challenge in both the carnitine supplemented as well as the control cows. Short-chain acylcarnitines (carbon chain length C2, C3, C4, and C5) and long-chain acylcarnitines (C14, C16, and C18) had the highest performance to indicate LPS response when testing the predictive power of single metabolites using receiver-operator characteristics (ROC) analysis. The maximum area under a ROC curve (AUC) was 0.93. Biogenic amines, including sarcosine, and amino acids such as glutamine and isoleucine had AUC > 0.80 indicating metabolic changes due to LPS challenge. In summary, the metabolites involved in the LPS response were acylcarnitines C2 and C5, sarcosine, glutamine, and isoleucine in plasma, and acylcarnitines C4 and C5 in milk. The interrelationship of plasma and milk metabolome included correlation of acylcarnitines C2, C4, and C5 between plasma and milk.
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http://dx.doi.org/10.1152/ajpregu.00072.2021DOI Listing
July 2021

Determining the critical factors of air-conditioning innovation using an integrated model of fuzzy Kano-QFD during the COVID-19 pandemic: The perspective of air purification.

PLoS One 2021 27;16(7):e0255051. Epub 2021 Jul 27.

School of Management, Shenyang University of Technology, Shenyang, China.

At present, people are demanding better indoor air quality during the COVID-19 pandemic. In addition to maintaining the basic functions, new air-conditioning should also add air purification functions to improve indoor air quality and reduce the possibility of virus transmission. Nowadays, there is lack of research results on the innovation of air-conditioning. The aim of this study is to present a two-stage mathematical model for identifying critical manufacturing factors in the innovation process of air conditioning. In this paper, Kano and quality function deployment (QFD) are used to analyze the critical factors affecting air-conditioning innovation. Some studies have proposed using Kano-QFD model to analyze product innovation, but the study only studies one stage, which loses the analysis of the subsequent stages of product innovation. Based on this, this paper studies the priority method of two-stage critical factors for air-conditioning innovation. Firstly, the questionnaire survey and fuzzy sets are used to collect demand information of multi-agent (customers and professional technicians). Secondly, the Kano model is used to classify and calculate satisfaction of multi-agent. Then, QFD is used to transform multi-agent demands into engineering property indexes (first stage) and technical property indexes (second stage) and calculate the weight of each index. Finally, the applicability and superiority of this method is illustrated by taking the central air-conditioning as an example.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0255051PLOS
July 2021

Characterization of MW06, a human monoclonal antibody with cross-neutralization activity against both SARS-CoV-2 and SARS-CoV.

MAbs 2021 Jan-Dec;13(1):1953683

Department of Antibody Discovery and Development, Mabwell (Shanghai) Bioscience Co., Ltd, Shanghai, China.

The global pandemic of COVID-19 caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has resulted in widespread social and economic disruption. Effective interventions are urgently needed for the prevention and treatment of COVID-19. Neutralizing monoclonal antibodies (mAbs) have demonstrated their prophylactic and therapeutic efficacy against SARS-CoV-2, and several have been granted authorization for emergency use. Here, we discover and characterize a fully human cross-reactive mAb, MW06, which binds to both SARS-CoV-2 and SARS-CoV spike receptor-binding domain (RBD) and disrupts their interaction with angiotensin-converting enzyme 2 (ACE2) receptors. Potential neutralization activity of MW06 was observed against both SARS-CoV-2 and SARS-CoV in different assays. The complex structure determination and epitope alignment of SARS-CoV-2 RBD/MW06 revealed that the epitope recognized by MW06 is highly conserved among SARS-related coronavirus strains, indicating the potential broad neutralization activity of MW06. In assays, no antibody-dependent enhancement (ADE) of SARS-CoV-2 infection was observed for MW06. In addition, MW06 recognizes a different epitope from MW05, which shows high neutralization activity and has been in a Phase 2 clinical trial, supporting the development of the cocktail of MW05 and MW06 to prevent against future escaping variants. MW06 alone and the cocktail show good effects in preventing escape mutations, including a series of variants of concern, B.1.1.7, P.1, B.1.351, and B.1.617.1. These findings suggest that MW06 recognizes a conserved epitope on SARS-CoV-2, which provides insights for the development of a universal antibody-based therapy against SARS-related coronavirus and emerging variant strains, and may be an effective anti-SARS-CoV-2 agent.
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http://dx.doi.org/10.1080/19420862.2021.1953683DOI Listing
July 2021

Improving the catalytic behaviors of Lactobacillus-derived fructansucrases by truncation strategies.

Enzyme Microb Technol 2021 Sep 24;149:109857. Epub 2021 Jun 24.

State Key Laboratory of Food Science and Technology, Jiangnan University, Wuxi, Jiangsu 214122, China; International Joint Laboratory on Food Safety, Jiangnan University, Wuxi, Jiangsu, 214122, China. Electronic address:

Fructansucrases (FSs), including inulosucrase (IS) and levansucrase (LS), are the members of the Glycoside Hydrolase family 68 (GH68) enzymes. IS and LS catalyze the polymerization of the fructosyl moiety from sucrose to inulin- and levan-type fructans, respectively. Lactobacillus-derived FSs have relatively extended N- and C-terminal sequences. However, the functional roles of these sequences in their enzymatic properties and fructan biosynthesis remain largely unknown. Limosilactobacillus reuteri (basionym: Lactobacillus reuteri) 121 could produce both IS and LS, abbreviated as Lare121-IS and Lare121-LS, respectively. In this study, it was found that the terminal truncation displayed an obvious effect on their activities and the N-terminal truncated variants, Lare121-ISΔ177-701 and Lare121-LSΔ154-686, displayed the highest activities. Melting temperature (T) and the thermostability at 50 °C were measured to evaluate the stability of various truncated versions, revealing the different effects of N-terminal on the stability. The average molecular weight and polymerization degree of the fructans produced by different truncated variants did not change considerably, indicating that N-terminal truncation had low influence on fructan biosynthesis. In addition, it was found that N-terminal truncation could also improve the activity of other reported FSs from Lactobacillus species.
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http://dx.doi.org/10.1016/j.enzmictec.2021.109857DOI Listing
September 2021

Afatinib induces pro-survival autophagy and increases sensitivity to apoptosis in stem-like HNSCC cells.

Cell Death Dis 2021 Jul 22;12(8):728. Epub 2021 Jul 22.

Department of Otolaryngology-Head and Neck Surgery, Shandong Provincial ENT Hospital, Cheeloo College of Medicine, Shandong University, Jinan, 250022, P.R. China.

Afatinib, a second-generation tyrosine kinase inhibitor (TKI), exerts its antitumor effects in head and neck squamous cell carcinoma (HNSCC) by inducing intrinsic apoptosis through suppression of mTORC1. However, the detailed mechanism and biological significance of afatinib-induced autophagy in HNSCC remains unclear. In the present study, we demonstrated that afatinib induced mTORC1 suppression-mediated autophagy in HNSCC cells. Further mechanistic investigation revealed that afatinib stimulated REDD1-TSC1 signaling, giving rise to mTORC1 inactivation and subsequent autophagy. Moreover, ROS generation elicited by afatinib was responsible for the induction of the REDD1-TSC1-mTORC1 axis. In addition, pharmacological or genetic inhibition of autophagy sensitized HNSCC cells to afatinib-induced apoptosis, demonstrating that afatinib activated pro-survival autophagy in HNSCC cells. Importantly, in vitro and in vivo assays showed that afatinib caused enhanced apoptosis but weaker autophagy in stem-like HNSCC cells constructed by CDH1 knockdown. This suggested that blocking autophagy has the potential to serve as a promising strategy to target HNSCC stem cells. In conclusion, our findings suggested that the combination treatment with afatinib and autophagy inhibitors has the potential to eradicate HNSCC cells, especially cancer stem cells in clinical therapy.
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http://dx.doi.org/10.1038/s41419-021-04011-0DOI Listing
July 2021

The CT morphological characteristics and the clinical management strategy of posterior malleolar fractures with talar subluxation.

Am J Transl Res 2021 15;13(6):6478-6487. Epub 2021 Jun 15.

Department of Orthopaedics, The Second Affiliated Hospital of Soochow University Suzhou 215004, Jiangsu Province, China.

Background: The optimal clinical treatment and the computed tomography (CT) morphological characteristics of posterior malleolar fractures (PMF) with talar subluxation remain inconclusive. Clinically, both plate screws and lag screws are widely used to fix posterior malleolar fragments using a direct or indirect approach. We sought to summarize the morphological characteristics and modified classification on the basis of CT and the intraoperative strategy for posterior talar subluxation in PMF.

Methods: Retrospectively, 46 adult PMF patients with subluxations of the talus were recruited as the study cohort. According to its morphological features, PMF with subluxation of the talus can be divided mainly into two types using this modified classification: a complete fracture (the single-fragment type) and PMF with two-angled fracture fragments (the double-fragment type). The cohort's demographic information, classifications, fracture morphology, fixation methods, pain levels, and functional scores were recorded for both fracture types.

Results: The average values of the depths and heights of the posterior malleolar fragments were (29.1±7.3) mm for the single-fragment type and (17.9±4.2) mm for the double-fragment type. There was a significant difference in the mean values between the two types ( < 0.05). Posterior plate fixation was suitable for the single-fragment type, while antero-posterior and postero-anterior (AP-PA) lag screws fixations were made available for the double-fragment type. Both methods achieved good results. No significant differences were found in terms of sex, age, body mass index (BMI), side, Haraguchi classification, Bartoníček and Rammelt classification, Visual Analog Scale (VAS) scores, or American Orthopedic Foot & Ankle Society scores (AOFAS) when comparing the single-/double-fragment type groups after the mid-term follow-up ( > 0.05).

Conclusion: According to the injury mechanism and the morphological characteristics of the fractures, the proposed improved classification system for PMF with subluxation of the talus based on the injury mechanism and the fracture morphology can provide guidance for surgical management strategies and achieve optimal outcomes.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8290741PMC
June 2021

The serum CK17 and CK19 expressions in cervical cancer patients and their prognostic value.

Am J Transl Res 2021 15;13(6):6439-6445. Epub 2021 Jun 15.

Department of Pathology, Zhejiang North Medical Center (Huzhou Central Hospital) Huzhou 313003, Zhejiang Province, China.

Objective: This study was designed to quantify the serum CK17 and CK19 expressions in cervical cancer (CC) patients and determine their predictive value.

Methods: A total of 124 CC patients admitted to Zhejiang North Medical Center (Huzhou Central Hospital) between November 2014 and November 2017 were recruited for the study and placed in a research group (the Res group), and 99 healthy individuals during the same period were also recruited for the study and placed in a control group (the Con group). Their serum CK17 and CK19 expressions were quantified, and the diagnostic significance of the two for CC was analyzed. Additionally, the patients were followed up for three years. The patients were then assigned to favorable and unfavorable prognosis groups, and then the predictive significance of CK17 and CK19 for such patients was evaluated.

Results: The Res group presented significantly higher serum CK17 and CK19 expression levels than the Con group, and the two factors were positively associated. Additionally, neither of the AUCs for serum CK17 and CK19 in identifying CC were less than 0.800, and the AUC of the combination of the two in identifying it was not smaller than 0.900. The AUC of the combination of serum CK17 and CK19 in identifying unfavorable CC prognoses was approximate 0.850, and high expression levels CK17 and CK19 were closely related with low three-year overall survival rates.

Conclusion: Serum CK17 combined with serum CK19 is of great diagnostic and predictive significance for CC.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8290704PMC
June 2021

Simultaneous determination of twenty-five compounds with anti-inflammatory activity in Spatholobi Caulis by using an optimized UFLC-MS/MS method: An application to pharmacokinetic study.

J Pharm Biomed Anal 2021 Jul 14;204:114267. Epub 2021 Jul 14.

Zhuzhou Qianjin Pharmaceutical Co., Ltd., Zhuzhou 412003, China.

As a kind of commonly used Traditional Chinese Medicine in clinical, Spatholobi Caulis (SPC) contains a wide variety of bioactive compounds, including protocatechuate (1), nicotinic acid (2), p-hydroxybenzoic acid (3), salicylic acid (4), 6,9-dihydroxy megastigma-4,7-dien-3-one (5), 8,9-dihydroxy megastigma-4,6-dien-3-one (6), daidzin (7), genistin (8), isolariciresinol (9), ononin (10), 4',8-dimethoxy-7-O-β-d-glucopyranosyl isoflavone (11), 3'-methoxydaidzein (12), odoratin (13), spasuberol A (14), (+)-pinoresinol (15), 4-hydroxy-3-methoxy cinnamic acid methyl ester (16), (+)-epipinoresinol (17), calycosin (18), 8-O-methylretusin (19), formononetin sodium (20), formononetin (21), biochanin A (22), butesuperin A (23), homovanillyl-4-oxo-nonanoate (24) and (6aR,11aR)-maackiain (25). The pharmacokinetic characteristics of these twenty-five compounds in rat plasma were quantitatively and simultaneously studied using a fast, sensitive and precise ultra fast liquid chromatography combined with electrospray ionization triple quadrupole tandem mass spectrometry (UFLC-MS/MS) method after oral administration of aqueous extract of SPC to rats. The mobile phase consists of acetonitrile and 0.5 mM ammonium acetate in water, and these compounds were well separated at a gradient elution program with flow rate of 0.35 mL/min. Carbamazepine was employed as the internal standard (IS) and all samples were precipitated with MeOH-ACN (2:1, v/v). The analytical method has been proved to be good linearity (R ≥ 0.9957), precise, accurate, stable, recovery and matrix effect, which applicated becomingly to study the pharmacokinetic processes of these compounds in rat plasma. In addition, these twenty-five compounds exhibited anti-inflammatory activity on the inflammatory model of NO over production in RAW264.7 cells stimulated by lipopolysaccharide (LPS). Isoflavones, especially compounds 20-22 (The IC of which were 22.75 μM, 21.11 μM and 48.29 μM, respectively.) might be the important constituents for anti-inflammatory activity of SPC. This study provides reference values for the clinical application, in-depth study on new dosage forms and pharmacological activities of SPC.
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http://dx.doi.org/10.1016/j.jpba.2021.114267DOI Listing
July 2021

The Antiviral Molecule 5-Pyridoxolactone Identified Post BmNPV Infection of the Silkworm, .

Int J Mol Sci 2021 Jul 10;22(14). Epub 2021 Jul 10.

Biological Science Research Center, Southwest University, Chongqing 400715, China.

nucleopolyhedrovirus (BmNPV) is a pathogen that causes great economic losses in sericulture. Many genes play a role in viral infection of silkworms, but silkworm metabolism in response to BmNPV infection is unknown. We studied BmE cells infected with BmNPV. We performed liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS)-based non-targeted metabolomics analysis of the cytosolic extract and identified 36, 76, 138, 101, 189, and 166 different molecules at 3, 6, 12, 24, 48, and 72 h post BmNPV infection (hpi) compared with 0 hpi. Compounds representing different areas of metabolism were increased in cells post BmNPV infection. These areas included purine metabolism, aminoacyl-tRNA biosynthesis, and ABC transporters. Glycerophosphocholine (GPC), 2-hydroxyadenine (2-OH-Ade), gamma-glutamylcysteine (γ-Glu-Cys), hydroxytolbutamide, and 5-pyridoxolactone glycerophosphocholine were continuously upregulated in BmE cells post BmNPV infection by heat map analysis. Only 5-pyridoxolactone was found to strongly inhibit the proliferation of BmNPV when it was used to treat BmE cells. Fewer infected cells were detected and the level of BmNPV DNA decreased with increasing 5-pyridoxolactone in a dose-dependent manner. The expression of BmNPV genes ie1, helicase, GP64, and VP39 in BmE cells treated with 5-pyridoxolactone were strongly inhibited in the BmNPV infection stage. This suggested that 5-pyridoxolactone may suppress the entry of BmNPV. The data in this study characterize the metabolism changes in BmNPV-infected cells. Further analysis of 5-pyridoxolactone, which is a robust antiviral molecule, may increase our understanding of antiviral immunity.
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http://dx.doi.org/10.3390/ijms22147423DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8307608PMC
July 2021

Symptomatic spinal metastases from neuroendocrine neoplasms: surgical outcomes and prognostic analysis.

Clin Neurol Neurosurg 2021 May 27;207:106710. Epub 2021 May 27.

Department of Orthopedic Oncology, Changzheng Hospital, Shanghai, China. Electronic address:

Objectives: In this article, we investigated the efficiency of surgery in treating symptomatic spinal metastases from neuroendocrine neoplasms and performed univariate analysis for identification of possible prognostic factors.

Methods: A retrospective study was performed, enrolling a total of 19 patients who received surgeries in our center for symptomatic spinal metastases from neuroendocrine neoplasms (NEN). The Kaplan-Meier method was adopted to estimate overall survival (OS) and recurrence free survival (RFS). Univariate analysis was performed for identification of possible prognostic factors.

Results: All patients recruited displayed stable recovery after surgical intervention, with a median OS of 27.3 months (95% Confidence Interval: 16.4-38.1 months) and a median RFS of 23.0 months (95% Confidence Interval: 12.1-33.8 months). Postoperatively, 15 patients exhibited improved neurological function based on the Frankel classification, while 16 patients experienced significant pain relief, with mean visual analog scale (VAS) score decreasing from 7.47 ± 2.32-2.47 ± 1.25 (p < 0.05). Univariate analysis revealed that the presence of visceral metastases (p = 0.034) and extraspinal bone metastases (p = 0.016) are both related with poor prognosis. Additionally, well histologic differentiation (p = 0.010) and administration of postoperative octreotide (p = 0.041) or bisphosphonate (p = 0.023) are all indicators for better outcome.

Conclusions: Surgery is an efficient option for treating symptomatic spinal metastases from NEN due to its immediate and assured benefits in pain alleviation, restoration of function and stability reconstruction.
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http://dx.doi.org/10.1016/j.clineuro.2021.106710DOI Listing
May 2021

Microbial production, molecular modification, and practical application of l-Asparaginase: A review.

Int J Biol Macromol 2021 Jul 19;186:975-983. Epub 2021 Jul 19.

State Key Laboratory of Food Science and Technology, Jiangnan University, Wuxi, Jiangsu 214122, China; International Joint Laboratory on Food Safety, Jiangnan University, Wuxi 214122, China.

L-Asparaginase (L-ASNase, EC 3.5.1.1), an antitumor drug for acute lymphoblastic leukemia (ALL) therapy, is widely used in the clinical field. Similarly, L-ASNase is also a powerful and significant biological tool in the food industry to inhibit acrylamide (AA) formation. This review comprehensively summarizes the latest achievements and improvements in the production, modification, and application of microbial L-ASNase. To date, the expression levels and optimization of expression hosts such as Escherichia coli, Bacillus subtilis, and Pichia pastoris, have made significant progress. In addition, examples of successful modification of L-ASNase such as decreasing glutaminase activity, increasing the in vivo stability, and enhancing thermostability have been presented. Impressively, the application of L-ASNase as a food addition aid, as well as its commercialization in the pharmaceutical field, and cutting-edge biosensor application developments have been summarized. The presented results and proposed ideas could be a good guide for other L-ASNase researchers in both scientific and practical fields.
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http://dx.doi.org/10.1016/j.ijbiomac.2021.07.107DOI Listing
July 2021

Anti-microbial antibody response is associated with future onset of Crohn's disease independent of biomarkers of altered gut barrier function, subclinical inflammation, and genetic risk.

Gastroenterology 2021 Jul 19. Epub 2021 Jul 19.

Zane Cohen Centre for Digestive Diseases, Mount Sinai Hospital, Toronto, Ontario, Canada; Division of Gastroenterology & Hepatology, Temerty Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada. Electronic address:

Background: /Aim: Altered host immune reactivity to microbial antigens is hypothesized to trigger the onset of Crohn's disease (CD). We aimed to assess whether increased serum anti-microbial antibody response in asymptomatic first-degree relatives (FDR) of CD patients is an independent risk factor for future CD development.

Methods: We measured host serum antibody response to six microbial antigens at enrollment (Prometheus ELISA test: ASCA IgA/IgG, anti-OmpC, anti-A4-Fla2, anti-FlaX, anti-CBir1) and derived the sum of positive antibodies (AS). We used samples at enrollment of prospectively followed healthy FDRs from a nested case-control cohort of the CCC-GEM Project. Those who later developed CD (n=77) were matched 1:4 by age, sex, follow-up duration, and geographical location with control FDRs remaining healthy (n=307). To address our research aims, we fitted a multivariable conditional logistic regression model and performed causal mediation analysis.

Results: High baseline AS (≥2) (43% of cases, 11% of controls) was associated with higher risk of developing CD (adjusted OR 6.5, 95% CI 3.4-12.7; p<0.001). Importantly, this association remained significant when adjusted for markers of gut barrier function, fecal calprotectin, C-reactive protein, and CD-polygenic risk score, and in subjects recruited more than 3 years before diagnosis. Causal mediation analysis showed that the effect of high AS on future CD development is partially mediated (42%) via preclinical gut inflammation.

Conclusions: Our results suggest that increased anti-microbial antibody responses are associated with risk of future development of CD, independent of biomarkers of abnormal gut barrier function, subclinical inflammation, and CD-related genetic risks. This suggests that anti-microbial antibody responses are an early pre-disease event in the development of CD.
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http://dx.doi.org/10.1053/j.gastro.2021.07.009DOI Listing
July 2021

Feeling better or not: Adjusting affective style moderates the association between sleep duration and positive affect on next day.

Psych J 2021 Jul 21. Epub 2021 Jul 21.

Beijing Key Lab of Applied Experimental Psychology, National Demonstration Center for Experimental Psychology Education (Beijing Normal University), Faculty of Psychology, Beijing Normal University, Beijing, China.

Affect is intertwined with sleep, yet how to adjust sleep duration to enhance affect remains unknown. Previous studies found that adjusting affective style, reflecting interindividual differences in emotion regulation, functions in processes where sleep modulates our affective state. Hence, this study examined whether and how it moderates the association between daily sleep duration and subsequent affect. An ambulatory assessment design was employed among 64 participants, wherein both within-person sleep duration and affect, and between-person affective styles were measured. Multilevel moderation analysis and simple-slope analysis were applied to test the moderation of adjusting affective style in the sleep-affect association. This study found that adjusting affective style significantly moderated the association between sleep duration and subsequent positive affect. Specifically, the association between sleep duration and subsequent positive affect was positive under higher adjusting affective style and negative under extremely lower adjusting affective style. However, such moderation was not observed in associations between subsequent negative affect and sleep duration. This study uncovers the relationship between sleep duration and subsequent affect, wherein the likelihood for individuals to reach more positive affective state by increasing sleeping duration might count on their ability of emotion regulation. Additionally, negative affect cannot be downregulated simply through long sleep duration.
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http://dx.doi.org/10.1002/pchj.474DOI Listing
July 2021

Posterior Locking Plate Fixation of Bartoníček Type IV Posterior Malleolar Fracture: A Focus on Die-Punch Fragment Size.

J Foot Ankle Surg 2021 Jun 23. Epub 2021 Jun 23.

Surgeon, Department of Orthopaedics, Second Affiliated Hospital of Soochow University, Jiangsu, China. Electronic address:

Die-punch fragments refer to articular cartilage and subchondral bone embedded in cancellous bone as part of an intra-articular fracture. Bartoníček type IV posterior malleolar fractures with associated die-punch fragments are rare, and the appropriate surgical approach remains unclear. We determined outcomes, and the effect of die-punch fragment size on outcomes, for 32 patients with Bartoníček type IV posterior malleolar fractures with die-punch fragments between January 2015 and December 2017. Mean follow-up for all patients was 23.8 (range 20.0-30.0) months. At the final follow-up visit, mean ankle dorsal extension was 24.6° and plantar flexion was 40.0°; American Orthopaedic Foot and Ankle Society ankle-hindfoot score was 88.6 ± 4.3; visual analog scale weightbearing pain score was 1.5 ± 0.6; and Bargon traumatic arthritis score was 0.8 ± 0.4. There were no severe complications. We divided patients into a small-fragment (≤3 mm) group (n = 12) and large-fragment (>3 mm) group (n = 20). The Bargon scores at final follow-up were 0.5 and 1, respectively (P=.02). There were no statistically significant differences between the 2 groups for the other outcome scores at various time intervals. The posterolateral approach with distal locking plate internal fixation for Bartoníček type IV posterior malleolar fractures with die-punch fragments can result in excellent anatomical reduction of the collapsed articular surface and the displaced fragment from the tibial plafond, recovery of articular surface congruity, and maintenance of joint stability. Die-punch fragment size may not impact clinical and functional outcomes but may contribute to post-traumatic arthritis.
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http://dx.doi.org/10.1053/j.jfas.2020.08.036DOI Listing
June 2021

A plate-based single-cell ATAC-seq workflow for fast and robust profiling of chromatin accessibility.

Nat Protoc 2021 Jul 19. Epub 2021 Jul 19.

Shenzhen Key Laboratory of Gene Regulation and Systems Biology, School of Life Sciences, Southern University of Science and Technology, Shenzhen, China.

Profiling chromatin accessibility at the single-cell level provides critical information about cell type composition and cell-to-cell variation within a complex tissue. Emerging techniques for the interrogation of chromatin accessibility in individual cells allow investigation of the fundamental mechanisms that lead to the variability of different cells. This protocol describes a fast and robust method for single-cell chromatin accessibility profiling based on the assay for transposase-accessible chromatin using sequencing (ATAC-seq). The method combines up-front bulk Tn5 tagging of chromatin with flow cytometry to isolate single nuclei or cells. Reagents required to generate sequencing libraries are added to the same well in the plate where cells are sorted. The protocol described here generates data of high complexity and excellent signal-to-noise ratio and can be combined with index sorting for in-depth characterization of cell types. The whole experimental procedure can be finished within 1 or 2 d with a throughput of hundreds to thousands of nuclei, and the data can be processed by the provided computational pipeline. The execution of the protocol only requires basic techniques and equipment in a molecular biology laboratory with flow cytometry support.
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http://dx.doi.org/10.1038/s41596-021-00583-5DOI Listing
July 2021

Targeting intracellular WT1 in AML with a novel RMF-peptide-MHC specific T-cell bispecific antibody.

Blood 2021 Jul 19. Epub 2021 Jul 19.

German Cancer Consortium (DKTK) and German Cancer Research Center (DKFZ), Heidelberg, Germany.

Antibody-based immunotherapy is a promising strategy for targeting chemo-resistant leukemic cells. However, classical antibody-based approaches are restricted to targeting lineage-specific cell-surface antigens. By targeting intracellular antigens, a large number of other leukemia-associated targets would become accessible. In this study, we evaluated a novel T-cell bispecific (TCB) antibody, generated using CrossMab and knob-into-holes technology, containing a bivalent T-cell receptor-like binding domain that recognizes the RMFPNAPYL peptide derived from the intracellular tumor antigen Wilms' tumor 1 (WT1) in the context of human leukocyte antigen (HLA) A*02. Binding to CD3ε recruits T cells irrespective of their T-cell receptor specificity. WT1-TCB elicited antibody-mediated T-cell cytotoxicity against AML cell lines in a WT1- and HLA-restricted manner. Specific lysis of primary AML cells was mediated in ex vivo long-term co-cultures utilizing allogenic (mean specific lysis: 67±6% after 13-14 days; ±SEM; n=18) or autologous, patient-derived T cells (mean specific lysis: 54±12% after 11-14 days; ±SEM; n=8). WT1-TCB-treated T cells exhibited higher cytotoxicity against primary AML cells than an HLA-A*02 RMF-specific T-cell clone. Combining WT1-TCB with the immunomodulatory drug lenalidomide further enhanced antibody-mediated T-cell cytotoxicity against primary AML cells (mean specific lysis on day 3-4: 45.4±9.0% vs 70.8±8.3%; p=0.015; ±SEM; n=9-10). In vivo, WT1-TCB-treated humanized mice bearing SKM-1 tumors showed a significant and dose-dependent reduction in tumor growth. In summary, we show that WT1-TCB facilitates potent in vitro, ex vivo and in vivo killing of AML cell lines and primary AML cells; these results led to the initiation of a phase I trial in patients with r/r AML (NCT04580121).
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http://dx.doi.org/10.1182/blood.2020010477DOI Listing
July 2021

Activation of Autophagy Relieves Linoleic Acid-Induced Inflammation in Large Yellow Croaker ().

Front Immunol 2021 30;12:649385. Epub 2021 Jun 30.

Key Laboratory of Aquaculture Nutrition and Feed (Ministry of Agriculture and Rural Affairs) & Key Laboratory of Mariculture (Ministry of Education), Ocean University of China, Qingdao, China.

High levels of soybean oil (SO) in fish diets enriched with linoleic acid (LA, 18:2n-6) could induce strong inflammation. However, the molecular mechanism underlying LA-induced inflammation in the liver of large yellow croaker () has not been elucidated. Based on previous research, autophagy has been considered a new pathway to relieve inflammation. Therefore, the present study was performed to investigate the role of autophagy in regulating LA-induced inflammation in the liver of large yellow croaker and The results of the present study showed that activation of autophagy in liver or hepatocytes could significantly reduce the gene expression of proinflammatory factors, such as tumor necrosis factor α (TNFα) and interleukin 1β (IL1β). The results of the present study also showed that inhibition of autophagy could upregulate the gene expression of proinflammatory factors and downregulate the gene expression of anti-inflammatory factors and . Furthermore, autophagy could alleviate LA-induced inflammatory cytokine gene expression and , while inhibition of autophagy obtained the opposite results. In conclusion, our study shows that autophagy could regulate inflammation and alleviate LA-induced inflammation in the liver of large yellow croaker and for the first time, which may offer considerable benefits to the aquaculture industry and human health.
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http://dx.doi.org/10.3389/fimmu.2021.649385DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8279755PMC
June 2021

Claudin-1/4 as directly target gene of HIF-1α can feedback regulating HIF-1α by PI3K-AKT-mTOR and impact the proliferation of esophageal squamous cell though Rho GTPase and p-JNK pathway.

Cancer Gene Ther 2021 Jul 19. Epub 2021 Jul 19.

Department of Otolaryngology-Head and Neck Surgery, Shandong Provincial ENT Hospital, Cheeloo College of Medicine, Shandong University, Jinan, 250022, P.R. China.

Immunohistochemical microarray comprising 80 patients with esophageal squamous cell carcinoma (ESCC) and discovered that the expression of CLDN1 and CLDN4 were significantly higher in cancer tissues compared to para-cancerous tissues. Furthermore, CLDN4 significantly affected the overall survival of cancer patients. When two ESCC cell lines (TE1, KYSE410) were exposed to hypoxia (0.1% O), CLDN1/4 was shown to influence the occurrence and development of esophageal cancer. Compared with the control culture group, the cancer cells cultured under hypoxic conditions exhibited obvious changes in CLDN1 and CLDN4 expression at both the mRNA and protein levels. Through genetic intervention and Chip, we found that HIF-1α could directly regulate the expression of CLDN1 and CLDN4 in cancer cells. Hypoxia can affect the proliferation and apoptosis of cancer cells by regulating the PI3K-Akt-mTOR pathway. Molecular analysis further revealed that CLDN1 and CLDN4 can participate in the regulation process and had a feedback regulatory effect on HIF-1α expression in cancer cells. In vitro cellular experiments and vivo experiments in nude mice further revealed that changes in CLDN4 expression in cancer cells could affect the proliferation of cancer cells via regulation of Rho GTP and p-JNK pathway. Whether CLDN4 can be target for the treatment of ESCC needs further research.
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http://dx.doi.org/10.1038/s41417-021-00328-2DOI Listing
July 2021

Combined effects of hydralazine and nitrate on serum biochemistry and left ventricular remodeling in chronic heart failure patients.

Pak J Pharm Sci 2021 Jan;34(1(Special)):381-386

Heart Rehabilitation Center, Department of Cardiology, Shanghai Fourth People's Hospital, Tongji University, Shanghai, China.

To investigate the effects of hydralazine combined with nitrate on serum levels of Adropin and brain natriuretic peptide (BNP), left ventricular remodeling and prognosis in patients with chronic heart failure (CHF). 126 CHF patients were divided into control group (n=13, sodium nitroprusside) and combined treatment group (n=63, sodium nitroprusside ± hydralazine). Serum Adropin and BNP levels and left ventricular mass index (LVMI) of patients before treatment and 10 days after treatment were recorded, so did patient's end-point events. It was found that compared with those before treatment, the serum levels of Adropin, BNP, and LVMI in combined group and control group after 10 days of treatment were lower (P<0.05). The end-point event rate in the combined group was 19.05% (12/63). The serum levels of Adropin, BNP, and LVMI in the combined group with end-point events were higher than those of patients without end-point events (P<0.05). Spearman correlation analysis showed that serum levels of Adropin and BNP were positively correlated with LVMI and the end-point events rate (P<0.05). To sum up, hydralazine combined with sodium nitroprusside treatment can effectively reduce serum Adropin and BNP levels, and the risk of left ventricular remodeling and poor prognosis in patients with CHF.
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January 2021

Phase II single-arm study of brentuximab vedotin in Chinese patients with relapsed/refractory classical Hodgkin lymphoma or systemic anaplastic large cell lymphoma.

Expert Rev Hematol 2021 Jul 19. Epub 2021 Jul 19.

Beijing Cancer Hospital, Beijing, China.

Background: Relapsed/refractory (R/R) classical HL (cHL) and systemic anaplastic large-cell lymphoma (sALCL) treatment options are limited in China and there is a need for new therapies.

Research Design And Methods: This single-arm, open-label, multicenter, Phase II study assessed efficacy, safety, and pharmacokinetics (PK) of single-agent brentuximab vedotin in Chinese patients with R/R cHL or sALCL. Patients received brentuximab vedotin as a 1.8 mg/kg intravenous infusion on Day 1 of a 3-week cycle (maximum 16 cycles).

Results: Patients (N=39) received a median of 10 cycles (range: 2-16) of brentuximab vedotin. The objective response rate was 69% (95% CI: 52-83%). Median duration of response, progression-free survival and overall survival were 12.1 months, 13.5 months (95% CI: 6.8 months-not estimable) and not reached after a median follow-up of 16.6 months. Twenty seven (69%) patients achieved an objective response (complete response: n=11 [28%]; partial response: n=16 [41%]). Brentuximab vedotin was well-tolerated with no on-study deaths. AEs were generally manageable and reversible. No new safety signals were identified. PK were consistent with those previously described in Western populations.

Conclusion: Brentuximab vedotin had a positive benefit-risk profile for Chinese patients with R/R cHL or sALCL confirming it as a potential treatment option.

Clinical Trial Registration: www.clinicaltrials.gov identifier is NCT02939014.
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http://dx.doi.org/10.1080/17474086.2021.1942831DOI Listing
July 2021

Assessing the pharmacokinetics of acalabrutinib in the treatment of chronic lymphocytic leukemia.

Expert Opin Drug Metab Toxicol 2021 Jul 28:1-8. Epub 2021 Jul 28.

Department of Hematology, The First Affiliated Hospital of Nanjing Medical University, Jiangsu Province Hospital, Nanjing, China.

Introduction: The first-in-class BTK inhibitor ibrutinib has substantially changed the therapeutic landscape of chronic lymphocytic leukemia (CLL). The next-generation BTK inhibitor acalabrutinib is more selective and may have less off-target toxicities as compared to ibrutinib. Acalabrutinib has demonstrated safety and efficacy in CLL and has been approved to treat CLL.

Areas Covered: Current clinical trials investigated acalabrutinib monotherapy or acalabrutinib-based combination therapies in relapsed/refractory and treatment-naive CLL. Data on the efficacy and safety of acalabrutinib in clinical trials were summarized in this review. The pharmacokinetic and pharmacodynamic data of acalabrutinib were also discussed.

Expert Opinion: Acalabrutinib selectively inhibits BTK by covalent binding and shows rapid absorption and elimination. Acalabrutinib does not inhibit EGFR, TEC, or ITK and shows fewer off-target toxicities. Completed phase 3 trials have demonstrated that acalabrutinib improves the outcomes of patients with relapsed/refractory CLL and patients with treatment-naive CLL. The phase 3 trial that evaluates acalabrutinib versus ibrutinib has met its primary endpoint. Early phase studies suggested the combinations of acalabrutinib with a CD20 antibody and venetoclax led to high rates of undetectable minimal residual disease in the bone marrow in CLL patients and might provide a fixed-duration therapeutic option for patients with CLL.
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http://dx.doi.org/10.1080/17425255.2021.1955855DOI Listing
July 2021

Low prevalence and independent prognostic role of del(11q) in Chinese patients with chronic lymphocytic leukemia.

Transl Oncol 2021 Jul 14;14(10):101176. Epub 2021 Jul 14.

Department of Hematology, the First Affiliated Hospital of Nanjing Medical University, Jiangsu Province Hospital, Nanjing 210029, China; Key Laboratory of Hematology of Nanjing Medical University, Nanjing 210029, China; Collaborative Innovation Center for Cancer Personalized Medicine, Nanjing 210029, China; Pukou CLL Center, Nanjing 210000, China. Electronic address:

The 11q deletion (del(11q)) is a conventional cytogenetic aberration observed in chronic lymphocytic leukemia (CLL) patients. However, the prevalence and the prognostic value of del(11q) are still controversial. In this research, we retrospectively explored the prevalence, association, and prognostic significance of del(11q) in 352 untreated and 99 relapsed/refractory Chinese CLL patients. Totally 11.4% of untreated and 19.2% of relapsed/refractory patients harbored del(11q). Del(11q) was more common in patients with β2-microglobulin > 3.5 mg/L, positive CD38, positive zeta-chain associated protein kinase 70, unmutated immunoglobulin heavy variable-region gene and ataxia telangiectasia mutated mutation. Kaplan-Meier method and univariate Cox regression indicated that del(11q) was an independent prognostic factor for overall survival (OS). Based on the results of univariate Cox regression analysis, two nomograms that included del(11q) were established to predict survival. Desirable area under curve of receiver operating characteristic curves was obtained in the training and validation cohorts. In addition, the calibration curves for the probability of survival showed good agreement between the prediction by nomogram and actual observation. In summary, the prevalence of del(11q) is relatively low in our cohort and del(11q) is an unfavorable prognostic factor for untreated CLL patients. Besides, these two nomograms could be used to accurately predict the prognosis of untreated CLL patients.
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http://dx.doi.org/10.1016/j.tranon.2021.101176DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8287238PMC
July 2021

Prognostic nutritional index, a novel biomarker which predicts worse prognosis in diffuse large B cell lymphoma.

Leuk Res 2021 Jul 7;110:106664. Epub 2021 Jul 7.

Department of Hematology, the First Affiliated Hospital of Nanjing Medical University, Jiangsu Province Hospital, Nanjing 210029, China; Key Laboratory of Hematology of Nanjing Medical University, Nanjing 210029, China; Collaborative Innovation Center for Cancer Personalized Medicine, Nanjing 210029, China. Electronic address:

The prognostic nutritional index (PNI), an indicator of nutritional status and systemic inflammation, is associated with survival in several types of lymphoma. The purpose of this study was to investigate the prognostic value of PNI in diffuse large B cell lymphoma (DLBCL). With three hundred and ten patients were enrolled, the median level of PNI was 45.90 (range 25.30-139.70). According to the receiver operating characteristic (ROC) curve, 44.85 was determined to be the best cutoff value to divide patients into two different groups. With a median follow-up of 33.3 months (range 3.5-118.5), compared with the high PNI group, the 3-year and adjusted 3-year progression-free survival (PFS) and overall survival (OS) were worse in the low PNI group (all P < 0.050). Multivariate Cox analysis suggested that low PNI was an independent risk factor for PFS (hazard ratio (HR) 2.196, 95 % CI 1.197-4.030, P = 0.011) and showed a tendency to predict inferior OS (HR 1.918, 95 % CI 0.932-3.948, P = 0.077). Furthermore, PNI combined with other significant prognostic factors to build a novel prognostic index, namely NPI, was more accurate than the National Comprehensive Cancer Network international prognostic index (NCCN-IPI) to predict worse PFS and had a similar effect on predicting OS. All these findings suggested that PNI, as a novel available biomarker, was of prognostic significance in DLBCL patients.
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http://dx.doi.org/10.1016/j.leukres.2021.106664DOI Listing
July 2021

Danshensu alleviates pseudo-typed SARS-CoV-2 induced mouse acute lung inflammation.

Acta Pharmacol Sin 2021 Jul 15. Epub 2021 Jul 15.

Guangdong Provincial Key Laboratory of New Drug Screening, School of Pharmaceutical Sciences, Southern Medical University, Guangzhou, 510515, China.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can induce acute inflammatory response like acute lung inflammation (ALI) or acute respiratory distress syndrome, leading to severe progression and mortality. Therapeutics for treatment of SARS-CoV-2-triggered respiratory inflammation are urgent to be discovered. Our previous study shows that Salvianolic acid C potently inhibits SARS-CoV-2 infection. In this study, we investigated the antiviral effects of a Salvia miltiorrhiza compound, Danshensu, in vitro and in vivo, including the mechanism of S protein-mediated virus attachment and entry into target cells. In authentic and pseudo-typed virus assays in vitro, Danshensu displayed a potent antiviral activity against SARS-CoV-2 with EC of 0.97 μM, and potently inhibited the entry of SARS-CoV-2 S protein-pseudo-typed virus (SARS-CoV-2 S) into ACE2-overexpressed HEK-293T cells (IC = 0.31 μM) and Vero-E6 cell (IC = 4.97 μM). Mice received SARS-CoV-2 S via trachea to induce ALI, while the VSV-G treated mice served as controls. The mice were administered Danshensu (25, 50, 100 mg/kg, i.v., once) or Danshensu (25, 50, 100 mg·kg·d, oral administration, for 7 days) before SARS-CoV-2 S infection. We showed that SARS-CoV-2 S infection induced severe inflammatory cell infiltration, severely damaged lung tissue structure, highly expressed levels of inflammatory cytokines, and activated TLR4 and hyperphosphorylation of the NF-κB p65; the high expression of angiotensinogen (AGT) and low expression of ACE2 at the mRNA level in the lung tissue were also observed. Both oral and intravenous pretreatment with Danshensu dose-dependently alleviated the pathological alterations in mice infected with SARS-CoV-2 S. This study not only establishes a mouse model of pseudo-typed SARS-CoV-2 (SARS-CoV-2 S) induced ALI, but also demonstrates that Danshensu is a potential treatment for COVID-19 patients to inhibit the lung inflammatory response.
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http://dx.doi.org/10.1038/s41401-021-00714-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8280584PMC
July 2021

A Nomogram to Predict Symptomatic Intracranial Hemorrhage After Intravenous Thrombolysis in Chinese Patients.

Neuropsychiatr Dis Treat 2021 6;17:2183-2190. Epub 2021 Jul 6.

Department of Neurology, Jinling Hospital, The First School of Clinical Medicine, Southern Medical University, Nanjing, Jiangsu, 210002, People's Republic of China.

Background And Aims: A reliable predictive score system to identify the risk of symptomatic intracranial hemorrhage (sICH) after intravenous thrombolysis (IVT) in acute ischemic stroke patients is of great essence. We aimed to develop a nomogram for predicting the risk of sICH after IVT in Chinese patients.

Methods: We recruited acute ischemic stroke patients who were treated with IVT from five advanced stroke centers in China from April 2014 to November 2020. sICH was diagnosed according to the European Cooperative Acute Stroke Study II (ECASS-II) definition. Multivariable logistic regression was performed to construct the best-fit nomogram. The discrimination and calibration of the nomogram were evaluated by the area under the receiver operating characteristic curve (AUC-ROC) and calibration plot.

Results: A total of 1200 patients were enrolled, of whom 66 (5.5%) developed sICH. In the multivariate logistic regression model, atrial fibrillation (odds ratio [OR] 3.25; 95% confidence interval [CI], 1.89-5.60; < 0.001), baseline glucose level (OR, 1.13; 95% CI, 1.07-1.20; < 0.001), neutrophil to lymphocyte ratio (OR, 1.05; 95% CI, 1.01-1.09; = 0.024) and baseline National Institute of Health Stroke Scale (NIHSS) (OR, 1.07; 95% CI, 1.04-1.10; < 0.001) were independent predictors for sICH and were used to generate the nomogram. The nomogram demonstrated good discrimination as the AUC-ROC value was 0.788 (95% CI, 0.737-0.840). The calibration plot revealed good calibration.

Conclusion: The nomogram consisted of atrial fibrillation, baseline glucose level, neutrophil to lymphocyte ratio, and NIHSS score may predict the risk of sICH in Chinese acute ischemic stroke patients treated with IVT.
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http://dx.doi.org/10.2147/NDT.S320574DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8274233PMC
July 2021

Efficacy and safety of tacrolimus monotherapy versus cyclophosphamide-corticosteroid combination therapy for idiopathic membranous nephropathy: A meta-analysis.

Medicine (Baltimore) 2021 Jul;100(28):e26628

Department of Nephrology, Wujin Hospital Affiliated with Jiangsu University, Changzhou, Jiangsu, China.

Objective: The objective of this meta-analysis was to compare the efficacy and safety of tacrolimus (TAC) monotherapy versus cyclophosphamide (CTX)-corticosteroid combination therapy in idiopathic membranous nephropathy (IMN) patients.

Methods: Databases including the PubMed, Embase, the Cochrane Library, China National Knowledge Infrastructure, and Wanfang databases were searched from inception to October 20, 2020. Eligible studies comparing TAC monotherapy and CTX-corticosteroid combination therapy in IMN patients were included. Data were analyzed using Review Manager Version 5.3.

Results: Nine studies were included in the meta-analysis. One randomized controlled trial and eight cohort studies involving 442 patients were identified. Compared with CTX-corticosteroid combination therapy for IMN, TAC monotherapy had higher complete remission (CR) at month 6 (odds ratio [OR] 2.18, 95% confidence interval [CI] 1.35-3.50, P < .01). The 2 therapeutic regimens had similar partial remission (OR 0.69, 95% CI 0.45-1.04, P = .08), total remission (OR 1.38, 95% CI 0.85-2.23, P = 0.19) at month 6, and similar CR (OR 1.64, 95% CI 0.84-3.19, P = .15), partial remission (OR 0.71, 95% CI 0.37-1.38, P = 0.31), and total remission (OR 1.29, 95% CI 0.55-3.01, P = .56) after 1 year. The relapse rate of the TAC group was higher than that of the CTX group, but the difference was not statistically significant (OR 1.85, 95% CI 0.75-4.53, P = .18). There was no difference between the 2 therapeutic regimens concerning glucose intolerance (OR 1.15, 95% CI 0.61-2.14, P = .67), acute renal failure (OR 1.14, 95% CI 0.39-3.33, P = .81), or tremors (OR 4.39, 95% CI 0.75-25.67, P = .10). Incidences of gastrointestinal symptoms (OR 0.29, 95% CI 0.10-0.79, P = .02), infection (OR 0.18, 95% CI 0.08-0.39, P < 0.01), leukopenia (OR 0.14, 95% CI 0.04-0.51, P < .01), and abnormal aminotransferase (OR 0.31, 95% CI 0.13-0.77, P = .01) in the TAC group were all lower than those in the CTX group. Subgroup analysis showed that there was no significant difference between the TAC group and the CTX combined with corticosteroid 0.8 to 1 mg/kg/day group concerning CR at month 6 (P > .05). There was no significant difference between the TAC group and the CTX combined with corticosteroid 0.5 mg/kg/day group concerning abnormal aminotransferase (P > .05).

Conclusion: TAC monotherapy is comparable to CTX-corticosteroid combination therapy for renal remission in IMN patients. TAC monotherapy had a higher CR in the early stage and had fewer drug-related adverse effects. The relapse rate of TAC monotherapy was higher than that of CTX-corticosteroid combination therapy, but the difference was not significant.
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http://dx.doi.org/10.1097/MD.0000000000026628DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8284768PMC
July 2021

Draft genome assembly of the Aral barbell Luciobarbus brachycephalus using PacBio sequencing.

Genome Biol Evol 2021 Jul 13. Epub 2021 Jul 13.

Heilongjiang River Fisheries Research Institute, Chinese Academy of Fishery Sciences, Key Open Laboratory of Cold Water Fish Germplasm Resources and Breeding of Heilongjiang Province, Harbin, China.

The endangered Aral barbell Luciobarbus brachycephalus is endemic to the water systems of the Caspian Sea and Aral Sea. Given the scarcity of genetic data for the species, we present a draft assembly based on PacBio long read sequencing technology. Approximate 299.4 Gb of long reads representing 166X of the estimated genome size were generated, and the final assembly was composed of 653 contigs totaling approximately 1,698.3 Mb, with a contig N50 length of 4.5 Mb. A total of 807.6 Mb represented approximately 47.6% of the assembly and were identified as repeats. Fifty-four thousand and six hundred possible protein genes were predicted, among which 50,727, representing approximately 92.9%, could be annotated by at least one database. Evolutionary analysis showed that L. brachycephalus and Labeo rohita diverged by approximately 42.6 Mya, and the obvious expansion of gene families residing in the L. brachycephalus genome may be attributed to the specific whole genome duplication of the species. The first genome assembly of L. brachycephalus can not only provide a foundation for genetic conservation and molecular breeding of this species but also contribute to comparative analyses of genome biology and evolution within Cyprinidae.
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http://dx.doi.org/10.1093/gbe/evab131DOI Listing
July 2021

Two-Target Quantitative PCR To Predict Library Composition for Shallow Shotgun Sequencing.

mSystems 2021 Jul 13:e0055221. Epub 2021 Jul 13.

Department of Medicine, University of Torontogrid.17063.33, Toronto, Canada.

When determining human microbiota composition, shotgun sequencing is a powerful tool that can generate high-resolution taxonomic and functional information at once. However, the technique is limited by missing information about host-to-microbe ratios observed in different body compartments. This limitation makes it difficult to plan shotgun sequencing assays, especially in the context of high sample multiplexing and limited sequencing output and is of particular importance for studies employing the recently described shallow shotgun sequencing technique. In this study, we evaluated the use of a quantitative PCR (qPCR)-based assay to predict host-to-microbe ratio prior to sequencing. Combining a two-target assay involving the bacterial 16S rRNA gene and the human beta-actin gene, we derived a model to predict human-to-microbe ratios from two sample types, including stool samples and oropharyngeal swabs. We then validated it on two independently collected sample types, including rectal swabs and vaginal secretion samples. This assay enabled accurate prediction in the validation set in a range of sample compositions between 4% and 98% nonhuman reads and observed proportions varied between -18.8% and +19.2% from the expected values. We hope that this easy-to-use assay will help researchers to plan their shotgun sequencing experiments in a more efficient way. When determining human microbiota composition, shotgun sequencing is a powerful tool that can generate large amounts of data. However, in sample compositions with low or variable microbial density, shallowing sequencing can negatively affect microbial community metrics. Here, we show that variable sequencing depth decreases measured alpha diversity at differing rates based on community composition. We then derived a model that can determine sample composition prior to sequencing using quantitative PCR (qPCR) data and validated the model using a separate sample set. We have included a tool that uses this model to be available for researchers to use when gauging shallow sequencing viability of samples.
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http://dx.doi.org/10.1128/mSystems.00552-21DOI Listing
July 2021
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