Publications by authors named "Dandan Chen"

274 Publications

Social support, anxiety symptoms, and depression symptoms among residents in standardized residency training programs: the mediating effects of emotional exhaustion.

BMC Psychiatry 2021 Sep 21;21(1):460. Epub 2021 Sep 21.

Department of Burn and Plastic Surgery, Guizhou Provincial People's Hospital, Guiyang, China.

Background: Although studies indicate that social support is related to emotional exhaustion, depression symptoms, and anxiety symptoms, the underlying mechanism between those variables remains unknown.

Methods: Based on a sample of 254 residents in standardized residency training programs, two mediation models were tested in which emotional exhaustion served as a mediator in the relationship between social support and anxiety symptoms/depression symptoms. We used the following self-reported questionnaires as instruments to collect data: zung self-rating depression scale, zung self-rating anxiety scale, social support rating scale, and emotional exhaustion scale.

Results: In the final study sample, the mean age of the residents was 25.92 years old (SD =1.88), and a total of 41.3% were male, and 58.7% were female. This current study suggested that social support was proven to be a relevant factor affecting anxiety symptoms and depression symptoms. Particularly, the results also indicated that emotional exhaustion partially mediated the impact of social support on anxiety symptoms and depression symptoms among Chinese residents in the standardized residency training program.

Conclusions: Our study signifies that enhancements in social support and reduction of emotional exhaustion can directly or indirectly affect anxiety symptoms and depression symptoms among Chinese residents in the standardized residency training program. These findings will offer insight for health-sector managers to develop programs aimed at social support and adopt individual-level interventions and organization-level interventions to reduce emotional exhaustion.
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http://dx.doi.org/10.1186/s12888-021-03381-1DOI Listing
September 2021

NocU is a cytochrome P450 oxygenase catalyzing -hydroxylation of the indolic moiety during the maturation of the thiopeptide antibiotics nocathiacins.

Org Biomol Chem 2021 Sep 15. Epub 2021 Sep 15.

State Key Laboratory of Bioorganic and Natural Products Chemistry, Center for Excellence on Molecular Synthesis, Shanghai Institute of Organic Chemistry, University of Chinese Academy of Sciences, 345 Lingling Road, Shanghai 200032, China.

The ribosomally synthesized and post-translationally modified peptide (RiPP) natural products include the family of thiopeptide antibiotics, where nocathiacins (NOCs) and nosiheptide (NOS) are structurally related bicyclic members featuring an indolic moiety within the side ring system. Compared with NOS, NOCs bear additional functionalities that lead to the improvement of water solubility and bioavailability, a problem inherent to most of the thiopeptide antibiotics, and thus hold potential for clinical use in anti-infective agent development. The process through which post-translational modifications (PTMs) occur to afford these functionalities remains unclear. In this study, an engineered NOS-producing strain is applied to study the function of NocU, a cytochrome P450 oxygenase unique during the PTMs in NOC biosynthesis. Benefiting from the isolation and structure characterization of nosiheptide U (NOS-U), a new NOS-type compound with an extra hydroxyl group at the indole nitrogen, we report that NocU is responsible for the -hydroxylation of the indolic moiety during the maturation of NOCs. This finding reveals the cause of structural differences at the indole nitrogen of NOCs, which will not only accelerate the biosynthetic studies of NOCs, but also promote new analog development by utilizing the compatibility of the biosynthetic machinery of thiopeptide antibiotics.
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http://dx.doi.org/10.1039/d1ob01284cDOI Listing
September 2021

Catalytic Stereoselective Conversion of Biomass-Derived 4'-Methoxypropiophenone to -Anethole with a Bifunctional and Recyclable Hf-Based Polymeric Nanocatalyst.

Polymers (Basel) 2021 Aug 21;13(16). Epub 2021 Aug 21.

State Key Laboratory Breeding Base of Green Pesticide & Agricultural Bioengineering, Key Laboratory of Green Pesticide & Agricultural Bioengineering, Ministry of Education, State-Local Joint Laboratory for Comprehensive Utilization of Biomass, Center for Research & Development of Fine Chemicals, Guizhou University, Guiyang 550025, China.

Anethole (AN) is widely used as an odor cleaner in daily necessities, and can also be applied in the fields of food additives, drug synthesis, natural preservatives, and polymeric materials' preparation. Considering environmental and economic benefits, the use of biomass raw materials with non-precious metal catalysts to prepare high-value fine chemicals is a very promising route. Here, we developed an acid-base bifunctional polymeric material (PhP-Hf (1:1.5)) composed of hafnium and phenylphosphonate in a molar ratio of 1:1.5 for catalytic conversion of biomass-derived 4'-methoxypropiophenone (4-MOPP) to AN via cascade Meerwein-Pondorf-Verley (MPV) reduction and dehydration reactions in a single pot. Compared with the traditional catalytic systems that use high-pressure hydrogen as a hydrogen donor, alcohol can be used as a safer and more convenient hydrogen source and solvent. Among the tested alcohols, 2-pentanol was found to be the best candidate in terms of pronounced selectivity. A high AN yield of 98.1% at 99.8% 4-MOPP conversion (TOF: 8.5 h) could be achieved over PhP-Hf (1:1.5) at 220 °C for 2 h. Further exploration of the reaction mechanism revealed that the acid and base sites of PhP-Hf (1:1.5) catalyst synergistically promote the MPV reduction step, while the Brønsted acid species significantly contribute to the subsequent dehydration step. In addition, the PhP-Hf polymeric nanocatalyst can be recycled at least five times, showing great potential in the catalytic conversion of biomass.
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http://dx.doi.org/10.3390/polym13162808DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8400820PMC
August 2021

Moderate Exercise Combined with Enriched Environment Enhances Learning and Memory through BDNF/TrkB Signaling Pathway in Rats.

Int J Environ Res Public Health 2021 08 5;18(16). Epub 2021 Aug 5.

College of Physical Education, Yangzhou University, Yangzhou 225127, China.

This study aimed to investigate the effects and potential mechanisms of exercise combined with an enriched environment on learning and memory in rats. Forty healthy male Wistar rats (7 weeks old) were randomly assigned into 4 groups ( = 10 in each group): control (C) group, treadmill exercise (TE) group, enriched environment (EE) group and the TE + EE group. The Morris water maze (MWM) test was used to evaluate the learning and memory ability in all rats after eight weeks of exposure in the different conditions. Moreover, we employed enzyme-linked immunosorbent assay (ELISA) to determine the expression of brain-derived neurotrophic factor (BDNF) and receptor tyrosine kinase B (TrkB) in the rats. The data showed that the escape latency and the number of platform crossings were significantly better in the TE + EE group compared to the TE, EE or C groups ( < 0.05). In addition, there was upregulation of BDNF and TrkB in rats in the TE + EE group compared to those in the TE, EE or C groups ( < 0.05). Taken together, the data robustly demonstrate that the combination of TE + EE enhances learning and memory ability and upregulates the expression of both BDNF and TrkB in rats. Thus, the BDNF/TrkB signaling pathway might be modulating the effect of exercise and enriched environment in improving learning and memory ability in rats.
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http://dx.doi.org/10.3390/ijerph18168283DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8392212PMC
August 2021

Influence of Aerobic Fitness on White Matter Integrity and Inhibitory Control in Early Adulthood: A 9-Week Exercise Intervention.

Brain Sci 2021 Aug 18;11(8). Epub 2021 Aug 18.

College of Physical Education, Yangzhou University, Yangzhou 225127, China.

Previous cross-sectional studies have related aerobic fitness to inhibitory control and white matter (WM) microstructure in young adults, but there is no longitudinal study to confirm whether these relationships exist. We carried out a longitudinal study comparing aerobic fitness, inhibitory control, and WM integrity across time points, before versus after completing an exercise intervention in young adults (18-20 years old) relative to a control group. The exercise group ( = 35) participated in a 9-week exercise protocol, while the control group ( = 24) did not receive any regular exercise training. Behavioral data and diffusion tensor imaging (DTI) data were collected prior to and following the intervention. After the exercise intervention, aerobic fitness and inhibitory control performance were significantly improved for the exercise group, but not for the control group. Analyses of variance (ANOVA) of the DTI data demonstrated significantly increased fractional anisotropy (FA) in the right corticospinal tract and significantly decreased FA in the left superior fronto-occipital fasciculus in the exercise group after the intervention versus before. The enhanced aerobic fitness induced by exercise was associated with better inhibitory control performance in the incongruent condition and lower FA in the Left superior fronto-occipital fasciculus (SFOF). Regression analysis of a mediation model did not support Left SFOF FA as a mediator of the relationship between improvements in aerobic fitness and inhibitory control. The present data provide new evidence of the relationship between exercise-induced changes in aerobic fitness, WM integrity, and inhibitory control in early adulthood. Longer-duration intervention studies with larger study cohorts are needed to confirm and further explore the findings obtained in this study.
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http://dx.doi.org/10.3390/brainsci11081080DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8391670PMC
August 2021

The efficacy and safety of bevacizumab combined with FOLFOX regimen in the treatment of advanced colorectal cancer: A systematic review and meta-analysis.

Medicine (Baltimore) 2021 Jul;100(30):e26714

Department of Gastroenterology, The Affiliated Suqian First People's Hospital of Nanjing Medical University, Suqian, China.

Background: It is necessary to systematically evaluate the clinical efficacy and safety of bevacizumab (BEV) combined with 5-fluorouracil + leucovorin + oxaliplatin (FOLFOX) regimen in the treatment of advanced colorectal cancer.

Methods: We searched the PubMed et al databases for randomized controlled trials (RCTs) on the BEV combined with the FOLFOX regimen in the treatment of advanced colorectal cancer up to January 20, 2021. The Cochrane Collaborations' risk of bias tool was used for the quality assessment of included RCTs. Revman5.3 software was used for meta-analysis.

Results: Eleven RCTs with a total of 3178 patients with advanced colorectal cancer were included, meta-analysis results showed that the objective response rate (odds ratio [OR] = 3.15, 95% confidence intervals [CI]: 2.25-4.40, P < .001) and cancer control rate (OR = 2.73, 95% CI: 1.91-3.90, P < .001) of BEV + FOLFOX were higher than that of FOLFOX group. And the incidence of gastrointestinal adverse reactions (OR = 1.29, 95% CI: 1.07-1.55, P = .008) in the BEV + FOLFOX group was higher than that of the FOLFOX group, there were no significant differences in the incidence of leukopenia (OR = 1.04, 95% CI: 0.72-1.50, P = .83), hypertension (OR = 3.92, 95% CI: 0.81-18.88, P = .09) and neurotoxicity (OR = 1.00, 95% CI: 0.8-1.27, P = .98) between the 2 groups.

Conclusion: BEV combined with the FOLFOX regimen is more effective than the FOLFOX regimen alone in the treatment of advanced colorectal cancer, but it may also increase the risk of gastrointestinal adverse reactions.
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http://dx.doi.org/10.1097/MD.0000000000026714DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8322501PMC
July 2021

Factors associated with treatment response to CD19 CAR-T therapy among a large cohort of B cell acute lymphoblastic leukemia.

Cancer Immunol Immunother 2021 Aug 7. Epub 2021 Aug 7.

Hebei Yanda Lu Daopei Hospital, Langfang, China.

CD19-targeted chimeric antigen receptor (CAR) T cell therapy has demonstrated striking responses among B cell acute lymphoblastic leukemia (B-ALL), but analyses of potential factors associated with poor response and relapse are lacking. Here, we summarize the long-term follow-up of 254 B-ALL treated with CD19 CAR-T cells from 5 clinical trials (NCT03173417, NCT02546739, and NCT03671460 retrospectively registered on May 23, 2017, March 1, 2018, and September 7, 2018, respectively, at www.clinicaltrials.gov ; ChiCTR-ONC-17012829, and ChiCTR1800016541 retrospectively registered on September 28, 2017, and June 7, 2018, at www.chictr.org.cn ). Our data showed that TP53 mutation, bone marrow blasts > 20%, prior CAR-T/blinatumomab treatment, and severe cytokine release syndrome (CRS) were associated with a lower complete remission (CR) rate while age, extramedullary disease, complex cytogenetics, history of prior transplant, prior courses of chemotherapy, CAR-T cell dose, and manufacturing source of the cellular product did not affect patients' CR rate. Risk factors related to leukemia-free survival (LFS) and overall survival (OS) were history of prior transplant, complex cytogenetics, TP53 mutation, severe CRS, neurotoxicity, and CAR-T therapy without consolidative allogeneic hematopoietic stem cell transplantation (allo-HSCT). Age and CAR-T cell dose did not influence LFS and OS. Patients with consolidative allo-HSCT after CAR-T therapy had a superior OS and LFS compared to those who did not. This benefit was also observed in both pediatric and adult patients as well as in patients either in high- or low-risk groups. This large study to identify risk factors of CR, LFS, and OS may help to maximize clinical outcomes of CAR-T therapy. Précis TP53 mutation and BM blasts > 20% are two independent factors associated with the CR rate. Patients with high tumor burden as well as those with bone marrow blasts < 5% can benefit from consolidative allo-HSCT post-CAR-T therapy.
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http://dx.doi.org/10.1007/s00262-021-03009-zDOI Listing
August 2021

The Rice Cation/H Exchanger Family Involved in Cd Tolerance and Transport.

Int J Mol Sci 2021 Jul 30;22(15). Epub 2021 Jul 30.

CAAS-IRRI Joint Laboratory for Genomics-Assisted Germplasm Enhancement, Agricultural Genomics Institute at Shenzhen, Chinese Academy of Agricultural Sciences, Shenzhen 518120, China.

Cadmium (Cd), a heavy metal toxic to humans, easily accumulates in rice grains. Rice with unacceptable Cd content has become a serious food safety problem in many rice production regions due to contaminations by industrialization and inappropriate waste management. The development of rice varieties with low grain Cd content is seen as an economic and long-term solution of this problem. The cation/H exchanger (CAX) family has been shown to play important roles in Cd uptake, transport and accumulation in plants. Here, we report the characterization of the rice family. The six rice genes all have homologous genes in . Phylogenetic analysis identified two subfamilies with three rice and three genes in both of them. All rice genes have trans-member structures. and were localized in the vacuolar while were localized in the plasma membrane in rice cell. The consequences of qRT-PCR analysis showed that all the six genes strongly expressed in the leaves under the different Cd treatments. Their expression in roots increased in a Cd dose-dependent manner. GUS staining assay showed that all the six rice genes strongly expressed in roots, whereas and also strongly expressed in rice leaves. The yeast () cells expressing , and grew better than those expressing the vector control on SD-Gal medium containing CdCl. and enhanced while reduced Cd accumulation in yeast. No auto-inhibition was found for all the rice genes. Therefore, , and are likely to involve in Cd uptake and translocation in rice, which need to be further validated.
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http://dx.doi.org/10.3390/ijms22158186DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8348036PMC
July 2021

The role of available phosphorous in vanadate decontamination by soil indigenous microbial consortia.

Environ Pollut 2021 Jul 22;289:117839. Epub 2021 Jul 22.

School of Water Resources and Environment, MOE Key Laboratory of Groundwater Circulation and Environmental Evolution, China University of Geosciences (Beijing), Beijing, 100083, PR China.

Indigenous microbial consortia are closely associated with soil inherent components including nutrients and minerals. Although indigenous microbial consortia present great prospects for bioremediation of vanadate [V(V)] contaminated soil, influences of some key components, such as available phosphorus (AP), on V(V) biodetoxification are poorly understood. In this study, surface soils sampled from five representative vanadium smelter sites were employed as inocula without pretreatment. V(V) removal efficiency ranged from 81.7 ± 1.4% to 99.5 ± 0.2% in batch experiment, and the maximum V(V) removal rates were positively correlated with AP contents. Long-term V(V) removal was achieved under fluctuant hydrodynamic and hydrochemical conditions in column experiment. Geobacter and Bacillus, which were found in both original soils and bioreactors, catalytically reduced V(V) to insoluble tetravalent vanadium. Phosphate-solubilizing bacterium affiliated to Gemmatimonadaceae were also identified abundantly. Microbial functional characterization indicated the enrichment of phosphate ABC transporter, which could accelerate V(V) transfer into intercellular space for efficient reduction due to the structural similarity of V(V) and phosphate. This study reveals the critical role of AP in microbial V(V) decontamination and provides promising strategy for in situ bioremediation of V(V) polluted soil.
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http://dx.doi.org/10.1016/j.envpol.2021.117839DOI Listing
July 2021

Psychometric properties of the ethical conflict in nursing questionnaire critical care version among Chinese nurses: a cross-sectional study.

BMC Nurs 2021 Jul 28;20(1):133. Epub 2021 Jul 28.

The Second Affiliated Hospital Zhejiang University School of Medicine (SAHZU), No.88 Jiefang road, Shangcheng District, Hangzhou, 310009, Zhejiang Province, China.

Background: Ethical conflicts are common in the critical care setting, and have compromised job satisfaction and nursing care quality. Using reliable and valid instruments to measure the ethical conflict is essential. This study aimed to translate the Ethical Conflict in Nursing Questionnaire - Critical Care Version into Chinese and determine the reliability and validity in the population of Chinese nurses.

Methods: Researchers obtained permission and followed the translation-backward method to develop the Chinese version of the Ethical Conflict in Nursing Questionnaire - Critical Care Version (ECNQ-CCV-C). Relevant psychometric properties were selected according to the Consensus-based standards for the selection of health status measurement instruments checklist. Critical care nurses were recruited from two tertiary public hospitals in Hangzhou, Zhejiang Province, and Kunming, Yunnan Province. Of the 264 nurses we approached, 248 gave their consent and completed the study.

Results: The ECNQ-CCV-C achieved Cronbach's alphas 0.902 and McDonald's omega coefficient 0.903. The test-retest reliability was satisfactory within a 2-week interval (intraclass correlation coefficient = 0.757). A unidimensional structure of the ECNQ-CCV-C was determined. Confirmatory factor analysis supported acceptable structure validity. Concurrent validity was confirmed by a moderate relation with a measure for hospital ethical climate (r = - 0.33, p < 0.01). The model structure was invariant across different gender groups, with no floor/ceiling effect.

Conclusions: The ECNQ-CCV-C demonstrated acceptable reliability and validity among Chinese nurses and had great clinical utility in critical care nursing.
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http://dx.doi.org/10.1186/s12912-021-00651-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8316889PMC
July 2021

Light-Controlled Precise Delivery of NIR-Responsive Semiconducting Polymer Nanoparticles with Promoted Vascular Permeability.

Adv Healthc Mater 2021 Jul 26:e2100569. Epub 2021 Jul 26.

Department of Biomedical Engineering, Southern University of Science and Technology, Shenzhen, Guangdong, 518055, China.

The endothelial barrier plays an essential role in health and disease by protecting organs from toxins while allowing nutrients to access the circulation. However, it is the major obstacle that limits the delivery of therapeutic drugs to the diseased tissue. Here, it is reported for the first time that near-infrared (NIR) laser pulses can transiently promote the delivery of semiconducting polymer nanoparticles passing the vascular barrier via photoacoustic-effect-induced accumulation, only by the aid of pulse laser irradiation. This strategy enables selective and substantial accumulation of the NIR-absorbing nanoparticles inside specific tissues, implying the discovery of an unprecedented approach for light-controlled nanoparticle delivery. Especially, the nanoparticle delivery in solid tumors by 10-min laser scanning is approximately six times higher than that of the enhanced permeability and retention (EPR) effect in 24 h under current experimental conditions. Further results confirm that this strategy facilitates substantial accumulation of nanoparticles in the mouse brain with intact skull. This approach thus opens a new door for tissue-specific delivery of nanomaterials with an unprecedented level of efficiency and precision.
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http://dx.doi.org/10.1002/adhm.202100569DOI Listing
July 2021

Residency program directors' perceptions about the impact of the American Board of Anesthesiology's Objective Structured Clinical Examination.

J Clin Anesth 2021 Jul 20;75:110439. Epub 2021 Jul 20.

Department of Anesthesiology, Perioperative and Pain Medicine, Stanford University, Stanford, CA, USA. Electronic address:

Study Objective: To describe how the introduction of an Objective Structured Clinical Examination (OSCE) by the American Board of Anesthesiology (ABA) to its initial certification impacted anesthesiology residencies in the United States.

Design And Setting: A sequential mixed-methods design with focus groups and online survey among program directors of Accreditation Council for Graduate Medical Education-accredited anesthesiology residencies.

Patients: No patients were included.

Intervention: None.

Measurements: A convenience sample of 34 program directors were interviewed to understand their perceptions of the ABA OSCE. Subsequently, an online survey, based on major themes identified from the focus groups, was sent to all 156 program directors.

Main Results: Several themes emerged from the focus group discussions: (1) a mock OSCE was most common for preparing residents for the ABA OSCE; 2) the ABA OSCE led to changes in residency curriculum; 3) the ABA OSCE assessed communication and professionalism skills well, and how well it assessed technical skills was less agreed on. Survey results from 87 program directors (response rate = 56%) were mostly consistent with the themes generated by the focus groups. Eight-one out of 87 programs (93%) specifically prepared their residents for the ABA OSCE. Fifty-two out of 81 program directors (64%) reported the introduction of the ABA OSCE led to curricular changes. Out of 79 program directors, 45 (57%) agreed the ABA OSCE assesses skills essential to anesthesiology practice, and 40 (51%) considered it added value to board certification.

Conclusions: The introduction of the OSCE by the ABA for board certification has affected the curriculum of many residencies. Approximately 3 in 5 program directors perceived the ABA OSCE measures skills essential to anesthesiologists' practice. Future studies should assess residency graduates' perspective on the usefulness of both mock OSCE preparation and the ABA OSCE, and whether the ABA OSCE performance predicts future clinical practice.
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http://dx.doi.org/10.1016/j.jclinane.2021.110439DOI Listing
July 2021

Profiling and Molecular Mechanism Analysis of Long Non-Coding RNAs and mRNAs in Pulmonary Arterial Hypertension Rat Models.

Front Pharmacol 2021 29;12:709816. Epub 2021 Jun 29.

Department of Cardiology, Zhongshan Hospital, Fudan University, Shanghai Institute of Cardiovascular Disease, Shanghai, China.

Pulmonary arterial hypertension (PAH) is an immune-mediated disease with poor prognosis and associated with various inflammatory immune diseases. In fact, its pathogenesis is far from clear. Although long non-coding RNAs (lncRNAs) have been implicated in PAH, the molecular mechanisms remain largely unknown. For the first time, in lungs of monocrotaline-induced PAH rat models, we simultaneously detected the expression profiles of lncRNAs and mRNAs by high-throughput sequencing, and explored their roles with bioinformatics analysis and cell assay to discover more potential pathogenesis about PAH. Our data identified that a total of 559 lncRNAs and 691 mRNAs were differentially expressed in lungs during the pathogenesis of PAH. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses demonstrated that these dysregulated lncRNAs and mRNAs participated in important biological processes and pathways of PAH, among which inflammatory and immune responses represented the chief enriched pathway. The lncRNA-mRNA co-expression network was developed to uncover the hidden interactions between lncRNAs and mRNAs. Further, the expression levels of lncRNAs (NONRATT018084.2, NONRATT009275.2, NONRATT007865.2, and NONRATT026300.2) and mRNAs (LGALS3, PDGFC, SERPINA1, and NFIL3) were confirmed using quantitative real-time PCR. In the end, lncRNA NONRATT009275.2 could facilitate macrophage polarization to M2 type and be involved in inflammatory immune response. In conclusion, this study provided candidate drug targets and potential roles on lncRNAs in the pathogenesis of PAH, and several key regulatory genes were identified, which laid the initial foundation for further mechanism study in PAH.
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http://dx.doi.org/10.3389/fphar.2021.709816DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8277419PMC
June 2021

First-in-Human Trial of EphA2-Redirected CAR T-Cells in Patients With Recurrent Glioblastoma: A Preliminary Report of Three Cases at the Starting Dose.

Front Oncol 2021 21;11:694941. Epub 2021 Jun 21.

Department of Neurosurgery, Xuanwu Hospital, Capital Medical University, Beijing, China.

Glioblastoma is the most common primary brain malignancy with limited treatment options. EphA2 is a tumor-associated-antigen overexpressed in glioblastoma. Pre-clinical studies have demonstrated the promise of EphA2-redirected CAR T-cells against glioblastoma. We conduct the first-in-human trial of EphA2-redirected CAR T-cells in patients with EphA2-positive recurrent glioblastoma and report the results of three patients enrolled as the first cohort receiving the starting dosage (1×10 cells/kg). A single infusion of EphA2-redirected CAR T-cells was administrated intravenously, with the lymphodepletion regimen consisting of fludarabine and Cyclophosphamide. In two patients, there was grade 2 cytokine release syndrome accompanied by pulmonary edema, which resolved completely with dexamethasone medication. Except that, there was no other organ toxicity including neurotoxicity. In both the peripheral blood and cerebral-spinal-fluid, we observed the expansion of CAR T-cells which persisted for more than four weeks. In one patient, there was a transit diminishment of the tumor. Among these three patients, one patient reported SD and two patients reported PD, with overall survival ranging from 86 to 181 days. At the tested dose level (1×10 cells/kg), intravenously infusion of EphA2-rediretected CAR T-cells were preliminary tolerable with transient clinical efficacy. Future study with adjusted dose and infusion frequency of CAR T-cells is warranted.

Trial Registration Numbers: NCT03423992.
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http://dx.doi.org/10.3389/fonc.2021.694941DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8256846PMC
June 2021

External Validation of the Prognostic Prediction Model for 4-Year Risk of Metabolic Syndrome in Adults: A Retrospective Cohort Study.

Diabetes Metab Syndr Obes 2021 1;14:3027-3034. Epub 2021 Jul 1.

Department of Nursing, Zhejiang University School of Medicine Sir Run Run Shaw Hospital, Hangzhou, Zhejiang, People's Republic of China.

Purpose: A prediction model for 4-year risk of metabolic syndrome in adults was previously developed and internally validated. However, external validity or generalizability for this model was not assessed so it is not appropriate for clinical application. We aimed to externally validate this model based on a retrospective cohort.

Patients And Methods: A retrospective cohort design and a temporal validation strategy were used in this study based on a dataset from 1 January 2015 to 31 December 2018. Multiple imputation was used for missing values. Model performance was evaluated by using discrimination, calibration (calibration plot, calibration slope, and calibration intercept), overall performance (Brier score), and decision curve analysis.

Results: In external validation, the C-statistic was 0.782 (95% CI, 0.771-0.793). The calibration plot shows good calibration, calibration slope was 1.006 (95% CI, -0.011-1.063), and calibration intercept was -0.045 (95% CI, -0.113-0.022). Brier score was 0.164.The discrimination and calibration of the prediction model were good in temporal external validation.

Conclusion: The discrimination and calibration of the prediction model were satisfactory in the temporal external validation. However, clinicians should be aware that this prediction model was developed and validated in a tertiary setting. It is strongly recommended that further studies validate this model in international cohorts and large, prospective cohorts in different institutions.
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http://dx.doi.org/10.2147/DMSO.S316950DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8257261PMC
July 2021

Increased levels of serum IL-17 and induced sputum neutrophil percentage are associated with severe early-onset asthma in adults.

Allergy Asthma Clin Immunol 2021 Jul 5;17(1):64. Epub 2021 Jul 5.

Emergency Department, Key Laboratory of Shenzhen Respiratory Diseases, Institute of Shenzhen Respiratory Diseases, Shenzhen People's Hospital (The First Affiliated Hospital of Southern University of Science and Technology, The Second Clinical Medical College of Jinan University), 1017 Dongmen North Road, Shenzhen, 518020, Guangdong, China.

Background: Differences between adult patients with severe early-onset and late-onset asthma have not been well studied.

Objectives: To determine the phenotypic distinction regarding age at onset in patients with severe asthma.

Methods: The present study enrolled thirty-two patients with severe early-onset (onset age < 12 years) asthma and thirty-two patients with severe late-onset (onset age > 12 years) asthma. Severe asthma was defined according to Global Initiative for Asthma criteria. The clinical, spirometric, and laboratory parameters were collected for group comparisons.

Results: Among the 64 patients included (mean age, 46.22 ± 13.90 years; 53.1% male), the mean percent of predicted forced expiratory volume in 1 s (FEV1) was 68.43 ± 20.55%. Patients with severe early-onset asthma had a younger age, longer duration of asthma, higher rate of family history, and better small-airway function (MEF25% and MMEF75/25%) compared with severe late-onset asthma. Furthermore, levels of serum IL-17 and sputum neutrophil percentage were significantly higher for patients with severe early-onset asthma (P = 0.016, 0.033, respectively). Multiple logistic regression analysis revealed that increased serum IL-17 (odds ratio = 1.065, P = 0.016) was independently associated with severe early-onset asthma. The combination of serum IL-17 and sputum neutrophil percentage yielded a sensitivity of 80.0% and a specificity of 86.7% for identifying patients with severe early-onset asthma.

Conclusions: Patients with severe early-onset asthma exhibit elevated levels of serum IL-17 and sputum neutrophil percentage, suggesting a potential role in the pathogenesis of severe early-onset phenotype.
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http://dx.doi.org/10.1186/s13223-021-00568-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8256593PMC
July 2021

Biogenic Gas Vesicles for Ultrasound Imaging and Targeted Therapeutics.

Curr Med Chem 2021 Jul 5. Epub 2021 Jul 5.

Department of Ultrasound, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

Ultrasound is not only the most widely used medical imaging mode for diagnostics owing to its real-time, non-radiation, portable, and low-cost merits, but also a promising targeted drug/gene delivery technique by exhibiting a series of powerful bioeffects. The development of micron-sized or nanometer-sized ultrasound agents or delivery carriers further makes ultrasound a distinctive modality in accurate diagnosis and effective treatment. In this review, we introduce one kind of unique biogenic gas-filled protein nanostructures called gas vesicles, presenting some unique characteristics than the conventional microbubbles. Gas vesicles can not only serve as ultrasound contrast agents with innovative imaging methods such as cross-amplitude modulation harmonic imaging but also can further be adjusted and optimized via genetic engineering techniques. Moreover, they could not only serve as acoustic gene reporters, acoustic biosensors to monitor the cell metabolism, but also serve as cavitation nuclei and drug carriers for therapeutic purposes. In this study, we focus on the latest development and applications in the area of ultrasound imaging and targeted therapeutics, and also provide a brief introduction of the corresponding mechanisms. In summary, these biogenic gas vesicles show some advantages over conventional MBs that deserve more efforts to promote their development.
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http://dx.doi.org/10.2174/0929867328666210705145642DOI Listing
July 2021

Human variation in gingival inflammation.

Proc Natl Acad Sci U S A 2021 Jul;118(27)

Department of Periodontics, University of Washington, Seattle, WA 98195;

Oral commensal bacteria actively participate with gingival tissue to maintain healthy neutrophil surveillance and normal tissue and bone turnover processes. Disruption of this homeostatic host-bacteria relationship occurs during experimental gingivitis studies where it has been clearly established that increases in the bacterial burden increase gingival inflammation. Here, we show that experimental gingivitis resulted in three unique clinical inflammatory phenotypes (high, low, and slow) and reveal that interleukin-1β, a reported major gingivitis-associated inflammatory mediator, was not associated with clinical gingival inflammation in the slow response group. In addition, significantly higher levels of spp. were also unique to this group. The low clinical response group was characterized by low concentrations of host mediators, despite similar bacterial accumulation and compositional characteristics as the high clinical response group. Neutrophil and bone activation modulators were down-regulated in all response groups, revealing novel tissue and bone protective responses during gingival inflammation. These alterations in chemokine and microbial composition responses during experimental gingivitis reveal a previously uncharacterized variation in the human host response to a disruption in gingival homeostasis. Understanding this human variation in gingival inflammation may facilitate the identification of periodontitis-susceptible individuals. Overall, this study underscores the variability in host responses in the human population arising from variations in host immune profiles (low responders) and microbial community maturation (slow responders) that may impact clinical outcomes in terms of destructive inflammation.
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http://dx.doi.org/10.1073/pnas.2012578118DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8271746PMC
July 2021

Hepatotoxicity of copper sulfide nanoparticles towards hepatocyte spheroids using a novel multi-concave agarose chip method.

Nanomedicine (Lond) 2021 07 29;16(17):1487-1504. Epub 2021 Jun 29.

School of Radiation Medicine & Protection, State Key Laboratory of Radiation Medicine & Protection, School for Radiological & Interdisciplinary Sciences (RAD-X), Collaborative Innovation Center of Radiation Medicine of Jiangsu Higher Education Institutions, Soochow University, Suzhou, 215123, PR China.

To explore the hepatotoxicity of copper sulfide nanoparticles (CuSNPs) toward hepatocyte spheroids. Other than the traditional agarose method to generate hepatocyte spheroids, we developed a multi-concave agarose chip (MCAC) method to investigate changes in hepatocyte viability, morphology, mitochondrial membrane potential, reactive oxygen species and hepatobiliary transporter by CuSNPs. The MCAC method allowed a large number of spheroids to be obtained per sample. CuSNPs showed hepatotoxicity through a decrease in spheroid viability, albumin/urea production and glycogen deposition. CuSNPs also introduced hepatocyte spheroid injury through alteration of mitochondrial membrane potential and reactive oxygen species, that could be reversed by N-acetyl-l-cysteine. CuSNPs significantly decreased the activity of BSEP transporter by downregulating its mRNA and protein levels. Activity of the MRP2 transporter remained unchanged. We observed the hepatotoxicity of CuSNPs with associated mechanisms in an advanced 3D culture system.
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http://dx.doi.org/10.2217/nnm-2021-0011DOI Listing
July 2021

Periostin deficiency attenuates lipopolysaccharide- and obesity-induced adipose tissue fibrosis.

FEBS Lett 2021 08 3;595(16):2099-2112. Epub 2021 Jul 3.

School of Life Sciences, Xiamen University, China.

Periostin (POSTN) is a type of matricellular protein, but its functions in adipose fibrosis remain unclear. Here, we found that POSTN expression is significantly increased in mouse adipose tissue after treatment with lipopolysaccharide (LPS) or a high-fat diet (HFD) and that adipose progenitor cells are the main source of POSTN. In our mouse model of fibrosis, POSTN deletion protected mice from adipose fibrosis, probably through reducing the accumulation of macrophages and promoting adipocyte differentiation of progenitor cells. Taken together, our study demonstrates that POSTN deficiency attenuates adipose tissue fibrosis and improves insulin resistance, providing new insights into the diagnosis and treatment of type II diabetes by targeting adipose tissue fibrosis.
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http://dx.doi.org/10.1002/1873-3468.14154DOI Listing
August 2021

In-Furnace Control of Arsenic Vapor Emissions Using FeO Microspheres with Good Sintering Resistance.

Environ Sci Technol 2021 07 24;55(13):8613-8621. Epub 2021 Jun 24.

School of Energy and Power Engineering, Huazhong University of Science and Technology, Wuhan, Hubei 430070, China.

The addition of FeO into furnaces is a promising method for arsenic pollution control. Nevertheless, FeO particles undergo serious sintering under actual furnace temperatures. To improve its sintering resistance, FeO hollow microspheres were synthesized by the template method and were tested in flue gas containing SO and NO in the range of 1000-1300 °C. The results demonstrated that the amount of arsenic captured could be steadily maintained above 5 mg/g throughout the operating temperature range, and FeO microspheres could maintain the originally developed pore structure and hollow morphology well even at 1200 °C. Based on product analysis and density functional theory calculations, the fixation pathway of arsenic was proposed. In no oxygen conditions, AsO was first bound to the FeO surface by forming an -O-As-O-Fe stable structure and then was oxidized by lattice oxygen. The introduction of O could regenerate the consumed lattice oxygen and therefore promote arsenic capture. Finally, the oxidized arsenic was fixed in products in the form of FeAsO. Additionally, the impact of acid gases was also investigated. SO showed a notable inhibiting effect on arsenic capture, while the impact of NO was less noticeable.
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http://dx.doi.org/10.1021/acs.est.1c02381DOI Listing
July 2021

The effect of non-pharmacological interventions on physical restraint reduction in intensive care units: a protocol for an umbrella review of systematic reviews and meta-analysis.

Ann Palliat Med 2021 Jun 18;10(6):6892-6899. Epub 2021 Jun 18.

The Second Affiliated Hospital Zhejiang University School of Medicine (SAHZU), Hangzhou, China; Changxing Branch Hospital of SAHZU, Huzhou, China.

Background: As the last resort in intensive care units, physical restraint reduction is affected by various interventions. Several non-pharmacological interventions may directly reduce physical restraints, such as staff education, or indirectly reduce physical restraint, such as delirium prevention; however, their effectiveness has remained inconclusive. Therefore, we devised a protocol for umbrella reviews to summarize the evidence integrating data of different non-pharmacological interventions that may reduce physical restraint use.

Methods: The umbrella review will be conducted following the methodology formulated by the Joanna Briggs Institute (JBI). Electronic databases, including Web of Science, PubMed, EMBASE, PsycInfo, Psyc Articles, Psychology and Behavioral Science Collection, Cumulative Index to Nursing and Allied Health Literature (CINAHL), JBISRIS (JBI Database of Systematic Reviews and Implementation Reports), Cochrane Database of Systematic Reviews, China National Knowledge Infrastructure (CNKI, for Chinese literature), SinoMed (for Chinese literature), and WANFANG DATA (for Chinese literature), will be searched to identify articles published from January 2016 to December 2020. A systematic review and meta-analysis quality will be critically assessed by AMSTAR 2 (A Measurement Tool to Assess Systematic Reviews). According to the GRADE (Grades of Recommendation, Assessment, Development, and Evaluation) guidelines, the evidence quality of each intervention will be assessed. Overlapping studies and the excess significance test will be performed to assess whether previous evidences are bias.

Discussion: This protocol was devised according to the guidelines of the Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols (PRISMA-P). Umbrella reviews will be an excellent supplement to the evidence of the guideline adaptation and provide a broader picture of non-pharmacological interventions that may reduce the use of physical restraint, which can provide critical care nurses in intensive care units with the evidence they need.

Trial Registration: This umbrella review protocol was documented in the PROSPERO registry (CRD42021242586).
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http://dx.doi.org/10.21037/apm-21-626DOI Listing
June 2021

A biodegradable nano-photosensitizer with photoactivatable singlet oxygen generation for synergistic phototherapy.

J Mater Chem B 2021 06;9(24):4826-4831

Department of Biomedical Engineering, Southern University of Science and Technology, Shenzhen, Guangdong 518055, China.

Photodynamic therapy (PDT) is a promising method for cancer therapy and also may initiate unexpected damages to normal cells and tissues. Herein, we develop a near-infrared (NIR) light-activatable nanophotosensitizer, which shows negligible phototoxicity before photoactivation to improve the specificity of PDT. The nanophotosensitizer is prepared by indocyanine green carboxylic (ICG), Chlorin e6 (Ce6), and biodegradable poly (lactic acid) (PLA) and poly (lactic-co-glycolic acid) (PLGA), and all these materials have been approved by the Food and Drug Administration. Initially the phototoxicity of Ce6 is effectively inhibited by ICG through fluorescence resonance energy transfer (FRET). Upon 808 nm laser activation, ICG generate hyperthermia for photothermal therapy (PTT) and simultaneously is degraded due to the inherently poor photostability. The FRET is disrupted and followed by the recovery of phototoxicity of Ce6 for PDT. We investigated the photoactivation and the resulting phototherapy by cellular assays and mouse models, which indicate a superior synergistic treatment effect and selective PDT activated by near-infrared 808 nm light. This study presents a promising strategy for activatable and synergistic phototherapy with minimal damage to normal tissues.
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http://dx.doi.org/10.1039/d1tb00937kDOI Listing
June 2021

Laparoscopic Uterine Artery Occlusion Combined with Uterine-sparing Pelvic Plexus Block and Partial Adenomyomectomy for Adenomyosis: A Video Case Report.

J Minim Invasive Gynecol 2021 May 26. Epub 2021 May 26.

Department of Obstetrics and Gynecology, Shanghai Tenth People's Hospital, Tongji University, and Institute of Gynecological Minimally Invasive Medicine, Tongji University School of Medicine, Shanghai, China (all authors).. Electronic address:

Objective: Adenomyosis usually causes dysmenorrhea and anemia. Clinically, it is difficult to be treated with medicine or by traditional surgery, however, hysterectomy is always performed for radical treatment. In this article, we introduce a new method that could control the dysmenorrhea and the anemia through laparoscopic uterine artery occlusion (LUAO) combined with uterine-sparing pelvic plexus block and partial adenomyomectomy for uterus preservation.

Design: Surgical video article. Local institutional review board approval for the video reproduction was obtained.

Setting: A 42-year-old patient, who had a history of a previous cesarean delivery, was admitted to our department with complaints of progressive dysmenorrhea for more than 5 years and aggravated with anemia for 1 year. The patient had failed treatment with traditional Chinese medicine and gonadotropin-releasing hormone and had to take painkillers for nearly half a year. The patient had no desire for another pregnancy. After careful consideration, the patient strongly rejected hysterectomy and demanded the preservation of the uterus, insisting on the integrity of the organs. A gynecologic examination showed that the uterus was hard and enlarged similar to one that is more than 8 gestational weeks, without tender nodules in the rectouterine pouch. The visual analog scale pain score was 7, and her hemoglobin was 93 g/L (after correction). The preoperative magnetic resonance imaging implied that there was 1 lesion in the posterior wall and the maximum diameter of the lesion was 7.8 cm.

Interventions: We performed laparoscopic partial adenomyomectomy combined with occlusion of uterine artery to limit the amount of intraoperative bleeding, dissected the uterine branch of pelvic plexus nerve, and performed electrocoagulation blocking to relieve the dysmenorrhea. The specific operation procedures are as follows (Video): Firstly, we opened the peritoneum through Cheng's triangle, which contained the external iliac blood vessels, the round ligament, and the infundibulopelvic ligament (Fig. 1). Secondly, we separated the lateral rectal space and exposed the ureter, the internal iliac artery, the uterine artery, and the deep uterine vein. Thirdly, we found that the pelvic plexus was located on the outside of the sacral ligament and was approximately 2 to 3 cm below the ureter, going against the sacral ligament and passing through below the deep uterine vein (Supplemental Video 1). Fourthly, we separated the 4 layers of the paracervix [1]. The first layer included the internal iliac artery and the uterine artery. The second layer was the ureter. The third layer was the deep uterine vein. The last layer was the pelvic plexus, which involved the forward-going bladder branch, the inward-going uterine branch, and the downward-going rectal branch (Supplemental Video 2). These anatomic structures are similar to the complex architecture of an overpass called the Cheng's Cross [2] (Fig. 2). In this operation, only the uterine artery and the uterine branch would be blocked. Finally, we performed the partial adenomyomectomy. The endometrium, the myometrial tissues, and the serosa were repaired in some layers with continuous suture, depending on the depth of incision. The operation time was 92 minutes, and the intraoperative hemorrhage was approximately 50 mL. The patient was able to get out of bed on the first day after the operation and urinate after removing the catheter. On the second day after the surgery, the patient had exhaustion and defecation. From the third day after the surgery, gonadotropin-releasing hormone (Goserelin Acetate Sustained-Release Depot,3.6mg each, subcutaneous injection, name of the enterprise: AstraZeneca UK Limited) was used every 4 weeks, with a total of 3 times. Menstruation began on the 67th day after withdrawal of the drug. The results of postoperative condition of the patient followed up at 6 months after surgery were collected as follows: dysmenorrhea was significantly relieved (visual analog scale score was 2), hemoglobin was 123 g/L, and uterine volume was reduced to 43% of preoperative volume. The comparison of the patient's preoperative and postoperative magnetic resonance imaging showed that the uterus was approximately the same size as that of a woman of the same age, and the incision healed well (Fig. 3).

Conclusion: Adenomyosis is a common gynecologic disease, mainly occurring in women of childbearing age. Adenomyosis is defined as endometrial glands and stroma that invade the myometrium and is surrounded by chronical inflammation in the endometrium [3]. Secondary dysmenorrhea and menorrhagia are the most common chief complaints in patients with adenomyosis, among which dysmenorrhea is the most unbearable symptom [2]. In the past, we had always treated adenomyosis by hysterectomy [4]. With the continuous pursuit of quality of life, it is difficult to meet clinical needs through drugs and traditional surgical methods. Uterine sparing surgery is a current trend in the treatment of adenomyosis, which enables women to maintain fertility and avoid the effects of hysterectomy on sexual function and mental discomfort. Dysmenorrhea can be divided into peripheral dysmenorrhea and central dysmenorrhea. According to our previous studies on dysmenorrhea, the uterine branch nerve has a controlling effect on dysmenorrhea [2]. The purpose of pelvic plexus uterine branch ablation is to further relieve dysmenorrhea by blocking nerve conduction pathways. Therefore, we selectively blocked the uterine branch nerve to alleviate the dysmenorrhea of adenomyosis. The uterine artery controls 90% of uterine blood flow. According to our team research, LUAO is an effective method to treat symptomatic uterine myomas and adenomyosis. We investigated the morphologic change and apoptosis occurring in myomal and adjacent myometrial tissues after LUAO. We concluded that apoptosis through mitochondrial pathways may lead to reduction of the volume of myoma and myometrium and eventually relief of symptoms [5,6]. We speculated "single organ shock uterine" to explain uterine artery occlusion (UAO) mechanism, which was different from uterine artery embolization. The single organ shock theory of UAO can still inhibit the growth of myomas effectively. It is difficult to completely remove adenomyosis lesions during surgery, especially for diffuse adenomyosis. Therefore, in our team, we performed UAO combined with resection of focal lesions in key areas for patients with diffuse adenomyosis, instead of pursuing radical resection [7,8]. The purpose of UAO is to reduce the amount of bleeding during surgery and further atrophy of residual and scattered adenomyosis lesions in utero [5,6]. The intraoperative blocking of the uterine artery can reduce intraoperative bleeding and operation time, improve operation quality, and decrease recurrence rate. In our team, this technique has been used in clinic for more than 10 years. Our previous studies have shown that LUAO combined with pelvic plexus uterine branch nerve block and resection of most of the adenomyosis has achieved satisfactory clinical efficacy as a treatment for adenomyosis [2,3]. With this procedure, we can help patients with adenomyosis retain their uterus and relieve the anxiety caused by hysterectomy. In conclusion, UAO and uterine branch ablation in uterine sparing laparoscopic treatment is a safe and effective method, which may be considered as a good choice for symptomatic adenomyosis.
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http://dx.doi.org/10.1016/j.jmig.2021.05.015DOI Listing
May 2021

Autologous manganese phosphates with different Mn sites for electrocatalytic water oxidation.

Chem Commun (Camb) 2021 Jun;57(50):6165-6168

Key Laboratory of Applied Surface and Colloid Chemistry, Ministry of Education, School of Chemistry and Chemical Engineering, Shaanxi Normal University, Xi'an 710119, China.

Herein, we report two autologous phosphates obtained from the same parent material for electrocatalytic water oxidation. These two phosphates have many similarities except the coordination structure of the Mn centers. It has been straightforwardly observed that the highly asymmetric geometry of Mn2P2O7 can stabilize the active Mn(iii) to promote water oxidation.
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http://dx.doi.org/10.1039/d1cc01004bDOI Listing
June 2021

Development and Internal Validation of a Prognostic Model for 4-Year Risk of Metabolic Syndrome in Adults: A Retrospective Cohort Study.

Diabetes Metab Syndr Obes 2021 18;14:2229-2237. Epub 2021 May 18.

Zhejiang University, School of Medicine, Sir Run Run Shaw Hospital, Hangzhou, Zhejiang, People's Republic of China.

Purpose: A prognostic prediction model for metabolic syndrome can help nurses or physicians evaluate the future individual absolute risk of MetS in order to develop personalized care strategies. We aimed to derive and internally validate a prognostic prediction model for 4-year risk of metabolic syndrome in adults.

Patients And Methods: This was a retrospective cohort study conducted in a tertiary care setting, and the dataset was obtained from the Healthcare Information and Management Systems of a tertiary hospital. The cohort included Chinese adults attending health examination from 1 January 2011 to 31 December 2014. A total of 6793 participants without metabolic syndrome were included in the cohort and were followed up for 4 years. Available candidate predictors in the dataset were weight, MCV, MCH, AST, ALT, BMI, NGC, TC, serum uric acid, gender, smoking, WBC, LC, Hb, HCT, and age. A logistic regression model was adopted to build the risk equation, and bootstrapping was used when considering internal validation. Calibration, discrimination, and the clinical utility were calculated for the model's performance.

Results: Of the 6793 participants, 1750 participants were diagnosed with metabolic syndrome within 4 years. The developed prediction model contained 5 predictors (body mass index, age, total cholesterol, alanine transaminase, and serum uric acid). After internal validation, the C-statistic was 0.783 (95% CI, 0.772-0.795). Additionally, the current model had good calibration. Calibration slope was 0.995 (95% CI, 0.934-1.058), and calibration intercept was -0.008 (95% CI, -0.088-0.073). The Brier score was 0.156. The decision-curve analysis indicated that the prediction model provided greater net benefit than the default strategies of providing treatment or not providing treatment for all patients.

Conclusion: A prognostic risk prediction model for determining 4-year risk of metabolic syndrome onset in adults was developed and internally validated. This model was based on routine clinical measurements that quantified individual future risk of metabolic syndrome.
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http://dx.doi.org/10.2147/DMSO.S288881DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8140900PMC
May 2021

Calcium phosphate-based composite cement: Impact of starch type and starch pregelatinization on its physicochemical properties and performance in the vertebral fracture surgical models in vitro.

J Biomed Mater Res B Appl Biomater 2021 May 24. Epub 2021 May 24.

Department of Orthopedics, Orthopedic Institute, The First Affiliated Hospital, Soochow University, Suzhou, China.

Calcium phosphate cement (CPC) modified with native and pregelatinized normal corn and waxy maize starches was studied. Effects of starch pregelatinization and starch type on the physicochemical properties of CPC were investigated. CPC modified with pregelatinized normal corn starch (CPB-PNC) or pregelatinized waxy maize starch (CPB-PW) was evaluated by two vertebral fracture surgical models in vitro. Both granular and pregelatinized starches significantly improved the setting times and injectability of CPC, but only the pregelatinized starches improved the anti-collapsibility and compressive strength of CPC significantly. CPB-PW, whose micro-structure was compact and uniform, showed the best physicochemical properties. Addition of starch did not inhibit the hydro-reaction of CPC. Unmodified CPC had very poor dispersibility and could not apply in the tests of the surgical models. Pregelatinized starch especially waxy maize starch improved the dispersibility of CPC and showed good dispersion area, volume, improved pull-out force and maximum torque in the Sawbones sponge model. Similarly, in the minimally invasive kyphoplasty model, CPB-PNC and CPB-PW could disperse in the osteoporotic sheep vertebrae and improve the compressive strength of the sheep vertebral body. In conclusion, starch pregelatinization and starch botanical source affect the physicochemical properties of CPC significantly. Bone cements modified by different starches also performed differently in surgical models for osteoporotic vertebral fracture. Pregelatinized waxy maize starch may be a better candidate for CPC modification comparing to the pregelatinized normal corn starch.
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http://dx.doi.org/10.1002/jbm.b.34855DOI Listing
May 2021

MiR-210-3p Enhances Cardiomyocyte Apoptosis and Mitochondrial Dysfunction by Targeting the NDUFA4 Gene in Sepsis-Induced Myocardial Dysfunction.

Int Heart J 2021 May 15;62(3):636-646. Epub 2021 May 15.

Department of Pulmonary and Critical Care Medicine, Hainan General Hospital.

Sepsis-induced myocardial dysfunction (SIMD) is a common complication with high incidence rates in sepsis patients. This study aimed to investigate the roles of miR-210-3p in regulating cardiomyocyte apoptosis and mitochondrial dysfunction associated with SIMD pathogenesis.A rat sepsis model was established by cecal ligation and puncture. Serum inflammatory factors, myocardial tissue apoptosis, and expression of miR-210-3p were evaluated. In vitro, miR-210-3p expression in H9C2 cells was altered by transfection with its mimics or inhibitors. H9C2 viability was assessed via CCK-8 assay, and reactive oxygen species (ROS) production and apoptosis were detected through flow cytometry. The targeting regulatory relations between miR-210-3p and NADH dehydrogenase (ubiquinone) 1 alpha subcomplex 4 (NDUFA4) were validated by dual luciferase reporter assay.The rat sepsis model showed increased serum TNF-α and IL-6 levels, significant myocardial tissue injuries and apoptosis with decreased Bcl-2 and increased Caspase-1 protein levels. In vitro, septic rat serum suppressed viability, promoted ROS production and apoptosis, impaired COX IV activities and increased cytochrome release in H9C2 cells. The expression of miR-210-3p was greatly increased in myocardial tissues of septic rats and septic serum-treated H9C2 cells. miR-210-3p directly binds to the 3' UTR of the NDUFA4 gene. Septic rat serum suppressed NDUFA4 and Iron-Sulfur Cluster Assembly Protein U gene expressions in H9C2 cells. The above cellular and molecular alterations in H9C2 cells induced by septic serum were enhanced by miR-210-3p mimics and abrogated by miR-210-3p inhibitors.miR-210-3p promoted SIMD pathogenesis by targeting NDUFA4 to enhance cardiomyocyte apoptosis and impair mitochondrial function.
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http://dx.doi.org/10.1536/ihj.20-512DOI Listing
May 2021

SET knockdown attenuated phenotype modulation and calcium channel associated markers of airway smooth muscle cells in asthmatic mice.

Ann Transl Med 2021 Apr;9(8):657

Key Laboratory of Shenzhen Respiratory Disease, Shenzhen Institute of Respiratory Disease, Shenzhen People's Hospital (The First Affiliated Hospital of Southern University of Science and Technology, The Second Clinical Medical College of Jinan University), Shenzhen, China.

Background: Dysfunctional phenotype modulation and calcium channels in airway smooth muscle cells (ASMCs) are important characteristics of airway remodeling in chronic asthma. However, the mechanisms underlying these pathological processes remain unclear. SET (I2PP2A, inhibitor-2 of protein phosphatase 2A) has many significant functions and is involved in various physiological and pathological processes. This study aimed to determine the function of SET in chronic asthma.

Methods: BALB/c mice were sensitized by ovalbumin injection and repeated inhalation of ovalbumin. The Penh value was measured using the Buxco whole body plethysmography system. A short hairpin RNA of the SET gene was designed and transfected into ASMCs derived from asthmatic mice. Flow cytometry of Annexin-V/propidium iodide staining was used for evaluating cell apoptosis. Western blot was adopted to measure the expression levels of ASMCs phenotype modulation markers and calcium channel-associated proteins.

Results: The results showed that shRNA targeting SET significantly decreased the expression of SET, and enhanced the apoptosis of ASMCs. SET knockdown promoted the expression of contractile phenotype markers such as α-SMA (alpha smooth muscle Actin), SM-MHC (smooth muscle Myosin heavy chain), and calponin, and inhibited the expression of synthetic phenotype markers including vimentin and CD44. The expression of the calcium channel-related proteins STIM1 (Stromal interaction molecule 1) and Orai1 were also inhibited after SET knockdown.

Conclusions: These data demonstrated that SET participated in the development of airway dysfunction in asthma, suggesting that the silencing of SET may be a new therapeutic target for the treatment of asthma patients.
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http://dx.doi.org/10.21037/atm-21-573DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8106076PMC
April 2021

Ultra-Conformable Ionic Skin with Multi-Modal Sensing, Broad-Spectrum Antimicrobial and Regenerative Capabilities for Smart and Expedited Wound Care.

Adv Sci (Weinh) 2021 05 15;8(9):2004627. Epub 2021 Feb 15.

Orthopedic Institute and Department of Orthopedics The First Affiliated Hospital, Soochow University Suzhou Jiangsu 215006 P. R. China.

While rapid wound healing is essential yet challenging, there is also an unmet need for functional restoration of sensation. Inspired by natural skin, an ultra-conformable, adhesive multi-functional ionic skin (MiS) with multi-modal sensing capability is devised for smart and expedited wound care. The base of MiS is a unique skin-like, conductive and self-adaptive adhesive polyacrylamide/starch double-network hydrogel (PSH) and self-powered, flexible, triboelectric sensor(s) is integrated on top of PSH for multi-tactile sensing. MiS could enhance wound contraction, collagen deposition, angiogenesis, and epidermis formation in a full-thickness skin defect wound model , while significantly inhibiting the biofilm formation of a wide range of microorganisms. MiS also exhibits multi-modal sensing capability for smart and instant therapeutics and diagnostics, including skin displacement or joint motion, temperature, pressure and tissue exudate changes of wound bed, and locally releasing drugs in a pH-responsive manner. More importantly, MiS could restore the skin-mimicking tactile sensing function of both touch location and intensity, and thus could be used as a human-machine interface for accurate external robotic control. MiS demonstrates a new comprehensive paradigm of combining wound diagnosis and healing, broad-spectrum anti-microbial capability and restoration of multi-tactile sensing for the reparation of severe wound.
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http://dx.doi.org/10.1002/advs.202004627DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8097371PMC
May 2021
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