Publications by authors named "Ranran Li"

71 Publications

A novel peptide promotes human trophoblast proliferation and migration through PI3K/Akt/mTOR signaling pathway.

Ann Transl Med 2021 Jun;9(12):981

Department of Obstetrics and Gynecology, the First Affiliated Hospital of Wannan Medical College, Wuhu, China.

Background: Preeclampsia (PE) is a complex pregnancy-related disease that endangers the safety of maternal and fetal. The purpose of this study is to reveal the pathogenesis of preeclampsia and discover new predictors from the perspective of peptidomics. The umbilical cord blood of PE and control group was analyzed by peptidomics. A peptide named Regulation of Proliferation Process in Preeclampsia (ROPPIP) was screened out to explore its role in the proliferation, migration and apoptosis of trophoblast cells in preeclampsia.

Methods: We compared and analyzed the umbilical cord blood of patients with PE and normal pregnant women using liquid chromatography-tandem mass spectrometry (LC-MS). hTR-8/Svneo cells cultured were divided into ROPPIP group and a disordered peptide group as control. Cell Counting Kit-8 (CCK-8) assay, flow cytometry, Transwell chamber assays and western blot analysis were performed to detect cell proliferation, invasion, migration and apoptosis, in addition to the expression of Matrix metalloproteinase-2 (MMP2), nuclear associated antigen Ki67, B-cell lymphoma-2 (Bcl2), Caspase 3, and β-actin protein.

Results: We identified 133 differential peptides. Of these, 51 were up-regulated while 82 were down-regulated. the polypeptide SFGVRMATASPTDGNV with low differential expression in the serum of PE patients was selected for the study, we named the polypeptide as Regulation of Proliferation Process in PE (ROPPIP). The experiment shows that ROPPIP can up-regulate the expression levels of MMP2, Ki67, and Bcl2 in HTR-8/Svneo cells, down-regulate the expression of caspase-3, promote the proliferation and migration of HTR-8/Svneo cells and inhibit the apoptosis induced by cisplatin, the activation of the phosphatidylinositol-3-kinase/protein kinase B/mammalian target of rapamycin (PI3K/Akt/mTOR) signaling pathway may be associated with the function of ROPPIP.

Conclusions: ROPPIP promotes HTR-8/Svneo cells migration and proliferation, and inhibits apoptosis, by regulating the activation of the PI3K/AKT/mTOR signaling pathway.
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http://dx.doi.org/10.21037/atm-21-2574DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8267276PMC
June 2021

Therapeutic Potential of TNFα and IL1β Blockade for CRS/ICANS in CAR-T Therapy Ameliorating Endothelial Activation.

Front Immunol 2021 19;12:623610. Epub 2021 May 19.

Shanghai Institute of Hematology, State Key Laboratory of Medical Genomics, National Research Center for Translational Medicine at Shanghai, Rui Jin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.

Severe cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS) strongly hampered the broad clinical applicability of chimeric antigen receptor T cell (CAR-T) therapy. Vascular endothelial activation has been suggested to contribute to the development of CRS and ICANS after CAR-T therapy. However, therapeutic strategies targeting endothelial dysfunction during CAR-T therapy have not been well studied yet. Here, we found that tumor necrosis factor α (TNFα) produced by CAR-T cells upon tumor recognition and interleukin 1β (IL1β) secreted by activated myeloid cells were the main cytokines in inducing endothelial activation. Therefore, we investigated the potential effectiveness of TNFα and IL1β signaling blockade on endothelial activation in CAR-T therapy. The blockade of TNFα and IL1β with adalimumab and anti-IL1β antibody respectively, as well as the application of focal adhesion kinase (FAK) inhibitor, effectively ameliorated endothelial activation induced by CAR-T, tumor cells, and myeloid cells. Moreover, adalimumab and anti-IL1β antibody exerted synergistic effect on the prevention of endothelial activation induced by CAR-T, tumor cells, and myeloid cells. Our results indicate that TNFα and IL1β blockade might have therapeutic potential for the treatment of CAR-T therapy-associated CRS and neurotoxicity.
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http://dx.doi.org/10.3389/fimmu.2021.623610DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8170323PMC
May 2021

Intravenous immunoglobulin treatment for patients with severe COVID-19: a retrospective multi-center study.

Clin Microbiol Infect 2021 May 18. Epub 2021 May 18.

Department of Critical Care Medicine, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, No.197 Ruijin 2nd Road, Shanghai 200025, China. Electronic address:

Objectives: Intravenous immunoglobulin (IVIG) is commonly used to treat severe COVID-19, although the clinical outcome of such treatment remains unclear. This study evaluated the effectiveness of IVIG treatment in severe COVID-19 patients.

Methods: This retrospective multicenter study evaluated 28-day mortality in severe COVID-19 patients with or without IVIG treatment. Each patient treated with IVIG was matched with one untreated patient. Logistic regression and inverse probability weighting(IPW)was used to control confounding factors.

Results: The study included 850 patients (421 IVIG treated patients and 429 non-IVIG treated patients). After matching, 406 patients per group remained. No significant difference in 28-day mortality was observed after IPW analysis (ATE = 0.008, 95% CI -0.081-0.097, p = 0.863). There were no significant differences between the IVIG group and non-IVIG group for acute respiratory distress syndrome, diffuse intravascular coagulation, myocardial injury, acute hepatic injury, shock, acute kidney injury, non-invasive mechanical ventilation, invasive mechanical ventilation, continuous renal replacement therapy, and extracorporeal membrane oxygenation except for prone position ventilation (ATE = -0.022, 95% CI -0.041- -0.002, p = 0.028).

Conclusions: IVIG treatment was not associated with significant changes in 28-day mortality in severe COVID-19 patients. The effectiveness of IVIG in treating patients with severe COVID-19 needs to be further investigated through future studies.
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http://dx.doi.org/10.1016/j.cmi.2021.05.012DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8131555PMC
May 2021

Risk factors for secondary hemophagocytic lymphohistiocytosis in severe coronavirus disease 2019 adult patients.

BMC Infect Dis 2021 Apr 29;21(1):398. Epub 2021 Apr 29.

Department of Critical Care Medicine, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, No 197, Rui Jin 2nd road, Shanghai, 200025, China.

Background: Secondary hemophagocytic lymphohistiocytosis (sHLH) is a life-threatening hyperinflammatory event and a fatal complication of viral infections. Whether sHLH may also be observed in patients with a cytokine storm induced by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is still uncertain. We aimed to determine the incidence of sHLH in severe COVID-19 patients and evaluate the underlying risk factors.

Method: Four hundred fifteen severe COVID-19 adult patients were retrospectively assessed for hemophagocytosis score (HScore). A subset of 7 patients were unable to be conclusively scored due to insufficient patient data.

Results: In 408 patients, 41 (10.04%) had an HScore ≥169 and were characterized as "suspected sHLH positive". Compared with patients below a HScore threshold of 98, the suspected sHLH positive group had higher D-dimer, total bilirubin, alanine aminotransferase, aspartate aminotransferase, blood urea nitrogen, serum creatinine, triglycerides, ferritin, interleukin-6, C-reactive protein, procalcitonin, lactate dehydrogenase, creatine kinase isoenzyme, troponin, Sequential Organ Failure Assessment (SOFA) score, while leukocyte, hemoglobin, platelets, lymphocyte, fibrinogen, pre-albumin, albumin levels were significantly lower (all P < 0.05). Multivariable logistic regression revealed that high ferritin (>1922.58 ng/mL), low platelets (<101 × 10/L) and high triglycerides (>2.28 mmol/L) were independent risk factors for suspected sHLH in COVID-19 patients. Importantly, COVID-19 patients that were suspected sHLH positive had significantly more multi-organ failure. Additionally, a high HScore (>98) was an independent predictor for mortality in COVID-19.

Conclusions: HScore should be measured as a prognostic biomarker in COVID-19 patients. In particular, it is important that HScore is assessed in patients with high ferritin, triglycerides and low platelets to improve the detection of suspected sHLH.
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http://dx.doi.org/10.1186/s12879-021-06094-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8084265PMC
April 2021

Research advances in add-on treatment for negative symptoms and cognitive dysfunction in schizophrenia.

Zhong Nan Da Xue Xue Bao Yi Xue Ban 2020 Dec;45(12):1457-1463

Department of Psychiatry, Second Xiangya Hospital, Central South University, Changsha 410011, China.

Antipsychotic medication is the primary treatment for schizophrenia, which is effective on ameliorating positive symptoms and can reduce the risk of recurrence, but it has limited efficacy for negative symptoms and cognitive dysfunction. The negative symptoms and cognitive dysfunction seriously affects the life quality and social function for the patients with schizophrenia. Currently, there is plenty evidence that antipsychotic drugs combined with adjuvant therapy drugs can effectively improve the negative symptoms and cognitive dysfunction. These drugs include anti-oxidants, nicotinic acetylcholine receptors and neuro-inflammatory drugs (anti-inflammatory drugs, minocycline), which show potential clinical effects.
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http://dx.doi.org/10.11817/j.issn.1672-7347.2020.190556DOI Listing
December 2020

Optimal Steady-State Regulator Design for a Class of Nonlinear Systems With Arbitrary Relative Degree.

IEEE Trans Cybern 2020 Dec 1;PP. Epub 2020 Dec 1.

In this article, we consider the regulator design problem for a class of uncertain multi-input-multioutput (MIMO) nonlinear systems with arbitrary relative degree. The objective is to regulate the output of the nonlinear system to an optimal steady state that solves a constrained optimization problem, without computing the optimal solution in advance. By embedding saddle-point dynamics, both state and output-feedback-based regulators are proposed and the resulting closed-loop systems are modeled in standard singularly perturbed forms. By invoking the singular perturbation analysis, exponential stability is established under some regularity condition. Compared with the existing methods, the proposed regulators can deal with a class of nonlinear systems with uncertainties and arbitrary relative degree. Furthermore, the current results can include some recent works on the distributed optimization problem as special cases. Finally, the effectiveness of the proposed methods is validated through numerical simulations.
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http://dx.doi.org/10.1109/TCYB.2020.3034930DOI Listing
December 2020

Distributed Model Reference Adaptive Optimization of Disturbed Multiagent Systems With Intermittent Communications.

IEEE Trans Cybern 2020 Nov 25;PP. Epub 2020 Nov 25.

This article pays close attention to a distributed optimization problem for multiagent systems subject to exogenous disturbances. A novel distributed model reference adaptive control (D-MRAC) scheme is proposed that no explicit disturbance observer or internal model unit is involved, which not only enhances robustness but also improves transient performance. In contrast to the continuous communication that is often assumed in the existing distributed optimization works, the new method allows for more realistic scenarios in which the agents communicate with each other at discrete-time instants. It is shown by Lyapunov analysis that the concerned distributed optimization problem can be solved by the proposed D-MRAC scheme as long as the communication interval is smaller than a given threshold, which can be calculated by following the steps given in this article. Numerical simulations have shown the effectiveness of the presented method.
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http://dx.doi.org/10.1109/TCYB.2020.3032429DOI Listing
November 2020

Computed tomography reveals microenvironment changes in premetastatic lung.

Eur Radiol 2021 Jun 21;31(6):4340-4349. Epub 2020 Nov 21.

Cancer Therapy and Research Center, Shandong Provincial Hospital affiliated to Shandong University, Shandong University, 324 Jingwuweiqi Road, Jinan, 250021, People's Republic of China.

Objectives: Microenvironment changes had occurred in the metastatic organs before the arriving of the metastatic tumor cells. In this study, we evaluated the effectiveness of computed tomography (CT) images in quantifying the microenvironment changes in the premetastatic lung under both laboratory and clinical conditions.

Method: Free-breathing Balb/c mice underwent micro-CT repeatedly after the implantation of 4T1 breast tumor. CT-derived indicators (aerated lung volume, lung tissue volume, total lung volume, mean lung density, and the ratio of aerated lung volume to the total lung volume) were quantified. Hematoxylin-eosin staining was used to display the microenvironment changes in premetastatic lung. Moreover, we examined healthy adult women, adult women with histopathologically confirmed primary breast cancer, and adult women with histopathologically confirmed primary breast cancer and lung metastases in our institution to test whether the indicators derived from lung CT images changed with the growth of breast cancer.

Results: In 4T1 tumor-bearing mice, lung density is increased before lung masses can be recognized on CT images and is correlated with the severity of inflammation in the lung microenvironment. In primary breast tumor-bearing patients, lung density is also increased before the clinical diagnosis of pulmonary metastasis and is correlated with disease score, which represents tumor progression.

Conclusions: CT is a reliable and quantitative tool that yields dynamic information on metastatic processes. Microenvironmental changes had occurred in patients' lung tissue before the clinical diagnosis of pulmonary metastasis. Our research will provide new insight for clinical research on the premetastatic niche.

Key Points: • CT, which provides dynamic information on metastatic processes, is a reliable and quantitative tool to bridge laboratory and clinical studies of the premetastatic niche. • We confirmed that microenvironmental changes occurred in patients' lung tissue before clinicians could diagnose pulmonary metastasis. • Our results provide evidence for the study of the premetastatic niche by analyzing information obtained from CT images.
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http://dx.doi.org/10.1007/s00330-020-07500-6DOI Listing
June 2021

Downregulation of the CB1-Mediated Endocannabinoid Signaling Underlies D-Galactose-Induced Memory Impairment.

Front Mol Neurosci 2020 28;13:130. Epub 2020 Jul 28.

Department of Physiology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

Imbalance in redox homeostasis is a major cause of age-related cognitive impairment. The endocannabinoid system (ECS) is a key player in regulating synaptic transmission, plasticity and memory. Increasing evidence indicates an important interplay between the two systems. However, how excessive oxidative stress could alter ECS and that, in turn, impairs its modulatory role in synaptic plasticity and cognitive function remains elusive. In the present study, we examined this causal link in D-galactose-induced oxidative rats. First, the reactive oxygen species generating enzymes, especially nitric oxide synthase (NOS), indeed show an elevated expression in D-galactose-treated rats, and this was correlated to an impaired hippocampal long-term potentiation (LTP) and spatial memory loss in animal behavioral tests. Second, the cannabinoid receptor type I (CB1)-mediated signaling is known to regulate synaptic plasticity. We show that a decrease in CB1 and increase in degradation enzymes for CB1 ligand endocannabinoid anandamide all occurred to D-galactose-treated rats. Surprisingly, application of low-dose anandamide, known to reduce LTP under physiological condition, now acted to enhance LTP in D-galactose-treated rats, most likely resulted from the inhibition of GABAergic synapses. Furthermore, this reversal behavior of CB1-signaling could be fully simulated by a NOS inhibitor, diphenyleneiodonium. These observations suggest that interaction between redox dysfunction and ECS should contribute significantly to the impaired synaptic plasticity and memory loss in D-galactose-treated rats. Therefore, therapies focusing on the balance of these two systems may shed lights on the treatment of age-related cognitive impairment in the future.
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http://dx.doi.org/10.3389/fnmol.2020.00130DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7399637PMC
July 2020

Detecting band profiles of devices with conductive atomic force microscopy.

Rev Sci Instrum 2020 Jul;91(7):073702

School of Physical Science and Technology, ShanghaiTech University, Shanghai 201210, China.

Band profiles of electronic devices are of fundamental importance in determining their properties. A technique that can map the band profile of both the interior and edges of a device at the nanometer scale is highly demanded. Conventional scanning tunneling spectroscopy (STS) can map band structure at the atomic scale but is limited to the interior of large and conductive samples. Here, we develop contact-mode STS based on a conductive atomic force microscope that can remove these constraints. With this technique, we map the band profile of MoS transistors with nanometer resolution at room temperature. A band bending of 0.6 eV within 18 nm of the edges of MoS on an insulating substrate is discovered. This technique will be of great use for both fundamental and applied studies of various electronic devices.
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http://dx.doi.org/10.1063/5.0008412DOI Listing
July 2020

Prevalence and impact of acute renal impairment on COVID-19: a systematic review and meta-analysis.

Crit Care 2020 06 18;24(1):356. Epub 2020 Jun 18.

Department of Critical Care Medicine, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, People's Republic of China.

Background: The aim of this study is to assess the prevalence of abnormal urine analysis and kidney dysfunction in COVID-19 patients and to determine the association of acute kidney injury (AKI) with the severity and prognosis of COVID-19 patients.

Methods: The electronic database of Embase and PubMed were searched for relevant studies. A meta-analysis of eligible studies that reported the prevalence of abnormal urine analysis and kidney dysfunction in COVID-19 was performed. The incidences of AKI were compared between severe versus non-severe patients and survivors versus non-survivors.

Results: A total of 24 studies involving 4963 confirmed COVID-19 patients were included. The proportions of patients with elevation of sCr and BUN levels were 9.6% (95% CI 5.7-13.5%) and 13.7% (95% CI 5.5-21.9%), respectively. Of all patients, 57.2% (95% CI 40.6-73.8%) had proteinuria, 38.8% (95% CI 26.3-51.3%) had proteinuria +, and 10.6% (95% CI 7.9-13.3%) had proteinuria ++ or +++. The overall incidence of AKI in all COVID-19 patients was 4.5% (95% CI 3.0-6.0%), while the incidence of AKI was 1.3% (95% CI 0.2-2.4%), 2.8% (95% CI 1.4-4.2%), and 36.4% (95% CI 14.6-58.3%) in mild or moderate cases, severe cases, and critical cases, respectively. Meanwhile, the incidence of AKI was 52.9%(95% CI 34.5-71.4%), 0.7% (95% CI - 0.3-1.8%) in non-survivors and survivors, respectively. Continuous renal replacement therapy (CRRT) was required in 5.6% (95% CI 2.6-8.6%) severe patients, 0.1% (95% CI - 0.1-0.2%) non-severe patients and 15.6% (95% CI 10.8-20.5%) non-survivors and 0.4% (95% CI - 0.2-1.0%) survivors, respectively.

Conclusion: The incidence of abnormal urine analysis and kidney dysfunction in COVID-19 was high and AKI is closely associated with the severity and prognosis of COVID-19 patients. Therefore, it is important to increase awareness of kidney dysfunction in COVID-19 patients.
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http://dx.doi.org/10.1186/s13054-020-03065-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7300374PMC
June 2020

Simultaneous determination of sutetinib and its active metabolite sutetinib N-oxide in human plasma by liquid chromatography-tandem mass spectrometry: Evaluation of plasma stability.

Biomed Chromatogr 2020 Oct 13;34(10):e4918. Epub 2020 Aug 13.

Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, China.

From the point of view of drug efficacy and safety, pharmacokinetic profiles of both In this work, a sensitive and reliable liquid chromatographic-tandem mass spectrometric method was established for simultaneous determination of sutetinib and N-oxide metabolite (SNO) in human plasma and further applied to a pharmacokinetic study. Analytes were extracted from plasma samples (100 μl) via acetonitrile-induced protein precipitation and separated on a C column using ammonium acetate with ammonium hydroxide and acetonitrile as the mobile phase. Positive electrospray ionization was carried out through multiple reaction monitoring with transitions of m/z 440.2 → 367.1 and 446.2 → 367.1 for sutetinib and SNO, respectively. The method was linear within the concentration range of 0.5-100 ng/ml for both analytes. The precision, accuracy, selectivity, recovery and matrix effect of this method all met the requirements of bioanalytical guidance. In addition, a plasma stability assessment demonstrated unexpected results. Sutetinib was prone to form covalent conjugates with plasma albumin in vitro. The degree of covalent binding increased with increasing temperature, resulting in a significant decrease in its plasma concentrations. However, SNO could not easily bind with albumin owing to steric hindrance or electronegativity. Furthermore, sutetinib and SNO remained stable when blood and plasma samples were kept on wet ice. The validated method was successfully employed for the pharmacokinetic evaluation of sutetinib in patients with advanced malignant solid tumors.
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http://dx.doi.org/10.1002/bmc.4918DOI Listing
October 2020

Therapeutic strategies for critically ill patients with COVID-19.

Ann Intensive Care 2020 Apr 20;10(1):45. Epub 2020 Apr 20.

Department of Critical Care Medicine, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, People's Republic of China.

Since the 2019 novel coronavirus disease (COVID-19) outbreak originated from Wuhan, Hubei Province, China, at the end of 2019, it has become a clinical threat to the general population worldwide. Among people infected with the novel coronavirus (2019-nCoV), the intensive management of the critically ill patients in intensive care unit (ICU) needs substantial medical resource. In the present article, we have summarized the promising drugs, adjunctive agents, respiratory supportive strategies, as well as circulation management, multiple organ function monitoring and appropriate nutritional strategies for the treatment of COVID-19 in the ICU based on the previous experience of treating other viral infections and influenza. These treatments are referable before the vaccine and specific drugs are available for COVID-19.
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http://dx.doi.org/10.1186/s13613-020-00661-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7167303PMC
April 2020

Identification of Crucial Genetic Factors, Such as PPARγ, that Regulate the Pathogenesis of Fatty Liver Disease in Dairy Cows Is Imperative for the Sustainable Development of Dairy Industry.

Animals (Basel) 2020 Apr 7;10(4). Epub 2020 Apr 7.

Key Laboratory of Animal Bioengineering and Disease Prevention, College of Animal Science and Technology, Shandong Agricultural University, Shandong, Tai'an 271018, China.

Frequently occurring fatty liver disease in dairy cows during the perinatal period, a typical type of non-alcoholic fatty liver disease (NAFLD), results in worldwide high culling rates of dairy cows (averagely about 25%) after calving. This has been developing into a critical industrial problem throughout the world, because the metabolic disease severely affects the welfare and economic value of dairy cows. Findings about the molecular mechanisms how the fatty liver disease develops would help scientists to discover novel therapeutic targets for NAFLD. Studies have shown that PPARγ participates or regulates the fat deposition in liver by affecting the biological processes of hepatic lipid metabolism, insulin resistance, gluconeogenesis, oxidative stress, endoplasmic reticulum stress and inflammation, which all contribute to fatty liver. This review mainly focuses on crucial regulatory mechanisms of PPARγ regulating lipid deposition in the liver via direct and/or indirect pathways, suggesting that PPARγ might be a potential critical therapeutic target for fatty liver disease, however, it would be of our significant interest to reveal the pathology and pathogenesis of NAFLD by using dairy cows with fatty liver as an animal model. This review will provide a molecular mechanism basis for understanding the pathogenesis of NAFLD.
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http://dx.doi.org/10.3390/ani10040639DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7222768PMC
April 2020

Texture analysis of early cerebral tissue damage in magnetic resonance imaging of patients with lung cancer.

Oncol Lett 2020 Apr 3;19(4):3089-3100. Epub 2020 Mar 3.

Cancer Therapy and Research Center, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, Shandong 250021, P.R. China.

Primary tumors can secrete many cytokines, inducing tissue damage or microstructural changes in distant organs. The purpose of this study was to investigate changes in texture features in the cerebral tissue of patients with lung cancer without brain metastasis. In this study, 50 patients with lung cancers underwent 3.0-T magnetic resonance imaging (MRI) within 2 weeks of being diagnosed with lung cancer. Texture analysis (TA) was carried out in 8 gray matter areas, including bilateral frontal cortices, parietal cortices, occipital cortices and temporal cortices, as well as 2 areas of bilateral frontoparietal white matter. The same procedure was performed for 57 healthy controls. A total of 32 texture parameters were separately compared between the patients and controls in the different cerebral tissue sites. Texture features among patients based on histological type and clinical stage were also compared. Of the 32 texture parameters, 27 showed significant differences between patients with lung cancer and healthy controls. There were significant differences in cerebral tissue, both gray matter and white matter between patients and controls, especially in several wavelet-based parameters. However, there were no significant differences between tissue at homologous sites in bilateral hemispheres, either in patients or controls. TA detected overt changes in the texture features of cerebral tissue in patients with lung cancer without brain metastasis compared with those of healthy controls. TA may be considered as a novel and adjunctive approach to conventional brain MRI to reveal cerebral tissue changes invisible on MRI alone in patients with lung cancer.
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http://dx.doi.org/10.3892/ol.2020.11426DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7074325PMC
April 2020

Neoadjuvant treatments for resectable rectal cancer: A network meta-analysis.

Exp Ther Med 2020 Apr 5;19(4):2604-2614. Epub 2020 Feb 5.

Department of General Surgery, The Affiliated Southeast Hospital of Xiamen University, Zhangzhou, Fujian 363000, P.R. China.

Different neoadjuvant therapy regimens are available for rectal cancer, but the relative effects are controversial. The aim of the present network meta-analysis (NMA) was to estimate the relative efficacy and safety of neoadjuvant therapies for resectable rectal cancer. MEDLINE, EMBASE and Cochrane Central Registry of Controlled Trials were searched for publications dated from 1946 up to June 2018. The present study included randomized clinical trials that compared treatments for resected rectal cancer: Surgery alone, surgery preceded by neoadjuvant radiotherapy (RT), neoadjuvant chemotherapy (CT) or neoadjuvant chemoradiotherapy (CRT). Direct pairwise comparisons and NMA were conducted. A total of 23 randomized controlled trials were included in the present study. RT had an overall survival (OS) benefit when compared with surgery alone [HR (hazard ratio), 0.89; 95% confidence interval (CI), 0.82-0.97; quality of evidence, high]. All three neoadjuvant regimens were associated with lower local recurrence (LR) when compared with surgery alone [RT: odds ratio (OR), 0.44; 95% CI, 0.35-0.65; quality of evidence, high; CRT: OR, 0.34; 95% CI, 0.23-0.56; quality of evidence, low and CT: OR, 0.32; 95% CI, 0.11-1.00; quality of evidence, low]. There were no significant differences in OS and LR between CRT and RT (OS: OR, 1.10); 95% CI, 0.93-1.20; LR: OR, 0.81; 95% CI, 0.61-1.10). Ranking probabilities indicated that CRT was the best strategy for local control, with a surface under the cumulative ranking curve (SUCRA) of 78.78%. Patients treated with RT had improved disease-free survival compared with those treated with surgery alone (HR, 0.82; 95% CI, 0.64-1.00; quality of evidence, low). Neoadjuvant RT or CRT did not significantly improve distant metastases compared with surgery alone (RT: OR, 0.87; 95% CI, 0.69-1.10 and CRT: OR, 0.75; 95% CI, 0.47-1.10). CRT had an improved pathological complete response rate compared with RT (OR, 4.90; 95% CI, 21.80-17.00; quality of evidence, low). No significant difference for the risk of anastomotic leak between each treatment was observed in the NMA. In conclusion, RT decreased the LR and improved OS compared with surgery alone for resected rectal cancer. CRT was the best neoadjuvant therapy analyzed and CT was likely the second best for all outcomes based on SUCRA. However, these findings were limited by overall low quality of evidence.
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http://dx.doi.org/10.3892/etm.2020.8494DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7086160PMC
April 2020

Identification of Whole-Genome Significant Single Nucleotide Polymorphisms in Candidate Genes Associated With Serum Biochemical Traits in Chinese Holstein Cattle.

Front Genet 2020 4;11:163. Epub 2020 Mar 4.

College of Animal Science and Technology, Shandong Key Laboratory of Animal Bioengineering and Disease Prevention, Shandong Agricultural University, Taian, China.

A genome-wide association study (GWAS) was conducted on 23 serum biochemical traits in Chinese Holstein cattle. The experimental population consisted of 399 cattle, each genotyped by a commercial bovine 50K SNP chip, which had 49,663 SNPs. After data cleaning, 41,092 SNPs from 361 Holstein cattle were retained for GWAS. The phenotypes were measured values of serum measurements of these animals that were taken at 11 days after parturition. Two statistical models, a fixed-effect linear regression model (FLM) and a mixed-effect linear model (MLM), were used to estimate the association effects of SNPs. Genome-wide significant and suggestive thresholds were set up to be 1.22E-06 and 2.43E-06, respectively. In the Chinese Holstein population, FLM identified 81 genome-wide significant (0.05/41,092 = 1.22E-06) SNPs associated with 11 serum traits. Among these SNPs, five SNPs (BovineHD0100005950, ARS-BFGL-NGS-115158, BovineHD1500021175, BovineHD0800028900, and BTB-00442438) were also identified by the MLM to have genome-wide suggestive effects on CHE, DBIL, and LDL. Both statistical models pinpointed two SNPs that had significant effects on the Holstein population. The SNP BovineHD0800028900 (located near the gene on chromosome 8) was identified to be significantly associated with serum high- and low-density lipoprotein (HDL and LDL), whereas BovineHD1500021175 (located in 73.4Mb on chromosome 15) was an SNP significantly associated with total bilirubin and direct bilirubin (TBIL and DBIL). Further analyses are needed to identify the causal mutations affecting serum traits and to investigate the correlation of effects for loci associated with fatty liver disease in dairy cattle.
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http://dx.doi.org/10.3389/fgene.2020.00163DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7065260PMC
March 2020

Radiomics analysis of lung CT image for the early detection of metastases in patients with breast cancer: preliminary findings from a retrospective cohort study.

Eur Radiol 2020 Aug 12;30(8):4545-4556. Epub 2020 Mar 12.

Cancer Therapy and Research Center, Shandong Provincial Hospital affiliated to Shandong University, Shandong University, Jinan, People's Republic of China.

Objectives: To investigate whether subtle changes in radiomics features are present in lung CT images prior to the development of CT-detectable lung metastases in patients with breast cancer.

Methods: Thirty-three radiomics features were measured in the metastasis region (MR) and in matched contralateral tissues (non-metastasis region, NMR) of 29 breast cancer patients at the last CT scan, as well as in the corresponding regions of the patients' pre-metastasis scan (pre-MR and pre-NMR). We also compared them with normal lung tissues (control group, CG) from 29 healthy volunteers. Then, 8 patients from the 29 patients with lung metastases and 8 patients who did not develop lung metastases were chosen for further study of the correlation between radiomics parameters and tumor growth.

Results: In the MR vs. NMR and MR vs. CG groups, almost all radiomics features were significantly different. Twenty-six parameters showed significant differences between the pre-MRs and pre-NMRs. Linear fitting demonstrated a significant correlation between 5 features and tumor growth in the metastasis group, but not in the non-metastasis group. Among them, run percentage was the most representative feature. The calculated area under curves (AUCs), based on run percentage for the classification of metastasis and pre-metastasis, were 0.954 and 0.852, respectively.

Conclusions: Radiomics features may allow early detection of lung metastases before they become visually detectable, and the feature run percentage may be a promising image surrogate marker for the microinvasion of tumor cells into the lung tissue.

Key Points: • The significant differences in radiomics features between pre-MR and pre-NMR are critical for the early detection of lung metastases. • Five radiomics features show a correlation with tumor growth. • The radiomics feature run percentage may be a potential imaging biomarker for the early detection of lung metastases.
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http://dx.doi.org/10.1007/s00330-020-06745-5DOI Listing
August 2020

A study of the physicochemical properties of rabbit glycated myofibrillary protein with high solubility in low ionic strength medium.

Int J Biol Macromol 2020 Mar 8;147:241-249. Epub 2020 Jan 8.

College of Food Science, Southwest University, Tiansheng Street, Chongqing 400716, PR China; Chongqing Engineering Research Center of Regional Food, Tiansheng Street, Chongqing 400716, PR China. Electronic address:

To analyze the physicochemical properties of rabbit glycated myofibrillary protein (GMP) with different solubility ((15.10 ± 0.76)%, (35.03 ± 1.01)%, (55.06 ± 1.25)%, and (75.07 ± 1.86)%) in low ionic strength medium, the changes in SDS-PAGE, foaming properties, emulsifying properties, gelling properties, rheological properties, and thermal stability under different pH conditions were determined. The results indicated that GMP with (75.07 ± 1.86)% solubility had better foaming and emulsifying properties than GMP with (35.03 ± 1.01)% solubility at pH 6.0 and pH 7.5 did; however, GMP with (75.07 ± 1.86)% solubility had lower gel strength and showed more cracks in gel networks. Furthermore, the storage modulus (G') of GMP increased as the solubility increased within the range of (15.10 ± 0.76)% to (35.03 ± 1.01)%, but decreased after the solubility reached (55.06 ± 1.25)%. Results also suggested that the glycation process can improve the thermal stability of myofibrillary protein; GMP with (75.07 ± 1.86)% solubility had the highest denaturation temperature. In conclusion, the physicochemical properties of rabbit GMP were affected by changes in solubility in low ionic strength medium; rabbit GMP with high solubility was more resistant to pH changes than native myofibrillary protein.
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http://dx.doi.org/10.1016/j.ijbiomac.2020.01.069DOI Listing
March 2020

Distribution Of Brain Metastasis From Lung Cancer.

Cancer Manag Res 2019 1;11:9331-9338. Epub 2019 Nov 1.

Cancer Therapy and Research Center, Shandong Provincial Hospital Affiliated to Shandong University, Jinan 250021, People's Republic of China.

Purpose: The prognosis of lung cancer with brain metastasis is poor. The purpose of this study was to investigate the distribution of brain metastasis and explore its relationship with pathology and genetic mutations.

Patients And Methods: Between June 2015 and July 2018, 335 patients from Shandong Provincial Hospital affiliated to Shandong University who had been firstly diagnosed with brain metastasis from lung cancer were retrospectively reviewed. All metastatic lesions were detected in the corresponding area using magnetic resonance imaging (MRI).

Results: A total of 2046 metastatic lesions were found. Of the 335 patients, 21.2% (71/335) had a single brain metastasis and 78.8% (264/335) had multiple lesions. The cerebellum (56%; 189/335), right parietal lobe (54%; 182/335), right frontal lobe (47%; 157/335), and left frontal lobe (45%; 152/335) were the regions with the highest incidence of brain metastasis. The different pathological types of lung cancer showed different distribution of brain metastasis. In lung adenocarcinoma, the left frontal lobe (53%; 111/208), right frontal lobe (48%; 100/208) and cerebellum (56%; 116/208) exhibited higher brain metastases, while the cerebellum (61%; 45/74) and the right frontal lobe (46%; 34/74) had the highest incidence of brain metastasis from small-cell carcinoma. For lung squamous cell carcinoma, the cerebellum (70%; 14/20) was the most common site for metastasis. Adenocarcinoma was the most common pathological type in patients regardless of the number of lesions (ie, single or multiple brain metastases). Comparison of 37 cases with epidermal growth factor receptor (EGFR) gene mutation versus 26 cases without mutations showed that there was no correlation between the distribution of brain metastasis and gene mutation.

Conclusion: The different pathological types of lung cancer demonstrate different distribution of brain metastasis. These findings may have significant implications in the diagnosis and treatment of brain metastasis from lung cancer.
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http://dx.doi.org/10.2147/CMAR.S222920DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6830371PMC
November 2019

Primary tumor-secreted VEGF induces vascular hyperpermeability in premetastatic lung via the occludin phosphorylation/ubiquitination pathway.

Mol Carcinog 2019 12 25;58(12):2316-2326. Epub 2019 Sep 25.

Cancer Therapy and Research Center, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, China.

Primary tumor can induce the formation of premetastatic niche. The hyperpermeability of the vessels in the premetastatic niche is the first step in the development of metastasis. However, the cellular and molecular mechanisms of vascular hyperpermeability remain to be elucidated. In this study, 4T1 breast cells were injected into the breasts of mice to establish a tumor model. Our results showed that primary tumors induced hyperpermeability of the vessels in the premetastatic lung. Subsequent studies showed that the level of vascular endothelial growth factor (VEGF) was elevated in the tumor-bearing mice serum and the levels of tight junction (TJ) proteins occludin and ZO-1 were decreased in the premetastatic lung. In vitro studies demonstrated that VEGF increased the permeability of dextran and decreased the levels of occludin and ZO-1 in human umbilical vein endothelial cells. Moreover, the hyperpermeability of vessels and the degradation of occludin was blocked by bevacizumab. Overexpression of occludin alleviated the VEGF-induced hyperpermeability. Further investigations revealed that VEGF-induced occludin phosphorylation at Ser-490 and ubiquitination. Finally, we showed that VEGF accelerated the process of occludin degradation through the ubiquitin-proteasome system. In conclusion, primary tumor-secrete VEGF induce the occludin phosphorylation/ubiquitination and downregulation, resulting in the disruption of TJs and hyperpermeability of vessels in premetastatic lung. The occludin phosphorylation/ubiquitination pathway may be the mechanism of VEGF-induced vascular hyperpermeability in the lung premetastatic niche.
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http://dx.doi.org/10.1002/mc.23120DOI Listing
December 2019

Surface-Functionalized Coating for Lithium-Rich Cathode Material To Achieve Ultra-High Rate and Excellent Cycle Performance.

ACS Nano 2019 Oct 26;13(10):11891-11900. Epub 2019 Sep 26.

Laboratory of Advanced Materials, School of Materials Science and Engineering , Tsinghua University , Haidian District , Beijing 100084 , China.

Although the lithium-rich cathode material LiMnNiCoO, as a promising cathode material, has a high specific capacity, it suffers from capacity decay and discharge voltage decay during cycling. In this work, the specific capacity and discharge voltage of LiMnNiCoO are stabilized by surface-functionalized LiCeO coating. We have conducted LiCeO coating a mild synchronous lithium strategy to protect the electrode surface from electrolyte attack. This optimized LiCeO coating has high Li conductivity and abundant oxygen vacancies. The results demonstrate that 3% LiCeO-coated LiMnNiCoO exhibits the highest capacity retention rate at 1, 2, and 5 C after 200 cycles, which were 84.3%, 85.4%, and 86.3%, respectively. The discharge specific capacity was almost 1.3, 1.4, and 1.4 times that of the pristine electrode. In addition, the 3% LiCeO electrode exhibited the least voltage decay of 0.409, 0.497, and 0.494 V at 1, 2, and 5 C, which was only about half of the pristine electrode. It should not be overlooked that the 3% LiCeO electrode still exhibits a high capacity at high current densities of 1250 mA g (5 C) and 2500 mA g (10 C), and its specific discharge capacities are 190.5 and 160.6 mAh g, respectively. These outstanding electrochemical properties benefit from surface-functionalized LiCeO coatings. To better understand the mechanism of oxygen loss of lithium-rich materials, we propose the lattice oxygen migration path of the LiCeO-coated electrodes during the cycle. Our research provides a possible solution to the poor rate capability and cycle performance of cathode materials through surface-functionalized coatings.
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http://dx.doi.org/10.1021/acsnano.9b05960DOI Listing
October 2019

Plasma PTX3, MCP1 and Ang2 are early biomarkers to evaluate the severity of sepsis and septic shock.

Scand J Immunol 2019 Dec 7;90(6):e12823. Epub 2019 Oct 7.

Department of Critical Care Medicine, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.

Sepsis is associated with significant mortality. Early diagnosis and prognosis of patients with sepsis is still a difficult clinical challenge. In this study, the ability of plasma PTX3 (pentraxin 3), MCP1 (monocyte chemoattractant protein 1) and Ang (angiopoietin)1/2 was investigated to evaluate the severity of sepsis. Blood samples were obtained from 43 patients with sepsis. A total of 33 post-surgery patients with infections and 25 healthy individuals served as controls. The results showed that plasma PTX3, MCP1 and Ang2 significantly increased in patients on the first day of septic shock onset, while sepsis patients had significantly higher Ang2 level, compared with controls. Furthermore, PTX3, MCP1 and Ang2 had high AUROC values in patients with septic shock on the first day of sepsis onset. The findings suggest that PTX3, MCP1 and Ang2 maybe early predictors to evaluate the severity of sepsis and septic shock with the latest Sepsis 3.0 definitions.
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http://dx.doi.org/10.1111/sji.12823DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6900011PMC
December 2019

p120 inhibits LPS/TNFα-induced endothelial Ang2 synthesis and release in an NF-κB independent fashion.

Cytokine 2019 11 26;123:154786. Epub 2019 Jul 26.

Department of Critical Care Medicine, Rui Jin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China. Electronic address:

Adherens junction protein p120 is thought to be crucial for maintaining vascular integrity, which is important in many pathologies and diseases including atherosclerosis, vascular malformations, hemorrhagic stroke, sepsis and others. However, the mechanisms responsible for this is not completely understood. In this study, using an unbiased proteomics approach, followed by other experimental techniques, we identified that in HUVECs p120 overexpression inhibits LPS/TNFα-induced angiopoietin-2 (Ang2) expression, a key switch of endothelial destabilization. Interestingly, p120 overexpression did not inhibit LPS/TNFα-induced expression of adhesion molecules/cytokines including VCAM-1, ICAM-1, E-selectin, MCP-1, IL-8 and IL-6 in our experimental system. Furthermore, this p120-mediated repression of Ang2 is in an NF-κB independent manner, possibly via transcription factor Ets1. Our results demonstrate that p120 influences vascular integrity by secreted signals, providing new insights into the mechanisms of p120-mediated vascular stability.
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http://dx.doi.org/10.1016/j.cyto.2019.154786DOI Listing
November 2019

VE-cadherin regulates migration inhibitory factor synthesis and release.

Inflamm Res 2019 Oct 24;68(10):877-887. Epub 2019 Jul 24.

Department of Critical Care Medicine, Rui Jin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, China.

Objective: Vascular endothelial (VE)-cadherin-mediated adherens junction is critical to maintain endothelial integrity. Besides its role of homophilic intercellular adhesion, VE-cadherin also has a role of outside-in signaling with functional consequences for vascular physiology. However, the nature of these signals remains not completely understood.

Materials And Methods: Human umbilical vein endothelial cells (HUVECs) were used in cell culture experiments. Confluent HUVECs were treated with VE-cadherin function-blocking antibodies BV9 (50 μg/ml) or IgG control. Antibody array was used to screen for cytokine/chemokine in supernatant. For VE-cadherin knockdown, siRNA transfection was used. ELISA, Western blot, and qRT-PCR were used to confirm the expression of screened cytokine/chemokine. To explore the possible mechanisms, Scr phosphorylation was detected and Scr inhibitor PP2 (1 μM) was used. To investigate in vivo relevance of the findings, BV9 and the indicated neutralizing antibodies were injected into mice and then lung vascular leak and inflammation were examined by Evans blue assay and lung tissue H&E, respectively.

Results: Using a non-biased, high-throughout human cytokine/chemokine antibody array, we first found that disruption of VE-cadherin-mediated adhesion by function-blocking antibody BV9 triggered the release of migration inhibitory factor (MIF). This VE-cadherin-mediated release of MIF further confirmed by ELISA with both VE-cadherin blocking antibody and siRNA technique was due to enhanced expression of MIF mRNA, which was mediated by Src kinase activation. In addition, in vivo lung vascular leak induced by VE-cadherin function-blocking antibody was partly alleviated by neutralizing MIF.

Conclusions: VE-cadherin regulates MIF synthesis and release via Src kinase. Our data provide additional evidence to the concept that VE-cadherin transfers intracellular signals to coordinate the state of cell-cell adhesion with gene expression.
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http://dx.doi.org/10.1007/s00011-019-01270-8DOI Listing
October 2019

[Role of sulforaphane in improving negative symptoms and cognitive symptoms of schizophrenia and the underlying mechanism].

Zhong Nan Da Xue Xue Bao Yi Xue Ban 2019 Jun;44(6):701-705

Department of Psychiatry, Second Xiangya Hospital, Central South University, Changsha 410011, China.

The negative symptoms and cognitive symptoms of schizophrenia patients are still clinical problems to be solved. Schizophrenia patients are abnormal in oxidative stress, immune regulation, and anti-histone deacetylase (HDAC), while sulforaphane plays a role in anti-oxidative stress, anti-inflammation, and anti-HDAC. Therefore, the sulforaphane could improve the negative symptoms and cognitive deficits of schizophrenia.
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http://dx.doi.org/10.11817/j.issn.1672-7347.2019.06.014DOI Listing
June 2019

Enantioselective determination of ketamine in dog plasma by chiral liquid chromatography-tandem mass spectrometry.

Biomed Chromatogr 2019 Sep 2;33(9):e4578. Epub 2019 Jun 2.

Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, China.

Ketamine is an N-methyl-d-aspartate receptor antagonist that is usually used clinically as a racemic mixture. Its two enantiomers exhibit different pharmacological activities. To determine whether the enantiomers have different pharmacokinetic profiles, a chiral liquid chromatography-tandem mass spectrometry method was developed and validated for the determination of ketamine enantiomers in dog plasma. The enantiomers of ketamine were extracted from 50 μL of plasma by methyl tert-butyl ether. Adequate chromatographic retention and baseline resolution of the enantiomers were achieved within a runtime of 5 min on a chiral column coated with polysaccharide derivatives, using a gradient mobile phase of acetonitrile and 10 mm ammonium bicarbonate aqueous solution. Ketamine enantiomers were detected by mass spectrometry with multiple reaction monitoring mode using the transitions of m/z 238.3 → 125.9 for the analytes and m/z 237.1 → 194.1 for carbamazepine (internal standard). The method was linear over the concentration range from 0.5 to 500 ng/mL for each enantiomer. The lower limit of quantification (LLOQ) for each enantiomer was 0.5 ng/mL. The intra- and inter-day precision was <7.3% and 8.5% for R- and S-ketamine, respectively. The accuracy was 92.9-110.4% for R-ketamine and 99.8-102.4% for S-ketamine. The method was successfully applied to characterize the stereoselective pharmacokinetic profiles of ketamine in beagle dogs.
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http://dx.doi.org/10.1002/bmc.4578DOI Listing
September 2019

Metformin ameliorates endotoxemia-induced endothelial pro-inflammatory responses via AMPK-dependent mediation of HDAC5 and KLF2.

Biochim Biophys Acta Mol Basis Dis 2019 06 16;1865(6):1701-1712. Epub 2019 Apr 16.

Department of Critical Care Medicine, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, PR China. Electronic address:

Exaggerated endothelial pro-inflammatory response is a hallmark in the early stage of sepsis and contributes to the subsequent tissue injury and organ failure. The anti-inflammatory effects of AMP-activated protein kinase (AMPK) activator metformin in sepsis has been revealed. However, the underlying mechanisms remain not fully understood. In the present study, the potential roles of histone deacetylase 5 (HDAC5) and kruppel-like factor 2 (KLF2) in the effects of metformin on endothelial pro-inflammatory responses were investigated. The results showed that metformin pretreatment increased the phosphorylation of HDAC5 at serine 498, leading to the upregulation of KLF2, and eliminated lipopolysaccharide (LPS) and tumor necrosis factor ⍺ (TNF⍺)-induced upregulation of vascular cell adhesion molecule 1 (VCAM1). Furthermore, the adhesion of HL60 leukocytes to endothelial monolayer was effectively inhibited by metformin. In addition, the in vivo data confirmed that AMPK activation attenuated local and systemic inflammation in endotoxic mice induced by LPS via mediating phosphorylating HDAC5 and restoring KLF2 expression. Our findings revealed that AMPK activation-mediated HDAC5 phosphorylation and KLF2 restoration is, at least partially, responsible to the anti-inflammatory effects of metformin in endotoxemia-induced endothelial cells, which has important implications for the future development of interfering therapies of sepsis.
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http://dx.doi.org/10.1016/j.bbadis.2019.04.009DOI Listing
June 2019

Memory Susceptibility to Retroactive Interference Is Developmentally Regulated by NMDA Receptors.

Cell Rep 2019 02;26(8):2052-2063.e4

Department of Physiology, School of Basic Medicine, Huazhong University of Science and Technology, Wuhan 430030, China; Institute of Brain Research, Collaborative Innovation Center for Brain Science, Huazhong University of Science and Technology, Wuhan 430030, China; Hubei Key Laboratory of Drug Target Research and Pharmacodynamic Evaluation, Huazhong University of Science and Technology, Wuhan 430030, China. Electronic address:

Retroactive interference (RI) occurs when new incoming information impairs an existing memory, which is one of the primary sources of forgetting. Although long-term potentiation (LTP) reversal shows promise as the underlying neural correlate, the key molecules that control the sensitivity of memory circuits to RI are unknown, and the developmental trajectory of RI effects is unclear. Here we found that depotentiation in the hippocampal dentate gyrus (DG) depends on GluN2A-containing NMDA receptors (NMDARs). The susceptibility of LTP to disruption progressively increases with the rise in the GluN2A/GluN2B ratio during development. The vulnerability of hippocampus-dependent memory to interference from post-learning novelty exploration is subject to similar developmental regulation by NMDARs. Both GluN2A overexpression and GluN2B downregulation in the DG promote RI-induced forgetting. Altogether, our results suggest that a switch in GluN2 subunit predominance may confer age-related differences to depotentiation and underlie the developmental decline in memory resistance to RI.
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http://dx.doi.org/10.1016/j.celrep.2019.01.098DOI Listing
February 2019

Soluble vascular endothelial cadherin: a promising marker of critical illness?

Crit Care 2019 02 19;23(1):57. Epub 2019 Feb 19.

Department of Critical Care Medicine, Rui Jin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, China.

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http://dx.doi.org/10.1186/s13054-019-2343-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6381610PMC
February 2019
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