Publications by authors named "Meng Xiao"

404 Publications

Diagnostic accuracy of the 1,3-beta-D-glucan test and lactate dehydrogenase for pneumocystis pneumonia in non-HIV patients.

Sci Rep 2021 Apr 29;11(1):9226. Epub 2021 Apr 29.

Emergency Department, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Science and Peking Union Medical College, Beijing, China.

We evaluated the serum levels of (1-3)-beta-D-glucan (BG) and lactate dehydrogenase (LDH) as a tool to support pneumocystis pneumonia (PCP) diagnostic procedures in non-HIV patients. We retrospectively collected non-HIV (human immunodeficiency virus) patients presenting clinical features of PCP between April 1st, 2013, and December 31st, 2018. A total of 225 included patients were tested for Pneumocystis jirovecii by polymerase chain reaction (PCR) and methenamine silver staining. Based on different exclusion criteria, 179 cases were included in the BG group, and 196 cases were included in the LDH group. In each group, cases with positive immunofluorescence (IF) microscopy and PCR were considered proven PCP, while cases with only positive PCR were considered probable PCP. Fifty patients with negative IF and PCR results and proven to be non-PCP infection were chosen randomly as the control group. The cut-off levels of BG and LDH to distinguish non-PCP from probable PCP were 110 pg/mL and 296 U/L with 88% sensitivity and 86% specificity, and 66% sensitivity and 88% specificity, respectively. The cut-off levels of BG and LDH to distinguish non-PCP from proven PCP were 285.8 pg/mL and 379 U/L with 92% sensitivity and 96% specificity, and 85% sensitivity and 77% specificity, respectively. The cut-off levels of BG and LDH to distinguish non-PCP from proven/probable PCP were 144.1 pg/mL and 363 U/L with 90% sensitivity, 86% specificity and 80% sensitivity, 76% specificity respectively. BG and LDH are reliable indicators for detecting P. jirovecii infection in HIV-uninfected immunocompromised patients.
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http://dx.doi.org/10.1038/s41598-021-88729-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8085008PMC
April 2021

Species distribution and antifungal susceptibilities of clinical isolates of Penicillium and Talaromyces species in China.

Int J Antimicrob Agents 2021 Apr 24:106349. Epub 2021 Apr 24.

Department of Clinical Laboratory, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing, China; Beijing Key Laboratory for Mechanisms Research and Precision Diagnosis of Invasive Fungal Diseases, Beijing, China. Electronic address:

Morphologically identified Penicillium (n = 103) and Talaromyces marneffei (n = 8) isolates were collected from various clinical sources between 2016 and 2017 at a medical centre in Beijing, China. Identification to species level was confirmed by sequencing of the internal transcribed spacer (ITS) region, β-tubulin gene (benA) and RNA polymerase II second largest subunit (RPB2) gene. Of the 111 isolates, 56 (50.5%) were identified as Penicillium spp. and 55 (49.5%) as Talaromyces spp. Eleven species of Penicillium were detected, of which Penicillium oxalicum was the commonest, accounting for 51.8% (29/56), followed by Penicillium rubens (10.7%; 6/56) and Penicillium citrinum (10.7%; 6/56). Among the 55 Talaromyces isolates, nine species were identified, with Talaromyces funiculosus (36.4%; 20/55), Talaromyces stollii (27.3%; 15/55) and Talaromyces marneffei (14.5%; 8/55) being the most common. Of note, 89.3% (50/56) of the Penicillium isolates and 98.2% (54/55) of the Talaromyces isolates exhibited growth at 37°C. The isolates were mainly recovered from patients with pulmonary disorders (56.8%; 63/111), autoimmune disease (12.6%; 14/111) and AIDS (5.4%; 6/111). The azoles and amphotericin B exhibited potent activity against T. marneffei, while various levels of activity were observed against Penicillium and other Talaromyces species The echinocandins had the lowest MECs (MEC ≤0.12 mg/L) against most Penicillium and Talaromyces species, with the exception of T. marneffei whose MEC (4 mg/L) was five or more dilutions higher than that of the other species tested. These data on the species distribution and antifungal susceptibility expand the current clinical knowledge of Penicillium and Talaromyces species.
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http://dx.doi.org/10.1016/j.ijantimicag.2021.106349DOI Listing
April 2021

Fluorogenic Biosensors Constructed via Aggregation-Induced Emission based on Enzyme-Catalyzed Coupling Reactions for Detection of Hydrogen Peroxide.

Anal Sci 2021 Apr 23. Epub 2021 Apr 23.

College of Pharmacy, State Key Laboratory of Medicinal Chemical Biology, Nankai University.

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http://dx.doi.org/10.2116/analsci.20P463DOI Listing
April 2021

Increased nuclear translation of YAP might act as a potential therapeutic target for NF1-related plexiform neurofibroma.

Int J Med Sci 2021 3;18(9):2008-2016. Epub 2021 Mar 3.

Department of Oral and Maxillofacial-Head and Neck Oncology, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University, School of Medicine, Shanghai 200011, P.R. China.

Plexiform neurofibroma (pNF) in the head and neck is a characteristic feature in patients with neurofibromatosis type 1 (NF1) and is associated with significant disfigurement and psychological distress. Yes-associated protein (YAP), the key molecule involved in the Hippo pathway, is a vital transductor that regulates the proliferation and remyelinating of Schwann cells. The functional status of YAP and its feasibility as a potential target are still unknown in pNF. A total of 17 pNF tumor tissue specimens from the head and neck were collected at the Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine. Histologically, diagnosis of the Schwann cell region in pNF was achieved with hematoxylin-eosin staining, positive reactions for S100, SOX10, ERK and p-ERK, and low identification of Ki67 and SMA. Compared with normal nerve tissue, obviously increased nuclear YAP was detected in the Schwann cell region of pNF, with a mean nuclear staining rate of 67.11%. Based on the Schwann cell model (the RSC96 cell line), with upregulated expression of RAS, ERK and p-ERK, p-YAP (Ser127) and p-YAP (Ser397) were significantly decreased and total YAP and nuclear YAP were increased. According to a confocal assay, the interference of substantially promoted YAP nuclear translocation. Compared with control Schwann cells, the YAP inhibitor CA3 might have a more sensitive effect (IC: NC=0.96±0.04, shNF1=0.71±0.02, <0.05) on the Schwann cell model than the classic MEK1/2 inhibitor selumetinib (IC: NC=14.36±0.95, shNF1=24.83±0.98, >0.05). For inhibition, the CA3 group and the selumetinib group displayed a similar inhibition effect with no significant difference. Increased nuclear translation and the functional state of YAP implies that the YAP-Hippo pathway might play an important role in the formation and remyelination of pNF. Compared with selumetinib, the YAP inhibitor can exhibit a similar but more sensitive effect on Schwann cells. These observations imply that YAP as a novel or adjuvant therapy target in the treatment of pNF.
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http://dx.doi.org/10.7150/ijms.52431DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8040406PMC
March 2021

Species identification and antifungal susceptibility testing of Aspergillus strains isolated from patients with otomycosis in northern China.

J Microbiol Immunol Infect 2021 Mar 29. Epub 2021 Mar 29.

Department of Laboratory Medicine, National Taiwan University Hospital, National Taiwan University College of Medicine, Taipei, Taiwan; Department of Internal Medicine, National Taiwan University Hospital, National Taiwan University College of Medicine, Taipei, Taiwan. Electronic address:

Background/purpose: There are limited studies on species distribution and susceptibility profiles of Aspergillus strains isolated from patients with otomycosis in China.

Methods: A total of 69 confirmed Aspergillus species isolates were obtained from ear swabs of patients diagnosed with otomycosis from 2017 to 2018 in northern China. Identification of these Aspergillus isolates at the species level was performed using conventional morphological methods and MALDI-TOF MS in combination with molecular sequencing, and in vitro susceptibility to nine antifungal agents was evaluated using the Sensititre YeastOne system.

Results: The Aspergillus section Nigri had the greatest distribution of Aspergillus isolates. A. welwitschiae (n = 25) was the most predominant isolate in section Nigri, followed by A. tubingensis (n = 12) and A. niger (n = 11). Other Aspergillus species were also isolated, including A. terreus (n = 11), A. flavus/A. oryzae (n = 8), and A. fumigatus (n = 2). Amphotericin B, posaconazole, and echinocandins were highly in vitro active against all the isolates tested. 2.9% (2/69) of the isolates were resistant to azoles in our study, including one A. niger isolate with a high MIC value for itraconazole (ITR) (16 mg/L) and one A. tubingensis isolate cross-resistant to both voriconazole (VOR) (MIC >8 mg/L) and ITR (MIC >16 mg/L). One A. welwitschiae and one A. niger isolate both had increased MIC values of 4 mg/L against VOR.

Conclusions: A. welwitschiae was the most prevalent Aspergillus species isolated from patients with otomycosis. Our findings also indicated that the azole-resistant Aspergillus section Nigri should be utilized to guide clinical medication for Otomycosis.
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http://dx.doi.org/10.1016/j.jmii.2021.03.011DOI Listing
March 2021

Co-culture fermentation of Pediococcus acidilactici XZ31 and yeast for enhanced degradation of wheat allergens.

Int J Food Microbiol 2021 Mar 31;347:109190. Epub 2021 Mar 31.

College of Food Science and Nutritional Engineering, China Agricultural University, Beijing 100083, China. Electronic address:

Previous researchers have shown the potential of sourdough and isolated lactic acid bacteria in reducing wheat allergens. As the interactions of lactic acid bacteria with yeast is a key event in sourdough fermentation, we wished to investigate how yeast affects metabolism of lactic acid bacteria, thereby affecting protein degradation and antigenic response. In this study, three strains isolated from sourdough were selected for dough fermentation, namely Pediococcus acidilactici XZ31, Saccharomyces cerevisiae JM1 and Torulaspora delbrueckii JM4. The changes in dough protein during the fermentation process were studied. Protein degradation and antigenic response in dough inoculated with Pediococcus acidilactici XZ31 monoculture and co-culture with yeast were mainly evaluated by SDS-PAGE, immunoblotting, ELISA and Liquid chromatography-tandem mass spectrometry assay. The whole-genome transcriptomic changes in Pediococcus acidilactici XZ31 were also investigated by RNA sequencing. The results showed that water/salt soluble protein and Tri a 28/19 allergens content significantly decreased after 24 h fermentation. Co-culture fermentation accelerated the degradation of protein, and reduced the allergen content to a greater extent. RNA-sequencing analysis further demonstrated that the presence of yeast could promote protein metabolism in Pediococcus acidilactici XZ31 for a certain period of time. These results revealed a synergistic effect between Pediococcus acidilactici XZ31 and yeast degrading wheat allergens, and suggested the potential use of the multi-strain leavening agent for producing hypoallergenic wheat products.
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http://dx.doi.org/10.1016/j.ijfoodmicro.2021.109190DOI Listing
March 2021

Long non-coding RNA TUG1 knockdown hinders the tumorigenesis of multiple myeloma by regulating the microRNA-34a-5p/NOTCH1 signaling pathway.

Open Life Sci 2020 9;15(1):284-295. Epub 2020 Jun 9.

Department of Hematology, Ji'ning No. 1 People's Hospital, Ji'ning, Shandong, China.

Multiple myeloma (MM) is a serious health issue in hematological malignancies. Long non-coding RNA taurine-upregulated gene 1 (TUG1) has been reported to be highly expressed in the plasma of MM patients. However, the functions of TUG1 in MM tumorigenesis along with related molecular basis are still undefined. In this study, increased TUG1 and decreased microRNA-34a-5p (miR-34a-5p) levels in MM tissues and cells were measured by the real-time quantitative polymerase reaction assay. The expression of relative proteins was determined by the Western blot assay. TUG1 knockdown suppressed cell viability, induced cell cycle arrest and cell apoptosis in MM cells, as shown by Cell Counting Kit-8 and flow cytometry assays. Bioinformatics analysis, luciferase reporter assay, and RNA pull-down assay indicated that miR-34a-5p was a target of TUG1 and directly bound to notch receptor 1 (NOTCH1), and TUG1 regulated the NOTCH1 expression by targeting miR-34a-5p. The functions of miR-34a-5p were abrogated by TUG1 upregulation. Moreover, TUG1 loss impeded MM xenograft tumor growth by upregulating miR-34a-5p and downregulating NOTCH1. Furthermore, TUG1 depletion inhibited the expression of Hes-1, Survivin, and Bcl-2 protein in MM cells and xenograft tumors. TUG1 knockdown inhibited MM tumorigenesis by regulating the miR-34a-5p/NOTCH1 signaling pathway and , deepening our understanding of the TUG1 function in MM.
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http://dx.doi.org/10.1515/biol-2020-0025DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7874539PMC
June 2020

Improved Breakdown Strength of Polypropylene Film by Polycyclic Compounds Addition for Power Capacitors.

Materials (Basel) 2021 Mar 3;14(5). Epub 2021 Mar 3.

Key Laboratory of Smart Grid of Education Ministry, School of Electrical and Information Engineering, Tianjin University, Tianjin 300072, China.

In this paper, an improved method for the electric performance of polypropylene (PP) film was proposed to promote the safety and stability of power capacitors. Modified PP films containing three different polycyclic compounds were prepared, which showed good thermal properties and decreased DC conductivity. The DC breakdown strength of the modified PP films under both positive and negative voltage is increased compared with that of the original film. The deep traps introduced by polycyclic compounds and the decreased carrier mobility give an explanation of the decreased DC conductivity. A quantum chemistry calculation was further performed to clarify the mechanism for improving electrical performance, presenting that polycyclic compounds with a high electron affinity and low ionization energy can capture high-energy electrons, protecting the PP molecular chain from attack, and then increase the breakdown strength. It is concluded that the modified PP films by polycyclic compounds have great potential in improving the insulating properties of power capacitors.
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http://dx.doi.org/10.3390/ma14051185DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7959306PMC
March 2021

Merging Bound States in the Continuum at Off-High Symmetry Points.

Phys Rev Lett 2021 Mar;126(11):117402

School of Physics and Technology, Center for Nanoscience and Nanotechnology, and Key Laboratory of Artificial Micro- and Nano-structures of Ministry of Education, Wuhan University, Wuhan 430072, China.

Bound states in the continuum (BICs) confine resonances embedded in a continuous spectrum by eliminating radiation loss. Merging multiple BICs provides a promising approach to further reduce the scattering losses caused by fabrication imperfections. However, to date, BIC merging has been limited to only the Γ point, which constrains potential application scenarios such as beam steering and directional vector beams. Here, we propose a new scheme to construct merging BICs at almost an arbitrary point in reciprocal space. Our approach utilizes the topological features of BICs on photonic crystal slabs, and we merge a Friedrich-Wintgen BIC and an accidental BIC. The Q factors of the resulting merging BIC are enhanced for a broad wave vector range compared with both the original Friedrich-Wintgen BIC and the accidental BIC. Since Friedrich-Wintgen BICs and accidental BICs are quite common in the band structure, our proposal provides a general approach to realize off-Γ merging BICs with superhigh Q factors that can substantially enhance nonlinear and quantum effects and boost the performance of on-chip photonic devices.
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http://dx.doi.org/10.1103/PhysRevLett.126.117402DOI Listing
March 2021

Topological Rainbow Concentrator Based on Synthetic Dimension.

Phys Rev Lett 2021 Mar;126(11):113902

Department of Physics, The Hong Kong University of Science and Technology, Clear Water Bay, Kowloon, Hong Kong, China.

Synthetic dimension provides a new platform for realizing topological photonic devices. Here, we propose a method to realize a rainbow concentrator of topological photonic states based on the synthetic dimension concept. The synthetic dimension is constructed using a translational degree of freedom of the nanostructures inside the unit cell of a two-dimensional photonic crystal. The translational deformation induces a nontrivial topology in the synthetic dimension, which gives rise to robust interface states at different frequencies. The topological rainbow can trap states with different frequencies, controlled by tuning the spatial modulation of interface state group velocities. The operation frequency as well as the bandwidth of the topological rainbow can be easily tuned by controlling the band gap of the photonic crystal. The topological principle can be applied to photonic crystals of any symmetry and arbitrary material composition, as long as a complete band gap exists. This Letter provides a new and general scheme for the realization of a topological rainbow concentrator and will be useful for the development of topological photonic devices.
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http://dx.doi.org/10.1103/PhysRevLett.126.113902DOI Listing
March 2021

Risk factors for mortality due to COVID-19 in intensive care units: a single-center study.

Ann Transl Med 2021 Feb;9(4):276

Department of Cardiology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing, China.

Background: Many studies have revealed several risk factors associated with the prognosis of patients with coronavirus disease 2019 (COVID-19), but the risk factors associated with death in critically ill COVID-19 patients still needs to be fully elucidated. Therefore, we analyzed clinical characteristics and laboratory data of ICU patients to identify risk factors associated with COVID-19 death.

Methods: Patients with COVID-19 from the ICU in the Sino-French New City Branch of Tongji Hospital Wuhan, China, between February 4 and February 29, 2020, were enrolled in this study. The final date of follow-up was April 4, 2020. Clinical manifestations, laboratory tests, treatment, and outcome of participants before and during the ICU stay were retrospectively collected and analyzed.

Results: A total of 92 patients were admitted or transferred to the ICU from February 4 to February 29, 2020. Compared to survivors, the majority of non-survivors (73.8%) presented with dyspnea. A random forest classifier and ROC curve were used to develop a predictive model. IL-6, D-dimer, lymphocytes, and albumin achieved good performance with AUCs of 0.9476, 0.9165, 0.8994, and 0.9251, respectively, which were consistent with clinical observations, such as inflammation, lymphopenia, and coagulation dysfunction. Combining IL-6 and D-dimer improved the performance of this model with an excellent AUC (0.997).

Conclusions: Mortality in COVID-19 was not rare in critically ill patients. The model that combined IL-6 and D-dimer was valuable for predicting the mortality of patients with COVID-19 with excellent performance. This model needs to be further optimized by adding more indicators and then evaluated with a multicenter study.
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http://dx.doi.org/10.21037/atm-20-4877DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7944265PMC
February 2021

Evaluation of Autof MS 1000 and Vitek MS MALDI-TOF MS System in Identification of Closely-Related Yeasts Causing Invasive Fungal Diseases.

Front Cell Infect Microbiol 2021 18;11:628828. Epub 2021 Feb 18.

Department of Laboratory Medicine, and Beijing Key Laboratory for Mechanisms Research and Precision Diagnosis of Invasive Fungal Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing, China.

Matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS) has been accepted as a rapid, accurate, and less labor-intensive method in the identification of microorganisms in clinical laboratories. However, there is limited data on systematic evaluation of its effectiveness in the identification of phylogenetically closely-related yeast species. In this study, we evaluated two commercially available MALDI-TOF systems, Autof MS 1000 and Vitek MS, for the identification of yeasts within closely-related species complexes. A total of 1,228 yeast isolates, representing 14 different species of five species complexes, including 479 of complex, 323 of complex, 95 of complex, 16 of complex (including two ), and 315 of complex, collected under the National China Hospital Invasive Fungal Surveillance Net (CHIF-NET) program, were studied. Autof MS 1000 and Vitek MS systems correctly identified 99.2% and 89.2% of the isolates, with major error rate of 0.4% versus 1.6%, and minor error rate of 0.1% versus 3.5%, respectively. The proportion of isolates accurately identified by Autof MS 1000 and Vitek MS per each yeast complex, respectively, was as follows; complex, 99.4% vs 96.3%; complex, 99.0% vs 79.1%; complex, 98.9% vs 94.7%; complex, 100% vs 93.8%; and , 99.4% vs 95.2%. Overall, Autof MS 1000 exhibited good capacity in yeast identification while Vitek MS had lower identification accuracy, especially in the identification of less common species within phylogenetically closely-related species complexes.
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http://dx.doi.org/10.3389/fcimb.2021.628828DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7930211PMC
February 2021

and to Gene Distribution Characteristics in Gut Specimens from Different Regions of China.

Antibiotics (Basel) 2021 Feb 25;10(3). Epub 2021 Feb 25.

State Key Laboratory of Infectious Disease Prevention and Control, National Institute for Communicable Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing 102206, China.

Antibiotic resistance has become a global public health concern. To determine the distribution characteristics of and in China, gene screening was conducted directly from gut specimens sourced from livestock and poultry, poultry environments, human diarrhea patients, and wild animals from 10 regions, between 2010-2020. The positive rate was 5.09% (356/6991) for and 0.41% (29/6991) for , as detected in gut specimens from seven regions, throughout 2010 to 2019, but not detected in 2020. The detection rate of showed significant differences among various sources: livestock and poultry (14.81%) > diarrhea patients (1.43%) > wild animals (0.36%). The detection rate of was also higher in livestock and poultry (0.88%) than in diarrhea patients (0.17%), and this was undetected in wildlife. This is consistent with the relatively high detection rate of multiple genotypes in livestock and poultry. All instances of coexistence of the and genes, as well as coexistence of genotypes within single specimens, and most new subtypes came from livestock, and poultry environments. Our study indicates that the emergence of and genes in China is closely related to the selective pressure of carbapenem and polymyxin. The gene-based strategy is proposed to identify more resistance genes of concern, possibly providing guidance for the prevention and control of antimicrobial resistance dissemination.
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http://dx.doi.org/10.3390/antibiotics10030233DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7996585PMC
February 2021

A Solvent-Free and Water-Resistant Dipole-Dipole Interaction-Based Super Adhesive.

Macromol Rapid Commun 2021 May 26;42(9):e2100010. Epub 2021 Feb 26.

School of Materials Science and Engineering, Tianjin Key Laboratory of Composite and Functional Materials, Tianjin University, Tianjin, 300350, China.

Water-resistant and high-strength adhesion on different surfaces has attracted considerable attention for decades. However, the adhesion performances of conventional adhesives suffer from deterioration in adhesion performances under water or wet conditions. This work proposes a dipole-dipole interaction strategy for fabricating a solvent-free adhesive that is synthesized via simple one-step copolymerization of dipole monomer acrylonitrile (AN), crosslinker poly(ethylene glycol) diacrylate (PEGDA) with variable length, and a monomer-soluble initiator that initiates room-temperature polymerization. The dipole-dipole interactions from cyan groups in AN concurrently contribute to strong cohesion and adhesion strength in bonding to a wide range of substrates including aluminum, ceramic, glass fiber, epoxy resin, polyethylene terephthalate, wood, and fractured large segmental bone. The adhesion strengths are dependent upon the length of PEGDA, and the shorter PEGDA-crosslinked PAN adhesive demonstrates outstanding water-resistant adhesion spanning pH 2 to pH 10 for 30 days with adhesion strength ranging from 3.31 to 3.97 MPa due to strong dipole-dipole pairing shielding. This dipole-dipole interaction and co-dissolution strategy open a new avenue for creating high-strength water-resistant adhesives for promising applications in engineering and hard-tissue repair.
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http://dx.doi.org/10.1002/marc.202100010DOI Listing
May 2021

Analysis on historical flood and countermeasures in prevention and control of flood in Daqing River Basin.

Environ Res 2021 Feb 17;196:110895. Epub 2021 Feb 17.

Institute of Urban and Rural Construction, Hebei Agricultural University, Baoding, 071000, China.

The Daqing River Basin has long been seriously threatened by floods. The construction of Xiong'an New Area has put forward higher requirements for the flood control system of the basin. Researches on the characteristics of the flood control system in the Daqing River Basin, the causes of the flood and the historical flood were conducted with the purpose to have a clear understanding of the deficiency of the existing flood control system in the Drainage Basin and figure out the countermeasures to improve the flood control capacity of the Drainage Basin by taking the development process of the flood control system in the Drainage Basin into consideration. Analysis was conducted on the causes, flood process, the process of regulation and storage of reservoirs and depressions as well as flood disaster with the flood occurred in August 1963 as the major research object. Besides, the deficiency of flood control system of the Drainage Basin in terms of flood control system and the flood occurred in August 1963 (also called 63.8 Flood). According to the research, the major problems in the current flood control system of the Daqing River Basin are mainly concentrated on Baiyang Lake with blocked internal water transmission and insufficient drainage capacity, which makes it difficult to cope with the flood exceeding the designed level. The great change of water level will also destroy the ecological balance of Baiyang Lake itself. In addition, during the construction of the New District, some flood storage and detention areas in Baiyang Lake will be deprived of the capability in regulation and storage, which will increase the difficulty of flood control in the downstream areas. Combined with the existing flood control system and aiming at the construction of Xiong'an New Area, the concepts of flood control system such as developing the Xiaoguan flood diversion way, rebuilding the new housing hub and strengthening the dredging of downstream river are put forward.
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http://dx.doi.org/10.1016/j.envres.2021.110895DOI Listing
February 2021

The Genome Copy Number of the Thermophilic Cyanobacterium Thermosynechococcus elongatus E542 Is Controlled by Growth Phase and Nutrient Availability.

Appl Environ Microbiol 2021 04 13;87(9). Epub 2021 Apr 13.

School of Environment and Energy, Peking University Shenzhen Graduate School, Shenzhen, China

The recently isolated thermophilic cyanobacterium PKUAC-SCTE542 (here E542) is a promising strain for fundamental and applied research. Here, we used several improved ploidy estimation approaches, which include quantitative PCR (qPCR), spectrofluorometry, and flow cytometry, to precisely determine the ploidy level in E542 across different growth stages and nutritional and stress conditions. The distribution of genome copies per cell among the populations of E542 was also analyzed. The strain tends to maintain 3 or 4 genome copies per cell in lag phase, early growth phase, or stationary phase under standard conditions. Increased ploidy (5.5 ± 0.3) was observed in exponential phase; hence, the ploidy level is growth phase regulated. Nearly no monoploid cells were detected in all growth phases, and prolonged stationary phase could not yield ploidy levels lower than 3 under standard conditions. During the late growth phase, a significantly higher ploidy level was observed in the presence of bicarbonate (7.6 ± 0.7) and high phosphate (6.9 ± 0.2) at the expense of reduced percentages of di- and triploid cells. Meanwhile, the reduction in phosphates decreased the average ploidy level by increasing the percentages of mono- and diploid cells. In contrast, temperature and antibiotic stresses reduced the percentages of mono-, di-, and triploid cells yet maintained average ploidy. The results indicate a possible causality between growth rate, stress, and genome copy number across the conditions tested, but the exact mechanism is yet to be elucidated. Furthermore, the spectrofluorometric approach presented here is a quick and straightforward ploidy estimation method with reasonable accuracy. The present study revealed that the genome copy number (ploidy) status in the thermophilic cyanobacterium E542 is regulated by growth phase and various environmental parameters to give us a window into understanding the role of polyploidy. An increased ploidy level is found to be associated with higher metabolic activity and increased vigor by acting as backup genetic information to compensate for damage to the other chromosomal copies. Several improved ploidy estimation approaches that may upgrade the ploidy estimation procedure for cyanobacteria in the future are presented in this work. Furthermore, the new spectrofluorometric method presented here is a rapid and straightforward method of ploidy estimation with reasonable accuracy compared to other laborious methods.
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http://dx.doi.org/10.1128/AEM.02993-20DOI Listing
April 2021

N-methyldeoxyadenine and histone methylation mediate transgenerational survival advantages induced by hormetic heat stress.

Sci Adv 2021 01 1;7(1). Epub 2021 Jan 1.

Zhuhai Precision Medical Center, Zhuhai People's Hospital (Zhuhai Hospital Affiliated with Jinan University), Jinan University, Guangzhou, Guangdong 510632, China.

Environmental stress can induce survival advantages that are passed down to multiple generations, representing an evolutionarily advantageous adaptation at the species level. Using the nematode worm as a model, we found that heat shock experienced in either parent could increase the longevity of themselves and up to the fifth generation of descendants. Mechanistic analyses revealed that transcription factor DAF-16/FOXO, heat shock factor HSF-1, and nuclear receptor DAF-12/FXR functioned transgenerationally to implement the hormetic stress response. Histone H3K9me3 methyltransferases SET-25 and SET-32 and DNA N-methyl methyltransferase DAMT-1 participated in transmitting high-temperature memory across generations. H3K9me3 and N-methyladenine could mark heat stress response genes and promote their transcription in progeny to extend life span. We dissected the mechanisms responsible for implementing and transmitting environmental memories in descendants from heat-shocked parents and demonstrated that hormetic stress caused survival benefits could be transmitted to multiple generations through H3K9me3 and N-mA modifications.
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http://dx.doi.org/10.1126/sciadv.abc3026DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7775758PMC
January 2021

Fast Screening and Primary Diagnosis of COVID-19 by ATR-FT-IR.

Anal Chem 2021 02 11;93(4):2191-2199. Epub 2021 Jan 11.

Department of Laboratory Medicine, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing 100730, China.

The outbreak of coronavirus disease 2019 (COVID-19) has led to substantial infections and mortality around the world. Fast screening and diagnosis are thus crucial for quick isolation and clinical intervention. In this work, we showed that attenuated total reflection-Fourier transform infrared spectroscopy (ATR-FT-IR) can be a primary diagnostic tool for COVID-19 as a supplement to in-use techniques. It requires only a small volume (∼3 μL) of the serum sample and a shorter detection time (several minutes). The distinct spectral differences and the separability between normal control and COVID-19 were investigated using multivariate and statistical analysis. Results showed that ATR-FT-IR coupled with partial least squares discriminant analysis was effective to differentiate COVID-19 from normal controls and some common respiratory viral infections or inflammation, with the area under the receiver operating characteristic curve (AUROC) of 0.9561 (95% CI: 0.9071-0.9774). Several serum constituents including, but not just, antibodies and serum phospholipids could be reflected on the infrared spectra, serving as "chemical fingerprints" and accounting for good model performances.
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http://dx.doi.org/10.1021/acs.analchem.0c04049DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7805601PMC
February 2021

[Correlation between Vitamin D Status and Gut Microbiota in Patients with Inflammatory Bowel Disease].

Zhongguo Yi Xue Ke Xue Yuan Xue Bao 2020 Dec;42(6):740-748

Department of Gastroenterology, PUMC Hospital, CAMS and PUMC,Beijing 100730,China.

Objective To investigate the correlation between serum total 25-hydroxyvitamin D[T-25(OH)D]level and fecal microbiota in patients with inflammatory bowel disease(IBD). Methods Twenty-three patients with IBD completed the tests for serum T-25(OH)D,and the fecal microbiota was studied using V4 hypervariable region of 16S ribosomal RNA(rRNA)gene sequencing.According to serum T-25(OH)D level,the patients were divided into three groups including vitamin D normal group(=5),vitamin D insufficiency group(=5),and vitamin D deficiency group(=13). Results There was no significant difference between these three groups in Alpha diversity or Beta diversity.Ternary pot at phylum level revealed that the abundance of was the highest in the vitamin D deficiency group and was the highest in the vitamin D sufficiency group.Spearman correlation analysis showed that at the phylum level serum T-25(OH)D level was negatively correlated with the abundance of (=-0.445,=0.033)and positively correlated with the abundance of ( =0.447,=0.033);at family level it was positively correlated with the abundance of ( =0.414,=0.049), ( =0.468,=0.024), ( =0.584,=0.003),and ( =0.507,=0.014)and negatively correlated with the abundance of (=-0.514, =0.012);and at genus level it was positively correlated with the abundance of (=0.459,=0.028), (=0.468,=0.024),unidentified (=0.485,=0.019), (=0.544,=0.007), (=0.475,=0.022), (=0.510,=0.013), (=0.455,=0.029),and (=0.617,=0.002). Conclusions The fecal microbiota composition varies in IBD patients with different serum T-25(OH)D levels.The abundance of increases and the abundance of decreases in IBD patients with vitamin D deficiency compared with IBD patients with normal vitamin D level.Serum T-25(OH)D level is negatively correlated with the abundance of some harmful bacteria(e.g.)but is positively correlated with the abundance of some probiotics such as ,,and .
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http://dx.doi.org/10.3881/j.issn.1000-503X.12105DOI Listing
December 2020

Clinical Course and Risk Factors of Disease Deterioration in Critically Ill Patients with COVID-19.

Hum Gene Ther 2021 03 22;32(5-6):310-315. Epub 2021 Feb 22.

The Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education, Chinese National Health Commission and Chinese Academy of Medical Sciences, The State and Shandong Province Joint Key Laboratory of Translational Cardiovascular Medicine, Department of Cardiology, Cheeloo College of Medicine, Shandong University, Qilu Hospital, Jinan, China.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) began in December 2019 and rapidly spread to other provinces in China as well as other countries. In this study, 262 patients diagnosed with moderate to severe SARS-CoV-2 pneumonia in Wuhan, China, were analyzed. Data were compared between survivors and nonsurvivors. Of all the 262 patients, 23 (8.8%) patients died and 239 (91.2%) were discharged. The median age was 63.5 years and 46.9% of patients were male. The main complaints were fever (83.6%), cough (63.4%), and fatigue (49.2%) in the surviving group, while there were more complaints of dyspnea (39.1%) and shortness of breath (56.5%) in the nonsurviving group. The main comorbidities were hypertension (35.5%), diabetes mellitus (16.4%), and coronary artery disease (9.9%). Morbidity is higher in elderly patients with more comorbidities. Patients were mainly treated with nasal cannula (93.9%), while the nonsurviving group received more invasive mechanical ventilation (39.1%). Arbidol (80.9%), ribavirin (36.6%), oseltamivir (38.9%), interferon (16.4%), and ganciclovir (14.5%) were used for the antiviral treatment. In the nonsurviving group, the number of white blood cells (WBC) was significantly increased and lymphocytes were decreased, and lymphopenia was more common. The levels of aspartate transaminase (AST), brain natriuretic peptide (BNP), creatine kinase isoenzyme MB (CK-MB), lactate dehydrogenase (LDH), and C-reactive protein (CRP) were also significantly increased in the nonsurviving group. The adjusted hazard ratios (HRs) for association of known variables for all-cause mortality due to the coronavirus disease 2019 were 2.467 (95% confidence interval [CI], 1.007-6.044;  = 0.048) for shortness of breath and 1.025 (95% CI, 1.001-1.049;  = 0.042) for AST. Elderly patients with more comorbidities and complaints of dyspnea and shortness of breath had increased risk of death. Patients with lymphopenia and high levels of WBC, AST, BNP, CK-MB, LDH, and CRP may be more likely to deteriorate.
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http://dx.doi.org/10.1089/hum.2020.255DOI Listing
March 2021

P-cresol degradation through Fe(III)-EDDS/HO Fenton-like reaction enhanced by manganese ion: Effect of pH and reaction mechanism.

Chemosphere 2021 Apr 27;269:129436. Epub 2020 Dec 27.

State Key Laboratory Base for Eco-Chemical Engineering in College of Chemical Engineering, Qingdao University of Science and Technology, Qingdao, 266042, China. Electronic address:

P-cresol is a highly toxic phenolic pollutant in coal chemical wastewater. The effective removal of p-cresol is of great significance to the ecological environment. In this study, the degradation of p-cresol by the Fe(III)-EDDS/HO Fenton-like reaction modified by Mn was investigated. The results showed that the removal rate of p-cresol could be significantly increased by the addition of Mn under neutral and weakly alkaline conditions (pH 6.5-8.5). Acidic conditions (pH 3.5) were not conducive to the Fenton-like reaction. This is because a neutral or weakly alkaline environment is conducive to Mn-EDDS complex formation, which can produce O to accelerate the reduction of Fe(III), and the efficiency of p-cresol degradation through a Fenton-like reaction catalyzed by the Fe(III)-EDDS complex is significantly improved. In addition, the degradation of EDDS through ·OH was reduced by O, which maintained and stabilized the Mn-EDDS complex and Fe(III)-EDDS complex. Under neutral conditions, the optimal dosage of Fe(III) is 0.7 mM, and the optimal molar ratios are EDDS/Fe(III) = 1: 1, Mn/Fe(III) = 1: 1, and HO/Fe(III) = 15: 1. The addition of free radical clearance isopropanol and CHCl proved that ·OH was the main active substance in the p-cresol degradation process.
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http://dx.doi.org/10.1016/j.chemosphere.2020.129436DOI Listing
April 2021

SARS-CoV-2 not found in pressure injury exudates from COVID-19 patients.

J Cosmet Dermatol 2021 Feb 21;20(2):372-380. Epub 2020 Dec 21.

Department of Plastic Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.

Background: The emergence of COVID-19 has become a global health emergency. The transmissibility of the disease is of great interest to healthcare workers and scientists alike. The primary route of transmission is via respiratory droplets, but viral RNA has also been found in feces and body fluids such as urine, serum, and semen. So far, there has been no report on whether SARS-CoV-2 is present in the exudates of cutaneous lesions. This study was designed to investigate whether SARS-CoV-2 can be found in the pressure injury exudates in patients with severe COVID-19 infections.

Methods: 46 critically ill COVID-19 patients who were admitted to the ICU of the Sino-French New City Branch of Tongji Hospital in Wuhan between February 4 and April 12 developed pressure injuries. 22 patients with pressure injuries had wound exudates. Wound and pharyngeal swabs of the 22 patients were collected and RT-PCRs were conducted to detect SARS-CoV-2 viral RNA.

Results: At the time of pressure injury, 5 patients still tested positive by pharyngeal swabs, the rest of the 17 patients tested negative. However, none of the wound exudate swabs from the participants tested positive for SARS-CoV-2 by RT-PCR.

Conclusion: Our study suggests that it is rather unlikely that COVID-19 can be transmitted via pressure injury exudates, but we still recommend standardized personal protective equipment, face shield and an additional pair of gloves when treating pressure injuries.
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http://dx.doi.org/10.1111/jocd.13887DOI Listing
February 2021

Injectable Hyaluronic Acid Hydrogel Loaded with Functionalized Human Mesenchymal Stem Cell Aggregates for Repairing Infarcted Myocardium.

ACS Biomater Sci Eng 2020 12 5;6(12):6926-6937. Epub 2020 Nov 5.

School of Materials Science and Engineering, Tianjin Key Laboratory of Composite and Functional Materials, Tianjin University, Tianjin 300350, China.

Conventional strategies of stem cell injection in treating myocardial infarction (MI) remain a challenge because of low retention rate and insufficient secretion of exogenous cytokines for efficiently improving the microenvironment in the infarcted myocardium, thus hampering the therapeutic effect. Herein, poly(lactic--glycolic acid) (PLGA) microparticles modified with human VE-cad-Fc fusion protein are fabricated and integrated with human mesenchymal stem cells (hMSCs) to construct functionalized MSC aggregates (FMAs). This fusion protein can effectively promote the paracrine activity of MSCs. The FMA is encapsulated with an injectable hyaluronic acid (HA)-based hydrogel, which is prepared by Schiff base reaction between oxidized HA (OHA) and hydrazided HA (HHA). The OHA@HHA hydrogel loading FMA is injected into the infarcted myocardium of rats, thereby efficiently improving the MI microenvironment in terms of decreased expressions of inflammatory cytokines and upregulated secretion of angiogenic factors compared to the plain hydrogel only and hydrogel encapsulating MSCs. The results of both echocardiography and histological analyses demonstrate the efficient reconstruction of cardiac function and structure and revascularization in the infarct myocardium. The delivery of functionalized stem cell aggregates with an injectable hydrogel offers a promising strategy for treating myocardial infarction and may be expanded to other tissue repair and reconstruction.
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http://dx.doi.org/10.1021/acsbiomaterials.0c01344DOI Listing
December 2020

Rapid detection of seven indexes in sheep serum based on Raman spectroscopy combined with DOSC-SPA-PLSR-DS model.

Spectrochim Acta A Mol Biomol Spectrosc 2021 Mar 28;248:119260. Epub 2020 Nov 28.

College of Information Science and Engineering, Xinjiang University, Urumqi 830046, China; Key Laboratory of Signal Detection and Processing, Xinjiang University, Urumqi 830046, China; College of Software, Xinjiang University, Urumqi 830002, China. Electronic address:

Hepatic fascioliasis, ketosis of pregnancy, toxemia of pregnancy and other common sheep diseases will directly affect the concentration (/enzymatic activity) of seven indicators, such as cortisol and high-density lipoprotein cholesterol (HDL-C) in sheep serum. Whether the concentrations (/enzymatic activity) of these indicators can be detected quickly will directly affect the prevention of sheep diseases and the targeted adjustment of breeding methods, thereby affecting the economic benefits of sheep breeding. In this research, we established partial least square regression (PLSR), support vector regression based on genetic algorithm optimization (GA-SVR) and extreme learning machine (ELM) models. Due to the large differences in the content of different substances, it is difficult to directly use the RMSE to evaluate the quantitative effect of the model. This study is the first to propose conducting deviation standardization (DS) for the determination results of various substances. To further improve the performance of the model, we use the successive projections algorithm (SPA) to optimize feature extraction and combine it with the better-performing PLSR model for training. The results show that the optimized DOSC-SPA-PLSR-DS quantitative model has better determination results for 101 sheep serum samples. The average RMSE of the concentration of the six substances decreased from 0.0408 to 0.0387, the R increased from 0.9758 to 0.9846, and the running time was reduced from 0.1659 to 0.0008 s. And the determination performance of lipase (LPS) enzymatic activity has also been improved. The results of this research show that sheep serum Raman spectroscopy combined with DOSC-SPA-PLSR-DS optimization can efficiently monitor the concentration (/enzyme activity) of seven indicators in real time and provide a new strategy for future intelligent supervision of animal husbandry.
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http://dx.doi.org/10.1016/j.saa.2020.119260DOI Listing
March 2021

The association study of Apolipoprotein E polymorphisms and chronic obstructive pulmonary disease in the Chinese population: A case-control study.

Medicine (Baltimore) 2020 Dec;99(49):e23442

Department of Geriatrics, Sichuan Academy of Medical Sciences & Sichuan Provincial People's Hospital, Chengdu, Sichuan, PR China.

Chronic obstructive pulmonary disease (COPD) patients have increased cardiovascular morbidity and mortality. Apolipoprotein E (ApoE) is involved in chronic inflammation which is the common characteristic of emphysema and cardiovascular disease. ApoE polymorphisms are associated with cardiovascular disorders and atherosclerosis. There is no report about the association between ApoE polymorphism and COPD.A total of 480 COPD patients and 322 controls who were unrelated Chinese Han individuals were enrolled. Rs429358 and rs7412 were genotyped and the associations between ApoE polymorphisms and COPD risk were analyzed by logistic regression analysis. Online software SHEsis were applied to perform linkage disequilibrium (LD) and haplotypes analysis. The interactions of ApoE and environmental factor on COPD susceptibility was analyzed by software MDR3.0.2.No significant association was found between rs429358, rs7412 and COPD under different genetic models. Rs429358 and smoking formed the best model in the MDR analysis. The frequency of E2/E2 phenotype was the lowest in 2 groups. E3/E3 was the most common phenotype, accounting for 69.8% of COPD patients and 68.9% of controls. No statistically difference was identified between the cases and controls under different phenotypes.This was the first genetic association study between ApoE and COPD. No positive association was found in the Chinese Han population. Rs429358 and smoking status existed significant interaction, indicating that both of ApoE and smoking may be involved in the development of COPD disease.
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http://dx.doi.org/10.1097/MD.0000000000023442DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7717833PMC
December 2020

Injectable Hypoxia-Induced Conductive Hydrogel to Promote Diabetic Wound Healing.

ACS Appl Mater Interfaces 2020 Dec 4;12(51):56681-56691. Epub 2020 Dec 4.

Guangdong Cardiovascular Institute, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou, Guangdong 510080, China.

Injectable hydrogels with the capability to cast a hypoxic microenvironment is of great potentialities to develop novel therapies for tissue regeneration. However, the relative research still remains at the conceptual phase. Herein, we chose diabetic wound as a representative injury model to explore the actual therapeutic results of tissue injury by injectable hypoxia-induced hydrogels. To enhance recovery and widen applicability, the hypoxia-induced system was incorporated with a conductive network by an original sequentially interpenetrating technique based on the combination of a fast "click chemistry" and a slow enzymatic mediated cross-linking. Hyperbranched poly(β-amino ester)-tetraaniline (PBAE-TA) was cross-linked with thiolated hyaluronic acid (HA-SH) via a thiol-ene click reaction, contributing to the rapid formation of the first conductive network, where vanillin-grafted gelatin (Geln-Van) and laccase (Lac) with a slow cross-linking rate were employed in casting a hypoxic microenvironment. The as-prepared injectable hydrogels possessed both suitable conductivity and sustainable hypoxia-inducing capability to upregulate the hypoxia-inducible factor-1α and connexin 43 expressions of the encapsulated adipose-derived stem cells, which enhanced vascular regeneration and immunoregulation and further promoted the reconstruction of blood vessels, hair follicles, and dermal collagen matrix, eventually leading to the recovery of diabetic rat skin wounds and restoration of skin functions. This work provides a promising strategy to broaden the applicability of diverse hydrogels with a long time-consuming gelation process and to integrate different networks with various biological functions for the therapies of diabetic wounds and other complex clinical symptoms.
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http://dx.doi.org/10.1021/acsami.0c13197DOI Listing
December 2020

Association between self-reported snoring and hypertension among Chinese Han population aged 30-79 in Chongqing, China.

Environ Health Prev Med 2020 Dec 3;25(1):78. Epub 2020 Dec 3.

School of Public Health and Management, Collaborative Innovation Center of Social Risks Governance in Health, Chongqing Medical University, No.1 Yixueyuan Road, Yuzhong District, Chongqing, 400016, China.

Background: We aim to explore the association between self-reported snoring and hypertension among adults aged 30-79 in Chongqing, China.

Methods: A total of 23,342 individuals aged 30-79 were included at baseline from August 2018 to January 2019, and the final sample size for the analysis was 22,423. Face-to-face interviews and physical examinations were conducted by trained investigators. Logistic regression was performed to study age-specific and gender-specific associations between snoring and hypertension.

Results: Frequent snoring was associated with the risk of hypertension for each age and gender group, and the frequency of snoring was positively correlated with the risk for hypertension. For the three age groups (< 45, 45-59, ≥ 60), compared with the non-snoring group, those who snore often had a 64.5%, 53.3%, and 24.5% increased risk of hypertension (< 45: OR = 1.65, 95%CI 1.34-2.02; 45-59: OR = 1.53, 95%CI 1.37-1.72; ≥ 60: OR = 1.25, 95%CI 1.09-1.42), respectively. For men and women, those who snore often had a 46.8% and 97.2% increased risk of hypertension, respectively, than the non-snoring group (men: OR = 1.47, 95%CI 1.33-1.63; women: OR = 1.97, 95%CI 1.75-2.23).

Conclusions: People who snore frequently should pay close attention to their blood pressure levels in order to achieve early prevention of hypertension, particularly for snorers who are female and aged under 45; importance should be attached to their blood pressure control.
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http://dx.doi.org/10.1186/s12199-020-00908-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7713023PMC
December 2020

Mixed adenoneuroendocrine carcinoma of the hepatic bile duct: a case report and review of the literature.

BMC Gastroenterol 2020 Nov 25;20(1):399. Epub 2020 Nov 25.

Department of Hepatobiliary Surgery, Hunan Provincial People's Hospital/The First Affiliated Hospital of Hunan Normal University, Changsha, Hunan Province, People's Republic of China.

Background: The World Health Organization's updated classification of digestive system neuroendocrine tumors in 2010 first proposed the classification of mixed adenoneuroendocrine carcinoma (MANEC). The incidence of biliary malignant tumors with neuroendocrine tumors accounts for less than 1% of all neuroendocrine tumors. Moreover, the incidence of hilar bile duct with MANEC is very rare.

Case Presentation: A 65-year-old female patient came to our hospital for repeated abdominal pain for more than 4 months and skin sclera yellow staining for 1 week. Contrast-enhanced computed tomography imaging and magnetic resonance results suggested a hilar tumor for Bismuth-Corlette Type II. The patient underwent radical surgery for hilar cholangiocarcinoma. Finally, the patient was diagnosed with hilar bile duct MANEC, staged 1 (pT1N0M0) based on the eighth edition of the AJCC. Histopathology showed that the tumor was a biliary tumor with both adenocarcinoma and neuroendocrine carcinoma. No evidence of recurrence and metastasis after 20 months of follow-up.

Conclusions: We first reported a MANEC that originated in the hilar bile duct. As far as we known, there were few reports of biliary MANEC, and the overall prognosis was poor. We also found that the higher the Ki-67 index, the worse the prognosis of this type of patient. Radical surgery is the most effective treatment.
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http://dx.doi.org/10.1186/s12876-020-01550-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7691051PMC
November 2020

Antimicrobial activity of omadacycline in vitro against bacteria isolated from 2014 to 2017 in China, a multi-center study.

BMC Microbiol 2020 11 16;20(1):350. Epub 2020 Nov 16.

Department of Clinical Laboratory, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, 100730, China.

Background: Omadacycline (ZL-2401) is a semi-synthetic derivative of minocycline. It has a broadspectrum activity against Gram-positive and Gram-negative bacteria, and atypical pathogens. The objective of this study was to evaluate the antibacterial activity of omadacycline against recently collected bacterial isolates from Chinese patients.

Results: Omadacycline showed potent activity against all Gram-positive pathogens: S. aureus MICs were low regardless of susceptibility to methicillin (methicillin-resistant Staphylococcus aureus, MRSA: N = 97, MIC 0.12/0.25 mg/L, 98.5% susceptible; methicillin-sensitive Staphylococcus aureus, MSSA: N = 100, MIC 0.12/0.12 mg/L, 100.0% susceptible). Omadacycline was also very effective against β-haemolytic streptococci (MIC, 0.06/0.12 mg/L), viridans group streptococci (MIC,<0.03/0. 06 mg/L), and enterococci (MIC, 0.03/0.12 mg/L). Against S. pneumoniae, omadacycline was highly active regardless of penicillin-resistance (MIC 0.06 mg/L) and despite the fact that less than 10.0% of these strains were susceptible to tetracycline. Omadacycline exhibited good in vitro activity against Enterobacterales isolates (MIC, 2/8 mg/L), inhibiting 81.7% of the isolates at ≤4 mg/L. M. catarrhalis isolates (MIC, 0.12/0.25 mg/L) were fully susceptible to omadacycline at ≤0.5 mg/L.

Conclusions: Omadacycline showed potent in vitro activity against most common bacterial pathogens, and even against highly resistant problem pathogens, such as MRSA, penicillin-R and tetracycline-R S. pneumoniae and enterococci. The susceptibility rate of Chinese isolates was similar to those reported in other countries, but the decreased activity against K. pneumoniae isolates in the present study should be noted.
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http://dx.doi.org/10.1186/s12866-020-02019-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7667747PMC
November 2020

Progressive emergence of an S153F plus R263K combination of integrase mutations in the proviral DNA of one individual successfully treated with dolutegravir.

J Antimicrob Chemother 2021 Feb;76(3):639-647

McGill AIDS Centre, Lady Davis Institute for Medical Research, Jewish General Hospital, Montréal, Québec, Canada.

Objectives: The development of HIV drug resistance against the integrase strand transfer inhibitor dolutegravir is rare. We report here the transient detection, by near full-genome ultradeep sequencing, of minority HIV-1 subtype B variants bearing the S153F and R263K integrase substitutions in the proviral DNA from blood cells of one patient who successfully initiated dolutegravir-based ART, over 24 weeks. Our objective was to study the effects of these substitutions.

Methods: Strand transfer and DNA-binding activities of recombinant integrase proteins were measured in cell-free assays. Cell-based resistance, infectivity and replicative capacities were measured using molecular clones. Structural modelling was performed to understand experimental results.

Results: R263K emerged first, followed by the addition of S153F at Week 12. By Week 24, both mutations remained present, but at lower prevalence. We confirmed the coexistence of S153F and R263K on single viral genomes. Combining S153F or S153Y with R263K decreased integration and viral replicative capacity and conferred high levels of drug resistance against all integrase inhibitors. Alone, S153Y and S153F did little to infectivity or dolutegravir resistance. We identified altered DNA binding as a mechanism of resistance. The patient remained with undetectable viral loads at all timepoints.

Conclusions: Drug-resistant minority variants have often been reported under suppressive ART. Our study adds to these observations by unravelling a progression towards higher levels of resistance through a novel pathway despite continuous undetectable viral loads. Poorly replicative HIV drug-resistant minority proviral variants did not compromise viral suppression in one individual treated with dolutegravir.
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http://dx.doi.org/10.1093/jac/dkaa471DOI Listing
February 2021