Publications by authors named "Yiming Li"

669 Publications

Carnosol and its analogues attenuate muscle atrophy and fat lipolysis induced by cancer cachexia.

J Cachexia Sarcopenia Muscle 2021 May 5. Epub 2021 May 5.

Shanghai Engineering Research Center of Molecular Therapeutics and New Drug Development, School of Chemistry and Molecular Engineering, East China Normal University, Shanghai, China.

Background: Cancer cachexia is a multifactorial debilitating syndrome that directly accounts for more than 20% of cancer deaths while there is no effective therapeutic approach for treatment of cancer cachexia. Carnosol (CS) is a bioactive diterpene compound present in Lamiaceae spp., which has been demonstrated to have antioxidant, anti-inflammatory, and anticancer properties. But its effects on cancer cachexia and the possible mechanism remain a mystery.

Methods: The in vitro cell models of C2C12 myotube atrophy and 3T3-L1 mature adipocyte lipolysis were used to check the activities of CS and its synthesized analogues. C26 tumour-bearing BALB/c mice were applied as the animal model to examine their therapeutic effects on cancer cachexia in vivo. Levels of related signal proteins in both in vitro and in vivo experiments were examined using western blotting to study the possible mechanisms.

Results: Carnosol and its analogues [dimethyl-carnosol (DCS) and dimethyl-carnosol-D6 (DCSD)] alleviated myotube atrophy of C2C12 myotubes and lipolysis of 3T3-L1 adipocytes in vitro. Interestingly, CS and its analogues exhibited stronger inhibitive effects on muscle atrophy induced by tumour necrosis factor-α (TNF-α) (CS, P < 0.001; DCS, P < 0.001; DCSD, P < 0.001) in C2C12 myoblasts than on muscle atrophy induced by IL-6 (CS, P < 0.05; DCS, P = 0.08; DCSD, P < 0.05). In a C26 tumour-bearing mice model, administration of CS or its analogue DCSD significantly prevented body weight loss without affecting tumour size. At the end of the experiment, the body weight of mice treated with CS and DCSD was significantly increased by 11.09% (P < 0.01) and 11.38% (P < 0.01) compared with that of the C26 model group. CS and DCSD also improved the weight loss of epididymal adipose tissue in C26 model mice by 176.6% (P < 0.01) and 48.2% (P < 0.05) increase, respectively. CS and DCSD treatment partly preserved gastrocnemius myofibres cross-sectional area. CS treatment decreased the serum level of TNF-α (-95.02%, P < 0.01) but not IL-6 in C26 tumour-bearing mice. Inhibition on NF-κB and activation of Akt signalling pathway were involved in the ameliorating effects of CS and its analogues on muscle wasting both in vitro and in vivo. CS and its analogues also alleviated adipose tissue loss by inhibiting NF-κB and AMPK signalling pathways both in vitro and in vivo.

Conclusions: CS and its analogues exhibited anticachexia effects mainly by inhibiting TNF-α/NF-κB pathway and decreasing muscle and adipose tissue loss. CS and its analogues might be promising drug candidates for the treatment of cancer cachexia.
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http://dx.doi.org/10.1002/jcsm.12710DOI Listing
May 2021

Sesquiterpene-Loaded Co-Polymer Hybrid Nanoparticle Effects on Human Mast Cell Surface Receptor Expression, Granule Contents, and Degranulation.

Nanomaterials (Basel) 2021 Apr 8;11(4). Epub 2021 Apr 8.

Nanotechnology Research Centre, National Research Council Canada, Edmonton, AB TG6 2M9, Canada.

Biodegradable polymeric nanoparticles (NPs) such as poly(lactic-co-glycolic acid) (PLGA) and polyvinyl alcohol (PVA) have been used as drug delivery systems for natural and synthetic compounds and are designed to control the loading and release of biodegradable materials to target cells, tissues, and organs. Eremophilane-type sesquiterpenes have anti-inflammatory properties but are lipophilic, cytotoxic, and not biocompatible with many cells. To determine whether biodegradable PLGA/PVA could improve the biocompatibility of sesquiterpenes, sesquiterpene-loaded NPs were synthesized and their effects on human mast cells (LAD2), the major effector cells of allergic inflammation, were determined. NPs composed of PLGA/PVA and two types of sesquiterpenes (fukinone, PLGA/PVA-21 and 10βH-8α,12-epidioxyeremophil-7(11)-en-8β-ol, PLGA/PVA-22) were produced using a microfluidic synthesis method. The NPs' size distribution and morphology were evaluated by dynamic light scattering and cryogenic transmission electron microscopy (TEM). PLGA/PVA-21 and PLGA/PVA-22 were 60 to 70 nm and were readily internalized by LAD2 as shown by flow cytometry, fluorescence microscopy, and TEM. While unencapsulated sesquiterpenes decreased LAD2 cell viability by 20%, PLGA/PVA-21 and PLGA/PVA-22 did not alter LAD2 viability, showing that encapsulation improved the biocompatibility of the sesquiterpenes. PLGA/PVA-21 and PLGA/PVA-22 decreased the expression of genes encoding the subunits of the high affinity immunoglobulin E receptor (, , ) and the stem cell factor receptor (), suggesting that hybrid NPs could alter mast cell responses to antigens and shift their maturation. Similarly, PLGA/PVA-21 and PLGA/PVA-22 inhibited tryptase expression but had no effect on chymase expression, thereby promoting a shift to the tryptase-positive phenotype (MC). Lastly, PLGA/PVA-21 and PLGA/PVA-22 inhibited mast cell degranulation when the LAD2 cells were activated by IgE crosslinking and FcεRI. Overall, our results suggest that PLGA/PVA-21 and PLGA/PVA-22 alter human mast cell phenotype and activation without modifying viability, making them a more biocompatible approach than treating cells with sesquiterpenes alone.
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http://dx.doi.org/10.3390/nano11040953DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8068390PMC
April 2021

Exosome-Mediated Delivery of the Neuroprotective Peptide PACAP38 Promotes Retinal Ganglion Cell Survival and Axon Regeneration in Rats With Traumatic Optic Neuropathy.

Front Cell Dev Biol 2021 6;9:659783. Epub 2021 Apr 6.

Department of Ophthalmology, Tianjin Medical University General Hospital, Tianjin, China.

Traumatic optic neuropathy (TON) refers to optic nerve damage caused by trauma, leading to partial or complete loss of vision. The primary treatment options, such as hormonal therapy and surgery, have limited efficacy. Pituitary adenylate cyclase-activating polypeptide 38 (PACAP38), a functional endogenous neuroprotective peptide, has emerged as a promising therapeutic agent. In this study, we used rat retinal ganglion cell (RGC) exosomes as nanosized vesicles for the delivery of PACAP38 loaded via the exosomal anchor peptide CP05 (EXO ). EXO showed greater uptake efficiency and than PACAP38. The results showed that EXO significantly enhanced the RGC survival rate and retinal nerve fiber layer thickness in a rat TON model. Moreover, EXO significantly promoted axon regeneration and optic nerve function after injury. These findings indicate that EXO can be used as a treatment option and may have therapeutic implications for patients with TON.
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http://dx.doi.org/10.3389/fcell.2021.659783DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8055942PMC
April 2021

Exosome-mediated delivery of an anti-angiogenic peptide inhibits pathological retinal angiogenesis.

Theranostics 2021 5;11(11):5107-5126. Epub 2021 Mar 5.

Department of Ophthalmology, Tianjin Medical University General Hospital, 300070, Tianjin, China.

Pathological angiogenesis is the hallmark of many vision-threatening diseases. Anti-VEGF is a primary treatment with substantial beneficial effects. However, such agents require frequent intravitreal injections. Our previous work established a method for effectively modifying exosomes (EXOs) for loading therapeutic peptides. Here, we used this system to load the anti-angiogenic peptide KV11, aiming to establish an EXO-based therapy strategy to suppress neovascularization in the retina. Using an anchoring peptide, CP05, we linked KV11 to endothelial cell (EC) derived EXOs, yielding EXO. We tested the delivery efficiency of EXO via two commonly used ocular injection methods: retro-orbital injection and intravitreal injection. Deploying an oxygen-induced retinopathy (OIR) model and a VEGF injection model, we tested the effects of EXO on neovascular formation, EC proliferation, and vascular permeability. experiments were used to test the mechanism and to analyze the effects of EXO on EC proliferation, migration, and sprouting. : By using the EXO loading system, KV11 was more efficiently delivered to the blood vessels of the mouse retina via retro-orbital injection. In both OIR model and VEGF injection model, EXO was more effective than KV11 alone in inhibiting neovascularization and vessel leakage. The therapeutic effect of retro-orbital injection of EXO was comparable to the intravitreal injection of VEGF-trap. Mechanistically, KV11 alone inhibited VEGF-downstream signaling, while EXO showed a stronger effect. We used EXOs as a carrier for intraocular delivery of KV11. We showed that KV11 itself has an anti-angiogenic effect through retro-orbital injection, but that this effect was greatly enhanced when delivered with EXOs. Thus, this system has the potential to treat proliferative retinopathy via retro-orbital injection which is a less invasive manner compared with intravitreal injection.
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http://dx.doi.org/10.7150/thno.54755DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8039955PMC
March 2021

Hierarchical Self-Assembly of Nanowires on the Surface by Metallo-Supramolecular Truncated Cuboctahedra.

J Am Chem Soc 2021 Apr 13;143(15):5826-5835. Epub 2021 Apr 13.

College of Chemistry and Environmental Engineering, Shenzhen University, Shenzhen, Guangdong 518060, China.

Parastichy, the spiral arrangement of plant organs, is an example of the long-range apparent order seen in biological systems. These ordered arrangements provide scientists with both an aesthetic challenge and a mathematical inspiration. Synthetic efforts to replicate the regularity of parastichy may allow for molecular-scale control over particle arrangement processes. Here we report the packing of a supramolecular truncated cuboctahedron (TCO) into double-helical (DH) nanowires on a graphite surface with a non-natural parastichy pattern ascribed to the symmetry of the TCOs and interactions between TCOs. Such a study is expected to advance our understanding of the design inputs needed to create complex, but precisely controlled, hierarchical materials. It is also one of the few reported helical packing structures based on Platonic or Archimedean solids since the discovery of the Boerdijk-Coxeter helix. As such, it may provide experimental support for studies of packing theory at the molecular level.
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http://dx.doi.org/10.1021/jacs.1c00625DOI Listing
April 2021

Identifying the critical transmission sectors with energy-water nexus pressures in China's supply chain networks.

J Environ Manage 2021 Jul 8;289:112518. Epub 2021 Apr 8.

School of Economics and Management, China University of Geosciences, 100083, Beijing, China.

Energy and water resources are drawing increasing attention in China as indispensable elements of economic development and social stability. Energy and water are interconnected in economic systems. Although the nexus between them has been widely studied, few insights can be acquired by the intermediate transmission pressures across supply chains. Combing betweenness-based method and multi-regional input-output (MRIO) analysis, we, in this study, identified critical transmission sectors and main driving factors resulting from the usage structure. In details, we found that Metallurgy (S14) in Shandong, Henan, Jiangxi, Anhui, Sichuan, Zhejiang, Hunan, and Jiangsu, Electricity and hot water production and supply (S22) in Beijing and Guizhou, and Nonmetal production (S13) in Henan are the most critical transmission sectors bearing energy-water nexus pressures, ranking at the top 100 in China's supply chain networks. Roughly, the usage structure was mainly dominated by fixed capital formation, urban household consumption and trade export, and therefore should be given priority to mitigate environmental pressures. Our study provides a novel perspective of sector-specific and province-typical policy recommendations for mitigating energy-water nexus pressures in China's supply chain networks.
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http://dx.doi.org/10.1016/j.jenvman.2021.112518DOI Listing
July 2021

Decreased amino acids in the brain might contribute to the progression of diabetic neuropathic pain.

Diabetes Res Clin Pract 2021 Apr 1:108790. Epub 2021 Apr 1.

Department of Endocrinology and Metabolism, Huashan Hospital, Fudan University, Shanghai 200040, China. Electronic address:

Aims: The pathophysiological alteration of diabetic neuropathic pain (DNP) in brain is unclear. Here we aimed to explore the metabolomic characteristics of brain in rats over the progression of DNP through metabolomic analysis.

Methods: Adult rats were randomly divided into control group and DNP group. Body weight, blood glucose and behavioral assessment of neuropathic pain were measured every week after streptozotocin (STZ) injection. Finally, the brains of 2 rats from control group and 6 rats from DNP group were removed every 4 weeks after STZ injection for metabolomics analysis.

Results: After 4 weeks of STZ-injection, the rats with diabetes developed DNP, which was characterized as mechanical allodynia and thermal nociception. As for metabolomic analysis, differentially expressed metabolites (DE metabolites) showed a dynamic alteration over the development of DNP and affected several KEGG pathways associated with amino acid metabolism. Furthermore, the expression of L-Threonine, L-Methionine, D-Proline, L-Lysine and N-Acetyl-L-alanine were significantly decreased at all time points of DNP group. The amino acids which were precursor of analgesic neurotransmitters were downregulated over the progression of DNP, including L-tryptophan, L-histidine and L-tyrosine.

Conclusions: The impairment of amino acid metabolism in brain might contribute to the progression of DNP through decreasing analgesic neurotransmitters.
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http://dx.doi.org/10.1016/j.diabres.2021.108790DOI Listing
April 2021

Investigating the Effectiveness of Nano-Montmorillonite on Asphalt Binder from Rheological, Thermodynamics, and Chemical Perspectives.

Materials (Basel) 2021 Mar 16;14(6). Epub 2021 Mar 16.

Civil Engineering Department, Northeast Forestry University, Harbin 150040, China.

In this research, the feasibility of using nano-montmorillonite (MMT) in asphalt binders was investigated in terms of rheological properties, thermomechanical properties, and chemical structure composition. Different doses of MMT were added to the base asphalt and styrene-butadiene-styrene (SBS) asphalt as test subjects. The effect of nanomaterials on the high-temperature resistance of asphalt binders to permanent deformation was analyzed from dynamic mechanical rheology using the multiple stress creep recovery (MSCR) test. The sessile drop method test based on surface free energy (SFE) theory was employed and thermodynamic parameters such as surface free energy, cohesive work, and adhesion work were calculated to analysis the change in energy of the asphalt binder. In addition, changes in the chemical structure and composition of the asphalt binder were examined by Fourier transform infrared (FTIR) and gel permeation chromatography (GPC) tests. The results showed that MMT can effectively enhance the high-temperature elastic recovery and plastic deformation resistance of the asphalt binder. The intercalation structure produced in the asphalt binder enhanced the overall cohesive power and adhesion to the aggregate. The anchoring effect of the intercalation structure resulted in an increase in the macromolecular weight of the binder was demonstrated, indicating that MMT enhanced the overall intermolecular forces of the binder. In addition, the molecular crystal structure was characterized by characteristic functional groups in the infrared spectra, while demonstrating that no chemical reaction occurs during the modification of the binder by the nanomaterials.
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http://dx.doi.org/10.3390/ma14061433DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8000306PMC
March 2021

New insights of the correlation between AXIN2 polymorphism and cancer risk and susceptibility: evidence from 72 studies.

BMC Cancer 2021 Apr 1;21(1):353. Epub 2021 Apr 1.

Department of Geriatric Surgery, Xiangya Hospital, Central South University, Changsha, 410008, China.

Background: Numerous studies have reported the correlation between AXIN2 polymorphism and cancer risk, but the results seem not consistent. In order to get an overall, accurate and updated results about AXIN2 polymorphism and cancer risk, we conducted this study.

Methods: An updated analysis was performed to analyze the correlation between AXIN2 polymorphisms and cancer risk. Linkage disequilibrium (LD) analysis was also used to show the associations.

Results: Seventy-two case-control studies were involved in the study, including 22,087 cases and 18,846 controls. The overall results showed rs11079571 had significant association with cancer risk (allele contrast model: OR = 0.539, 95%CI = 0.478-0.609, PAdjust = 0.025; homozygote model: OR = 0.22, 95% CI = 0.164-0.295, PAdjust< 0.001; heterozygote model: OR = 0.292, 95% CI = 0.216-0.394, PAdjust< 0.001; dominant model: OR = 0.249, 95% CI = 0.189-0.33, PAdjust< 0.001). The same results were obtained with rs1133683 in homozygote and recessive models (PAdjust< 0.05), and in rs35285779 in heterozygote and dominant models (PAdjust< 0.05). LD analysis revealed significant correlation between rs7210356 and rs9915936 in the populations of CEU, CHB&CHS, ESN and JPT (CEU: r = 0.91; CHB&CHS: r = 0.74; ESN: r = 0.62, JPT: r = 0.57), and a significant correlation between rs9915936 and rs7224837 in the populations of CHB&CHS, ESN and JPT (r>0.5), between rs7224837 and rs7210356 in the populations of CEU, CHB&CHS, JPT (r>0.5), between rs35435678 and rs35285779 in the populations of CEU, CHB&CHS and JPT (r>0.5).

Conclusions: AXIN2 rs11079571, rs1133683 and rs35285779 polymorphisms have significant correlations with overall cancer risk. What's more, two or more polymorphisms such as rs7210356 and rs9915936, rs9915936 and rs7224837, rs7224837 and rs7210356, rs35435678 and rs35285779 have significant correlation with cancer susceptibility in different populations.
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http://dx.doi.org/10.1186/s12885-021-08092-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8017882PMC
April 2021

Single-pixel ptychography.

Opt Lett 2021 Apr;46(7):1624-1627

Ptychography is a predominant non-interferometric technique to image large complex fields but with quite a narrow working spectrum, because diffraction measurements require dense array detection with an ultra-high dynamic range. Here we report a single-pixel ptychography technique that realizes non-interferometric and non-scanning complex-field imaging in a wide waveband, where 2D dense detector arrays are not available. A single-pixel detector is placed in the far field to record the DC-only component of the diffracted wavefront scattered from the target field, which is illuminated by a sequence of binary modulation patterns. This decreases the measurements' dynamic range by several orders of magnitude. We employ an efficient single-pixel phase-retrieval algorithm to jointly recover the field's 2D amplitude and phase maps from the 1D intensity-only measurement sequence. No a priori object information is needed in the recovery process. We validate the technique's quantitative phase imaging nature using both calibrated phase objects and biological samples and demonstrate its wide working spectrum with both 488-nm visible light and 980-nm near-infrared light.
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http://dx.doi.org/10.1364/OL.417039DOI Listing
April 2021

3D iPSC modeling of the retinal pigment epithelium-choriocapillaris complex identifies factors involved in the pathology of macular degeneration.

Cell Stem Cell 2021 May 29;28(5):846-862.e8. Epub 2021 Mar 29.

Department of Ophthalmology, University of Rochester, Rochester, NY 14620, USA; Department of Biomedical Genetics, University of Rochester, Rochester, NY 14620, USA; Department of Orthopedics and Center for Musculoskeletal Research, University of Rochester, Rochester, NY 14642, USA; Center for Visual Science, University of Rochester, Rochester, NY 14620, USA; UR Stem Cell and Regenerative Medicine Center, Rochester, NY 14620, USA. Electronic address:

The retinal pigment epithelium (RPE)-choriocapillaris (CC) complex in the eye is compromised in age-related macular degeneration (AMD) and related macular dystrophies (MDs), yet in vitro models of RPE-CC complex that enable investigation of AMD/MD pathophysiology are lacking. By incorporating iPSC-derived cells into a hydrogel-based extracellular matrix, we developed a 3D RPE-CC model that recapitulates key features of both healthy and AMD/MD eyes and provides modular control over RPE and CC layers. Using this 3D RPE-CC model, we demonstrated that both RPE- and mesenchyme-secreted factors are necessary for the formation of fenestrated CC-like vasculature. Our data show that choroidal neovascularization (CNV) and CC atrophy occur in the absence of endothelial cell dysfunction and are not necessarily secondary to drusen deposits underneath RPE cells, and CC atrophy and/or CNV can be initiated systemically by patient serum or locally by mutant RPE-secreted factors. Finally, we identify FGF2 and matrix metalloproteinases as potential therapeutic targets for AMD/MDs.
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http://dx.doi.org/10.1016/j.stem.2021.02.006DOI Listing
May 2021

3D Cationic Polymeric Network Nanotrap for Efficient Collection of Perrhenate Anion from Wastewater.

Small 2021 Mar 21:e2007994. Epub 2021 Mar 21.

Department of Chemistry, University of North Texas, Denton, TX, 76201, USA.

Rhenium is one of the most valuable elements found in nature, and its capture and recycle are highly desirable for resource recovery. However, the effective and efficient collection of this material from industrial waste remains quite challenging. Herein, a tetraphenylmethane-based cationic polymeric network (CPN-tpm) nanotrap is designed, synthesized, and evaluated for ReO recovery. 3D building units are used to construct imidazolium salt-based polymers with positive charges, which yields a record maximum uptake capacity of 1133 mg g for ReO collection as well as fast kinetics ReO uptake. The sorption equilibrium is reached within 20 min and a k value of 8.5 × 10 mL g is obtained. The sorption capacity of CPN-tpm remains stable over a wide range of pH values and the removal efficiency exceeds 60% for pH levels below 2. Moreover, CPN-tpm exhibits good recyclability for at least five cycles of the sorption-desorption process. This work provides a new route for constructing a kind of new high-performance polymeric material for rhenium recovery and rhenium-contained industrial wastewater treatment.
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http://dx.doi.org/10.1002/smll.202007994DOI Listing
March 2021

Subarachnoid hemorrhage after full endoscopic transforaminal lumbar interbody fusion: a case report.

Br J Neurosurg 2021 Mar 19:1-6. Epub 2021 Mar 19.

Department of Orthopaedics, Xuzhou Central Hospital, Xuzhou Clinical School of Xuzhou Medical University, Xuzhou Clinical College of Nanjing Medical University, Xuzhou, China.

Purpose: Intracranial hemorrhage such as subarachnoid hemorrhage (SAH) is a rare but severe complication of spinal surgery. Current case reports of open lumbar surgery are typically accompanied by intraoperative dural tears and cerebrospinal fluid (CSF) leakage. We report a case of non-aneurysmal SAH without CSF leakage after full endoscopic transforaminal lumbar interbody fusion (FE-TLIF).

Design: Case report and literature review.

Results: A 62-year-old male patient underwent FE-TLIF for L4/5 lumbar spinal stenosis. There was no intraoperative dural tear or postoperative CSF leakage. The patient reported neck pain immediately after the surgery. Around 12 h after the surgery, the patient complained of mild headaches. One day after the surgery, the patient reported severe headaches, accompanied by nausea and vomiting. CT showed a high-density shadow in part of the sulcus and cistern, suggesting SAH. No apparent neurological symptoms were present. The patient's condition improved after conservative treatment including bed rest, fluid infusions, and blood pressure control. Twelve days after the surgery, CT and MRA of the brain showed no hemorrhage and the patient was discharged.

Conclusion: This case was among the first that developed SAH without CSF leakage after FE-TLIF. Although the underlying pathologic mechanism is unknown, epidural hypertension may be a possible cause of the hemorrhage. Timely CT or magnetic resonance imaging (MRI) examinations may help to detect this complication and initiate early treatment.
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http://dx.doi.org/10.1080/02688697.2021.1902473DOI Listing
March 2021

Association between thrombocytopenia and 180-day prognosis of COVID-19 patients in intensive care units: A two-center observational study.

PLoS One 2021 18;16(3):e0248671. Epub 2021 Mar 18.

Department of Critical Care Medicine, Zhongnan Hospital of Wuhan University, Wuhan, Hubei, China.

Background: Thrombocytopenia has been proved to be associated with hospital mortality in patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections. However, the detailed association of thrombocytopenia with subsequent progression of organ functions and long-term prognosis in critically ill COVID-19 patients remains to be explored.

Methods: Medical records of 167 confirmed cases of critically ill COVID-19 from February 16 to March 21, 2020 were collected in this two-center retrospective study. 180-day's outcome and clinical organ development in patients with thrombocytopenia and non-thrombocytopenia were analyzed.

Findings: Among all 167 patients, the median age was 66 years and 67.07% were male. Significant differences were noticed in laboratory findings including white blood cells, blood urea, total bilirubin, lactate dehydrogenase and SOFA score between groups of thrombocytopenia and non-thrombocytopenia. Older age, lower platelet count and longer activated partial thromboplastin time at admission were determined to be risk factors of 28-day mortality, and all three, together with higher white blood cells were risk factors of 180-day mortality. Subsequent changes of six-point ordinal scale score, oxygenation index, and SOFA score in patients with thrombocytopenia showed marked worsening trends compared with patients without thrombocytopenia. Patients with thrombocytopenia had significantly higher mortality not only in 28 days, but also in 90 days and 180 days. The time-course curves in non-survival group showed a downtrend of platelet count and oxygenation index, while the curve of six-point ordinal scale kept an uptrend. Kaplan-Meier analysis indicated that patients with thrombocytopenia had much lower probability of survival (p<0.01).

Interpretation: The thrombocytopenia was associated with the deterioration of respiratory function. Baseline platelet count was associated with subsequent and long-term mortality in critically ill COVID-19 patients.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0248671PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7972743PMC
April 2021

Validating eDNA measurements of the richness and abundance of anurans at a large scale.

J Anim Ecol 2021 Mar 10. Epub 2021 Mar 10.

Key Laboratory of Animal Ecology and Conservation Biology, Institute of Zoology, The Chinese Academy of Sciences, Beijing, China.

In some situations, environmental DNA (eDNA) metabarcoding is a more accurate tool for measuring species richness of a taxon than conventional methods. Whether this tool can reliably estimate the abundance of a taxon remains unresolved. We examined the reliability of metabarcoding for measuring anuran diversity compared to a commonly used traditional line transect method (TLTM) through the replicate sampling of three visits across 71 waterbodies (ponds or reservoirs) in Liuheng, China. We also investigated the relative contributions of species-specific characteristics and the physiochemical properties of a waterbody on the relative read count across species and waterbodies. We found that eDNA metabarcoding had a higher detection probability for each of seven anuran species found in the sampling region than TLTM. Furthermore, the relative read count estimated by metabarcoding was positively correlated with the density or relative density of individuals identified with the TLTM across waterbodies for every species. Species-specific characteristics of anurans, such as density, relative density, body mass, biomass and relative biomass, accounted for substantial variations in the read count across species and waterbodies, while physiochemical factors, including pH, temperature, water volume, vegetation and elevation, had little effect on the read count. Our results based on robust sampling suggest that metabarcoding enables more reliable and efficient measurements of anuran occurrence at a large scale during a short-term survey (within 15 days) than that obtained by the TLTM, and offers an alternative tool for quantifications of anuran abundance. Density or biomass is better and more reliable indicator of anuran abundance associated with read count than relative density or relative biomass.
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http://dx.doi.org/10.1111/1365-2656.13468DOI Listing
March 2021

Accumulation Pattern of Amygdalin and Prunasin and Its Correlation with Fruit and Kernel Agronomic Characteristics during Apricot ( L.) Kernel Development.

Foods 2021 Feb 11;10(2). Epub 2021 Feb 11.

Key Comprehensive Laboratory of Forestry, College of Forestry, Northwest A&F University, Shaanxi Province, Yangling 712100, China.

To reveal the accumulation pattern of cyanogenic glycosides (amygdalin and prunasin) in bitter apricot kernels to further understand the metabolic mechanisms underlying differential accumulation during kernel development and ripening and explore the association between cyanogenic glycoside accumulation and the physical, chemical and biochemical indexes of fruits and kernels during fruit and kernel development, dynamic changes in physical characteristics (weight, moisture content, linear dimensions, derived parameters) and chemical and biochemical parameters (oil, amygdalin and prunasin contents, β-glucosidase activity) of fruits and kernels from ten apricot ( L.) cultivars were systematically studied at 10 day intervals, from 20 days after flowering (DAF) until maturity. High variability in most of physical, chemical and biochemical parameters was found among the evaluated apricot cultivars and at different ripening stages. Kernel oil accumulation showed similar sigmoid patterns. Amygdalin and prunasin levels were undetectable in the sweet kernel cultivars throughout kernel development. During the early stages of apricot fruit development (before 50 DAF), the prunasin level in bitter kernels first increased, then decreased markedly; while the amygdalin level was present in quite small amounts and significantly lower than the prunasin level. From 50 to 70 DAF, prunasin further declined to zero; while amygdalin increased linearly and was significantly higher than the prunasin level, then decreased or increased slowly until full maturity. The cyanogenic glycoside accumulation pattern indicated a shift from a prunasin-dominated to an amygdalin-dominated state during bitter apricot kernel development and ripening. β-glucosidase catabolic enzyme activity was high during kernel development and ripening in all tested apricot cultivars, indicating that β-glucosidase was not important for amygdalin accumulation. Correlation analysis showed a positive correlation of kernel amygdalin content with fruit dimension parameters, kernel oil content and β-glucosidase activity, but no or a weak positive correlation with kernel dimension parameters. Principal component analysis (PCA) showed that the variance accumulation contribution rate of the first three principal components totaled 84.56%, and not only revealed differences in amygdalin and prunasin contents and β-glucosidase activity among cultivars, but also distinguished different developmental stages. The results can help us understand the metabolic mechanisms underlying differential cyanogenic glycoside accumulation in apricot kernels and provide a useful reference for breeding high- or low-amygdalin-content apricot cultivars and the agronomic management, intensive processing and exploitation of bitter apricot kernels.
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http://dx.doi.org/10.3390/foods10020397DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7918717PMC
February 2021

Radiomics Features Predict Promoter Mutations in World Health Organization Grade II Gliomas a Machine-Learning Approach.

Front Oncol 2020 11;10:606741. Epub 2021 Feb 11.

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

The detection of mutations in telomerase reverse transcriptase promoter (p) is important since preoperative diagnosis of p status helps with evaluating prognosis and determining the surgical strategy. Here, we aimed to establish a radiomics-based machine-learning algorithm and evaluated its performance with regard to the prediction of mutations in p in patients with World Health Organization (WHO) grade II gliomas. In total, 164 patients with WHO grade II gliomas were enrolled in this retrospective study. We extracted a total of 1,293 radiomics features from multi-parametric magnetic resonance imaging scans. Elastic net (used for feature selection) and support vector machine with linear kernel were applied in nested 10-fold cross-validation loops. The predictive model was evaluated by receiver operating characteristic and precision-recall analyses. We performed an unpaired t-test to compare the posterior predictive probabilities among patients with differing p statuses. We selected 12 valuable radiomics features using nested 10-fold cross-validation loops. The area under the curve (AUC) was 0.8446 (95% confidence interval [CI], 0.7735-0.9065) with an optimal summed value of sensitivity of 0.9355 (95% CI, 0.8802-0.9788) and specificity of 0.6197 (95% CI, 0.5071-0.7371). The overall accuracy was 0.7988 (95% CI, 0.7378-0.8598). The F1-score was 0.8406 (95% CI, 0.7684-0.902) with an optimal precision of 0.7632 (95% CI, 0.6818-0.8364) and recall of 0.9355 (95% CI, 0.8802-0.9788). Posterior probabilities of p mutations were significantly different between patients with wild-type and mutant promoters. Our findings suggest that a radiomics analysis with a machine-learning algorithm can be useful for predicting p status in patients with WHO grade II glioma and may aid in glioma management.
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http://dx.doi.org/10.3389/fonc.2020.606741DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7905226PMC
February 2021

Integrated study of miR-215 promoting breast cancer cell apoptosis by targeting RAD54B.

J Cell Mol Med 2021 Apr 26;25(7):3327-3338. Epub 2021 Feb 26.

Department of Geratic Surgery, Xiangya Hospital, Central South University, Changsha, China.

Background: MicroRNAs (miRNAs) are widely distributed in cells and participate in the regulation of the pathophysiological process of many diseases. As an important part of non-coding RNA, miRNAs regulate a variety of molecules and signal pathways in tumour cells. However, the evidence for regulatory mechanisms of specific miRNAs in tumour cells is still lacking.

Methods: In this study, we used transcriptomics analysis and integrated a variety of public databases to screen miRNAs that have key regulatory effects on breast cancer (BC). In addition, we used in vitro and in vivo studies and combined clinical samples to verify its regulatory mechanism.

Results: We found that among the specific miRNAs, miR-215-5p is a key regulator in BC. Compared with normal adjacent tissues, miR-215-5p has a lower expression level in BC tissues. Patients with high expression levels of miR-215-5p have a longer survival time. miR-215-5p can specifically target the 3'UTR region of RAD54B mRNA and down-regulate the expression of RAD54B, thereby inhibiting the proliferation of BC cells and promoting the apoptosis of BC cells.

Conclusions: Finally, we found that miR-215-5p can be used as an important biomarker for BC. We have clarified its function and revealed its mechanism of targeting RAD54B mRNA for the first time. This may provide important clues to reveal the deeper molecular regulation mechanism of BC.
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http://dx.doi.org/10.1111/jcmm.16402DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8034472PMC
April 2021

Elevated preoperative neutrophil-to-lymphocyte ratio predicts early adverse outcomes in uncomplicated type B aortic dissection undergoing TEVAR.

BMC Cardiovasc Disord 2021 Feb 16;21(1):95. Epub 2021 Feb 16.

Department of Vascular Surgery, Changhai Hospital, Navy Medical University, Shanghai, 200433, China.

Background: Thoracic aortic endovascular repair (TEVAR) of uncomplicated type B aortic dissection (uTBAD) has favorable long-term outcomes but higher early adverse events compared with the optimal medical treatment. Recently, clinical evidence concerning vascular surgery indicates that elevated preoperative systemic inflammatory response predicts adverse clinical events. The aim of our study was to evaluate the relationship between preoperative neutrophil-to-lymphocyte ratio (NLR) and early outcomes of uTBAD patients undergoing TEVAR.

Results: 216 patients diagnosed with uTBAD were included in this retrospective study between January 2015 and December 2018. The median (IQR) follow-up period was 21 (15-33) months. An early adverse event was defined as occurring within 2 years after the procedure. Median patient age was 60 (IQR, 48-68) years and 78.7 % were male. Early adverse events occurred in 24 patients (11.1 %). In the multivariable analysis, preoperative NLR (HR per SD, 1.98; 95 % CI, 1.14-3.44; P = 0.015) was associated with 2-year adverse events.

Conclusions: NLR is an independent predictive factor of early adverse events in uTBAD patients undergoing TEVAR.
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http://dx.doi.org/10.1186/s12872-021-01904-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7885432PMC
February 2021

Clinical Parameters of Silent Corticotroph Adenomas With Positive and Negative Adrenocorticotropic Hormone Immunostaining: A Large Retrospective Single-Center Study of 105 Cases.

Front Endocrinol (Lausanne) 2020 18;11:608691. Epub 2021 Jan 18.

Department of Neurosurgery, Shanghai Huashan Institute of Neurological Surgery, Huashan Hospital, Shanghai Medical School, Fudan University, Shanghai, China.

Purpose: To investigate the different clinical characteristics of silent corticotroph adenomas (SCAs) with positive and negative adrenocorticotropic hormone (ACTH) immunostaining, and to explore the value of pituitary-restricted transcription factor (Tpit) immunostaining for diagnosing SCAs.

Methods: The clinical materials of patients with SCAs who had a typical pathological feature with positive Tpit immunostaining and positive/negative ACTH immunostaining, and without clinical features and biochemical evidence for Cushing's Syndrome in our center from April 2018 to March 2019 were analyzed retrospectively. The differences in clinical characteristics and surgical results between ACTH-positive and -negative SCAs were explored.

Results: A total of one hundred and five patients (94.3% female) with SCAs were included. There were 66 SCAs with ACTH-negative (66/105, 62.9%), and 39 SCAs with ACTH-positive (39/105, 37.1%). Cases with ACTH-negative SCAs were more likely to have lower ACTH levels (27.5 ± 24.0 vs. 54.4 ± 58.6, P = 0.011), more multiple microcysts (81.8% vs. 61.5%, P = 0.022) and lower levels of Ki-67 expression (low expression rate 90.9% vs. 74.4%, P = 0.023). No statistical significant differences were observed between patients with ACTH-positive and -negative SCAs regarding gender (97.0% vs. 89.7%, P = 0.192), age (50.3 ± 10.3 vs. 49.0 ± 11.2, P = 0.543), surgical history (16.7% vs. 23.1%, P = 0.419), suprasellar extension (66.7% vs. 74.4%, P = 0.408), sphenoid sinus extension (51.5% vs. 56.4%, P = 0.627), cavernous sinus invasion (75.8% vs. 66.7%, P = 0.314), large cyst on Magnetic Resonance Imaging (MRI) (47.0% vs. 61.5%, P = 0.149), or gross total resection rate (42.4% vs. 51.3%, P = 0.379).

Conclusions: ACTH-negative SCAs were observed to be more clinically silent and more likely to demonstrate multiple microcysts on MRI. The prevalence of SCAs, especially ACTH-negative SCAs, proved to be substantially underestimated and thus they should be given enough attention in consideration of the high aggressiveness of this subtype of refractory pituitary adenoma (PA).
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http://dx.doi.org/10.3389/fendo.2020.608691DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7873875PMC
January 2021

Synthesis of Four Pentacyclic Triterpene-Sialylglycopeptide Conjugates and Their Affinity Assays with Hemagglutinin.

Molecules 2021 Feb 8;26(4). Epub 2021 Feb 8.

School of Pharmacy, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China.

Influenza outbreaks pose a serious threat to human health. Hemagglutinin (HA) is an important target for influenza virus entry inhibitors. In this study, we synthesized four pentacyclic triterpene conjugates with a sialylglycopeptide scaffold through the Cu(I)-catalyzed alkyne-azide cycloaddition reaction (CuAAC) and prepared affinity assays of these conjugates with two HAs, namely H1N1 (A/WSN/1933) and H5N1 (A/Hong Kong/483/97), respectively. With a dissociation constant () of 6.89 μM, SCT-Asn-betulinic acid exhibited the strongest affinity with the H1N1 protein. Furthermore, with a value of 9.10 μM, SCT-Asn-oleanolic acid exhibited the strongest affinity with the H5N1 protein. The conjugates considerably enhanced antiviral activity, which indicates that pentacyclic triterpenes can be used as a ligand to improve the anti-influenza ability of the sialylglycopeptide molecule by acting on the HA protein.
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http://dx.doi.org/10.3390/molecules26040895DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7915185PMC
February 2021

Circ_0091579 Serves as a Tumor-Promoting Factor in Hepatocellular Carcinoma Through miR-1225-5p/PLCB1 Axis.

Dig Dis Sci 2021 Feb 8. Epub 2021 Feb 8.

Department of General Surgery, The Second Affiliated Hospital of Xi'an Jiaotong University, No. 157 Xiwu Road, Xincheng District, Xi'an, 710004, Shaanxi, China.

Background: Hepatocellular carcinoma (HCC) is a dreadful threaten to human health worldwide. Many circular RNAs were reported to influence the malignant development of HCC. The aim of this study was to elucidate the role of circ_0091579 in HCC progression and the molecular fundamentation.

Methods: Expression of circ_0091579, microRNA-1225-5p (miR-1225-5p), and phospholipase C, β1 (PLCB1) was examined by quantitative reverse transcription-polymerase chain reaction or Western blotting. Cell viability, clonogenicity capacity, and apoptosis were determined via Cell Counting Kit-8 assay, colony formation assay, and flow cytometry, respectively. Transwell assay was employed to detect cell migration and invasion. Target relationship between miR-1225-5p and circ_0091579 or PLCB1 was demonstrated by dual-luciferase reporter assay. Moreover, role of circ_0091579 in vivo was assessed by Xenograft model assay.

Results: Expression of circ_0091579 and PLCB1 was increased, while miR-1225-5p expression was decreased in HCC tissues and cells. Circ_0091579 or PLCB1 depletion had inhibitory effects on HCC cell proliferation and metastasis. Circ_0091579 sponged miR-1225-5p to upregulate PLCB1 expression in HCC cells. Silencing of miR-1225-5p contributed to HCC progression, which was mitigated by PLCB1 depletion. Circ_0091579 deficiency could suppress HCC tumor growth in vivo.

Conclusion: Circ_0091579 knockdown repressed HCC progression and tumorigenesis by regulating miR-1225-5p/PLCB1 axis, affording a novel molecular basis for HCC development.
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http://dx.doi.org/10.1007/s10620-021-06861-2DOI Listing
February 2021

Metabolomics study reveals the potential evidence of metabolic reprogramming towards the Warburg effect in precancerous lesions.

J Cancer 2021 10;12(5):1563-1574. Epub 2021 Jan 10.

Guanghua School of Stomatology, Guangdong Provincial Key Laboratory of Stomatology, Sun Yat-sen University, Guangzhou 510055, People's Republic of China.

Most tumors have an enhanced glycolysis flux, even when oxygen is available, called the aerobic glycolysis or the Warburg effect. Metabolic reprogramming promotes cancer progression, and is even related to the tumorigenesis. However, it is not clear whether the observed metabolic changes act as a driver or a bystander in cancer development. In this study, the metabolic characteristics of oral precancerous cells and cervical precancerous lesions were analyzed by metabolomics, and the expression of glycolytic enzymes in cervical precancerous lesions was evaluated by RT-PCR and Western blot analysis. In total, 115 and 23 metabolites with reliable signals were identified in oral cells and cervical tissues, respectively. Based on the metabolome, oral precancerous cell DOK could be clearly separated from normal human oral epithelial cells (HOEC) and oral cancer cells. Four critical differential metabolites (pyruvate, glutamine, methionine and lysine) were identified between DOK and HOEC. Metabolic profiles could clearly distinguish cervical precancerous lesions from normal cervical epithelium and cervical cancer. Compared with normal cervical epithelium, the glucose consumption and lactate production increased in cervical precancerous lesions. The expression of glycolytic enzymes LDHA, HK II and PKM2 showed an increased tendency in cervical precancerous lesions compared with normal cervical epithelium. Our findings suggest that cell metabolism may be reprogrammed at the early stage of tumorigenesis, implying the contribution of metabolic reprogramming to the development of tumor.
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http://dx.doi.org/10.7150/jca.54252DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7847643PMC
January 2021

One step stereoselective synthesis of oxazoline-fused saccharides and their conversion into the corresponding 1,2- glycosylamines bearing various protected groups.

Org Biomol Chem 2021 02;19(7):1580-1588

Shanghai University of Traditional Chinese Medicine, 1200 Cailun Road, Shanghai 201203, China. and CAS Key Laboratory of Receptor Research; Drug Discovery and Design Center, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, 555 Zuchongzhi Road, Shanghai 201203, China. and School of Pharmacy, University of Chinese Academy of Sciences, No. 19A Yuquan Road, Beijing 100049, China.

Herein we disclosed a straightforward synthesis of oxazoline-fused saccharides (oxazolinoses) from peracetylated saccharides and benzonitriles under acidic conditions with stoichiometric amounts of water. The density functional theory (DFT) calculations have revealed the origin of the stereoselectivity and the key role of water in promoting the departure of the acetyl group at C-2. The resulting oxazolinoses can be concisely converted into the corresponding 1,2-cis glycosylamines bearing various protected groups, allowing the access to schisandrin derivatives.
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http://dx.doi.org/10.1039/d0ob02477eDOI Listing
February 2021

Nontrivial band geometry in an optically active system.

Nat Commun 2021 Jan 29;12(1):689. Epub 2021 Jan 29.

Institut Pascal, PHOTON-N2, Université Clermont Auvergne, CNRS, SIGMA Clermont, F-63000, Clermont-Ferrand, France.

Optical activity, also called circular birefringence, is known for two hundred years, but its applications for topological photonics remain unexplored. Unlike the Faraday effect, the optical activity provokes rotation of the linear polarization of light without magnetic effects, thus preserving the time-reversal symmetry. In this work, we report a direct measurement of the Berry curvature and quantum metric of the photonic modes of a planar cavity, containing a birefringent organic microcrystal (perylene) and exhibiting emergent optical activity. This experiment, performed at room temperature and at visible wavelength, establishes the potential of organic materials for implementing non-magnetic and low-cost topological photonic devices.
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http://dx.doi.org/10.1038/s41467-020-20845-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7846789PMC
January 2021

Comparison of growth performance and biochemical components between parent and hybrid offspring in the oriental river prawn, Macrobrachium nipponense.

Anim Genet 2021 Apr 27;52(2):185-197. Epub 2021 Jan 27.

School of Life Science, East China Normal University, Shanghai, 200241, China.

Macrobrachium nipponense, as one of the large-yield farmed shrimp, is facing germplasm degradation. Genetic improvement through hybridization is one of the effective methods to solve this problem. In this study, using a three-line hybrid strategy, two-hybrid F1 populations were obtained using three local populations of M. nipponense as parents for crossbreeding. Five populations were then cultured for 3 months. Growth rate performance was measured by the hepatosomatic index, weight gain, body length growth rate and special growth rate. Biochemical components were also assessed. The results showed that the survival rate and growth performance of the hybrid progeny were better than those of the parents. The levels of triglycerides, total cholesterol, glycogen and lactic acid of the hybrid population were higher than those of the parents. This was consistent with variation in the activity of four digestive enzymes. Compared with the results of the fatty acid and amino acid analysis, it was found that the contents of polyunsaturated fatty acids such as eicosapentaenoic acid, docosapentaenoic acid and docosahexaenoic acid and eight essential amino acids in the hybrid populations were significantly higher than those of their parents, and the contents of flavor amino acids were higher. The expression level of molting genes related to the growth of the parent populations was lower than that of the hybrids. These results show that crossbreeding is effective for the genetic improvement of M. nipponense germplasm. Hybrids showed advantages in growth and nutrition and multigenerational breeding will be required to form a stable germplasm.
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http://dx.doi.org/10.1111/age.13041DOI Listing
April 2021

Acetate Ringer's solution versus 0.9% saline for septic patients: study protocol for a multi-center parallel controlled trial.

Trials 2021 Jan 25;22(1):89. Epub 2021 Jan 25.

Department of Critical Care Medicine, Zhongnan Hospital of Wuhan University, 169 Donghu Road, Wuhan, 430071, Hubei, China.

Background: Previous study drew different conclusions on significant differences between saline and balanced crystalloid solution infused in critical illness but both showed a statistical difference in the sepsis subgroup. Thus, we will specifically focus on septic patients in this study to compare the effects of saline and balanced solution. We hypothesize that effects of saline on renal outcomes are related to the underline acute kidney injury (AKI) severity and total volumes of infusion.

Methods/design: The investigators designed a pragmatic, multi-center parallel controlled trial recruiting 312 patients who are diagnosed with sepsis/septic shock in the intensive care unit (ICU) and will be assigned with either acetate Ringer's solution or saline in the corresponding month. Patients with an end-stage renal disease (ESRD) or who need renal replacement therapy (RRT) prior to or at the time of enrolment are excluded. Enrolled patients will be regarded as with mild, moderate, or severe sepsis on the basis of the severity of their illness and will be divided into subgroups according to their initial renal function and various intravenous infusion volumes when being analyzed. The primary outcome is major adverse kidney events within 28 days (MAKE28), including the composite of in-hospital death, receipt of new renal replacement therapy, or persistent renal dysfunction. Secondary outcomes include 28-day mortality, internal environment disturbance, incidence and duration of vasoactive drug treatment, duration of mechanical ventilation, duration of RRT, and ICU and hospital length of stay.

Results And Conclusions: To our knowledge, this study will be the first to focus on septic patients and provide credible and evident data on the comparison of outcome between acetate Ringer's solution and saline for intravenous infusion in adult septic patients on the basis of baseline renal function and infusion volumes taken into consideration.

Trial Registration: ClinicalTrials.gov NCT03685214 . Registered on August 15, 2018.
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http://dx.doi.org/10.1186/s13063-020-05007-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7830046PMC
January 2021

A multi-level hypoglycemia early alarm system based on sequence pattern mining.

BMC Med Inform Decis Mak 2021 01 21;21(1):22. Epub 2021 Jan 21.

Department of Endocrinology and Metabolism, Huashan Hospital, Fudan University, Shanghai, 200040, China.

Background: Early alarm of hypoglycemia, detection of asymptomatic hypoglycemia, and effective control of blood glucose fluctuation make a great contribution to diabetic treatment. In this study, we designed a multi-level hypoglycemia early alarm system to mine potential information in Continuous Glucose Monitoring (CGM) time series and improve the overall alarm performance for different clinical situations.

Methods: Through symbolizing the historical CGM records, the Prefix Span was adopted to obtain the early alarm/non-alarm frequent sequence libraries of hypoglycemia events. The longest common subsequence was used to remove the common frequent sequence for achieving the hypoglycemia early alarm in different clinical situations. Then, the frequent sequence pattern libraries with different risk thresholds were designed as the core module of the proposed multi-level hypoglycemia early alarm system.

Results: The model was able to predict hypoglycemia events in the clinical dataset of level-I (sensitivity 85.90%, false-positive 23.86%, miss alarm rate 14.10%, average early alarm time 20.61 min), level-II (sensitivity 80.36%, false-positive 17.37%, miss alarm rate 19.63%, average early alarm time 27.66 min), and level-III (sensitivity 78.07%, false-positive 13.59%, miss alarm rate 21.93%, average early alarm time 33.80 min), respectively.

Conclusions: The proposed approach could effectively predict hypoglycemia events based on different risk thresholds to meet different prevention and treatment requirements. Moreover, the experimental results confirm the practicality and prospects of the proposed early alarm system, which reflects further significance in personalized medicine for hypoglycemia prevention.
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http://dx.doi.org/10.1186/s12911-021-01389-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7819198PMC
January 2021