Publications by authors named "Qing Cao"

409 Publications

Inhibition of histone deacetylase 5 ameliorates abnormalities in 16p11.2 duplication mouse model.

Neuropharmacology 2021 Nov 22;204:108893. Epub 2021 Nov 22.

Department of Physiology and Biophysics, State University of New York at Buffalo, Jacobs School of Medicine and Biomedical Sciences, Buffalo, NY, 14214, USA. Electronic address:

Microduplication of the human 16p11.2 gene locus is associated with a range of neurodevelopmental outcomes, including autism spectrum disorder (ASD). Mice carrying heterozygous 16p11.2 duplication (16p11.2) display social deficits, which is attributable to impaired GABAergic synaptic function in prefrontal cortex (PFC) driven by downregulation of Npas4, an activity-dependent transcription factor that regulates GABA synapse formation. However, the molecular mechanisms underlying the diminished transcription of Npas4 in 16p11.2 duplication remain unknown. Npas4 is one of the target genes regulated by histone deacetylase 5 (HDAC5), an epigenetic enzyme repressing gene expression via removal of transcription-permissive acetyl groups from histones. Here we report that HDAC5 expression is elevated and histone acetylation is reduced at the Npas4 promoter in PFC of 16p11.2 mice. Treatment with the HDAC5 inhibitor LMK235 normalizes histone acetylation, restores GABAergic signaling in PFC, and significantly improves social preference in 16p11.2 mice. These findings suggest that HDAC5 inhibition is a promising therapeutic avenue to alleviate genetic, synaptic and behavioral deficits in 16p11.2 duplication conditions.
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http://dx.doi.org/10.1016/j.neuropharm.2021.108893DOI Listing
November 2021

Evaluation of different air distribution systems in a commercial airliner cabin in terms of comfort and COVID-19 infection risk.

Build Environ 2021 Nov 18:108590. Epub 2021 Nov 18.

Department of Building Environment and Energy Engineering, The Hong Kong Polytechnic University, Hong Kong.

The air distribution system in an airliner plays a key role in maintaining a comfortable and healthy environment in the aircraft cabin. To evaluate the performance of a novel displacement ventilation (DV) system and a traditional mixing ventilation (MV) system in an airliner cabin, this study conducted experiments and simulations in a seven-row cabin mockup. This investigation used ultrasonic anemometers and T-thermocouples to measure the air velocity, temperature and distribution of 1 μm and 5 μm particles. Simulation verifications were performed for these operating conditions, and additional scenarios with different occurrence source locations were also simulated. This study combined the Wells-Riley equation with a real case based on a COVID-19 outbreak among passengers on a long-distance bus to obtain the COVID-19 quanta value. Through an evaluation of the airflow organization, thermal comfort, and risk of COVID-19 infection, the two ventilation systems were compared. This investigation found that polydisperse particles should be used to calculate the risk of infection in airliner cabins. In addition, at the beginning of the pandemic, the infection risk with DV was lower than that with MV. In the middle and late stages of the epidemic, the infection risk with MV can be reduced when passengers wear masks, leading to an infection risk approximately equal to that of DV.
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http://dx.doi.org/10.1016/j.buildenv.2021.108590DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8599143PMC
November 2021

Electroacupuncture modulates the intestinal microecology to improve intestinal motility in spinal cord injury rats.

Microb Biotechnol 2021 Nov 19. Epub 2021 Nov 19.

The Second Affiliated Hospital of Hainan Medical University, Haikou, China.

Spinal cord injury (SCI) is a disease involving gastrointestinal disorders. The underlying mechanisms of the potential protective effects of electroacupuncture (EA) and 5-hydroxytryptamine (5-HT) system on SCI remain unknown. We investigated whether EA improves gut microbial dysbiosis in SCI and regulates the 5-HT system. 16S rDNA gene sequencing was applied to investigate alterations in the gut microbiome of the rats. Faecal metabolites and the expression of the 5-HT system were detected. EA and faecal microbiota transplantation (FMT) treatment facilitated intestinal transmission functional recovery and restored the colon morphology of SCI rats. The composition of the intestinal microbiota, including numbers of phylum Proteobacteria, class Clostridia, order Bacteroidales, and genus Dorea, were amplified in SCI rats, and EA and FMT significantly reshaped the intestinal microbiota. SCI resulted in disturbed metabolic conditions in rats, and the EA and FMT group showed increased amounts of catechin compared with SCI rats. SCI inhibited 5-HT system expression in the colon, which was significantly reversed by EA and FMT treatment. Therefore, EA may ameliorate SCI by modulating microbiota and metabolites and regulate the 5-HT system. Our study provides new insights into the pathogenesis and therapy of SCI from the perspective of microbiota and 5-HT regulation.
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http://dx.doi.org/10.1111/1751-7915.13968DOI Listing
November 2021

A donor-DNA-free CRISPR/Cas-based approach to gene knock-up in rice.

Nat Plants 2021 Nov 15;7(11):1445-1452. Epub 2021 Nov 15.

Department of Plant Biosecurity, Key Laboratory of Pest Monitoring and Green Management, Ministry of Agriculture and Rural Affairs, College of Plant Protection, China Agricultural University, Beijing, China.

Structural variations (SVs), such as inversion and duplication, contribute to important agronomic traits in crops. Pan-genome studies revealed that SVs were a crucial and ubiquitous force driving genetic diversification. Although genome editing can effectively create SVs in plants and animals, the potential of designed SVs in breeding has been overlooked. Here, we show that new genes and traits can be created in rice by designed large-scale genomic inversion or duplication using CRISPR/Cas9. A 911 kb inversion on chromosome 1 resulted in a designed promoter swap between CP12 and PPO1, and a 338 kb duplication between HPPD and Ubiquitin2 on chromosome 2 created a novel gene cassette at the joint, promoter::HPPD. Since the original CP12 and Ubiquitin2 genes were highly expressed in leaves, the expression of PPO1 and HPPD in edited plants with homozygous SV alleles was increased by tens of folds and conferred sufficient herbicide resistance in field trials without adverse effects on other important agronomic traits. CRISPR/Cas-based genome editing for gene knock-ups has been generally considered very difficult without inserting donor DNA as regulatory elements. Our study challenges this notion by providing a donor-DNA-free strategy, thus greatly expanding the utility of CRISPR/Cas in plant and animal improvements.
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http://dx.doi.org/10.1038/s41477-021-01019-4DOI Listing
November 2021

Deficiency of autism risk factor ASH1L in prefrontal cortex induces epigenetic aberrations and seizures.

Nat Commun 2021 11 15;12(1):6589. Epub 2021 Nov 15.

Department of Physiology and Biophysics, State University of New York at Buffalo, Jacobs School of Medicine and Biomedical Sciences, Buffalo, NY, 14203, USA.

ASH1L, a histone methyltransferase, is identified as a top-ranking risk factor for autism spectrum disorder (ASD), however, little is known about the biological mechanisms underlying the link of ASH1L haploinsufficiency to ASD. Here we show that ASH1L expression and H3K4me3 level are significantly decreased in the prefrontal cortex (PFC) of postmortem tissues from ASD patients. Knockdown of Ash1L in PFC of juvenile mice induces the downregulation of risk genes associated with ASD, intellectual disability (ID) and epilepsy. These downregulated genes are enriched in excitatory and inhibitory synaptic function and have decreased H3K4me3 occupancy at their promoters. Furthermore, Ash1L deficiency in PFC causes the diminished GABAergic inhibition, enhanced glutamatergic transmission, and elevated PFC pyramidal neuronal excitability, which is associated with severe seizures and early mortality. Chemogenetic inhibition of PFC pyramidal neuronal activity, combined with the administration of GABA enhancer diazepam, rescues PFC synaptic imbalance and seizures, but not autistic social deficits or anxiety-like behaviors. These results have revealed the critical role of ASH1L in regulating synaptic gene expression and seizures, which provides insights into treatment strategies for ASH1L-associated brain diseases.
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http://dx.doi.org/10.1038/s41467-021-26972-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8593046PMC
November 2021

Association of CD34 cell dose with 5-year overall survival after peripheral blood allogeneic hematopoietic cell transplantation in adults with hematologic malignancies.

Transplant Cell Ther 2021 Nov 10. Epub 2021 Nov 10.

Blood and Marrow Transplant Program. Electronic address:

Background: Higher CD34 cell dose is associated with improved engraftment after peripheral blood allogeneic hematopoietic stem cell transplantation (alloHCT), but may also increase the risk of long-term complications, such as graft-versus-host disease (GVHD). Prior studies examining the relationship between CD34 cell dose and long-term survival outcomes have yielded conflicting results.

Objective: This study sought to clarify the prognostic impact of CD34 cell dose by examining a large, contemporary cohort of patients undergoing alloHCT with matched sibling peripheral blood stem cell (PBSC) donors.

Study Design: We retrospectively examined the impact of CD34 cell dose on overall survival (OS), neutrophil engraftment, platelet engraftment, treatment-related mortality (TRM), relapse, acute GVHD grades II-IV and III-IV, and chronic GVHD in 377 consecutive patients undergoing alloHCT with PBSC graft source from matched sibling donors at the University of Minnesota from 2002-2015. Patients were classified into three groups based on tertile (T) of CD34 cell dose received (T1, < 5 × 10 cells/kg; T2, 5-7.5 × 10 cells/kg; T3, ≥ 7.5 × 10 cells/kg).

Results: Multivariable analysis demonstrated that high CD34 cell dose was associated with superior 5-year OS (hazard ratio [HR] 0.57, P = 0.01) and more rapid platelet engraftment (HR 1.70, P < 0.01). Higher CD34 cell doses were also associated with improved absolute neutrophil count engraftment (T2, HR 1.54; T3, HR 1.52; P < 0.01). There was no association between CD34 cell dose and TRM or relapse at 5 years. Although higher CD34 cell doses were not associated with acute GVHD stages II-IV, they were associated with chronic GVHD (T2, HR 1.68; T3, HR 1.50; P = 0.04).

Conclusion: Higher CD34 cell dose (>7.5 × 10/kg) is associated with superior OS at 5 years and improved engraftment but does carry an increased risk of chronic GVHD. These data support a target CD34 cell dose goal of 7.5 × 10/kg for peripheral blood sibling donors.
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http://dx.doi.org/10.1016/j.jtct.2021.11.004DOI Listing
November 2021

Bacterial Epidemiology and Antimicrobial Resistance Profiles in Children Reported by the ISPED Program in China, 2016 to 2020.

Microbiol Spectr 2021 Nov 3:e0028321. Epub 2021 Nov 3.

Department of Clinical Microbiology Laboratory, Children's Hospital of Fudan University, National Children's Medical Center, Shanghai, China.

The Infectious Disease Surveillance of Pediatrics (ISPED) program was established in 2015 to monitor and analyze the trends of bacterial epidemiology and antimicrobial resistance (AMR) in children. Clinical bacterial isolates were collected from 11 tertiary care children's hospitals in China in 2016 to 2020. Antimicrobial susceptibility testing was carried out using the Kirby-Bauer method or automated systems, with interpretation according to the Clinical and Laboratory Standards Institute 2019 breakpoints. A total of 288,377 isolates were collected, and the top 10 predominant bacteria were Escherichia coli, Streptococcus pneumoniae, Staphylococcus aureus, Haemophilus influenzae, Klebsiella pneumoniae, Moraxella catarrhalis, Streptococcus pyogenes, Staphylococcus epidermidis, Pseudomonas aeruginosa, and Acinetobacter baumannii. In 2020, the coronavirus disease 2019 (COVID-19) pandemic year, we observed a significant reduction in the proportion of respiratory tract samples (from 56.9% to 44.0%). A comparable reduction was also seen in the primary bacteria mainly isolated from respiratory tract samples, including S. pneumoniae, H. influenzae, and S. pyogenes. Multidrug-resistant organisms (MDROs) in children were commonly observed and presented higher rates of drug resistance than sensitive strains. The proportions of carbapenem-resistant K. pneumoniae (CRKP), carbapenem-resistant A. baumannii (CRAB), carbapenem-resistant P. aeruginosa (CRPA), and methicillin-resistant S. aureus (MRSA) strains were 19.7%, 46.4%%, 12.8%, and 35.0%, respectively. The proportions of CRKP, CRAB, and CRPA strains all showed decreasing trends between 2015 and 2020. Carbapenem-resistant (CRE) and CRPA gradually decreased with age, while CRAB showed the opposite trend with age. Both CRE and CRPA pose potential threats to neonates. MDROs show very high levels of AMR and have become an urgent threat to children, suggesting that effective monitoring of AMR and antimicrobial stewardship among children in China are required. AMR, especially that involving multidrug-resistant organisms (MDROs), is recognized as a global threat to human health; AMR renders infections increasingly difficult to treat, constituting an enormous economic burden and producing tremendous negative impacts on patient morbidity and mortality rates. There are many surveillance programs in the world to address AMR profiles and MDRO prevalence in humans. However, published studies evaluating the overall AMR rates or MDRO distributions in children are very limited or are of mixed quality. In this study, we showed the bacterial epidemiology and resistance profiles of primary pathogens in Chinese children from 2016 to 2020 for the first time, analyzed MDRO distributions with time and with age, and described MDROs' potential threats to children, especially low-immunity neonates. Our study will be very useful to guide antiinfection therapy in Chinese children, as well as worldwide pediatric patients.
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http://dx.doi.org/10.1128/Spectrum.00283-21DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8567242PMC
November 2021

CRISPR-dependent endogenous gene regulation is required for virulence in piscine .

Emerg Microbes Infect 2021 Dec;10(1):2113-2124

Joint International Research Laboratory of Animal Health and Food Safety, College of Veterinary Medicine, Nanjing Agricultural University, Nanjing, People's Republic of China.

The clustered regularly interspaced palindromic repeats (CRISPR)-Cas (CRISPR-associated) system is a prokaryotic defence against invading mobile genetic elements, such as bacteriophages or exogenous plasmids. Beyond this, this system has been shown to play an important role in controlling the virulence of some bacterial pathogens. strain GD201008-001, a causative agent of septicemia and meningitis in tilapia, contains a single type II CRISPR-Cas system with Cas9 as a signature protein. In this study, we found that the deletion of CRISPR significantly reduced adhesion, invasion, cytotoxicity and haemolysis, and caused severely attenuated virulence in the piscine strain. RNA-Seq identified 236 endogenous genes regulated by CRISPR, with 159 genes upregulated and 77 genes downregulated. The resulting change in gene transcription by CRISPR was much more pronounced than that by in this bacterium, indicating CRISPR-mediated endogenous gene regulation was mostly independently of . Subsequent studies showed that CovR/S two-component system was transcriptionally upregulated due to CRISPR deletion, which repressed the expression of the gene coding for a cytolytic toxin, and thus decreased the activity of β-haemolysin/cytolysin. However, upregulation of CovR/S was not the contributor to the attenuation phenotype of ΔCRISPR. Further, we demonstrated that CRISPR is capable of repressing the expression of Toll-like receptor 2 (TLR2)-activating lipoprotein Sag0671 and thus dampens the innate immune response. This study revealed that the CRISPR system of exhibited extraordinary potential capability in the regulation of endogenous transcripts, which contributes to bacterial innate immune evasion and virulence.
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http://dx.doi.org/10.1080/22221751.2021.2002127DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8592606PMC
December 2021

Genetic transformation and growth index determination of the Larix olgensis LoHDZ2 transcription factor gene in tobacco.

Sci Rep 2021 Oct 20;11(1):20746. Epub 2021 Oct 20.

State Key Laboratory of Tree Genetics and Breeding (Northeast Forestry University), Harbin, 150040, China.

Homeodomain-leucine zippers (HD-Zip) are plant-specific transcription factors that participate in different plant development processes and differentially regulate metabolic processes. LoHDZ2 is an HD-ZipII subfamily transcription factor gene that we identified from a transcriptomic analysis of Larix olgensis. To understand its function, we built a LoHDZ2 expression vector and then inserted it into tobacco by genetic transformation. Transgenic plants were identified at the DNA and RNA levels. Phenotypic index analysis of transgenic tobacco showed dwarfed growth with larger leaves and earlier flowering than the wild type. LoHDZ2 was expressed differently after hormone treatment with IAA, MeJA and 2,4-D. The results suggested that LoHDZ2 may respond to hormones and be involved in regulating growth and metabolism. These results helped us better understand the function of LoHDZ2 and provided a candidate gene for Larix olgensis molecular breeding.
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http://dx.doi.org/10.1038/s41598-021-99533-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8528859PMC
October 2021

Utility and applicability of rapid diagnostic testing in antimicrobial stewardship in Asia Pacific: A Delphi consensus.

Clin Infect Dis 2021 Oct 19. Epub 2021 Oct 19.

Clinical Pathology, Faculty of Medicine, Ramathibodi Hospital, Mahidol University, Bangkok, Thailand.

Rapid diagnostic tests (RDTs) facilitate fast and accurate identification of infectious disease microorganisms and are a valuable component of multimodal antimicrobial stewardship (AMS) programs, but are currently underutilized in Asia Pacific. An experienced group of infectious diseases clinicians, clinical microbiologists and a clinical pharmacist used a modified Delphi consensus approach to construct 10 statements aiming to optimize the utility and applicability of infection-related RDTs for AMS in the Asia Pacific region. They provide guidance on definition, types, optimal deployment, measuring effectiveness, and overcoming key challenges. The Grading of Recommendations Assessment, Development and Evaluation (GRADE) system was applied to indicate the strength of the recommendation and the quality of the underlying evidence. Given the diversity of Asia Pacific, the trajectory of RDT development will vary widely; the collection of local data should be prioritized to allow realization and optimization of the full benefits of RDT in AMS.
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http://dx.doi.org/10.1093/cid/ciab910DOI Listing
October 2021

Using soil amendments to reduce microcystin-LR bioaccumulation in lettuce.

Environ Pollut 2022 Jan 11;292(Pt A):118354. Epub 2021 Oct 11.

State Key Laboratory of Lake Science and Environment, Nanjing Institute of Geography and Limnology, Chinese Academy of Sciences, 73 East Beijing Road, Nanjing, 210008, China.

Contamination of microcystins (MCs) in plant-soil system have become a serious problem worldwide, however, it remains largely unknown how to alleviate the potential risk of consuming MCs-contaminated plants. In the present study, attapulgite, biochar and peat were used as soil amendments to reduce MCs bioaccumulation in lettuce. Lettuce irrigated with 10 μg L microcystin-LR (MC-LR) were growing in two different kinds of soils with or without soil amendments. Results showed that all soil amendments effectively reduced MC-LR bioaccumulation in lettuce roots and leaves. Compared with the control treatment, the MC-LR concentrations in leaves in treatments with attapulgite, biochar and peat decreased by 41.5%, 30.6%, 57.0% in soil A and 38.9%, 43.2%, 54.7% in soil B, respectively. Peat application was most effective in reducing MC-LR bioaccumulation. The decreased soil free MC-LR concentrations were positively correlated with MC-LR concentrations in lettuce, indicating decreased bioavailability of MC-LR by soil amendments. It is noteworthy that soil total MC-LR concentration in peat treatment significantly decreased by 33.3% and 29.4% in soil A and soil B, respectively, compared with the controls. According to the results from high-throughput sequencing, peat amendment increased the α-diversity of soil bacterial community and boosted the abundance of Sphingomonas and Methylobacillus (dozens of MC-degrading bacteria belong to these genera). This was in line with the results of soil total MC-LR concentration. It can be speculated that peat application directly and/or indirectly promoted microbial degradation of MC-LR in soils. This work proposed an effective way to alleviate the potential risks of MCs contamination in plant-soil system.
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http://dx.doi.org/10.1016/j.envpol.2021.118354DOI Listing
January 2022

Embryogenic callus induction from immature zygotic embryos and genetic transformation of Larix kaempferi 3x Larix gmelinii 9.

PLoS One 2021 14;16(10):e0258654. Epub 2021 Oct 14.

State Key Laboratory of Tree Genetics and Breeding (Northeast Forestry University), Harbin, China.

To date, there are few reports of the successful genetic transformation of larch and other conifers, mainly because it is difficult to transform and integrate exogenous genes. In this study, hybrid larch Larix kaempferi 3x Larix gmelinii 9 cones were collected on June 27, July 1, July 4, July 7 and July 16, 2017. Embryogenic callus induction was studied using a combination of different plant growth regulators and concentrations. The results showed that July 1 was the best stage; the highest induction rate was 10.83%, which cultured in BM medium (Button medium, which formula was listed in S1 Table) with 1.0 mg/L 2,4-D (2,4-dichlorophenoxyacetic acid) and 0.2 mg/L KT(kinetin). When cultured on a proliferation medium for 12 days, proliferation was the fastest, reaching 323.08%, which could also maintain the freshness and vitality. The suitable pre-culture medium for somatic embryogenesis was 1/4 BM medium containing 10 g/L inositol and 60 g/L sucrose. The combination of 45 mg/L ABA (abscisic acid) and 75 g/L PEG4000 (Polyethyene glycol 4000) could promote the number of somatic embryos, and reached the maximum, 210 140 per 1 g FW. The genetic transformation was carried out by the Agrobacterium-mediated transformation method with embryogenic callus cultured for 12 days. The results showed the optimal OD600 of the infection solution(suspension of A. tumefaciens) was 0.5, co-culture time was 2 days, and screening concentration of Hyg (hygromycin B) was 4 mg/L. In this study, the transformation rate of resistance callus was 32.1%. It provides a reference for low genetic transformation efficiency of larch at present. This study could be beneficial for the innovation and breeding of larch by genetic engineering and provides a certain basis for rapid propagation of excellent larch germplasm resources and genetic engineering breeding of larch and other conifers.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0258654PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8516217PMC
November 2021

Phosphorescent Carbon-Nanodots-Assisted Förster Resonant Energy Transfer for Achieving Red Afterglow in an Aqueous Solution.

ACS Nano 2021 10 8;15(10):16242-16254. Epub 2021 Oct 8.

Henan Key Laboratory of Diamond Optoelectronic Materials and Devices, Key Laboratory of Material Physics, Ministry of Education, School of Physics and Microelectronics, Zhengzhou University, Zhengzhou 450001, China.

Water-soluble red afterglow imaging agents based on ecofriendly nanomaterials have potential application in time-gated afterglow bioimaging due to their larger penetration depth and nondurable excitation. Herein, red afterglow imaging agents consisted of Rhodamine B (RhB) and carbon nanodots (CNDs) have been designed and demonstrated. In these agents, CNDs act as energy donors, and RhB acts as an energy acceptor. Both of them are confined into a hydrophilic silica shell to form a [email protected] nanocomposite. The phosphorescence emission spectrum of the CNDs and the absorption spectrum of the RhB match well, and efficient energy transfer from the CNDs to the RhB via Förster resonant energy transfer process can be achieved, with a transfer efficiency can reach 99.2%. Thus, the as-prepared nanocomposite can emit a red afterglow in aqueous solution, and the afterglow spectrum of [email protected] nanocomposite can extend to the first near-infrared window (NIR-I). The luminescence lifetime and afterglow quantum yield (QY) of the [email protected] can reach 0.91 s and 3.56%, respectively, which are the best results in red afterglow region. Time-gated afterglow imaging has been demonstrated by using the [email protected] as afterglow agents.
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http://dx.doi.org/10.1021/acsnano.1c05234DOI Listing
October 2021

Regiochemically Oxo-functionalized Graphene, Guided by Defect Sites, as Catalyst for Oxygen Reduction to Hydrogen Peroxide.

J Phys Chem Lett 2021 Oct 7;12(41):10009-10014. Epub 2021 Oct 7.

Institute of Chemistry and Biochemistry, Freie Universität Berlin, Takustraße 3, 14195 Berlin, Germany.

Heteroatom-doped graphene attracted tremendous attention because of advanced electrocatalytic properties, for example, for oxygen reduction. However, the role of oxygen atoms as heteroatoms in graphene should be explored more deeply. Here, we used statistical Raman spectroscopy for single-layer material analysis and found that the regiochemistry close to vacancy defects plays a decisive role. Accordingly, defects possess a guiding effect on the introduction of oxygen functional groups close to those defect-sites. After the addition of oxo-groups close to vacancy defects, the activity and hydrogen peroxide (HO) selectivity of the material on hydrogen peroxide production improved significantly. The selectivity of HO is above 84%, which is higher than the initial oxo-functionalized graphene and electrochemically reduced graphene. The half-wave potential is 0.73 V, which is more positive than the initial oxo-functionalized graphene.
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http://dx.doi.org/10.1021/acs.jpclett.1c02957DOI Listing
October 2021

infection in children after allogeneic hematopoietic stem cell transplantation: A case report and literature review.

Pediatr Investig 2021 Sep 22;5(3):239-243. Epub 2021 Sep 22.

Department of Infectious Diseases Shanghai Children's Medical Center School of Medicine Shanghai Jiao Tong University Shanghai China.

Introduction: Toxoplasmosis is a life-threatening complication after hematopoietic stem cell transplantation (HSCT). However, for several reasons, clinicians know little about infection.

Case Presentation: We report a case of toxoplasmosis that was diagnosed by bone marrow smear and metagenomic next-generation sequencing (mNGS) after HSCT in a boy. Additionally, we summarize the characteristics of toxoplasmosis after pediatric HSCT reported in the literature published in PubMed.

Conclusion: Clinicians should increase their awareness of toxoplasmosis in children after HSCT and implement pre-transplant screening and post-transplant monitoring and prevention in future according to the national conditions of our country.
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http://dx.doi.org/10.1002/ped4.12290DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8458717PMC
September 2021

Antimicrobial resistance of Haemophilus influenzae isolates from pediatric hospitals in Mainland China: Report from the ISPED program, 2017-2019.

Indian J Med Microbiol 2021 Oct-Dec;39(4):434-438. Epub 2021 Sep 21.

Department of Infectious Diseases, Kaifeng Children's Hospital, Kaifeng, 475099, PR China.

Purpose: This study set out to determine the antimicrobial resistance trends of Haemophilus influenzae isolates from pediatric hospitals in Mainland China, which would provide basis for clinical treatment.

Methods: The Infectious Disease Surveillance of Pediatrics (ISPED) collaboration group conducted this study. H. influenzae strains isolated from nine pediatric hospitals in Mainland China were included. Disk diffusion method was used for antimicrobial susceptibility test. Cefinase disc was used for detection of β-lactamase.

Results: In total, 13810 H. influenzae isolates were included during 2017-2019: 93.17% of which were from respiratory tract specimens, 4.63% from vaginal swabs, 1.10% from secretion, and 1.10% from others. Of all strains, 63.32% isolates produced β-lactamase; 8.22% isolates were β-lactamase-negative and ampicillin-resistant (BLNAR). The resistance to sulfamethoxazole-trimethoprim was 70.98%, followed by resistance to ampicillin (69.37%), cefuroxime (51.35%), ampicillin-sulbactam (38.82%), azithromycin (38.21%), amoxicillin-clavulanate (35.28%). More than 90% of H. influenzae isolates were susceptible to ceftriaxone, cefotaxime, meropenem, levofloxacin and chloramphenicol. The resistance rate of ampicillin and azithromycin in H. influenzae showed an increasing trend through the years. Statistically significant differences in antibiotic-resistance rates of all the antibiotics except chloramphenicol were found in different regions. The major Multi-Drug Resistance pattern was resistant to β-lactams, macrolides, and sulfonamides.

Conclusions: There is a rising trend of resistance rate of ampicillin and azithromycin in H. influenzae. Antimicrobial resistance of H. influenzae deserves our ongoing attention. Third-generation cephalosporin could be the preferred treatment option of infections caused by ampicillin-resistant H. influenzae.
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http://dx.doi.org/10.1016/j.ijmmb.2021.09.001DOI Listing
September 2021

Identification and clinical validation of gene signatures with grade and survival in head and neck carcinomas.

Braz J Med Biol Res 2021 20;54(11):e11069. Epub 2021 Sep 20.

Department of Otolaryngology - Head and Neck Surgery, Nanjing Drum Tower Hospital Clinical College of Nanjing Medical University, Nanjing, Jiangsu, China.

This study aimed to explore gene expression profiles that drive malignancy from low- to high-grade head and neck carcinomas (HNC), as well as to analyze their correlations with survival. Gene expressions and clinical data of HNC were downloaded from the Gene Expression Omnibus (GEO) repository. The significantly differential genes (SDGs) between low- and high-grade HNC were screened. Cox regressions were performed to identify prognostic SDGs of progression-free survival (PFS) and disease-specific survival (DSS). The genes were experimentally validated by RT-PCR in clinical tissue specimens. Thirty-five SDGs were identified in 47 low-grade and 30 high-grade HNC samples. Cox regression analyses showed that CXCL14, SLC44A1, and UBD were significantly associated with DSS, and PPP2R2C and SLC44A1 were associated with PFS. Patients were grouped into high-risk or low-risk groups for prognosis based on gene signatures. High-risk patients had significantly shorter DSS and PFS than low-risk patients (P=0.033 and P=0.010, respectively). Multivariate Cox regression showed HPV (P=0.033), lymph node status (P=0.032), and residual status (P<0.044) were independent risk factors for PFS. ROC curves showed the risk score had better efficacy to predict survival both for DSS and PFS (AUC=0.858 and AUC=0.901, respectively). The results showed CXCL14 and SLC44A1 were significantly overexpressed in the low-grade HNC tissues and the UBD were overexpressed in the high-grade HNC tissues. Our results suggested that SDGs had different expression profiles between the low-grade and high-grade HNC, and these genes may serve as prognostic biomarkers to predict survival.
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http://dx.doi.org/10.1590/1414-431X2020e11069DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8457684PMC
September 2021

Epigenetic treatment of behavioral and physiological deficits in a tauopathy mouse model.

Aging Cell 2021 10 21;20(10):e13456. Epub 2021 Sep 21.

Department of Physiology and Biophysics, Jacobs School of Medicine and Biomedical Sciences, State University of New York at Buffalo, Buffalo, New York, USA.

Epigenetic abnormality is implicated in neurodegenerative diseases associated with cognitive deficits, such as Alzheimer's disease (AD). A common feature of AD is the accumulation of neurofibrillary tangles composed of hyperphosphorylated tau. Transgenic mice expressing mutant P301S human tau protein develop AD-like progressive tau pathology and cognitive impairment. Here, we show that the euchromatic histone-lysine N-methyltransferase 2 (EHMT2) is significantly elevated in the prefrontal cortex (PFC) of P301S Tau mice (5-7 months old), leading to the increased repressive histone mark, H3K9me2, which is reversed by treatment with the selective EHMT inhibitor UNC0642. Behavioral assays show that UNC0642 treatment induces the robust rescue of spatial and recognition memory deficits in P301S Tau mice. Concomitantly, the diminished PFC neuronal excitability and glutamatergic synaptic transmission in P301S Tau mice are also normalized by UNC0642 treatment. In addition, EHMT inhibition dramatically attenuates the hyperphosphorylated tau level in PFC of P301S Tau mice. Transcriptomic analysis reveals that UNC0642 treatment of P301S Tau mice has normalized a number of dysregulated genes in PFC, which are enriched in cytoskeleton and extracellular matrix organization, ion channels and transporters, receptor signaling, and stress responses. Together, these data suggest that targeting histone methylation enzymes to adjust gene expression could be used to treat cognitive and synaptic deficits in neurodegenerative diseases linked to tauopathies.
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http://dx.doi.org/10.1111/acel.13456DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8520711PMC
October 2021

Practical fine-grained learning based anomaly classification for ECG image.

Artif Intell Med 2021 09 21;119:102130. Epub 2021 Jul 21.

Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, China. Electronic address:

As a widely used vital sign within cardiology, Electrocardiography (ECG) provides the basis for assessing heart function and diagnosing cardiovascular diseases. Automated anomaly detection for ECG plays an important role in improving patient diagnosis efficiency and reducing healthcare costs. Practically, due to the limits of electronics support or the medical system setting, image is a more common format for large-scale ECG storage in most clinical institutions. To guarantee an automated ECG detection model's scalability and practicality in clinical applications, taking good advantage of ECG images is crucial. However, existing time digital-based discriminative models fail to learn from images effectively for two reasons. First of all, the signals recorded on images have much lower resolution and higher noise, which makes it impractical to extract precise ECG signals following existing techniques. Meanwhile, the differences between abnormal signals are usually subtle, and they may be overwhelmed by the noises in the images as well. Towards this end, we design a novel neural framework that can be directly applied to massive ECG images determining various types of cardiology abnormalities. It classifies fine-grained ECG images based on weakly supervised strategy, in which case only image-level labeling is required. By eliminating the need for part annotations, the proposed method can result in significant savings in annotation time and cost. The effectiveness of the method is demonstrated by experimental results on two real ECG datasets.
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http://dx.doi.org/10.1016/j.artmed.2021.102130DOI Listing
September 2021

Interlayer electron modulation in van der Waals heterostructures assembled by stacking monolayer MoS onto monolayer graphene with different electron transfer ability.

Nanoscale 2021 Sep 23;13(36):15464-15470. Epub 2021 Sep 23.

Institute of Chemistry and Biochemistry, Freie Universität Berlin, Takustraße 3, 14195 Berlin, Germany.

Achieving tunable optoelectronic properties and clarifying interlayer interactions are key challenges in the development of 2D heterostructures. Herein, we report the feasible modulation of the optoelectronic properties of monolayer MoS (1L-MoS) on three different graphene monolayers with varying ability in extracting electrons. Monolayer oxygen-functionalized graphene (1L-oxo-G, a high amount of oxygen of 60%) with a work function (WF) of 5.67 eV and its lowly oxidized reduction product, namely reduced-oxo-G (1L-r-oxo-G, a low amount of oxygen of 0.1%), with a WF of 5.85 eV serving as hole injection layers significantly enhance the photoluminescence (PL) intensity of MoS, whereas pristine monolayer graphene (1L-G) with a work function (WF) of 5.02 eV results in PL quenching of MoS. The enhancement in the PL intensity is due to increase of neutral exciton recombination. Furthermore, 1L-r-oxo-G/MoS exhibited a higher increase (5-fold) in PL than 1L-oxo-G/MoS (3-fold). Our research can help modulate the carrier concentration and electronic type of 1L-MoS and has promising applications in optoelectronic devices.
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http://dx.doi.org/10.1039/d1nr03708kDOI Listing
September 2021

Early Clostridioides difficile infection characterizations, risks, and outcomes in allogeneic hematopoietic stem cell and solid organ transplant recipients.

Transpl Infect Dis 2021 Aug 28:e13720. Epub 2021 Aug 28.

Division of Hematology, Oncology and Transplant, Department of Medicine, University of Minnesota, Minneapolis, Minnesota, USA.

Background: Clostridioides difficile infection (CDI) frequently complicates allogeneic hematopoietic stem cell (allo-HCT) and solid organ transplantation (SOT).

Methods: We retrospectively analyzed risk factors and outcomes of CDI occurring within 30 days of transplant.

Results: Between March 2010 and June 2015, 466 allo-HCT and 1454 SOT were performed. The CDI cumulative incidence (95% CI) was 10% (8-13) and 4% (3-5), following allo-HCT and SOT, respectively (p < .01), occurring at a median (range) 7.5 days (1-30) and 11 (1-30), respectively (p = .18). In multivariate analysis, fluoroquinolones use within 14 days pre-transplantation was a risk factor for CDI following allo-HCT (HR 4.06 [95% CI 1.31-12.63], p = .02), and thoracic organ(s) transplantation was a risk factor for CDI following SOT (HR 3.03 [95% CI 1.31-6.98]) for lung and 3.90 (1.58-9.63) for heart and heart/kidney transplant, p = .02. Compared with no-CDI patients, the length of stay (LOS) was prolonged in both allo-HCT (35 days [19-141] vs. 29 [13-164], p < .01) and SOT with CDI (16.5 [4-101] vs. 7 [0-159], p < .01), though not directly attributed to CDI. In allo-HCT, severe acute graft-versus-host disease (aGVHD) occurred more frequently in patients with CDI (33.3% vs. 15.8% without CDI, p = .01) and most aGVHD (87.5%) followed CDI. Non-relapse mortality or overall survival, not attributed to CDI, were also similar in both allo-HCT and SOT.

Conclusions: Early post-transplant CDI is frequent, associated with fluoroquinolones use in allo-HCT and the transplanted organ in SOT, and is associated with longer LOS in both the groups without difference in survival but with increased aGVHD in allo-HCT.
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http://dx.doi.org/10.1111/tid.13720DOI Listing
August 2021

Transcriptomic analysis of human brains with Alzheimer's disease reveals the altered expression of synaptic genes linked to cognitive deficits.

Brain Commun 2021 3;3(3):fcab123. Epub 2021 Jun 3.

Department of Physiology and Biophysics, State University of New York at Buffalo, Jacobs School of Medicine and Biomedical Sciences, Buffalo, NY 14203, USA.

Alzheimer's disease is a progressive neurodegenerative disorder associated with memory loss and impaired executive function. The molecular underpinnings causing cognitive deficits in Alzheimer's disease are loosely understood. Here, we performed cross-study large-scale transcriptomic analyses of postmortem prefrontal cortex derived from Alzheimer's disease patients to reveal the role of aberrant gene expression in this disease. We identified that one of the most prominent changes in prefrontal cortex of Alzheimer's disease humans was the downregulation of genes in excitatory and inhibitory neurons that are associated with synaptic functions, particularly the SNARE-binding complex, which is essential for vesicle docking and neurotransmitter release. Comparing genomic data of Alzheimer's disease with proteomic data of cognitive trajectory, we found that many of the lost synaptic genes in Alzheimer's disease encode hub proteins whose increased abundance is required for cognitive stability. This study has revealed potential molecular targets for therapeutic intervention of cognitive decline associated with Alzheimer's disease.
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http://dx.doi.org/10.1093/braincomms/fcab123DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8374979PMC
June 2021

Comparative Transcriptome Profiling Reveals Changes of microRNAs Response to Exercise in Rats with Neuropathic Pain.

Neural Plast 2021 2;2021:5597139. Epub 2021 Aug 2.

Department of Sport Rehabilitation, Shanghai University of Sport, Shanghai, China.

There is accumulating evidence showing that exercise therapy may play an active role in peripheral neuropathic pain (NP), but its mechanism is still unclear. Studies have found that microRNAs (miRNAs) may play a role in NP by regulating pain-related target genes. Therefore, we aimed to explore the changes of miRNA and mRNA of dorsal root ganglion (DRG) after NP in response to exercise with transcriptome technology. The chronic constriction injury (CCI) model was established, and rats were randomly allocated into three groups, namely, the sham-operated, CCI, and CCI-exercised groups. L4-L6 DRG tissue was taken for RNA-sequencing, and the differentially expressed genes (DEGs) were determined through bioinformatics analysis. Real-time PCR was used to confirm the accuracy. A total of 4 overlapping differentially expressed miRNAs and 186 overlapping differentially expressed mRNAs were identified in the two comparisons of the sham-operated group versus the CCI group and the CCI group versus the CCI-exercised group. Among these DEGs, miR-145-5p, miR-341, miR-300-5p, miR-653-5p, Atf3, Cacna2d1, Gal, and Ctss related to NP were validated by real-time PCR. DEGs between the CCI and CCI-exercised groups were enriched in HIF-1 signaling pathway, Rap1 signaling pathway, and neurotrophin signaling pathway. This study provides an understanding of the adaptive mechanisms after exercise of NP, and these DEGs in DRG might play a role in NP by stimulating the enriched pathways.
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http://dx.doi.org/10.1155/2021/5597139DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8356008PMC
August 2021

HER2 Protein Overexpression and Gene Amplification in Tubo-Ovarian High-grade Serous Carcinomas.

Int J Gynecol Pathol 2021 Jul 28. Epub 2021 Jul 28.

Department of Pathology, University of Massachusetts Medical School-Baystate Health, Springfield, Massachusetts.

Most tubo-ovarian high-grade serous carcinomas (TO-HGSC) are diagnosed in advanced stages. Although the majority of patients achieve initial remission with cytoreductive surgery and chemotherapy, mortality rate remains high due to recurrent/progressive disease. The addition of trastuzumab to carboplatin-paclitaxel improved progression-free survival of patients with human epidermal growth factor receptor 2 (HER2)-positive uterine serous carcinoma. After this encouraging result of transtuzumab in HER2-positive uterine serous carcinoma, we aimed to determine the frequency of HER2 overexpression/amplification in TO-HGSC and reveal the utility of 2018 ASCO/CAP HER2 testing guideline in breast cancer for TO-HGSC. For 100 cases, HER2 protein expression was assessed by immunohistochemistry and scored from 0 to 3+ according to 2018 ASCO/CAP HER2 testing guideline. HER2 gene amplification was assessed by florescence in situ hybridization for all the 2+ and 3+ cases as well as 5 of the 0/1+ cases. Among 100 cases, immunohistochemistry scores were 0/1+ in 81 cases, 2+ in 18 cases and 3+ in 1 case. By florescence in situ hybridization, the only 3+ case and 1 of the 2+ cases were HER2-amplified and all 5 of the 0/1+ cases were HER2 nonamplified. Subclonal HER2 overexpression/amplification was identified in 1 of the neoadjuvant cases comprising <10% of the entire tumor. In summary, HER2 overexpression/amplification was found in 2% of TO-HGSC. The 2018 ASCO/CAP HER2 testing guideline in breast cancer can be utilized for TO-HGSC. Future studies are needed to explore HER2-targeted therapies in TO-HGSC and expand the patient population who may benefit from HER2-targeted therapies such as patients with activating mutations in HER2 gene without overexpression/amplification.
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http://dx.doi.org/10.1097/PGP.0000000000000812DOI Listing
July 2021

Analysis of gut microbiota alteration and application as an auxiliary prognostic marker for sepsis in children: a pilot study.

Transl Pediatr 2021 Jun;10(6):1647-1657

The Laboratory of Pediatric Infectious Diseases, Pediatric Translational Medicine Institute, Shanghai Children's Medical Center, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.

Background: Emerging evidence suggests that gut microbiota dysbiosis plays a role in sepsis. Recent advances in sequencing technology enable the characterization of the gut microbiota and can provide clues for the pathogenesis of sepsis, which may help develop biomarkers for diagnosis or prognosis prediction in children with sepsis.

Methods: The gut microbiota from 25 children with sepsis and 15 age- and sex-matched healthy controls were extracted and sequenced by high-throughput Illumina Hiseq, targeting the 16S rDNA genes. The differences of gut microbiota between the two groups were analyzed to assess if the gut microbiota can be used as an auxiliary prognostic marker for sepsis.

Results: The diversity of gut microbiota in children with sepsis was significantly lower than that of healthy controls (P<0.001). The overall community structure of gut microbiota was also altered considerably. On the genus level, children with sepsis had more opportunistic pathogens, such as and , while fewer beneficial bacterial, such as , , , , and , were detected. Further analysis of the association between the gut microbiota and clinical features revealed that the pathogens from bacteria culture correlated to the dominant bacteria genus detected in the intestinal flora. Furthermore, the gut microbiota diversity was negatively associated with the antibiotic therapy duration, but did not correlate with type of antibiotics used. Finally, gut microbiota disturbance was correlated with increased mortality rate.

Conclusions: Overall, we confirmed that gut microbiota disturbance occurred in the children with sepsis, and changes in the fecal microbiota were closely related to clinical characteristics. Elucidation of such dysbiosis could improve our understanding of sepsis pathogenesis and help develop microbiota-based diagnosis, monitoring, and therapy for sepsis.
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http://dx.doi.org/10.21037/tp-21-51DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8261590PMC
June 2021

Differences in cytokine and chemokine profiles in cerebrospinal fluid caused by the etiology of cryptococcal meningitis and tuberculous meningitis in HIV patients.

Clin Exp Immunol 2021 Oct 8;206(1):82-90. Epub 2021 Aug 8.

National Clinical Research Center for Infectious Diseases, College of Medicine, the First Affiliated Hospital, Zhejiang University, Hangzhou, China.

The roles of cytokines and chemokines in HIV-associated cryptococcal meningitis (HCM) and HIV-associated tuberculous meningitis (HTBM) are debatable. In sum, 34 HIV-infected patients without meningitis, 44 HCM patients and 27 HTBM patients were enrolled for study. The concentrations of 22 cytokines/chemokines in cerebrospinal fluid (CSF) were assayed at admission. Principal component analysis (PCA), Pearson's and logistic regression analyses were used to assess the role of cytokines/chemokines in HCM and HTBM. We found the levels of T helper (Th)17, Th1 [interleukin (IL)-12p40, interferon (IFN)-γ, tumor necrosis factor (TNF)-α and TNF-β and Th2 (IL-2/4/5/6/10)] cytokines were elevated in patients with meningitis compared with those in HIV-infected patients without central nervous system (CNS) infection. Furthermore, the IL-1Ra, IL-12p40, IL-17α and monocyte chemotactic protein-1 (MCP-1) levels were higher in HCM patients, while the IFN-γ, regulated upon activation, normal T cell expressed and secreted (RANTES) and interferon-inducible protein-10 (IP)-10 levels were higher in HTBM patients. Elevated CSF concentrations of IL-17a, TNF-β, IL-5, IL-12p40 and IL-1Rα were closely related to meningitis, but elevated IP-10, MCP-1, RANTES and IFN-γ levels and CSF white blood cells (WBCs) were protective factors against HCM. Our study suggested that HIV-infected patients with low CSF WBCs have a high risk of HCM. Th1, Th2 and Th17 cytokines/chemokines mediate differences in the pathogenesis of HCM and TBM. Overexpressed proinflammatory MCP-1, RANTES, IFN-γ and IP-10 in CSF are protective factors against HCM but not HTBM.
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http://dx.doi.org/10.1111/cei.13644DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8446401PMC
October 2021

Solution-focused brief therapy for adolescent and young adult cancer patients in China: a pilot randomized controlled trial.

J Psychosoc Oncol 2021 Jul 7:1-18. Epub 2021 Jul 7.

Department of Medicine, University of Chicago, Chicago, IL, USA.

Objective: This pilot clinical trial investigated solution-focused brief therapy (SFBT) for psychological distress among adolescent and young adult (AYA) patients with cancer in China.

Methods: Fifty Chinese AYA patients diagnosed with cancer were randomized into the treatment group (SFBT) and control group (active control). Psychological distress was measured by the brief symptom inventory and hope was measured by the Herth-Hope-Index. Treatment effects were analyzed using analysis-of-covariance and between-group small-sample-size corrected Hedges' .

Results: The results indicated that SFBT resulted in a significant reduction in the psychological distress and improvement in hope of AYA patients with cancer. Analyses of the 4-week posttreatment score suggest the short-term sustainability of SFBT for psychological distress among AYAs diagnosed with cancer.

Conclusions And Implications: This study has demonstrated that SFBT's impact is statistically significant and clinically meaningful. The inclusion of positive emotions, i.e., hope, as part of the investigation also highlighted the significance of promoting positive emotions among AYA patients with cancer.
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http://dx.doi.org/10.1080/07347332.2021.1931627DOI Listing
July 2021

Rapid diagnostic testing for antimicrobial stewardship: Utility in Asia Pacific.

Infect Control Hosp Epidemiol 2021 07 15;42(7):864-868. Epub 2021 Jun 15.

Clinical Pathology, Faculty of Medicine, Ramathibodi Hospital, Mahidol University, Bangkok, Thailand.

Rapid diagnostic testing (RDT) can provide prompt, accurate identification of infectious organisms and be a key component of antimicrobial stewardship (AMS) programs. However, their use is less widespread in Asia Pacific than western countries. Cost can be prohibitive, particularly in less resource-replete settings. A selective approach is required, possibly focusing on the initiation of antimicrobials, for differentiating bacterial versus viral infections and identifying locally relevant tropical diseases. Across Asia Pacific, more data are needed on RDT use within AMS, focusing on the impact on antimicrobial usage, patient morbidity and mortality, and cost effectiveness. Moreover, in the absence of formal guidelines, regional consensus statements to guide clinical practice are warranted. These will provide a regionally relevant definition for RDT; greater consensus on its role in managing infections; advice on implementation and overcoming barriers; and guidance on optimizing human resource capacity. By addressing these issues, the outcomes of AMS programs should improve.
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http://dx.doi.org/10.1017/ice.2021.149DOI Listing
July 2021

The miR-106b/NR2F2-AS1/PLEKHO2 Axis Regulates Migration and Invasion of Colorectal Cancer through the MAPK Pathway.

Int J Mol Sci 2021 May 30;22(11). Epub 2021 May 30.

Key Laboratory of Resource Biology and Biotechnology in Western China, School of Medicine, Northwest University, Ministry of Education, Xi'an 710069, China.

Increasing numbers of miRNAs have been observed as oncogenes or tumor suppressors in colorectal cancer (CRC). It was recently reported that hsa-miR-106b-5p (miR-106b) promoted CRC cell migration and invasion. However, there were also studies showing contradictory results. Therefore, in the present study, we further explore the role of miR-106b and its downstream networks in the carcinogenesis of CRC. We observed that the expression of miR-106b is significantly increased in Pan-Cancer and CRC tissues compared with normal tissues from The Cancer Genome Atlas (TCGA) database. Furthermore, we used Transwell, Cell Counting Kit-8, and colony formation assays to clarify that miR-106b promotes the migratory, invasive, and proliferative abilities of CRC cells. For the first time, we systematically screened the target mRNAs and lncRNAs of miR-106b using TCGA database and the bioinformatics algorithms. Dual-luciferase reporter assay confirmed that NR2F2-AS1 and PLEKHO2 are the direct targets of miR-106b. Furthermore, NR2F2-AS1 acts as a competing endogenous RNA (ceRNA) to regulate PLEKHO2 expression by sponging miR-106b. The results of Gene set enrichment analysis (GSEA) and Western blot indicated that they play important roles in CRC progression by regulating MAPK pathway. Thus, miR-106b/NR2F2-AS1/PLEKHO2/MAPK signaling axis may suggest the potential usage in CRC treatment.
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http://dx.doi.org/10.3390/ijms22115877DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8198404PMC
May 2021

Higher Fludarabine and Cyclophosphamide Exposures Lead to Worse Outcomes in Reduced-Intensity Conditioning Hematopoietic Cell Transplantation for Adult Hematologic Malignancy.

Transplant Cell Ther 2021 09 24;27(9):773.e1-773.e8. Epub 2021 May 24.

Department of Experimental and Clinical Pharmacology, College of Pharmacy, University of Minnesota, Minneapolis, Minnesota. Electronic address:

Reduced-intensity conditioning regimens using fludarabine (Flu) and cyclophosphamide (Cy) have been widely used in hematopoietic cell transplantation (HCT) recipients. The optimal exposure of these agents remains to be determined. We aimed to delineate the exposure-outcome associations of Flu and Cy separately and then both combined on HCT outcomes. This is a single-center, observational, pharmacokinetic (PK)-pharmacodynamic (PD) study of Flu and Cy in HCT recipients age ≥18 years who received Cy (50 mg/kg in a single dose), Flu (150 to 200 mg/m given as 5 daily doses), and total body irradiation (TBI; 200 cGy). We measured trough concentrations of 9-β-D-arabinosyl-2-fluoradenine (F-ara-A), an active metabolite of Flu, on days -5 and -4 (F-ara-A and F-ara-A, respectively), and measured phosphoramide mustard (PM), the final active metabolite of Cy, and estimated the area under the curve (AUC). The 89 enrolled patients had a nonrelapse mortality (NRM) of 9% (95% confidence interval [CI], 3% to 15%) at day +100 and 15% (95% CI, 7% to 22%) at day +180, and an overall survival (OS) of 73% (95% CI, 63% to 81%) at day +180. In multivariate analysis, higher PM area under the curve (AUC) for 0 to 8 hours (PM AUC) was an independent predictor of worse NRM (P < .01 at both day +100 and day +180) and worse day +180 OS (P < .01), but no associations were identified for F-ara-A trough levels. We observed lower day +100 NRM in those with both high F-ara-A trough levels (≥40 ng/mL; >25th percentile) and low PM AUC (<34,235 hr ng/mL; <75th percentile), compared with high exposures to both agents (hazard ratio, 0.06; 95% CI, 0.01 to 0.48). No patients with low F-ara-A (<40 ng/mL; <25th percentile) had NRM by day +100, regardless of PM AUC. The interpatient PK variability was large in F-ara-A trough and PM AUC (29-fold and 5.0-fold, respectively). Flu exposure alone was not strongly associated with NRM or OS in this reduced Flu dose regimen; however, high exposure to both Flu and Cy was associated with a >16-fold higher NRM. These results warrant further investigation to optimize reduced-intensity regimens based on better PK-PD understanding and possible adaptation to predictable factors influencing drug clearance.
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http://dx.doi.org/10.1016/j.jtct.2021.05.013DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8627667PMC
September 2021
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