Publications by authors named "Yang Shen"

950 Publications

The RNA binding protein hnRNPK protects against adriamycin-induced podocyte injury.

Ann Transl Med 2021 Aug;9(16):1303

Department of Nephrology, The First Affiliated Hospital of Jinan University, Guangzhou, China.

Background: Podocytes maintain the integrity of the glomerular filtration barrier and serve as the final barrier to protein loss. Podocyte injury may induce severe apoptosis, which can result in serious kidney damage and disease. Therefore, it is necessary to explore how podocyte injury can be prevented and to thereby discover a feasible therapy for kidney disease. However, the mechanism of podocyte injury is still unclear.

Methods: The mRNA and protein expression levels of synaptopodin and nephrin in MPC5 podocytes with adriamycin (ADR)-induced injury were detected by quantitative real-time PCR and western blot. The expression levels of heterogeneous nucleotide protein K (hnRNPK), caspase-3, Bax, and Bcl-2 protein in cells and tissues were measured using western blot. Proliferation were measured in treated MPC5 podocytes by Cell Counting Kit-8 (CCK-8) assay, EdU assay, and apoptosis was measured by Hoechst 32258 staining. Mitochondrial membrane potential disruption, lactate dehydrogenase (LDH) leakage, and reactive oxygen species (ROS) generation were measured using JC-1 staining, an LDH reagent kit, and a ROS detection kit. Hematoxylin and eosin (HE) staining was used to observe histological changes in mouse tissues.

Results: Synaptopodin and nephrin were downregulated in ADR-treated podocytes. Overexpression of hnRNPK ameliorated the inhibitive effect of ADR treatment on podocyte proliferation and reduced its promotion of podocyte apoptosis. LDH leakage and ROS generation were increased in ADR-treated podocytes, but were reduced by hnRNPK treatment.

Conclusions: ADR-induced podocyte injury is ameliorated by hnRNPK both and . This observation provides a basis for a feasible therapy to prevent podocyte injury and subsequent kidney disease.
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http://dx.doi.org/10.21037/atm-21-3577DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8422093PMC
August 2021

The Prognostic Effect of Dexamethasone on Patients With Glioblastoma: A Systematic Review and Meta-Analysis.

Front Pharmacol 2021 31;12:727707. Epub 2021 Aug 31.

Department of Public Health and Preventive Medicine, Wuxi School of Medicine, Jiangnan University, Wuxi, China.

Dexamethasone (DEX) is widely adopted to reduce tumor-associated edema in glioblastoma (GBM) patients despite its side effects. However, the benefits of using DEX in GBM patients remains elusive. In this study, we performed a comprehensive meta-analysis to address this concern. We searched the relevant studies from PubMed, Web of Science, and EMBASE databases, and then applied random or fixed-effects models to generate estimated summary hazard radios (HRs) and the 95% confidence intervals (CIs). Moreover, subgroup and sensitivity analysis were conducted and publication bias were further evaluated. Ten articles with a total of 2,230 GBM patients were eligible according to the inclusion criteria. In the assessment of overall survival (OS), meta-analysis data revealed that DEX was significantly associated with the poor prognosis of GBM patients (HR=1.44, 95% CI=1.32-1.57). In the progression-free survival (PFS), the pooled results indicated that the use of DEX can increase 48% death risk for GBM patients (HR=1.48, 95% CI=1.11-1.98). Subgroup analyses revealed that DEX was associated with poorer outcome of GBM in subgroup of newly diagnosed patients and GBM patients treated with ≥ 2mg/day. Sensitivity analyses showed that no study changed the pooled results materially for both OS and PFS analyses. The funnel plot had no obvious asymmetry. Our findings partly confirmed that use of DEX was associated with poor treatment outcome in GBM patients. To reach a definitive conclusion, large samples from multi-centers are urgent to address this concern.
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http://dx.doi.org/10.3389/fphar.2021.727707DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8438116PMC
August 2021

In Situ Reactor-Integrated Electrospray Ionization Mass Spectrometry for Heterogeneous Catalytic Reactions and Its Application in the Process Analysis of High-Pressure Liquid-Phase Lignin Depolymerization.

Anal Chem 2021 Sep 14. Epub 2021 Sep 14.

School of Mechanical Engineering, Shanghai Jiao Tong University, 800 Dongchuan Road, Shanghai 200240, P.R. China.

Process analysis of heterogeneous catalytic reactions such as lignin depolymerization is essential to understand the reaction mechanism at the molecular level, but it is always challenging due to harsh conditions. Herein, we report an operando process analysis strategy by combining a microbatch reactor with high-resolution mass spectrometry (MS) via a reactor-integrated electrospray ionization (R-ESI) technique. R-ESI-MS expands the applications of traditional in situ MS to a heterogeneous and high-pressure liquid-phase system. With this strategy, we present the evolution of a series of monomers, dimers, and oligomers during lignin depolymerization under operando conditions (methanol solvent, 260 °C, ∼8 MPa), which is the first experimental elucidation of a progressive depolymerization pathway and evidence of repolymerization of active monomers. The proposed R-ESI-MS is crucial in probing depolymerization intermediates of lignin; it also provides a flexible strategy for process analysis of heterogeneous catalytic reactions under operando conditions.
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http://dx.doi.org/10.1021/acs.analchem.1c02710DOI Listing
September 2021

Stress Granules Modulate SYK to Cause Tau-Associated Neurocognitive Deterioration in 5XFAD Mouse After Anesthesia and Surgery.

Front Aging Neurosci 2021 27;13:718701. Epub 2021 Aug 27.

Department of Anesthesiology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.

Background: Alzheimer's disease (AD) is the most common type of dementia. However, no curative therapy has been found effective to slow down the process of AD. It is reported that anesthesia and surgery will induce neurocognitive deterioration in AD, but the mechanism is not quite clear. In this study, we aim to compare the cognitive impairment between 5XFAD transgenic (Tg) mice and its littermate (LM) after isoflurane anesthesia and surgery to clarify the specific impacts of anesthesia and surgery on individuals with AD and to explore the mechanisms.

Methods: We performed abdominal surgery in cognitively impaired, 4-month-old female 5XFAD mice and LM control mice. Isoflurane anesthesia (1.4%) was induced and maintained over 2 h. Open field and fear conditioning tests were conducted on 1, 3 and 7 days after anesthesia and surgery. The total distance, velocity and freezing time were the major outcomes. P-tau (AT8), tau oligomers (T22), stress granules (SGs), the SYK tyrosine kinase and p-SYK in the hippocampus at postoperative day 1 were evaluated by Western Blot assays. The colocalization of SGs, SYK, p-SYK, and neurons in the hippocampus section was assessed using qualitative immunofluorescence.

Results: In the open field test, no difference between the distance moved and the velocity of LM mice and 5XFAD Tg mice were found on day 1 after anesthesia and surgery. 5XFAD Tg mice exhibited reduced freezing time of fear conditioning context test on postoperative day 3, but not on day 7; the LM mice showed no changes in FCTs. Furthermore, p-tau, tau oligomers, SGs, SYK and p-SYK were evident in the hippocampus region of 5XFAD Tg mice on a postoperative day 1. In addition, SGs, SYK, p-SYK were colocalized with hippocampus neurons, as shown by immunofluorescence.

Conclusion: This study demonstrates that anesthesia and surgery may induce tau-associated neurocognitive deterioration in individuals with AD. The mechanism under it may be associated with SGs and the tyrosine kinase, SYK. After anesthesia and surgery, in 5XFAD Tg mice, SGs were formed and SYK was phosphorylated, which may contribute to the phosphorylation of tau protein. This study provided hints that individuals with AD may be more vulnerable to anesthesia and surgery.
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http://dx.doi.org/10.3389/fnagi.2021.718701DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8430336PMC
August 2021

Blood glucose concentration prediction based on VMD-KELM-AdaBoost.

Med Biol Eng Comput 2021 Sep 12. Epub 2021 Sep 12.

School of Science, Wuhan University of Science and Technology, Wuhan, 430065, China.

The time series of blood glucose concentration in diabetic patients are time-varying, nonlinear, and non-stationary. In order to improve the accuracy of blood glucose prediction, a multi-scale combination short-term blood glucose prediction model was constructed by combining the variational mode decomposition (VMD) method, the kernel extreme learning machine (KELM), and the AdaBoost algorithm (VMD-ELM-AdaBoost). Firstly, the blood glucose concentration series were decomposed into a set of intrinsic modal functions (IMFs) with different scales by the VMD method. On this basis, the KELM neural network and AdaBoost algorithm are combined to predict each IMF component. Finally, the cumulative blood glucose concentration prediction value is obtained by accumulating the KELM-AdaBoost prediction results of each IMF. The time series of measured blood glucose concentration were used for experimental analysis; the experimental results show that the proposed VMD-KELM-AdaBoost method has higher prediction accuracy compared with the classical prediction models such as ELM, KELM, SVM, and LSTM. The proposed VMD-KELM-AdaBoost model can still achieve high prediction accuracy 60 min in advance (the mean values of RMSE, MAPE, and CC are about 10.1422, 4.8629%, and 0.8737 respectively); in Clarke error mesh analysis, the proportion of falling into A region is about 95.7%; the sensitivity and false alarm rate of early alarm of hypoglycemia were 94.8% and 7.7%, respectively. Graphical abstract We have proposed a new prediction model. In the first part, for reducing thenon-stationarity, the data of blood glucose concentration was decomposed as a series ofIMF by VMD. In the second part, a prediction model based KELM and Adaboost wasestablished. In the third part, the KELM-Adaboost model was used to predict each IMF,and the predicted values of all IMFS were superimposed to obtain the final predictionresult of blood glucose concentration.
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http://dx.doi.org/10.1007/s11517-021-02430-xDOI Listing
September 2021

Molecular characterization and cell type composition deconvolution of fibrosis in NAFLD.

Sci Rep 2021 Sep 10;11(1):18045. Epub 2021 Sep 10.

Liver Center, Division of Gastroenterology, Massachusetts General Hospital, 55 Fruit St, Boston, MA, 02114, USA.

Non-alcoholic fatty liver disease (NAFLD) is the most common cause of liver disease worldwide. In adults with NAFLD, fibrosis can develop and progress to liver cirrhosis and liver failure. However, the underlying molecular mechanisms of fibrosis progression are not fully understood. Using total RNA-Seq, we investigated the molecular mechanisms of NAFLD and fibrosis. We sequenced liver tissue from 143 adults across the full spectrum of fibrosis stage including those with stage 4 fibrosis (cirrhosis). We identified gene expression clusters that strongly correlate with fibrosis stage including four genes that have been found consistently across previously published transcriptomic studies on NASH i.e. COL1A2, EFEMP2, FBLN5 and THBS2. Using cell type deconvolution, we estimated the loss of hepatocytes versus gain of hepatic stellate cells, macrophages and cholangiocytes with advancing fibrosis stage. Hepatocyte-specific functional analysis indicated increase of pro-apoptotic pathways and markers of bipotent hepatocyte/cholangiocyte precursors. Regression modelling was used to derive predictors of fibrosis stage. This study elucidated molecular and cell composition changes associated with increasing fibrosis stage in NAFLD and defined informative gene signatures for the disease.
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http://dx.doi.org/10.1038/s41598-021-96966-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8433177PMC
September 2021

Effects of warm compress on tear film, blink pattern and Meibomian gland function in dry eyes after corneal refractive surgery.

BMC Ophthalmol 2021 Sep 10;21(1):330. Epub 2021 Sep 10.

Department of Ophthalmology and Optometry, Eye and ENT Hospital of Fudan University, Shanghai, China.

Background: To assess the effects of warm compress (WC) on tear film lipid layer, blink pattern and Meibomian gland function in patients with dry eye following femtosecond laser small incision lenticule extraction (SMILE) and laser-assisted subepithelial keratomileusis (LASEK).

Methods: We enrolled 37 eyes of 37 participants, each with dry eye for more than 2 years following SMILE (25 eyes) or LASEK (12 eyes). WC was performed using a spontaneously heating eye mask. Tear film break-up time (TBUT), tear film lipid layer thickness (TFLLT), blink pattern, Meibomian secretory function scores (MGS), visual acuity, spherical equivalent (SE), keratometry, central corneal thickness (CCT) and aberration were assessed before and after WC.

Results: After WC, the following mean values all increased relative to baselines: CCT, SE, minimum (Min-), maximum (Max-) and average (Ave-) TFLLT, TBUT, total MGS (TMGS), number of glands secreting any liquid (MGL), and complete blink rate (CBR) (p values ranging from < 0.001 to 0.042). Partial blink frequency (PBF) and partial blink rate (PBR) decreased (p = 0.002 in both cases). The decrease of PBF was higher in SMILE subgroup than in LASEK (p = 0.030). TBUT variation was positively correlated with that of Ave-TFLLT and TMGS (p = 0.046, 0.028, respectively). Max-TFLLT variation was correlated with that of TMGS (p = 0.020).

Conclusions: WC may temporarily increase tear film thickness and stability, decrease partial blink, and partly augment Meibomian gland function in dry eye patients after corneal refractive surgeries. Future studies are required to investigate long term clinical efficacy and safety.
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http://dx.doi.org/10.1186/s12886-021-02091-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8431912PMC
September 2021

The Driving Influence of Multi-Dimensional Urbanization on PM Concentrations in Africa: New Evidence from Multi-Source Remote Sensing Data, 2000-2018.

Int J Environ Res Public Health 2021 Sep 6;18(17). Epub 2021 Sep 6.

Hunan Institute of Economic Geography, Hunan University of Finance and Economics, Changsha 410205, China.

Africa's PM pollution has become a security hazard, but the understanding of the varying effects of urbanization on driven mechanisms of PM concentrations under the rapid urbanization remains largely insufficient. Compared with the direct impact, the spillover effect of urbanization on PM concentrations in adjacent regions was underestimated. Urbanization is highly multi-dimensional phenomenon and previous studies have rarely distinguished the different driving influence and interactions of multi-dimensional urbanization on PM concentrations in Africa. This study combined grid and administrative units to explore the spatio-temporal change, spatial dependence patterns, and evolution trend of PM concentrations and multi-dimensional urbanization in Africa. The differential influence and interaction effects of multi-dimensional urbanization on PM concentrations under Africa's rapid urbanization was further analyzed. The results show that the positive spatial dependence of PM concentrations gradually increased over the study period 2000-2018. The areas with PM concentrations exceeding 35 μg/m increased by 2.2%, and 36.78% of the African continent had an increasing trend in Theil-Sen index. Urbanization was found to be the main driving factor causing PM concentrations changes, and economic urbanization had a stronger influence on air quality than land urbanization or population urbanization. Compared with the direct effect, the spillover effect of urbanization on PM concentrations in two adjacent regions was stronger, particularly in terms of economic urbanization. The spatial distribution of PM concentrations resulted from the interaction of multi-dimensional urbanization. The interaction of urbanization of any two different dimensions exhibited a nonlinear enhancement effect on PM concentrations. Given the differential impact of multi-dimensional urbanization on PM concentrations inside and outside the region, this research provides support for the cross-regional joint control strategies of air pollution in Africa. The findings also indicate that PM pollution control should not only focus on urban economic development strategies but should be an optimized integration of multiple mitigation strategies, such as improving residents' lifestyles, optimizing land spatial structure, and upgrading the industrial structure.
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http://dx.doi.org/10.3390/ijerph18179389DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8430555PMC
September 2021

A highly selective ratiometric molecular probe for imaging peroxynitrite during drug-induced acute liver injury.

J Mater Chem B 2021 Sep 9. Epub 2021 Sep 9.

State Key Laboratory of Chemo/Biosensing and Chemometrics, College of Chemistry and Chemical Engineering, Hunan University, Changsha, 410082, P. R. China.

Drug-induced acute liver injury (DIALI) is a common liver disease, affecting a number of people worldwide with increasing morbidity each year. Thus, it is vital to develop new tools for intervention and diagnosis. Peroxynitrite (ONOO), a highly reactive species, plays an important role in the DIALI process. Thus, molecular imaging of endogenous ONOO levels is considerably significant for detecting ONOO. In this work, we present two destroyed-type ratiometric fluorescent probes, AHC and AHMC, for ONOO detection by using a molecular hybridization strategy. The probe AHMC was developed by introducing the ester structure to AHC directly to enhance its membrane penetrability for living cell imaging. Probe AHC exhibited good analytical performance toward ONOO compared to other reactive species, with a low detection limit (≈1.8 nM) and a strong ratiometric fluorescence response (134-fold). In cell imaging experiments, AHMC showed outstanding selectivity, favourable biocompatibility and mitochondria-targeting ability, which not only was used to detect endogenous and exogenous ONOO changes, but also enabled noninvasive visualization of ONOO generation in a different drug-induced DIALI model. We hope that these ratiometric probes can be useful chemical tools for the in-depth research of drug-induced acute hepatotoxicity.
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http://dx.doi.org/10.1039/d1tb01534fDOI Listing
September 2021

Experimental Comparative Investigation of Hot Solvent/Steam-Assisted Gravity Drainage in Oil Sand Reservoirs.

ACS Omega 2021 Aug 18;6(34):22333-22343. Epub 2021 Aug 18.

PetroChina Research Institute of Petroleum Exploration & Development, Beijing 100083, China.

Hot solvent-assisted gravity drainage (HS-AGD) is an effective way to exploit oil sands and heavy oil both economically and environmentally. The visualized microscopic seepage experiments and two-dimensional (2-D) macroscopic simulation experiments of HS-AGD are carried out, and the results are compared with that of steam-assisted gravity drainage (SAGD) in detail for the first time in order to compare their development effects of the oil sand reservoir. MacKay River oil sand bitumen is taken as an oil sample in the experiments, with -hexane as the solvent. Micro seepage characteristics of the hot solvent and steam and the remaining oil distribution of the solvent and steam drive are investigated through microseepage experiments. The expanding process of the solvent/steam chamber and production performance of HS-SAGD and SAGD are investigated through macrosimulation experiments. The study found that the sweep efficiency of hot solvent is higher than that of steam at the same temperature due to the small interfacial tension between the condensed solvent and heated bitumen. Due to the severe gravity segregation, the steam accumulated at the top of the model during the 2-D physical simulation experiment, which results in the huge heat loss at the top of the model. The temperature of the steam chamber is significantly lower than that of the solvent chamber. The oil recovery of 200 °C hot solvent vapor is twice as much as that of 300 °C steam owing to the different drainage mechanisms of the HS-AGD and SAGD. In SAGD, only heat transfer reduces the viscosity of oil sand bitumen. The components of oil produced in SAGD have little difference compared with that of the original bitumen. In HS-AGD, both mass transfer and the sensible heat transfer reduce the viscosity of oil sand bitumen. The in situ asphaltene precipitation induced by heated-solvent extraction also upgrades the bitumen. The results of component analysis show that in HS-AGD, the content of heavy components in the oil sand bitumen is obviously reduced. This paper aims to reveal the oil drainage mechanism of HS-AGD and SAGD from the macroscopic and microscopic view and to provide theoretical guidance for the field application of this technology.
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http://dx.doi.org/10.1021/acsomega.1c03090DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8412906PMC
August 2021

The SFRP1 inhibitor WAY-316606 attenuates osteoclastogenesis through dual modulation of canonical Wnt signaling.

J Bone Miner Res 2021 Sep 7. Epub 2021 Sep 7.

Department of Orthopaedic Surgery, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, China.

Osteoporosis, a noteworthy age-related disease induced by imbalanced osteogenesis and osteoclastogenesis, is a serious economic burden on both individuals and society. Small molecule drugs with dual effects on both bone resorption and mineralization are pressingly needed. Secreted frizzled-related protein 1 (SFRP1), a well-known extracellular repressor of canonical Wnt signaling, has been reported to regulate osteogenesis. Global SFRP1 knockout mice show significantly elevated bone mass. Although osteoclasts (OCs) express and secrete SFRP1, the role of SFRP1 produced by OCs in osteoclastogenesis and osteoporosis remains unclear. In this work, we found that the levels of SFRP1 increased in osteoporotic patients compared to healthy controls. Pharmacological inhibition of SFRP1 by WAY-316606 (WAY) attenuated osteoclastogenesis and bone resorption in vitro. The expressions of OC-specific genes were suppressed by the SFRP1 inhibitor, WAY. Mechanistically, both extracellular and intracellular SFRP1 could block activation of the canonical Wnt signaling pathway, and WAY reversed the silent status of canonical Wnt through dual effects, leading to osteoclastogenesis inhibition and osteogenesis promotion. Severe osteopenia was observed in the ovariectomized (OVX) mouse model, and WAY treatment effectively improved the OVX-induced osteoporosis. In summary, this work indicates that SFRP1 supports OC differentiation and function, which could be attenuated by WAY through dual modulation of canonical Wnt signaling, suggesting its therapeutic potential. This article is protected by copyright. All rights reserved.
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http://dx.doi.org/10.1002/jbmr.4435DOI Listing
September 2021

Safety and Accuracy of Suction Rectal Biopsy in Preterm Infants.

Front Pediatr 2021 20;9:642342. Epub 2021 Aug 20.

Beijing Children's Hospital, Capital Medical University, National Center for Children's Health, Beijing, China.

Most pediatric surgeons give little attention to the diagnosis of Hirschsprung disease (HD) in preterm infants. We aimed to explore the safety and accuracy of suction rectal biopsy (SRB) for diagnosing HD in preterm infants. A retrospective review was conducted of 45 preterm patients who underwent SRB from 2015 to 2019 in our hospital. We collected the clinical characteristics and pathology results of the patients and information on follow-up. The sensitivity and specificity of SRB for HD diagnosis were calculated. The median gestational age of the patients was 35 weeks (range: 28.9-36.9 weeks), the median gestational age at biopsy was 38.6 weeks (range: 33.4-60.0 weeks), and the median weight was 2,790 g (range: 1,580-4,100 g). Fifteen patients (33.3%) were positive for HD, which was confirmed after pull-through surgery. Ganglion cells were present in 30 patients. The diagnosis of HD was excluded in 29 patients after discharge follow-up. The sensitivity of SRB ranged from 93.7 to 100%, and the specificity was 100%. No complications occurred after SRB among the patients whose biopsy age was <37 weeks (10 patients) or biopsy weight was <2,000 g (five patients). SRB is accurate and safe for diagnosing HD in late preterm infants.
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http://dx.doi.org/10.3389/fped.2021.642342DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8417823PMC
August 2021

Big-data and artificial-intelligence-assisted vault prediction and EVO-ICL size selection for myopia correction.

Br J Ophthalmol 2021 Sep 6. Epub 2021 Sep 6.

Department of Ophthalmology and Optometry, Fudan University Eye Ear Nose and Throat Hospital, Shanghai, China

Aims: To predict the vault and the EVO-implantable collamer lens (ICL) size by artificial intelligence (AI) and big data analytics.

Methods: Six thousand two hundred and ninety-seven eyes implanted with an ICL from 3536 patients were included. The vault values were measured by the anterior segment analyzer (Pentacam HR). Permutation importance and Impurity-based feature importance are used to investigate the importance between the vault and input parameters. Regression models and classification models are applied to predict the vault. The ICL size is set as the target of the prediction, and the vault and the other input features are set as the new inputs for the ICL size prediction. Data were collected from 2015 to 2020. Random Forest, Gradient Boosting and XGBoost were demonstrated satisfying accuracy and mean area under the curve (AUC) scores in vault predicting and ICL sizing.

Results: In the prediction of the vault, the Random Forest has the best results in the regression model (R=0.315), then follows the Gradient Boosting (R=0.291) and XGBoost (R=0.285). The maximum classification accuracy is 0.828 in Random Forest, and the mean AUC is 0.765. The Random Forest predicts the ICL size with an accuracy of 82.2% and the Gradient Boosting and XGBoost, which are also compatible with 81.5% and 81.8% accuracy, respectively.

Conclusions: Random Forest, Gradient Boosting and XGBoost models are applicable for vault predicting and ICL sizing. AI may assist ophthalmologists in improving ICL surgery safety, designing surgical strategies, and predicting clinical outcomes.
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http://dx.doi.org/10.1136/bjophthalmol-2021-319618DOI Listing
September 2021

Anti-tumor effect of Yanggan Huayu granule by inducing AKT-mediated apoptosis in hepatocellular carcinoma.

J Ethnopharmacol 2021 Sep 4;282:114601. Epub 2021 Sep 4.

College of Pharmacy, Nanjing University of Chinese Medicine, Nanjing, Jiangsu, China. Electronic address:

Ethnopharmacological Relevance: Yanggan Huayu granule (YGHY) is a formula of traditional Chinese medicine that has been widely used to treat patients with liver cancer. But its working mechanism is still poorly understood.

Aim Of The Study: To investigate the anti-tumor effect of YGHY and its working mechanisms in hepatocellular carcinoma (HCC).

Materials And Methods: H22 mouse xenograft model was used to detect the effect of YGHY on hepatocellular carcinoma (HCC). MTT and CCK8 assays were performed to assess the effect of YGHY on HCC cell growth. Transwell assay was performed to detect the invasion and migration activities of HCC cells. Effect of YGHY drug-contained serum on apoptosis was detected by flow cytometry. Western blot was performed to detect the protein expressions.

Results: Results showed that YGHY inhibited tumor volume and weight, induced the apoptosis of HepG2 and SMMC-7721 cells and increased the protein expressions of Cleaved-Caspase3 and Cleaved-PARP. Furthermore, YGHY significantly down-regulated the protein expression of p-AKT. SC79, as an activator of AKT signaling, was able to increase the expression of p-AKT, and regulate the protein expressions of Cleaved-Caspase3, Cleaved-PARP, BCL-2 and BAX. YGHY drug-contained serum negated the protein expression change provided by SC79.

Conclusions: Taken together, this data indicates that YGHY could inhibit HCC growth by inducing apoptosis, operating through AKT signaling.
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http://dx.doi.org/10.1016/j.jep.2021.114601DOI Listing
September 2021

A Correspondence between Normalization Strategies in Artificial and Biological Neural Networks.

Neural Comput 2021 Aug 30:1-25. Epub 2021 Aug 30.

Cold Spring Harbor Laboratory, Simons Center for Quantitative Biology, Cold Spring Harbor, NY 11724, U.S.A.

A fundamental challenge at the interface of machine learning and neuroscience is to uncover computational principles that are shared between artificial and biological neural networks. In deep learning, normalization methods such as batch normalization, weight normalization, and their many variants help to stabilize hidden unit activity and accelerate network training, and these methods have been called one of the most important recent innovations for optimizing deep networks. In the brain, homeostatic plasticity represents a set of mechanisms that also stabilize and normalize network activity to lie within certain ranges, and these mechanisms are critical for maintaining normal brain function. In this article, we discuss parallels between artificial and biological normalization methods at four spatial scales: normalization of a single neuron's activity, normalization of synaptic weights of a neuron, normalization of a layer of neurons, and normalization of a network of neurons. We argue that both types of methods are functionally equivalent-that is, both push activation patterns of hidden units toward a homeostatic state, where all neurons are equally used-and we argue that such representations can improve coding capacity, discrimination, and regularization. As a proof of concept, we develop an algorithm, inspired by a neural normalization technique called synaptic scaling, and show that this algorithm performs competitively against existing normalization methods on several data sets. Overall, we hope this bidirectional connection will inspire neuroscientists and machine learners in three ways: to uncover new normalization algorithms based on established neurobiological principles; to help quantify the trade-offs of different homeostatic plasticity mechanisms used in the brain; and to offer insights about how stability may not hinder, but may actually promote, plasticity.
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http://dx.doi.org/10.1162/neco_a_01439DOI Listing
August 2021

Isolation, Purification, Characterization, and Immunomodulatory Activity Analysis of α-Glucans from .

ACS Omega 2021 Aug 12;6(33):21384-21394. Epub 2021 Aug 12.

College of Food and Biological Engineering, Jimei University, Xiamen 361021, P. R. China.

Crude polysaccharides from (SP) were isolated by maceration with a hot alkali solution and further fractionated by DEAE-52 cellulose and Sephadex G-100 chromatography into two purified fractions PSP-1 and PSP-2. The monosaccharide composition analysis indicated that SP was mainly composed of rhamnose and glucose, while PSP-1 and PSP-2 were composed only of glucose. The composition analysis of PSP-1 and PSP-2 by HPLC, FT-IR, and NMR showed that PSP-1 and PSP-2 were branching dextran, and their structures were (1 → 4)-linked-α-D-Glcp as the main chain, and C-6 replaced the single α-D-Glcp as the linear structure of the branch chain. The glucans (SP/PSP-1/PSP-2) can significantly improve the phagocytic ability of macrophages, enhance iNOS activity, promote NO production, and increase IL-6 mRNA expression, so they may possess certain immunomodulatory activity.
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http://dx.doi.org/10.1021/acsomega.1c02175DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8387993PMC
August 2021

Interfacial "Anchoring Effect" Enables Efficient Large-Area Sky-Blue Perovskite Light-Emitting Diodes.

Adv Sci (Weinh) 2021 Aug 28:e2102213. Epub 2021 Aug 28.

Jiangsu Key Laboratory for Carbon-Based Functional Materials & Devices, Institute of Functional Nano & Soft Materials (FUNSOM), Soochow University, Suzhou, 215123, China.

While tremendous progress has recently been made in perovskite light-emitting diodes (PeLEDs), large-area blue devices feature inferior performance due to uneven morphologies and vast defects in the solution-processed perovskite films. To alleviate these issues, a facile and reliable interface engineering scheme is reported for manipulating the crystallization of perovskite films enabled by a multifunctional molecule 2-amino-1,3-propanediol (APDO)-triggered "anchoring effect" at the grain-growth interface. Sky-blue perovskite films with large-area uniformity and low trap states are obtained, showing the distinctly improved radiative recombination and hole-transport capability. Based on the APDO-induced interface engineering, synergistical boost in device performance is achieved for large-area sky-blue PeLED (measuring at 100 mm ) with a peak external quantum efficiency (EQE) of 9.2% and a highly prolonged operational lifetime. A decent EQE up to 6.1% is demonstrated for the largest sky-blue device emitting at 400 mm .
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http://dx.doi.org/10.1002/advs.202102213DOI Listing
August 2021

Prediction of protein assemblies, the next frontier: The CASP14-CAPRI experiment.

Proteins 2021 Aug 28. Epub 2021 Aug 28.

Faculty of Chemistry, University of Gdansk, Gdansk, Poland.

We present the results for CAPRI Round 50, the fourth joint CASP-CAPRI protein assembly prediction challenge. The Round comprised a total of twelve targets, including six dimers, three trimers, and three higher-order oligomers. Four of these were easy targets, for which good structural templates were available either for the full assembly, or for the main interfaces (of the higher-order oligomers). Eight were difficult targets for which only distantly related templates were found for the individual subunits. Twenty-five CAPRI groups including eight automatic servers submitted ~1250 models per target. Twenty groups including six servers participated in the CAPRI scoring challenge submitted ~190 models per target. The accuracy of the predicted models was evaluated using the classical CAPRI criteria. The prediction performance was measured by a weighted scoring scheme that takes into account the number of models of acceptable quality or higher submitted by each group as part of their five top-ranking models. Compared to the previous CASP-CAPRI challenge, top performing groups submitted such models for a larger fraction (70-75%) of the targets in this Round, but fewer of these models were of high accuracy. Scorer groups achieved stronger performance with more groups submitting correct models for 70-80% of the targets or achieving high accuracy predictions. Servers performed less well in general, except for the MDOCKPP and LZERD servers, who performed on par with human groups. In addition to these results, major advances in methodology are discussed, providing an informative overview of where the prediction of protein assemblies currently stands.
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http://dx.doi.org/10.1002/prot.26222DOI Listing
August 2021

Bmal1 Downregulation Worsens Critical Limb Ischemia by Promoting Inflammation and Impairing Angiogenesis.

Front Cardiovasc Med 2021 10;8:712903. Epub 2021 Aug 10.

Department of Vascular Surgery, Institute of Vascular Surgery, Zhongshan Hospital, Fudan University, Shanghai, China.

Critical limb ischemia (CLI) is the most advanced clinical stage of peripheral vascular disease with high mobility and mortality. CLI patients suffer from lower extremity rest pain, ulceration, and gangrene caused by insufficient blood and oxygen supply. Seeking for effective biomarkers and therapeutic targets is of great significance for improving the life quality of CLI patients. The circadian clock has been reported to be involved in the progression of kinds of cardiovascular diseases. Whether and how circadian genes play a role in CLI remains unknown. In this study, by collecting femoral artery and muscle specimens of CLI patients who underwent amputation, we confirmed that the circadian gene Bmal1 is downregulated in the CLI femoral artery and ischemic distal lower limb muscle. Furthermore, we verified that Bmal1 affects CLI by regulating lipid metabolism, inflammation, and angiogenesis. A hindlimb ischemia model performed in wild-type and Bmal1 mice confirmed that Bmal1 disruption would lead to impaired angiogenesis. experiments indicated that the decreased expression of Bmal1 would increase ox-LDL uptake and impair endothelial cell functions, including proliferation, migration, and tube formation. As for mechanisms, Bmal1 represses inflammation by inhibiting lipid uptake and by activating IL-10 transcription and promotes angiogenesis by transcriptionally regulating VEGF expression. In conclusion, we provide evidence that the circadian gene Bmal1 plays an important role in CLI by inhibiting inflammation and promoting angiogenesis. Thus, Bmal1 may be an effective biomarker and a potential therapeutic target in CLI.
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http://dx.doi.org/10.3389/fcvm.2021.712903DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8384109PMC
August 2021

Ultrasound-guided microwave ablation for secondary hyperparathyroidism: a systematic review and meta-analysis.

Int J Hyperthermia 2021 ;38(1):1285-1294

Department of Nephrology, Changshu Hospital Affiliated to Nanjing University of Chinese Medicine, Changshu, China.

Objectives: Microwave ablation (MWA) is used for the treatment of severe secondary hyperparathyroidism (SHPT), but its efficacy and safety still remained unclear. This study aimed to investigate the efficacy and safety of ultrasound (US)-guided MWA in patients with SHPT.

Methods: The PubMed, Cochrane library, Embase, China national knowledge infrastructure (CNKI) and Wanfang databases were searched to identify published studies that evaluated the efficacy and safety of US-guided MWA in patients with SHPT. The primary outcomes were parathyroid hormone (PTH), serum calcium and phosphorus levels.

Results: A total of 26 studies with 932 patients were identified. The PTH levels showed significant reduction at 1 month [weighted mean difference (WMD) = 945.33, 95% CI: 797.15∼1093.52] and 6 months (WMD = 1,151.91, 95% CI: 990.93∼1312.89) after MWA of SHPT patients. The serum calcium (WMD = 0.39, 95% CI: 0.30 ∼ 0.48) and phosphorus levels (WMD = 0.64, 95% CI: 0.43 ∼ 0.85) showed significant reduction at 6 months after MWA of SHPT patients. The most common complications observed were hypocalcemia (35.2%) and transient hoarseness (9.2%). No other major complications or death occurred in our study patients.

Conclusion: These findings suggest MWA as a safe and effective minimally invasive technique for the management of SHPT. PTH, calcium, and phosphorus levels were significantly reduced at 1 and 6 months after MWA.
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http://dx.doi.org/10.1080/02656736.2021.1965664DOI Listing
September 2021

Fold2Seq: A Joint Sequence(1D)-Fold(3D) Embedding-based Generative Model for Protein Design.

Proc Mach Learn Res 2021 Jul;139:1261-1271

Texas A&M University.

Designing novel protein sequences for a desired 3D topological fold is a fundamental yet nontrivial task in protein engineering. Challenges exist due to the complex sequence-fold relationship, as well as the difficulties to capture the diversity of the sequences (therefore structures and functions) within a fold. To overcome these challenges, we propose , a novel transformer-based generative framework for designing protein sequences conditioned on a specific target fold. To model the complex sequence-structure relationship, Fold2Seq jointly learns a sequence embedding using a transformer and a fold embedding from the density of secondary structural elements in 3D voxels. On test sets with single, high-resolution and complete structure inputs for individual folds, our experiments demonstrate improved or comparable performance of Fold2Seq in terms of speed, coverage, and reliability for sequence design, when compared to existing state-of-the-art methods that include data-driven deep generative models and physics-based RosettaDesign. The unique advantages of fold-based Fold2Seq, in comparison to a structure-based deep model and RosettaDesign, become more evident on three additional real-world challenges originating from low-quality, incomplete, or ambiguous input structures. Source code and data are available at https://github.com/IBM/fold2seq.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8375603PMC
July 2021

Effect of Postoperative Specific Immunotherapy Combined with Nasal Irrigation on Chronic Rhinosinusitis with Allergic Rhinitis.

Iran J Allergy Asthma Immunol 2021 Aug 7;20(4):432-440. Epub 2021 Aug 7.

Department of Otorhinolaryngology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China.

Patients with chronic rhinosinusitis (CRS) and allergic rhinitis (AR) (CRSwAR) have a more severe condition with a higher rate of recurrence after endoscopic sinus surgery (ESS). This study aimed to explore the effect of specific subcutaneous immunotherapy (SCIT) and nasal irrigation on CRSwAR after ESS. Sixty-four patients who were diagnosed as CRSwAR and received ESS were enrolled and divided into groups A, B, and C to receive different postoperative treatment strategies (conventional medication, medication with nasal irrigation, and medication with nasal irrigation and SCIT), and their prognosis was evaluated by scoring, electron microscopy, and inflammatory factors. One year after ESS, the recurrence rate of group C was significantly reduced; and the scoring from baseline was significantly different among the three groups, which of group C were the best. The epithelium arrangement, cilia morphology, and inflammation of nasal mucosa in each group were better than those in the preoperative state; and those in group C were the best. After one year, the expression levels of eosinophil cationic protein (ECP), interleukin (IL)-8, and IL-17 in group B were lower than those of group A; and the expression levels of ECP, IL-8, IL-25, IL-33, IL-17 in group C were lower than those in group A. SCIT combined with nasal irrigation can improve the patients' symptoms and quality of life, promote the epithelialization of the mucosa in the surgical cavity, regulate the local immune response of the nasal cavity; thus improve the prognosis of patients with ESS after 1 year.
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August 2021

Minimum effective volume of 0.2% ropivacaine for ultrasound-guided axillary brachial plexus block in preschool-age children.

Sci Rep 2021 Aug 20;11(1):17002. Epub 2021 Aug 20.

Department of Anesthesiology, Shengjing Hospital of China Medical University, No.36 Sanhao Street, Heping District, Shenyang, 110004, Liaoning Province, China.

Ultrasound-guided axillary brachial plexus block is increasingly used in preschool-age patients. However, the minimum effective volume of local anaesthetics has not been determined. With ethical committee approval and written informed consent from the guardians of all paediatric patients, we studied 27 consecutive patients aged 3 to 6 years who were scheduled for hand surgery. After general anaesthesia, eligible patients received a set volume of ultrasound-guided axillary brachial plexus block. We determined the volume of 0.2% ropivacaine for consecutive patients from the preceding patient's outcome. The initial volume was 0.4 ml/kg. The testing interval was set at 0.05 ml/kg, and the lowest volume was 0.1 ml/kg. The following conditions were defined as a successful block: no heart rate changes, body movement, or ventilatory disorders during the operation; no use of fentanyl in the PACU; and a postoperative sensory block score < 3. The sequences of positive and negative blocks in consecutive patients were recorded. Using probit regression analysis, the 50% effective volume was 0.185 ml/kg (95% CI 0.123-0.234), and the 95% effective volume was 0.280 ml/kg (95% CI 0.232-0.593). EV50 and EV95 values of 0.2% ropivacaine for ultrasound-guided axillary brachial plexus block were 0.185 ml/kg and 0.280 ml/kg, respectively.
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http://dx.doi.org/10.1038/s41598-021-96582-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8379224PMC
August 2021

Co-Occurrence of NDM-9 and MCR-1 in a Human Gut Colonized ST1011.

Infect Drug Resist 2021 10;14:3011-3017. Epub 2021 Aug 10.

Department of Infectious Diseases, The First Hospital of Taizhou, Taizhou, People's Republic of China.

Background: The emergence of the plasmid-borne colistin-resistant gene () poses a great threat to human health. What is worse, the recent observations of the coexistence of with carbapenemase encoding genes in some bacteria caused even more concern. Yet, there is a lack of observations of such strains in the human gut.

Methods: The isolation of L889 was performed on selective medium plates. Antibiotic susceptibilities were determined by an agar dilution and a broth microdilution method. Multi-locus sequence typing (MLST) and acquired resistance genes were also characterized. Transferability of /-carrying plasmids was determined by conjugation, replicon typing and S1-Pulsed-field gel electrophoresis (S1-PFGE), and Southern blotting. The sequences of these plasmids were analyzed by using whole-genome sequencing with Illumina Novaseq and Nanopore platforms.

Results: L889 was identified as ST1101 concomitantly carrying and from a stool sample. Antimicrobial susceptibility tests showed that it was resistant to various antimicrobial agents and only susceptible to tigecycline. Notably, was located on a ~114-kb untypable plasmid, while was located on a ~63-kb IncI2 plasmid.

Conclusion: Our research, to our knowledge, first reported an ST1101 strain with an untypeable -harbouring plasmid and an IncI2 -carrying plasmid. The colonized strains potentially contribute to the dissemination and transfer of and to clinical isolates, which is a considerable threat to public health and should be closely monitored.
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http://dx.doi.org/10.2147/IDR.S321732DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8370297PMC
August 2021

ICAM1 initiates CTC cluster formation and trans-endothelial migration in lung metastasis of breast cancer.

Nat Commun 2021 08 11;12(1):4867. Epub 2021 Aug 11.

Department of Pharmacology, Northwestern University Feinberg School of Medicine, Chicago, IL, USA.

Circulating tumor cell (CTC) clusters mediate metastasis at a higher efficiency and are associated with lower overall survival in breast cancer compared to single cells. Combining single-cell RNA sequencing and protein analyses, here we report the profiles of primary tumor cells and lung metastases of triple-negative breast cancer (TNBC). ICAM1 expression increases by 200-fold in the lung metastases of three TNBC patient-derived xenografts (PDXs). Depletion of ICAM1 abrogates lung colonization of TNBC cells by inhibiting homotypic tumor cell-tumor cell cluster formation. Machine learning-based algorithms and mutagenesis analyses identify ICAM1 regions responsible for homophilic ICAM1-ICAM1 interactions, thereby directing homotypic tumor cell clustering, as well as heterotypic tumor-endothelial adhesion for trans-endothelial migration. Moreover, ICAM1 promotes metastasis by activating cellular pathways related to cell cycle and stemness. Finally, blocking ICAM1 interactions significantly inhibits CTC cluster formation, tumor cell transendothelial migration, and lung metastasis. Therefore, ICAM1 can serve as a novel therapeutic target for metastasis initiation of TNBC.
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http://dx.doi.org/10.1038/s41467-021-25189-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8358026PMC
August 2021

The Role of Non-Coding RNAs in the Sorafenib Resistance of Hepatocellular Carcinoma.

Front Oncol 2021 22;11:696705. Epub 2021 Jul 22.

Department of Oncology, Renmin Hospital of Wuhan University, Wuhan, China.

Hepatocellular carcinoma (HCC) is the second most common cause of cancer-related death. Sorafenib is approved by the U.S. Food and Drug Administration to be a first-line chemotherapy agent for patients with advanced HCC. A portion of advanced HCC patients can benefit from the treatment with sorafenib, but many patients ultimately develop sorafenib resistance, leading to a poor prognosis. The molecular mechanisms of sorafenib resistance are sophisticated and indefinite. Notably, non-coding RNAs (ncRNAs), which include long ncRNAs (lncRNAs), microRNAs (miRNAs) and circular RNAs (circRNAs), are critically participated in the occurrence and progression of tumors. Moreover, growing evidence has suggested that ncRNAs are crucial regulators in the development of resistance to sorafenib. Herein, we integrally and systematically summarized the molecular mechanisms and vital role of ncRNAs impact sorafenib resistance of HCC, and ultimately explored the potential clinical administrations of ncRNAs as new prognostic biomarkers and therapeutic targets for HCC.
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http://dx.doi.org/10.3389/fonc.2021.696705DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8340683PMC
July 2021

A Novel Germline Compound Heterozygous Mutation of Gene Associated With Familial Peripheral Neuroblastic Tumors in Two Siblings.

Front Genet 2021 23;12:652718. Epub 2021 Jul 23.

Beijing Key Laboratory for Pediatric Diseases of Otolaryngology, Head and Neck Surgery, MOE Key Laboratory of Major Diseases in Children, National Center for Children's Health, Beijing Children's Hospital, Beijing Pediatric Research Institute, Capital Medical University, Beijing, China.

Objectives: To investigate the genetic variants that are responsible for peripheral neuroblastic tumors (PNTs) oncogenesis in one family case.

Materials And Methods: One family was recruited, including the healthy parents, sister affected by neuroblastoma (NB), and brother who suffered from ganglioneuroma (GN). Whole-genome sequencing (WGS) of germline DNA from all the family members and RNA-seq of tumor RNA from the siblings were performed. Mutants were validated by Sanger sequencing and co-IP was performed to assess the impact of the mutant on chemosensitivity in the SH-SY5Y cell line.

Results: A novel compound heterozygous mutation of was locked as the cause of carcinogenesis. One allele was BRCA2-S871X (stop-gain) from the siblings' mother, the other was BRCA2-N372H (missense) from their father. This novel compound heterozygous mutations of the gene associated with PNTs by disordering DNA damage and response (DDR) signal pathway. Moreover, chemosensitivity was reduced in the NB cell line due to the BRCA2-N372H mutant.

Conclusion: In summary, these results revealed a novel germline compound heterozygous mutation of the gene associated with familial PNTs.
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http://dx.doi.org/10.3389/fgene.2021.652718DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8343186PMC
July 2021

Comparison of the ED50 propofol requirements during the insertion of laryngeal mask airway Ambu AuraFlex with Ambu AuraOnce in children undergoing strabismus surgery.

J Clin Pharm Ther 2021 Aug 2. Epub 2021 Aug 2.

Department of Anesthesiology, Shanghai Children's Medical Center, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.

What Is Known And Objective: Optimal airway management is crucial in strabismus surgery due to the inaccessibility of the airway throughout the procedure. Laryngeal mask airway offers advantages over tracheal intubation in ophthalmic surgery as it does not increase the intraocular pressure. The purpose of this study was to determine the median effective dose of propofol required, when combined with 0.2 µg/kg of sufentanil, for smooth insertion of Ambu AuraFlex in the first attempt in children undergoing strabismus surgery, and to compare it with that for Ambu AuraOnce.

Methods: Forty-three paediatric patients undergoing strabismus surgery under general anaesthesia were recruited. For induction, the initial dosage of propofol was 2 mg/kg in the AuraOnce group or 3 mg/kg in the AuraFlex group. In accordance with Dixon's up-and-down method, the dose of propofol for consecutive patients in each group was adjusted in increments or decrements of 0.25 mg/kg based on the previous patient's "three-point, six-category scale" response to the first attempt of insertion of the randomized device. Insertion of the device was attempted when the bispectral index was ≤60 for 5 s after propofol administration without the use of neuromuscular blocking agents.

Results And Discussion: The median effective dose (95% confidence interval) of propofol was significantly lower in the Ambu AuraOnce group than in the Ambu AuraFlex group (1.92 [1.50-2.32] mg/kg vs. 2.98 [2.49-3.94] mg/kg; p = 0.002). The incidence of dislodgement of the device was significantly higher with the use of the Ambu AuraOnce than with the use of AuraFlex (p = 0.023), whereas insignificant differences were observed between the two groups in the incidence of other perioperative adverse events.

What Is New And Conclusion: Ambu AuraFlex requires a significantly higher dose of propofol for insertion and provides more effective and stable airway management in strabismus surgery than AuraOnce.
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http://dx.doi.org/10.1111/jcpt.13506DOI Listing
August 2021

Develop a Clinical Prediction Model for Postoperative Cognitive Dysfunction after Major Noncardiac Surgery in Elderly Patients: A Protocol for a Prospective Observational Study.

Gerontology 2021 Jul 27:1-8. Epub 2021 Jul 27.

Department of Anesthesia, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.

Perioperative neurocognitive disorders (PNDs) refer to cognitive decline identified in the preoperative or postoperative period. It has been reported that the incidence of postoperative neurocognitive impairment after noncardiac surgery in patients older than 65 at 1 week was 25.8∼41.4%, and at 3 months 9.9∼12.7%. PNDs will last months or even develop to permanent dementia, leading to prolonged hospital stays, reduced quality of life, and increased mortality within 1 year. Despite the high incidence and poor prognosis of PNDs in the aged population, no effective clinical prediction model has been established to predict postoperative cognitive decline preoperatively. To develop a clinical prediction model for postoperative neurocognitive dysfunction, a prospective observational study (Clinical trial registration number: ChiCTR2000036304) will be performed in the Shanghai General Hospital during January 2021 to October 2022. A sample size of 675 patients aged >65 years old, male or female, and scheduled for elective major noncardiac surgery will be recruited. A battery of neuropsychological tests will be used to test the cognitive function of patients at 1 week, 1 month, and 3 months postoperatively. We will evaluate the associations of PNDs with a bunch of candidate predictors including general characteristics of patients, blood biomarkers, indices associated with anesthesia and surgery, retinal nerve-fiber layer thickness, and frailty index to develop the clinical prediction model by using multiple logistic regression analysis and least absolute shrinkage and the selection operator (LASSO) method. The k-fold cross-validation method will be utilized to validate the clinical prediction model. In conclusion, this study was aimed to develop a clinical prediction model for postoperative cognitive dysfunction of old patients. It is anticipated that the knowledge gained from this study will facilitate clinical decision-making for anesthetists and surgeons managing the aged patients undergoing noncardiac surgery.
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http://dx.doi.org/10.1159/000517511DOI Listing
July 2021
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