Publications by authors named "Zhou Cheng"

482 Publications

Maternal RNF114-mediated target substrate degradation regulates zygotic genome activation in mouse embryos.

Development 2021 Jun 9. Epub 2021 Jun 9.

State Key Laboratory of Reproductive Medicine, Department of Histology and Embryology, Suzhou Affiliated Hospital of Nanjing Medical University, Suzhou Municipal Hospital, Gusu School, Nanjing Medical University, Nanjing 211166, China.

Zygotic genomic activation (ZGA) is a landmark event in the maternal-to-zygotic transition (MZT), and the regulation of ZGA by maternal factors remains to be elucidated. In this study, the depletion of maternal ring finger protein 114 (RNF114), a ubiquitin E3 ligase, led to 2-cell embryos developmental arrest in mice. RNF114 was proven to play a crucial role in major ZGA using immunofluorescence and transcriptome analysis. To study the underlying mechanism, we performed protein profiling in mature oocytes and found a potential substrate for RNF114, Chromobox 5 (CBX5), whose ubiquitination and degradation was regulated by RNF114. The overexpression of CBX5 prevented embryonic development and impeded major ZGA. Furthermore, TAB1 was abnormally accumulated in mutant 2-cell embryos, which was consistent with the result of in vitro knockdown of Rnf114. Knockdown of Cbx5 or Tab1 in maternal RNF114-depleted embryos partially rescued developmental arrest and the defect of major ZGA. In summary, our study reveals that maternal RNF114 plays a precise role in degrading some important substrates during MZT, the mis-regulation of which may impede the appropriate activation of major ZGA in mouse embryos.
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http://dx.doi.org/10.1242/dev.199426DOI Listing
June 2021

Early Prediction Model of Gestational Hypertension by Multi-Biomarkers Before 20 Weeks Gestation.

Diabetes Metab Syndr Obes 2021 31;14:2441-2451. Epub 2021 May 31.

Department of Laboratory, Guangzhou Women and Children's Medical Centre, Guangzhou Medical University, Guangzhou, 510623, People's Republic of China.

Background: Gestational hypertension (GH), a hypertensive disorder of pregnancy (HDP), is a leading cause of maternal and fetal mortality due to the lack of clarity on its exact etiology and clinically feasible prediction models. This study was performed to discover novel biomarkers before 20 weeks gestation and thereby construct an early GH prediction model.

Methods: This study was designed based on differentially expressed protein screening followed by clinical validation. In the screening phase, a nested case-controlled study was conducted by plasma proteomic analyses using label-free LC-MS/MS and plasma samples from seven pre-GH cases before 20-week gestation and seven age- and gestational week-matched controls. In the validation phase, 10 proteins with differential expression in the screening phase were validated by ELISA or electrochemiluminescence in an independent study consisting of 29 pre-GH cases before 20-week gestation and 29 matched controls.

Results: In the screening phase, 149 proteins were found to be differentially expressed between the two groups and were predominantly involved in complement and coagulation cascades, platelet degranulation and positive regulation of cell motility. Further validation showed that serpin family C member 1 (SERPINC1), serpin family A member 5 (SERPINA5), complement factor H-related protein 5 (CFHR5), clusterin, cytokeratin 18 (CK18) and histidine-rich glycoprotein (HRG) levels were significantly higher in women who later developed GH compared to women with uncomplicated pregnancies (<0.05). Binary logistic regression analysis was used to determine the combination efficacy of models for early prediction of GH. The model with a combination of SERPINC1, CK18 and HRG had a significantly better discriminatory power (AUC = 0.91, 95% CI 0.83-0.98) compared to the models with those proteins alone as independent predictors of GH.

Conclusion: Plasma levels of SERPINC1, SERPINA5, CFHR5, clusterin, CK18 and HRG are potential novel predictive biomarkers of GH, and a prediction model using a combination of SERPINC1, CK18 and HRG has good discriminatory performance for GH before 20 weeks gestation.
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http://dx.doi.org/10.2147/DMSO.S309725DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8178612PMC
May 2021

Separated parabiont reveals the fate and lifespan of peripheral-derived immune cells in normal and ischaemia-induced injured kidneys.

Open Biol 2021 Jun 9;11(6):200340. Epub 2021 Jun 9.

Division of Nephrology, Huazhong University of Science and Technology, 1095 Jiefang Ave, Wuhan, Hubei 430030, People's Republic of China.

Immune cell infiltration plays a key role in acute kidney injury (AKI) to chronic kidney disease (CKD) progression. T lymphocytes, neutrophils, monocytes/macrophages and other immune cells regulate inflammation, tissue remodelling and repair. To determine the kinetics of accumulation of various immune cell populations, we established an animal model combining parabiosis and separation surgery to explore the fate and lifespan of peripheral leucocytes that migrate to the kidney. We found that peripheral T lymphocytes could survive for a long time (more than 14 days), whereas peripheral neutrophils survived for a short time in both healthy and ischaemia-induced damaged kidneys. Nearly half of the peripheral-derived macrophages disappeared after 14 days in normal kidneys, while their existing time in the inflammatory kidneys was prolonged. A fraction of F4/80 macrophages were renewed from the circulating monocyte pool. In addition, we found that after renal ischaemia reperfusion, neutrophils increased significantly in the early phase, and T lymphocytes mainly accumulated in the late stage, whereas macrophages infiltrated throughout AKI-CKD progression and were sustained longer in injured as opposed to normal kidneys. In conclusion, peripheral-derived macrophages, T lymphocytes and neutrophils exhibit different lifespans in the kidney, which may play different roles during AKI-CKD progression.
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http://dx.doi.org/10.1098/rsob.200340DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8187026PMC
June 2021

Individualized Nomogram for Predicting Survival in Patients with Brain Metastases After Stereotactic Radiosurgery Utilizing Driver Gene Mutations and Volumetric Surrogates.

Front Oncol 2021 13;11:659538. Epub 2021 May 13.

Department of Oncology, Guangdong Sanjiu Brain Hospital, Guangzhou, China.

It is well-known that genomic mutational analysis plays a significant role in patients with NSCLC for personalized treatment. Given the increasing use of stereotactic radiosurgery (SRS) for brain metastases (BM), there is an emerging need for more precise assessment of survival outcomes after SRS. Patients with BM and treated by SRS were eligible in this study. The primary endpoint was overall survival (OS). Cox regression models were used to identify independent prognostic factors. A survival predictive nomogram was developed and evaluated by Concordance-index (C-index), area under the curve (AUC), and calibration curve. From January 2016 to December 2019, a total of 356 BM patients were eligible. The median OS was 17.7 months [95% confidence interval (CI) 15.5-19.9] and the actual OS at 1- and 2-years measured 63.2 and 37.6%, respectively. A nomogram for OS was developed by incorporating four independent prognostic factors: Karnofsky Performance Score, cumulative tumor volume, gene mutation status, and serum lactate dehydrogenase. The nomogram was validated in a separate cohort and demonstrated good calibration and good discriminative ability (C-index = 0.780, AUC = 0.784). The prognostic accuracy of the nomogram (0.792) was considerably enhanced when compared with classical prognostic indices, including the Graded Prognostic Assessment (0.708), recursive partitioning analysis (0.587), and the SRS (0.536). Kaplan-Meier curves showed significant differences in OS among the stratified low-, median- and high-risk groups ( < 0.001). In conclusion, we developed and validated an individualized prognostic nomogram by integrating physiological, volumetric, clinical chemistry, and molecular biological surrogates. Although this nomogram should be validated by independent external study, it has a potential to facilitate more precise risk-stratifications to guide personalized treatment for BM.
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http://dx.doi.org/10.3389/fonc.2021.659538DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8158152PMC
May 2021

Research on the dynamic identification method of weak parts in cantilever structures.

Sci Prog 2021 Apr-Jun;104(2):368504211016969

Institute of Advanced Manufacturing and Intelligent Technology, Beijing University of Technology, Beijing, China.

Determining the weak parts of a structure is one of the key issues in the field of machine tool stiffness improvement. However, studies show that overcoming the static deformation with acquisition difficulty is a complex problem in practical structures. This study considers the machine tool cantilever structure, as a cantilever beam and bar structure, where the objective is to propose a weakness index, to identify the weak part, using system reconstruction to extract the measured static deformation data and the fitting data. Stiffness reduction is used to simulate weak parts, while the effectiveness of the method is evaluated, in the case of various weakness values and of different noise levels, using the finite element simulation approach. The validity of the proposed method is illustrated through comparison of the theoretical results to the experimental ones, using the cantilever structure of a test machine tool. The research content provides some means of improving the machining accuracy of machine tools.
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http://dx.doi.org/10.1177/00368504211016969DOI Listing
May 2021

High-sensitivity relative humidity fiber-optic sensor based on an internal-external Fabry-Perot cavity Vernier effect.

Opt Express 2021 Apr;29(8):11854-11868

This study experimentally demonstrates a high-sensitivity fiber-optic relative humidity (RH) sensor based on sensitivity amplification and a reduction mechanism, employing an internal-external Fabry-Perot cavity (IEFPC) Vernier effect and a chitosan film as a Fabry-Perot (FP)-sensing cavity. The proposed sensor is constructed using cascaded FP interferometers comprised of an air cavity formed by a hollow-core fiber (HCF), a chitosan cavity, and an air-chitosan hybrid cavity. The chitosan cavity is fabricated by dipping the HCF into a chitosan solution to form a thin chitosan film. Thus, the thickness of the chitosan film could be controlled precisely based on dipping time and capillary effect. As the optical path lengths of an air-chitosan hybrid cavity and an air cavity are similar, the IEFPC Vernier effect is generated, amplifying the air-chitosan hybrid cavity's low sensitivity to the chitosan cavity's high sensitivity. The experimental results agree with the theoretical analysis, supporting the fact that the sensor's sensitivity is related only to the thickness of the chitosan film. The sensitivity of the sensor reaches up to 7.15 nm/% RH, ranging 40%-92% RH at 25°C. Fabrication of the proposed sensor is cost-effective. The proposed sensor also exhibits superior stability performance, a low-temperature cross-sensitivity of 0.0068% RH/°C, and repeatable fabrication. The proposed IEFPC Vernier effect model functions well for cascaded cavities, which plays a guiding role in the sensitivity improvement of such a structure within a fiber-optic sensing context.
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http://dx.doi.org/10.1364/OE.421060DOI Listing
April 2021

Apatinib-Induced Hand-Foot Skin Reaction in Chinese Patients With Liver Cancer.

Front Oncol 2021 26;11:624369. Epub 2021 Apr 26.

Department of Hepatobiliary Surgery, Wuhan No. 1 Hospital, Wuhan, China.

Apatinib, an anti-tumor drug selectively targeting VEGFR2 (Vascular Endothelia Growth Factor Recpetor-2), has been proven effective in Chinese patients with liver cancer. Generally, treatment with apatinib achieves 16.1% of the overall objective remission rate (ORR) and 55.83% of the disease control rate (DCR) in Chinese patients with liver cancer. However, the prevalence of apatinib-induced hand-foot skin reaction (AI-HFSR) is noticeably high. The incidence of AI-HFSR is about 50.5%, of which Grades 1/2 and 3 are 38.8 and 11.6%, respectively. In addition, potential molecular mechanisms underlying the development of AI-HFSR are poorly understood and urgently needed to be investigated histologically. In this review, we summarize and review the current efficacy of apatinib and the prevalence of AI-HFSR in Chinese patients with liver cancer. Besides, we postulate the potential mechanisms underlying the development of AI-HFSR and discuss the optimal clinical management for this unwanted cutaneous side effect.
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http://dx.doi.org/10.3389/fonc.2021.624369DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8107464PMC
April 2021

NMDAR1-Src-Pannexin1 Signal Pathway in the Trigeminal Ganglion Contributed to Orofacial Ectopic Pain Following Inferior Alveolar Nerve Transection.

Neuroscience 2021 Jul 6;466:77-86. Epub 2021 May 6.

State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, China; Department of Prosthodontics, West China Hospital of Stomatology, Sichuan University, Chengdu, China. Electronic address:

The N-methyl-d-aspartate receptor (NMDAR) is a glutamate-gated receptor channel that plays a role in peripheral neuropathic pain. Src, a protein tyrosine kinase, can regulate the activation of NMDARs in chronic pain conditions. Pannexin 1 (Panx1), a plasma membrane channel, plays an important role in neuropathic pain and functionally interacts with NMDARs in the pathological condition of epilepsy. In this study, the roles of NMDAR1 (NR1), Src, and Panx1 and their interactions in the trigeminal ganglion (TG) in orofacial ectopic pain attributed to inferior alveolar nerve transection (IANX) were investigated. IANX induced mechanical allodynia in the whisker pad with increased expression levels of NR1, Src phosphorylation (p-Src), and Panx1 in the TG. Double immunostaining revealed that NR1, Src, and Panx1 all colocalized with glutamine synthetase (GS) and neuronal nuclei (NeuN), and they overlapped in the TG, suggesting that they might be structurally connected to one another. In addition, trigeminal injection of memantine, PP2, or Panx attenuated IANX-induced mechanical allodynia in the whisker pad. Continuous intraganglionic administration of memantine (an antagonist of NMDAR) decreased IANX-induced upregulated expression of p-Src and Panx1. Similarly, PP2 (an inhibitor of Src) also decreased Panx1 protein expression but had no effect on NR1. In addition, intraganglionic injection of Panx (a blocker of Panx1) decreased NR1 protein expression but did not affect Src. In general, our findings demonstrated that NR1, Src, and Panx1 all contributed to orofacial ectopic pain following IANX and that they composed a signalling pathway in the TG involved in mechanical allodynia.
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http://dx.doi.org/10.1016/j.neuroscience.2021.04.032DOI Listing
July 2021

Isoflurane Suppresses Hippocampal High-frequency Ripples by Differentially Modulating Pyramidal Neurons and Interneurons in Mice.

Anesthesiology 2021 May 5. Epub 2021 May 5.

Background: Isoflurane can induce anterograde amnesia. Hippocampal ripples are high-frequency oscillatory events occurring in the local field potentials of cornu ammonis 1 involved in memory processes. The authors hypothesized that isoflurane suppresses hippocampal ripples at a subanesthetic concentration by modulating the excitability of cornu ammonis 1 neurons.

Methods: The potencies of isoflurane for memory impairment and anesthesia were measured in mice. Hippocampal ripples were measured by placing recording electrodes in the cornu ammonis 1. Effects of isoflurane on the excitability of hippocampal pyramidal neurons and interneurons were measured. A simulation model of ripples based on the firing frequency of hippocampal cornu ammonis 1 neurons was used to validate the effects of isoflurane on neuronal excitability in vitro and on ripples in vivo.

Results: Isoflurane at 0.5%, which did not induce loss of righting reflex, impaired hippocampus-dependent fear memory by 97.4 ± 3.1% (mean ± SD; n = 14; P < 0.001). Isoflurane at 0.5% reduced ripple amplitude (38 ± 13 vs. 42 ± 13 μV; n = 9; P = 0.003), rate (462 ± 66 vs. 538 ± 81 spikes/min; n = 9; P = 0.002) and duration (36 ± 5 vs. 48 ± 9 ms; n = 9; P < 0.001) and increased the interarrival time (78 ± 7 vs. 69 ± 6 ms; n = 9; P < 0.001) and frequency (148.2 ± 3.9 vs. 145.0 ± 2.9 Hz; n = 9; P = 0.001). Isoflurane at the same concentration depressed action potential frequency in fast-spiking interneurons while slightly enhancing action potential frequency in cornu ammonis 1 pyramidal neurons. The simulated effects of isoflurane on hippocampal ripples were comparable to recordings in vivo.

Conclusions: The authors' results suggest that a subanesthetic concentration of isoflurane can suppress hippocampal ripples by differentially modulating the excitability of pyramidal neurons and interneurons, which may contribute to its amnestic action.

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http://dx.doi.org/10.1097/ALN.0000000000003803DOI Listing
May 2021

Serum Ceruloplasmin Depletion is Associated With Magnetic Resonance Evidence of Widespread Accumulation of Brain Iron in Parkinson's Disease.

J Magn Reson Imaging 2021 May 5. Epub 2021 May 5.

Department of Radiology, the Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.

Background: Excessive iron accumulation is one of the main pathogeneses of Parkinson's disease (PD). Ceruloplasmin plays an important role in keeping the iron homoeostasis.

Purpose: To explore the association between serum ceruloplasmin depletion and subcortical iron distribution in PD.

Study Type: Prospective.

Population: One hundred and twenty-one normal controls, 34 PD patients with low serum ceruloplasmin (PD-LC), and 28 patients with normal serum ceruloplasmin (PD-NC).

Sequence: Enhanced susceptibility-weighted angiography (ESWAN) on a 3 T scanner.

Assessment: Quantitative susceptibility mapping was employed to quantify the regional iron content by using a semi-automatic method. Serum ceruloplasmin concentration was measured from peripheral blood sample. Clinical assessments were conducted by a neurologist.

Statistical Tests: General linear model was used to compare the intergroup difference of region iron distribution among groups, and the statistics was adjusted by Bonferroni method (P < 0.01). Partial correlation analysis was used to detect the association between regional iron distribution and serum ceruloplasmin concentration (P < 0.05).

Results: Compared with normal controls, significant iron accumulation in substantia nigra, putamen, and red nucleus was observed in PD-LC, while the only region showing significant iron accumulation was SN in PD-NC. Between PD-NC and PD-LC, the iron accumulation in putamen remained significantly different, which had a negative correlation with serum ceruloplasmin in whole PD patients (r = -0.338, P = 0.008).

Data Conclusion: Nigral iron accumulation characterizes PD patients without significant association with serum ceruloplasmin. Differentially, when PD patients appear with reduced serum ceruloplasmin, more widespread iron accumulation would be expected with additionally involving putamen and red nucleus. All these findings provide insightful evidence for the abnormal iron metabolism behind the ceruloplasmin depletion in PD. EVIDENCE LEVEL: 2 TECHNICAL EFFICACY: 2.
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http://dx.doi.org/10.1002/jmri.27680DOI Listing
May 2021

Nomogram to predict survival outcome of patients with veno-arterial extracorporeal membrane oxygenation after refractory cardiogenic shock.

Postgrad Med 2021 May 20:1-10. Epub 2021 May 20.

Department of Critical Care Medicine, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, The Second School of Clinical Medicine, Southern Medical University, Gaozhou, Guangdong, China.

: This study aims to develop a nomogram model to predict the survival of refractory cardiogenic shock (RCS) patients that received veno-arterial extracorporeal membrane oxygenation (VA-ECMO).: A total of 235 and 209 RCS patients were supported with VA-ECMO from January 2018 to December 2019 in Guangdong Provincial People's Hospital, and from January 2020 to December 2020 in four third-grade and class-A hospitals were a development cohort (DC) and validation cohort (VC), respectively. Finally, 137 and 98 patients were included in the DC and VC. Multivariate logistic regression analysis was used to identify variables, and only these independent risk factors were used to establish the nomogram model. The receiver operating characteristic curve (ROC), calibration plot, decision curve, and clinical impact curves were used to evaluate the nomogram's discriminative ability, predictive accuracy, and clinical application value.: Pre-ECMO cardiogenic arrest (pre-ECA), lactate (Lac), inotropic score (IS), and modified nutrition risk in the critically ill score (mNUTRIC score) were incorporated into the nomogram. This showed good discrimination in the DC, with an area under ROC (AUROC) and a 95% confidence interval (CI) of 0.959 (0.911-0.986). The AUROC (95% CI) of the VC was 0.928 (0.858-0.971). The calibration plots of the DC and VC presented good calibration results. The decision curve and clinical impact curve of the nomogram provided improved benefits for RCS patients.: This study established a prediction nomogram composed of pre-ECA, Lac, IS, and mNUTRIC scores that could help clinicians to predict the survival probability at hospital discharge precisely and rapidly for RCS patients that received VA-ECMO.
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http://dx.doi.org/10.1080/00325481.2021.1925562DOI Listing
May 2021

The complex roles of neutrophils in APAP-induced liver injury.

Cell Prolif 2021 Jun 4;54(6):e13040. Epub 2021 May 4.

The State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.

Acetaminophen (APAP) is a widely applied drug for the alleviation of pain and fever, which is also a dose-depedent toxin. APAP-induced acute liver injury has become one of the primary causes of liver failure which is an increasingly serious threat to human health. Neutrophils are the major immune cells in human serving as the first barrier against the invasion of pathogen. It has been reported that neutrophils patriciate in the occurrence and development of APAP-induced liver injury. However, evolving evidences suggest that neutrophils also contribute to tissue repair and actively orchestrate resolution of inflammation. Here, we addressed the complex roles in APAP-induced liver injury on the basis of brief introduction of neutrophil's activation, recruitment and migration.
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http://dx.doi.org/10.1111/cpr.13040DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8168408PMC
June 2021

Wearable Sensors and Systems for Wound Healing-Related pH and Temperature Detection.

Micromachines (Basel) 2021 Apr 14;12(4). Epub 2021 Apr 14.

Department of Chemical Engineering and Russell Berrie Nanotechnology Institute, Technion-Israel Institute of Technology, Haifa 3200003, Israel.

Wound healing is a complex tissue regeneration process involving many changes in multiple physiological parameters. The pH and temperature of a wound site have long been recognized as important biomarkers for assessing wound healing status. For effective wound management, wound dressings integrated with wearable sensors and systems used for continuous monitoring of pH and temperature have received much attention in recent years. Herein, recent advances in the development of wearable pH and temperature sensors and systems based on different sensing mechanisms for wound status monitoring and treatment are comprehensively summarized. Challenges in the areas of sensing performance, infection identification threshold, large-area 3-dimensional detection, and long-term reliable monitoring in current wearable sensors/systems and emerging solutions are emphasized, providing critical insights into the development of wearable sensors and systems for wound healing monitoring and management.
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http://dx.doi.org/10.3390/mi12040430DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8070747PMC
April 2021

Neutrophil: An emerging player in the occurrence and progression of metabolic associated fatty liver disease.

Int Immunopharmacol 2021 Apr 19;97:107609. Epub 2021 Apr 19.

The State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital of School of Medicine, Zhejiang University, Hangzhou 310000, China; Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Hangzhou 310000, China; National Clinical Research Center for Infectious Diseases, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou 310000, China. Electronic address:

Metabolic-associated fatty liver disease (MAFLD) is a common type of chronic liver disease characterized by excessive lipid accumulation in hepatocytes, but the pathogenesis is still unclear. Neutrophils, the most abundant immune cells in the human body, defend against pathogens and regulate the inflammatory response. Recent studies have indicated that excessive liver infiltration of neutrophils is a significant histological hallmark of MAFLD, and neutrophils and their derived granule proteins participate in different stages of MAFLD, including hepatic steatosis, inflammation, fibrosis, cirrhosis and hepatocellular carcinoma. Hence, in this review, we summarize the role of neutrophils in the occurrence and progression of MAFLD and provide a perspective for the clinical application of neutrophils in MAFLD diagnosis and treatment.
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http://dx.doi.org/10.1016/j.intimp.2021.107609DOI Listing
April 2021

Female Pattern Hair Loss in Female and Male: A Quantitative Trichoscopic Analysis in Chinese Han Patients.

Front Med (Lausanne) 2021 26;8:649392. Epub 2021 Mar 26.

Department of Dermatology, Peking University People's Hospital, Beijing, China.

To investigate the trichoscopic features of female pattern hair loss (FPHL) in Chinese Han patients and analyze the difference between male and female patients with FPHL. Trichoscopic images were taken in four different scalp areas, including right frontal hairline, vertex, right parietal and occipital areas. Hair density, hair shaft diameter, vellus hair ratio and single hair follicle unit ratio were counted manually and analyzed. Seventy-three subjects were enrolled in this study, including 38 patients with FPHL (28 females and 10 males) and 35 normal controls without hair loss. The hair density and hair shaft diameter of FPHL patients reduced in the whole scalp. Vellus hair ratio and single hair follicle unit ratio were both increased in FPHL compared to normal controls. The vertex was the most affected area and the hair shaft diameter showed the most significant difference. Parietal and occipital area were also affected in FPHL. The reduction or increase was correlated with the severity of Ludwig staging. Very few gender differences were detected in male and female FPHL patients. FPHL patients showed decreased hair density and hair shaft diameter, accompanied by increased vellus hair ratio and single hair follicle unit ratio. Parietal and occipital area can be also affected in FPHL, though not as severe as in vertex area. FPHL in male basically has the same characteristic as those in female patients. The main limitation of the study is the small sample size which only enrolled 10 male FPHL patients, in comparison to the female cases. The findings could not be representative of the normal population with the limited sample size.
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http://dx.doi.org/10.3389/fmed.2021.649392DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8032947PMC
March 2021

[Effect of Long-time Postnatal Exposure to Sevoflurane on Causing Attention-deficit/Hyperactivity Disorder in Rats].

Sichuan Da Xue Xue Bao Yi Xue Ban 2021 Mar;52(2):207-215

Department of Anesthesiology, West China Hospital, Sichuan University, Chengdu 610041, China.

Objective: To investigate whether long-term exposure to inhaled sevoflurane, a volatile anesthetic, causes abnormal activities and memory impairment related to attention-deficit/hyperactivity disorder (ADHD) in neonatal rats.

Methods: On postnatal day 5 (P5), Sprague-Dawley rats were randomly assigned to two sevoflurane subgroups and two control subgroups and underwent experimental intervention. The two sevoflurane (SEVO) subgroups were exposed to 3% sevoflurane for 2 h and 4 h respectively, while the two control subgroups were given pure oxygen for the same amount and duration. Behavioral tests, including open-field test (OFT), five-choice serial reaction time task (5-CSRTT), fear-conditioning (FC) and Morris water maze (MWM), were applied to evaluate changes in cognition, memory, anxiety and ADHD-related behavioral changes in the rats in adolescence (-P25) and in adulthood (-P65).

Results: In OFT, the SEVO 2 h and SEVO 4 h subgroups displayed activity level and exploratory behaviors similar to those of the control subgroups on P21 and P61, with no statistically significant difference identified in the data. 5-CSRTT results on P25 and P65 indicated no statistically significant difference between the SEVO subgroups and the control subgroups in regard to ADHD-related abnormal behaviors, including number of immature reaction, rate of correct response and omission rate. In the FC experiment, SEVO 4 h group had a shorter freezing period and longer period of freezing latency ( =0.029) in comparison to the control groups. The results of the MWM test showed that the escape latency period of rats in the SEVO 4 h group was significantly prolonged on the second day and the third day, compared to the control groups ( <0.05). The average swimming speed of SEVO groups did no exhibit any statistically significant difference on P69 or P76. The time the SEVO 4 h group spent in the target quadrant was significantly shorter than that of the control group ( =0.039) and percentage of distance traveled in the target quadrant was significantly reduced compared to that the control group ( =0.048).

Conclusion: The findings suggest that four hours of inhaled sevoflurane exposure in neonate rats may cause memory impairment, but does no increase risks for ADHD-related abnormal activities.
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http://dx.doi.org/10.12182/20210360601DOI Listing
March 2021

[Design of Gas Detection System Based on STM32 Infusion Set].

Zhongguo Yi Liao Qi Xie Za Zhi 2021 Apr;45(2):159-162

Nanchang University, Nanchang, 330031.

Aiming at the low efficiency and low quality detection level of the manual infusion set, a gas detection system for infusion set based on STM32 single-chip microcomputer was designed. The detection system includes hardware system design and software system design. The hardware system is based on the STM32F103 single-chip microcomputer. It mainly designs the gas pressure sensor acquisition circuit and the multi-way solenoid valve control circuit. The software system uses a C ++ real-time operating system to ensure system monitoring's real-time performance and validity. Test data is transmitted to the upper computer and displayed via USB serial communication. The experiment proves that the infusion set gas detection system can perform gas detection on the infusion set. The system has the characteristics of stability and high accuracy. The relative error of the experimental measurement is within ±5%, and the detection efficiency is better than manual detection.
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http://dx.doi.org/10.3969/j.issn.1671-7104.2021.02.008DOI Listing
April 2021

The α2δ-1-NMDAR1 interaction in the trigeminal ganglion contributes to orofacial ectopic pain following inferior alveolar nerve injury.

Brain Res Bull 2021 Jun 31;171:162-171. Epub 2021 Mar 31.

State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, China; Department of Prosthodontics, West China Hospital of Stomatology, Sichuan University, Chengdu, China. Electronic address:

Orofacial ectopic pain can often arise following nerve injury. However, the exact mechanism responsible for orofacial ectopic pain induced by trigeminal nerve injury remains unknown. The α2δ-1 and glutamate N-methyl-d-aspartic acid receptor (NMDAR) interactions have been demonstrated to participate in neuropathic pain regulation in the spinal cord. In this study, a rat model of inferior alveolar nerve transection (IANX) was used to investigate the role of α2δ-1-NMDAR1 interaction in the trigeminal ganglion (TG) in regard to the regulation of orofacial ectopic pain. Western blot (WB) analysis indicated that α2δ-1 and NMDAR1 in the TG were substantially higher in IANX rats than they were in sham/naive rats. Additionally, immunofluorescence (IF) results revealed that α2δ-1 and NMDAR1 were co-expressed and distributed within neurons and activated satellite glial cells in the TG. Co-immunoprecipitation (Co-IP) results indicated that α2δ-1-NMDAR1 complex levels in the TG were higher in IANX rats than they were in sham rats. Furthermore, the results of behavioral tests demonstrated that intra-TG injection of gabapentin (α2δ-1 inhibitory ligand) or memantine hydrochloride (NMDAR antagonist) reversed the decrease in mechanical head-withdrawal threshold (HWT) in IANX rats. Moreover, inhibition of α2δ-1 by intra-TG administration of gabapentin suppressed the upregulation of the NMDAR1 protein, and the inhibition of NMDAR by intra-TG administration of memantine hydrochloride inhibited the increased expression of α2δ-1 protein induced by IANX. In conclusion, the physical and functional interaction between α2δ-1 and NMDAR1 is critical for the development of orofacial ectopic pain, indicating that α2δ-1, NMDAR1, and the α2δ-1-NMDAR1 complex may represent potential targets for the treatment of orofacial ectopic pain.
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http://dx.doi.org/10.1016/j.brainresbull.2021.03.019DOI Listing
June 2021

Sodium leak channel contributes to neuronal sensitization in neuropathic pain.

Prog Neurobiol 2021 Jul 22;202:102041. Epub 2021 Mar 22.

Laboratory of Anesthesia & Critical Care Medicine, Translational Neuroscience Center, West China Hospital of Sichuan University, Chengdu 610041, Sichuan, China; Department of Anesthesiology, West China Hospital of Sichuan University, Chengdu 610041, Sichuan, China. Electronic address:

Neuropathic pain affects up to 10 % of the total population and no specific target is ideal for therapeutic need. The sodium leak channel (NALCN), a non-selective cation channel, mediates the background Na leak conductance and controls neuronal excitability and rhythmic behaviors. Here, we show that increases of NALCN expression and function in dorsal root ganglion (DRG) and dorsal spinal cord contribute to chronic constriction injury (CCI)-induced neuropathic pain in rodents. NALCN current and neuronal excitability in acutely isolated DRG neurons and spinal cord slices of rats were increased after CCI which were decreased to normal levels by NALCN-siRNA. Accordingly, pain-related symptoms were significantly alleviated by NALCN-siRNA-mediated NALCN knockdown and completely prevented by NALCN-shRNA-mediated NALCN knockdown in rats or by conditional NALCN knockout in mice. Our results indicate that increases in NALCN expression and function contribute to CCI-induced neuronal sensitization; therefore, NALCN may be a novel molecular target for control of neuropathic pain.
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http://dx.doi.org/10.1016/j.pneurobio.2021.102041DOI Listing
July 2021

Risk stratification by long non-coding RNAs profiling in COVID-19 patients.

J Cell Mol Med 2021 05 23;25(10):4753-4764. Epub 2021 Mar 23.

Department of Radiation Oncology, Nanfang Hospital, Southern Medical University, Guangzhou, China.

Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has become a global pandemic worldwide. Long non-coding RNAs (lncRNAs) are a subclass of endogenous, non-protein-coding RNA, which lacks an open reading frame and is more than 200 nucleotides in length. However, the functions for lncRNAs in COVID-19 have not been unravelled. The present study aimed at identifying the related lncRNAs based on RNA sequencing of peripheral blood mononuclear cells from patients with SARS-CoV-2 infection as well as health individuals. Overall, 17 severe, 12 non-severe patients and 10 healthy controls were enrolled in this study. Firstly, we reported some altered lncRNAs between severe, non-severe COVID-19 patients and healthy controls. Next, we developed a 7-lncRNA panel with a good differential ability between severe and non-severe COVID-19 patients using least absolute shrinkage and selection operator regression. Finally, we observed that COVID-19 is a heterogeneous disease among which severe COVID-19 patients have two subtypes with similar risk score and immune score based on lncRNA panel using iCluster algorithm. As the roles of lncRNAs in COVID-19 have not yet been fully identified and understood, our analysis should provide valuable resource and information for the future studies.
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http://dx.doi.org/10.1111/jcmm.16444DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8107096PMC
May 2021

Extracorporeal membrane oxygenation for coronavirus disease 2019-associated acute respiratory distress syndrome: Report of two cases and review of the literature.

World J Clin Cases 2021 Mar;9(8):1953-1967

Department of Surgery and Cancer, Imperial College London, London SW10 9NH, United Kingdom.

Background: Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus-2, is a worldwide pandemic. Some COVID-19 patients develop severe acute respiratory distress syndrome and progress to respiratory failure. In such cases, extracorporeal membrane oxygenation (ECMO) treatment is a necessary life-saving procedure.

Case Summary: Two special COVID-19 cases-one full-term pregnant woman and one elderly (72-year-old) man-were treated by veno-venous (VV)-ECMO in the Second People's Hospital of Zhongshan, Zhongshan City, Guangdong Province, China. Both patients had developed refractory hypoxemia shortly after hospital admission, despite conventional support, and were therefore managed by VV-ECMO. Although both experienced multiple ECMO-related complications on top of the COVID-19 disease, their conditions improved gradually. Both patients were weaned successfully from the ECMO therapy. At the time of writing of this report, the woman has recovered completely and been discharged from hospital to home; the man remains on mechanical ventilation, due to respiratory muscle weakness and suspected lung fibrosis. As ECMO itself is associated with various complications, it is very important to understand and treat these complications to achieve optimal outcome.

Conclusion: VV-ECMO can provide sufficient gas exchange for COVID-19 patients with acute respiratory distress syndrome. However, it is crucial to understand and treat ECMO-related complications.
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http://dx.doi.org/10.12998/wjcc.v9.i8.1953DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7953388PMC
March 2021

Hepatic stellate cells promote intrahepatic cholangiocarcinoma progression via NR4A2/osteopontin/Wnt signaling axis.

Oncogene 2021 Apr 19;40(16):2910-2922. Epub 2021 Mar 19.

The Liver Cancer Institute, Zhongshan Hospital and Shanghai Medical School, Fudan University, Key Laboratory for Carcinogenesis and Cancer Invasion, The Chinese Ministry of Education, 180 Fenglin Road, Shanghai, 200032, China.

Intrahepatic cholangiocarcinoma (ICC) is a highly fatal malignancy characterized by a vast amount of intra-tumoral fibroblasts. These fibroblasts are potentially implicated in maintaining the high aggressiveness of ICC, whereas its pro-cancer mechanisms remain scarcely reported. Here, by establishing co-culture models of ICC cells and hepatic stellate cells (HSCs), we identified that HSCs triggered the expression of nuclear receptor family 4 subgroup A member 2 (NR4A2), a transcription factor previously reported as a molecular switch between inflammation and cancer, in ICC cells. Functionally, NR4A2 promotes tumor proliferation, metastatic potentiality and represents an independent prognostic indicator for overall survival in ICC patients. Mechanistically, NR4A2 upregulates osteopontin (OPN) expression through transcriptional activation and thereby augments the activity of Wnt/β-catenin signaling. Intriguingly, in the context of co-culture, vascular endothelial growth factor (VEGF), a previously proved NR4A2 stimulus, not only enhances NR4A2 expression, but also can be blunted by the interference of the NR4A2-OPN axis. Altogether, this study suggests the NR4A2/OPN/Wnt signaling axis to be a pivotal executor of HSC-instigated cancer-promoting roles in ICC, and the NR4A2/OPN/VEGF positive feedback loop may help to reinforce the effect.
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http://dx.doi.org/10.1038/s41388-021-01705-9DOI Listing
April 2021

Effects of sevoflurane anesthesia and abdominal surgery on the systemic metabolome: a prospective observational study.

BMC Anesthesiol 2021 Mar 17;21(1):80. Epub 2021 Mar 17.

Laboratory of Anesthesia & Critical Care Medicine, Translational Neuroscience Center, West China Hospital of Sichuan University, 37# Guoxue Xiang, Chengdu, 610041, Sichuan, China.

Background: Metabolic status can be impacted by general anesthesia and surgery. However, the exact effects of general anesthesia and surgery on systemic metabolome remain unclear, which might contribute to postoperative outcomes.

Methods: Five hundred patients who underwent abdominal surgery were included. General anesthesia was mainly maintained with sevoflurane. The end-tidal sevoflurane concentration (ET) was adjusted to maintain BIS (Bispectral index) value between 40 and 60. The mean ET from 20 min after endotracheal intubation to 2 h after the beginning of surgery was calculated for each patient. The patients were further divided into low ET group (mean - SD) and high ET group (mean + SD) to investigate the possible metabolic changes relevant to the amount of sevoflurane exposure.

Results: The mean ET of the 500 patients was 1.60% ± 0.34%. Patients with low ET (n = 55) and high ET (n = 59) were selected for metabolomic analysis (1.06% ± 0.13% vs. 2.17% ± 0.16%, P < 0.001). Sevoflurane and abdominal surgery disturbed the tricarboxylic acid cycle as identified by increased citrate and cis-aconitate levels and impacted glycometabolism as identified by increased sucrose and D-glucose levels in these 114 patients. Glutamate metabolism was also impacted by sevoflurane and abdominal surgery in all the patients. In the patients with high ET, levels of L-glutamine, pyroglutamic acid, sphinganine and L-selenocysteine after sevoflurane anesthesia and abdominal surgery were significantly higher than those of the patients with low ET, suggesting that these metabolic changes might be relevant to the amount of sevoflurane exposure.

Conclusions: Sevoflurane anesthesia and abdominal surgery can impact principal metabolic pathways in clinical patients including tricarboxylic acid cycle, glycometabolism and glutamate metabolism. This study may provide a resource data for future studies about metabolism relevant to general anaesthesia and surgeries.

Trial Registration: www.chictr.org.cn . identifier: ChiCTR1800014327 .
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http://dx.doi.org/10.1186/s12871-021-01301-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7968205PMC
March 2021

Cancer-associated fibroblast-derived CXCL11 modulates hepatocellular carcinoma cell migration and tumor metastasis through the circUBAP2/miR-4756/IFIT1/3 axis.

Cell Death Dis 2021 03 11;12(3):260. Epub 2021 Mar 11.

Department of Liver Surgery and Transplantation, Liver Cancer Institute and Biomedical Research Center, Zhongshan Hospital, Fudan University, Shanghai, 200032, PR China.

Cancer-associated fibroblasts (CAFs) are commonly acquired activated extracellular matrix (ECM)-producing myofibroblasts, a phenotypes with multiple roles in hepatic fibrogenesis and carcinogenesis via crosstalk with cohabitating stromal/cancer cells. Here, we discovered a mechanism whereby CAF-derived cytokines enhance hepatocellular carcinoma (HCC) progression and metastasis by activating the circRNA-miRNA-mRNA axis in tumor cells. CAFs secreted significantly higher levels of CXCL11 than normal fibroblasts (NFs), and CXCL11 also had comparatively higher expressions in HCC tissues, particularly in metastatic tissues, than para-carcinoma tissues. Both CAF-derived and experimentally introduced CXCL11 promoted HCC cell migration. Likewise, CAFs promoted tumor migration in orthotopic models, as shown by an increased number of tumor nodules, whereas CXCL11 silencing triggered a decrease of it. CXCL11 stimulation upregulated circUBAP2 expression, which was significantly higher in HCC tissues than para-carcinoma tissues. Silencing circUBAP2 reversed the effects of CXCL11 on the expression of IL-1β/IL-17 and HCC cell migration. Further downstream, the IFIT1 and IFIT3 levels were significantly upregulated in HCC cells upon CXCL11 stimulation, but downregulated upon circUBAP2 silencing. IFIT1 or IFIT3 silencing reduced the expression of IL-17 and IL-1β, and attenuated the migration capability of HCC cells. Herein, circUBAP2 counteracted miR-4756-mediated inhibition on IFIT1/3 via sponging miR-4756. miR-4756 inhibition reversed the effects induced by circUBAP2 silencing on the IL-17 and IL-1β levels and HCC cell migration. In orthotopic models, miR-4756 inhibition also reversed the effects on metastatic progression induced by silencing circUBAP2.
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http://dx.doi.org/10.1038/s41419-021-03545-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7952559PMC
March 2021

Homogeneous and heterogeneous catalysts for hydrogenation of CO to methanol under mild conditions.

Chem Soc Rev 2021 Apr 9;50(7):4259-4298. Epub 2021 Mar 9.

Center for Sustainable Catalysis and Engineering, KU Leuven, Celestijnenlaan 200F, 3001 Heverlee, Belgium.

In the context of a carbon neutral economy, catalytic CO hydrogenation to methanol is one crucial technology for CO mitigation providing solutions for manufacturing future fuels, chemicals, and materials. However, most of the presently known catalyst systems are used at temperatures over 220 °C, which limits the theoretical yield of methanol production due to the exothermic nature of this transformation. In this review, we summarize state-of-the-art catalysts, focusing on the rationales behind, for CO hydrogenation to methanol at temperatures lower than 170 °C. Both hydrogenation with homogeneous and heterogeneous catalysts is covered. Typically, additives (alcohols, amines or aminoalcohols) are used to transform CO into intermediates, which can further be reduced into methanol. In the first part, molecular catalysts are discussed, organized into: (1) monofunctional, (2) M/NH bifunctional, and (3) aromatization-dearomatization bifunctional molecular catalysts. In the second part, heterogeneous catalysts are elaborated, organized into: (1) metal/metal or metal/support, (2) active-site/N or active-site/OH bifunctional heterogeneous catalysts, and (3) cooperation of catalysts and additives in a tandem process via crucial intermediates. Although many insights have been gained in this transformation, in particular for molecular catalysts, the mechanisms in the presence of heterogeneous catalysts remain descriptive and insights unclear.
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http://dx.doi.org/10.1039/d0cs01331eDOI Listing
April 2021

GLI1 reduces drug sensitivity by regulating cell cycle through PI3K/AKT/GSK3/CDK pathway in acute myeloid leukemia.

Cell Death Dis 2021 03 3;12(3):231. Epub 2021 Mar 3.

Department of Hematology, The First Affiliated Hospital of Jinan University, Guangzhou, Guangdong, 510630, China.

Acute myeloid leukemia (AML) is a hematological malignancy with high incidence and recurrence rates. Gene expression profiling has revealed that transcriptional overexpression of glioma-associated oncogene 1 (GLI1), a vital gene in the Hedgehog (Hh) signaling pathway, occurs in poor-prognosis AML, and high levels of phosphoinositide-3-kinase, regulatory subunit 1 (PIK3R1) and AKT3 predict shorter overall survival in AML patients. In this study, we discovered that GLI1 overexpression promotes cell proliferation and reduces chemotherapy sensitivity in AML cells while knocking down GLI1 has the opposite effect. Moreover, GLI1 promoted cell cycle progression and led to elevated protein levels of cyclins and cyclin-dependent kinases (CDKs) in AML cells. By luciferase assays and co-immunoprecipitation, we demonstrated that the PI3K/AKT pathway is directly activated by GLI1. GLI1 overexpression significantly accelerates tumor growth and upregulated p-AKT, CDK4, and cyclinD3 in vivo. Notably, the GLI1 inhibitor GANT61 and the CDK4/6 inhibitor PD 0332991 had synergistic effects in promoting Ara-c sensitivity in AML cell lines and patient samples. Collectively, our data demonstrate that GLI1 reduces drug sensitivity by regulating cell cycle through the PI3K/AKT/GSK3/CDK pathway, providing a new perspective for involving GLI1 and CDK4/6 inhibitors in relapsed/refractory (RR) patient treatment.
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http://dx.doi.org/10.1038/s41419-021-03504-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7930050PMC
March 2021

A Global eDelphi Exercise to Identify Core Domains and Domain Items for the Development of a Global Registry of Alopecia Areata Disease Severity and Treatment Safety (GRASS).

JAMA Dermatol 2021 Apr;157(4):1-11

Clinical Medicine, Trinity College Dublin, Dublin, Ireland.

Importance: A recent expert consensus exercise emphasized the importance of developing a global network of patient registries for alopecia areata to redress the paucity of comparable, real-world data regarding the effectiveness and safety of existing and emerging therapies for alopecia areata.

Objective: To generate core domains and domain items for a global network of alopecia areata patient registries.

Evidence Review: Sixty-six participants, representing physicians, patient organizations, scientists, the pharmaceutical industry, and pharmacoeconomic experts, participated in a 3-round eDelphi process, culminating in a face-to-face meeting at the World Congress of Dermatology, Milan, Italy, June 14, 2019.

Findings: Ninety-two core data items, across 25 domains, achieved consensus agreement. Twenty further noncore items were retained to facilitate data harmonization in centers that wish to record them. Broad representation across multiple stakeholder groups was sought; however, the opinion of physicians was overrepresented.

Conclusions And Relevance: This study identifies the domains and domain items required to develop a global network of alopecia areata registries. These domains will facilitate a standardized approach that will enable the recording of a comprehensive, comparable data set required to oversee the introduction of new therapies and harness real-world evidence from existing therapies at a time when the alopecia areata treatment paradigm is being radically and positively disrupted. Reuse of similar, existing frameworks in atopic dermatitis, produced by the Treatment of Atopic Eczema (TREAT) Registry Taskforce, increases the potential to reuse existing resources, creates opportunities for comparison of data across dermatology subspecialty disease areas, and supports the concept of data harmonization.
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http://dx.doi.org/10.1001/jamadermatol.2020.5839DOI Listing
April 2021

A Case Report of Sedation Strategy for a Patient With Coronavirus Disease 2019 Supported by Extracorporeal Membrane Oxygenation After Cesarean Section.

Heart Surg Forum 2021 01 14;24(1):E019-E021. Epub 2021 Jan 14.

Department of Anesthesiology, Zhongshan City People's Hospital, Zhongshan, China.

Pneumonia caused by coronavirus disease 2019 (COVID-19) is a highly contagious disease. Unfortunately, research on extracorporeal membrane oxygenation (ECMO) assisted treatments for patients with COVID-19 infection is limited. In this case study, a patient who was in late pregnancy (35+2 weeks of pregnancy) and suffering from severe COVID-19 was extremely irritable during ECMO-assisted treatment after she underwent a cesarean section. Her Richmond Agitation Sedation Scale (RASS) score reached +3. Nevertheless, the patient successfully was treated with a continuous single/combined application of propofol, midazolam, dexmedetomidine, hibernation mixture, and other drugs for several days (maintaining RASS -2 to -4) and provided with anti-infection, mechanical ventilation, nutritional support, fluid balance under hemodynamic monitoring, liver support, and other organ function support treatments. ECMO-assisted sedation strategy for patients was introduced and discussed in this case to provide a certain reference for the clinical diagnosis and treatment of such patients.
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http://dx.doi.org/10.1532/hsf.3459DOI Listing
January 2021

Construction and validation of an N6-methyladenosine-associated prognostic signature in hepatocellular carcinoma.

Oncol Lett 2021 Mar 21;21(3):221. Epub 2021 Jan 21.

Department of Hepatobiliary Surgery, Wuhan No. 1 Hospital, Wuhan, Hubei 430022, P.R. China.

Hepatocellular carcinoma (HCC) is among the most common types of cancer that threat the public health worldwide. N6-methyladenosine (m6A) RNA methylation is associated with cancer initiation and progression, and is dynamically regulated by m6A RNA methylation-associated genes. However, little is known about the expression status and the prognostic value of m6A-associated genes in HCC. The present study aimed to identify the expression profiling pattern and clinical significance of m6A-associated genes in HCC. Consensus clustering analysis was performed to identify the clusters of HCC with different clinical outcomes. A prognostic signature built by the least absolute shrinkage and selection operator Cox regression model was utilized to discover subtypes associated with different clinical outcomes of patients with HCC in the discovery cohort from The Cancer Genome Atlas. The differences between subgroups were characterized in terms of epigenetic dysregulation and somatic mutation frequencies. The International Cancer Genome Consortium cohort and two independent cohorts from the meta-Gene Expression Omnibus database were used for external validation. Most of the m6A-associated genes were upregulated and involved in the prognosis and malignancy of HCC. A four-gene prognostic signature revealed two HCC subtypes (namely, high- and low-risk group) that was associated with different clinical outcomes. Patients in the high-risk group were accompanied with increased epigenetic silencing and significant mutations in TP53 and FLG, while ALB was frequently mutated in the low-risk group. In conclusion, an m6A-based signature was constructed to predict the prognosis of patients with HCC, which may provide a tool for reliable prognosis assessment for clinicians, and aid clinical treatment decision-making.
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http://dx.doi.org/10.3892/ol.2021.12482DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7859476PMC
March 2021

SL18r Induces Tomato Resistance Against , Involving Activation of Long Non-coding RNA, MSTRG18363, to Decoy miR1918.

Front Plant Sci 2020 3;11:634819. Epub 2021 Feb 3.

Institute of Horticulture, Anhui Academy of Agricultural Sciences, Hefei, China.

Mounting evidence has indicated that beneficial rhizobacteria can suppress foliar pathogen invasion via elicitation of induced systemic resistance (ISR). However, it remains elusive whether long non-coding RNAs (lncRNAs) are involved in the mediation of the rhizobacteria-primed ISR processes in plants. Herein, we demonstrated the ability of the rhizobacterial strain SL18r to trigger ISR in tomato plants against the foliar pathogen . Comparative transcriptome analysis was conducted to screen differentially expressed lncRNAs (DELs) between the non-inoculated and SL18r-inoculated plants. Among these DELs, four variants of MSTRG18363 possessed conserved binding sites for miR1918, which negatively regulates immune systems in tomato plants. The expression of MSTRG18363 in tomato leaves was significantly induced by SL18r inoculation. The transcription of MSTRG18363 was negatively correlated with the expression of miR1918, but displayed a positive correlation with the transcription of the RING-H2 finger gene (a target gene of miR1918). Moreover, MSTRG18363-overexpressing plants exhibited the enhanced disease resistance, reduction of miR1918 transcripts, and marked increases of expression. However, the SL18r-induced disease resistance was largely impaired in the MSTRG18363-silenced plants. VIGS-mediated silencing also greatly weakened the SL18r-induced disease resistance. Collectively, our results suggested that induction of MSTRG18363 expression in tomato plants by SL18r was conducive to promoting the decoy of miR1918 and regulating the expression of , thereby provoking the ISR responses against foliar pathogen infection.
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http://dx.doi.org/10.3389/fpls.2020.634819DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7887324PMC
February 2021