Publications by authors named "Qin Liu"

1,183 Publications

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CO2 pneumoperitoneum pressure: an important factor influenced ovarian function after laparoscopy.

Ann Palliat Med 2021 Jul 20. Epub 2021 Jul 20.

Department of Obstetrics and Gynecology, The Maternal and Child Health Care Hospital of Guizhou Medical University, Guiyang, China.

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http://dx.doi.org/10.21037/apm-2021-05DOI Listing
July 2021

Unsupervised Learning of Reference Bony Shapes for Orthognathic Surgical Planning with a Surface Deformation Network.

Med Phys 2021 Jul 26. Epub 2021 Jul 26.

Department of Oral and Maxillofacial Surgery, Houston Methodist Hospital, Houston, TX, 77030, USA.

Purpose: To reduce the experience dependence during the orthognathic surgical planning that involves virtually simulating the corrective procedure for jaw deformities.

Methods: We introduce a geometric deep learning framework for generating reference facial bone shape models for objective guidance in surgical planning. First, we propose a surface deformation network to warp a patient's deformed bone to a set of normal bones for generating a dictionary of patient-specific normal bony shapes. Subsequently, sparse representation learning is employed to estimate a reference shape model based on the dictionary.

Results: We evaluated our method on a clinical dataset containing 24 patients, and compared it with a state-of-the-art method that relies on landmark-based sparse representation. Our method yields significantly higher accuracy than the competing method for estimating normal jaws, and maintains the midfaces of patients' facial bones as well as the conventional way.

Conclusions: Experimental results indicate that our method generates accurate shape models that meet clinical standards.
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http://dx.doi.org/10.1002/mp.15126DOI Listing
July 2021

Ethical frameworks in clinical research processes during COVID-19: a scoping review.

BMJ Open 2021 07 23;11(7):e047076. Epub 2021 Jul 23.

Division of Medical Oncology and Hematology, Princess Margaret Hospital Cancer Centre, Toronto, Ontario, Canada

Objectives: In response to the COVID-19 pandemic there have been significant developments in research, its conduct and the supporting ethical framework. While many protocols have been delayed, halted or modified, other research efforts have been accelerated, generating controversy. The goal of this paper is to determine the rates of references surrounding the ethical oversight of research as reported in current COVID-19-related research publications.

Design: Scoping review.

Setting: Population-based observational or interventional studies from December 2019 to May 2020 with sample size of two or more. Studies were searched through electronic databases including Medline, EMBASE, and Cochrane CENTRAL Register of Controlled Trials.

Participants: Eligibility criteria included participants within published studies who tested positive for COVID-19.

Main Outcomes And Measures: Data were extracted and charting methods included taking note of references to ethical frameworks, institutional review board (IRB), ethics committee (EC) or research ethics board (REB) involvement, consent processes, and other variables.

Results: 11 556 articles were screened, with 656 included in the final analysis. References to ethics were present in 530 (80.8%) studies, with 491 (74.8%) involving IRB/ECs/REBs and 126 (19.2%) not referencing ethics. Consent processes were outlined in 201 (30.6%) studies, with 198 (30.2%) reporting that they obtained consent waivers, however, 257 (39.2%) did not mention consent at all. Differences (p<0.001) in ethics-related references were apparent when analysed by continent, publication type, sample size and IF.

Conclusions: The majority of published articles pertaining to COVID-19 research made mention of ethical considerations, however, national and regional variations in research ethics review requirements introduce heterogeneity between studies and raise important questions about the conduct of scientific research during global public emergencies.

Trial Registration Number: Open Science Framework: https://osfio/z67wb.
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http://dx.doi.org/10.1136/bmjopen-2020-047076DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8313312PMC
July 2021

Prenatal case of Simpson-Golabi-Behmel syndrome with a de novo 370Kb-sized microdeletion of Xq26.2 compassing partial GPC3 gene and review.

Mol Genet Genomic Med 2021 Jul 22:e1750. Epub 2021 Jul 22.

Department of Medical Genetics, Hunan Provincial Maternal and Child Health Care Hospital, Changsha, Hunan, China.

Background: Simpson-Golabi-Behmel syndrome type 1 (SGBS1) is a rare X-linked recessive disorder characterized by pre- and postnatal overgrowth and a broad spectrum of anomalies including craniofacial dysmorphism, heart defects, renal, and genital anomalies. Due to the ultrasound findings are not pathognomonic for this syndrome, most clinical diagnosis of SGBS1 are made postnatally.

Methods: A pregnant woman with abnormal prenatal sonographic findings was advised to perform molecular diagnosis. Single nucleotide polymorphism array (SNP array) was performed in the fetus, and the result was validated with multiplex ligation-dependent probe amplification (MLPA) and real-time quantitative PCR (qPCR).

Results: The prenatal sonographic presented with increased nuchal translucency at 13 gestational weeks, and later at 21 weeks with cleft lip and palate, heart defect, increased amniotic fluid index and over growth. A de novo 370Kb-deletion covering the 5'-UTR and exon 1 of GPC3 gene was detected in the fetus by SNP array, which was subsequently confirmed by MLPA and qPCR.

Conclusion: The de novo 370Kb hemizygous deletion of 5'-UTR and exon 1 of GPC3 results in the SGBS1 of this Chinese family. Combination of ultrasound and genetics tests helped us effectively to diagnose the prenatal cases of SGBS1. Our findings also enlarge the spectrum of mutations in GPC3 gene.
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http://dx.doi.org/10.1002/mgg3.1750DOI Listing
July 2021

Humoral immune durability of IgG for anti-SARS-CoV-2 in the normal pregnant women in Wuhan, China.

Immunol Res 2021 Jul 22. Epub 2021 Jul 22.

Department of ObstetricsMaternal, Child Health Hospital of Hubei Province, Tongji Medical College, Huazhong University of Science and Technology, No. 745, Wuluo Road, Hongshan District, Wuhan, 430070, China.

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http://dx.doi.org/10.1007/s12026-021-09213-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8295631PMC
July 2021

Cross-Cultural Associations of Four Parenting Behaviors With Child Flourishing: Examining Cultural Specificity and Commonality in Cultural Normativeness and Intergenerational Transmission Processes.

Child Dev 2021 Jul 22. Epub 2021 Jul 22.

Temple University.

Families from nine countries (N = 1,338) were interviewed annually seven times (M child = 7-15) to test specificity and commonality in parenting behaviors associated with child flourishing and moderation of associations by normativeness of parenting. Participants included 1,338 children (M = 8.59 years, SD = 0.68, range = 7-11 years; 50% girls), their mothers (N = 1,283, M = 37.04 years, SD = 6.51, range = 19-70 years), and their fathers (N = 1,170, M = 40.19 years, SD = 6.75, range = 22-76 years) at Wave 1 of 7 annual waves collected between 2008 and 2017. Families were recruited from 12 ethnocultural groups in nine countries including: Shanghai, China (n = 123); Medellín, Colombia (n = 108); Naples (n = 102) and Rome (n = 111), Italy; Zarqa, Jordan (n = 114); Kisumu, Kenya (n = 100); Manila, Philippines (n = 120); Trollhättan & Vänersborg, Sweden (n = 129); Chiang Mai, Thailand (n = 120); and Durham, NC, United States (n = 110 White, n = 102 Black, n = 99 Latinx). Intergenerational parenting (parenting passed from Generation 1 to Generation 2) demonstrated specificity. Children from cultures with above-average G2 parent warmth experienced the most benefit from the intergenerational transmission of warmth, whereas children from cultures with below-average G2 hostility, neglect, and rejection were best protected from deleterious intergenerational effects of parenting behaviors on flourishing. Single-generation parenting (Generation 2 parenting directly associated with Generation 3 flourishing) demonstrated commonality. Parent warmth promoted, and parent hostility, neglect, and rejection impeded the development of child flourishing largely regardless of parenting norms.
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http://dx.doi.org/10.1111/cdev.13634DOI Listing
July 2021

Disseminated intravascular coagulation complicating diagnosis of ROS1-mutant non-small cell lung cancer: A case report and literature review.

Thorac Cancer 2021 Jul 22. Epub 2021 Jul 22.

Department of Medical Oncology, St George Cancer Care Centre, Kogarah, New South Wales, Australia.

Disseminated intravascular coagulation (DIC) is a rare paraneoplastic complication in advanced solid malignancies, with success of treatment and survival dependent on treatment of the underlying malignancy. Best estimates suggest an incidence of 1.6-6.8% in cancer, with risk factors being advanced disease, older age, and adenocarcinoma, especially of lung origin. Few cases, however, have reported on an association between DIC and oncogene-addicted lung cancers, especially those containing ROS proto-oncogene 1 (ROS1) mutations, however precedent exists to suggest increased prothrombotic rates in tumors harboring this mutation. We present a young woman with ROS1-mutant non-small-cell lung cancer who presented in DIC and subsequently developed complications of both hemorrhage and thrombosis. Following initiation of targeted treatment, rapid resolution of laboratory coagulation derangement was observed and clinical improvement quickly followed. This event underscores the need for rapid evaluation of lung molecular panels and the dramatic resolution of life-threatening illness that can occur with institution of appropriate therapy. This case contributes to growing evidence for a possible underlying link between oncogene addicted tumors and abnormalities of coagulation.
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http://dx.doi.org/10.1111/1759-7714.14071DOI Listing
July 2021

Retrospective comparison of high-resolution computed tomography of eosinophilic granulomatosis with polyangiitis with severe asthma.

Ann Transl Med 2021 Jun;9(12):983

Pulmonary and Critical Care Medicine, Guangzhou Institute of Respiratory Health, National Clinical Research Center for Respiratory Disease, National Center for Respiratory Medicine, State Key Laboratory of Respiratory Diseases, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, China.

Background: Eosinophilic granulomatosis with polyangiitis (EGPA) is often misdiagnosed as severe asthma due to their similar clinical presentations. We compared the pulmonary radiologic features of EGPA to those of severe asthma by high-resolution computed tomography (HRCT) in order to early diagnose EGPA.

Methods: We retrospectively reviewed clinical records and HRCT findings of 96 patients with EGPA and 82 patients with severe asthma who were seen at our hospital from 2011 to 2017. We used a semi-quantitative grading system to evaluate radiological findings. A radiological only and a clinical-radiological model were used to differentiate EGPA from severe asthma.

Results: Bronchial wall thickening, air trapping, tree-in-bud opacities, bronchial mucus plugging, bronchiectasis, diffuse ground-glass opacities (GGOs), consolidation, and increased small vascular markings were more common in EGPA patients than in severe asthmatics (P<0.05). The gradings of GGO (grade 2 grade 1) and tree-in-bud opacities (grade 2 grade 0) were higher in EGPA patients than in severe asthmatics. The total image score of EGPA patients was significantly higher than that of severe asthmatics (P<0.05). In the radiological only and the clinical-radiological model, the area under the receiver operating characteristic (ROC) curves (AUCs) for the identification of EGPA and severe asthma were 0.904 [95% confidence interval (CI): 0.860 to 0.948] and 0.974 (95% CI: 0.955 to 0.993), respectively.

Conclusions: Lung HRCT scan is useful in differentiating EGPA from severe asthma. In patients with difficult-to-treat asthma, an HRCT scan of the thorax should be performed should there be features that raise the suspicion of EGPA.
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http://dx.doi.org/10.21037/atm-21-2243DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8267300PMC
June 2021

Comprehensive Characterization of Immune Landscape Based on Epithelial-Mesenchymal Transition Signature in OSCC: Implication for Prognosis and Immunotherapy.

Front Oncol 2021 1;11:587862. Epub 2021 Jul 1.

Guangdong Provincial Key Laboratory of Stomatology, Guanghua School of Stomatology, Hospital of Stomatology, Sun Yat-sen University, Guangzhou, China.

Current anatomic TNM stage classification fails to capture the immune heterogeneity of oral squamous cell carcinoma (OSCC). Increasing evidence indicates the strong association between epithelial-mesenchymal transition (EMT) and tumor immune response. In this study, we employed an EMT signature to classify OSCC patients into epithelial- (E-) and mesenchymal- (M-) phenotypes using TCGA and GSE41613 transcriptome data. The ESTIMATE and CIRBERSORT analyses implied that the EMT signature genes originated from the stroma of the bulk tissue. The M-subtype tumors were characterized as "immune-hot" with more immune cell infiltration than the E-subtype ones. The low infiltration of active immune cells, the high infiltration of inactive immune cells, and the high expressions of immune checkpoints demonstrated an immunosuppressive characteristic of the M-subtype tumors. Moreover, we developed and validated a novel prognostic classifier based on the EMT score, the expressions of seven immune checkpoints, and the TNM stages, which could improve the prediction efficiency of the current clinical parameter. Together, our findings provide a better understanding of the tumor immune heterogeneity and may aid guiding immunotherapy in OSCC.
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http://dx.doi.org/10.3389/fonc.2021.587862DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8281347PMC
July 2021

Intraoperative Neurophysiology and Transcranial Doppler for Detection of Cerebral Ischemia and Hyperperfusion during Carotid Endarterectomy.

World Neurosurg 2021 Jul 13. Epub 2021 Jul 13.

Department of Neurosurgery, Cangzhou Central Hospital, Hebei province, China.

Objective: To evaluate and compare the efficacy of intraoperative neurophysiological monitoring (IONM) and intraoperative transcranial Doppler (TCD) techniques for identification of hypoperfusion during carotid artery (CA) clamp and hyperperfusion after release of occlusion during carotid endarterectomy (CEA).

Methods: A retrospective, consecutive case series of 152 patients undergoing CEA between June 2018 and March 2020 were reviewed. Monitoring of somatosensory evoked potentials (SEPs), motor evoked potentials (MEPs), electroencephalogram (EEG) and TCD were investigated.

Results: Three patient cohorts were observed after clamping CA: A, in 132 of the 152 patients (87%), TCD blood flow velocity decreased by less than 50%, and there were no changes in IONM; B, in 5 of 152 (3%) patients, TCD blood flow rate was reduced between 50% and 100% with no changes in IONM; C, in 15 patients (10%), blood flow velocity was reduced by 50% to 100%, and all IONM modalities met warning criteria. With increased blood pressure, IONM and blood flow velocities improved to less than warning criteria in 8/15 patients. In 6 of the 7 remaining patients, IONM modalities recovered to baseline immediately after clamps were removed from CA. The one patient with persistent MEP deterioration experienced a postoperative proximal muscle weakness which recovered 48 hours later. In 22 patients, TCD detected hyperperfusion at the moment of clamp release.

Conclusions: TCD blood flow velocity is correlated with MEP and SEP amplitude changes after clamping. After declamping, TCD can detect hyperperfusion and help to regulate blood pressure to prevent hyperperfusion.
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http://dx.doi.org/10.1016/j.wneu.2021.07.023DOI Listing
July 2021

Heterogeneity response to afatinib in gastric cancer patient with uncommon epidermal growth factor receptor (EGFR) mutations: a case report.

Ann Transl Med 2021 May;9(9):814

The Comprehensive Cancer Centre of Drum Tower Hospital, Medical School of Nanjing University & Clinical Cancer Institute of Nanjing University, Nanjing, China.

Despite concerted efforts that have been made to characterize and understand the genomic landscape of gastric cancer (GC), only HER2 has been validated as a molecular target for GC treatment. Identifying new valid therapeutic targets is important for the treatment of this disease. The present report describes a Chinese male with a history of smoking two packs per day, who did not have a family history of cancer or other hereditary diseases, we discovered a small painless lump in the right groin in February 2018. Histopathology revealed a primary gastric adenocarcinoma. Positron emission tomography-computed tomography (PET-CT) showed multiple hypermetabolic nodules in the right upper lung, greater curvature of the stomach, and muscles. The patient had received treatment included oxaliplatin, docetaxel, and tegafur for two cycles, and second-line therapy of irinotecan and capecitabine, inguinal mass excision followed by concurrent radio-chemotherapy. However, the disease rapidly progressed. Whole exome sequencing (WES) showed uncommon epidermal growth factor receptor (EGFR) mutation of G719S + L861Q. The following EGFR tyrosine kinase inhibitors (TKIs) afatinib demonstrated partial response. Two months after targeted therapy, gastroscopy indicated rapid progression. With subsequent gastric specimen WES analysis, secondary MET amplification was found. The patient received local radiotherapy for gastric lesions as well as oral administration of apatinib. However, the disease rapidly progressed. A month later, he died of hepatic encephalopathy caused by obstructive jaundice combined with pulmonary and biliary tract infection. The present study indicated that afatinib might be a beneficial therapeutic option for a subset of GC patients with rare EGFR mutation in their tumors.
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http://dx.doi.org/10.21037/atm-20-7312DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8246221PMC
May 2021

RAB27A-dependent release of exosomes by liver cancer stem cells induces Nanog expression in their differentiated progenies and confers Regorafenib resistance.

J Gastroenterol Hepatol 2021 Jul 14. Epub 2021 Jul 14.

Department of Gastroenterology, The Second Affiliated Hospital of Chongqing Medical University, Yu zhong, Chongqing, P. R. China.

Background And Aim: Regorafenib is a potent multi-kinase inhibitor for the second-line targeted therapy against hepatocellular carcinoma (HCC), however drug resistance is emerging in clinical settings. Although cancer stem cells (CSCs) are considered as key determinate of drug sensitivity, it remains unclear how CSCs may communicate with the differentiated counterparts (non-CSC) to dictate therapeutic efficacy. Therefore, we sought to investigate the Regorafenib resistance mechanism of CSCs in HCC.

Methods: We used sphere formation and soft agar colony formation assays to evaluate the stemness capacity of cancer cells. Cell viability assay was performed to detect the sensitivity of cancer cells to Regorafenib. Real-time quantitative PCR and western blot were used to analyze gene expression. Mouse xenograft tumor model was performed to assess Regorafenib sensitivity in vivo.

Results: Exosomes are highly enriched in CSC supernatant compared to that of non-CSC. And RAB27A mediates exosome secretion from CSCs to maintain stem-like phenotype and Regorafenib insensitivity. Moreover, exosomes released by CSCs up-regulate the expression of Nanog in non-CSC, while depleting Nanog sensitizes non-CSC to Regorafenib in the presence of CSC exosomes. Consistently, analysis of TCGA datasets reveals that RAB27A expression tightly correlates with Nanog in HCC tissues. More importantly, Depletion of RAB27A down-regulates Nanog expression and sensitizes cancer cells to Regorafenib in nude mice.

Conclusions: Our findings suggest that CSCs release exosomes in a RAB27A-dependent manner to induce Nanog expression and Regorafenib resistance in differentiated cells, targeting this exosome signaling between distinct cellular subsets may be a potential therapeutic strategy for HCC patients.
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http://dx.doi.org/10.1111/jgh.15619DOI Listing
July 2021

Comparative study of adsorptions, reactions and electronic properties of U atoms on Cu(111), Ag(111), Au(111) and Ru(0001) surfaces.

Nanotechnology 2021 Jul 29;32(42). Epub 2021 Jul 29.

Science and Technology on Surface Physics and Chemistry Laboratory, Mianyang, Sichuan 621908, People's Republic of China.

The mysterious properties of individual U atoms on transition metal surfaces play indispensable parts in supplementing our understanding of uranium-transition metal systems, which are important subjects for both nuclear energy applications and fundamental scientific studies. By using scanning tunneling microscopy and density functional theory calculations, the adsorptions, reactions and electronic properties of individual U atoms on Cu(111), Ag(111), Au(111) and Ru(0001) surfaces were comparatively studied for the first time in this work. Upon the deposition of a small amount of U onto Cu(111) or Ag(111) at 8 K, individual U atoms show relatively high activity and can either be adsorbed on intact substrate surfaces or induce various surface vacancies surrounded by clusters of substrate atoms. By contrast, the majority of U atoms tend to dispersedly adsorb on intact surfaces of Au(111) and Ru(0001) rather than producing surface vacancies at the same temperature. In all cases, Kondo resonance manifested as asymmetric dip feature around Fermi energy is only observed in the differential tunneling conductance spectra of single U adatoms on Ag(111).
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http://dx.doi.org/10.1088/1361-6528/ac13e9DOI Listing
July 2021

Metabolism-related long non-coding RNAs (lncRNAs) as potential biomarkers for predicting risk of recurrence in breast cancer patients.

Bioengineered 2021 Dec;12(1):3726-3736

Department of Breast Surgery, Thyroid Surgery, Huangshi Central Hospital of Edong Healthcare Group, Hubei Polytechnic University, Huangshi, Hubei, China.

Metabolism affects the development, progression, and prognosis of various cancers, including breast cancer (BC). Our aim was to develop a metabolism-related long non-coding RNA (lncRNA) signature to assess the prognosis of BC patients in order to optimize treatment. Metabolism-related genes between breast tumors and normal tissues were screened out, and Pearson correlation analysis was used to investigate metabolism-related lncRNAs. In total, five metabolism-related lncRNAs were enrolled to establish prognostic signatures. Kaplan-Meier plots and the receiver operating characteristic (ROC) curves demonstrated good performance in both training and validation groups. Further analysis demonstrated that the signature was an independent prognostic factor for BC. A nomogram incorporating risk score and tumor stage was then constructed to evaluate the 3 - and 5-year recurrence-free survival (RFS) in patients with BC. In conclusion, this study identified a metabolism-related lncRNA signature that can predict RFS of BC patients and established a prognostic nomogram that helps guide the individualized treatment of patients at different risks.
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http://dx.doi.org/10.1080/21655979.2021.1953216DOI Listing
December 2021

Zebrafish gasdermin E cleavage-engaged pyroptosis by inflammatory and apoptotic caspases.

Dev Comp Immunol 2021 Nov 10;124:104203. Epub 2021 Jul 10.

State Key Laboratory of Bioreactor Engineering, East China University of Science and Technology, Shanghai, 200237, China; Shanghai Engineering Research Center of Maricultured Animal Vaccines, Shanghai, 200237, China. Electronic address:

As the executor of pyroptosis known to date, gasdermins (GSDMs), consists of GSDMA, GSDMB, GSDMC, GSDMD, GSDME and pejvakin, might play critical roles in anti-bacterial infection as well as inflammatory diseases. However, zebrafish only harbors a pair of Gsdme (Gsdmea/b), and their activation mechanisms remain largely unknown. Herein, we investigate the activation mechanism of Gsdmea/b cleaved by inflammatory and apoptotic caspases in zebrafish,and found that Gsdmea/b are equally cleaved by Caspase 19b, a sister of Caspy2, but not Caspy. Moreover, the zebrafish apoptotic effector caspases, including Caspase 3a/b and Caspase 7, also can cleave Gsdmea/b at the same sites as inflammatory caspases recognized. Importantly, our results reveal that Caspase 8a/b can cleave Gsdmeb, but only Caspase 8a can cleave Gsdmea. Taken together, these findings suggest that zebrafish Gsdmea/b can concurrently function as GSDMD and GSDME in mammals, which will contribute to better understanding the mechanism of pyroptosis activation in teleost, as well as provide a clue for drug screening model against inflammatory diseases.
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http://dx.doi.org/10.1016/j.dci.2021.104203DOI Listing
November 2021

OX40 agonist combined with irreversible electroporation synergistically eradicates established tumors and drives systemic antitumor immune response in a syngeneic pancreatic cancer model.

Am J Cancer Res 2021 15;11(6):2782-2801. Epub 2021 Jun 15.

Department of Radiology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine No. 197, Ruijin Er Road, Shanghai 200025, China.

In this study, we intended to explore a novel combination treatment scheme for pancreatic cancer, using irreversible electroporation (IRE) and OX40 agonist. We further aimed to investigate the capacity and mechanism of this combination treatment using an mouse aggressive pancreatic cancer model. To this end, mice subcutaneously injected with KPC1199 pancreatic tumor cells were treated with IRE, followed by intraperitoneal injection of OX40 agonist. Tumor growth and animal survival were observed. Flow cytometry analysis, immunohistochemistry, and immunofluorescence were used to evaluate the immune cell populations within the tumors. The tumor-specific immunity was assessed using ELISpot assay. Besides, the cytokine patterns both in serum and tumors were identified using Luminex assay. After combination therapy with IRE and OX40 agonist, 80% of the mice completely eradicated the established subcutaneous tumors, during the 120 days observation period. Rechallenging these tumor-free mice at day 120 with KPC1199 tumor cells leads to complete resistance to tumor growth, suggesting that the combination therapy generated long-term-specific antitumor immune memory. Moreover, combination therapy significantly delayed the growth of contralateral untreated tumors, and significantly prolonged animal survival, suggesting that a potent systematic anti-tumor immunity was induced by combination therapy. Mechanically, combination therapy amplified antitumor immune response induced by IRE, as manifested by the increased quality and quantity of CD8 T cells trigged by IRE. Together, these results provide strong evidence for the clinical assessment of the combination of IRE and OX40 agonist in patients with pancreatic cancer.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8263674PMC
June 2021

Prognostic Nomograms Based on Three Lymph Node Classification Systems for Resected Gastric Adenocarcinoma: A Large Population-Based Cohort Study and External Validation.

Ann Surg Oncol 2021 Jul 9. Epub 2021 Jul 9.

The Comprehensive Cancer Centre of Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School & Clinical Cancer Institute of Nanjing University, Nanjing, China.

Backgrounds: The optimal lymph node classification system for prognostic assessment in gastric adenocarcinoma (GAC) patients who undergo lymph node dissection remains unclear. Therefore, this study aimed to compare prognostic nomograms based on AJCC N stage, lymph node ratio (LNR), and log odds of metastatic lymph nodes (LODDS) to evaluate the prognosis and differentiate risk subgroups of patients with resected GAC.

Patients And Methods: We collected 4633 patients with resected stage I-III GAC receiving chemotherapy from the Surveillance, Epidemiology, and End Results (SEER) database between 2004 and 2015. Independent prognostic factors were selected by Cox regression analyses, based on which nomograms were constructed. External validation was performed in 228 cases from Nanjing Drum Tower Hospital. Kaplan-Meier survival analysis was used to evaluate the effect of postoperative radiotherapy (PORT) for different lymph node classifications.

Results: Multivariate analysis indicated that age, grade, primary site, T stage, N stage, LNR, LODDS, and radiotherapy were independent predictors. Good discrimination power and high consistency of calibration plots were obtained from the LODDS system nomogram. The LODDS classification could more precisely differentiate risk subgroups and improve the discrimination of the resected GAC prognosis. A user-friendly webserver of LODDS system was built based on the nomogram for convenient clinical application.

Conclusions: The LODDS seems to be the most reliable lymph node classification in predicting the prognosis of patients with resected GAC and should be recommended in clinical prognostic assessment. Incorporating LODDS into the staging system will enable clinicians to more accurately predict prognosis and guide radiotherapy regimen decisions.
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http://dx.doi.org/10.1245/s10434-021-10299-1DOI Listing
July 2021

ASO Visual Abstract: Prognostic Nomograms Based on Three-Lymph-Node Classification Systems for Resected Gastric Adenocarcinoma: A Large Population-Based Cohort Study and External Validation.

Ann Surg Oncol 2021 Jul 8. Epub 2021 Jul 8.

The Comprehensive Cancer Centre of Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School and Clinical Cancer Institute of Nanjing University, Nanjing, 210008, China.

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http://dx.doi.org/10.1245/s10434-021-10348-9DOI Listing
July 2021

CT Quantification of COVID-19 Pneumonia at Admission Can Predict Progression to Critical Illness: A Retrospective Multicenter Cohort Study.

Front Med (Lausanne) 2021 17;8:689568. Epub 2021 Jun 17.

Department of Radiology, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, China.

Early identification of coronavirus disease 2019 (COVID-19) patients with worse outcomes may benefit clinical management of patients. We aimed to quantify pneumonia findings on CT at admission to predict progression to critical illness in COVID-19 patients. This retrospective study included laboratory-confirmed adult patients with COVID-19. All patients underwent a thin-section chest computed tomography (CT) scans showing evidence of pneumonia. CT images with severe moving artifacts were excluded from analysis. Patients' clinical and laboratory data were collected from medical records. Three quantitative CT features of pneumonia lesions were automatically calculated using a care.ai Intelligent Multi-disciplinary Imaging Diagnosis Platform Intelligent Evaluation System of Chest CT for COVID-19, denoting the percentage of pneumonia volume (PPV), ground-glass opacity volume (PGV), and consolidation volume (PCV). According to Chinese COVID-19 guidelines (trial version 7), patients were divided into noncritical and critical groups. Critical illness was defined as a composite of admission to the intensive care unit, respiratory failure requiring mechanical ventilation, shock, or death. The performance of PPV, PGV, and PCV in discrimination of critical illness was assessed. The correlations between PPV and laboratory variables were assessed by Pearson correlation analysis. A total of 140 patients were included, with mean age of 58.6 years, and 85 (60.7%) were male. Thirty-two (22.9%) patients were critical. Using a cutoff value of 22.6%, the PPV had the highest performance in predicting critical illness, with an area under the curve of 0.868, sensitivity of 81.3%, and specificity of 80.6%. The PPV had moderately positive correlation with neutrophil (%) ( = 0.535, < 0.001), erythrocyte sedimentation rate ( = 0.567, < 0.001), d-Dimer ( = 0.444, < 0.001), high-sensitivity C-reactive protein ( = 0.495, < 0.001), aspartate aminotransferase ( = 0.410, < 0.001), lactate dehydrogenase ( = 0.644, < 0.001), and urea nitrogen ( = 0.439, < 0.001), whereas the PPV had moderately negative correlation with lymphocyte (%) ( = -0.535, < 0.001). Pneumonia volume quantified on initial CT can non-invasively predict the progression to critical illness in advance, which serve as a prognostic marker of COVID-19.
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http://dx.doi.org/10.3389/fmed.2021.689568DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8245676PMC
June 2021

Serum calponin 2 is a novel biomarker of tubal ectopic pregnancy.

Fertil Steril 2021 Jun 30. Epub 2021 Jun 30.

Department of Obstetrics and Gynecology, Shanghai ZhongShan Hospital, Shanghai FuDan University School of Medicine, Shanghai, China. Electronic address:

Objective: To evaluate serum protein calponin 2 (CNN2) as a candidate biomarker for tubal ectopic pregnancy (EP).

Design: Retrospective study.

Setting: Single University affiliated tertiary hospital.

Patient(s): Serum samples were obtained from 84 patients with EP, 39 with viable intrauterine pregnancy (vIUP), and 42 with miscarriage. Moreover, 10 fallopian tube and corresponding villous tissue samples from patients with EP, 6 villous tissue samples from patients with vIUP, and 10 villous tissue samples from patients with miscarriage were collected.

Intervention(s): Serum CNN2 concentrations were measured using enzyme-linked immunosorbent assay; CNN2 expression in tissues was evaluated via immunohistochemistry and quantitative real-time polymerase chain reaction analysis.

Main Outcome Measure(s): The diagnostic performance of serum CNN2 to discriminate an EP from vIUP and miscarriage.

Result(s): CNN2 was highly expressed in villous stromal cells isolated from patients with EP, and CNN2 messenger ribonucleic acid expression was upregulated in villous tissues from women with EP compared with that in women with vIUPs and miscarriages. Serum CNN2 concentration was higher in women with EP than that in women with vIUP and miscarriage. The serum CNN2 predicted EP from vIUP and miscarriage with areas under the curve (AUCs) of 0.931 (95% confidence interval: 0.889-0.975). For discriminating EP from miscarriage only, the AUC was 0.906 (95% confidence interval: 0.835-0.977). In contrast, the AUCs for serum human chorionic gonadotropin were 0.809 and 0.637, respectively.

Conclusion(s): Our data highlight the possibility of serum CNN2 as a single biomarker for the diagnosis of EP.

Clinical Trial Registration Number: ChiCTR 1900020483.
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http://dx.doi.org/10.1016/j.fertnstert.2021.05.101DOI Listing
June 2021

Insights into Temperature and Hypoxia Tolerance in Cowpea Weevil via HIF-1.

Pathogens 2021 Jun 5;10(6). Epub 2021 Jun 5.

School of Life Sciences, Jianghan University, Wuhan 430056, China.

Cowpea weevil () is a major pest that leads to severe damage of the stored leguminous grains. Several management approaches, including physical barriers, biological or chemical methods, are used for controlling bruchid in cowpea. These methods usually target the metabolically active state of weevil. However, it becomes less effective at early stages as egg, larva, or pupa under low temperature and oxygen conditions. Since hypoxia-inducible factor-1 (HIF-1) is known to coordinate multiple gene responses to low oxygen or low temperature signals, we examined the gene expression under low temperature and hypoxic treatments. At -20 °C, it took 4 h to reduce the survival rate for eggs, larvae, and pupae down to 10%, while at 4 °C and 15 °C, the survival rate remained higher than 50% even after 128 h as gene expression peaked at 15 °C. Moreover, HIF-1 protein offers a valuable target for early stage pest control complementary to traditional methods. In particular, HIF-1 inhibitor camptothecin (CPT), one of the five HIF-1 inhibitors examined, achieved a very significant reduction of 96.2% and 95.5% relative to the control in weevil survival rate into adult at 4 °C and 30 °C, respectively. Our study can be used as one model system for drug development in virus infections and human cancer.
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http://dx.doi.org/10.3390/pathogens10060704DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8228136PMC
June 2021

Sleep status of psychiatric nurses: A survey from China.

Nurs Open 2021 Jul 1. Epub 2021 Jul 1.

Suzhou Psychiatric Hospital, The Affiliated Guangji Hospital of Soochow University, Suzhou, China.

Aim: Our study aimed to evaluate the sleep status of psychiatric nurses in Chinese population and analyse the influencing factors.

Design: Cross-sectional, correlation design with logistic regression analysis.

Methods: We investigated 1,044 psychiatric nurses from seven psychiatric hospitals in China. Pittsburgh Sleep Quality Index and Maslach Burnout Inventory General Survey were used as main measures.

Results: The average Pittsburgh Sleep Quality Index score of 1,044 psychiatric nurses was 7.00 ± 3.59, and 38.63% of nurses had a total Pittsburgh Sleep Quality Index score >7. Our study found that middle-night shift nurses had poor sleep quality and sleep disorders are positively correlated with emotional exhaustion and cynical disregard for job burnout. Middle-night shift nurses showed 1.586 times more likely to suffer from sleep disorders than those non-middle-night shift. The higher the score of emotional exhaustion, the greater the risk of sleep disorders.
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http://dx.doi.org/10.1002/nop2.972DOI Listing
July 2021

Non-invasive plasma glycomic and metabolic biomarkers of post-treatment control of HIV.

Nat Commun 2021 06 29;12(1):3922. Epub 2021 Jun 29.

The Wistar Institute, Philadelphia, PA, USA.

Non-invasive biomarkers that predict HIV remission after antiretroviral therapy (ART) interruption are urgently needed. Such biomarkers can improve the safety of analytic treatment interruption (ATI) and provide mechanistic insights into the host pathways involved in post-ART HIV control. Here we report plasma glycomic and metabolic signatures of time-to-viral-rebound and probability-of-viral-remission using samples from two independent cohorts. These samples include a large number of post-treatment controllers, a rare population demonstrating sustained virologic suppression after ART-cessation. These signatures remain significant after adjusting for key demographic and clinical confounders. We also report mechanistic links between some of these biomarkers and HIV latency reactivation and/or myeloid inflammation in vitro. Finally, machine learning algorithms, based on selected sets of these biomarkers, predict time-to-viral-rebound with 74% capacity and probability-of-viral-remission with 97.5% capacity. In summary, we report non-invasive plasma biomarkers, with potential functional significance, that predict both the duration and probability of HIV remission after treatment interruption.
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http://dx.doi.org/10.1038/s41467-021-24077-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8241829PMC
June 2021

Identification and validation of a robust autophagy-related molecular model for predicting the prognosis of breast cancer patients.

Aging (Albany NY) 2021 06 29;13(12):16684-16695. Epub 2021 Jun 29.

Department of Thyroid and Breast Surgery, Zhongnan Hospital of Wuhan University, Wuhan, China.

Despite a relatively low mortality rate, high recurrence rates represent a significant problem for breast cancer (BC) patients. Autophagy affects the development, progression, and prognosis of various cancers, including BC. The aim of the present study was to identify candidate autophagy-related genes (ARGs) and construct a molecular-clinicopathological signature to predict recurrence risk in BC. A 10-ARG-based signature was established in a training cohort (GEO-BC dataset GSE25066) with LASSO Cox regression and assessed in an independent validation cohort (GEO-BC GSE22219). Significant differences in recurrence-free survival were observed for high- and low-risk patients segregated based on their signature-based risk score. Time-dependent receiver operating characteristic (tdROC) analysis of signature performance demonstrated satisfactory accuracy and predictive power in both the training and validation cohorts. Moreover, we developed a nomogram to predict 3- and 5-year recurrence-free survival by combining the autophagy-related risk score and clinicopathological data. Both the tdROC and calibration curves indicated high discriminating ability for the nomogram. This study indicates that our ARG-based signature is an independent prognostic classifier for recurrence-free survival in BC. In addition, individualized survival risk assessment and treatment decisions might be effectively improved by implementing the proposed nomogram.
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http://dx.doi.org/10.18632/aging.203187DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8266368PMC
June 2021

Plasma Markers of Disrupted Gut Permeability in Severe COVID-19 Patients.

Front Immunol 2021 9;12:686240. Epub 2021 Jun 9.

The Wistar Institute, Philadelphia, PA, United States.

A disruption of the crosstalk between the gut and the lung has been implicated as a driver of severity during respiratory-related diseases. Lung injury causes systemic inflammation, which disrupts gut barrier integrity, increasing the permeability to gut microbes and their products. This exacerbates inflammation, resulting in positive feedback. We aimed to test whether severe Coronavirus disease 2019 (COVID-19) is associated with markers of disrupted gut permeability. We applied a multi-omic systems biology approach to analyze plasma samples from COVID-19 patients with varying disease severity and SARS-CoV-2 negative controls. We investigated the potential links between plasma markers of gut barrier integrity, microbial translocation, systemic inflammation, metabolome, lipidome, and glycome, and COVID-19 severity. We found that severe COVID-19 is associated with high levels of markers of tight junction permeability and translocation of bacterial and fungal products into the blood. These markers of disrupted intestinal barrier integrity and microbial translocation correlate strongly with higher levels of markers of systemic inflammation and immune activation, lower levels of markers of intestinal function, disrupted plasma metabolome and glycome, and higher mortality rate. Our study highlights an underappreciated factor with significant clinical implications, disruption in gut functions, as a potential force that may contribute to COVID-19 severity.
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http://dx.doi.org/10.3389/fimmu.2021.686240DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8219958PMC
July 2021

Alterations in the gut virome in obesity and type 2 diabetes mellitus.

Gastroenterology 2021 Jun 24. Epub 2021 Jun 24.

Center for Gut Microbiota Research, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong, China; Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong, China; Institute of Digestive Disease, State Key Laboratory of Digestive Diseases, LKS Institute of Health Science, The Chinese University of Hong Kong, Hong Kong, China; Microbiota I-Center (MagIC) Limited, Hong Kong, China. Electronic address:

Background & Aims: Obesity and type 2 diabetes mellitus (T2DM) are associated with changes in the gut bacterial composition, but little is known about the role of the viral community (virome) in disease development. This study aims to characterize the gut virome alterations in obese subjects with or without T2DM.

Methods: 128 obese subjects (Body Mass Index (BMI) ≥28Kg/m) and 101 lean controls (BMI ≥ 18.5 and < 23 Kg/m) were recruited from two regions in China (Hong Kong: HK; Kunming: KM). Fecal virome and bacteriome were profiled by shotgun metagenomic sequencing. Gut virome, bacteriome and viral-bacterial correlations were compared between obese subjects and lean controls.

Results: Obese subjects especially those with T2DM (ObT2) had a decreased gut viral richness and diversity compared with lean controls in the HK cohort (p < .05), while no significant differences were observed in the KM cohort. Eleven viruses, including Escherichia phage, Geobacillus phage and Lactobacillus phage were enriched in obese subjects (q < .1). Besides, seventeen differentially abundant viruses were identified between ObT2 and lean controls (q < .1). Further ecological analysis revealed that intensive trans-kingdom correlations between viruses and bacteria observed in lean controls were significantly decreased in ObT2 subjects (p < .001).

Conclusions: Obesity is characterized by altered viral taxonomic composition and weakened viral-bacterial correlations compared with lean controls. Accompanied with T2DM may aggravate the obesity-associated virus signatures, signifying that gut virome may play an important role in the development of obesity and T2DM. Geographic factors also contributed to the variations of gut virome in obesity and T2DM.
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http://dx.doi.org/10.1053/j.gastro.2021.06.056DOI Listing
June 2021

Determination of Phthalates in Marine Sediments Using Ultrasonic Extraction Followed by Dispersive Solid-Phase Extraction and Gas Chromatography-Mass Spectrometry.

J Chromatogr Sci 2021 Jun 22. Epub 2021 Jun 22.

Key Laboratory of Sustainable Utilization of Technology Research for Fisheries Resources of Zhejiang Province, Zhejiang Marine Fisheries Research Institute, Tiyu Road 28, Dinghai District, Zhoushan 316021, Zhejiang, P.R. China.

A simple, rapid and novel method has been developed and validated for determination of 16 phthalates in marine sediment samples by gas chromatography coupled to mass spectrometry. Freeze dried samples were first ultrasonic extraction by n-hexane:methylene chloride (1:1, v/v) and n-hexane:ethyl acetate (1:1, v/v) and followed by dispersive solid-phase extraction cleanup. The linearity of this method ranged from 1 to 1,000 μg/L, with regression coefficients ranging between 0.9993 and 0.9999. The limits of detection were in ng/g level, ranging between 0.1 and 0.25 ng/g (dry weight). The concentration of the total phthalates in marine sediment samples from Waters of Dongji (Zhoushan, China), Yueqing Bay (Wenzhou, China) and Coastal Waters of Yuhuan (Taizhou, China) ranged from 235.4 to 608.7 μg/kg with diisobutyl phthalate, dibutyl phthalate and di(2-ethylhexyl) phthalate being the major species, which constitutes of 94.6 and 98.1% of the total phthalates. The recoveries of spiked 16 phthalates at different concentration levels in sediment sample 3 of Waters of Dongji (Zhoushan, China) and sediment sample 3 of Yueqing bay (Wenzhou, China) were in the range of 78-117% and 83-114%, respectively, with relative standard deviations of 2.4-6.8% and 3.4-7.5% (n = 5), respectively. The performance of the proposed method was also compared with traditional Soxhlet extraction and column chromatography cleanup on the same genuine sediment samples and comparable efficiencies were obtained. It is concluded that this method can be successfully applied for the determination of phthalates in different marine sediment samples.
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http://dx.doi.org/10.1093/chromsci/bmab080DOI Listing
June 2021

Smoking increases oral mucosa susceptibility to Candida albicans infection via the Nrf2 pathway: In vitro and animal studies.

J Cell Mol Med 2021 Jun 21. Epub 2021 Jun 21.

Nanjing Stomatological Hospital & State Key Laboratory of Analytical Chemistry for Life Science, Medical School, Nanjing University, Nanjing, China.

Smoking and Candida albicans (C. albicans) infection are risk factors for many oral diseases. Several studies have reported a close relationship between smoking and the occurrence of C. albicans infection. However, the exact underlying mechanism of this relationship remains unclear. We established a rat infection model and a C. albicans-Leuk1 epithelial cell co-culture model with and without smoke exposure to investigate the mechanism by which smoking contributes to C. albicans infection. Oral mucosa samples from healthy individuals and patients with oral leucoplakia were also analysed according to their smoking status. Our results indicated that smoking induced oxidative stress and redox dysfunction in the oral mucosa. Smoking-induced Nrf2 negatively regulated the NLRP3 inflammasome, impaired the oral mucosal defence response and increased the oral mucosa susceptibility to C. albicans. The results suggest that the Nrf2 pathway could be involved in the pathogenesis of oral diseases by mediating an antioxidative response to cigarette smoke exposure and suppressing host immunity against C. albicans.
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http://dx.doi.org/10.1111/jcmm.16724DOI Listing
June 2021

Agreement and Accuracy of Ischemic Core Volume Evaluated by Three CT Perfusion Software Packages in Acute Ischemic Stroke.

J Stroke Cerebrovasc Dis 2021 Aug 18;30(8):105872. Epub 2021 Jun 18.

Department of Interventional Radiology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China. Electronic address:

Purpose: To compare the ischemic core volume estimated by CT Perfusion 4D and Vue PACS with that estimated by RAPID software in acute ischemic stroke (AIS).

Materials And Methods: CT perfusion data from AIS patients were retrospectively post-processed with RAPID, CT Perfusion 4D and Vue PACS software. The Vue PACS application included three different settings: method A (Circular Singular Value Decomposition), method B (Oscillating index Singular Value Decomposition) and method C (Standard Singular Value Decomposition). Bland-Altman analysis, intraclass correlation coefficients (ICCs) and Kappa analysis were used to evaluate concordance between estimated ischemic core values. Final infarct volume (FIV) was measured by follow-up non-contrast CT or MRI 5-7 days after mechanical thrombectomy (MT) in patients with successful recanalization.

Results: A total of 82 patients were included in the study. Concordance with RAPID ranged from good (method B: ICC 0.780; method C: ICC 0.852) to excellent (CT perfusion 4D: ICC 0.950; method A: ICC 0.954). The limits of agreement (-32.3, 41.8 mL) were the narrowest with method A. For detecting core volumes ≤ 70 ml, method A and CT perfusion 4D showed almost perfect concordance with RAPID (CT perfusion 4D, kappa=0.87; method A, kappa=0.87), whereas methods B and C showed substantial concordance with RAPID (method B, kappa=0.77; method C, kappa =0.73). Thirty-two patients had good reperfusion after MT. RAPID showed the highest accuracy for predicting FIV, followed by method A.

Conclusion: CT perfusion 4D and Vue PACS method A showed excellent concordance with RAPID for quantifying ischemic core volume, which can be considered as alternatives in selecting patients for MT in clinical practice.
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http://dx.doi.org/10.1016/j.jstrokecerebrovasdis.2021.105872DOI Listing
August 2021

Sneezing reflex is mediated by a peptidergic pathway from nose to brainstem.

Cell 2021 Jul 15;184(14):3762-3773.e10. Epub 2021 Jun 15.

Department of Anesthesiology, Center for the Study of Itch and Sensory Disorders, and Washington University Pain Center, Washington University School of Medicine, St. Louis, MO 63110, USA; Division of Dermatology, Department of Medicine, Washington University School of Medicine, St. Louis, MO 63110, USA; Department of Ophthalmology & Visual Sciences, Washington University School of Medicine, St. Louis, MO 63110, USA; Department of Neuroscience, Washington University School of Medicine, St. Louis, MO 63110, USA. Electronic address:

Sneezing is a vital respiratory reflex frequently associated with allergic rhinitis and viral respiratory infections. However, its neural circuit remains largely unknown. A sneeze-evoking region was discovered in both cat and human brainstems, corresponding anatomically to the central recipient zone of nasal sensory neurons. Therefore, we hypothesized that a neuronal population postsynaptic to nasal sensory neurons mediates sneezing in this region. By screening major presynaptic neurotransmitters/neuropeptides released by nasal sensory neurons, we found that neuromedin B (NMB) peptide is essential for signaling sneezing. Ablation of NMB-sensitive postsynaptic neurons in the sneeze-evoking region or deficiency in NMB receptor abolished the sneezing reflex. Remarkably, NMB-sensitive neurons further project to the caudal ventral respiratory group (cVRG). Chemical activation of NMB-sensitive neurons elicits action potentials in cVRG neurons and leads to sneezing behavior. Our study delineates a peptidergic pathway mediating sneezing, providing molecular insights into the sneezing reflex arc.
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http://dx.doi.org/10.1016/j.cell.2021.05.017DOI Listing
July 2021
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