Publications by authors named "Yongjun Chen"

202 Publications

Effect of virtual reality simulation training on the response capability of public health emergency reserve nurses in China: a quasiexperimental study.

BMJ Open 2021 Sep 22;11(9):e048611. Epub 2021 Sep 22.

School of Nursing, Xi'an Jiaotong University Health Science Center, Xi'an, Shaanxi, China

Objective: To develop a virtual reality simulation training programme, and further verify the effect of the programme on improving the response capacity of emergency reserve nurses confronting public health emergencies.

Design: A prospective quasiexperimental design with a control group.

Participants: A total of 120 nurses were recruited and randomly divided into the control group and the intervention group.

Intervention: Participants underwent a 3-month training. The control group received the conventional training of emergency response (eg, theoretical lectures, technical skills and psychological training), while the intervention group underwent the virtual reality simulation training in combination with skills training. The COVID-19 cases were incorporated into the intervention group training, and the psychological training was identical to both groups. At the end of the training, each group conducted emergency drills twice. Before and after the intervention, the two groups were assessed for the knowledge and technical skills regarding responses to fulminate respiratory infectious diseases, as well as the capacity of emergency care. Furthermore, their pandemic preparedness was assessed with a disaster preparedness questionnaire.

Results: After the intervention, the scores of the relevant knowledge, the capacity of emergency care and disaster preparedness in the intervention group significantly increased (p<0.01). The score of technical skills in the control group increased more significantly than that of the intervention group (p<0.01). No significant difference was identified in the scores of postdisaster management in two groups (p>0.05).

Conclusion: The virtual reality simulation training in combination with technical skills training can improve the response capacity of emergency reserve nurses as compared with the conventional training. The findings of the study provide some evidence for the emergency training of reserve nurses in better response to public health emergencies and suggest this methodology is worthy of further research and popularisation.
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http://dx.doi.org/10.1136/bmjopen-2021-048611DOI Listing
September 2021

Inappropriate use of antibiotics exacerbates inflammation through OMV-induced pyroptosis in MDR Klebsiella pneumoniae infection.

Cell Rep 2021 Sep;36(12):109750

Laboratory of Molecular Immunology, Institute of Medical Biology, Chinese Academy of Medical Sciences & Peking Union Medical College, Kunming, Yunnan 650106, China. Electronic address:

The inappropriate use of antibiotics is a severe public health problem worldwide, contributing to the emergence of multidrug-resistant (MDR) bacteria. To explore the possible impacts of the inappropriate use of antibiotics on the immune system, we use Klebsiella pneumoniae (K. pneumoniae) infection as an example and show that imipenem increases the mortality of mice infected by MDR K. pneumoniae. Further studies demonstrate that imipenem enhances the secretion of outer membrane vesicles (OMVs) with significantly elevated presentation of GroEL, which promotes the phagocytosis of OMVs by macrophages that depends on the interaction between GroEL and its receptor, lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1). OMVs cause the pyroptosis of macrophages and the release of proinflammatory cytokines, which contribute to exacerbated inflammatory responses. We propose that the inappropriate use of antibiotics in the cases of infection by MDR bacteria such as K. pneumoniae might cause damaging inflammatory responses, which underlines the pernicious effects of inappropriate use of antibiotics.
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http://dx.doi.org/10.1016/j.celrep.2021.109750DOI Listing
September 2021

Prognostic Value of Glucose-to-Lymphocyte Ratio in Critically Ill Patients with Acute Pancreatitis.

Int J Gen Med 2021 8;14:5449-5460. Epub 2021 Sep 8.

Department of Gastroenterology, Qianjiang Central Hospital of Chongqing Municipality, Chongqing, 409000, People's Republic of China.

Background: Glucose metabolism and systemic inflammation have been associated with prognosis in acute pancreatitis (AP) patients. However, the possible value as a prognostic marker of the glucose-to-lymphocyte ratio (GLR) has not been evaluated in critically ill patients with AP.

Methods: This study included 1,133 critically ill patients with AP from the Medical Information Mart for Intensive Care-IV (MIMIC-IV) database, who were randomly divided into the training cohort (n=806) and the validation cohort (n=327) at a ratio of 7:3. X-tile software was used to determine the optimal cut-off values for GLR. Area under the curve (AUC) analysis was performed to compare the performance between GLR and other blood-based inflammatory biomarkers. Univariate and multivariate Cox regression analyses were applied to select prognostic factors associated with in-hospital mortality. A nomogram model was developed based on the identified prognostic factors and the validation cohort was used to further validate the nomogram.

Results: The optimal cut-off value for GLR was 0.9. The ROC analyses showed that the discrimination abilities of GLR were better than other blood-based inflammatory biomarkers. Multivariate Cox regression analysis demonstrated that age, platelet, albumin, bilirubin, Sequential Organ Failure Assessment (SOFA) score, and GLR are independent predictors of poor overall survival in the training cohort and were incorporated into the nomogram for in-hospital mortality as independent factors. The nomogram exhibited better discrimination with C-indexes in the training cohort and the validation cohort of 0.886 (95% CI=0.849-0.922) and 0.841 (95% CI=0.767-0.915), respectively. The calibration plot revealed an adequate fit of the nomogram for predicting the risk of in-hospital mortality in both sets.

Conclusion: As an easily available biomarker, GLR can independently predict the in-hospital mortality of critically ill patients with AP. The nomogram combining GLR with other significant features exerted favorable predictive performance for in-hospital mortality.
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http://dx.doi.org/10.2147/IJGM.S327123DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8436258PMC
September 2021

A Novel Immunomodulator Delivery Platform Based on Bacterial Biomimetic Vesicles for Enhanced Antitumor Immunity.

Adv Mater 2021 Sep 12:e2103923. Epub 2021 Sep 12.

Laboratory of Molecular Immunology, Institute of Medical Biology, Chinese Academy of Medical Sciences and Peking Union Medical College, 935 Jiaoling Road, Kunming, 650118, China.

T cell activation-induced cell death (AICD) during tumor pathogenesis is a tumor immune escape process dependent on dendritic cells (DCs). Proper immune-modulatory therapies effectively inhibit tumor-specific CD8 T cell exhaustion and enhance antitumor immune responses. Here, high-pressure homogenization is utilized to drive immunomodulator IL10-modified bacteria to extrude through the gap and self-assemble into bacterial biomimetic vesicles exposing IL10 (IL10-BBVs) on the surface with high efficiency. IL10-BBVs efficiently target DCs in tumor-draining lymph nodes and thus increase the interaction between IL10 on BBVs and IL10R on DCs to suppress AICD and mitigate CD8 T cell exhaustion specific to tumor antigens. Two subcutaneous peripheral injections of IL10-BBVs 1 week apart in tumor-bearing mice effectively increase systemic and intratumoral proportions of CD8 T cells to suppress tumor growth and metastasis. Tumor-specific antigen E7 is enclosed into the periplasm of IL10-BBVs (IL10-E7-BBVs) to realize concurrent actions of the immunomodulator IL10 and the tumor antigen human papillomavirus (HPV) 16E7 in lymph nodes, further enhancing the antitumor effects mediated by CD8 T cells. The development of this modified BBV delivery platform will expand the application of bacterial membranes and provide novel immunotherapeutic strategies for tumor treatment.
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http://dx.doi.org/10.1002/adma.202103923DOI Listing
September 2021

Exploration of differentially-expressed exosomal mRNAs, lncRNAs and circRNAs from serum samples of gallbladder cancer and xantho-granulomatous cholecystitis patients.

Bioengineered 2021 Dec;12(1):6134-6143

Department of General Surgery, Shanghai Institute of Digestive Surgery, Ruijin Hospital, Shanghai Jiao Tong University, School of Medicine, Shanghai, China.

Gallbladder cancer (GBC) is the most common biliary tract malignancy worldwide. Although a growing number of studies have explored the mechanism of GBC, thus far, few molecules have been discovered that can be utilized as specific biomarkers for the early diagnosis and therapeutic treatment of GBC. Recent studies have shown that exosomes not only participate in the progression of tumors, but also carry specific information that can define multiple cancer types. The present study investigated the expression profiles of coding (or messenger) ribonucleic acids (mRNAs) and non-coding RNAs (ncRNAs, including long non-coding RNAs [lncRNAs] and circular RNAs [circRNAs]) in plasma-derived exosomes from GBC patients. Using high-throughput RNA sequencing and subsequent bioinformatic analysis, a number of differentially expressed (DE) mRNAs, lncRNAs, and circRNAs were identified in GBC exosomes, compared to their expressions in xantho-granulomatous cholecystitis (XGC) exosomes. Gene Ontology (GO) and Kyoto Encyclopedia of Gene and Genome (KEGG) analyses were then conducted to investigate the potential functions of these DE RNAs. Furthermore, the interaction networks and competing endogenous RNA networks of these DE RNAs and their target genes were investigated, revealing a complex regulatory network among mRNAs and ncRNAs. In summary, this study demonstrates the diagnostic value of plasma-derived exosomes in GBC and provides a new perspective on the mechanism of GBC.
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http://dx.doi.org/10.1080/21655979.2021.1972780DOI Listing
December 2021

Expression and Possible Significance of ACE2 in the Human Liver, Esophagus, Stomach, and Colon.

Evid Based Complement Alternat Med 2021 25;2021:6949902. Epub 2021 Aug 25.

The Affifiliated Nanhua Hospital, Department of Gastroenterology, Hengyang Medical School, University of South China, Hengyang 421001, Hunan, China.

Angiotensin-converting enzyme 2 (ACE2) has been identified as the key receptor of SARS coronavirus that plays a key role in the pathogenesis of SARS. It is known that ACE2 mRNA can be expressed in most organs. However, the protein expression of ACE2 is not clear yet. To explore the role of ACE2 as a precipitating factor in digestive organ damage in COVID-19, this study investigated the expression of ACE2 protein in the human liver, esophagus, stomach, and colon. The result showed that ACE2 can be expressed in the liver, esophagus, stomach, and colon, which suggests SARS-CoV-2 may enter the digestive system through ACE2 and cause liver damage and gastrointestinal damage. It is hoped that the result of the study will provide a new strategy for the prevention and treatment of digestive organ damage under COVID-19.
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http://dx.doi.org/10.1155/2021/6949902DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8410421PMC
August 2021

Predictive Nomogram for the Prediction of Early Recurrence of Colorectal Cancer.

Int J Gen Med 2021 26;14:4857-4866. Epub 2021 Aug 26.

Department of Gastroenterology, Qianjiang Central Hospital of Chongqing Municipality, Chongqing, 409099, People's Republic of China.

Aim: The prognosis of colorectal cancer (CRC) individuals after curative resection is not satisfactory due to the early recurrence. We sought to identify the affecting features of early recurrence in CRC patients.

Methods: A total of 3500 CRC patients underwent curative resection were retrospectively incorporated into our study. Among them, 246 patients exhibited tumor recurrence: 121 had early recurrence (≤1 year after operation) and 125 had late recurrence (>1 year after operation). A total of 246 CRC patients with recurrence were randomly assigned into the training group (N=177) or validation group (N=69) based on the ratio of 7:3. LASSO COX regression and support vector machine (SVM) were utilized to screen for the significant clinical indexes associated with the presence of early recurrence. Recurrent nomogram was created based on the above informative parameters to predict the probability of early recurrence.

Results: Proportion of advanced TNM stage, platelet count, systemic immune-inflammation index (SII), mean corpuscular hemoglobin concentration (MCHC), CA-199, CA-125, lactate dehydrogenase, total bile acid (TBA), urea nitrogen were significantly higher in early recurrence group compared with that in late recurrence group. Results from LASSO COX regression and support vector machine (SVM) revealed that TNM stage, CA-199, CA125, SII and TBA were strong predictors for the presence of early recurrence among postoperative CRC patients in the training group. The recurrent nomogram based on the five predictors exhibited good predictive performance as calculated by C-index (0.846, 95% CI 0.789-0.902 in the training group and 0.799, 95% CI 0.697-0.902 in the validation group) for the prediction of early recurrence. Moreover, the recurrent nomogram exhibited not only encouraging calibration ability, but also great clinical utility both in the training group and validation group.

Conclusion: TNM stage, CA-199, CA125, SII and TBA were closely correlated with the presence of early recurrence of CRC patients. The recurrent nomogram held well predictive ability for the identification of CRC patients with early recurrence.
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http://dx.doi.org/10.2147/IJGM.S321171DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8405163PMC
August 2021

Real-world data on the clinicopathological traits and outcomes of hospitalized liver hemangioma patients: a multicenter study.

Ann Transl Med 2021 Jul;9(13):1067

The Institute of Hepatobiliary Surgery, Southwest Hospital, Army Medical University, Chongqing, China.

Background: There is currently a lack of consensus regarding the clinical features, diagnosis, treatment indications and options, and risk assessment of hepatic hemangioma patients.

Methods: This was a multicenter, real-world study that analyzed a large number of hepatic hemangioma cases in China and included patient data on epidemiology, diagnosis, treatment methods, and outcomes.

Results: A total of 5,143 patients hospitalized for hepatic hemangioma were included, of whom 34.42% were male and 65.58% were female. The age distribution was concentrated between 30 and 60 years old, accounting for 87.41% of the patients. Among the hepatic hemangioma patients, 60.8% had only one tumor, with the most common pathological type being cavernous hemangioma (96.07% of cases). The treatment motivations and indications included anxiety, obvious clinical symptoms, rapid tumor growth, unclear diagnoses and acute emergencies. Overall, 41.4% of the patients were treated for psychological reasons, while 30.59% were treated because they presented obvious (primarily nonspecific) clinical symptoms. Hepatic resection was the main therapeutic method and was based on various indications. There were a small number of patients with Kasabach-Merritt syndrome, according to its generally recognized definition.

Conclusions: Most patients in this study who were hospitalized for hepatic hemangioma did not meet the indications for requiring treatment. Surveillance is the recommended course of action for definitively diagnosed hepatic hemangioma, and a new classification system is needed to standardize the diagnosis of this condition.
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http://dx.doi.org/10.21037/atm-20-4684DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8339840PMC
July 2021

Effects of Starch Synthesis-Related Genes Polymorphism on Quality of Glutinous Rice.

Front Plant Sci 2021 6;12:707992. Epub 2021 Aug 6.

Lab of Plant Molecular Genetics and Breeding, Southwest University of Science and Technology, Mianyang, China.

Glutinous rice ( L.) quality includes thermal properties, retrogradation and pasting viscosity properties, and so on, which have little or no amylose. However, the genetic network regulation of different quality indices has not been systematically studied. The aim was to investigate the relationship between starch synthesis-related genes (SSRGs) and the physicochemical properties of glutinous rice by targeted-gene association analysis (TGAS). The genotypes of 17 SSRGs were analyzed using 46 gene-specific molecular markers in 63 glutinous rice accessions. TGAS and gene interactions analysis indicated that () () , and () had significant genetic effects on glutinous rice quality. and were the major genes that regulated thermal properties and retrogradation properties (RP). was central in the regulation of gel consistency (GC), and it participated in the regulation of pasting viscosity parameters (PVP) except for the pasting time and the pasting temperature. , and their interactions with regulated gelatinization temperature (GT) and PVP. The starch properties of glutinous rice are mainly controlled by , and their interactions, but is central among them. These findings indicate that starch properties in glutinous rice have a complex genetic system. It provides crucial information for promoting glutinous rice quality.
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http://dx.doi.org/10.3389/fpls.2021.707992DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8377722PMC
August 2021

Acetylation of calmodulin regulates synaptic plasticity and fear learning.

J Biol Chem 2021 Jul 31;297(3):101034. Epub 2021 Jul 31.

Key Laboratory of Brain Functional Genomics, Ministry of Education and Shanghai, School of Life Science, East China Normal University, Shanghai, China. Electronic address:

Synaptic plasticity is critical for brain function, including learning and memory. It is regulated by gene transcription and protein synthesis as well as posttranslational modifications at synapses. Although protein acetylation has been shown to be involved in the regulation of synaptic plasticity, this was mainly for histone protein acetylation. To investigate whether acetylation of nonhistone proteins is important for synaptic plasticity, we analyzed mouse brain acetylome and found that calmodulin (CaM), a ubiquitous Ca sensor, was acetylated on three lysine residues, which were conserved across species. NMDA receptor-dependent long-term potentiation (LTP) is considered the most compelling form of synaptic plasticity. During LTP induction, activation of NMDA receptor triggers Ca influx, and the Ca binds with CaM and activates calcium/calmodulin-dependent protein kinase IIα (CaMKIIα), which is essential for LTP induction. By using home-generated and site-specific antibodies against acetylated CaM, we show that CaM acetylation is upregulated by neural activities in an NMDA receptor-dependent manner. Moreover, mutation of acetyllysines in CaM1 proteins disrupts synaptic plasticity and fear learning in a mouse model. We further demonstrate that acetylation of CaM reduces the binding free energy and increases the binding affinity toward CaMKIIα, a protein kinase pivotal to synaptic plasticity and learning. Taken together, our results demonstrate importance of CaM acetylation in regulating synaptic plasticity and learning.
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http://dx.doi.org/10.1016/j.jbc.2021.101034DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8383114PMC
July 2021

Feasibility and application of trimetazidine in F-FDG PET myocardial metabolic imaging of diabetic mellitus patients with severe coronary artery disease: A prospective, self-controlled study.

J Nucl Cardiol 2021 Jul 30. Epub 2021 Jul 30.

Department of Nuclear Medicine, The Third Affiliated Hospital of Soochow University, Changzhou, 213003, Jiangsu, China.

Background: F-FDG PET myocardial metabolic imaging (MMI) is sometimes uninterpretable due to background activity from uncontrolled glucose homeostasis in diabetic mellitus (DM) patients. Trimetazidine is an oral medication that promotes the transformation of myocardial energy supply from free fatty acids to glucose. We aimed to investigate the feasibility and application of trimetazidine in F-FDG PET MMI of DM patients.

Methods: With DM patients exhibiting severe coronary artery disease (CAD) symptoms serving as self-controls, the effects of trimetazidine on PET MMI image quality, myocardial viability assessment, quantitative analytical parameters, and F-FDG uptake of different myocardial segments were elucidated.

Results: The image quality of F-FDG MMI was graded visually as good, moderate, and uninterpretable. After trimetazidine, grades of good, moderate, and uninterpretable were observed in 14 (60.9%), 8 (34.8%), and 1 (4.3%) patients, respectively, and in 4 (17.4%), 15 (65.2%), 4 (17.4%) patients without trimetazidine. The myocardial SUV and myocardial to blood pool SUV ratio (M/B ratio) were significantly higher after trimetazidine administration than those before (3.11 ± 1.07 vs 2.32 ± 1.00, 2.67 ± 1.41 vs 1.81 ± 0.75, P all < 0.01). 6 (3, 7) viable myocardium segments were detected with a mismatch score of 10 (6, 17) after trimetazidine, significantly higher than those before trimetazidine [5 (2, 7) and 8 (2, 17), P < 0.05]. Meanwhile, the F-FDG uptake in myocardial segments with decreased and normal perfusion showed different ranges of increase (by 15.30%-57.77%).

Conclusion: Trimetazidine is feasible and effective in DM patients with severe CAD before F-FDG PET MMI, which can significantly improve the image quality and increase the number of viable myocardium segments detected.

Trial Registry: The study was registered in the Chinese Clinical Trial Registry (ChiCTR2000038559).
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http://dx.doi.org/10.1007/s12350-021-02749-wDOI Listing
July 2021

Identification of prognostic long non-coding RNA signature with potential drugs in hepatocellular carcinoma.

Aging (Albany NY) 2021 07 20;13(14):18789-18805. Epub 2021 Jul 20.

Department of General Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, P.R. China.

Hepatocellular carcinoma (HCC) is the primary malignancy in the liver with high rate of death and recurrence. Novel prognostic model would be crucial for early diagnosis and improved clinical decision. The study aims to provide an effective lncRNA-based signature to predict survival time and tumor recurrence for HCC. Based on public database, lncRNA-based classifiers for overall survival and tumor recurrence were built with regression analysis and cross validation strategy. According to the risk-score of the classifiers, the whole cohorts were divided into groups with high and low risk. Afterwards, the efficiency of the lncRNA-based classifiers was evaluated and compared with other clinical factors. Finally, candidate small molecules for high risk groups were further screened using drug response databases to explore potential drugs for HCC treatment.
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http://dx.doi.org/10.18632/aging.203322DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8351707PMC
July 2021

RBD-Modified Bacterial Vesicles Elicited Potential Protective Immunity against SARS-CoV-2.

Nano Lett 2021 07 19;21(14):5920-5930. Epub 2021 Jul 19.

Laboratory of Molecular Immunology, Institute of Medical Biology, Chinese Academy of Medical Sciences and Peking Union Medical College, Kunming, China.

The disease caused by SARS-CoV-2 infection threatens human health. In this study, we used high-pressure homogenization technology not only to efficiently drive the bacterial membrane to produce artificial vesicles but also to force the fusion protein ClyA-receptor binding domain (RBD) to pass through gaps in the bacterial membrane to increase the contact between ClyA-RBD and the membrane. Therefore, the load of ClyA-RBD on the membrane is substantially increased. Using this technology, we constructed a "ring-like" bacterial biomimetic vesicle (BBV) loaded with polymerized RBD (RBD-BBV). RBD-BBVs injected subcutaneously can accumulate in lymph nodes, promote antigen uptake and processing, and elicit SARS-CoV-2-specific humoral and cellular immune responses in mice. In conclusion, we evaluated the potential of this novel bacterial vesicle as a vaccine delivery system and provided a new idea for the development of SARS-CoV-2 vaccines.
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http://dx.doi.org/10.1021/acs.nanolett.1c00680DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8315139PMC
July 2021

Clinical Efficacy of the Preservation of the Hepatic Branch of the Vagus Nerve on Delayed Gastric Emptying After Laparoscopic Pancreaticoduodenectomy.

J Gastrointest Surg 2021 08 5;25(8):2172-2183. Epub 2021 May 5.

Department of Biliary-Pancreatic Surgery, Affiliated Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1095 Jiefang Ave., Wuhan, 430030, Hubei, China.

Background: Delayed gastric emptying (DGE) is a common complication following laparoscopic pancreaticoduodenectomy (LPD), although it remains incompletely understood, and only few studies have investigated the clinical benefits of hepatic branch of the vagus nerve (HBVN) preservation on DGE after LPD until now. We intended to evaluate the effect of preservation of the HBVN during LPD on the incidence of DGE.

Methods: A total of 274 consecutive LPDs performed at a single center between July 2014 and December 2019 with available videos were retrospectively reviewed. DGE was defined according to the International Study Group of Pancreatic Surgery (ISGPS) criteria, and HBVN condition during the LPD procedure was evaluated through a video review. Risk factors associated with DGE were assessed by performing univariate and multivariate logistic regression analyses. Postoperative outcomes between the HBVN-preserved and HBVN-injury groups were compared before and after propensity score matching (PSM).

Results: One hundred fifty-six (56.93%) patients underwent LPD with HBVN-preserved and 118 (43.07%) with HBVN injury. DGE occurred in 33.2% of patients (n = 91) with grades B and C occurring at 13.9% (n = 38) and 7.7% (n = 21), respectively. Longer operative time, more EIBL, HBVN injury, POPF (grades B and C), postoperative hemorrhage, intra-abdominal infection, and Clavien-Dindo ≥III were identified as risk factors for DGE in the univariate analysis. Then, in the multivariate analysis, HBVN injury and intra-abdominal infection were found to be independent risk factors affecting the incidence of DGE (any grade) or clinically relevant DGE (grades B and C). Furthermore, the prevalence of DGE was significantly higher in the HBVN-injury group than in the HBVN-preserved group before and after PSM analysis (46.61% vs. 23.08%, P<0.001; 42.59% vs. 23.15%, P=0.013).

Conclusions: HBVN preservation during LPD might be associated with a reduced incidence of DGE as a framework for prospective quality improvement.
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http://dx.doi.org/10.1007/s11605-021-05024-yDOI Listing
August 2021

Case Report: Compound Heterozygous Variants in Identified in a Chinese Infant With Molybdenum Cofactor Deficiency.

Front Genet 2021 8;12:651878. Epub 2021 Apr 8.

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

The molybdenum cofactor (Moco) deficiency in humans results in the inactivity of molybdenum-dependent enzymes and is caused by pathogenic variants in (), (), and (). These genes along with () are involved in Moco biosynthesis and providing cofactors to Moco-dependent enzymes. Until now, there was no study to confirm that is a causative gene of Moco deficiency. Detailed clinical information was collected in the pedigree. The Whole-exome sequencing (WES) accompanied with Sanger sequencing validation were performed. We described the clinical presentations of an infant, born to a non-consanguineous healthy family, diagnosed as having variants caused Moco deficiency and showing typical features of Moco deficiency including severe neurologic symptoms and cystic encephalomalacia in the brain MRI, resulting in neonatal death. Compound heterozygous variants in the gene were identified by WES. Positive sulfite and decreased levels of uric acid in plasma and urine were detected. To our knowledge, this is the first case of variants causing Moco deficiency. Our study may contribute to genetic diagnosis of Moco deficiency and future genetic counseling.
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http://dx.doi.org/10.3389/fgene.2021.651878DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8060434PMC
April 2021

Spine impairment in mice high-expressing neuregulin 1 due to LIMK1 activation.

Cell Death Dis 2021 04 14;12(4):403. Epub 2021 Apr 14.

School of Life Sciences, Nanchang University, Nanchang, 330031, China.

The genes encoding for neuregulin1 (NRG1), a growth factor, and its receptor ErbB4 are both risk factors of major depression disorder and schizophrenia (SZ). They have been implicated in neural development and synaptic plasticity. However, exactly how NRG1 variations lead to SZ remains unclear. Indeed, NRG1 levels are increased in postmortem brain tissues of patients with brain disorders. Here, we studied the effects of high-level NRG1 on dendritic spine development and function. We showed that spine density in the prefrontal cortex and hippocampus was reduced in mice (ctoNrg1) that overexpressed NRG1 in neurons. The frequency of miniature excitatory postsynaptic currents (mEPSCs) was reduced in both brain regions of ctoNrg1 mice. High expression of NRG1 activated LIMK1 and increased cofilin phosphorylation in postsynaptic densities. Spine reduction was attenuated by inhibiting LIMK1 or blocking the NRG1-LIMK1 interaction, or by restoring NRG1 protein level. These results indicate that a normal NRG1 protein level is necessary for spine homeostasis and suggest a pathophysiological mechanism of abnormal spines in relevant brain disorders.
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http://dx.doi.org/10.1038/s41419-021-03687-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8047019PMC
April 2021

[Analysis of clinical features and genetic variants in a Chinese pedigree affected with tuberous sclerosis].

Zhonghua Yi Xue Yi Chuan Xue Za Zhi 2021 Apr;38(4):363-365

Department of Nephrology, Nanhua Hospital Affiliated to South China University, Hengyang, Hunan 421002, China.

Objective: To analyze the clinical features of a Chinese pedigree affected with tuberculosis sclerosis and explore its molecular pathogenesis.

Methods: Clinical data of the proband and members of his pedigree were collected. Whole exome sequencing was carried out to detect variants of the TSC1 and TSC2 genes. Candidate variants was verified by Sanger sequencing and bioinformatic analysis.

Results: The proband and his mother, who also had mild features of tuberous sclerosis, were found to harbor a novel heterozygous c.4183C>T (p.Q1395X) variant of the TSC2 gene, which was absent in the 4 healthy relatives. Bioinformatic analysis suggested the variant to be likely pathogenic.

Conclusion: The heterozygous c.4183C>T (p.Q1395X) variant of the TSC2 gene probably underlay the disease in this pedigree. Above finding has expanded the spectrum of TSC2 gene variants. The more severe symptoms in the proband may be attributed to phenotypic heterogeneity of this disease.
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http://dx.doi.org/10.3760/cma.j.cn511374-20200519-00355DOI Listing
April 2021

Protection against Doxorubicin-Induced Cardiotoxicity through Modulating iNOS/ARG 2 Balance by Electroacupuncture at PC6.

Oxid Med Cell Longev 2021 20;2021:6628957. Epub 2021 Mar 20.

South China Research Center for Acupuncture and Moxibustion, Medical College of Acu-Moxi and Rehabilitation, Guangzhou University of Chinese Medicine, Guangzhou, 510006, China.

Background: Doxorubicin (DOX) is a commonly used chemotherapeutic drug but is limited in clinical applications by its cardiotoxicity. acupoint (PC6) is a well-recognized acupoint for the treatment of cardiothoracic disease. However, whether acupuncture at PC6 could be effective in preventing DOX-induced cardiotoxicity is still unknown.

Methods: A set of experiments were performed with myocardial cells, wild type, inducible nitric oxide synthase knockout (iNOS-/-), and myocardial-specific ablation arginase 2 (Myh6-ARG 2-/-) mice. We investigated the protective effect and the underlying mechanisms for electroacupuncture (EA) against DOX-induced cardiotoxicity by echocardiography, immunostaining, biochemical analysis, and molecular biotechnology in vivo and in vitro analysis.

Results: We found that DOX-mediated nitric oxide (NO) production was positively correlated with the iNOS level but has a negative correlation with the arginase 2 (ARG 2) level in both myocardial cells and tissues. Meanwhile, EA at PC6 alleviated cardiac dysfunction and cardiac hypertrophy in DOX-treated mice. EA at PC6 blocked the upregulation of NO production in accompanied with the downregulated iNOS and upregulated ARG 2 levels in myocardial tissue induced by DOX. Furthermore, knockout iNOS prevented cardiotoxicity and EA treatment did not cause the further improvement of cardiac function in iNOS-/- mice treated by DOX. In contrast, deficiency of myocardial ARG 2 aggravated DOX-induced cardiotoxicity and reduced EA protective effect.

Conclusion: These results suggest that EA treatment at PC6 can prevent DOX-induced cardiotoxicity through modulating NO production by modulating the iNOS/ARG 2 balance in myocardial cells.
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http://dx.doi.org/10.1155/2021/6628957DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8007344PMC
May 2021

Neuregulin1-ErbB4 Signaling in Spinal Cord Participates in Electroacupuncture Analgesia in Inflammatory Pain.

Front Neurosci 2021 28;15:636348. Epub 2021 Jan 28.

South China Research Center for Acupuncture and Moxibustion, Medical College of Acu-Moxi and Rehabilitation, Guangzhou University of Chinese Medicine, Guangzhou, China.

Chronic inflammatory pain is a severe clinical symptom that aggravates the life quality of patients and places a huge economic burden on individuals and society. As one complementary and alternative therapy, electroacupuncture (EA) is widely used in clinical practice to treat chronic inflammatory pain based on its safety and efficacy. Previous studies have revealed the potential role of adenosine, neuropeptides, and inflammatory factors in EA analgesia in various pain models, but the identity of some of the signaling pathways involved remain unknown. In the present study, we explored whether neuregulin1 (NRG1)-ErbB4 signaling is involved in EA analgesia in inflammatory pain. Repeated EA treatment at the acupoints Zusanli (ST36) and Sanyinjiao (SP6) for 3 consecutive days remarkably attenuated mechanical allodynia and thermal hyperalgesia in complete Freund's adjuvant (CFA)-treated mice, with an increased expression of NRG1 in spinal cord (SC). We found that ErbB4 kinase participated in both the EA and NRG1 mediated analgesic effects on inflammatory pain by pharmacological inhibition or genetic ablation ErbB4 . Intriguingly, the mice with conditional knockout of ErbB4 from PV interneurons in SC showed abnormal basal mechanical threshold. Meanwhile, NRG1 treatment could not relieve tactile allodynia in PV-Erbb4 mice or AAV-PV-Erbb4 mice after CFA injection. These experimental results suggest that regulating NRG1-ErbB4 signaling in SC could reduce pain hypersensitivity and contribute to EA analgesia in inflammatory pain.
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http://dx.doi.org/10.3389/fnins.2021.636348DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7875897PMC
January 2021

Clinical characteristics of inpatients with coronavirus disease 2019 (COVID-19) in Sichuan province.

BMC Infect Dis 2021 Feb 8;21(1):155. Epub 2021 Feb 8.

Department of Respiratory and Critical Care Medicine, West China Hospital, Sichuan University, Chengdu, 610041, China.

Background: The outbreak of COVID-19 has resulted in serious concerns in China and abroad. To investigate clinical features of confirmed and suspected patients with COVID-19 in west China, and to examine differences between severe versus non-severe patients.

Methods: Patients admitted for COVID-19 between January 21 and February 11 from fifteen hospitals in Sichuan Province, China were included. Experienced clinicians trained with methods abstracted data from medical records using pre-defined, pilot-tested forms. Clinical characteristics between severe and non-severe patients were compared.

Results: Of the 169 patients included, 147 were laboratory-confirmed, 22 were suspected. For confirmed cases, the most common symptoms from onset to admission were cough (70·7%), fever (70·5%) and sputum (33·3%), and the most common chest CT patterns were patchy or stripes shadowing (78·0%); throughout the course of disease, 19·0% had no fever, and 12·4% had no radiologic abnormality; twelve (8·2%) received mechanical ventilation, four (2·7%) were transferred to ICU, and no death occurred. Compared to non-severe cases, severe ones were more likely to have underlying comorbidities (62·5% vs 26·2%, P = 0·001), to present with cough (92·0% vs 66·4%, P = 0·02), sputum (60·0% vs 27·9%, P = 0·004) and shortness of breath (40·0% vs 8·2%, P <  0·0001), and to have more frequent lymphopenia (79·2% vs 43·7%, P = 0·003) and eosinopenia (84·2% vs 57·0%, P = 0·046).

Conclusions: The symptoms of patients in west China were relatively mild, and an appreciable proportion of infected cases had no fever, warranting special attention.
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http://dx.doi.org/10.1186/s12879-021-05825-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7868861PMC
February 2021

Mild Cognitive Impairment Patients Have Higher Regulatory T-Cell Proportions Compared With Alzheimer's Disease-Related Dementia Patients.

Front Aging Neurosci 2020 22;12:624304. Epub 2021 Jan 22.

Eastern Department of Neurology, Guangdong Geriatrics Institute, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou, China.

The role of neuroinflammation in the pathogenesis of Alzheimer's disease (AD) has attracted much attention recently. Regulatory T-cells (Tregs) play an important role in modulating inflammation. We aimed to explore the Treg-related immunosuppression status at different stages of AD. Thirty healthy control (HC) subjects, 26 patients with mild cognitive impairment (MCI), 30 patients with mild probable AD-related dementia, and 28 patients with moderate-to-severe probable AD-related dementia underwent detailed clinical history taking, structural MRI scanning, and neuropsychological assessment. Peripheral blood samples were taken to measure the percentage of CD4CD25CD127 Tregs by flow cytometry and the levels of interleukin (IL-10), interleukin (IL-35), and transforming growth factor β (TGF-β) by ELISA. The percentage of Tregs in the blood of MCI patients was the highest (9.24%); there was a significant difference between patients with MCI and patients with probable AD-related dementia. The level of TGF-β in patients with MCI (47.02 ng/ml) was significantly increased compared with patients with AD-related dementia. There were positive correlations between Treg percentage, IL-35, and Mini-mental state evaluation scores in patients with MCI and probable AD-related dementia. Patients with MCI have stronger Treg-related immunosuppression status compared with patients with probable AD-related dementia.
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http://dx.doi.org/10.3389/fnagi.2020.624304DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7862571PMC
January 2021

Observation of the analgesic effect of superficial or deep anterior serratus plane block on patients undergoing thoracoscopic lobectomy.

Medicine (Baltimore) 2021 01;100(3):e24352

Department of Anesthesiology, Intensive Care Medicine and Pain Medicine, the First Affiliated Hospital of Soochow University, Suzhou.

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http://dx.doi.org/10.1097/MD.0000000000024352DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7837840PMC
January 2021

Accurate Analysis of Tricarboxylic Acid Cycle Metabolites and Anion Components in Hemocytes by IC-CD/ESI-MS for Quantifying Insecticide Impairment on Cellular Immunity in .

J Agric Food Chem 2021 Feb 3;69(6):1984-1993. Epub 2021 Feb 3.

Shanghai Key Lab of Chemical Biology, School of Pharmacy, East China University of Science and Technology, Shanghai 200237, China.

Insecticides are more broadly known to affect insect cellular immunity, but the components in hemocytes and their response to insecticide stress are still unknown. In this paper, a method based on trifluoroacetic acid extraction, followed by IC-CD/ESI-MS analysis, was developed to simultaneously determine tricarboxylic acid (TCA) cycle metabolites and anion components in hemocytes from larvae. Validation gave excellent selectivity, recovery (88.7-107.6%), linear correlation ( > 0.9961), precision (<3.89%), LOD (0.002-0.006 mg/L), LOQ (0.006-0.020 mg/L), and a short chromatographic run. The method was verified by administration of 4-((3-chloro-4-fluorophenyl)amino)-7-methoxyquinazolin-6-yl 3-(1,3-dioxoiso-indolin-2-yl) propanoate (QDP) or emamectin benzoate (EMB) to hemocytes in vitro and larvae in vivo. TCA metabolites including citrate, α-ketoglutarate, fumarate, malate, and oxaloacetate, and anions including acetate, oxalate, chloride, carbonate, and sulfate were identified and clearly separated. QDP and EMB showed a biphasic dose effect on TCA metabolites, and the contrary hormesis paralleled the different actions of QDP and EMB. The inhibition or improvement of cellular immunity depended on the QDP concentration. In conclusion, a highly sensitive, reliable, and robust method was developed, enabling the monitoring of hemocyte immunity by the quantification of TCA metabolites and anion components in minute hemocyte samples.
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http://dx.doi.org/10.1021/acs.jafc.0c07481DOI Listing
February 2021

Longitudinal evaluation of diastolic dyssynchrony by SPECT gated myocardial perfusion imaging early after acute myocardial infarction and the relationship with left ventricular remodeling progression in a swine model.

J Nucl Cardiol 2021 Jan 27. Epub 2021 Jan 27.

Department of Nuclear Medicine, The Third Affiliated Hospital of Soochow University, No. 185, Juqian Street, Changzhou, 213003, Jiangsu Province, China.

Background: Left ventricular diastolic dyssynchrony (LVDD), a dyssynchronous relaxation pattern, has been known to develop after myocardial damage. We aimed to evaluate the dynamic changes in LVDD in the early stage of acute myocardial infarction (AMI) by phase analysis of technetium methoxyisobutylisonitrile (Tc-MIBI) single-photon emission computed tomography (SPECT) gated myocardial perfusion imaging (GMPI) and explore its relationship with the progression of left ventricular remodeling (LVR).

Methods: The left anterior descending coronary arteries of 16 Bama miniature swine were occluded with a balloon to build AMI models. Animals were imaged by SPECT GMPI before AMI and at 1 day, 1 week and 4 weeks after AMI, and quantitative analysis was performed to determine the extent of left ventricle (LV) perfusion defects, left ventricular systolic dyssynchrony (LVSD) and the LVDD parameters: phase histogram bandwidth (PBW) and phase standard deviation (PSD). Echocardiography was simultaneously applied to evaluate left ventricular end-diastolic volume (LVEDV), left ventricular end-systolic volume (LVESV), left ventricular ejection fraction (LVEF), and the LVDD parameters: Te-12-diff and Te-12-SD. Myocardial injury markers were measured, and 12-lead ECGs were performed. The degree of LVR progression was defined as ΔLVESV (%) = (LVESV - LVESV)/LVESV.

Results: Thirteen swine completed the study. LVDD parameters changed dynamically at different time points after AMI. LVDD occurred as early as 1 day after AMI, peaked at 1 week, and trended toward a partial recovery at 4 weeks. Phase analysis on SPECT GMPI showed a significant correlation with tissue Doppler imaging for the assessment of LVDD during the longitudinal evaluation (r = 0.569 to 0.787, both P <0.05). During the univariate and multivariate regression analyses, the LVDD parameters PBW and PSD as of 1 day after AMI were significantly associated with the progression of LVR, respectively (PBW, β = 0.004, 95% CI 0.001 to 0.007, P = 0.024; PSD, β = 0.008, 95% CI 0.000 to 0.017, P = 0.049). Adjusted smooth curve fitting and threshold effect analysis indicated PBW and PSD break-point values of 142° and 60.4°, respectively, to predict the progression of LVR after AMI.

Conclusions: Phase analysis of SPECT GMPI can accurately and reliably characterize LVDD. LVDD occurred on the first day after AMI, reached its peak at 1 week, and partially recovered at 4 weeks after AMI. LVDD as evaluated by phase analysis of SPECT GMPI early after AMI was significantly associated with the progression of LVR. The early assessment of LVDD after AMI may provide helpful information for predicting the progression of LVR in the future.
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http://dx.doi.org/10.1007/s12350-020-02483-9DOI Listing
January 2021

Electroacupuncture Ameliorates Neuroinflammation-Mediated Cognitive Deficits through Inhibition of NLRP3 in Presenilin1/2 Conditional Double Knockout Mice.

Neural Plast 2021 6;2021:8814616. Epub 2021 Jan 6.

South China Research Center for Acupuncture and Moxibustion, Medical College of Acu-Moxi and Rehabilitation, Guangzhou University of Chinese Medicine, Guangzhou 510006, China.

Neuroinflammation is considered as one of the crucial pathogenesis in promoting neurodegenerative progress of Alzheimer's disease (AD). As complementary and alternative therapy, electroacupuncture (EA) stimulation has been widely used in clinical practice for anti-inflammation. However, whether EA promotes the cognitive deficits resulting from neuroinflammation in AD remains unclear. In this study, the presenilin 1 and 2 conditional double knockout (PS cDKO) mice, exhibited a series of AD-like pathology, robust neuroinflammatory responses, and memory deficits, were used to evaluate the potential neuroprotective effect of EA at (GV 20) and (GV 24) by behavioral testing, electrophysiology recording, and molecular biology analyzing. First, we observed that EA improved memory deficits and impaired synaptic plasticity. Moreover, EA possesses an ability to suppress the hyperphosphorylated tau and robust elevated NLRP3, ASC, Caspase-1, IL-1, and IL-18 in PS cDKO mice. Importantly, MCC950, a potent and selective inhibitor of NLPR3 inflammasome, has similar effects on inhibiting the hyperphosphorylated tau and the robust elevated NLRP3 components and neuroinflammatory responses of PS cDKO mice as well as EA treatment. Furthermore, EA treatment is not able to further improve the AD-like phenotypes of PS cDKO mice in combination with the MCC950 administration. Therefore, EA stimulation at GV 20 and GV 24 acupoints may be a potential alternative therapy for deterring cognitive deficits in AD through suppression of NLRP3 inflammasome activation.
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http://dx.doi.org/10.1155/2021/8814616DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7806385PMC
January 2021

Both Age and Disease Duration are Associated with Clinical Phenotype of Hori's Nevus in Chinese: A Retrospective Analysis of 497 Cases.

Clin Cosmet Investig Dermatol 2021 18;14:65-71. Epub 2021 Jan 18.

Aesthetic Department, Dermatology Hospital, Southern Medical University, Guangzhou, Guangdong 510091, People's Republic of China.

Background: Hori's nevus is a common pigmented disorder on the face, preferentially in females. The clinical features have not been well characterized.

Aim: To characterize the clinical features of Hori's nevus in Chinese adults.

Subjects And Methods: Data were collected from files of patients who visited our hospital from 2015 to 2018. Age- and disease duration-related characteristics were analyzed.

Results: A total of 497 patients, including 486 females and 11 males, were included in this analysis. One fifth of the patients had a family history of Hori's nevus. Over 70% of patients were aged 21-30 years. Age at onset was comparable between males and females (20.64 ± 1.01 vs 18.99 ± 0.24). Out of 497 subjects, 218 subjects (44%) displayed yellow-brown lesions while blue-brown lesions wwere observed in 103 subjects (21%). The rest (176 cases, 35%) showed slate-grey lesions. Involvement in the zygomatic area was observed in 496/497 subjects. Involvement in a single area accounted for 74% of patients, while two areas were involved in 19% of patients. The number of involved areas correlated positively with disease duration. However, the proportion of subjects with yellow-brown lesions correlated negatively with disease duration, while the proportion of subjects with slate-grey lesions correlated positively with disease duration. The proportion of subjects with lesions involving the lower eyelids, the root of the nose, the temple and the outer frontal area correlated positively with age.

Conclusion: Hori's nevus mainly involves the zygomatic area in subjects aged 21-30 years. Lesion color is associated with age, age at onset, and disease duration.
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http://dx.doi.org/10.2147/CCID.S285935DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7823097PMC
January 2021

A Comparison of Efficacy and Safety of Fractional Carbon Dioxide Laser and Fractional Er:YAG Laser for the Treatment of Xanthelasma Palpebrarum: A Two-Center Randomized Split-Face Controlled Trial.

Photobiomodul Photomed Laser Surg 2021 Feb 15;39(2):131-136. Epub 2021 Jan 15.

Department of Dermatology, School of Clinical Medicine, Beijing Tsinghua Changgung Hospital, Tsinghua University, Beijing, China.

Xanthelasma palpebrarum (XP) is a form of cutaneous xanthoma that presents as collections of yellowish papules or plaques around the eyelids or canthus, affecting patients cosmetically. This study aimed to compare the efficacy and safety of fractional carbon dioxide (CO) laser to that of fractional Er:YAG laser for the treatment of XP. Two centers recruited patients diagnosed with XP of bilaterally symmetrical lesions. The lesion on one side was randomly assigned to be treated with fractional CO laser while the lesion on the other side was treated with fractional Er:YAG laser. All subjects received up to five treatments, with a 4-week interval between each treatment. Thirty-nine patients completed the study and a total of 82 lesions were available for final assessment. The percentage of "Excellent Improvement" on third and fourth visit was 60.98% versus 39.02% and 90.24% versus 63.41%, respectively,  < 0.05. In a follow-up for 12 to 25 months, the number of lesions recurred on the side treated with fractional CO laser and fractional Er:YAG laser are 9 (22%) and 10 (24%), respectively. In this study, fractional CO laser therapy appears superior since a fewer treatments are required for patients to show significant clinical improvement.
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http://dx.doi.org/10.1089/photob.2020.4874DOI Listing
February 2021

Guidelines for the Diagnosis and Treatment of Hepatocellular Carcinoma (2019 Edition).

Liver Cancer 2020 Dec 11;9(6):682-720. Epub 2020 Nov 11.

Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.

Background: Primary liver cancer, around 90% are hepatocellular carcinoma in China, is the fourth most common malignancy and the second leading cause of tumor-related death, thereby posing a significant threat to the life and health of the Chinese people.

Summary: Since the publication of in 2018, additional high-quality evidence has emerged with relevance to the diagnosis, staging, and treatment of liver cancer in and outside China that requires the guidelines to be updated. The new edition was written by more than 70 experts in the field of liver cancer in China. They reflect the real-world situation in China regarding diagnosing and treating liver cancer in recent years.

Key Messages: Most importantly, the new guidelines were endorsed and promulgated by the Bureau of Medical Administration of the National Health Commission of the People's Republic of China in December 2019.
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http://dx.doi.org/10.1159/000509424DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7768108PMC
December 2020

Synthesis of boron carbonitride nanosheets using for delivering paclitaxel and their antitumor activity.

Colloids Surf B Biointerfaces 2021 Feb 21;198:111479. Epub 2020 Nov 21.

School of Materials Science and Engineering, Key Lab of Advanced Materials of Tropical Island Resources, Ministry of Education, Hainan University, Haikou, 570228, China. Electronic address:

As a structural analog of graphene and boron nitride, hexagonal boron carbonitride nanosheets (BCNNSs) are supposed to be a potential drug deliverer. In the present work, an improved solid-state reaction method combined with ultrasonic exfoliating was reported for preparing BCNNSs. Vapor-solid (VS) mechanism was proposed to be responsible for the formation of BCNNSs. The BCNNSs were further modified by DSPE-mPEG-5000 to improve their dispersion in aqueous solution. It was found that the BCNNSs-PEG nanocomplex could be efficiently taken in by MDA-MB-231 breast cancer cells evidenced by inverted fluorescence microscopy. The PEGylated BCNNSs showed an outstanding ability to load paclitaxel through π-π interaction and hydrophobic interaction, and BCNNSs-PEG-loaded paclitaxel presented higher cytotoxicity in comparison with free paclitaxel. BCNNSs may become a promising candidate for delivering paclitaxel and other hydrophobic drugs.
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http://dx.doi.org/10.1016/j.colsurfb.2020.111479DOI Listing
February 2021

Employing ATP as a New Adjuvant Promotes the Induction of Robust Antitumor Cellular Immunity by a PLGA Nanoparticle Vaccine.

ACS Appl Mater Interfaces 2020 Dec 20;12(49):54399-54414. Epub 2020 Nov 20.

Laboratory of Molecular Immunology, Institute of Medical Biology, Chinese Academy of Medical Sciences & Peking Union Medical College, Kunming 650118, China.

Tumor vaccines based on synthetic human papillomavirus (HPV) oncoprotein E7 and/or E6 peptides have shown encouraging results in preclinical model studies and human clinical trials. However, the clinical efficacy may be limited by the disadvantages of vulnerability to enzymatic degradation and low immunogenicity of peptides. To further improve the potency of vaccine, we developed a poly(lactide--glycolide)-acid (PLGA) nanoparticle, which encapsulated the antigenic peptide HPV16 E7, and used adenosine triphosphate (ATP), one of the most important intracellular metabolites and an endogenous extracellular danger signal for the immune system, as a new adjuvant component. The results showed that PLGA nanoparticles increased the stability, lymph node accumulation, and dendritic cell (DC) uptake of the E7 peptide; in addition, ATP further increased the migration, nanoparticle uptake, and maturation of DCs. Preventive immunization with ATP-adjuvanted nanoparticles completely abolished the growth of TC-1 tumors in mice and produced long-lasting immunity against tumor rechallenge. When tumors were fully established, therapeutic immunization with ATP-adjuvanted nanoparticles still significantly inhibited tumor progression. Mechanistically, ATP-adjuvanted nanoparticles significantly improved the systemic generation of antitumor effector cells, boosted the local functional status of these cells in tumors, and suppressed the generation and tumor infiltration of immunosuppressive Treg cells and myeloid-derived suppressor cells. These findings indicate that ATP is an effective vaccine adjuvant and that nanoparticles adjuvanted with ATP were able to elicit robust antitumor cellular immunity, which may provide a promising therapeutic vaccine candidate for the treatment of clinical malignancies, such as cervical cancer.
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http://dx.doi.org/10.1021/acsami.0c15522DOI Listing
December 2020
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