Publications by authors named "Lili Zhao"

577 Publications

Bayesian Analysis of RNA-Seq Data Using a Family of Negative Binomial Models.

Bayesian Anal 2018 Jun 8;13(2):411-436. Epub 2017 Apr 8.

Department of Statistics, University of Michigan, Ann Arbor.

The analysis of RNA-Seq data has been focused on three main categories, including gene expression, relative exon usage and transcript expression. Methods have been proposed independently for each category using a negative binomial (NB) model. However, counts following a NB distribution on one feature (e.g., exon) do not guarantee a NB distribution for the other two features (e.g., gene/transcript). In this paper we propose a family of Negative Binomial models, which integrates the gene, exon and transcript analysis under a coherent NB model. The proposed model easily incorporates the uncertainty of assigning reads to transcripts and simplifies substantially the estimation for the relative usage. We developed simple Gibbs sampling algorithms for the posterior inference by exploiting fully tractable closed-forms of computation via suitable conjugate priors. The proposed models were investigated under extensive simulations. Finally, we applied our model to a real data set.
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http://dx.doi.org/10.1214/17-BA1055DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8052637PMC
June 2018

In vitro and in vivo synergistic effects of tigecycline combined with aminoglycosides on carbapenem-resistant Klebsiella pneumoniae.

J Antimicrob Chemother 2021 Apr 16. Epub 2021 Apr 16.

Department of Respiratory Diseases, Chinese PLA General Hospital, Beijing 100853, China.

Objectives: Carbapenem-resistant Klebsiella pneumoniae (CR-KP) infections represent severe threats to public health worldwide. The aim of this study was to assess potential synergistic interaction between tigecycline and aminoglycosides via in vitro and in vivo studies.

Methods: Antibiotic resistance profiles and molecular characteristics of 168 CR-KP clinical isolates were investigated by susceptibility testing, PCR and MLST. Chequerboard tests and time-kill assays were performed for 20 CR-KP isolates to evaluate in vitro synergistic effects of tigecycline combined with aminoglycosides. A tissue-cage infection model of rats was established to evaluate in vivo synergistic effects. Different doses of tigecycline and aminoglycosides alone or in combination were administered for 7 days via tail vein injection. Antibiotic efficacy was evaluated in tissue-cage fluid and emergence of resistance was screened.

Results: The chequerboard tests showed that this combination displayed synergistic or partial synergistic activity against CR-KP. The time-kill assays further demonstrated that strong synergistic effects of such a combination existed against isolates that were susceptible to both drugs but for resistant isolates no synergy was observed if clinical pharmacokinetics were taken into consideration. The in vivo study showed that the therapeutic effectiveness of combination therapies was better than that of monotherapy for susceptible isolates, suggesting in vivo synergistic effects. Furthermore, combinations of tigecycline with an aminoglycoside showed significant activity in reducing the occurrence of tigecycline-resistant mutants.

Conclusions: Compared with single drugs, tigecycline combined with aminoglycosides could exert synergistic effects and reduce the emergence of tigecycline resistance. Such a combination might be an effective alternative when treating CR-KP infections in clinical practice.
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http://dx.doi.org/10.1093/jac/dkab122DOI Listing
April 2021

Switchable CAR-T Cells Outperformed Traditional Antibody-Redirected Therapeutics Targeting Breast Cancers.

ACS Synth Biol 2021 Apr 15. Epub 2021 Apr 15.

California Institute for Biomedical Research, 11119 North Torrey Pines Road, La Jolla, California 92037, United States.

Various antibody-redirected immunotherapeutic approaches, including antibody-drug conjugates (ADCs), bispecific antibodies (bsAbs), and chimeric antigen receptor-T (CAR-T) cells, have been devised to produce specific activity against various cancer types. Using genetically encoded unnatural amino acids, we generated a homogeneous Her2-targeted ADC, a T cell-redirected bsAb, and a FITC-modified antibody capable of redirecting anti-FITC CAR-T (switchable CAR-T; sCAR-T) cells to target different Her2-expressing breast cancers. sCAR-T cells showed activity against Her2-expressing tumor cells comparable to that of conventional anti-Her2 CAR-T cells and superior to that of ADC- and bsAb-based approaches. To prevent antigen escape, we designed bispecific sCAR-T cells targeting both the Her2 receptor and IGF1R, which showed an overall improved activity against cancer cells with low Her2 expression. This study increases our understanding of various explored cancer therapeutics and underscores the efficient application of sCAR-T cells as a promising therapeutic option for breast cancer patients with low or heterogeneous antigen expression.
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http://dx.doi.org/10.1021/acssynbio.1c00007DOI Listing
April 2021

IL-27 Protects the Brain from Ischemia-Reperfusion Injury via the gp130/STAT3 Signaling Pathway.

J Mol Neurosci 2021 Apr 13. Epub 2021 Apr 13.

Department of Neurology, National Hospital of Guangxi Zhuang Autonomous Region, No. 232, Mingxiu East Road, 530001 Nanning, Guangxi Province, China.

The occurrence of ischemia-reperfusion (I/R) injury leads to dysfunction as well as high rates of morbidity and mortality in stroke, and new effective therapeutic strategies for I/R are still needed. We investigated the effect of IL-27 on I/R injury-induced neurological function impairment, cerebral infarction volume and variation in levels of inflammatory factors in mice with middle cerebral artery occlusion (MCAO), as well as concentration of LDH and neuronal apoptosis in a neuron oxygen-glucose deprivation and reperfusion (OGD/R) model mediated by gp130/STAT3 signaling in vitro. Our results indicated that IL-27 could bind to its receptor of gp130 to attenuate the I/R injury-induced impairment function and cerebral infarction volume, and decrease inflammatory cytokines TNF-α, IL-1β and MCP-1 but increase anti-inflammatory factors IL-10 and TGF-β in vivo, while inhibiting LDH leakage and neuronal apoptosis through activation of STAT3 to antagonize I/R induction. Our results suggest that IL-27 may protect the brain from I/R injury through the gp130/STAT3 signaling pathway.
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http://dx.doi.org/10.1007/s12031-021-01802-0DOI Listing
April 2021

Mechanistic Study of the -Quaternized Pyridoxal-Catalyzed Biomimetic Asymmetric Mannich Reaction: Insights into the Origins of Enantioselectivity and Diastereoselectivity.

J Org Chem 2021 Apr 8. Epub 2021 Apr 8.

Institute of Advanced Synthesis, School of Chemistry and Molecular Engineering, Nanjing Tech University, Nanjing 211816, China.

Density functional theory calculations have been performed to gain insights into the catalytic mechanism of the -quaternized pyridoxal (i.e., )-mediated biomimetic asymmetric Mannich reaction of -butyl glycinate with -diphenylphosphinyl imine to give the diamino acid ester in high yield with excellent enantiomeric and diastereomeric selectivity (, , 1438). The study reveals that the whole catalysis can be characterized via three stages: (i) the catalyst reacts with the -butyl glycinate to generate the active carbanion complex . (ii) then reacts with the -diphenylphosphinyl imine giving the imine intermediate . (iii) undergoes hydrolysis to give the final product anti- and regenerate the catalyst for the next catalytic cycle. Each stage is kinetically and thermodynamically feasible for experimental realization. The hydrolysis step in the stage III is predicted to be the rate-determining step during the whole catalytic cycle. Furthermore, the origins of the enantioselectivity and diastereoselectivity for the target reaction, as well as the deactivation of the catalyst , are also discussed.
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http://dx.doi.org/10.1021/acs.joc.1c00381DOI Listing
April 2021

Highly Coordinated Heteronuclear Calcium-Iron Carbonyl Cation Complexes [CaFe(CO)n]+ (n = 5 - 12) with d-d Bonding.

Angew Chem Int Ed Engl 2021 Apr 7. Epub 2021 Apr 7.

Fudan University, Department of Chemistry, CHINA.

Heteronuclear calcium-iron carbonyl cation complexes in the form of [CaFe(CO) n ] + (n = 5 - 12) are produced in the gas phase. Infrared photodissociation spectroscopy in conjunction with quantum chemical calculations confirm that the n = 10 complex is the coordination saturated ion where a Fe(CO) 4 fragment is bonded with a Ca(CO) 6 fragment through two side-on bridging carbonyl ligands. Bonding analysis indicates that it is best described by the bonding interactions between a [Ca(CO) 6 ] 2+ dication and an [Fe(CO) 4 ] - anion forming a Fe→Ca d-d dative bond in the [(CO) 6 Ca-Fe(CO) 4 ] + structure, which enriches the pool of experimentally observed complexes of calcium that mimic transition metal compounds. The molecule is the first example of a heteronuclear carbonyl complex featuring a d-d bond between calcium and a transition metal.
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http://dx.doi.org/10.1002/anie.202103267DOI Listing
April 2021

A Bayesian mixture model for changepoint estimation using ordinal predictors.

Int J Biostat 2021 Apr 6. Epub 2021 Apr 6.

Department of Biostatistics, University of Michigan, 1415 Washington Heights, 48109Ann Arbor, MI, USA.

In regression models, predictor variables with inherent ordering, such ECOG performance status or novel biomarker expression levels, are commonly seen in medical settings. Statistically, it may be difficult to determine the functional form of an ordinal predictor variable. Often, such a variable is dichotomized based on whether it is above or below a certain cutoff. Other methods conveniently treat the ordinal predictor as a continuous variable and assume a linear relationship with the outcome. However, arbitrarily choosing a method may lead to inaccurate inference and treatment. In this paper, we propose a Bayesian mixture model to consider both dichotomous and linear forms for the variable. This allows for simultaneous assessment of the appropriate form of the predictor in regression models by considering the presence of a changepoint through the lens of a threshold detection problem. This method is applicable to continuous, binary, and survival outcomes, and it is easily amenable to penalized regression. We evaluated the proposed method using simulation studies and apply it to two real datasets. We provide JAGS code for easy implementation.
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http://dx.doi.org/10.1515/ijb-2020-0151DOI Listing
April 2021

Cribriform colon cancer: a morphological growth pattern associated with extramural venous invasion, nodal metastases and microsatellite stability.

J Clin Pathol 2021 Mar 29. Epub 2021 Mar 29.

Department of Pathology, University of Michigan, Ann Arbor, Michigan, USA.

Background: Cribriform comedo-type adenocarcinoma was a colon cancer subtype recognised in the previous WHO classification of tumours that is no longer included in the recent edition. Previous reports have described colon cancers with cribriform growth as having worse overall survival and being associated with microsatellite stability. We sought to validate whether cribriform carcinoma (CC) is a distinct morphological subtype with clinical relevance in the context of modern colon cancer diagnosis.

Methods: Consecutive cases of non-neoadjuvantly treated colon cancer resections were identified (n=177) and reviewed to evaluate for CC and other histopathological and clinical features. CC was defined as solid nests of cancer with round, 'punched out' spaces and intraluminal bridges, reminiscent of ductal carcinoma in situ of the breast.

Results: CC was present in 18.6% of the consecutive case cohort. Compared with all other cases, CC was associated with positive lymph nodes, increased depth of invasion, extramural venous involvement (EMVI), and microsatellite stability, and was less likely to have tumour infiltrating lymphocytes (p<0.05). In contrast to previous reports, we did not find significantly worse overall, disease-specific or recurrence-free survival for CC. Morphological features mimicking CC occurred in 33.3% of all other colon cancer cases.

Conclusion: Identifying CC may be useful due to its association with worse stage at presentation and EMVI, but given that cribriform-like appearance may be found in many colon cancer cases and that we did not find a survival difference for CC, CC may not necessitate its own subtype classification.
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http://dx.doi.org/10.1136/jclinpath-2021-207485DOI Listing
March 2021

Similar Quality of Life After Conventional and Robotic Transhiatal Esophagectomy.

Ann Thorac Surg 2021 Mar 18. Epub 2021 Mar 18.

Department of Surgery, University of Michigan, Ann Arbor, MI, USA; University of Michigan Medical School, Ann Arbor, MI, USA; Section of Thoracic Surgery, University of Michigan, Ann Arbor, MI, USA. Electronic address:

Background: Patient-reported outcomes (PROs) for minimally invasive esophagectomy (MIE) have demonstrated benefits compared to open transthoracic or 3-hole esophagectomy. PROs including quality of life (QoL) and fear of recurrence (FoR) comparing open transhiatal esophagectomy (THE) and transhiatal robotic-assisted MIE (Th-RAMIE) have been limited.

Methods: At a single, high-volume academic center, patients undergoing THE and Th-RAMIE with gastric conduit for clinical stage I-III esophageal cancer from 2013 to 2018 were evaluated. The European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (QLQ-C30), EORTC Quality of Life Questionnaire in Esophageal Cancer (QLQ-OES18), and FoR survey were administered preoperatively, and at 1, 6- and 12-months post-operatively. Linear mixed-effects models were used for QoL and FoR score comparisons. Perioperative outcomes were also compared.

Results: 309 patients (212 THE and 97 Th-RAMIE) were included. The Th-RAMIE cohort had a significantly higher number of lymph nodes harvested (14 ±0.8 vs. 11.2 ±0.4; p = 0.01), shorter length of stay (days, 10.0 ± 6.7 vs. 12.1 ±7.0; p = 0.03), lower rates of postoperative ileus (5% vs. 15%; p = 0.02), and had fewer opioids prescribed at discharge (71% vs. 85%; p = 0.03). After adjustment, there were no significant differences in QLQ-C30, QLQ-OES18, and FoR scores between groups out to 1 year following surgery.

Conclusions: There were no clear patient-reported benefits of Th-RAMIE over THE for esophageal cancer. However, Th-RAMIE conferred a number of perioperative benefits.
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http://dx.doi.org/10.1016/j.athoracsur.2021.03.018DOI Listing
March 2021

Concerns for cold endoscopic mucosal resection of large serrated polyps.

Gastrointest Endosc 2021 Apr;93(4):990

Digestive Endoscopy Department, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China.

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http://dx.doi.org/10.1016/j.gie.2020.11.015DOI Listing
April 2021

Characterization of pneumonia and other factors leading to poorer survival across all age groups in patients with non-small cell lung cancer (NSCLC).

J Thorac Dis 2021 Feb;13(2):986-994

Division of Hematology/Oncology, Department of Internal Medicine, University of Michigan, MI, USA.

Background: Lung cancer death rates and incidence in both men and women have decreased over the past two decades. However, certain subsets of non-small cell lung cancer (NSCLC) have arisen with poor outcomes. Identifying factors which contribute to poorer outcomes as well as those that inform early detection strategies remain unmet needs. We present data from a contemporaneous group of NSCLC patients that received care at a single University teaching hospital to understand clinical and pathological factors influencing outcomes in the past decade.

Methods: A cohort of 2,289 patients with NSCLC who established care at the Rogel Cancer Center, University of Michigan between January 2011 and April 2019 were identified. Patient characteristics and clinical outcomes were recorded using electronic health records. The Kaplan-Meier method and the Cox proportional model were used to assess relationship between clinic-pathological factors and survival.

Results: Of the 2,289 patients, 92% were >50 years of age while 8% were <50 years of age. The majority (70%) of older patients were former smokers. The majority (61%) of younger patients were diagnosed as having Stage IV NSCLC. Among younger patients, 87% had histologically confirmed non-squamous histology. Univariate analysis revealed that overall survival was significantly lower in patients diagnosed with pneumonia prior to the diagnosis of NSCLC than in those who were not diagnosed with pneumonia (1.9 21.8 months; P<0.001). Multivariate analysis revealed that older patients had poorer survival than younger patients (HR 1.57, 95% CI: 1.10-2.06, P=0.01) and that patients diagnosed with pneumonia prior to their lung cancer diagnosis had poorer survival across all age groups, particularly in those with advanced-stage disease.

Conclusions: Findings from this study merit prospective studies to understand cost-benefit ratio of follow- up cross sectional imaging of all patients diagnosed with unprovoked pneumonia, including in younger non/current smokers.
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http://dx.doi.org/10.21037/jtd-20-2891DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7947482PMC
February 2021

Lipid profiles and differential lipids in serum related to severity of community-acquired pneumonia: A pilot study.

PLoS One 2021 11;16(3):e0245770. Epub 2021 Mar 11.

Department of Respiratory & Critical Care Medicine, Peking University People's Hospital, Beijing, China.

This study aimed to characterize the lipidomic responses to community-acquired pneumonia (CAP) and provide new insight into the underlying mechanisms of pathogenesis and potential avenues for diagnostic and therapeutic treatments. This study was performed from January 2017 to October 2018. Lipidomic profiles were generated using ultra high-performance liquid chromatography with tandem mass spectrometry (UHPLC-MS/MS) platform. Spearman's rank correlation test and multiple linear regression analysis were applied to explore the correlation between changes in the relative abundance of lipids and clinical parameters. Kaplan-Meier methods were used to build 30-day survival curves. From the UHPLC-MS/MS results, a total of 509 and 195 lipid species were detected in the positive and negative ionization mode respectively. Positive ionization covered six lipid classes (glycerol-phospholipids, glycerolipids, sphingolipids, sterol-lipids, prenol-lipids, and fatty acid), whilst negative ionization covered three (glycerol-phospholipids, sphingolipids, fatty acid). Four lipids were selected as targets: PC (16:0_18:1), PC (18:2_20:4), PC (36:4), and PC (38:6). The relative increase of the areas under the curves for all four lipids were superior to the pneumonia severity index and CURB-65 (confusion, urea, respiratory rate, blood pressure, and age ≥65 years old) for discriminating severe CAP from CAP. Decreasing relative levels of PC (18:2_20:4), PC (38:6), and PC (36:4) were negatively related to fraction of inspiration O2; Changes in the relative abundance of PC (16:0_18:1) and PC (18:2_20:4) had significantly linear relationship with procalcitonin. Patients with an elevated level of PC (16:0_18:1) had significantly longer duration of hospital stays. As the relative abundance of PC (18:2_20:4), PC (36:4), and PC (38:6) decreased, the length of hospitalization days and 30-day mortality rate increased significantly (all log-rank p<0.05). Therefore, using the UHPLC-MS/MS platform's serum lipidomic approach can help reveal changes in lipid abundance during CAP and establish lipid profiles related to disease severity.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0245770PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7951898PMC
March 2021

Admission lysophosphatidylethanolamine acyltransferase level predicts the severity and prognosis of community-acquired pneumonia.

Infection 2021 Mar 10. Epub 2021 Mar 10.

Department of Respiratory and Critical Care Medicine, Peking University People's Hospital, Beijing, China.

Purpose: Early diagnosis and prognosis of patients with community-acquired pneumonia (CAP) are still difficult clinical challenges. This study aimed to investigate the role of lysophosphatidylethanolamine acyltransferase (LPEAT) in CAP and to evaluate the effectiveness of this enzyme as an indicator of disease severity and risk of death in CAP.

Methods: This retrospective, multi-center study was conducted in 2017. A total of 267 patients with CAP were included. Of these 267 patients, 175 patients had non-severe CAP (non-SCAP) and 92 patients had severe CAP (SCAP). In addition, we recruited 15 healthy volunteers and 42 hospitalized disease controls in our study. The demographic and clinical characteristics were recorded for all participants. Admission levels of LPEAT were determined by quantitative enzyme-linked immunosorbent assay.

Results: Admission levels of LPEAT in patients with SCAP were significantly higher, particularly in non-survivors and were not affected by the causative etiology. Furthermore, when the patients were stratified according to PSI and CURB-65 scores, the patients with high severity scores had higher LPEAT levels upon admission than patients with low severity scores. LPEAT also performed well in predicting SCAP in patients with CAP. Moreover, LPEAT could predict the 30-day mortality rate of patients with CAP, and combining LPEAT with the clinical severity score further improved the accuracy of mortality prediction.

Conclusion: Elevated LPEAT levels can reliably predict the severity of illness in patients with CAP at the time of admission. Adding LPEAT to clinical scoring methods could improve prognostic accuracy. Trial registration ClinicalTrials.gov, NCT03093220. Registered on March 28th, 2017.
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http://dx.doi.org/10.1007/s15010-021-01585-xDOI Listing
March 2021

Appropriate duration of endoscopic dilation for postoperative benign esophageal strictures.

Surg Endosc 2021 Mar 10. Epub 2021 Mar 10.

Digestive Endoscopy Department and General Surgery Department, The First Affiliated Hospital With Nanjing Medical University and Jiangsu Province Hospital, 300 Guangzhou Road, Nanjing, Jiangsu Province, China.

Background: Benign esophageal strictures are a frequent complication after esophageal surgery or extensive endoscopic submucosal dissection. Endoscopic dilation is the preferred treatment in clinical practice. However, the allocation of time for each dilation is unclear. The aim of this study was to evaluate the appropriate duration of endoscopic dilation for benign esophageal strictures after esophageal surgery or endoscopic submucosal dissection.

Methods: Patients with benign esophageal strictures after esophageal surgery or endoscopic submucosal dissection between July 2010 and July 2018 were retrospectively included in this study. According to the dilation time (1, 3, 5 min), patients were divided into three groups. The clinical effects and adverse events were compared among the three groups.

Results: Altogether, 57 patients, including 21 in the 1-min group, 18 in the 3-min group and 18 in the 5-min group, were included. All patients underwent endoscopic treatment successfully. The stricture recurrence rate was 76.19% in the 1-min group, 55.56% in the 3-min group and 61.11% in the 5-min group. The median overall dysphagia-free period was 2.60 (range, 0.80-12.00) months in the 1-min group, 6.60 (range, 1.80-12.00) months in the 3-min group and 6.25 (range, 2.40-12.00) months in the 5-min group (P < 0.05). For patients who developed stricture recurrence, the mean dysphagia-free periods were 2.26  ±  1.27 months, 4.00  ±  1.76 months and 4.23  ±  1.63 months, respectively (P < 0.05). The dysphagia-free periods were comparable between the 3- and 5-min groups and were longer than those in the 1-min group. Muscle layer damage occurred in two patients (11.11%) in the 5-min group and in no patients in the other two groups.

Conclusion: Three minutes was considered a safe and effective dilation duration for benign esophageal strictures after esophageal surgery or endoscopic submucosal dissection.
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http://dx.doi.org/10.1007/s00464-021-08400-6DOI Listing
March 2021

miR-20a Promotes the Axon Regeneration of DRG Neurons by Targeting Nr4a3.

Neurosci Bull 2021 Apr 8;37(4):569-574. Epub 2021 Mar 8.

Key Laboratory of Neuroregeneration of Jiangsu and the Ministry of Education, Co-innovation Center of Neuroregeneration, Nantong University, Nantong, 226001, China.

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http://dx.doi.org/10.1007/s12264-021-00647-2DOI Listing
April 2021

Copper-catalyzed regioselective [3+2] annulation of malonate-tethered acyl oximes with isatins.

Chem Commun (Camb) 2021 Apr 8;57(27):3379-3382. Epub 2021 Mar 8.

College of Biotechnology and Pharmaceutical Engineering, State Key Laboratory of Materials-Oriented Chemical Engineering, Nanjing Tech University, 30 Puzhu Rd S, Nanjing, 211816, China.

A copper-catalyzed regioselective [3+2] annulation of malonate-tethered acyl oximes with isatins was developed, affording valuable 2,3-dihydrooxazole-spirooxindoles in moderate to good yields with excellent diastereoselectivity. The reaction sequence involves Cu(i) initiated N-O bond cleavage, 1,5-HAT and C-N bond formation. The protocol features mild reaction conditions and broad substrate scope. DFT calculations demonstrated that the [3+2] annulation pathway is more energetically favourable in both kinetics and thermodynamics.
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http://dx.doi.org/10.1039/d0cc07995bDOI Listing
April 2021

Relationship between oral health-related knowledge, attitudes, practice, self-rated oral health and oral health-related quality of life among Chinese college students: a structural equation modeling approach.

BMC Oral Health 2021 Mar 6;21(1):99. Epub 2021 Mar 6.

Department of Stomatology, First Affiliated Hospital of Bengbu Medical College, Bengbu, 233004, Anhui, China.

Background: This study aimed to evaluate the associations among oral health-related knowledge, attitudes, practice (KAP), self-rated oral health and oral health-related quality of life (OHRQoL) among Chinese college students.

Methods: Of the 2000 participants, 1751 (87.55%) students answered an online questionnaire between October 2019 and January 2020. The questionnaire included demographic characteristics, knowledge, attitudes, and practice related to oral health, self-rated oral health, and OHRQoL. Structural equation modelling was applied to assess the associations among study variables.

Results: Among the total students, oral health-related knowledge and attitudes were satisfactory, while the oral health practice was not optimistic. The final model showed satisfactory fitness to the data. Oral health knowledge was associated with attitudes directly and positively. Attitudes toward oral health had a direct and positive effect on practice. Oral health knowledge had an indirect effect on practice through attitudes. Oral health practice was directly associated with self-rated oral health. Oral health knowledge, practice, and self-rated oral health all affected OHRQoL directly and positively, while attitudes had a direct negative impact on OHRQoL.

Conclusions: OHRQoL was influenced by oral health knowledge, attitudes, practice, and self-rated oral health. Our findings support the KAP theory. Limitations of the KAP model were also found.
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http://dx.doi.org/10.1186/s12903-021-01419-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7936478PMC
March 2021

The prognostic value of serum albumin levels and respiratory rate for community-acquired pneumonia: A prospective, multi-center study.

PLoS One 2021 4;16(3):e0248002. Epub 2021 Mar 4.

Department of Respiratory and Critical Care Medicine, Peking University People's Hospital, Beijing, People's Republic of China.

Community-acquired pneumonia (CAP) is a respiratory disease frequently requiring hospital admission, and a significant cause of death worldwide. This study aimed to investigate the prognostic value of clinical indicators. A prospective, multi-center study was conducted (January 2017-December 2018) where patient demographic and clinical data were recorded (N = 366). The 30-day mortality rate was 5.46%. Cox Regression analyses showed that serum albumin (ALB) and respiratory rate (RR) were independent prognostic variables for 30-day survival in patients with CAP. Albumin negatively correlated with the Pneumonia Severity Index (PSI) and CURB-65 scores using Pearson and Spearman tests. Survival curves showed that a RR >24 breaths/min or ALB ≤30 g/L were associated with a significantly higher risk of mortality. The area-under-the-curve (AUC) for predicting 30-day mortality in patients with CAP was 0.762, 0.763, 0.790, and 0.784 for ALB, RR, PSI, and CURB-65, respectively. The AUC for the prediction of 30-day mortality using ALB combined with PSI, CURB-65 scores, and RR was 0.822 (95% CI 0.731-0.912), 0.847 (95% CI 0.755-0.938), and 0.847 (95% CI 0.738-0.955), respectively. Albumin and RR were found to be reliable prognostic factors for CAP. This combination showed equal predictive value when compared to adding ALB assessment to PSI and CURB-65 scores, which could improve their prognostic accuracy.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0248002PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7932099PMC
March 2021

Aptamer-targeting of Aleutian mink disease virus (AMDV) can be an effective strategy to inhibit virus replication.

Sci Rep 2021 Feb 25;11(1):4649. Epub 2021 Feb 25.

State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Harbin, 150069, China.

Aleutian mink disease (AMD), which is caused by Aleutian mink disease virus (AMDV), is an important contagious disease for which no effective vaccine is yet available. AMD causes major economic losses for mink farmers globally and threatens some carnivores such as skunks, genets, foxes and raccoons. Aptamers have exciting potential for the diagnosis and/or treatment of infectious viral diseases, including AMD. Using a magnetic beads-based systemic evolution of ligands by exponential enrichment (SELEX) approach, we have developed aptamers with activity against AMDV after 10 rounds of selection. After incubation with the ADVa012 aptamer (4 μM) for 48 h, the concentration of AMDV in the supernatant of infected cells was 47% lower than in the supernatant of untreated cells, whereas a random library of aptamers has no effect. The half-life of ADVa012 was ~ 32 h, which is significantly longer than that of other aptamers. Sequences and three dimensions structural modeling of selected aptamers indicated that they fold into similar stem-loop structures, which may be a preferred structure for binding to the target protein. The ADVa012 aptamer was shown to have an effective and long-lasting inhibitory effect on viral production in vitro.
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http://dx.doi.org/10.1038/s41598-021-84223-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7907208PMC
February 2021

Paediatric magnet ingestion: Urging for a national database.

Acta Paediatr 2021 Feb 24. Epub 2021 Feb 24.

Department of Digestive Endoscopy, The First Affiliated Hospital with Nanjing Medical University, Nanjing, China.

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http://dx.doi.org/10.1111/apa.15816DOI Listing
February 2021

Does dual red imaging work better?

Gastrointest Endosc 2021 Mar;93(3):775-776

Digestive Endoscopy Department, Department of General Surgery, The First Affiliated Hospital with Nanjing Medical University, Nanjing, China.

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http://dx.doi.org/10.1016/j.gie.2020.09.047DOI Listing
March 2021

Icariin Promotes the Osteogenesis of Bone Marrow Mesenchymal Stem Cells through Regulating Sclerostin and Activating the Wnt/-Catenin Signaling Pathway.

Biomed Res Int 2021 22;2021:6666836. Epub 2021 Jan 22.

Department of Orthopedics, The Second Affiliated Hospital of Guangzhou Medical University, Guangzhou, China.

Osteoporosis (OP) is a metabolic disease characterized by decreased bone mass and increased risk of fragility fractures, which significantly reduces the quality of life. Stem cell-based therapies, especially using bone marrow mesenchymal stem cells (BMSCs), are a promising strategy for treating OP. Nevertheless, the survival and differentiation rates of the transplanted BMSCs are low, which limits their therapeutic efficiency. Icariin (ICA) is a traditional Chinese medicine formulation that is prescribed for tonifying the kidneys. It also promotes the proliferation and osteogenic differentiation of BMSCs, although the specific mechanism remains unclear. Based on our previous research, we hypothesized that ICA promotes bone formation via the sclerostin/Wnt/-catenin signaling pathway. We isolated rat BMSCs and transfected them with sclerostin gene () overexpressing or knockdown constructs and assessed osteogenic induction in the presence or absence of ICA. Sclerostin significantly inhibited BMSC proliferation and osteogenic differentiation, whereas the presence of ICA not only increased the number of viable BMSCs but also enhanced ALP activity and formation of calcium nodules during osteogenic induction. In addition, the osteogenic genes including Runx2, -catenin, and c-myc as well as antioxidant factors (Prdx1, Cata, and Nqo1) were downregulated by sclerostin and restored by ICA treatment. Mechanistically, ICA exerted these effects by activating the Wnt/-catenin pathway. In conclusion, ICA can promote the proliferation and osteogenic differentiation of BMSCs in situ and therefore may enhance the therapeutic efficiency of BMSC transplantation in OP.
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http://dx.doi.org/10.1155/2021/6666836DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7847333PMC
January 2021

Biological characteristic and cytokines response of passages duck plague virus in ducks.

Virus Res 2021 Apr 4;295:198320. Epub 2021 Feb 4.

State Key Laboratory of Veterinary Biotechnology, Heilongjiang Provincial Key Laboratory of Laboratory Animal and Comparative Medicine, Harbin Veterinary Research Institute, the Chinese Academy of Agriculture Sciences, 678 Haping Road, Harbin, 150069, China. Electronic address:

To better understand the pathogenicity of duck plague virus (DPV). The DPV Chinese standard challenge strain (DPV CSC) was continuously passaged 20 times in duck embryo fibroblasts (DEFs). DPV F1 was lethal for 2-week-ducks, but DPV F10 and F20 were not lethal for 2-week ducks, the 528 bp in UL2 region of DPV F1-F20 was deleted, which suggested that the deletion in UL2 region was not related with the virulence of DPV. Compared with DPV F20 infected ducks, IL-8 in DPV F1 infected ducks was significantly upregulated, but IL-1, IL-2,IFNγ and MHC-II were significantly downregulated. ISKNV copies in DPV F10 and F20 infected ducks were lower than the DPV F1 infected ducks. These results showed that massive viruses replication, upregulation of IL-8 expresssion, repression of IL-1, IL-2, IFNγ and MHC-II expression resulted in serious lesions and high mortality. This study provided a in-depth understanding of the immune-related genes expression in the different virulence of DPV.
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http://dx.doi.org/10.1016/j.virusres.2021.198320DOI Listing
April 2021

Virus-positive Merkel Cell Carcinoma Is an Independent Prognostic Group with Distinct Predictive Biomarkers.

Clin Cancer Res 2021 Feb 5. Epub 2021 Feb 5.

Department of Dermatology, University of Michigan, Ann Arbor, Michigan.

Purpose: Merkel cell carcinoma (MCC) is an aggressive cutaneous neuroendocrine carcinoma that can be divided into two classes: virus-positive (VP) MCC, associated with oncogenic Merkel cell polyomavirus (MCPyV); and virus-negative (VN) MCC, associated with photodamage.

Experimental Design: We classified 346 MCC tumors from 300 patients for MCPyV using a combination of IHC, ISH, and qPCR assays. In a subset of tumors, we profiled mutation status and expression of cancer-relevant genes. MCPyV and molecular profiling results were correlated with disease-specific outcomes. Potential prognostic biomarkers were further validated by IHC.

Results: A total of 177 tumors were classified as VP-MCC, 151 tumors were VN-MCC, and 17 tumors were indeterminate. MCPyV positivity in primary tumors was associated with longer disease-specific and recurrence-free survival in univariate analysis, and in multivariate analysis incorporating age, sex, immune status, and stage at presentation. Prioritized oncogene or tumor suppressor mutations were frequent in VN-MCC but rare in VP-MCC. mutation developed with recurrence in one VP-MCC case. Importantly, for the first time we find that VP-MCC and VN-MCC display distinct sets of prognostic molecular biomarkers. For VP-MCC, shorter survival was associated with decreased expression of immune markers including granzyme and IDO1. For VN-MCC, shorter survival correlated with high expression of several genes including .

Conclusions: MCPyV status is an independent prognostic factor for MCC. Features of the tumor genome, transcriptome, and microenvironment may modify prognosis in a manner specific to viral status. MCPyV status has clinicopathologic significance and allows for identification of additional prognostic subgroups.
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http://dx.doi.org/10.1158/1078-0432.CCR-20-0864DOI Listing
February 2021

Poly(hydrophobic amino acid)-Based Self-Adjuvanting Nanoparticles for Group A Vaccine Delivery.

J Med Chem 2021 Mar 2;64(5):2648-2658. Epub 2021 Feb 2.

School of Chemistry and Molecular Biosciences, The University of Queensland, St. Lucia, QLD 4072, Australia.

Peptide antigens have been widely used in the development of vaccines, especially for those against autoimmunity-inducing pathogens and cancers. However, peptide-based vaccines require adjuvant and/or a delivery system to stimulate desired immune responses. Here, we explored the potential of self-adjuvanting poly(hydrophobic amino acids) (pHAAs) to deliver peptide-based vaccine against Group A (GAS). We designed and synthesized self-assembled nanoparticles with a variety of conjugates bearing a peptide antigen (J8-PADRE) and polymerized hydrophobic amino acids to evaluate the effects of structural arrangement and pHAAs properties on a system's ability to induce humoral immune responses. Immunogenicity of the developed conjugates was also compared to commercially available human adjuvants. We found that a linear conjugate bearing J8-PADRE and 15 copies of leucine induced equally effective, or greater, immune responses than commercial adjuvants. Our fully defined, adjuvant-free, single molecule-based vaccine induced the production of antibodies capable of killing GAS bacteria.
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http://dx.doi.org/10.1021/acs.jmedchem.0c01660DOI Listing
March 2021

A Strained Ion Pair Permits Carbon Dioxide Fixation at Atmospheric Pressure by C-H H-Bonding Organocatalysis.

J Org Chem 2021 Feb 29;86(4):3422-3432. Epub 2021 Jan 29.

State Key Laboratory of Materials-Oriented Chemical Engineering, College of Biotechnology and Pharmaceutical Engineering, Nanjing Tech University, 30 Puzhu Road South, Nanjing, Jiangsu 211816, China.

The cycloadditions of carbon dioxide into epoxides to afford cyclic carbonates by H-bond donor (HBD) and onium halide (X) cocatalysis have emerged as a key strategy for CO fixation. However, if the HBD is also a halide receptor, the two will quench each other, decreasing the catalytic activity. Here, we propose a strained ion pair tris(alkylamino)cyclopropenium halide (TAC·X), in which TAC repels X. TAC possesses a positively charged cyclopropenium core that makes the vicinal C-H or N-H a nonclassical HBD. The interionic strain within TAC·X makes TAC a more electrophilic HBD, allowing it to activate the oxygen of the epoxide and making X more nucleophilic and better able to attack the methylene carbon of the epoxide. NMR titration spectra and computational studies were employed to probe the mechanism of the cycloaddition of CO to epoxides reactions under the catalysis of TAC·X. The H and C{H}NMR titration spectra of the catalyst with the epoxide substrate unambiguously confirmed H-bonding between TAC and the epoxide. DFT computational studies identified the transition states in the ring-opening of the epoxide (TS1) and in the ring-closure of the cyclic carbonate (TS2).
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http://dx.doi.org/10.1021/acs.joc.0c02790DOI Listing
February 2021

A novel circulating miRNA-based signature for the early diagnosis and prognosis prediction of non-small-cell lung cancer.

J Clin Lab Anal 2020 Nov 9;34(11):e23505. Epub 2020 Aug 9.

Department of Thoracic Surgery, The Affiliated Hospital of Medical School of Ningbo University, Ningbo, China.

Background: Non-small-cell lung cancer (NSCLC) is a significant public health issue worldwide. The aim of our study was to develop a serum miRNA-based molecular signature for the early detection and prognosis prediction of NSCLC.

Methods: The significantly altered circulating miRNAs were profiled in GSE24709. The top ten upregulated miRNAs were miR-432, miR-942, miR-29c-5p, miR-601, miR-613, miR-520d-3p, miR-1261, miR-132-5p, miR-302b, and miR-154-5p, while the top ten downregulated miRNAs were miR-562, miR-18b, miR-9-3p, miR-154-3p, miR-20b, miR-18a, miR-487a, miR-20a, miR-103, and miR-144. Then, the top four upregulated serum miRNAs (miR-432, miR-942, miR-29c-5p, and miR-601) were validated by real-time quantitative PCR. The clinical significance of two candidate serum miRNAs, miR-942 and miR-601, was further explored.

Results: Our results showed that the expression levels of serum miR-942 and serum miR-601 were significantly upregulated in NSCLC. In addition, serum miR-942 and serum miR-601 showed better performance than CEA, CYFRA21-1, and SCCA for early diagnosis of NSCLC. Combining serum miR-942 and serum miR-601 enhanced the efficacy of detecting early-stage NSCLC. Moreover, high serum miR-942 and serum miR-601 were both associated with adverse clinical variables and poor survival. The NSCLC patients with simultaneously high serum miR-942 and serum miR-601 suffered worst clinical outcome, while those with simultaneously low serum miR-942 and serum miR-601 had most favorable outcome. The multivariate analysis showed that serum miR-942 and serum miR-601 were independent prognostic factors for NSCLC.

Conclusions: Taken together, serum miR-942 and serum miR-601 might serve as a promising molecular signature for the early detection and prognosis prediction of NSCLC.
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http://dx.doi.org/10.1002/jcla.23505DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7676218PMC
November 2020

Mechanistic study of the cooperative palladium/Lewis acid-catalyzed transfer hydrocyanation reaction: the origin of the regioselectivity.

Dalton Trans 2021 Feb;50(4):1233-1238

Institute of Advanced Synthesis, School of Chemistry and Molecular Engineering, Nanjing Tech University, Nanjing 211816, China.

Density functional theory (DFT) calculations have been performed to gain insights into the catalytic mechanism of the palladium/Lewis acid-catalyzed transfer hydrocyanation of terminal alkenes to reach the linear alkyl nitrile with excellent anti-Markovnikov selectivity. The study reveals that the whole catalysis can be characterized via three stages: (i) oxidative addition generates the π-allyl complex IM2, followed by β-hydride elimination leading to the intermediate IM4, (ii) ligand exchange followed by Pd-H migratory alkene insertion gives the anti-Markovnikov intermediate IM6 and (iii) IM6 undergoes a reductive elimination step to form the linear terminal nitrile 3a and regenerates the active species for the next catalytic cycle. Each stage is kinetically and thermodynamically feasible. The oxidative addition step, with a barrier of 30.9 kcal mol-1, should be the rate-determining step (RDS) in the whole catalysis, which agrees with the experimental high temperature of 110 °C. Furthermore, the origin of the high regioselectivity of the product with excellent anti-Markovnikov selectivity is discussed.
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http://dx.doi.org/10.1039/d0dt03941aDOI Listing
February 2021

Investigating the efficacy and safety of mineral smectite granules on wound healing.

Exp Ther Med 2021 Feb 18;21(2):160. Epub 2020 Dec 18.

Digestive Endoscopy Department and General Surgery Department, The First Affiliated Hospital with Nanjing Medical University and Jiangsu Province Hospital, Nanjing, Jiangsu 210029, P.R. China.

Mineral smectite granules have traditionally been used for diarrhea and gastrointestinal bleeding; however, the wound healing ability of mineral smectite granules has not been investigated in detail. Therefore, the present study explored the efficacy and safety of mineral smectite granules on wound healing. An excision wound rat model was established. The experimental group was treated with smectite granules, the positive control group was treated with starch and the blank control group was left untreated. Wound closure rates, wound healing times and histopathological analysis were compared among the three groups. The mechanism underlying the effects of mineral smectite granules on wound healing was assessed by performing picrosirius red staining and immunohistochemical staining and measuring hydroxyproline content. Based on wound closure rates, wound healing times and histopathological analysis, the results indicated that rats treated with smectite granules displayed increased wound healing efficacy compared with the other two groups. Investigation of the underlying mechanism suggested that mineral smectite granules could promote wound healing by inducing collagen fiber synthesis and increasing the number of neovessels. The present study indicated the efficacy and safety of mineral smectite granules on wound healing and provided a theoretical basis for its application in a clinical setting.
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http://dx.doi.org/10.3892/etm.2020.9591DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7792489PMC
February 2021

Whole genome sequencing of 10K patients with acute ischaemic stroke or transient ischaemic attack: design, methods and baseline patient characteristics.

Stroke Vasc Neurol 2020 Dec 18. Epub 2020 Dec 18.

Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, Beijing, China

Background And Purpose: Stroke is the second leading cause of death worldwide and the leading cause of mortality and long-term disability in China, but its underlying risk genes and pathways are far from being comprehensively understood. We here describe the design and methods of whole genome sequencing (WGS) for 10 914 patients with acute ischaemic stroke or transient ischaemic attack from the Third China National Stroke Registry (CNSR-III).

Methods: Baseline clinical characteristics of the included patients in this study were reported. DNA was extracted from white blood cells of participants. Libraries are constructed using qualified DNA, and WGS is conducted on BGISEQ-500 platform. The average depth is intended to be greater than 30× for each subject. Afterwards, Sentieon software is applied to process the sequencing data under the Genome Analysis Toolkit best practice guidance to call genotypes of single nucleotide variants (SNVs) and insertion-deletions. For each included subject, 21 fingerprint SNVs are genotyped by MassARRAY assays to verify that DNA sample and sequencing data originate from the same individual. The copy number variations and structural variations are also called for each patient. All of the genetic variants are annotated and predicted by bioinformatics software or by reviewing public databases.

Results: The average age of the included 10 914 patients was 62.2±11.3 years, and 31.4% patients were women. Most of the baseline clinical characteristics of the 10 914 and the excluded patients were balanced.

Conclusions: The WGS data together with abundant clinical and imaging data of CNSR-III could provide opportunity to elucidate the molecular mechanisms and discover novel therapeutic targets for stroke.
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http://dx.doi.org/10.1136/svn-2020-000664DOI Listing
December 2020