Publications by authors named "Qin Sun"

232 Publications

Sensing of mycobacterial arabinogalactan by galectin-9 exacerbates mycobacterial infection.

EMBO Rep 2021 May 13:e51678. Epub 2021 May 13.

Department of Thoracic Surgery, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, China.

Mycobacterial arabinogalactan (AG) is an essential cell wall component of mycobacteria and a frequent structural and bio-synthetical target for anti-tuberculosis (TB) drug development. Here, we report that mycobacterial AG is recognized by galectin-9 and exacerbates mycobacterial infection. Administration of AG-specific aptamers inhibits cellular infiltration caused by Mycobacterium tuberculosis (Mtb) or Mycobacterium bovis BCG, and moderately increases survival of Mtb-infected mice or Mycobacterium marinum-infected zebrafish. AG interacts with carbohydrate recognition domain (CRD) 2 of galectin-9 with high affinity, and galectin-9 associates with transforming growth factor β-activated kinase 1 (TAK1) via CRD2 to trigger subsequent activation of extracellular signal-regulated kinase (ERK) as well as induction of the expression of matrix metalloproteinases (MMPs). Moreover, deletion of galectin-9 or inhibition of MMPs blocks AG-induced pathological impairments in the lung, and the AG-galectin-9 axis aggravates the process of Mtb infection in mice. These results demonstrate that AG is an important virulence factor of mycobacteria and galectin-9 is a novel receptor for Mtb and other mycobacteria, paving the way for the development of novel effective TB immune modulators.
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http://dx.doi.org/10.15252/embr.202051678DOI Listing
May 2021

Efficacy of the Xpert Mycobacterium tuberculosis/rifampicin assay for diagnosing sputum-smear negative or sputum-scarce pulmonary tuberculosis in bronchoalveolar lavage fluid.

Int J Infect Dis 2021 Apr 20;107:121-126. Epub 2021 Apr 20.

Department of Tuberculosis, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, China; Shanghai Clinical Research Center for Infectious Disease (Tuberculosis), Shanghai, China. Electronic address:

Objective: To evaluate he diagnostic performance of the Xpert Mycobacterium tuberculosis/Rifampin (MTB/RIF) assay in bronchoalveolar lavage fluid (BALF).

Methods: We retrospectively reviewed the clinical data from 671 sputum-smear negative or sputum-scarce adult patients with suspected pulmonary tuberculosis (PTB) who had an Xpert MTB/RIF assay performed on BALF. The diagnostic performance of the Xpert MTB/RIF assay, smear microscopy (SM) and MTB culture was evaluated using MTB culture or final clinical diagnosis as the reference standard.

Results: Compared with MTB culture, the sensitivity and specificity were 87.8% and 72.7% for the Xpert MTB/RIF assay and 11.0% and 99.2% for SM, respectively. Compared with final diagnosis, diagnostic performance was 58.9% and 83.9% for the Xpert MTB/RIF assay, 5.0% and 98.3% for SM, and 43.3% and 100% for culture, for sensitivity and specificity respectively. The Xpert MTB/RIF assay had low specificity and high sensitivity. When very low results were re-evaluated and considered MTB-negative, the specificity increased significantly. The sensitivity remained higher than SM and was similar to that of culture.

Conclusions: The Xpert MTB/RIF assay adds microbiologic evidence to clinical decisions; however, close attention should be paid to very low semi-quantitative positive results.
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http://dx.doi.org/10.1016/j.ijid.2021.04.040DOI Listing
April 2021

Identifying breast cancer recurrence histories via patient-reported outcomes.

J Cancer Surviv 2021 Apr 14. Epub 2021 Apr 14.

Fred Hutchinson Cancer Research Center, Public Health Sciences, Biostatistics Program, 1100 Fairview Avenue North, M2-B500, Seattle, WA, 98109, USA.

Purpose: To test accuracy of patient self-report of breast cancer recurrence for enhancing standard population-based cancer registries that do not routinely collect cancer recurrence data despite the importance of this outcome.

Methods: Potential research subjects were identified in the Breast Cancer Research Database (BCRD) of the Swedish Cancer Institute (SCI). The BCRD has collected data within 45 days of each medical encounter on new primary breast cancer patients receiving all or part of their initial care at SCI. Females diagnosed with a new primary breast cancer 2004-2016, Stages I-III, and alive at the time of study initiation (2018) were identified. Recurrent breast cancer patients were matched 1:1 to surviving non-recurrent patients by patient age, date of diagnosis, and single or multiple primary tumors. Consented research subjects were surveyed about their initial and subsequent diagnostic, therapeutic, and recurrent events. PRO survey responses were compared with BCRD information for each individual participant. Discrepancies were reviewed in medical records.

Results: A matched sample of 88 recurrent and 88 non-recurrent patients were used in analyses. Respondents correctly identified the date of diagnosis of first primary breast cancer within 1 year 94% (165/176). Recurrence was reported by 97% (85/88) of recurrent patients. No recurrence was reported by 100% (88/88) of non-recurrent patients. Recurrence date within 1 year was correctly identified in 79% (67/85). Recurrence site was correctly identified in 82% (70/85). Medical record review of survey-registry discrepancies led to BCRD corrections in 4.5% (8/176) of cases.

Implications For Cancer Survivors: Breast cancer patients can accurately report their disease characteristics, treatments, and recurrence history. Patient-reported information would enhance cancer registry data.
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http://dx.doi.org/10.1007/s11764-021-01033-7DOI Listing
April 2021

Investigation of the combined use of capping and oxidizing agents in the immobilization of arsenic in sediments.

Sci Total Environ 2021 Apr 6;782:146930. Epub 2021 Apr 6.

State Key Laboratory of Lake Science and Environment, Nanjing Institute of Geography and Limnology, Chinese Academy of Sciences, Nanjing 210008, China.

The combined use of capping (lanthanum modified bentonite; LMB) and oxidizing (calcium nitrate; CN) agents was investigated to immobilize arsenic (As) in sediments. The vertical changes in labile As and dissolved As were measured using diffusive gradients in thin films (DGT) and Rhizon devices. The results showed that the combined application of LMB and CN had the optimal effect on the immobilization of both DGT-labile As and dissolved As, compared to single treatments using LMB or CN. After 60 days of incubation, the maximum reduction efficiencies of DGT-labile As at sediment depths were 76.4%, 70.8%, and 44.9% of those treated with LMB + CN, CN, and LMB, respectively. After 32 days of incubation, the average concentrations of dissolved total As throughout the depths decreased from 7.71 μg/L after the control treatment without any amendments to 5.25, 4.03, and 3.15 μg/L after the addition of LMB, CN, and LMB + CN, respectively. The larger part of exchangeable As at sediment depths was converted into the reducible As mainly bound Fe/Mn oxide-hydroxides after combining LMB and CN. Due to the As(III) existing mainly in the form of electrically neutral HAsO in sediments, it is hard to adsorb As(III) for the LMB and iron/manganese oxide-hydroxides formed by the oxidation effect of calcium nitrate. Thus, the single or combined LMB and CN use had much weaker effect on the immobilization of As(III) compared with As(V). The results of current study indicated that the combined use of LMB and CN could be a promising method to control the potential release of As from the sediment to the overlying water. However, this method needs further improvement to achieve a better immobilization effect on As(III) in sediments.
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http://dx.doi.org/10.1016/j.scitotenv.2021.146930DOI Listing
April 2021

Polypharmacy, chemotherapy receipt, and medication-related out-of-pocket costs at end of life among commercially insured adults with advanced cancer.

J Oncol Pharm Pract 2021 Apr 7:10781552211006180. Epub 2021 Apr 7.

Hutchinson Institute for Cancer Outcomes Research, Fred Hutchinson Cancer Research Center, Seattle, WA, USA.

Background: Polypharmacy raises the risk of drug-drug interactions and adverse events among patients with cancer. Most polypharmacy research has focused on adults age 65 or older enrolled in Medicare insurance. To better inform pharmacy practice and cancer care delivery, data are needed on polypharmacy among commercially insured patients with cancer and those younger than 65.

Methods: We performed a retrospective analysis of insurance enrollment and claims files linked to the Puget Sound Cancer Surveillance System for adults age 18 and older who were commercially insured, diagnosed with stage IV cancer, survived 30+ days after diagnosis, and did not enroll in hospice. We describe the prevalence of polypharmacy, chemotherapy use, and medication-related out-of-pocket (OOP) costs in the last month of life.

Results: Of 606 patients, 390 (64%) experienced polypharmacy (i.e. 5+ medications) in the last 30 days of life. Almost half (n = 297, 49%) received chemotherapy or targeted agents; chemotherapy was associated with significantly higher odds of polypharmacy (odds ratio (OR) 2.93, 95% confidence interval (CI) 2.04-4.20). The most commonly prescribed medications at end of life were opioids, benzodiazepines and anti-emetics. Among 484 patients (80%) incurring medication-related costs in the last month of life, median total OOP cost was $82 (interquartile range $30-$200). Seven patients (1%) had total costs above $5,000. The median chemotherapy-related OOP cost was $446 (IQR $150-$1896); 32 patients (7%) had chemotherapy-related OOP costs between $1,000 and $5,000.

Conclusion: Most patients with advanced cancer experienced polypharmacy at end of life, although most medications observed herein are commonly used for supportive care. Patients receiving chemotherapy had higher medication-related OOP costs, and chemotherapy was significantly associated with polypharmacy at end of life. Evaluation of polypharmacy at end of life may represent an important opportunity to improve quality of life and reduce costs for patients and families.
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http://dx.doi.org/10.1177/10781552211006180DOI Listing
April 2021

Body composition measured by bioelectrical impedance analysis is a viable alternative to magnetic resonance imaging in children with nonalcoholic fatty liver disease.

JPEN J Parenter Enteral Nutr 2021 Apr 2. Epub 2021 Apr 2.

Division of Gastroenterology, Hepatology, and Nutrition, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, USA.

Objective: To determine the relationship between bioelectrical impedance analysis (BIA) and magnetic resonance imaging (MRI) obtained measures of body composition in children with nonalcoholic fatty liver disease (NAFLD).

Methods: Youth with obesity and NAFLD who had BIA and abdominal MRI testing were included. BIA measured skeletal muscle mass (SMM), appendicular lean mass (ALM), trunk muscle mass (TMM), and percent body fat. MRI measured total psoas muscle surface area (tPMSA) and fat compartments. Univariate analysis described the relationship between BIA- and MRI-derived measurements. Multivariable regression analyses built a model with body composition measured via MRI.

Results: 115 patients (82 (71%) male, 38 (33%) Hispanic, median age14 years) were included. There was a strong correlation between tPMSA and SMM, ALM, and TMM (correlation coefficients [CCs]: 0.701, 0.689, 0.708, respectively; all P < .001). Higher SMM, ALM, and TMM were associated with higher tPMSA. This association remained after controlling for age, sex, ethnicity, type 2 diabetes mellitus status, and body mass index z-score. Total fat mass by BIA and MRI-determined total, subcutaneous, and intraperitoneal fat area correlated significantly (CCs: 0.813, 0.808, 0.515, respectively; all P < .001). In univariate regression, higher total fat mass by BIA was associated with increased total fat area and increased fat in each of the four regions measured by MRI. After controlling for confounders, the association between total fat mass by BIA and total fat area by MRI persisted.

Conclusions: BIA measures of muscle and fat mass correlate strongly with MRI measures of tPMSA and fat areas in children with obesity and NAFLD.
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http://dx.doi.org/10.1002/jpen.2113DOI Listing
April 2021

Effects of pre-mixed hydraulic calcium silicate putties on osteogenic differentiation of human dental pulp stem cells in vitro.

J Dent 2021 May 30;108:103653. Epub 2021 Mar 30.

Department of Endodontics, The Dental College of Georgia, Augusta University, Augusta, GA, USA. Electronic address:

Objectives: An experimental tricalcium silicate and dicalcium silicate-containing endodontic putty has been designed to overcome the issue of reduced shelf life after exposure to atmospheric moisture during repeated opening of the container for clinical retrieval. The present study examined the effects of this experimental hydraulic putty on the mineralogenic characteristics of osteogenic lineage-committed human dental pulp stem cells (hDPSCs), by comparing the cellular responses with a commercially available putty (EndoSequence BC RRM Putty).

Methods: The osteogenic potential of hDPSCs that had been exposed to the putties was examined using quantitative reverse-transcription polymerase chain reaction for osteogenic gene expressions and western blot for osteogenic protein expressions. Alkaline phosphatase activity assay and alizarin red S staining were performed to detect changes in production of the intracellular enzyme and extracellular matrix mineralization respectively.

Results: Osteogenic differentiation of the hDPSCs was significantly enhanced after exposure to the pre-mixed hydraulic putties, with no significant difference between these two examined putties.

Conclusions: The experimental hydraulic tricalcium silicate putty enhances osteogenic differentiation of hDPSCs to the same extent as a commercially available tricalcium silicate putty.

Clinical Significance: The experimental hydraulic putty appears to be an alternative to the commercial putty when used for applications involving the regeneration of bone in endodontics. Animal models are required for validating its potential in enhancing osteogenesis in vivo.
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http://dx.doi.org/10.1016/j.jdent.2021.103653DOI Listing
May 2021

Research progress of traditional Chinese medicine against COVID-19.

Biomed Pharmacother 2021 May 3;137:111310. Epub 2021 Feb 3.

National Traditional Chinese Medicine Clinical Research Base, Affiliated Traditional Chinese Medicine Hospital, Southwest Medical University, Luzhou 646000, China; Drug Research Center of Integrated Traditional Chinese and Western Medicine, Affiliated Traditional Chinese Medicine Hospital, Southwest Medical University, Luzhou 646000, Sichuan, China. Electronic address:

Background: Currently, the number of confirmed cases and deaths of COVID-19 worldwide continues to rise, receiving great concern from the international community. However, there is no specific and widely accepted effective vaccines. The experience in controlling the outbreak in China has proven the effectiveness of traditional Chinese medicine (TCM).

Objectives: This review aims to evaluate the role of TCM in COVID-19 treatment, hoping to provide references for prevention and control of global pandemic.

Data Sources: China National Knowledge Infrastructure, Web of Science, Baidu Scholar, ScienceDirect, Elsevier and PubMed were used to search literatures published from December 2019 to December 2020 by entering the keywords "Traditional Chinese medicine", "COVID-19″, "Severe acute respiratory syndrome coronavirus 2″, "Pathogenesis", "Syndrome differentiation", "Prescriptions" and their combinations. Hence, we have performed an extensive review of research articles, reviews and primary scientific studies to identify TCM against COVID-19.

Results: Among clinical treatments of COVID-19, several TCM prescriptions and characteristic therapies have been effectively suggested, the underlying mechanisms of which are mainly involved in antiviral, anti-inflammatory, immunomodulatory and organ-protective effects of multi-components acting on multi-targets at multi-pathways.

Conclusions: This review may provide meaningful and feasible information that can be considered for the treatment of COVID-19 pandemic globally.
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http://dx.doi.org/10.1016/j.biopha.2021.111310DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7857050PMC
May 2021

Integrated analysis of RNA-binding proteins in thyroid cancer.

PLoS One 2021 12;16(3):e0247836. Epub 2021 Mar 12.

Department of Geriatric Endocrinology, Sichuan Academy of Medical Sciences and Sichuan Provincial People's Hospital, Chengdu, P.R. China.

Recently, the incidence of thyroid cancer (THCA) has been on the rise. RNA binding proteins (RBPs) and their abnormal expression are closely related to the emergence and pathogenesis of tumor diseases. In this study, we obtained gene expression data and corresponding clinical information from the TCGA database. A total of 162 aberrantly expressed RBPs were obtained, comprising 92 up-regulated and 70 down-regulated RBPs. Then, we performed a functional enrichment analysis and constructed a PPI network. Through univariate Cox regression analysis of key genes and found that NOLC1 (p = 0.036), RPS27L (p = 0.011), TDRD9 (p = 0.016), TDRD6 (p = 0.002), IFIT2 (p = 0.037), and IFIT3 (p = 0.02) were significantly related to the prognosis. Through the online website Kaplan-Meier plotter and multivariate Cox analysis, we identified 2 RBP-coding genes (RPS27L and IFIT3) to construct a predictive model in the entire TCGA dataset and then validate in two subsets. In-depth analysis revealed that the data gave by this model, the patient's high-risk score is very closely related to the overall survival rate difference (p = 0.038). Further, we investigated the correlation between the model and the clinic, and the results indicated that the high-risk was in the male group (p = 0.011) and the T3-4 group (p = 0.046) was associated with a poor prognosis. On the whole, the conclusions of our research this time can make it possible to find more insights into the research on the pathogenesis of THCA, this could be beneficial for individualized treatment and medical decision making.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0247836PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7954316PMC
March 2021

Preferential Use of Stainless Steel Crowns as a Strategy to Minimize Retreatment of Primary Molars under General Anesthesia.

Pediatr Dent 2021 Jan;43(1):24-27

Dr. Cully is an assistant professor, Cincinnati, Ohio;, Email:

The purpose of this study was to investigate whether primary molars treated with composite resins (CRs) and stainless steel crowns (SSCs) during an oral rehabilitation under general anesthesia (GA1) required retreatment at a second oral rehabilitation under GA (GA2). Records were examined from 296 healthy patients with more than one dental rehabilitation under general anesthesia from June 2012 to January 2019. Data included treatment details and demographic information. Frequencies and means were recorded. An analysis was completed using logistic regression and chi-square for categorical variables. For primary first molars, 43 percent of CRs placed at GA1 were treated with SSCs at GA2. For primary second molars, 35 percent of CRs placed at GA1 were treated with SSCs at GA2. There was no statistically significant difference in retreatment rates by molar type (P equals 0.27). Eight percent of SSCs placed on any molar at GA1 required retreatment at GA2. Primary molars treated with stainless steel crowns using general anesthesia had the lowest percentage of retreatment compared to those treated with composite resins. Strong consideration should be given to the placement of SSCs on primary molars in patients with early childhood caries under general anesthesia. Placement of primary molar SSCs during initial treatment under general anesthesia may reduce the need for additional treatment in the future.
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January 2021

Bactericidal/Permeability-Increasing Protein Improves Cognitive Impairment in Diabetic Mice Blockade of the LPS-LBP-TLR4 Signaling Pathway.

Front Physiol 2020 11;11:718. Epub 2021 Feb 11.

School of Medicine, University of Electronic Science and Technology of China, Chengdu, China.

Emerging evidence suggests that the bactericidal/permeability-increasing protein (BPI) is involved in the process of cognitive impairment in diabetes. However, its underlying mechanism remains elusive. In this study, we found that BPI affects cognitive impairment due to diabetes through the lipopolysaccharide (LPS)-lipopolysacharide-binding protein (LBP)-toll-like receptor 4 (TLR4) signaling pathway. We examined the expression of BPI, LPS, LBP, CD14, and TLR4 in established mouse models of diabetes induced by high-fat diet (HFD) in combination with streptozotocin (STZ). Diabetic mice were then injected with adeno-associated-virus carrying BPI overexpression vectors and LPS. Fasting blood glucose, plasma insulin, and serum levels of inflammatory factors were examined. Then, glucose tolerance and, insulin resistance tests were used to measure systemic insulin sensitivity. Next, hippocampal tissue injury and cell apoptosis were examined by hematoxylin-eosin (HE) and terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling (TUNEL) staining. Diabetic mice displayed increased LPS expression and activation of the LPS-CD14-TLR4 signaling pathway. HFD mice following LPS treatment showed significantly increased serum levels of tumor necrosis factor-α (TNF-α), interleukin (IL)-1β, and IL-6, and expressions of Bcl-2-associated X protein (Bax) and Aβ but decreased expression of Bcl-2 in hippocampal tissues, as well as enhanced fasting blood glucose, plasma insulin, glucose tolerance, insulin tolerance, cell apoptosis, aggravated hippocampal tissue injury and, ultimately, cognitive impairment. However, overexpression of BPI was able to rescue the aforementioned phenotypes driven by LPS treatment. Taken together, BPI could potentially provide relief from cognitive impairment in diabetic mice by disrupting the LPS-LBP-TLR4 signaling pathway, underscoring a possible alternative therapeutic strategy against the cognitive impairment associated with diabetes.
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http://dx.doi.org/10.3389/fphys.2020.00718DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7905103PMC
February 2021

Pulmonary midkine inhibition ameliorates sepsis induced lung injury.

J Transl Med 2021 02 27;19(1):91. Epub 2021 Feb 27.

Jiangsu Provincial Key Laboratory of Critical Care Medicine, Department of Critical Care Medicine, Zhongda Hospital, School of Medicine, Southeast University, 87 Dingjiaqiao Rd., Nanjing, 210009, People's Republic of China.

Background: Midkine is a multi-functional molecule participating in a various key pathological process. We aimed to evaluate the change of midkine in sepsis and its association with angiotensin-converting enzyme (ACE) system, as well as the mechanism by which midkine induced in sepsis and lung injury.

Methods: The peripheral blood sample of septic patients on admission was obtained and measured for midkine, ACE and angiotensin II. Cecal ligation and puncture (CLP) mouse model was used, and adeno-associated virus (AAV) was stilled trans-trachea for regional targeting midkine expression, comparing the severity of lung injury. Furthermore, we studied the in vitro mechanism of midkine activates ACE system by using inhibitors targeting candidate receptors of midkine, and its effects on the vascular endothelial cells.

Results: Plasma midkine was significantly elevated in sepsis, and was closely associated with ACE system. Both circulating and lung midkine was increased in CLP mouse, and was related to severe lung injury. Regional interfering midkine expression in lung tissue by AAV could alleviate acute lung injury in CLP model. In vitro study elucidated that Notch 2 participated in the activation of ACE system and angiotensin II release, induced by midkine and triggered vascular endothelial injury by angiotensin II induced reactive oxygen species production.

Conclusions: Midkine inhibition ameliorates sepsis induced lung injury, which might via ACE/Ang II pathway and the participation of Notch 2 in the stimulation of ACE. Trial registration Clinicaltrials.gov NCT02605681. Registered 12 November 2015.
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http://dx.doi.org/10.1186/s12967-021-02755-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7913048PMC
February 2021

Prognostic Significance of Plasma Hepatocyte Growth Factor in Sepsis.

J Intensive Care Med 2021 Feb 22:885066621993423. Epub 2021 Feb 22.

Department of Critical Care Medicine, Zhongda Hospital, School of Medicine, Southeast University, Nanjing, People's Republic of China.

Background: To assess any correlation of plasma hepatocyte growth factor (HGF) levels with relevant endothelial cell injury parameters and determine the prognostic value in septic patients.

Methods: A prospective, observational study was conducted in patients with sepsis admitted to the Department of Critical Care Medicine at the Zhongda Hospital from November 2017 to March 2018. Plasma HGF levels were measured by enzyme-linked immunosorbent assay in the first 24 h after admission (day 1) and on day 3. The primary endpoint was defined as all-cause 28-day mortality. Furthermore, we analyzed the correlation of HGF with relevant endothelial cell injury markers.

Results: Eighty-six patients admitted with sepsis were included. HGF levels of nonsurvivors were elevated compared to those of survivors on day 1 (1940.62 ± 74.66 pg/mL vs. 1635.61 ± 47.49 pg/mL; = 0.002) and day 3 (1824.82 ± 137.52 pg/mL vs. 1309.77 ± 83.49 pg/mL; = 0.001) and showed a strong correlation with von Willebrand factor (r = 0.45, < 0.0001), lactate (r = 0.35, = 0.0011), pulmonary vascular permeability index (r = 0.38, = 0.0241), first 24 h fluid administration (r = 0.38, < 0.0001), and sequential organ failure assessment score (r = 0.40, = 0.0001). Plasma HGF levels were able to prognostically discriminate between survivors and nonsurvivors on day 1 (AUC: 0.72, 95%CI: 0.60-0.84) and day 3 (AUC: 0.77, 95%CI: 0.63-0.91).

Conclusions: HGF levels are associated with sepsis and correlated with established markers of endothelial cell injury. Elevated HGF levels in sepsis patients are an efficient indicator of poor prognosis.

Trial Registration: The study was registered in Clinical Trial (Registration Number: NCT02883231).
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http://dx.doi.org/10.1177/0885066621993423DOI Listing
February 2021

Research Advance on Qingfei Paidu Decoction in Prescription Principle, Mechanism Analysis and Clinical Application.

Front Pharmacol 2020 27;11:589714. Epub 2021 Jan 27.

National Traditional Chinese Medicine Clinical Research Base, Affiliated Traditional Chinese Medicine Hospital, Southwest Medical University, Luzhou, China.

Since the sudden epidemic of coronavirus disease 2019 (COVID-19), the State Administration of Traditional Chinese Medicine immediately organized experts to formulate and screen the effective prescriptions of traditional Chinese medicine according to the characteristics of the novel coronavirus infection. Qingfei Paidu decoction (QFPDD) has been proven to be effective in multi-provincial clinical trials, and has been selected as a general prescription for the treatment of COVID-19 in different stages that was later promoted to be used nationwide. This review highlights the latest advances of QFPDD, focusing on the TCM theory, mechanism analysis, clinical application of QFPDD and its future perspectives. Moreover, an in-depth discussion of some valuable issues and possible development for future research on QFPDD is also discussed, aiming to provide a novel guide to combat the global epidemic COVID-19.
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http://dx.doi.org/10.3389/fphar.2020.589714DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7873690PMC
January 2021

Neural control of pressure support ventilation improved patient-ventilator synchrony in patients with different respiratory system mechanical properties: a prospective, crossover trial.

Chin Med J (Engl) 2021 Jan 19;134(3):281-291. Epub 2021 Jan 19.

Jiangsu Provincial Key Laboratory of Critical Care Medicine, Department of Critical Care Medicine, Zhongda Hospital, School of Medicine, Southeast University, Nanjing, Jiangsu 210009, China.

Background: Conventional pressure support ventilation (PSP) is triggered and cycled off by pneumatic signals such as flow. Patient-ventilator asynchrony is common during pressure support ventilation, thereby contributing to an increased inspiratory effort. Using diaphragm electrical activity, neurally controlled pressure support (PSN) could hypothetically eliminate the asynchrony and reduce inspiratory effort. The purpose of this study was to compare the differences between PSN and PSP in terms of patient-ventilator synchrony, inspiratory effort, and breathing pattern.

Methods: Eight post-operative patients without respiratory system comorbidity, eight patients with acute respiratory distress syndrome (ARDS) and obvious restrictive acute respiratory failure (ARF), and eight patients with chronic obstructive pulmonary disease (COPD) and mixed restrictive and obstructive ARF were enrolled. Patient-ventilator interactions were analyzed with macro asynchronies (ineffective, double, and auto triggering), micro asynchronies (inspiratory trigger delay, premature, and late cycling), and the total asynchrony index (AI). Inspiratory efforts for triggering and total inspiration were analyzed.

Results: Total AI of PSN was consistently lower than that of PSP in COPD (3% vs. 93%, P = 0.012 for 100% support level; 8% vs. 104%, P = 0.012 for 150% support level), ARDS (8% vs. 29%, P = 0.012 for 100% support level; 16% vs. 41%, P = 0.017 for 150% support level), and post-operative patients (21% vs. 35%, P = 0.012 for 100% support level; 15% vs. 50%, P = 0.017 for 150% support level). Improved support levels from 100% to 150% statistically increased total AI during PSP but not during PSN in patients with COPD or ARDS. Patients' inspiratory efforts for triggering and total inspiration were significantly lower during PSN than during PSP in patients with COPD or ARDS under both support levels (P < 0.05). There was no difference in breathing patterns between PSN and PSP.

Conclusions: PSN improves patient-ventilator synchrony and generates a respiratory pattern similar to PSP independently of any level of support in patients with different respiratory system mechanical properties. PSN, which reduces the trigger and total patient's inspiratory effort in patients with COPD or ARDS, might be an alternative mode for PSP.

Trial Registration: ClinicalTrials.gov, NCT01979627; https://clinicaltrials.gov/ct2/show/record/NCT01979627.
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http://dx.doi.org/10.1097/CM9.0000000000001357DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7846453PMC
January 2021

Fine mapping of a kernel length-related gene with potential value for maize breeding.

Theor Appl Genet 2021 Apr 18;134(4):1033-1045. Epub 2021 Jan 18.

National Key Laboratory of Crop Genetic Improvement, Huazhong Agricultural University, No.1, Shizishan Street, Hongshan District, Wuhan, 430070, People's Republic of China.

Key Message: A key candidate gene for maize kernel length was fine mapped to an interval of 942 kb; the locus significantly increases kernel length (KL) and hundred-kernel weight (HKW). Kernel size is a major determinant of yield in cereals. Kernel length, one of the determining factors of kernel size, is a target trait for both domestication and artificial breeding. However, there are few reports of fine mapping and quantitative trait loci (QTLs)/cloned genes for kernel length in maize. In this project, a novel major QTL, named qKL9, controlling maize kernel length was identified. We verified the authenticity and stability of qKL9 via BCF and BCF populations, respectively, and ultimately mapped qKL9 to an ~ 942-kb genomic interval by testing the progenies of recombination events derived from BCF and BCF populations in multiple environments. Additionally, one new line (Mc) containing the ~ 942-kb segment was screened from the BCF population. Combining transcriptome analysis between Mc and Mc at 6, 9 and 14 days after pollination and candidate regional association mapping, Zm00001d046723 was preliminarily identified as the key candidate gene for qKL9. Importantly, the replacement in the Mc line of the Mc's alleles by the V671's alleles in the qKL9 region improved the performances of single-cross hybrids obtained with elite lines, illustrating the potential value of this QTL for the genetic improvement in maize kernel-related traits. These findings facilitate molecular breeding for kernel size and cloning of the gene underlying qKL9, shedding light on the genetic basis of kernel size in maize.
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http://dx.doi.org/10.1007/s00122-020-03749-zDOI Listing
April 2021

Corticosteroid Therapy Is Associated With Improved Outcome in Critically Ill Patients With COVID-19 With Hyperinflammatory Phenotype.

Chest 2021 05 13;159(5):1793-1802. Epub 2020 Dec 13.

Jiangsu Provincial Key Laboratory of Critical Care Medicine, Department of Critical Care Medicine, Zhongda Hospital, School of Medicine, Southeast University, Nanjing. Electronic address:

Background: Corticosteroid therapy is used commonly in patients with COVID-19, although its impact on outcomes and which patients could benefit from corticosteroid therapy are uncertain.

Research Question: Are clinical phenotypes of COVID-19 associated with differential response to corticosteroid therapy?

Study Design And Methods: Critically ill patients with COVID-19 from Tongji Hospital treated between January and February 2020 were included, and the main exposure of interest was the administration of IV corticosteroids. The primary outcome was 28-day mortality. Marginal structural modeling was used to account for baseline and time-dependent confounders. An unsupervised machine learning approach was carried out to identify phenotypes of COVID-19.

Results: A total of 428 patients were included; 280 of 428 patients (65.4%) received corticosteroid therapy. The 28-day mortality was significantly higher in patients who received corticosteroid therapy than in those who did not (53.9% vs 19.6%; P < .0001). After marginal structural modeling, corticosteroid therapy was not associated significantly with 28-day mortality (hazard ratio [HR], 0.80; 95% CI, 0.54-1.18; P = .26). Our analysis identified two phenotypes of COVID-19, and compared with the hypoinflammatory phenotype, the hyperinflammatory phenotype was characterized by elevated levels of proinflammatory cytokines, higher Sequential Organ Failure Assessment scores, and higher rates of complications. Corticosteroid therapy was associated with a reduced 28-day mortality (HR, 0.45; 95% CI, 0.25-0.80; P = .0062) in patients with the hyperinflammatory phenotype.

Interpretation: For critically ill patients with COVID-19, corticosteroid therapy was not associated with 28-day mortality, but the use of corticosteroids showed significant survival benefits in patients with the hyperinflammatory phenotype.
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http://dx.doi.org/10.1016/j.chest.2020.11.050DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7834518PMC
May 2021

LncRNA NEAT1 participates in inflammatory response in macrophages infected by mycobacterium tuberculosis through targeted regulation of miR-377-3p.

Microb Pathog 2021 Jan 30;150:104674. Epub 2020 Nov 30.

Shanghai Clinical Research Center for Tuberculosis, Shanghai Key Laboratory of Tuberculosis, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, 200433, China. Electronic address:

Background Tuberculosis (TB) is a very serious public health problem in the world at present. The incidence rate is rising continuously. Once it develops to the middle and late stage, it can cause serious tissue damage and necrosis, directly threatening the life and health of patients. Because of its high incidence, high infectivity and high mortality, clinical research on TB has never stopped. Previous studies have confirmed the effect of macrophages on mycobacterium tuberculosis (MTB) infection, and its regulatory mechanism has not yet been fully clarified. Objective To analyze the effects of NEAT1 and miR-377-3p on macrophages infected by MTB and provide new reference for the diagnosis and treatment of TB in the future. Methods The pulmonary TB patients admitted to our hospital from July 2017 to July 2019 and the healthy cases at the same time were selected as the research objects for prospective analysis. In addition, THP-1 cells and mycobacterium tuberculosis H37Ra were purchased to construct macrophages infected by H37Ra, and the effects of NEAT1 and miR-377-3p on macrophages and their relationship with inflammatory factors were analyzed. Results NEAT1 was highly expressed in pulmonary TB patients and miR-377-3p was poorly expressed (p < 0.05). The concentrations of inflammatory factors in serum of patients with pulmonary TB were significantly higher than those in healthy cases (P < 0.001). After infection with H37Ra, the inflammatory factors in macrophages increased significantly (p < 0.001), while miR-377-3p decreased (p < 0.001). Inhibition of NEAT1 and increase of miR-377-3p could decrease inflammatory factors and proliferation ability of cells, and increase apoptosis rate (p < 0.001). The double luciferase reporter assay showed that the fluorescence activity of NEAT1-WT was inhibited by the transfection of miR-377-3pmimics (P < 0.001). Conclusion NEAT1 participates in inflammatory response in macrophages infected by MTB through targeted regulation of miR-377-3p.
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http://dx.doi.org/10.1016/j.micpath.2020.104674DOI Listing
January 2021

Manoeuvrability and biocompatibility of endodontic tricalcium silicate-based putties.

J Dent 2021 01 19;104:103530. Epub 2020 Nov 19.

Department of Endodontics, The Dental College of Georgia, Augusta University, Augusta, GA, USA. Electronic address:

Objectives: The present study evaluated the indentation depth, storage modulus and biocompatibility of an experimental endodontic putty designed for endodontic perforation repair and direct pulp-capping (NeoPutty). The results were compared with the properties associated with the commercially available EndoSequence BC RRM Putty (ES Putty).

Methods: Indentation depth was measured by a profilometer following indentation with the 1/4 lb Gilmore needle. Elastic modulus was evaluated using a strain-controlled rheometer. The effects of eluents derived from these two putties were examined on the viability and proliferation of human dental pulp stem cells (hDPSCs) and human periodontal ligament fibroblasts (hPDLFs), before (1 st testing cycle) and after complete setting (2nd testing cycle).

Results: The ES Putty became more difficult to ident and acquired a larger storage modulus after exposure to atmospheric moisture. Biocompatibility results indicated that both putties were relatively more cytotoxic than the bioinert Teflon negative control, but much less cytotoxic than the zinc oxide-eugenol cement negative control. NeoPutty was less cytotoxic than ES putty in the 1st testing cycle, particularly with hDPSCs. Both putties exhibited more favourable cytotoxicity profiles after complete setting.

Conclusions: NeoPutty has a better window of maneuverability after exposure to atmospheric moisture. From an in vitro cytotoxicity perspective, the NeoPutty may be considered more biocompatible than ES putty.

Clinical Significance: The experimental NeoPutty is biocompatible and is capable of reducing the frustration of shortened shelf life when jar-stored endodontic putties are exposed to atmospheric moisture during repeated opening of the lid for clinical retrieval.
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http://dx.doi.org/10.1016/j.jdent.2020.103530DOI Listing
January 2021

The effect of thymosin α1 on mortality of critical COVID-19 patients: A multicenter retrospective study.

Int Immunopharmacol 2021 Jan 31;90:107143. Epub 2020 Oct 31.

Jiangsu Provincial Key Laboratory of Critical Care Medicine, Department of Critical Care Medicine, Zhongda Hospital, School of Medicine, Southeast University, No. 87, Dingjiaqiao Road, Gulou District, Nanjing 210009, PR China. Electronic address:

Background: Thymosin α1 therapy was commonly used in patients with coronavirus disease 2019 (COVID-19), while its impact on outcomes and which patients could benefit from thymosin α1 therapy were uncertain.

Study Design And Methods: Patients with COVID-19 from 19 designated hospitals between January 1 to February 29, 2020 were included, and the main exposure of interest was administration of thymosin α1. The primary outcome was 28-day mortality. Propensity score matching (PSM) was used to account for baseline confounders, cluster analysis and Cox proportional hazard model was used to account for subgroup analysis.

Results: A total of 771 patients were included, and 327/771 (42.4%) patients received thymosin α1 therapy. The 28-day mortality in thymosin group was significantly lower than that in control group (41.3% vs. 60.6%, p < 0.001). After PSM 522 patients were included in analysis and the 28-day mortality in thymosin α1 group and control group were 51.0% and 52.9% respectively, with no significant difference. In subgroup analyses, the association between thymosin α1 therapy and 28-day mortality appeared to be stronger among male patients (HR 0.673, 95% CI 0.454-0.998; p = 0.049). There were no benefits of thymosin α1 in 28-day mortality in other subgroups. There were two phenotypes after cluster analysis, but no benefits of thymosin α1 were shown in phenotype 1 (HR 0.823 95% CI 0.581-1.166; p = 0.273) and phenotype 2 (HR 1.148 95% CI 0.710-1.895; p = 0.442).

Conclusion: There was no association between use of thymosin α1 and decreased mortality in critically ill COVID-19 patients. Subgroups analysis and phenotype analysis also showed no differences on mortality after thymosin α1 therapy.
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http://dx.doi.org/10.1016/j.intimp.2020.107143DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7604217PMC
January 2021

Integrated network pharmacology and molecular docking approaches to reveal the synergistic mechanism of multiple components in for ameliorating heart failure.

PeerJ 2020 30;8:e10107. Epub 2020 Oct 30.

School of Life Sciences, Beijing University of Chinese Medicine, Beijing, China.

(VB), also called Chan Su in China, has been extensively used as a traditional Chinese medicine (TCM) for treating heart failure (HF) since ancient time. However, the active components and the potential anti-HF mechanism of VB remain unclear. In the current study, the major absorbed components and metabolites of VB after oral administration in rats were first collected from literatures. A total of 17 prototypes and 25 metabolites were gathered. Next, a feasible network-based pharmacological approach was developed and employed to explore the therapeutic mechanism of VB on HF based on the collected constituents. In total, 158 main targets were screened out and considered as effective players in ameliorating HF. Then, the VB components-main HF putative targets-main pathways network was established, clarifying the underlying biological process of VB on HF. More importantly, the main hubs were found to be highly enriched in adrenergic signalling in cardio-myocytes. After verified by molecular docking studies, four key targets (ATP1A1, GNAS, MAPK1 and PRKCA) and three potential active leading compounds (bufotalin, cinobufaginol and 19-oxo-bufalin) were identified, which may play critical roles in cardiac muscle contraction. This study demonstrated that the integrated strategy based on network pharmacology and molecular docking was helpful to uncover the synergistic mechanism of multiple constituents in TCM.
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http://dx.doi.org/10.7717/peerj.10107DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7605218PMC
October 2020

Can Baseline Characteristics be Used to Predict Liver Disease Outcomes in Pediatric Nonalcoholic Fatty Liver Disease?

Obesity (Silver Spring) 2021 Jan 13;29(1):171-176. Epub 2020 Nov 13.

Division of Gastroenterology, Hepatology and Nutrition, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, USA.

Objective: Longitudinal studies on childhood predictors of nonalcoholic fatty liver disease (NAFLD) progression are lacking. The objective of this study was to determine whether baseline clinical or laboratory measures predict liver disease outcomes in a pediatric NAFLD cohort.

Methods: A retrospective study of patients with presumed NAFLD was conducted using baseline and follow-up clinical and laboratory measures. Disease outcomes were defined using the mean serum alanine aminotransferase (ALT) levels from 24 to 36 months after the first visit. Logistic regression assessed the relationship between ALT progression/regression and predictor variables. Multivariable regression determined the best model for predicting the ALT outcome. Markov process modeling explored the likelihood for a patient to transition between ALT states.

Results: Of a total of 816 patients identified, 144 had sufficient data. Regression was seen in 26%, whereas 30% progressed. No baseline clinical or laboratory measurements had a significant effect on disease outcomes. Markov modeling demonstrated that subjects were more likely to either remain in their baseline ALT group or worsen rather than improve.

Conclusions: Routinely obtained baseline clinical or laboratory measures cannot help risk-stratify youth with presumed NAFLD in terms of long-term outcomes. Close clinical, radiographic, and histologic evaluation of patients is warranted to determine those at risk of progression.
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http://dx.doi.org/10.1002/oby.22999DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7902314PMC
January 2021

[Effectiveness of Saccharomyces boulardii combined with phototherapy in the treatment of hyperbilirubinemia in neonates: a prospective randomized controlled trial].

Zhongguo Dang Dai Er Ke Za Zhi 2020 Nov;22(11):1149-1153

Department of Pediatrics, Affiliated Hospital of Jiangsu University, Zhenjiang, Jiangsu 212000, China.

Objective: To study the effectiveness of Saccharomyces boulardii combined with phototherapy in the treatment of hyperbilirubinemia in neonates.

Methods: The neonates with hyperbilirubinemia who were hospitalized from January to December 2018 were enrolled and randomly divided into an observation group (n=61) and a control group (n=63). The neonates in the observation group were treated with phototherapy combined with Saccharomyces boulardii, and those in the control group were treated with phototherapy combined with placebo. Treatment outcomes were compared between the two groups. Fecal samples were collected 72 hours after treatment and 16s rRNA high-throughput sequencing was used to compare the features of gut microbiota between the two groups.

Results: There was no significant difference in the total serum bilirubin level between the two groups before treatment (P>0.05). At 24, 48, and 72 hours after treatment, the observation group had a significantly lower level of total serum bilirubin than the control group (P<0.05). Compared with the control group, the observation group had a significantly lower proportion of neonates requiring phototherapy again [20% (12/61) vs 75% (47/63), P<0.05]. Compared with the control group, the observation group had a significantly higher abundance of Bacteroides (P<0.05) and a significantly lower abundance of Escherichia coli and Staphylococcus in the intestine at 72 hours after treatment (P<0.05).

Conclusions: In neonates with hyperbilirubinemia, phototherapy combined with Saccharomyces boulardii can effectively reduce bilirubin level and prevent the recurrence of jaundice. Saccharomyces boulardii can favour the treatment outcome by regulating the gut microbiota of neonates.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7666384PMC
November 2020

LncRNA MEG3 control Mycobacterium Tuberculosis infection via controlled MiR-145-5p expression and modulation of macrophages proliferation.

Microb Pathog 2020 Dec 6;149:104550. Epub 2020 Oct 6.

Clinic and Research Center of Tuberculosis, Shanghai Key Laboratory of Tuberculosis, Shanghai Pulmonary Hospital, Tongji University School of Medicine, No.507 Zhengmin Road, Yangpu District, Shanghai, 200433, China. Electronic address:

Background: Mycobacterium tuberculosis (Mtb) is an intractable pathogen for humans to overcome. While as an important part of innate immunity, macrophages play an important role in resisting foreign pathogenic microorganisms, and it has been proved that there is a close relationship between macrophages and Mtb. In recent years, with the in-depth study of LncRNA, there have been crucial breakthroughs in the diagnosis and treatment of a number of diseases, and understanding the impact of LncRNA on Mtb may also be conducive to providing new therapeutic targets for tuberculosis prevention and treatment in the future. Therefore, this study explore the role of MEG3 in the proliferation and apoptosis of Mtb-infected macrophages.

Methods: Between September 2017 and September 2019, 84 consecutive pulmonary Mtd patients admitted to our hospital were selected as the observation group (OG), and concurrently, 88 healthy controls were selected as the control group (CG). MEG3 and miR-145-5p in peripheral blood of the two groups were detected, and their diagnostic value in pulmonary tuberculosis (PTB) was analyzed by receiver operating characteristic (ROC) curves. In addition, Bacillus Calmette-Guérin (BCG) and mouse Raw264.7 macrophage strains were purchased to establish the Mtb-infected macrophage model. Colony forming unit (CFU) and flow cytometry were employed to determine the effects of MEG3 and miR-145-5p on macrophages, and the correlation between the two was performed by dual-luciferase reporter (DLR) assay.

Results: MEG3 was highly expressed in PTB, while miR-145-5p was lowly expressed (P < 0.050). ROC analysis demonstrated that both MEG3 and miR-145-5p enjoyed favorable predictive value for the occurrence of PTB (P < 0.001). In the Mtb-infected macrophage model, MEG3 decreased (P < 0.050) while miR-145-5p increased with the time of infection (P < 0.050). Inhibited MEG3 and overexpressed miR-145-5p resulted in increased CFU and decreased apoptosis ability of macrophages (P < 0.050). The DLR assay identified a targeting relationship between miR-145-5p and MEG3 (P < 0.050). The increase of MEG3 could inhibit the expression of in miR-145-5p (P < 0.050).

Conclusion: MEG3 affects the biological activity of Mtb-infected macrophages by targeting miR-145-5p, which may be the key to the diagnosis and treatment of PTB and even all kinds of tuberculosis in the future.
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http://dx.doi.org/10.1016/j.micpath.2020.104550DOI Listing
December 2020

HLA Class II alleles and association with HPV Infection prevalence in high-risk HPV-positive Han women in southern China.

Infect Dis Now 2021 02 29;51(1):67-70. Epub 2020 Sep 29.

School of Life Sciences, Xiang'an Campus of Xiamen University, Xiang'an Nan road, Xiang'an District, 361100 Xiamen, China. Electronic address:

Objective: To investigate the prevalence of different human papillomavirus (HPV) subtypes and their association with human leukocyte antigen (HLA) class II alleles in China.

Patients And Methods: A total of 16,168 married Chinese women in Maoming City of Guangdong province were tested for high-risk HPV infection. High-resolution typing of HLA-DRB1/DQB1 alleles was also performed on samples found to be infected with HPV.

Results: All in all, HPV-52, -58, -16, -18, and -53 were the five most common subtypes of HPV, with an incidence of high-risk HPV infection of 7.14%. Among women at high-risk of HPV infection, -DRB1*0403 (3.12% vs. 1.67%, odds ratio [OR] 1.894), -DQB1*0602 (3.74% vs. 1.82%, OR 2.094), and -DQB1*0609 (2.02% vs. 0.91%, OR 2.249) frequencies were higher than in controls. In contrast, -DQB1*0402 (0.31% vs. 1.29%, OR 0.239) in women with high-risk HPV infection exhibited a significantly decreased frequency compared to the controls.

Conclusion: Our results strongly support previous findings from other populations that -DRB1*0403 and -DQB1*0602 may be risk factors for HPV infection and subsequent development of cervical cancer. Moreover, unlike the European population, -DQB1*0402 may protect rather than render Maoming women susceptible to HPV infection.
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http://dx.doi.org/10.1016/j.medmal.2020.09.006DOI Listing
February 2021

ZmSRL5 is involved in drought tolerance by maintaining cuticular wax structure in maize.

J Integr Plant Biol 2020 Dec 17;62(12):1895-1909. Epub 2020 Jul 17.

National Key Laboratory of Crop Genetic Improvement, Huazhong Agricultural University, Wuhan, 430070, China.

Cuticular wax is a natural barrier on terrestrial plant organs, which protects plants from damages caused by a variety of stresses. Here, we report the identification and functional characterization of a cuticular-wax-related gene, Zea mays L. SEMI-ROLLED LEAF 5 (ZmSRL5). The loss-of-function mutant srl5, which was created by a 3,745 bp insertion in the first intron that led to the premature transcript, exhibited abnormal wax crystal morphology and distribution, which, in turn, caused the pleiotropic phenotypes including increased chlorophyll leaching and water loss rate, decreased leaf temperature, sensitivity to drought, as well as semi-rolled mature leaves. However, total wax amounts showed no significant difference between wild type and semi-rolled leaf5 (srl5) mutant. The phenotype of srl5 was confirmed through the generation of two allelic mutants using CRISPR/Cas9. ZmSRL5 encodes a CASPARIAN-STRIP-MEMBRANE-DOMAIN-LIKE (CASPL) protein located in plasma membrane, and highly expressed in developing leaves. Further analysis showed that the expressions of the most wax related genes were not affected or slightly altered in srl5. This study, thus, primarily uncovers that ZmSRL5 is required for the structure formation of the cuticular wax and could increase the drought tolerance by maintaining the proper cuticular wax structure in maize.
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http://dx.doi.org/10.1111/jipb.12982DOI Listing
December 2020

Clinical laboratory characteristics of severe patients with coronavirus disease 2019 (COVID-19): A systematic review and meta-analysis.

Clin Epidemiol Glob Health 2021 Jan-Mar;9:184-190. Epub 2020 Sep 15.

Department of Clinical Medicine, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu Province, China.

Objectives: To identify clinical characteristics of severe patients with COVID-19.

Methods: The WHO database of publications on COVID-19 and PubMed were searched from inception to March 20, 2020 and all valuable studies were analyzed using Stata 15.0.

Results: We selected forty-four studies with 13,497 patients. In the comparison of severe and non-severe groups, age over 50 (OR = 4.090; 95% CI = 2.422-6.907, P = 0.000) and underlying disease (OR = 3.992; 95% CI = 2.631-6.507, P = 0.000) are risk factors. Female gender (OR = 0.740; 95% CI = 0.622-0.881, P = 0.001) is a protective factor. Characteristics like dyspnea (OR = 4.914; 95% CI = 3.069-7.867, P = 0.000), lymphopenia (OR = 5.528; 95% CI = 3.484-8.772, P = 0.000), thrombocytopenia (OR = 3.623; 95% CI = 1.034-12.691, P = 0.044), elevated C-reactive protein (OR = 5.217; 95% CI = 2.459-11.070, P = 0.000) and D-dimer (OR = 3.780; 95% CI = 1.481-9.648, P = 0.005) were more frequently in severe cases. Diffuse lesions and consolidation (OR = 4.680; 95% CI = 3.183-6.881, P = 0.000) in imaging was considered reliable.

Conclusions: Men older than 50 with underlying disease are susceptible to develop severe pneumonia while female gender is protective. The typical symptom of severe pneumonia was dyspnea, but high fever, headache and diarrhea were not significantly different among patients with varying degrees of severity. Lymphopenia, thrombocytopenia, elevated C-reactive protein and D-dimer occurred more frequently in severe patients and yet leukopenia is not a characteristic laboratory indicator. Diffuse lesions and consolidation are important imaging features to distinguish severe pneumonia.
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http://dx.doi.org/10.1016/j.cegh.2020.08.012DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7491425PMC
September 2020

Neurally adjusted ventilatory assist in acute respiratory failure: a randomized controlled trial.

Intensive Care Med 2020 Dec 6;46(12):2327-2337. Epub 2020 Sep 6.

CIBER de Enfermedades Respiratorias, Instituto de Salud Carlos III, Madrid, Spain.

Purpose: We hypothesized that neurally adjusted ventilatory assist (NAVA) compared to conventional lung-protective mechanical ventilation (MV) decreases duration of MV and mortality in patients with acute respiratory failure (ARF).

Methods: We carried out a multicenter, randomized, controlled trial in patients with ARF from several etiologies. Intubated patients ventilated for ≤ 5 days expected to require MV for ≥ 72 h and able to breathe spontaneously were eligible for enrollment. Eligible patients were randomly assigned based on balanced treatment assignments with a computerized randomization allocation sequence to two ventilatory strategies: (1) lung-protective MV (control group), and (2) lung-protective MV with NAVA (NAVA group). Allocation concealment was maintained at all sites during the trial. Primary outcome was the number of ventilator-free days (VFDs) at 28 days. Secondary outcome was all-cause hospital mortality. All analyses were done according to the intention-to-treat principle.

Results: Between March 2014 and October 2019, we enrolled 306 patients and randomly assigned 153 patients to the NAVA group and 153 to the control group. Median VFDs were higher in the NAVA than in the control group (22 vs. 18 days; between-group difference 4 days; 95% confidence interval [CI] 0 to 8 days; p = 0.016). At hospital discharge, 39 (25.5%) patients in the NAVA group and 47 (30.7%) patients in the control group had died (between-group difference - 5.2%, 95% CI - 15.2 to 4.8, p = 0.31). Other clinical, physiological or safety outcomes did not differ significantly between the trial groups.

Conclusion: NAVA decreased duration of MV although it did not improve survival in ventilated patients with ARF.
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http://dx.doi.org/10.1007/s00134-020-06181-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7474954PMC
December 2020

Untargeted metabolomics as an unbiased approach to the diagnosis of inborn errors of metabolism of the non-oxidative branch of the pentose phosphate pathway.

Mol Genet Metab 2020 Sep - Oct;131(1-2):147-154. Epub 2020 Aug 5.

Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX, USA; Baylor Genetics, Houston, TX, USA. Electronic address:

Inborn errors of metabolism (IEM) involving the non-oxidative pentose phosphate pathway (PPP) include the two relatively rare conditions, transketolase deficiency and transaldolase deficiency, both of which can be difficult to diagnosis given their non-specific clinical presentations. Current biochemical testing approaches require an index of suspicion to consider targeted urine polyol testing. To determine whether a broad-spectrum biochemical test could accurately identify a specific metabolic pattern defining IEMs of the non-oxidative PPP, we employed the use of clinical metabolomic profiling as an unbiased novel approach to diagnosis. Subjects with molecularly confirmed IEMs of the PPP were included in this study. Targeted quantitative analysis of polyols in urine and plasma samples was accomplished with chromatography and mass spectrometry. Semi-quantitative unbiased metabolomic analysis of urine and plasma samples was achieved by assessing small molecules via liquid chromatography and high-resolution mass spectrometry. Results from untargeted and targeted analyses were then compared and analyzed for diagnostic acuity. Two siblings with transketolase (TKT) deficiency and three unrelated individuals with transaldolase (TALDO) deficiency were identified for inclusion in the study. For both IEMs, targeted polyol testing and untargeted metabolomic testing on urine and/or plasma samples identified typical perturbations of the respective disorder. Additionally, untargeted metabolomic testing revealed elevations in other PPP metabolites not typically measured with targeted polyol testing, including ribonate, ribose, and erythronate for TKT deficiency and ribonate, erythronate, and sedoheptulose 7-phosphate in TALDO deficiency. Non-PPP alternations were also noted involving tryptophan, purine, and pyrimidine metabolism for both TKT and TALDO deficient patients. Targeted polyol testing and untargeted metabolomic testing methods were both able to identify specific biochemical patterns indicative of TKT and TALDO deficiency in both plasma and urine samples. In addition, untargeted metabolomics was able to identify novel biomarkers, thereby expanding the current knowledge of both conditions and providing further insight into potential underlying pathophysiological mechanisms. Furthermore, untargeted metabolomic testing offers the advantage of having a single effective biochemical screening test for identification of rare IEMs, like TKT and TALDO deficiencies, that may otherwise go undiagnosed due to their generally non-specific clinical presentations.
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http://dx.doi.org/10.1016/j.ymgme.2020.07.013DOI Listing
August 2020

Imaging VOC distribution in cities and tracing VOC emission sources with a novel mobile proton transfer reaction mass spectrometer.

Environ Pollut 2020 Oct 1;265(Pt B):114628. Epub 2020 May 1.

Anhui Province Key Laboratory of Medical Physics and Technology, Center of Medical Physics and Technology, Hefei Institutes of Physical Science, Chinese Academy of Sciences, Hefei, 230031, China.

Volatile organic compounds (VOCs) are important precursors of ozone (O) and secondary organic aerosols (SOAs). Tracing VOC pollution sources is important for controlling VOC emissions and reducing O and SOAs. We built a novel mobile proton transfer reaction mass spectrometry (M-PTR-MS) instrument to image the distribution of VOCs and trace their emission sources in cities and industrial parks. The M-PTR-MS is composed of a vibration-resistant proton transfer reaction mass spectrometry (PTR-MS) with a global positioning system receiver, modified box vehicle, and geographic information system (GIS) software. The PTR-MS, mounted on a vehicle, sends VOC data and vehicle position information to the GIS software. These data are used to image the space distribution of VOCs in real time while the vehicle platform is in motion and the VOC sources are precisely traced using the GIS. The spatial data resolution of the M-PTR-MS is typically 0.8 m. The limits of detection, sensitivity, and repeatability of the M-PTR-MS are 43.5 ppt, 347 counts ppb, and 2.4% (RSD, n = 5), respectively. The intensity of reagent ions is stable over 8 h (RSD = 0.45%). Compared with commercial PTR-MS equipment, the M-PTR-MS demonstrated high consistency, with a correlation coefficient of 92.665%. Several field experiments were conducted in China using the M-PTR-MS. In one field experiment, the VOC distribution along three different routes was surveyed; the navigation monitoring lasted 1.8 h over a distance of 26.7 km at an average speed of 15 km h. The VOC sources in an industrial park were identified by analyzing the components near different factories. The main species from a VOC source in an underground garage was related to paint. The M-PTR-MS instrument can be used by environmental protection agencies to trace VOC pollution sources in real time, and by researchers to survey VOC emissions in regions of concern.
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http://dx.doi.org/10.1016/j.envpol.2020.114628DOI Listing
October 2020