Publications by authors named "Xiaobin Zheng"

96 Publications

Transformation of a cold to hot tumor and a durable response to immunotherapy in a patient with non-small cell lung cancer after chemoradiotherapy: a case report.

Ann Palliat Med 2021 Apr;10(4):4982-4986

Department of Thoracic Oncology, Fujian Cancer Hospital and Fujian Medical University Cancer Hospital, Fuzhou, China.

Immune checkpoint inhibitors (ICIs) have become an important milestone in the treatment of non-small cell lung cancer (NSCLC). High expression of protein ligand 1 (PD-L1) and tumor mutation burden (TMB) can help to select the dominant population for immunotherapy, but the expression of PD-L1 does not seem to be unchanged. A 61-year-old man with adenocarcinoma of the lung experienced postoperative recurrence. PD-L1 expression was negative before recurrence, and TMB was stable by next-generation sequencing (NGS) test. However, after radiotherapy and chemotherapy, PD-L1 positive expression was found in a re-biopsy specimen, and NGS detection indicated the loss of immune negative predictive genes. The patient achieved a durable response to a posterior-line immunotherapy combined chemotherapy. The tumor microenvironment maybe changed after chemoradiotherapy, which provides an opportunity for patients to benefit from immunotherapy. The use of NGS in dynamic detection and PD-L1 expression may help monitor this change in the tumor microenvironment, the transition from cold to hot tumor. This case maybe provides new clinical evidence that a non-immuno-dominant population in the initial state can be converted to a population with the benefit of immunotherapy after chemoradiotherapy. However, patients who are initially unsuitable for immunotherapy may still need to undergo combined immunotherapy to achieve a clinical benefit.
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http://dx.doi.org/10.21037/apm-21-761DOI Listing
April 2021

Insecticide Resistance Monitoring of the Diamondback Moth (Lepidoptera: Plutellidae) Populations in China.

J Econ Entomol 2021 Jun;114(3):1282-1290

Institute of Vegetables and Flowers, Chinese Academy of Agricultural Sciences, Beijing, P.R. China.

The diamondback moth, Plutella xylostella L., is a worldwide crop pest that is difficult to control because of its ability to develop resistance to many insecticides. To provide a reference for resistance management of P. xylostella in China, the present study used a leaf-dip bioassay to monitor the resistance of P. xylostella to nine insecticides in eight regions of China. The results showed that P. xylostella had developed a high level of resistance to beta-cypermethrin (resistance ratio [RR] > 112), and moderate (RR < 40) to high levels of resistance to indoxacarb, abamectin, and chlorfluazuron. For chlorantraniliprole, RRs > 100 were found in Midu (Yunnan Province) and Jinghai (Tianjin). In most regions, the resistance to spinetoram and chlorfenapyr and Bacillus thuringiensis (Bt) was low. No resistance was detected to diafenthiuron. Overall, P. xylostella resistance to insecticides was higher in Midu than in other regions. The data in this study should help guide the selection of insecticides for management of P. xylostella in China.
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http://dx.doi.org/10.1093/jee/toab027DOI Listing
June 2021

Clinical characteristics and overall survival prognostic nomogram for invasive cribriform carcinoma of breast: a SEER population-based analysis.

BMC Cancer 2021 Feb 16;21(1):168. Epub 2021 Feb 16.

Department of Breast Surgery, Fujian Medical University Union Hospital, Fuzhou, 350001, Fujian Province, China.

Background: The prognositc factors in patient with invasive cribriform carcinoma (ICC) of breast is still remain controversal. The study aims to establish a nomogram to predict the survival outcomes in patients with ICC based on the Surveillance, Epidemiology and End Results (SEER) database.

Methods: We retrieved SEER database for clinical data about patients including ICC and infiltrating ductal carcinoma (IDC) from 2004 to 2015. Kaplan-Meier survival was used to compare the difference survival outcomes between ICC and IDC. ICC patients were randomly allocated to training cohort and validation cohort. A nomogram was built to predict individual patient's 3-year and 5-year survival status for ICC. The established TMN model and the newly established nomogram was further evaluated by the concordance index (C-index) and the decision curve analysis (DCA).

Results: Comparing the baseline clinical data between IDC and ICC, a significant of smaller tumor mass, less infiltrated lymph nodes, lower metastases rate, better tumor differentiation degree, higher proportion of estrogen receptor (ER) and progesterone receptor (PR) positive and lower rate of chemotherapy and radiotherapy was found in ICC. Age at diagnosis, marriage status, tumor location, T stage, M stage, ER status, surgery were independent significant prognostic factors for the overall survival (OS). A significantly higher C-index was found in nomogram compared with established TNM model in validation cohort.

Conclusions: The prognosis of ICC patients is better than that of IDC patients. The nomogram is recommended for future patient with ICC to survival analysis.
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http://dx.doi.org/10.1186/s12885-021-07895-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7887783PMC
February 2021

Successful Sequential Treatment for Severe Asthma Coexisting COVID-19 via Budesonide/Glycopyrrolate/Formoterol Fumarate.

Int J Gen Med 2021 4;14:357-359. Epub 2021 Feb 4.

Department of Pulmonary and Critical Care Medicine (PCCM), The Fifth Affiliated Hospital of Sun Yat-Sen University, Zhuhai, People's Republic of China.

Awareness of the management of coronavirus disease 2019 (COVID-19) and airway diseases can effectively help clinical physician during the coronavirus pandemic. Herein, we elucidated a COVID-19 case coexisting with severe asthma. Budesonide/glycopyrrolate/formoterol fumarate (BGF) was used as sequential medicine to systemic glucocorticoids for his persisted symptoms related to bronchospasms. Our case suggests patients with long-term airway diseases like asthma probably attribute their symptoms to COVID-19 instead of primary diseases, which make it more difficult in the symptom control. BGF is able to be an effective and convenient choice as sequential medicine to systemic glucocorticoids in some refractory asthmatic patients complicated with COVID-19.
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http://dx.doi.org/10.2147/IJGM.S291695DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7869710PMC
February 2021

Multiple combination therapy based on intrathecal pemetrexed in non-small cell lung cancer patients with refractory leptomeningeal metastasis.

Ann Palliat Med 2020 Nov;9(6):4233-4245

Department of Thoracic Oncology, Fujian Cancer Hospital and Fujian Medical University Cancer Hospital, Fuzhou, China.

Background: Leptomeningeal metastasis (LM) is a fatal complication, and its incidence is increasing in non-small cell lung cancer (NSCLC). Refractory LM (rLM) has become problematic due to the lack of uniform definition and standardized treatment guidelines. In this study, we assessed the efficacy and safety of multiple therapy based on intrathecal pemetrexed (IP) in patients with rLM in NSCLC.

Methods: From March 2019 to June 2020, patients with cytologically confirmed rLM who received IP and systemic salvage therapy were retrospectively analyzed. Our objectives were to assess progression-free survival (PFS), overall survival (OS), clinical response, and safety. Clinical response was assessed by an investigator according to the Response Assessment in Neuro-Oncology (RANO) proposal criteria. We performed next generation sequencing (NGS) of cerebrospinal fluid (CSF) to explore the gene profile of rLM.

Results: A total of 23 patients were enrolled, and the genetic status of the primary tissue was 16 epidermal growth factor receptor (EGFR) mutations (69.6%), two anaplastic lymphoma kinase (ALK) fusions (8.7%), one ROS proto-oncogene 1 (ROS1) fusion (4.3%), one Erb-B2 receptor tyrosine kinase 2 (ERBB2) mutation (4.3%), and three wild-type (13.0%). On the basis of IP therapy, 19 patients were rechallenged with tyrosine-kinase inhibitors (TKIs), 10 patients were treated with systemic chemotherapy, 10 patients were treated with antivascular therapy, one patient was treated with immunotherapy, and one patient was treated with whole-brain radiotherapy (WBRT). Thirteen patients received two or more of the aforementioned combination treatment modes. The median PFS (mPFS) was 9.6 months [95% confidence interval (CI): 3.4-15.8 months]. OS was not mature at the final follow-up. The clinical assessment was: response in eight patients (34.8%), stable in 11 patients (47.8%), worse in two patients (8.7%), and non-evaluable in two patients (8.7%). Adverse events (AEs) related to any component occurred in 14 patients (60.9%). The driver mutation status was highly consistent between the CSF and primary tumor samples (14/14), but we detected EGFR mutations in the CSF of two patients whose primary tumor samples tested wild-type.

Conclusions: IP-based multimodal therapy has significant efficacy and a controlled safety profile in patients with rLM in NCSLC.
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http://dx.doi.org/10.21037/apm-20-2086DOI Listing
November 2020

Extracellular vesicle-encapsulated microRNA-425-derived from drug-resistant cells promotes non-small-cell lung cancer progression through DAPK1-medicated PI3K/AKT pathway.

J Cell Physiol 2021 May 30;236(5):3808-3820. Epub 2020 Nov 30.

State Key Laboratory of Respiratory Disease, Department of Thoracic Surgery and Oncology, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, China.

Investigations in the area of tumor-derived extracellular vesicles (EVs) open a new horizon in developing cancer biology and its potential as cancer biomarkers. Following this prospect, we aimed to identify that the role of successfully isolated EVs from drug-resistance cells in the progression of non-small-cell lung cancer (NSCLC). P-EVs and R-EVs secreted by A549 cells and drug-resistant A549-R cells respectively were extracted and characterized. The targeting relationship between miR-425 and MED1 was verified. Cell proliferation, invasion, migration and apoptosis after treatment of P-EVs, R-EVs, miR-425 inhibitor, miR-425 mimic, pcDNA-MED1, or phosphatidylinositol-3-kinase (PI3K)/AKT inhibitor LY294002 were detected. Furthermore, xenograft tumor in nude mice was established for further confirming our in vitro findings. P-EVs and R-EVs were successfully extracted and could be internalized by A549 cells. A549-R cells and R-EVs showed higher miR-425 expression compared with A549 cells and P-EVs, respectively. miR-425 delivered by R-EVs could promote the proliferation, migration, and invasion, while inhibit apoptosis of NSCLC cells. MED1 was the target gene of miR-425. EVs-encapsulated miR-425-derived from A549-R cells could promote the progression of NSCLC in vivo through regulating DAPK1-medicated PI3K/AKT pathway. Moreover, miR-425 delivered by R-EVs promoted tumorigenesis in vivo. Taken together, the result suggested that EVs-delivered miR-425-derived from A549-R cells promoted the progression of NSCLC through regulating DAPK1-medicated PI3K/AKT signaling pathway.
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http://dx.doi.org/10.1002/jcp.30126DOI Listing
May 2021

Hyperlipidaemic acute pancreatitis complicated with multiple deep vein thromboses and pulmonary embolism: a case successfully salvaged by radiologic intervention.

Curr Med Res Opin 2021 Jan 3;37(1):53-57. Epub 2020 Dec 3.

Department of Gastroenterology, Shantou Central Hospital, Shantou, China.

Acute pancreatitis complicated with pulmonary embolism has been described in literature, however, hyperlipidaemic acute pancreatitis complicated with pulmonary embolism and deep vein thrombosis has rarely been reported. We reported here a rare case of hyperlipidaemic acute pancreatitis. Although he had undergone plasmapheresis and his TG level reduced to normal range with symptoms relieved, he developed pulmonary embolism and multiple deep vein thromboses. The patient was diagnosed early and successfully salvaged by interventional radiology and oral anticoagulants. The patient was a 51-year-old man, he experienced a sudden upper abdomen pain for 24 h before being admitted to a local hospital where diagnosis of acute pancreatitis was made, and he had no relief of the symptoms after treatment. The patient was a non-smoker and did not consume alcohol. He had no history of diabetes, gallstones or cholelithasis. After transferring to our unit, the patient was treated with plasmapheresis along with low molecular weight heparin, insulin, antibiotics and proton pump inhibitors and the abdomen pain was alleviated gradually. However, 8 days after admission, the patient developed a sudden chest tightness and shortness of breath. Examination revealed a high level of D-dimer (16700 ug/L), a computer tomography angiography of chest revealed pulmonary embolism. Urokinase was started intravenously. Pulmonary angiography and venography demonstrated pulmonary embolism and extensive lower limb deep vein thrombosis. Catheter directed thrombolysis and urokinase was initiated through catheter followed by an IVC filter implantation. Dyspnea of the patient got well with thrombolytic treatment and anticoagulation therapy. This is a rare case of hyperlipidaemic acute pancreatitis complicated pulmonary embolism and Deep vein thrombosis even after treated with plasmapheresis. The case we present here will aid in its early recognition, interventional radiology hence the prevention for this rare but catastrophic complication.
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http://dx.doi.org/10.1080/03007995.2020.1854702DOI Listing
January 2021

Comprehensive Assessment of Diet Quality and Risk of Precursors of Early-Onset Colorectal Cancer.

J Natl Cancer Inst 2021 May;113(5):543-552

Division of Public Health Sciences, Department of Surgery, Washington University School of Medicine, St. Louis, MO, USA.

Background: The role of poor diet quality in the rising incidence of colorectal cancer (CRC) diagnosed younger than age 50 years has not been explored. Based on molecular features of early-onset CRC, early-onset adenomas are emerging surrogate endpoints.

Methods: In a prospective cohort study (Nurses' Health Study II), we evaluated 2 empirical dietary patterns (Western and prudent) and 3 recommendation-based indexes (Dietary Approaches to Stop Hypertension [DASH], Alternative Mediterranean Diet [AMED], and Alternative Healthy Eating Index [AHEI]-2010) with risk of early-onset adenoma overall and by malignant potential (high-risk: ≥1 cm, tubulovillous or villous histology, high-grade dysplasia, or ≥3 adenomas), among 29 474 women with 1 or more lower endoscopy before age 50 years (1991-2011). Multivariable logistic regressions were used to estimate odds ratios (ORs) and 95% confidence intervals (CIs).

Results: We documented 1157 early-onset adenomas with 375 at high risk. Western diet was positively associated, whereas prudent diet, DASH, AMED, and AHEI-2010 were inversely associated with risk of early-onset adenoma. The associations were largely confined to high-risk adenomas (the highest vs lowest quintile: Western, OR = 1.67, 95% CI = 1.18 to 2.37; prudent, OR = 0.69, 95% CI = 0.48 to 0.98; DASH, OR = 0.65, 95% CI = 0.45 to 0.93; AMED, OR = 0.55, 95% CI = 0.38 to 0.79; AHEI-2010, OR = 0.71, 95% CI = 0.51 to 1.01; all Ptrend ≤ .03), driven by those identified in the distal colon and rectum (all Ptrend ≤ .04, except AMED: Ptrend = .14).

Conclusion: Poor diet quality was associated with an increased risk of early-onset distal and rectal adenomas of high malignant potential. These findings provide preliminary but strong support to the role of diet in early-onset CRC.
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http://dx.doi.org/10.1093/jnci/djaa164DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8096368PMC
May 2021

The psychological status of frontline health workers confronting COVID-19 after local cases eradication in Zhuhai, Southern China.

Eur Arch Psychiatry Clin Neurosci 2021 Mar 1;271(2):403-404. Epub 2020 Nov 1.

Department of Pulmonary and Critical Care Medicine (PCCM), Fifth Affiliated Hospital of Sun Yat-Sen University, 52 East Meihua Rd, Zhuhai City, 519000, China.

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http://dx.doi.org/10.1007/s00406-020-01204-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7603895PMC
March 2021

TLT2 Suppresses Th1 Response by Promoting IL-6 Production in Monocyte Through JAK/STAT3 Signal Pathway in Tuberculosis.

Front Immunol 2020 11;11:2031. Epub 2020 Sep 11.

Center for Infection and Immunity, The Fifth Affiliated Hospital, Sun Yat-sen University, Zhuhai, China.

The function of triggering receptor expressed on myeloid cell-like transcript 2 (TLT2) has not been characterized and their role in pulmonary tuberculosis (TB) remains unclear. In this study, we found that surface TLT2 was up-regulated in human monocytes of patients with active TB compared to healthy subjects. , TLT2 expression was induced in human monocyte cell line THP-1 cells after bacillus Calmette-Guérin (BCG) or () H37Rv infection. Knockdown of TLT2 by siRNA transfection suppressed IL-6 expression, whereas over-expression of TLT2 increased IL-6 production in THP-1 cells infected by H37Rv. TLT2CD14 monocytes produced higher level of IL-6 compared to TLT2 subset in active TB patients. Western blot and immunocoprecipitation revealed that TLT2 interacted with kinase JAK1/JAK2/Tyk2 to enhance STAT3 phosphorylation. Moreover, we showed that tyrosine residues 297 and 315 of TLT2 cytoplasmic domain were involved in STAT3 activation. In monocyte/CD4 T cell co-culture assay, blockage of TLT2 fusion protein facilitated IFN-γ production by CD4 T cells. Plate count assay showed that monocyte-mediated bacterial killing was promoted by TLT2 fusion protein. treatment with TLT-2 fusion protein reduced IL-6 production by macrophage but increased IFN-γ production by CD4 T cell in H37Rv and BCG infected mice. Furthermore, TLT2 fusion protein attenuated inflammation, and reduced bacterial load in lung of infected mice. Together, these findings demonstrate that TLT2 negatively regulates Th1 response against mycobacterial infection, which promotes IL-6 production through JAK/STAT3 signal pathway.
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http://dx.doi.org/10.3389/fimmu.2020.02031DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7516513PMC
April 2021

Metabolic syndrome, metabolic comorbid conditions and risk of early-onset colorectal cancer.

Gut 2021 Jun 9;70(6):1147-1154. Epub 2020 Oct 9.

Division of Public Health Sciences, Department of Surgery, Washington University School of Medicine in Saint Louis, Saint Louis, Missouri, USA

Objective: Factors that lead to metabolic dysregulation are associated with increased risk of early-onset colorectal cancer (CRC diagnosed under age 50). However, the association between metabolic syndrome (MetS) and early-onset CRC remains unexamined.

Design: We conducted a nested case-control study among participants aged 18-64 in the IBM MarketScan Commercial Database (2006-2015). Incident CRC was identified using pathologist-coded International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) codes, and controls were frequency matched. MetS was defined as presence of ≥3 conditions among obesity, hypertension, hyperlipidaemia and hyperglycaemia/type 2 diabetes, based on ICD-9-CM and use of medications. Multivariable logistic regressions were used to estimate ORs and 95% CIs.

Results: MetS was associated with increased risk of early-onset CRC (n=4673; multivariable adjusted OR 1.25; 95% CI 1.09 to 1.43), similar to CRC diagnosed at age 50-64 (n=14 928; OR 1.21; 95% CI 1.15 to 1.27). Compared with individuals without a metabolic comorbid condition, those with 1, 2 or ≥3 conditions had a 9% (1.09; 95% CI 1.00 to 1.17), 12% (1.12; 95% CI 1.01 to 1.24) and 31% (1.31; 95% CI 1.13 to 1.51) higher risk of early-onset CRC (p <0.001). No associations were observed for one or two metabolic comorbid conditions and CRC diagnosed at age 50-64. These positive associations were driven by proximal (OR per condition 1.14; 95% CI 1.06 to 1.23) and distal colon cancer (OR 1.09; 95% CI 1.00 to 1.18), but not rectal cancer (OR 1.03; 95% CI 0.97 to 1.09).

Conclusions: Metabolic dysregulation was associated with increased risk of early-onset CRC, driven by proximal and distal colon cancer, thus at least in part contribute to the rising incidence of early-onset CRC.
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http://dx.doi.org/10.1136/gutjnl-2020-321661DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8032822PMC
June 2021

A microfluidic cell-migration assay for the prediction of progression-free survival and recurrence time of patients with glioblastoma.

Nat Biomed Eng 2021 01 28;5(1):26-40. Epub 2020 Sep 28.

Department of Chemical and Biomolecular Engineering, Johns Hopkins University, Baltimore, MD, USA.

Clinical scores, molecular markers and cellular phenotypes have been used to predict the clinical outcomes of patients with glioblastoma. However, their clinical use has been hampered by confounders such as patient co-morbidities, by the tumoral heterogeneity of molecular and cellular markers, and by the complexity and cost of high-throughput single-cell analysis. Here, we show that a microfluidic assay for the quantification of cell migration and proliferation can categorize patients with glioblastoma according to progression-free survival. We quantified with a composite score the ability of primary glioblastoma cells to proliferate (via the protein biomarker Ki-67) and to squeeze through microfluidic channels, mimicking aspects of the tight perivascular conduits and white-matter tracts in brain parenchyma. The assay retrospectively categorized 28 patients according to progression-free survival (short-term or long-term) with an accuracy of 86%, predicted time to recurrence and correctly categorized five additional patients on the basis of survival prospectively. RNA sequencing of the highly motile cells revealed differentially expressed genes that correlated with poor prognosis. Our findings suggest that cell-migration and proliferation levels can predict patient-specific clinical outcomes.
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http://dx.doi.org/10.1038/s41551-020-00621-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7855796PMC
January 2021

Assessing Pesticide Residue and Spray Deposition in Greenhouse Eggplant Canopies to Improve Residue Analysis.

J Agric Food Chem 2020 Oct 13;68(43):11920-11927. Epub 2020 Oct 13.

Department of Plant Protection, Institute of Vegetables and Flowers, Chinese Academy of Agricultural Sciences, Beijing 100081, China.

Pesticide residue analysis is critically important for ensuring food safety and regulating international trade. In a greenhouse setting, we assessed pesticide residue and exposure patterns using liquid chromatography-mass spectrometry and Allura Red tracer analysis. Our results show significant effects of eggplant canopy position and spray concentration on deposition parameters. Specifically, spray coverage, spray density, deposition, and residue were generally greater for leaves in the higher canopy. Deposition and residue, unlike spray coverage and spray density, linearly correlated with spray concentration. Pesticide residues on leaves linearly correlated with depositions on artificial targets, and a correction factor was constructed to estimate residues from tracer depositions. This comparative analysis suggests that tracer analysis using Allura Red in combination with artificial targets is a time- and cost-saving alternative to conventional residue analysis for assessing spray parameters under high-volume spraying scenarios. A better understanding of pesticide residue and spray patterns will not only enhance the safety of our food supply chain but also improve pest control efficacy within the sustainable integrated pest management framework.
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http://dx.doi.org/10.1021/acs.jafc.0c04082DOI Listing
October 2020

Effect of Infection on the Microbial Composition of Upper Airway.

Infect Drug Resist 2020 31;13:2637-2640. Epub 2020 Jul 31.

Department of Pulmonary and Critical Care Medicine (PCCM), The Fifth Affiliated Hospital of Sun Yat-sen University, Zhuhai, People's Republic of China.

Methods: Forty-four COVID-19 patients (severe/critical: N = 8, non-severe: N = 36) were examined by next generation sequencing (NGS) of nasopharyngeal test paper to observe the effect of novel coronavirus infection to the microbial composition in upper airway.

Results: In these nasopharyngeal test paper samples, 38 kinds of bacteria, 10 kinds of viruses except , nine kinds of fungi and three kinds of atypical pathogens had been found. There was some difference in microbial composition in the upper airway between severe and non-severe cases.

Summary: These results are important for us to study the effect of on the local microbial composition of upper airway and prevent opportunistic infection in severe patients.
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http://dx.doi.org/10.2147/IDR.S259984DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7406177PMC
July 2020

Upper Gastrointestinal Bleeding Caused by SARS-CoV-2 Infection.

Am J Gastroenterol 2020 09;115(9):1541-1542

Guangdong Provincial Key Laboratory of Biomedical Imaging, the Fifth Affiliated Hospital, Sun Yat-sen University, Zhuhai, Guangdong, China.

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http://dx.doi.org/10.14309/ajg.0000000000000757DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7396212PMC
September 2020

Maternal microbiome regulation prevents early allergic airway diseases in mouse offspring.

Pediatr Allergy Immunol 2020 11 28;31(8):962-973. Epub 2020 Jul 28.

Department of Clinical Laboratory, The Second Hospital of Jilin University, Changchun, China.

Background: Asthma is a serious global health problem, severely affecting the lives of sufferers and their families. An exceptionally hygienic home and reduced microbial exposure can aggravate the incidence of childhood asthma.

Methods: Specific-pathogen-free BALB/c mice were pre-treated with bacterial lysate (BL; 1 mg/kg) as a high microbial load maternal mouse model, and then, the offspring mice were established as an allergic airway disease (AAD) model. The expression levels of TLR2, TLR4, and HDAC9 in the mother's intestine and the offspring's lungs were detected. Relevant indicators of regulatory T cells (Tregs) were identified in the mother and offspring mice. The changes in the expression of Th1-, Th2-, Th9-, and Th17-related cytokines in the offspring mice were evaluated among different pre-treated groups.

Results: After augmenting the mothers' intestinal microbiota through oral BL gavage, the expression of TLR2 and TLR4 in the colon mucosa and colon lymphoid tissues was enhanced and that of HDAC9 in the colon mucosa was decreased, and the proportion of spleen Tregs was increased. The offspring showed similar changes in the AAD model compared with the offspring of the control-group mothers: TLR2 and TLR4 expression in the lungs and the proportion of spleen Tregs increased, HDAC9 expression in the lungs decreased, and AAD-induced airway pathologic characteristics were reversed; additionally, Th1/Th2 and Th9 imbalances were rectified.

Conclusions: This study presents a new framework for the prevention of childhood asthma, elucidating the mechanism of regulating the mother's intestinal microbiome to protect the offspring's early asthma via animal experiments.
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http://dx.doi.org/10.1111/pai.13315DOI Listing
November 2020

Lineage dynamics of the endosymbiotic cell type in the soft coral Xenia.

Nature 2020 06 17;582(7813):534-538. Epub 2020 Jun 17.

Department of Embryology, Carnegie Institution for Science, Baltimore, MD, USA.

Many corals harbour symbiotic dinoflagellate algae. The algae live inside coral cells in a specialized membrane compartment known as the symbiosome, which shares the photosynthetically fixed carbon with coral host cells while host cells provide inorganic carbon to the algae for photosynthesis. This endosymbiosis-which is critical for the maintenance of coral reef ecosystems-is increasingly threatened by environmental stressors that lead to coral bleaching (that is, the disruption of endosymbiosis), which in turn leads to coral death and the degradation of marine ecosystems. The molecular pathways that orchestrate the recognition, uptake and maintenance of algae in coral cells remain poorly understood. Here we report the chromosome-level genome assembly of a Xenia species of fast-growing soft coral, and use this species as a model to investigate coral-alga endosymbiosis. Single-cell RNA sequencing identified 16 cell clusters, including gastrodermal cells and cnidocytes, in Xenia sp. We identified the endosymbiotic cell type, which expresses a distinct set of genes that are implicated in the recognition, phagocytosis and/or endocytosis, and maintenance of algae, as well as in the immune modulation of host coral cells. By coupling Xenia sp. regeneration and single-cell RNA sequencing, we observed a dynamic lineage progression of the endosymbiotic cells. The conserved genes associated with endosymbiosis that are reported here may help to reveal common principles by which different corals take up or lose their endosymbionts.
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http://dx.doi.org/10.1038/s41586-020-2385-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7332420PMC
June 2020

Co-Occurrence of and in Isolated from a Patient with Bloodstream Infection.

Infect Drug Resist 2020 12;13:1397-1402. Epub 2020 May 12.

Department of Microbiology, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou 510080, People's Republic of China.

Background: Bloodstream infection (BSI) caused by carbapenem-resistant Enterobacteriaceae are potentially life-threatening related to poorer outcomes. Colistin is considered one of the last-resort treatments against human infections caused by multidrug-resistant (MDR) Gram-negative bacteria. Therefore, emergence of strains from the blood that co-harboring and carbapenem resistance genes were considered as a serious problem.

Purpose: In this study, two -harboring MDR isolates BSI034 and BSI072 recovered from BSI patients were identified, one of which co-harbored and The genetic characteristics of the MDR plasmid needed to be clarified.

Methods: S1-PFGE and Southern blotting were conducted to determine the location of . Whole-genome sequencing was performed to obtain the complete genome and plasmid sequences. The resistome and virulence genes of the strains, accompanied by the genetic characteristics of - and -harboring plasmids, were analyzed.

Results: Whole-genome sequencing showed that BSI034 harbored -carrying IncHI2-type pBSI034-MCR9 and -carrying IncX3-type pBSI034-NDM1. The 278,517 bp pBSI034-MCR9 carried along with the other 19 resistance genes. was flanked by IS (1057 bp) and IS (820 bp) in the same orientation. In addition to resistance genes, strain BSI034 also carried a chromosome-located high-pathogenicity island, which harbored genes of yersiniabactin biosynthesis operon , and .

Conclusion: We described the complete genome and /-co-harboring plasmid of from a BSI patient. Notable differences were observed within mosaic modules between pBSI034-MCR9 and other -harboring plasmids due to extensive recombination via horizontal gene transfer.
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http://dx.doi.org/10.2147/IDR.S248342DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7229791PMC
May 2020

Successful use of methylprednisolone for treating severe COVID-19.

J Allergy Clin Immunol 2020 08 29;146(2):325-327. Epub 2020 May 29.

Department of Pulmonary and Critical Care Medicine, The Fifth Affiliated Hospital of Sun Yat-sen University, Zhuhai, China; Guangdong Provincial Key Laboratory of Biomedical Imaging and Guangdong Provincial Engineering Research Center of Molecular Imaging, The Fifth Affiliated Hospital of Sun Yat-sen University, Zhuhai, China. Electronic address:

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http://dx.doi.org/10.1016/j.jaci.2020.05.021DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7256545PMC
August 2020

Maize and Genes Have Overlapping and Distinct Functions in Cuticular Lipid Deposition.

Plant Physiol 2020 07 19;183(3):840-853. Epub 2020 May 19.

Roy J. Carver Department of Biochemistry, Biophysics and Molecular Biology, Iowa State University, Ames, Iowa

Plant epidermal cells express unique molecular machinery that juxtapose the assembly of intracellular lipid components and the unique extracellular cuticular lipids that are unidirectionally secreted to plant surfaces. In maize (), mutations at the locus affect the deposition of extracellular cuticular lipids. Sequence-based genome scanning identified a new homolog in the maize genome, namely Both the and genes are members of the BAHD superfamily of acyltransferases, with close sequence similarity to the Arabidopsis () gene. Transgenic experiments demonstrated that and functionally complement the Arabidopsis mutation, with differential influences on the cuticular lipids and the lipidome of the plant, particularly affecting the longer alkyl chain acyl lipids, especially at the 32-carbon chain length. Site-directed mutagenesis of the putative BAHD catalytic HXXXDX-motif indicated that requires this catalytic capability to fully complement the function, but can accomplish complementation without the need for this catalytic motif. These findings demonstrate that and overlap in their cuticular lipid function, but have evolutionarily diverged to acquire nonoverlapping functions.
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http://dx.doi.org/10.1104/pp.20.00241DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7333722PMC
July 2020

Household Transmission of SARS-CoV-2, Zhuhai, China, 2020.

Clin Infect Dis 2020 11;71(16):2099-2108

Department of Pulmonary and Critical Care Medicine, Fifth Affiliated Hospital of Sun Yat-sen University, Zhuhai, China.

Background: To illustrate the extent of transmission, identify affecting risk factors and estimate epidemiological modeling parameters of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in household setting.

Methods: We enrolled 35 confirmed index cases and their 148 household contacts, January 2020-February 2020, in Zhuhai, China. All participants were interviewed and asked to complete questionnaires. Household contacts were then prospectively followed active symptom monitoring through the 21-day period and nasopharyngeal and/or oropharyngeal swabs were collected at 3-7 days intervals. Epidemiological, demographic, and clinical data (when available) were collected.

Results: Assuming that all these secondary cases were infected by their index cases, the second infection rate in household context is 32.4% (95% confidence interval [CI]: 22.4%-44.4%), with 10.4% of secondary cases being asymptomatic. Multivariate analysis showed that household contacts with underlying medical conditions, a history of direct exposure to Wuhan and its surrounding areas, and shared vehicle with an index patient were associated with higher susceptibility. Household members without protective measures after illness onset of the index patient seem to increase the risk for SARS-CoV-2 infection. The median incubation period and serial interval within household were estimated to be 4.3 days (95% CI: 3.4-5.3 days) and 5.1 days (95% CI: 4.3-6.2 days), respectively.

Conclusion: Early isolation of patients with coronavirus disease 2019 and prioritizing rapid contact investigation, followed by active symptom monitoring and periodic laboratory evaluation, should be initiated immediately after confirming patients to address the underlying determinants driving the continuing pandemic.
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http://dx.doi.org/10.1093/cid/ciaa557DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7239243PMC
November 2020

Intestinal CD14+ Macrophages Protect CD4+ T Cells From Activation-induced Cell Death via Exosomal Membrane TNF in Crohn's Disease.

J Crohns Colitis 2020 Nov;14(11):1619-1631

Department of Colorectal Surgery, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, China.

Background And Aims: Sustained activation of CD4+ T cells plays important roles in the pathogenesis of Crohn's disease [CD]. Under physiologic conditions, activated T cells can be timely eliminated by a process termed activation-induced cell death [AICD], restraining T cell over-activation and preventing immunological destruction. We inquired whether defective AICD might explain CD4+ T cell over-activation in CD and investigated the underlying mechanisms.

Methods: CD14+ macrophages [Mφ] and CD4+ T cells were isolated from intestinal tissues or peripheral blood of controls and CD patients. An ex vivo evaluation system was employed to simulate AICD and cell apoptosis was measured by flow cytometry.

Results: CD4+ T cells from CD patients fail to undergo AICD in the ex vivo system. Specifically, proinflammatory type 1 helper T [Th1] and type 17 helper T [Th17] cells, rather than immunosuppressive regulatory T [Treg] cells evade AICD in CD. CD14+ Mφ in the intestinal inflammatory microenvironment of CD promote AICD resistance in CD4+ T cells via a cell-to-cell contact-independent manner. Mechanistically, CD14+ Mφ released exosomes express membrane tumour necrosis factor [TNF] which engages TNFR2 on CD4+ T cells and triggers NF-κB signalling, thereby causing AICD resistance. Importantly, clinically applicable anti-TNF antibodies effectively blocked exosomal membrane TNF-induced CD4+ T cell AICD resistance.

Conclusions: CD14+ Mφ participate in CD pathogenesis by inducing AICD resistance through release of exosomal membrane TNF to activate the TNFR2/NF-κB pathway in CD4+ T cells. These results present new insights into CD pathogenesis and extend mechanistic understanding of anti-TNF agents.

Proposed Model: CD14+ Mφ in the intestinal microenvironment of CD patients maintain the sustained activation of CD4+ T cells through exosomal membrane TNF to induce apoptosis resistance via TNFR2/NF-κB signalling, which could be effectively blocked by clinically applicable anti-TNF agents.
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http://dx.doi.org/10.1093/ecco-jcc/jjaa083DOI Listing
November 2020

Establishing a high microbial load maternal-offspring asthma model in adult mice.

Int Immunopharmacol 2020 Jun 3;83:106453. Epub 2020 Apr 3.

Department of Respiratory and Critical Care Medicine, The Fifth Affiliated Hospital of Sun Yat-Sen University, Zhuhai, Guangdong 519000, PR China. Electronic address:

Background: Although it is widely accepted that the "hygiene hypothesis" explains the increased incidence of asthma, the lack of suitable animal models hinders further in-depth studies of the underlying molecular immune mechanisms. Therefore, we aimed to develop a robust mouse asthma model to investigate the role of bacteria in preventing asthma.

Methods: BALB/c female mice were fed a mixture of eight common bacterial lysates (BL; Broncho-Vaxom®) and a commercial probiotic (Bifidobacterium tetravaccine tablets) at different concentrations before and during pregnancy to simulate different microbial load levels. Faeces from the mother mice were subjected to bacterial 16S rRNA sequencing to quantify the maternal microbial load. TLR2/4 expression and the proportion of regulatory T cells (Tregs) in the intestinal tract of female mice were determined, and the safety of the microbial load was evaluated. An asthma model was established in the offspring mice after weaning, and the extent of pulmonary pathological changes and Treg proportion were evaluated.

Results: A BL concentration of 1 mg/kg enriched the intestinal flora, increased the proportion of Tregs, and increased the expression of TLR2/4 in the maternal mice. The proportion of peripheral blood Tregs was increased, whereas the risk of asthma decreased only in the offspring from mothers with a high microbial load relative to control mice.

Conclusion: This study established a safe and stable high microbial load maternal-offspring mouse asthma model, laying the foundation for a study on the molecular mechanism underlying the protective effects of a high microbial load against asthma.
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http://dx.doi.org/10.1016/j.intimp.2020.106453DOI Listing
June 2020

Tumor-intrinsic CD47 signal regulates glycolysis and promotes colorectal cancer cell growth and metastasis.

Theranostics 2020 4;10(9):4056-4072. Epub 2020 Mar 4.

Department of Colorectal Surgery, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, 510655, China.

: CD47 plays a vital role in the immune escape of tumor cells, but its role in regulating immune-unrelated biological processes such as proliferation and metastasis remains unclear. We seek to explore the immune-independent functions of CD47 in colorectal cancer (CRC). : The expression of CD47 in CRC was determined by immunohistochemistry. The biological effect of CD47 signaling on tumor cell proliferation and metastasis was evaluated and . RNA sequencing analysis was performed to identify pivotal signaling pathways modulated by CD47. The interaction between CD47 and ENO1 was verified by co-immunoprecipitation (co-IP). The effect of CD47 on glycolytic metabolites was analyzed by seahorse XF and targeted metabolomics. : The expression of CD47 was upregulated and correlated to poor prognosis in CRC patients. Functional assays revealed that CD47 promoted CRC cell growth and metastasis and . Our mechanistic investigations demonstrated that CD47 interacted with ENO1 and protected it from ubiquitin-mediated degradation, subsequently promoting glycolytic activity and phosphorylation of ERK in CRC cells. Inhibition of ENO1 diminished CD47-mediated cell growth and migration. Clinically, the combined expression of CD47 and ENO1 provided reliable predictive biomarkers for the prognosis of CRC patients. : CD47 is overexpressed in CRC, and its expression is associated with poor prognosis. Through stabilizing ENO1, CD47 enhances the aerobic glycolysis and ERK activity in CRC cells, thereby promoting the progression of CRC. Our studies reveal an unconventional role of CD47, suggesting that targeting the CD47-ENO1 axis may provide a novel therapeutic avenue for CRC.
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http://dx.doi.org/10.7150/thno.40860DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7086360PMC
May 2021

Screening for Chinese medical staff mental health by SDS and SAS during the outbreak of COVID-19.

J Psychosom Res 2020 06 21;133:110102. Epub 2020 Mar 21.

Department of Pulmonary and Critical Care Medicine (PCCM), The Fifth Affiliated Hospital of Sun Yat-sen University, Zhuhai 519000, China. Electronic address:

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http://dx.doi.org/10.1016/j.jpsychores.2020.110102DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7139244PMC
June 2020

Evidence for Gastrointestinal Infection of SARS-CoV-2.

Gastroenterology 2020 05 3;158(6):1831-1833.e3. Epub 2020 Mar 3.

Guangdong Provincial Engineering Research Center of Molecular Imaging, the Fifth Affiliated Hospital, Sun Yat-sen University, Zhuhai, Guangdong Province, China; Guangdong Provincial Key Laboratory of Biomedical Imaging, the Fifth Affiliated Hospital, Sun Yat-sen University, Zhuhai, Guangdong Province, China; Department of Interventional Medicine, the Fifth Affiliated Hospital, Sun Yat-sen University, Zhuhai, Guangdong Province, China. Electronic address:

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http://dx.doi.org/10.1053/j.gastro.2020.02.055DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7130181PMC
May 2020

Muscle stem cell renewal suppressed by Gas1 can be reversed by GDNF in mice.

Nat Metab 2019 10 30;1(10):985-995. Epub 2019 Sep 30.

Department of Biology, Johns Hopkins University, Baltimore, MD, USA.

Muscle undergoes progressive weakening and regenerative dysfunction with age due in part to the functional decline of skeletal muscle stem cells (MuSCs). MuSCs are heterogeneous but whether their gene expression changes with age and the implication of such changes are unclear. Here we show that in mice, Growth arrest-specific gene 1 (Gas1) is expressed in a small subset of young MuSCs with its expression progressively increasing in larger fractions of MuSCs later in life. Over-expression of Gas1 in young MuSCs and inactivation of Gas1 in aged MuSCs support that Gas1 reduces the quiescence and self-renewal capacity of MuSCs. Gas1 reduces Ret signaling, which is required for MuSC quiescence and self-renewal. Indeed, we show that the Ret ligand, Glial Cell-Derived Neurotrophic Factor (GDNF), can counteract Gas1 by stimulating Ret signaling and enhancing MuSC self-renewal and regeneration, thus improving muscle function. We propose that strategies aimed to target this pathway can be exploited to improve the regenerative decline of muscle stem cells.
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http://dx.doi.org/10.1038/s42255-019-0110-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7000153PMC
October 2019

Association of Hot Tea Consumption with Regional Adiposity Measured by Dual-Energy X-Ray Absorptiometry in NHANES 2003-2006.

Obesity (Silver Spring) 2020 02;28(2):445-451

The Cambridge Centre for Sport and Exercise Sciences, Anglia Ruskin University, Cambridge, UK.

Objective: This study aimed to investigate the potential antiobesity benefits of hot tea consumption at the population level.

Methods: Using data from the National Health and Nutrition Examination Survey (NHANES) 2003-2006, the association between hot tea consumption and dual-energy x-ray-measured body fat was examined in a large representative sample of US adults (n = 5,681, 51.9% women).

Results: Compared with non-tea drinkers, men who consumed 0.25 to 1 cup per day of hot tea had 1.5% (95% CI: 0.4% to 2.6%) and 1.7% (95% CI: 0.4% to 3.0%) less total and trunk body fat, respectively. The associations were stronger among men 45 to 69 years old compared with younger men (20-44 years). For men who consumed 1 or more cups per day of hot tea, lower total (-1.2%, 95% CI: -2.3% to -0.2%) and trunk body fat (-1.3%, 95% CI: -2.6 to -0.1%) was observed among men 45 to 69 years old only. In women, those who drank 1 or more cups per day had 1.5% lower (95% CI: -2.7% to -0.3%) trunk body fat compared with non-tea drinkers.

Conclusions: Consumption of hot tea might be considered as part of a healthy diet in order to support parameters associated with metabolic health and may be particularly important in older male age groups in supporting reduced central adiposity.
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http://dx.doi.org/10.1002/oby.22705DOI Listing
February 2020

Incidence and Survival Changes in Patients with Esophageal Adenocarcinoma during 1984-2013.

Biomed Res Int 2019 12;2019:7431850. Epub 2019 Dec 12.

Department of Oncology, The Fifth Affiliated Hospital of Sun Yat-sen University, Zhuhai, Guangdong 519000, China.

Purpose: The morbidity of esophageal adenocarcinoma (EAC) has significantly increased in Western countries. We aimed to identify trends in incidence and survival in patients with EAC in the recent 30 years and then analyzed potential risk factors, including race, sex, age, and socioeconomic status (SES).

Methods: All data were collected from the Surveillance, Epidemiology, and End Results or SEER database. Kaplan-Meier analysis and the Cox proportional hazards model were conducted to compare the differences in survival between variables, including sex, race, age, and SES, as well as to evaluate the association of these factors with prognosis.

Results: A total of 16,474 patients with EAC were identified from 1984 to 2013 in the United States. Overall incidence increased every 10 years from 1.8 to 3.1 to 3.9 per 100. Overall survival gradually improved ( < 0.0001), which was evident in male patients ((hazard ratio (HR) = 1.111; 95% confidence interval (CI) (1.07, 1.15)); however, the 5-year survival rate remained low (20.1%). The Cox proportional hazards model identified old age, black ethnicity, and medium/high poverty as risk factors for EAC (HR = 1.018; 95% CI (1.017, 1.019; HR = 1.240, 95% CI (1.151,1.336), HR = 1.000, 95% CI (1.000, 1.000); respectively).

Conclusions: The incidence of EAC in the United States increased over time. Survival advantage was observed in white patients and patients in the low-poverty group. Sex was an independent prognostic factor for EAC, but this finding has to be confirmed by further research.
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http://dx.doi.org/10.1155/2019/7431850DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6930790PMC
May 2020

[Application of intracranial lead reconstruction in deep brain stimulation therapy in patients with Parkinson's disease].

Nan Fang Yi Ke Da Xue Xue Bao 2019 Dec;39(12):1461-1468

Department of Neurosurgery, Neuromedicine Center of Fujian Province, First Affiliated Hospital of Fujian Medical University, Fuzhou 350000, China.

Objective: To evaluate the feasibility of applying intracranial lead reconstruction in deep brain stimulation (DBS) therapy for Parkinsonism.

Methods: We retrospectively collected the clinical data from 27 patients with Parkinson's disease (PD), who received bilateral subthalamic nucleus (STN) DBS therapy between January, 2016 and December, 2017. According to the position of the selected optimal stimulating contact of the implanted leads, the patients were divided into group A with the stimulating contacts of the bilateral leads in the STN, group B with unilateral stimulating contacts in the STN, and group C with bilateral stimulating contacts outside the STN. All the patients were assessed for improvement using Hoehn-Yahr stage, the third part of United Parkinson's Disease Rating Scale (UPDRS Ⅲ), Schwab and England Activities of Daily Living (SE-ADL), and L-dopa equivalent daily dose (LEDD). The consistency between the optimal stimulating contact selected by lead reconstruction and that by standard postoperative programming procedure was also evaluated.

Results: The patients in all the 3 groups showed postoperative improvements in Hoehn-Yahr stage, UPDRS Ⅲ score, SE-ADL score, and LEDD in the medication-off state. But at 12 months of the follow-up, such improvements were maintained only in the patients of group A. The optimal stimulating contacts selected by lead reconstruction and standard postoperative programming procedure had a matching rate of up to 77.78% (42/54), and the coordinates of the optimal contacts selected by the two methods showed no significant difference.

Conclusions: Intracranial lead reconstruction facilitates the study of the association between the implant site of the leads and the clinical outcome of DBS therapy for PD and allows the precise selection of the optimal contact of the implanted leads in postoperative programming of DBS.
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http://dx.doi.org/10.12122/j.issn.1673-4254.2019.12.10DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6942991PMC
December 2019