Publications by authors named "Fang Chen"

2,154 Publications

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Clinical analysis of 99 children with Henoch-Schönlein purpura complicated with overt gastrointestinal bleeding.

Clin Rheumatol 2022 Aug 8. Epub 2022 Aug 8.

Department of Traditional Chinese Medicine, Beijing Children's Hospital, Capital Medical University, National Center for Children's Health, China, Beijing, 100045, China.

Objective: To analyze and summarize the clinical features, diagnosis, and treatment of children with Henoch-Schönlein purpura (HSP) complicated by overt gastrointestinal bleeding (GI bleeding) for achieving early identification, prevention, and treatment in terms of severe GI bleeding.

Methods: A retrospective analysis was conducted on children with HSP complicated by overt GI bleeding who were admitted to the Department of Traditional Chinese Medicine of Beijing Children's Hospital from January 2017 to December 2019. According to the severity of GI bleeding, the patients were divided into mild bleeding group (61 cases) and moderate and severe bleeding group (38 cases). Inflammatory parameters, coagulation function, GI ultrasound findings, and clinical features were compared. Logistic regression analysis was used to determine the related variables affecting the severity of GI bleeding, and the ROC curve was used to determine the variable test efficacy.

Results: Onset in summer, wide distribution of skin rash with facial involvement, the elevation of D-dimer and high neutrophil-to-lymphocyte ratio (NLR) had significant effects on the severity of GI bleeding. ROC curve analysis showed that the optimal cut-off points of NLR and D-dimer for predicting severe GI bleeding in children with HSP were 10.56 and 0.89 mg/L, respectively.

Conclusion: Facial rash may be a warning sign of GI bleeding. Enhanced monitoring of NLR and D-dimer is helpful for early recognition of GI bleeding as well as assessment of severity.
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http://dx.doi.org/10.1007/s10067-022-06323-8DOI Listing
August 2022

Pan-cancer analysis of the FAM83 family and its association with prognosis and tumor microenvironment.

Front Genet 2022 22;13:919559. Epub 2022 Jul 22.

Department of Medical Oncology, The First Affiliated Hospital of Nanchang University, Nanchang, China.

Family with sequence similarity 83 (FAM83) is a newly identified family of oncogenes whose members play important roles in signaling and cancer progression. However, a thorough understanding of the FAM83 family in tumors is still lacking. Here, we performed a comprehensive analysis of the expression levels of the FAM83 family across cancers and patient prognoses using bioinformatics methods. We found that the expression levels of FAM83 family genes were upregulated in most tumors, and importantly, high expression levels of FAM83 family genes were related to poor prognosis in most tumors. In addition, we analyzed the relationship of FAM83 family genes with immune subtypes and the tumor microenvironment (TME). The results showed that FAM83 family genes were significantly associated with immune infiltrative subtypes and to varying degrees with the level of stromal cell infiltration and tumor stem cells. Finally, our study also showed the relationship between FAM83 family genes and drug sensitivity. Therefore, this pan-cancer analysis demonstrates the critical role of FAM83 family genes in tumor development and provides new clues for therapeutic strategies for cancer.
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http://dx.doi.org/10.3389/fgene.2022.919559DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9353330PMC
July 2022

A fast online questionnaire for screening mental illness symptoms during the COVID-19 pandemic.

Transl Psychiatry 2022 Aug 4;12(1):311. Epub 2022 Aug 4.

Department of Psychiatry, Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China.

The COVID-19 pandemic has caused massive effects on the situation of public mental health. A fast online questionnaire for screening and evaluating mental symptoms is urgent. In this work, we developed a new 19-item self-assessment Fast Screen Questionnaire for Mental Illness Symptoms (FSQ-MIS) to quickly identify mental illness symptoms. The FSQ-MIS was validated on a total of 3828 young adult mental disorder patients and 984 healthy controls. We applied principal component analysis (PCA), receiver operating characteristic (ROC) curve, and general log-linear analysis (GLA) to evaluate the construct and parallel validity. Results demonstrate that the proposed FSQ-MIS shows high test-retest reliability (0.852) and split-half reliability (0.844). Six factors obtained using PCA explained 54.3% of the variance and showed high correlations with other widely used scales. The ROC results (0.716-0.983) revealed high criterion validity of FSQ-MIS. GLA demonstrated the advantage of FSQ-MIS in predicting anxiety and depression prevalence in COVID-19, supporting the efficiency of FSQ-MIS as a tool for research and clinical practice.
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http://dx.doi.org/10.1038/s41398-022-02086-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9352665PMC
August 2022

Evaluation of a Functional Single Nucleotide Polymorphism of the SARS-CoV-2 Receptor That Is Potentially Involved in Long COVID.

Front Genet 2022 18;13:931562. Epub 2022 Jul 18.

Center for Applied Bioinformatics, St. Jude Children's Research Hospital, Memphis, TN, United States.

Since the occurrence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in December 2019, SARS-CoV-2 has led to a global coronavirus disease 2019 (COVID-19) pandemic. A better understanding of the SARS-CoV-2 receptor at the genetic level would help combat COVID-19, particularly for long COVID. We performed a genetic analysis of and searched for its common potential single nucleotide polymorphisms (SNPs) with minor allele frequency >0.05 in both European and Chinese populations that would contribute to gene expression variation. We thought that the variation of the expression would be an important biological feature that would strongly affect COVID-19 symptoms, such as "brain fog", which is highlighted by the fact that ACE2 acts as a major cellular receptor for SARS-CoV-2 attachment and is highly expressed in brain tissues. Based on the human GTEx gene expression database, we found rs2106809 exhibited a significant correlation with the expression among multiple brain and artery tissues. This expression correlation was replicated in an independent European brain eQTL database, Braineac. rs2106809*G also displays significantly higher frequency in Asian populations than in Europeans and displays a protective effect ( = 0.047) against COVID-19 hospitalization when comparing hospitalized COVID-19 cases with non-hospitalized COVID-19 or SARS-CoV-2 test-negative samples with European ancestry from the UK Biobank. Furthermore, we experimentally demonstrated that rs2106809*G could upregulate the transcriptional activity of . Therefore, integrative analysis and functional experiment strongly support that SNP rs2106809 is a functional brain eQTL and its potential involvement in long COVID, which warrants further investigation.
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http://dx.doi.org/10.3389/fgene.2022.931562DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9340221PMC
July 2022

Continuous infusion versus intermittent infusion of vancomycin in critically ill patients undergoing continuous venovenous hemofiltration: a prospective interventional study.

BMC Infect Dis 2022 Aug 2;22(1):667. Epub 2022 Aug 2.

Department of Pharmacy, The Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou Municipal Hospital, Suzhou, 215002, China.

Background: A prospective interventional study comparing outcomes in critically ill patients receiving intermittent infusion (II) or continuous infusion (CI) of vancomycin during continuous venovenous hemofiltration (CVVH) is lacking. The objective of this study was to compare the pharmacokinetic/pharmacodynamics (PK/PD) target attainment, therapeutic efficacy and safety among critically ill patients who received CI or II of vancomycin in a prospective interventional trial and to explore the correlations of effluent flow rate (EFR) with PK/PD indices.

Methods: This prospective interventional study was conducted in two independent intensive care units (ICUs) from February 2021 to January 2022. Patients in one ICU were assigned to receive CI (intervention group) of vancomycin, whereas patients in the other ICU were assigned to receive II regimen (control group). The primary outcome was to compare the PK/PD target attainment, including target concentration and target area under the curve over 24 h to minimum inhibitory concentration (AUC/MIC).

Results: Overall target attainment of PK/PD indices was higher with CI compared with II, irrespective of target concentration (78.7% vs. 40.5%; P < 0.05) or AUC/MIC (53.2% vs. 28.6%; P < 0.05). There were no significant differences in clinical success (72.2% vs. 50.0%; P = 0.183) and microbiological success (83.3% vs. 75.0%, P = 0.681) between the patients treated with CI or II of vancomycin. Adverse reactions occurred at similar rates (0.0% vs. 4.4%; P = 0.462), and mortality between the two modalities was also not significant different (21.7% vs. 17.9%; P = 0.728). Correlation analysis showed a weak to moderately inverse correlation of EFR with observed concentration (r = - 0.3921, P = 0.01) and AUC/MIC (r = - 0.3811, P = 0.013) in the II group, whereas the correlation between EFR and observed concentration (r = - 0.5711, P < 0.001) or AUC/MIC (r = - 0.5458, P < 0.001) in the CI group was stronger.

Conclusion: As compared to II, CI of vancomycin in critically ill patients undergoing CVVH was associated with improved attainment of PK/PD indices. Furthermore, the inverse correlation of PK/PD indices with EFR was stronger among patients treated with CI of vancomycin. Trial registration The trial was registered in the Chinese clinical trial registration center (21/01/2021-No. ChiCTR2100042393).
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http://dx.doi.org/10.1186/s12879-022-07618-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9344630PMC
August 2022

Targeting microbiota-host interactions with resveratrol on cancer: Effects and potential mechanisms of action.

Crit Rev Food Sci Nutr 2022 Aug 2:1-23. Epub 2022 Aug 2.

Institute of Agri-food Processing and Nutrition, Beijing Academy of Agriculture and Forestry Sciences, Beijing Key Laboratory of Agricultural Products of Fruits and Vegetables Preservation and Processing, Key Laboratory of Vegetable Postharvest Processing, Ministry of Agriculture and Rural Affairs, Beijing, China.

Resveratrol (RSV) is a natural polyphenolic compound detected in grapes, berries, and red wine. The anticancer activities of RSV have been observed in vivo and in vitro studies. However, the pharmacology mechanism of RSV is confusing due to its low bioavailability. According to studies of the metabolic characteristics of RSV, the gut intestine is a crucial site of its health benefits. Dietary RSV exhibits a profound effect on the gut microbiota structure and metabolic function. In addition, emerging evidence demonstrates a protective effect of RSV metabolites against carcinogenesis. Therefore, to better understand the anticancer mechanisms of dietary RSV, it is vital to evaluate the role of RSV-microbiota-host interactions in cancer therapy. In this review, we summarized significant findings on the anticancer activities of RSV based on epidemiological, experimental and clinical studies involved in investigating the metabolic characteristics and the traditional anticancer mechanisms of RSV. Special attention is given to the putative mechanisms involving microbiota-host interactions, such as the modulation of gut microecology and the anticancer effects of RSV metabolites. The changes in microbiota-host interactions after RSV supplementation play vital roles in cancer prevention and thus offering a new perspective on nutritional interventions to treat cancer.
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http://dx.doi.org/10.1080/10408398.2022.2106180DOI Listing
August 2022

Effects of a standardized patient-based simulation in anaphylactic shock management for new graduate nurses.

BMC Nurs 2022 Aug 1;21(1):209. Epub 2022 Aug 1.

Nursing department, Zhejiang Hospital, No. 1229 Gudun Road, Zhejiang, Hangzhou, China.

Background: Patients may be endangered if new graduate nurses cannot recognize and manage anaphylactic shock. Consequently, enhancing the new graduate nurses' understanding of their roles and responsibilities during the rescue of a patient with anaphylactic shock is important. However, due to its inherent limitations, traditional classroom-based teaching makes it difficult to explore the potential of the students. Although popular simulation teaching has several notable advantages, it has not been proven to be effective in training inexperienced nurses on anaphylactic shock. We investigated the effect of a standardized patient-based simulation on the behaviors of new graduate nurses' during anaphylactic shock rescue to identify an effective and safe method for contemporary nursing education.

Methods: Except for the ill or pregnant, all the new graduate nurses were included in the study as students to undergo a standardized patient-based simulation conducted in the clinical skills center of a general hospital. The simulation training was designed to teach students to recognize the signs and symptoms of anaphylactic shock, place the patient in the correct position, stop the ongoing intravenous infusion of the antibiotic which triggers the anaphylactic shock, restart an intravenous infusion on a new infusion apparatus, give 100% oxygen via a nasal cannula or mask, preserve airway patency, call the rapid response team, and correctly administer the medications prescribed by the clinicians. Before and after the training, the instructors evaluated each student's skills and behaviors using a clinical competency evaluation list. After the training, all students completed the Chinese version of the Simulation Design Scale (SDS) to demonstrate their satisfaction with the program and then participated in semi-structured interviews with their instructors.

Results: All 104 graduate nurses had a significant improvement on the 6 competencies of the clinical competency evaluation list after the simulation training (P < 0.001). The SDS scores revealed that the students were highly satisfied with all the aspects of the simulation training (the 20 satisfaction rates were all above 90.00%). During the semi-structured interviews, most of the new graduate nurses reported that simulation training in the management of anaphylactic shock was critical and would guide them in clinical practice.

Conclusion: Simulation training in anaphylactic shock is a potentially viable and effective method for teaching new graduate nurses to manage clinical incidents.
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http://dx.doi.org/10.1186/s12912-022-00995-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9341083PMC
August 2022

Knockdown of Chk1 inhibits proliferation and promotes apoptosis in mouse granulosa cells and its regulation mechanism by miR-15a and miR-16.

In Vitro Cell Dev Biol Anim 2022 Aug 1. Epub 2022 Aug 1.

Reproductive Medicine Centre, Department of Obstetrics and Gynecology, the Second Affiliated Hospital of Wenzhou Medical University, Wenzhou, 325000, People's Republic of China.

Checkpoint kinase 1 (Chk1) is a protein kinase which preserves the genome integrity, and works as an evolutionally conserved DNA damage response and cell cycle checkpoint. However, the functional roles and regulatory mechanism of Chk1 in mouse granulosa cells (GCs) have not been fully elucidated. In this study, by RNA interfering, Chk1 gene was knocked down in GCs. Knockdown of Chk1 inhibited proliferation and increased apoptosis of GCs (p < 0.05), respectively; in addition, cell cycle of GCs was arrested at S and G2/M phases. Further qRT-PCR results showed that cell cycle factors (Cyclin B1 and Cyclin D 1) and a marker gene of proliferation (PCNA) were downregulated (p < 0.001), while apoptotic factors (p53b, p21, caspase-3, and Bax) were upregulated (p < 0.01), which suggested that knockdown of Chk1 may inhibit proliferation, regulate cell cycle, and promote apoptosis at the transcriptional level in GCs. In vitro studies showed a negative correlation between Chk1 mRNA and miR-16 expression during follicular development. To elucidate the relationship between Chk1 and miR-15a/16, luciferase reporter plasmids were constructed and luciferase assays revealed that both miR-15a and miR-16 could bind to the 3' UTR of Chk1 mRNA, and significantly downregulate the protein level of Chk1 (p < 0.01), while miR-16, not miR-15a, could significantly decrease the mRNA level of Chk1 (p < 0.05). This result indicated that miR-16 directly induced Chk1 mRNA destabilization, while miR-15a regulated Chk1 expression through translational repression. Taken together, this study uncovered the roles of Chk1 in mouse granulosa cells and its regulation by miR-15a and miR-16 through different mechanisms.
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http://dx.doi.org/10.1007/s11626-022-00705-7DOI Listing
August 2022

Rif1 interacts with non-canonical polycomb repressive complex PRC1.6 to regulate mouse embryonic stem cells fate potential.

Cell Regen 2022 Aug 2;11(1):25. Epub 2022 Aug 2.

Hunan Key Laboratory of Molecular Precision Medicine, Department of Oncology, Xiangya Hospital, Central South University, Changsha, Hunan, China.

Mouse embryonic stem cells (mESCs) cycle in and out of a transient 2-cell (2C)-like totipotent state, driven by a complex genetic circuit involves both the coding and repetitive sections of the genome. While a vast array of regulators, including the multi-functional protein Rif1, has been reported to influence the switch of fate potential, how they act in concert to achieve this cellular plasticity remains elusive. Here, by modularizing the known totipotency regulatory factors, we identify an unprecedented functional connection between Rif1 and the non-canonical polycomb repressive complex PRC1.6. Downregulation of the expression of either Rif1 or PRC1.6 subunits imposes similar impacts on the transcriptome of mESCs. The LacO-LacI induced ectopic colocalization assay detects a specific interaction between Rif1 and Pcgf6, bolstering the intactness of the PRC1.6 complex. Chromatin immunoprecipitation followed by sequencing (ChIP-seq) analysis further reveals that Rif1 is required for the accurate targeting of Pcgf6 to a group of genomic loci encompassing many genes involved in the regulation of the 2C-like state. Depletion of Rif1 or Pcgf6 not only activates 2C genes such as Zscan4 and Zfp352, but also derepresses a group of the endogenous retroviral element MERVL, a key marker for totipotency. Collectively, our findings discover that Rif1 can serve as a novel auxiliary component in the PRC1.6 complex to restrain the genetic circuit underlying totipotent fate potential, shedding new mechanistic insights into its function in regulating the cellular plasticity of embryonic stem cells.
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http://dx.doi.org/10.1186/s13619-022-00124-9DOI Listing
August 2022

Potential Gut Microbiota Features for Non-Invasive Detection of Schistosomiasis.

Front Immunol 2022 14;13:941530. Epub 2022 Jul 14.

Key Laboratory of Tropical Disease Control, Ministry of Education, Guangzhou, China.

The gut microbiota has been identified as a predictive biomarker for various diseases. However, few studies focused on the diagnostic accuracy of gut microbiota derived-signature for predicting hepatic injuries in schistosomiasis. Here, we characterized the gut microbiomes from 94 human and mouse stool samples using 16S rRNA gene sequencing. The diversity and composition of gut microbiomes in infection-induced disease changed significantly. Gut microbes, such as , , , and , showed a significant correlation with the level of hepatic granuloma, fibrosis, hydroxyproline, ALT or AST in infection-induced disease. We identified a range of gut bacterial features to distinguish schistosomiasis from hepatic injuries using the random forest classifier model, LEfSe and STAMP analysis. Significant features , , and and their combinations have a robust predictive accuracy (AUC: from 0.8182 to 0.9639) for detecting liver injuries induced by infection in humans and mice. Our study revealed associations between gut microbiota features and physiopathology and serological shifts of schistosomiasis and provided preliminary evidence for novel gut microbiota-derived features for the non-invasive detection of schistosomiasis.
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http://dx.doi.org/10.3389/fimmu.2022.941530DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9330540PMC
August 2022

Relevance of RNA N6-Methyladenosine Regulators for Pulmonary Fibrosis: Implications for Chronic Hypersensitivity Pneumonitis and Idiopathic Pulmonary Fibrosis.

Front Genet 2022 14;13:939175. Epub 2022 Jul 14.

Department of Respiratory and Critical Care Medicine, Changhai Hospital, Second Military Medical University, Shanghai, China.

N6-methyladenosine (m6A) modification plays a pivotal role in post-transcriptionally regulating gene expression and biological functions. Nonetheless, the roles of m6A modification in the regulation of chronic hypersensitivity pneumonitis (CHP) and idiopathic pulmonary fibrosis (IPF) remain unclear. Twenty-two significant m6A regulators were selected from differential gene analysis between the control and treatment groups from the GSE150910 dataset. Five candidate m6A regulators (insulin-like growth factor binding protein 2, insulin-like growth factor binding protein 3, YTH domain-containing protein 1, zinc finger CCCH domain-containing protein 13, and methyltransferase-like 3) were screened by the application of a random forest model and nomogram model to predict risks of pulmonary fibrosis. The consensus clustering method was applied to divide the treatment samples into two groups with different m6A patterns (clusters A and B) based on the 22 m6A regulators. Our study performed principal component analysis to obtain the m6A-related score of the 288 samples to quantify the two m6A patterns. The study reveals that cluster A was linked to T helper cell (Th) 2-type cytokines, while the immune infiltration of Th1 cytokines was higher in cluster B. Our results suggest that m6A cluster A is likely related to pulmonary fibrosis, indicating m6A regulators play notable roles in the occurrence of pulmonary fibrosis. The m6A patterns could be considered as biomarkers to identify CHP and IPF, which will be helpful to develop immunotherapy strategies for pulmonary fibrosis in the future.
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http://dx.doi.org/10.3389/fgene.2022.939175DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9329921PMC
July 2022

Influence of sperm DNA fragmentation on the clinical outcome of fertilization-embryo transfer (IVF-ET).

Front Endocrinol (Lausanne) 2022 14;13:945242. Epub 2022 Jul 14.

Institute of Epigenetics and Epigenomics, College of Animal Science and Technology, Yangzhou University, Yangzhou, China.

Purpose: To evaluate the effect of elevated sperm DNA fragmentation index (DFI) on fresh and frozen embryo transfer cycles.

Methods: A retrospective study was performed with 549 fresh embryo transfer cycles and 1340 frozen embryo transfer cycles after fertilization/intracytoplasmic sperm injection (IVF/ICSI) from 2016 to 2021.

Results: The statistical results of 549 fresh embryo transfer cycles showed that the delivery rate in the normal sperm DFI group (43.9% vs. 27.1%, = 0.014) was significantly higher than that in the abnormal sperm DFI group, and there were no significant differences in the biochemical pregnancy rate (59.0% vs. 50.8%, = 0.232), clinical pregnancy rate (53.1% vs. 40.7%, = 0.072), or miscarriage rate (17.3% vs. 33.3%, = 0.098) between the two groups. The results of 1340 frozen embryo transfer cycles showed that the biochemical pregnancy rate (57.9% vs. 45.6%, = 0.006) and clinical pregnancy rate (50.3% vs. 40.7%, = 0.027) in the normal sperm DFI group were significantly higher than those in the abnormal sperm DFI group. The delivery rate (40.9% vs. 33.3%, = 0.074) and miscarriage rate (18.6% vs. 18.0%, = 0.919) were not significantly different between the two groups.

Conclusion: The increase of sperm DFI significantly reduced the delivery rate of fresh embryo transfer cycles and the biochemical pregnancy rate and clinical pregnancy rate of frozen embryo transfer cycles.
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http://dx.doi.org/10.3389/fendo.2022.945242DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9329669PMC
July 2022

Genome-Wide Association Study for Idiopathic Ventricular Tachyarrhythmias Identifies Key Role of and in Calcium Homeostasis and Cardiac Rhythm Maintenance.

Circ Genom Precis Med 2022 Jul 27:101161CIRCGEN121003603. Epub 2022 Jul 27.

The Center for Human Genome Research, Key Laboratory of Molecular Biophysics of the Ministry of Education, College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan (C.F., P.W., D.Y., X.Z., D.G.,L.L., X.B., W.X., H.L., Y.Y., X.R., T.K., X.T., C.X., Q.K.W.).

Background: Idiopathic ventricular tachycardia (VT) occurs in structurally normal hearts and accounts for a significant number of all types of VT. The genome-wide association study is the most effective strategy for identifying novel genetic variants for common diseases. However, no genome-wide association study has been reported for idiopathic VT.

Methods: We conducted the first genome-wide association study for idiopathic VT in the Chinese Han population using a discovery population with 246 cases and 648 controls and a replication population with 222 cases and >4072 controls. Candidate VT genes were functionally characterized in zebrafish. Real-time RT-PCR analysis was used to determine the effects of candidate genes on expression of ion channels and regulators. Patch-clamping was used to record L-type calcium current from neonatal rat cardiomyocytes with overexpression of candidate genes.

Results: We identified 4 significant loci represented by rs78960694 (minor allele frequency [MAF]=5.02% in cases and 1.84% in controls; =4.30×1012, odds ratio [OR]=3.91) and rs2229095 (MAF=3.25% in cases and 1.63% in controls; =1.02×107, OR=3.44) near and in , respectively, rs68126098 in (MAF=40.98% in cases and 32.07% in controls; 2.40×108, OR=1.53), rs2390325 between and (MAF=21.19% in cases and 15.12% in controls; =1.92×107, OR=1.62), and rs270065 in (MAF=33.63% in cases and 40.25% in controls; =9.51×107, OR=0.69). Note that the associations of idiopathic VT for variant rs78960694 and variant rs68126098 reach genome-wide significance (<5.00×108). Overexpression of either or increased the heart rate in zebrafish, and enhanced expression of , , or in zebrafish embryos, HEK293, and AC16 cardiomyocytes. Overexpression of either or significantly increased L-type Ca2+ current density.

Conclusions: The first genome-wide association study identifies 4 novel loci and 2 risk genes ( and ) for idiopathic VT. These findings identify new molecular determinants for cardiac calcium homeostasis and rhythm maintenance and provide novel targets for diagnosis and treatment for idiopathic VT.
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http://dx.doi.org/10.1161/CIRCGEN.121.003603DOI Listing
July 2022

Acceleration effect of galacturonic acid on acrylamide generation: evidence in model reaction systems.

J Sci Food Agric 2022 Jul 27. Epub 2022 Jul 27.

College of Food Science and Nutritional Engineering, National Engineering Research Center for Fruit and Vegetable Processing, Key Laboratory of Fruits and Vegetables Processing, Ministry of Agriculture; Engineering Research Centre for Fruits and Vegetables Processing, Ministry of Education; Beijing Key Laboratory for Food Non-thermal Processing, China Agricultural University, Beijing, 100083, China.

Background: Acrylamide (AA) is a potential carcinogen formed in food rich in carbohydrate during heating. Recently, AA has been found in several fruit products, such as prune juice, sugarcane molasses and canned black olives. This study focused on the role of galacturonic acid (GalA), the main acid hydrolysis product of fruit pectin, in AA formation in three model systems asparagine (Asn)/glucose (Glc), Asn/GalA and Asn/Glc/GalA during heating under different pH values (pH 3.8-7.8), Glc concentration (0-0.1 mol L ), molar ratio of substrates (Asn/Glc=1:1, 0.025-0.5 mol L ) and temperature (120-180°C) for 30 min, respectively.

Results: The results suggested that the addition of 0.1 mol L GalA strongly accelerated AA formation in a pH value and temperature dependent manner (p<0.05). AA concentration under different Glc concentration and molar ratio of substrates suggested that GalA was more reactive than Glc when reacted with Asn. Furthermore, the Amadori rearrangement product/Schiff base/oxazolidine-5-one was identified as the intermediates formed in Asn/GalA model system by using ultra performance liquid chromatography-quadrupole-time-of-flight-mass spectrometry (UPLC-QTOF-MS).

Conclusion: The results suggested that Maillard reaction between Asn and GalA might contribute to AA formation. This study is significant to elucidate the contribution of interaction between components for AA formation in fruit products. This article is protected by copyright. All rights reserved.
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http://dx.doi.org/10.1002/jsfa.12149DOI Listing
July 2022

Comparison of computer-assisted navigated technology and conventional technology in high tibial osteotomy (HTO): a meta-analysis.

Comput Assist Surg (Abingdon) 2022 Dec;27(1):63-73

Department of Joint Surgery, Huangshan City People's Hospital, Huangshan, Anhui, China.

Background: Though some studies have reported navigated high tibial osteotomy (HTO) is a useful procedure to correct knee deformity. There is still great controversy whether navigated HTO can achieve better accuracy of limb alignment and greater clinical outcomes. Current meta-analysis was conducted to investigate whether better radiographic outcomes and clinical outcomes could be acquired in navigated HTO compared with the conventional procedure.

Method: We conducted a literature search in the electronic databases, including Medline, Embase, the Cochrane Library, and Web of Science. We identified studies published before August 2020. We also checked the references of the related articles for any relevant studies. We strictly followed the Preferred Reporting Items for Systematics reviews and Meta-Analysis (PRISMA) guidelines in this review. This research was performed using Review Manager 5.4 software.

Results: Fourteen articles were included, involving 1399 knees. Our meta-analysis indicated that patients undergoing navigated HTO had significantly better outcomes in outliers of aimed limb alignment (RD=-0.24, 95% CI: =-0.34 to -0.13,  < 0.01), outliers of aimed tibial posterior slope (TPS) (RD=-0.41, 95% CI: -0.51 to -0.30,  < 0.01), Range of Motion (ROM) (MD = 6.37, 95%CI: 0.83-11.91,  = 0.02), and American knee society knee score (AKS knee score) (MD = 3.88, 95%CI: 1.37-6.39,  = 0.002). No significant differences were found in Lysholm score (MD = 1.30, 95%CI: -0.31 to 2.90,  = 0.11), American knee society function score (AKS function score) (RD = 1.42, 95%CI: -0.15 to 2.99,  = 0.08), complications (RD=-0.01, 95% CI: = -0.05 to 0.04,  = 0.77), delayed union (RD=-0.01, 95% CI: = -0.02 to 0.03,  = 0.59), and reoperation (RD = 0, 95% CI: -0.09 to 0.10,  = 0.98) between the two groups. The operation time in the navigated group was 15.46 min longer than in the conventional group.

Conclusion: Navigated HTO provided more accurate and reproducible radiographic outcomes in the correction of the malalignment than conventional techniques, and there is no difference in the risk of complications compared with conventional HTO. However, it is unclear whether navigation HTO can achieve better clinical results. More randomized controlled trials (RCTs) with high quality, large sample size, and sufficient follow-up period are required.
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http://dx.doi.org/10.1080/24699322.2022.2078739DOI Listing
December 2022

Sulfite activation by cobaltosic oxide nanohydrangeas for tetracycline degradation: Performance, degradation pathways and mechanism.

J Hazard Mater 2022 Jul 16;439:129618. Epub 2022 Jul 16.

Engineering Research Center of Eco-Environment in Three Gorges Reservoir Region of Ministry of Education, College of Materials and Chemical Engineering, China Three Gorges University, Yichang, Hubei 443002 , China; Hubei Three Gorges Laboratory, 443007 Yichang, Hubei, China. Electronic address:

Sulfite has been used as a classic reductant for the dehalogenation and reduction of organic compounds for a long time, it is recently deemed as a promising alternative (for persulfate) to generate sulfate radical for wastewater treatment due to its low price and eco-toxicity. In contrast with the enormous work developed in the field of tetracycline (TC) degradation via PMS activization, sulfite activization could play a important role in TC degradation but there is only very few available reports in this area. Herein, the novel and efficient CoNHs nanocatalyst is designed and developed, via immobilization of hydrangea-shaped CoO nanoparticles onto graphitic carbon nanosheet (GCN), for the degradation of tetracycline via sulfite activation. The detailed characterizations have confirmed that CoNHs possesses a nanohydrangea-shaped structure with high microporosity. The comparison with other supports (such as CeO and MoS), CoNHs provides the highest degradation efficiency in TC degradation, due to the synergistic effect between CoO and GCN. Free radical quenching experiments and EPR analysis confirm that SO• and O• are major reactive oxygen species in the CoNHs/sulfite system. This work could provide a simple, economical and durable cobalt-based catalyst for organic wastewater treatment via sulfite activation.
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http://dx.doi.org/10.1016/j.jhazmat.2022.129618DOI Listing
July 2022

Phenotypic modulation of vascular smooth muscle cells in the corpus spongiosum surrounding the urethral plate in hypospadias.

Andrologia 2022 Jul 22:e14540. Epub 2022 Jul 22.

Department of Urology, Shanghai Children's Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.

Hypospadias is an abnormal ventral development of the penis caused by incomplete virilization of the male genital tubercle. This study investigated the phenotypic modulation of vascular smooth muscle cells (VSMCs) in the corpus spongiosum surrounding the urethral plate in hypospadias. The urethral corpus spongiosum tissue was collected for HE, Masson and α-SMA immunohistochemical staining. Spongiosum VSMCs were cultured and identified by α-SMA fluorescence. qRT-PCR and Western blotting and fluorescence were performed. The results showed that the vascular lumen of the corpus spongiosum around the urethral plate was larger and that the vascular smooth muscle layer was thicker in hypospadias. The expression of the contractile markers α-SMA and Calponin 1 in VSMCs was decreased, the expression of the synthetic marker OPN was increased, and the transcription of the phenotypic switching factors SRF and MYOCD was decreased. The expression of Ki67, PCNA and BAX was increased, and the expression of Bcl-2 was decreased. The phenotype of corpus spongiosum VSMCs in hypospadias changed from the contractional type to the synthetic type. This phenotypic modulation was associated with increased proliferation and apoptosis rates. SRF and MYOCD may be the main factors mediating the phenotypic modulation of urethral corpus spongiosum VSMCs.
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http://dx.doi.org/10.1111/and.14540DOI Listing
July 2022

Association between perinatal factors and hypospadias in newborns: a retrospective case-control study of 42,244 male infants.

BMC Pregnancy Childbirth 2022 Jul 20;22(1):579. Epub 2022 Jul 20.

Department of Neonatology, International Peace Maternity and Child Health Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.

Background: Hypospadias is one of the most common male congenital malformations worldwide. It is characterised by the abnormal positioning of the opening of urethra, and may lead to problems with urination and sexual function. Various factors were suggested to contribute to hypospadias pathogen. This study aimed to evaluate the relationship between perinatal factors and neonatal hypospadias based on a large sample of male newborns.

Methods: This retrospective case-control study was conducted at the International Peace Maternal and Child Health Hospital, Shanghai Jiao Tong University School of Medicine. Male infants with hypospadias (N = 97) and without any birth defects (N = 42,147) who were born in January 2015 to December 2019 were enrolled in this study. A statistical analysis of perinatal factors, such as maternal age, primiparity, multiple births, hypertensive disorders of pregnancy (HDP), diabetes mellitus (DM), placenta previa, thyroid diseases, hepatitis B, obesity, meconium-stained amniotic fluid, gestational age, low birth weight (LBW), small for gestational age (SGA) and in vitro fertilization (IVF) was used to assess the risk factors for hypospadias.

Results: The overall incidence of hypospadias in male infants was 0.23% (97/42,244). The univariate analysis of potential risk factors for hypospadias showed that HDP, primiparity, multiple births, hyperthyroidism, preterm delivery, LBW and SGA had a statistical association with hypospadias. After adjusting for potential confounders in a multivariate regression analysis, the odds ratios (OR) and 95% confidence intervals (CI) were calculated for the following risk factors for hypospadias: HDP (OR: 3.965, 95% CI: 2.473-6.359, P <  0.01), multiple births (OR: 2.607, 95% CI: 1.505-4. 514, P <  0.01) and hyperthyroidism (OR:4.792, 95% CI: 1.700-13.506, P <  0.01), which suggested these factors were significant independent risk factors for hypospadias.

Conclusions: Perinatal factors, such as HDP, multiple births and hyperthyroidism may be associated with hypospadias in male infants.
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http://dx.doi.org/10.1186/s12884-022-04906-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9301865PMC
July 2022

Polyadenylation ligation-mediated sequencing (PALM-Seq) characterizes cell-free coding and non-coding RNAs in human biofluids.

Clin Transl Med 2022 Jul;12(7):e987

BGI-Shenzhen, Shenzhen, China.

Background: Cell-free messenger RNA (cf-mRNA) and long non-coding RNA (cf-lncRNA) are becoming increasingly important in liquid biopsy by providing biomarkers for disease prediction, diagnosis and prognosis, but the simultaneous characterization of coding and non-coding RNAs in human biofluids remains challenging.

Methods: Here, we developed polyadenylation ligation-mediated sequencing (PALM-Seq), an RNA sequencing strategy employing treatment of RNA with T4 polynucleotide kinase to generate cell-free RNA (cfRNA) fragments with 5' phosphate and 3' hydroxyl and RNase H to deplete abundant RNAs, achieving simultaneous quantification and characterization of cfRNAs.

Results: Using PALM-Seq, we successfully identified well-known differentially abundant mRNA, lncRNA and microRNA in the blood plasma of pregnant women. We further characterized cfRNAs in blood plasma, saliva, urine, seminal plasma and amniotic fluid and found that the detected numbers of different RNA biotypes varied with body fluids. The profiles of cf-mRNA reflected the function of originated tissues, and immune cells significantly contributed RNA to blood plasma and saliva. Short fragments (<50 nt) of mRNA and lncRNA were major in biofluids, whereas seminal plasma and amniotic fluid tended to retain long RNA. Body fluids showed distinct preferences of pyrimidine at the 3' end and adenine at the 5' end of cf-mRNA and cf-lncRNA, which were correlated with the proportions of short fragments.

Conclusion: Together, PALM-Seq enables a simultaneous characterization of cf-mRNA and cf-lncRNA, contributing to elucidating the biology and promoting the application of cfRNAs.
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http://dx.doi.org/10.1002/ctm2.987DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9299576PMC
July 2022

Annotation-guided encoder-decoder network for bone extraction in ultrasound-assisted orthopedic surgery.

Comput Biol Med 2022 Jul 14;148:105813. Epub 2022 Jul 14.

Department of Orthopaedics, Beijing Tsinghua Changgung Hospital, Tsinghua University, China.

The patients and surgeons are usually exposed in massive ionizing radiation during fluoroscopy-based navigation orthopedic surgery. Comparatively, ultrasound-assisted orthopedic surgery could not only decrease the risk of radiation but also provide rich navigation information. However, due to the artifacts in ultrasound images, the extraction of bone structure from ultrasound sequences can be a particularly difficult task, which leads to some major challenges in ultrasound-assisted orthopedic navigation. In this paper, we propose an annotation-guided encoder-decoder network (AGN) to extract bone structure from the radiation-free ultrasound sequences. Specifically, the variability of the ultrasound probe's pose leads to the change of the ultrasound frame during the acquisition of ultrasound sequences. Therefore, a feature alignment module deployed in the AGN model is used to achieve reliable matching across ultrasound frames. Moreover, inspired by the interactive ultrasound analysis, where user annotated foreground information can help target extraction, our AGN model incorporates the annotation information obtained by Siamese networks. Experimental results validated that the AGN model not only produced better bone surface extraction than state-of-the-art methods (IOU: 0.92 versus. 0.88), but also achieved almost real-time extraction with the speed about 15 frames per second. In addition, the acquired bone surface further provided radiation-free 3D intraoperative bone structure for the intuitive navigation of orthopedic surgery.
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http://dx.doi.org/10.1016/j.compbiomed.2022.105813DOI Listing
July 2022

Non-Invasive Prenatal Diagnosis of Monogenic Disorders Through Bayesian- and Haplotype-Based Prediction of Fetal Genotype.

Front Genet 2022 1;13:911369. Epub 2022 Jul 1.

Prenatal Diagnosis Centre, Guangdong Women and Children's Hospital, Guangzhou, China.

Non-invasive prenatal diagnosis (NIPD) can identify monogenic diseases early during pregnancy with negligible risk to fetus or mother, but the haplotyping methods involved sometimes cannot infer parental inheritance at heterozygous maternal or paternal loci or at loci for which haplotype or genome phasing data are missing. This study was performed to establish a method that can effectively recover the whole fetal genome using maternal plasma cell-free DNA (cfDNA) and parental genomic DNA sequencing data, and validate the method's effectiveness in noninvasively detecting single nucleotide variations (SNVs), insertions and deletions (indels). A Bayesian model was developed to determine fetal genotypes using the plasma cfDNA and parental genomic DNA from five couples of healthy pregnancy. The Bayesian model was further integrated with a haplotype-based method to improve the inference accuracy of fetal genome and prediction outcomes of fetal genotypes. Five pregnancies with high risks of monogenic diseases were used to validate the effectiveness of this haplotype-assisted Bayesian approach for noninvasively detecting indels and pathogenic SNVs in fetus. Analysis of healthy fetuses led to the following accuracies of prediction: maternal homozygous and paternal heterozygous loci, 96.2 ± 5.8%; maternal heterozygous and paternal homozygous loci, 96.2 ± 1.4%; and maternal heterozygous and paternal heterozygous loci, 87.2 ± 4.7%. The respective accuracies of predicting insertions and deletions at these types of loci were 94.6 ± 1.9%, 80.2 ± 4.3%, and 79.3 ± 3.3%. This approach detected pathogenic single nucleotide variations and deletions with an accuracy of 87.5% in five fetuses with monogenic diseases. This approach was more accurate than methods based only on Bayesian inference. Our method may pave the way to accurate and reliable NIPD.
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http://dx.doi.org/10.3389/fgene.2022.911369DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9283829PMC
July 2022

Commensal microbe-derived SCFA alleviates atrial fibrillation via GPR43/NLRP3 signaling.

Int J Biol Sci 2022 27;18(10):4219-4232. Epub 2022 Jun 27.

Heart Center & Beijing Key Laboratory of Hypertension, Beijing Chaoyang Hospital, Capital Medical University, Beijing 100020, China.

Dysbiotic gut microbiota (GM) and NLRP3 inflammasome are proarrhythmic factors in atrial fibrillation (AF). Herein, whether short-chain fatty acid (SCFA) produced from GM fermentation of dietary fiber serving as invisible mediators is yet unclear. Thus, the current study aimed to determine whether SCFA alleviated from NLRP3 signaling-mediated atrial remodeling protects AF development. First, a cross-sectional study based on the GC-MS metabolomics was performed to explore the association between fecal SCFA levels and AF traits in a cohort consisted of 48 individuals. Then, a well-established mice model fed diet deficient or enriched in dietary fiber was established to elucidate the pathophysiological role of SCFA involved in AF susceptibility, atrial remodeling, and G-protein-coupled receptor 43 (GPR43)/NLRP3 signaling. Finally, the effects of SCFA were verified on HL-1 cells. Fecal SCFA levels were remarkably reduced in AF patients with a declining trend from paroxysmal to persistent AF. Prolonged P wave duration based on surface ECG and increased left atrial diameter gained from echocardiography was identified in low-fiber diet mice but lost in SCFA-supplemented group. Lack of dietary fiber enhanced susceptibility to AF under burst pacing, whereas SCFA might exert a protective effect. The supplementation of SCFA prevented dietary fiber deficiency-upregulated phosphorylation of calmodulin-dependent protein kinase II and ryanodine receptor 2, the disarray fibrosis, collagen expression, and NLRP3 inflammasome activation in atrial tissue. Finally, the AF protective roles of SCFA were identified through GPR43 mediated deactivation of NLRP3 by GPR43 knockdown in HL-1 cells. SCFA derived from dietary fiber fermentation by gut commensals alleviates AF development via GPR43/NLRP3 signaling.
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http://dx.doi.org/10.7150/ijbs.70644DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9274492PMC
July 2022

Membrane-covered composting significantly decreases methane emissions and microbial pathogens: Insight into the succession of bacterial and fungal communities.

Sci Total Environ 2022 Jul 14;845:157343. Epub 2022 Jul 14.

Engineering Laboratory for AgroBiomass Recycling & Valorizing, College of Engineering, China Agricultural University, Beijing 100083, China. Electronic address:

In this study, the effects of semipermeable membrane-covered on methane emissions and potential pathogens during industrial-scale composting of the solid fraction of dairy manure were investigated. The results showed that the oxygen concentration in the membrane-covered group (CT) was maintained above 10 %, and the cumulative methane emission in CT was >99 % lower than that in the control group (CK). Microbial analysis showed that the bacterial genus Thermus and the fungal genus Mycothermus were dominant in CT, and the richness and diversity of the bacterial community were greater than those of the fungal community. At the end of the composting, the relative abundance of potential bacterial pathogens in CT was 32.59 % lower than that in CK, and the relative abundance of potential fungal pathogens in each group was <2 %. Structural equation models revealed that oxygen concentration was a major factor influencing the bacterial diversity in CT, and the increase of oxygen concentration could limit methane emissions by inhibiting the growth of anaerobic bacteria. Therefore, membrane-covered composting could effectively improve compost safety and reduce methane emissions by regulating microbial community structure.
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http://dx.doi.org/10.1016/j.scitotenv.2022.157343DOI Listing
July 2022

Assessment as Learning: How Does Peer Assessment Function in Students' Learning?

Front Psychol 2022 27;13:912568. Epub 2022 Jun 27.

School of Foreign Languages, Shanghai Jiao Tong University, Shanghai, China.

Peer assessment (PA) is employed as one fundamental practice of classroom-based assessment in terms of its learning-oriented and formative nature. The exercise of peer assessment has multiple and additional benefits for student learning. However, research into the learning processes in peer assessment is scarce both in theory and in practice, making it difficult to evaluate and pinpoint its value as a tool in assessment as learning (AaL). This study focuses both on the learning process and outcome through assessment activities. We set out with three goals in mind: (1) to examine students' assessment performance in context, (2) to evaluate its impact on student progress, and (3) to illuminate teachers on organizing assessment activities. Three specific research questions are answered in this study: (1) How do student raters perform in the process of PA in an advanced English class? (2) To what extent do assessment activities influence the students' speaking ability? (3) What are students' perceptions of PA regarding its benefits and caveats? A total of 29 undergraduate students participated in two assessment activities on argumentative speaking. Many-Facet Rasch Model analysis was conducted to measure the rater effects both at the group level and the individual level. Bias/interaction analyses were performed to diagnose rater behavior in different contexts including the rating session, speaking session, and peer assessment vs. self-assessment. Questionnaire and semi-structured interview data were also collected to explore factors and strategies that could interfere with PA as AaL. Results show that students exhibited stable rating behavior and made progress in argumentative speaking in all dimensions, including delivery, organization, and language use. They are more stringent with themselves than with peers although there is one rare case with a bias against peers. Participants acknowledged the benefits of PA but also shared reasonable concerns in practice. This study validated the feasibility and the effectiveness of PA for student learning. Discussion on findings and guidelines for effective implementation of PA as AaL are provided.
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http://dx.doi.org/10.3389/fpsyg.2022.912568DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9271947PMC
June 2022

Characteristics of macular morphology and microcirculation in diabetic macular edema patients with serous retinal detachment.

BMC Ophthalmol 2022 Jul 11;22(1):299. Epub 2022 Jul 11.

Department of Ophthalmology, Subei People's Hospital affiliated to Yangzhou University, Yangzhou, China.

Background: To analyze and compare the characteristics of macular morphology and microcirculation in diabetic macular edema (DME) patients with and without macular serous retinal detachment (SRD).

Methods: One hundred eyes in 81 patients diagnosed with the DME (the central macular thickness (CMT) of ≥ 300 μm) from March 2020 to November 2020 were selected. According to whether complicated with SRD, patients were divided into DME with SRD (60 eyes) and without SRD (40 eyes) groups. We analyzed the following parameters: CMT, central retinal thickness (CRT), subfoveal choroidal thickness (SFCT), number of hyperreflective foci (HF) in the complete retina, inner retina, outer retina, and subretinal space, the integrity of the ellipsoid zone (EZ) and external limiting membrane (ELM), the presence of disorganization of inner retinal layers (DRIL), foveal avascular zone (FAZ) area, and the vascular flow density of superficial capillary plexus (SCP), deep capillary plexus (DCP), and choriocapillaris.

Results: (1) Compared to the group without SRD, the group with SRD had a greater CMT (P < 0.05) and a smaller CRT (P < 0.001); (2) The number of the HF in the complete retina, outer retina, and the subretinal space was larger in the group with SRD (P < 0.001); 3.The proportion of the EZ disruption (P < 0.05) and ELM disruption (P < 0.001) were higher in the group with SRD; 4. The SFCT (P < 0.05) and the vascular flow density of choriocapillaris (P < 0.05) were greater in the group with SRD; 5. There were no significant differences in the FAZ area and the vascular flow density of the DCP and SCP (P > 0.05); 6. The presence of the SRD was correlated with the integrity of the ELM, the number of HF in the complete retina, outer retina, and subretinal space (χ2 = 26.930, OR = 0.707, 0.263, 0.995, P < 0.001), as well as the SFCT (OR = 0.992, P < 0.05).

Conclusions: The results support the hypothesis that the presence of the ELM disruption, the larger number of the HF, and the thickening and hyperperfusion of the choroid may be involved in the pathogenesis of SRD in DME.
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http://dx.doi.org/10.1186/s12886-022-02523-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9277895PMC
July 2022

Design, synthesis, and biological evaluation of membrane-active honokiol derivatives as potent antibacterial agents.

Eur J Med Chem 2022 Jul 8;240:114593. Epub 2022 Jul 8.

School of Pharmaceutical Sciences, Liaocheng University, Liaocheng, China. Electronic address:

Infections caused by drug-resistant bacteria have emerged to be one of the greatest threats to global public health, and new antimicrobial agents with novel mechanisms of action hence are in an urgent need to combat bacterial resistance. Herein, we reported the design, synthesis, and antibacterial evaluation of novel honokiol derivatives as mimics of antimicrobial peptides (AMPs). These mimics showed potent antimicrobial properties against Gram-positive bacteria. Among them, the most promising compound 13b exhibited excellent antibacterial activity, rapid bactericidal properties, avoidance of antibiotic resistance, and weak hemolytic and cytotoxic activities. In addition, compound 13b not only inhibited the biofilm formation but also destroy the preformed biofilm. Mechanism studies further revealed that compound 13b killed bacteria rapidly by interrupting the bacterial membrane. More intriguingly, compound 13b exhibited potent in vivo antibacterial efficacy in a mouse septicemia model induced by Staphylococcus aureus ATCC43300. These results highlight the potential of 13b to be used as therapeutic agents.
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http://dx.doi.org/10.1016/j.ejmech.2022.114593DOI Listing
July 2022

P3H4 Promotes Malignant Progression of Lung Adenocarcinoma via Interaction with EGFR.

Cancers (Basel) 2022 Jul 1;14(13). Epub 2022 Jul 1.

Department of Thoracic Surgery, The First Affiliated Hospital of Soochow University, Suzhou 215000, China.

Lung cancer is associated with the greatest number of cancer-related deaths worldwide. Lung adenocarcinoma (LUAD) accounts for 85% of all cases of lung cancer. Despite recent advances in treatment, the 5-year survival rate remains less than 15%. Thus, the diagnostic and therapeutic role of LUAD remain to be further studied. The prolyl 3-hydroxylase family member 4 (P3H4) is involved in various cancers, but little is known about its role in LUAD. Our study demonstrated that the P3H4 gene was upregulated in LUAD. Clinically, the expression of P3H4 was positively correlated with an advanced TNM stage and shorter survival. Functionally, P3H4 plays a significant role in the metastasis and proliferation of LUAD both in vitro and in vivo. Mechanistically, P3H4 might interact with EGFR to regulate the metabolic substances. Our study indicated that P3H4 is a critical gene in the malignant progression of LUAD and represents a potential biomarker and therapeutic target.
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http://dx.doi.org/10.3390/cancers14133243DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9264976PMC
July 2022

Potential Determinants for Radiation-Induced Lymphopenia in Patients With Breast Cancer Using Interpretable Machine Learning Approach.

Front Immunol 2022 21;13:768811. Epub 2022 Jun 21.

Department of Clinical Oncology, University of Hong Kong-Shenzhen Hospital, Shenzhen, China.

Radiation-induced lymphopenia is known for its survival significance in patients with breast cancer treated with radiation therapy. This study aimed to evaluate the impact of radiotherapy on lymphocytes by applying machine learning strategies. We used Extreme Gradient Boosting (XGboost) to predict the event of lymphopenia (grade≥1) and conduced an independent validation. Then, we induced feature attribution analysis (Shapley additive explanation, SHAP) in explaining the XGboost models to explore the directional contribution of each feature to lymphopenia. Finally, we implemented the proof-of-concept clinical validation. The results showed that the XGboost models had rigorous generalization performances (accuracies 0.764 and ROC-AUC 0.841, respectively) in the independent cohort. The baseline lymphocyte counts are the most protective feature (SHAP = 5.226, direction of SHAP = -0.964). Baseline platelets and monocytes also played important protective roles. The usage of taxane only chemotherapy was less risk on lymphopenia than the combination of anthracycline and taxane. By the contribution analysis of dose, we identified that firstly lymphocytes were sensitive to a radiation dose less than 4Gy; secondly the irradiation volume was more important in promoting lymphopenia than the irradiation dose; thirdly the irradiation dose promoted the event of lymphopenia when the irradiation volume was fixed. Overall, our findings paved the way to clarifying the radiation dose volume effect. To avoid radiation-induced lymphopenia, irradiation volume should be kept to a minimum during the planning process, as long as the target coverage is not compromised.
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http://dx.doi.org/10.3389/fimmu.2022.768811DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9253393PMC
June 2022

Co-evolved plant and blast fungus ascorbate oxidases orchestrate the redox state of host apoplast to modulate rice immunity.

Mol Plant 2022 08 6;15(8):1347-1366. Epub 2022 Jul 6.

Department of Plant Pathology, College of Plant Protection, Nanjing Agricultural University, and Key Laboratory of Integrated Management of Crop Diseases and Pests, Ministry of Education, Nanjing, China; The Key Laboratory of Plant Immunity, Nanjing Agricultural University, Nanjing, China. Electronic address:

Apoplastic ascorbate oxidases (AOs) play a critical role in reactive oxygen species (ROS)-mediated innate host immunity by regulating the apoplast redox state. To date, little is known about how apoplastic effectors of the rice blast fungus Magnaporthe oryzae modulate the apoplast redox state of rice to subvert plant immunity. In this study, we demonstrated that M. oryzae MoAo1 is an AO that plays a role in virulence by modulating the apoplast redox status of rice cells. We showed that MoAo1 inhibits the activity of rice OsAO3 and OsAO4, which also regulate the apoplast redox status and plant immunity. In addition, we found that MoAo1, OsAO3, and OsAO4 all exhibit polymorphic variations whose varied interactions orchestrate pathogen virulence and rice immunity. Taken together, our results reveal a critical role for extracellular redox enzymes during rice blast infection and shed light on the importance of the apoplast redox state and its regulation in plant-pathogen interactions.
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http://dx.doi.org/10.1016/j.molp.2022.07.001DOI Listing
August 2022

rhG-CSF is associated with an increased risk of metastasis in NSCLC patients following postoperative chemotherapy.

BMC Cancer 2022 Jul 7;22(1):741. Epub 2022 Jul 7.

Department of Medical Oncology, The First Affiliated Hospital of Nanchang University, 17 Yongwai Zheng Road, Nanchang, 330000, China.

Background: Recombinant human granulocyte colony-stimulating factor (rhG-CSF) reduces neutropenia events and is widely used in cancer patients receiving chemotherapy. However, the effects of rhG-CSF on distant organ metastasis (DOM) in non-small-cell lung cancer (NSCLC) patients following postoperative chemotherapy are not clear.

Methods: A retrospective cohort study was performed on NSCLC patients who underwent complete surgical resection and postoperative systemic chemotherapy at The First Affiliated Hospital of Nanchang University between 1 January 2012 and 31 December 2017. The effect of rhG-CSF on DOM was assessed with other confounding factors using Cox regression analyses.

Results: We identified 307 NSCLC patients who received postoperative systemic chemotherapy (n = 246 in the rhG-CSF group, n = 61 in the No rhG-CSF group). The incidence of DOM in postoperative NSCLC patients with rhG-CSF treatment was observably higher than in patients without rhG-CSF treatment (48.3% vs. 27.9%, p < 0.05). Univariate regression analysis revealed that rhG-CSF and pathological stage were independent risk factors for metastasis-free survival (MFS) (p < 0.05). RhG-CSF users had a higher risk of DOM (adjusted HR: 2.33, 95% CI: 1.31-4.15) than nonusers of rhG-CSF. The association between rhG-CSF and the risk of DOM was significant only in patients presenting with myelosuppression (HR: 3.34, 95% CI: 1.86-6.02) and not in patients without myelosuppression (HR: 0.71, 95% CI: 0.17-2.94, Interaction p-value< 0.01). The risk increased with higher dose density of rhG-CSF compared to rhG-CSF versus no users (p for trend< 0.001).

Conclusion: These analyses indicate that rhG-CSF use is related to DOM following postoperative chemotherapy in NSCLC.
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http://dx.doi.org/10.1186/s12885-022-09850-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9261064PMC
July 2022
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