Publications by authors named "Yu Xue"

604 Publications

A COVID-19 Outbreak Emerging in a Food Processing Company - Harbin City, Heilongjiang Province, China, January-February 2021.

China CDC Wkly 2021 Aug;3(32):681-687

National Institute for Radiological Protection, Chinese Center for Disease Control and Prevention, Beijing, China.

The coronavirus disease 2019 (COVID-19) epidemic in China had been effectively controlled for several months, but as the ambient temperature dropped, large gathering-initiated epidemics occurred in northern China, including Hebei, Liaoning, and Jilin provinces.



A sudden epidemic emerged in Wangkui County, Suihua City, Heilongjiang Province, on January 9, 2021. An asymptomatically-infected resident of Harbin City returned from Suihua and triggered a large-scale outbreak in the Zhengda Food Processing Company in Harbin, Heilongjiang. The epidemic was associated with widespread community transmission inside and outside the company, eventually leading to 260 persons being infected (87.8% of 296 patients in Harbin).



This study demonstrates the importance of screening for infections in the COVID-19 prevention and control system, shares experiences identifying and managing asymptomatic infections, and recommends food processing enterprises like the Zhengda Company to improve preventative measures. Our evidence-based epidemiological analyses provide methods for finding high-risk settings and evaluating epidemic situations when many asymptomatic patients are identified in a short period of time.
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http://dx.doi.org/10.46234/ccdcw2021.153DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8393005PMC
August 2021

Electrochemical Immunosensor for Cardiac Troponin I Detection Based on Covalent Organic Framework and Enzyme-Catalyzed Signal Amplification.

Anal Chem 2021 10 30;93(40):13572-13579. Epub 2021 Sep 30.

State Key Laboratory of Electroanalytical Chemistry, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun, Jilin 130022, China.

Herein, a highly sensitive electrochemical immunosensor was presented for the cardiac troponin I (cTnI) determination using a multifunctional covalent organic framework-based nanocomposite (HRP-Ab2-Au-COF) as the signal amplification probe. The spherical COF with a large surface area was synthesized in a short time by a simple solution-based method at room temperature. The good biocompatibility, low toxicity, and high stability in water of the COF guarantee its application in biosensing. Besides, its high porosity makes it an excellent carrier for loading abundant horseradish peroxidase (HRP). The modified gold nanoparticles on the surface of COF not only provide a load platform for secondary antibody (Ab2) but also improve the conductivity of COF. Under the synergistic effect of the hydrogen peroxide (HO) and HRP, hydroquinone (HQ) in the solution is catalytically oxidized to benzoquinone (BQ), which is then reduced on the electrode surface to generate the electrochemical signal. The designed probes not only show the specific recognition behavior of Ab2 to cTnI but also improve the sensitivity of the biosensing system due to the signal amplification caused by the excellent enzyme catalytic performance of HRP. Based on the HO-HRP-HQ signal amplification system, the biosensor for cTnI was fabricated and exhibited a linear response as a function of logarithmic cTnI concentration ranging from 5 pg/mL to 10 ng/mL, and the detection limit was 1.7 pg/mL. Moreover, the biosensor exhibited excellent recovery and reproducibility in the actual sample testing. This work provided a simple approach to determine cTnI quantitatively in practical samples and broadened the utilization scope of the COF-based nanocomposite in the electrochemical immunosensor.
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http://dx.doi.org/10.1021/acs.analchem.1c02636DOI Listing
October 2021

CPLM 4.0: an updated database with rich annotations for protein lysine modifications.

Nucleic Acids Res 2021 Sep 28. Epub 2021 Sep 28.

MOE Key Laboratory of Molecular Biophysics, Hubei Bioinformatics and Molecular Imaging Key Laboratory, Center for Artificial Intelligence Biology, College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan, Hubei 430074, China.

Here, we reported the compendium of protein lysine modifications (CPLM 4.0, http://cplm.biocuckoo.cn/), a data resource for various post-translational modifications (PTMs) specifically occurred at the side-chain amino group of lysine residues in proteins. From the literature and public databases, we collected 450 378 protein lysine modification (PLM) events, and combined them with the existing data of our previously developed protein lysine modification database (PLMD 3.0). In total, CPLM 4.0 contained 592 606 experimentally identified modification events on 463 156 unique lysine residues of 105 673 proteins for up to 29 types of PLMs across 219 species. Furthermore, we carefully annotated the data using the knowledge from 102 additional resources that covered 13 aspects, including variation and mutation, disease-associated information, protein-protein interaction, protein functional annotation, DNA & RNA element, protein structure, chemical-target relation, mRNA expression, protein expression/proteomics, subcellular localization, biological pathway annotation, functional domain annotation, and physicochemical property. Compared to PLMD 3.0 and other existing resources, CPLM 4.0 achieved a >2-fold increase in collection of PLM events, with a data volume of ∼45GB. We anticipate that CPLM 4.0 can serve as a more useful database for further study of PLMs.
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http://dx.doi.org/10.1093/nar/gkab849DOI Listing
September 2021

Efficacy of sentinel lymph node mapping in endometrial cancer with low- or high-intermediate risk.

J Surg Oncol 2021 Sep 27. Epub 2021 Sep 27.

Department of Gynecology, Obstetrics and Gynecology Hospital, Fudan University, Shanghai, China.

Background And Objectives: This study was aimed to evaluate the efficacy of sentinel lymph node (SLN) mapping using indocyanine green (ICG) in Chinese women with endometrial cancer (EC).

Methods: Consecutive EC patients undergoing SLN mapping at Obstetrics and Gynecology Hospital of Fudan University were retrospectively reviewed. Overall and bilateral SLN detection rates and SLN locations were presented. Sensitivity, negative predictive value (NPV), and agreement rate were calculated and were compared between patients with low-intermediate (LIR) or high-intermediate risk (HIR).

Results: There were 454 patients screened, with SLN mapping with ICG performed in 428 patients and systematic lymphadenectomy performed in 159 patients. Overall and bilateral SLN detection rates were 96.50% and 82.71%, respectively. The sensitivity of SLN mapping was 80.00%, and the NPV was 97.76%. SLNs were most commonly located in obturator and external iliac regions. Efficacy of SLN mapping was higher in LIR patients than in HIR patients, with sensitivities of 100.00% and 75.00% (p > 0.05), NPVs of 100.00% and 90.00% (p = 0.002), and agreement rates of 100.00% and 92.31% (p = 0.007), respectively.

Conclusion: SLN mapping with ICG had acceptable diagnostic efficacy in Chinese women with EC, but may cause more missed diagnoses in patients with HIR due to relatively low NPV and agreement rate.
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http://dx.doi.org/10.1002/jso.26694DOI Listing
September 2021

Comparative Efficacy of Haizao Yuhu Decoction Composed of Different Varieties of in Goiter Rats.

Evid Based Complement Alternat Med 2021 15;2021:4343239. Epub 2021 Sep 15.

Beijing University of Chinese Medicine, Beijing 100029, China.

In traditional Chinese medicine, and are one pair of the "18 incompatible medicaments," which in theory cannot be used together. However, since ancient times, many reports have described using compounds containing both and to treat diseases. Haizao Yuhu Decoction (HYD), which contains both ingredients, is mainly used to treat goiter. Chinese Pharmacopoeia officially recorded three varieties of : , , and . These three varieties have certain differences in chemical composition and pharmacological effects. The purpose of the present study was to investigate whether the HYD containing different varieties of and had different therapeutic effects in rats with goiter and to elucidate the underlying mechanism of any difference. In this study, propylthiouracil (PTU) was used to replicate the goiter model, then HYDs containing different varieties of were used for treatment for four weeks, and then the relevant indicators were tested. The results demonstrated that HYD had antigoiter effects, alleviated the pathological changes in the thyroid tissue, and restored the abnormal serum levels of hormones related to thyroid function induced by PTU. HYD containing had the best therapeutic effect in rats with PTU-induced goiter. The antigoiter effect of HYD may function through the hypothalamic-pituitary-thyroid (HPT) axis, inhibit the expression of the Tg and NIS genes, and regulate the synthesis of thyroid hormones, thereby reducing the excessive stimulation of TSH in thyroid cells. In addition, HYD also prevented goiter by promoting thyroid cell apoptosis and inhibiting the ERK/RSK1 pathway of cell proliferation. In conclusion, three types of HYD had different therapeutic effects in rats with goiter, which might be caused by the compatibility of different varieties of and .
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http://dx.doi.org/10.1155/2021/4343239DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8460382PMC
September 2021

The efficiency of a combined injection technique for sentinel lymph node mapping in intermediate-high-risk endometrial cancer.

J Surg Oncol 2021 Sep 8. Epub 2021 Sep 8.

Department of Obstetrics and Gynecology, Obstetrics and Gynecology Hospital, Fudan University, Shanghai, China.

Background And Objectives: Sentinel lymph node (SLN) mapping was considered for treating endometrial cancer (EC) which was apparent confined to the uterus. Nevertheless, intermediate-high-risk EC patients have super high risk to undergo isolated para-aortic lymph node metastases comparing with low-risk patients. Therefore, this investigation aimed to compare the efficacy of two SLN methods in detecting para-aortic lymph node metastases.

Methods: According to SLN mapping injection methods, intermediate-high-risk EC patients who received both SLN mapping and systematic lymphadenectomy were divided into the combined group (fundal and cervical injections) and the cervical group (cervical injection only).

Results: The para-aortic SLN detection rate in the combined group (40.4%) was higher than that in the cervical group (4.4%) with p < 0.001. While the differences concerning the sensitivity, false-negative rate, and negative predictive value between the two groups were not significant. The survival outcomes of patients were comparable between the two groups.

Conclusion: Our data showcased that the combined (fundal and cervical) injection had a higher detection rate of para-aortic SLNs than cervical injection only. The efficiency of SLN mapping and the survival outcomes were not significantly different between the two groups. Further investigations are warranted to assess the value of combined injection regarding SLN technique.
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http://dx.doi.org/10.1002/jso.26666DOI Listing
September 2021

Tailored Luminescence Output of Bi-Doped BaGaO Phosphors with the Assistance of the Introduction of Sr Ions as Secondary Cations.

Inorg Chem 2021 Sep 8;60(18):14467-14474. Epub 2021 Sep 8.

College of Materials Science and Engineering, Kunming University of Science and Technology, Kunming 650093, China.

In this work, a tunable luminescence color from yellow to orange of photoluminescence (PL), long persistent luminescence (LPL), and photostimulated luminescence (PSL) is successfully achieved in BaGaO:Bi phosphors with the introduction of Sr ions as secondary cations. It is confirmed that broad-band emissions located at 500 and 600 nm originate from the occupation of Bi ions at different lattice sites in the BaGaO host matrix. The replacement of Sr for Ba ions makes the emission red-shift from 600 to 650 nm; moreover, two additional emissions appeare at 743 and 810 nm due to the occupational preference of Bi ions at Ga sites. Furthermore, the doped Sr ions promote the reconstruction of the trapping centers, which conduces to the fundamental improvement of the optical storage capacity behavior of Bi-doped phosphors. Our results clarify the dependence of the luminescence performance on the crystal sites of Bi ions with fascinating broad-band emissions in the BaGaO:0.01Bi host matrix and will benefit the design and exploration of Bi-doped solid solutions for optical storage applications.
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http://dx.doi.org/10.1021/acs.inorgchem.1c02271DOI Listing
September 2021

Sentinel Lymph Node Mapping and Biopsy for Endometrial Cancer at Early Stage with Laparoscopy.

J Vis Exp 2021 08 19(174). Epub 2021 Aug 19.

Obstetrics and Gynecology Hospital of Fudan University;

Sentinel lymph node (SLN) mapping and biopsy is a promising technique for visualizing and evaluating lymph node status in cancer. This approach has been recommended for low-risk endometrial cancer (EC) patients by authoritative international guidelines, but it has not been performed broadly in China and worldwide. This work aims to describe detailed SLN mapping and biopsy procedures to promote the clinical application. SLN mapping and postoperative pathologic ultrastaging were conducted in a patient with low-risk EC using indocyanine green (ICG) dye to track the SLNs under laparoscopy and resecting them completely for ultrastaging. In conclusion, this protocol describes details of ICG injection, and SLN mapping and biopsy in EC patients based on the experiences gained during clinical practice.
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http://dx.doi.org/10.3791/63044DOI Listing
August 2021

The high expression of miR-31 in lung adenocarcinoma inhibits the malignancy of lung adenocarcinoma tumor stem cells.

Biochem Biophys Rep 2021 Dec 30;28:101122. Epub 2021 Aug 30.

School of Traditional Chinese Medicine, Beijing University of Chinese Medicine, Beijing, China.

Therapies for lung adenocarcinoma (LUAD) are mainly limited by drug resistance, metastasis or recurrence related to cancer stem cells (CSCs) with high proliferation and self-renewing. This research validated that miR-31 was over-expressed in LUAD by the analysis of generous clinical samples data. And the results of clinical data analysis showed that high expression of miR-31 was more common in patients with worse prognosis. The genes differentially expressed in LUAD tissues compared with normal tissues and A549CD133 cells (LUAD CSCs) compared with A549 cells were separately screened from Gene Expression Profiling Interactive Analysis and GEO datasets. The target genes that may play a role in the regulation of lung adenocarcinoma was screened by comparison between the differential genes and the target genes of miR-31. The functional enrichment analysis of GO Biological Processes showed that the expression of target genes related to cell proliferation was increased, while the expression of target genes related to cell invasion and metastasis was decreased in LUAD tissues and A549CD133 cells. The results suggested that miR-31 may have a significant inhibitory effect on the differentiation, invasion, metastasis and adhesion of LUAD CSCs, which was verified and experiments. Knock down of miR-31 accelerated xenograft tumor growth and liver metastasis . Likewise, the carcinogenicity, invasion and metastasis of A549CD133 CSCs were promoted after miR-31 knockdown. The study validated that miR-31 was up regulated in LUAD and its expression may affect the survival time of patients with lung adenocarcinoma, which indicated that miR-31 may have potential value for diagnosis and prognosis of LUAD. However, the inhibitory effect of miR-31 on tumorigenesis, invasion and metastasis of lung adenocarcinoma CSCs suggested its complexity in the regulation of lung adenocarcinoma, which may be related to its extensive regulation of various target genes.
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http://dx.doi.org/10.1016/j.bbrep.2021.101122DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8408630PMC
December 2021

Efficacy of Novel Aminooxyacetic Acid Prodrugs in Colon Cancer Models: Towards Clinical Translation of the Cystathionine β-Synthase Inhibition Concept.

Biomolecules 2021 07 21;11(8). Epub 2021 Jul 21.

Department of Anesthesiology, University of Texas, Medical Branch, Galveston, TX 77555, USA.

Upregulation of hydrogen sulfide (HS) biosynthesis, at least in part related to the upregulation of cystathionine β-synthetase (CBS) in cancer cells, serves as a tumor-promoting factor and has emerged as a possible molecular target for antitumor drug development. To facilitate future clinical translation, we have synthesized a variety of novel CBS-targeting, esterase-cleavable prodrugs based on the structure of the prototypical CBS inhibitor aminooxyacetic acid (AOAA). The pharmacological properties of these compounds were evaluated in cell-free assays with recombinant human CBS protein, the human colon cancer cell line HCT116, and in vivo using various tumor-bearing mice models. The prodrug YD0251 (the isopropyl ester derivative of AOAA) was selected for detailed characterization. YD0251 exhibits improved antiproliferative efficacy in cell culture models when compared to AOAA. It is up to 18 times more potent than AOAA at suppressing HCT116 tumor growth in vivo and is effective when administered to tumor-bearing mice either via subcutaneous injection or oral gavage. Patient-derived xenografts (PDTXs) with higher levels of CBS protein grew significantly larger than tumors with lower levels, and YD0251 treatment inhibited the growth of PDTXs with elevated CBS, whereas it had no significant effect on PDTXs with low CBS protein levels. The toxicity of YD0251 was assessed in mice subjected to subchronic administration of supratherapeutic doses the inhibitor; no significant alteration in circulating markers of organ injury or histopathological alterations were noted, up to 60 mg/kg/day × 5 days. In preparation to a future theranostic concept (to match CBS inhibitor therapy to high-CBS expressors), we identified a potential plasma marker of CBS-expressing tumors. Colon cancer cells produced significant levels of lanthionine, a rare metabolic intermediate of CBS-mediated HS biosynthesis; forced expression of CBS into non-transformed epithelial cells increased lanthionine biogenesis in vitro and in vivo (measured in the urine of tumor-bearing mice). These current results may be useful to facilitate the translation of a CBS inhibition-based antitumor concept into the clinical space.
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http://dx.doi.org/10.3390/biom11081073DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8394431PMC
July 2021

Reproducible X-ray Imaging with a Perovskite Nanocrystal Scintillator Embedded in a Transparent Amorphous Network Structure.

Adv Mater 2021 Oct 21;33(40):e2102529. Epub 2021 Aug 21.

College of Materials Science and Engineering, Key Laboratory of Advanced Materials of Yunnan Province, Kunming University of Science and Technology, Kunming, Yunnan, 650093, China.

Metal halide perovskites are emerging scintillator materials in X-ray detection and imaging. However, the vulnerable structure of perovskites triggers unreliable performance when they are utilized in X-ray detectors under cumulative dose irradiation. Herein, a self-limited growth strategy is proposed to construct CsPbBr nanocrystals that are embedded in a transparent amorphous network structure, featuring X-imaging with excellent resolution (≈16.8 lp mm ), and fast decay time (τ = 27 ns). Interestingly, it is found that the performance degradation of the scintillator, caused by the damage from high-dose X-ray irradiation, can be fully recovered after a facile thermal treatment process. This indicates a superior recycling behavior of the explored perovskites scintillator for practical applications. The recoverability of the as-explored scintillator is attributed to the low atom-migration rate in the amorphous network with high-viscosity (1 × 10  cP). This result highlights the practical settlement of the promising perovskites for long-term, cost-effective scintillator devices.
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http://dx.doi.org/10.1002/adma.202102529DOI Listing
October 2021

Neurolytic Splanchnic Nerve Block and Pain Relief, Survival, and Quality of Life in Unresectable Pancreatic Cancer: A Randomized Controlled Trial.

Anesthesiology 2021 10;135(4):686-698

From the Department of Pain Medicine, The First Affiliated Hospital, China Medical University, Shenyang, China.

Background: Neurolytic splanchnic nerve block is used to manage pancreatic cancer pain. However, its impact on survival and quality of life remains controversial. The authors' primary hypothesis was that pain relief would be better with a nerve block. Secondarily, they hypothesized that analgesic use, survival, and quality of life might be affected.

Methods: This randomized, double-blind, parallel-armed trial was conducted in five Chinese centers. Eligible patients suffering from moderate to severe pain conditions were randomly assigned to receive splanchnic nerve block with either absolute alcohol (neurolysis) or normal saline (control). The primary outcome was pain relief measured on a visual analogue scale. Opioid consumption, survival, quality of life, and adverse effects were also documented. Analgesics were managed using a protocol common to all centers. Patients were followed up for 8 months or until death.

Results: Ninety-six patients (48 for each group) were included in the analysis. Pain relief with neurolysis was greater for the first 3 months (largest at the first month; mean difference, 0.7 [95% CI, 0.3 to 1.0]; adjusted P < 0.001) compared with placebo injection. Opioid consumption with neurolysis was lower for the first 5 months (largest at the first month; mean difference, 95.8 [95% CI, 67.4 to 124.1]; adjusted P < 0.001) compared with placebo injection. There was a significant difference in survival (hazard ratio, 1.56 [95% CI, 1.03 to 2.35]; P = 0.036) between groups. A significant reduction in survival in neurolysis was found for stage IV patients (hazard ratio, 1.94 [95% CI, 1.29 to 2.93]; P = 0.001), but not for stage III patients (hazard ratio, 1.08 [95% CI, 0.59 to 1.97]; P = 0.809). No differences in quality of life were observed.

Conclusions: Neurolytic splanchnic nerve block appears to be an effective option for controlling pain and reducing opioid requirements in patients with unresectable pancreatic cancer.

Editor’s Perspective:
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http://dx.doi.org/10.1097/ALN.0000000000003936DOI Listing
October 2021

Anti-malarial drug dihydroartemisinin downregulates the expression levels of and in liver cancer.

Oncol Lett 2021 Sep 9;22(3):653. Epub 2021 Jul 9.

Department of Pathobiology and Immunology, Hebei University of Chinese Medicine, Shijiazhuang, Hebei 050200, P.R. China.

Liver cancer is the third leading cause of cancer-associated mortality worldwide. By the time liver cancer is diagnosed, it is already in the advanced stage. Therefore, novel therapeutic strategies need to be identified to improve the prognosis of patients with liver cancer. In the present study, the profiles of GSE84402, GSE19665 and GSE121248 were used to screen differentially expressed genes (DEGs). Subsequently, Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses for DEGs were conducted using the Database for Annotation, Visualization and Integrated Discovery. The protein-protein interaction network was established to screen the hub genes associated with liver cancer. Additionally, the expression levels of hub genes were validated using the Gene Expression Profiling Interactive Analysis and Oncomine databases. In addition, the prognostic value of hub genes in patients with liver cancer was analyzed using Kaplan-Meier Plotter. It was demonstrated that 132 and 246 genes were upregulated and downregulated, respectively, in patients with liver cancer. Among these DEGs, 10 hub genes with high connected node values were identified, which were and . CDK1 and CCNB1 had the most connection nodes and the highest score and were therefore, the most significantly expressed. In addition, it was demonstrated that high expression levels of and were associated with poor overall survival time of patients with liver cancer. Dihydroartemisinin (DHA) is a Food and Drug Administration-approved drug, which is derived from the traditional Chinese medicine . DHA inhibits cell proliferation in numerous cancer types, including liver cancer. In our previous study, it was revealed that DHA inhibited the proliferation of HepG2215 cells. In the present study, it was further demonstrated that DHA reduced the expression levels of and in liver cancer. Overall, CDK1 and CCNB1 were the potential therapeutic targets of liver cancer, and DHA reduced the expression levels of CDK1 and CCNB1, and inhibited the proliferation of liver cancer cells.
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http://dx.doi.org/10.3892/ol.2021.12914DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8299009PMC
September 2021

Identification and Splicing Characterization of Novel and Variants Associated With Epidermodysplasia Verruciformis in Three Chinese Families.

Front Genet 2021 27;12:712275. Epub 2021 Jul 27.

McKusick-Zhang Center for Genetic Medicine, State Key Laboratory of Medical Molecular Biology, Institute of Basic Medical Sciences Chinese Academy of Medical Sciences, School of Basic Medicine Peking Union Medical College, Beijing, China.

: Epidermodysplasia verruciformis (EV) is a rare genodermatosis characterized by abnormal susceptibility to human beta papillomavirus infections and a particular propensity to develop non-melanoma skin cancers (NMSCs). The majority of EV cases are caused by biallelic null variants in , , and . This study aimed to identify disease-causing variants in three Chinese families with EV and to elucidate their molecular pathogenesis. : Genomic DNA from the probands of three EV families was analyzed by whole-exome sequencing (WES). cDNA sequencing was performed to investigate abnormal splicing of the variants. Quantitative RT-PCR (qRT-PCR) was conducted to quantify the mRNA expression of mutant and . : Whole-exome sequencing identified two novel homozygous variants (c.2278-2A > G in and c.559G > A in ) in families 1 and 2, respectively. In family 3, WES revealed a recurrent and a novel compound heterozygous variant, c.559G > A and c.1389G > A, in . The c.2278-2A > G variant led to the skipping of exon 19 and resulted in premature termination at codon 776. Subsequent qRT-PCR revealed that the aberrantly spliced transcript was partly degraded. Notably, the c.559G > A variant created a novel acceptor splice site at c.561 and yielded three different aberrant transcripts. qRT-PCR revealed that most of the mutant transcripts were degraded nonsense-mediated mRNA decay (NMD). : We identified three novel disease-causing variants in or in three Chinese families with EV. The EV phenotypes of the three patients were due to a reduction in TMC6 or TMC8. Our findings expand the genetic causes of EV in the Chinese population.
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http://dx.doi.org/10.3389/fgene.2021.712275DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8353250PMC
July 2021

Carbohydrate Antigen 125 Is a Biomarker of the Severity and Prognosis of Pulmonary Hypertension.

Front Cardiovasc Med 2021 20;8:699904. Epub 2021 Jul 20.

Center for Pulmonary Vascular Diseases, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.

Emerging evidence has showed that serum carbohydrate antigen 125 (CA 125) levels are associated with the severity and prognosis of heart failure. However, its role in pulmonary hypertension remains unclear. This study aimed to investigate the clinical, echocardiographic, hemodynamic, and prognostic associations of CA 125 in pulmonary hypertension. We conducted a retrospective cohort study of all idiopathic pulmonary arterial hypertension and chronic thromboembolic pulmonary hypertension patients receiving CA 125 measurement in Fuwai Hospital (January 1, 2014-December 31, 2018). The primary end-point was cumulative 1-year clinical worsening-free survival rate. Linear regression was performed to assess the association between CA 125 and clinical, echocardiographic, and hemodynamic parameters. Cox proportional hazards models were used to assess the association between CA 125 and clinical worsening events. Receiver operating characteristic (ROC) curve analysis was performed to determine the predictive performance of CA 125. A total of 231 patients were included. After adjustment, CA 125 still positively correlated with World Health Organization functional class, NT-proBNP, right ventricular end-diastolic diameter, pericardial effusion, mean right atrial pressure and pulmonary arterial wedge pressure; negatively correlated with 6-min walk distance, left ventricular end-diastolic diameter, mixed venous oxygen saturation, and cardiac index. After adjustment, CA 125 > 35 U/ml was associated with over 2 folds increased risk of 1-year clinical worsening. Further, ROC analysis showed that CA 125 provided additional predictive value in addition to the established pulmonary hypertension biomarker NT-proBNP. CA 125 was associated with functional status, echocardiography, hemodynamics and prognosis of pulmonary hypertension.
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http://dx.doi.org/10.3389/fcvm.2021.699904DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8330972PMC
July 2021

Editorial: Computational Resources for Understanding Biomacromolecular Covalent Modifications.

Front Cell Dev Biol 2021 14;9:728127. Epub 2021 Jul 14.

Department of Electrical Engineer and Computer Science and Christopher S. Bond Life Science Center, University of Missouri, Columbia, MO, United States.

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http://dx.doi.org/10.3389/fcell.2021.728127DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8318359PMC
July 2021

Multi-omic profiling of plasma reveals molecular alterations in children with COVID-19.

Theranostics 2021 6;11(16):8008-8026. Epub 2021 Jul 6.

Guangzhou Institute of Pediatrics, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou, 510120, China.

Children usually develop less severe symptoms responding to Coronavirus Disease 2019 (COVID-19) than adults. However, little is known about the molecular alterations and pathogenesis of COVID-19 in children. We conducted plasma proteomic and metabolomic profilings of the blood samples of a cohort containing 18 COVID-19-children with mild symptoms and 12 healthy children, which were enrolled from hospital admissions and outpatients, respectively. Statistical analyses were performed to identify molecules specifically altered in COVID-19-children. We also developed a machine learning-based pipeline named inference of biomolecular combinations with minimal bias (iBM) to prioritize proteins and metabolites strongly altered in COVID-19-children, and experimentally validated the predictions. By comparing to the multi-omic data in adults, we identified 44 proteins and 249 metabolites differentially altered in COVID-19-children against healthy children or COVID-19-adults. Further analyses demonstrated that both deteriorative immune response/inflammation processes and protective antioxidant or anti-inflammatory processes were markedly induced in COVID-19-children. Using iBM, we prioritized two combinations that contained 5 proteins and 5 metabolites, respectively, each exhibiting a total area under curve (AUC) value of 100% to accurately distinguish COVID-19-children from healthy children or COVID-19-adults. Further experiments validated that all the 5 proteins were up-regulated upon coronavirus infection. Interestingly, we found that the prioritized metabolites inhibited the expression of pro-inflammatory factors, and two of them, methylmalonic acid (MMA) and mannitol, also suppressed coronaviral replication, implying a protective role of these metabolites in COVID-19-children. The finding of a strong antagonism of deteriorative and protective effects provided new insights on the mechanism and pathogenesis of COVID-19 in children that mostly underwent mild symptoms. The identified metabolites strongly altered in COVID-19-children could serve as potential therapeutic agents of COVID-19.
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http://dx.doi.org/10.7150/thno.61832DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8315065PMC
August 2021

Label-free immunosensor for cardiac troponin I detection based on aggregation-induced electrochemiluminescence of a distyrylarylene derivative.

Biosens Bioelectron 2021 Nov 24;192:113532. Epub 2021 Jul 24.

State Key Laboratory of Electroanalytical Chemistry, Changchun Institute of Applied Chemistry, Changchun, Jilin, 130022, PR China; University of Science and Technology of China, Hefei, Anhui, 230026, PR China. Electronic address:

Herein, the aggregation-induced electrochemiluminescence (AIECL) of a distyrylarylene derivative, 4,4'-bis(2,2-diphenylvinyl)-1,1'-biphenyl (DPVBi), was investigated for the first time. This luminophore exhibits significantly enhanced photoluminescence (PL) and electrochemiluminescence (ECL) emission with the increases of water content in organic/water mixtures. This high luminescence efficiency of DPVBi in aggregate state is due to the fact that the aggregates can reduce the energy loss by restricting the intramolecular motions. The ECL behavior of DPVBi in acetonitrile was investigated by ECL transients and so-called "half-scan" technology, where singlet-singlet annihilation ECL was generated under continuous potential switching. The DPVBi nanobulks (DPVBi NBs) were prepared to improve its application in aqueous media, which could be conveniently cast on electrode surface for developing sensing platform due to its good film-forming nature. The constructed heterogeneous AIECL platform can produce reductive-oxidative and oxidative-reductive ECL by using trimethylamine (TEA) and potassium peroxodisulfate (KSO) as coreactant. On the basis of the higher ECL efficiency of DPVBi NBs/TEA system, a label free immunosensor for cardiac troponin I (cTnI) was developed with the assistance of electrodeposited gold nanoparticles, and it showed a wide linear range of 20 ng/mL~100 fg/mL and low detection limit of 43 fg/mL. Moreover, the constructed immunosensor also exhibited good specificity, stability and satisfied performance in practical sample analysis.
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http://dx.doi.org/10.1016/j.bios.2021.113532DOI Listing
November 2021

Cudraxanthone L inhibits gastric cancer by regulating the MAPK signalling and promoting FAS-mediated pathway.

Biomed Pharmacother 2021 Sep 10;141:111876. Epub 2021 Jul 10.

College of Traditional Chinese Medicine, Beijing University of Chinese Medicine, 100029, Beijing, China. Electronic address:

Gastric cancer (GC) is one of the most common malignancies and has the second highest lethal rate in the world; thus, finding new medicines with high potency and low toxicity is urgent. Cudrania tricuspidata (Carr.) Bur. ex Lavallee (Moraceae) is a traditional medicinal herb that is considered to have antitumour efficacy. We extracted and isolated cudraxanthone L (CXL) from Cudrania tricuspidata and evaluated its anti-cancer efficacy. CXL treatment inhibited angiogenesis of chorioallantoic membrane (CAM) and repressed the cell viability of various human cancer cells, indicating it presented the antitumour potential. Among them, CXL presented the best inhibitory effects on MGC803 cells. In addition, the invasion, migration and clonogenicity were significantly repressed, S phase of the cell cycle was arrested, and apoptosis was induced when MGC803 cells were treated with CXL. The results of RNA sequencing, qRT-PCR and western blotting verified that CXL regulated the MAPK signalling pathway and induced apoptosis by FAS-mediated pathway. The in vivo data revealed that CXL arrested tumour growth without toxic effects and upregulated the protein levels in FAS-mediated pathway in MGC803 gastric cancer-bearing mice. In summary, we demonstrate CXL presents impactful anti-GC efficacy by regulating the MAPK signalling pathway and promoting the FAS-mediated pathway.
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http://dx.doi.org/10.1016/j.biopha.2021.111876DOI Listing
September 2021

Insulin signaling regulates longevity through protein phosphorylation in Caenorhabditis elegans.

Nat Commun 2021 07 27;12(1):4568. Epub 2021 Jul 27.

National Institute of Biological Sciences, Beijing, China.

Insulin/IGF-1 Signaling (IIS) is known to constrain longevity by inhibiting the transcription factor FOXO. How phosphorylation mediated by IIS kinases regulates lifespan beyond FOXO remains unclear. Here, we profile IIS-dependent phosphorylation changes in a large-scale quantitative phosphoproteomic analysis of wild-type and three IIS mutant Caenorhabditis elegans strains. We quantify more than 15,000 phosphosites and find that 476 of these are differentially phosphorylated in the long-lived daf-2/insulin receptor mutant. We develop a machine learning-based method to prioritize 25 potential lifespan-related phosphosites. We perform validations to show that AKT-1 pT492 inhibits DAF-16/FOXO and compensates the loss of daf-2 function, that EIF-2α pS49 potently inhibits protein synthesis and daf-2 longevity, and that reduced phosphorylation of multiple germline proteins apparently transmits reduced DAF-2 signaling to the soma. In addition, an analysis of kinases with enriched substrates detects that casein kinase 2 (CK2) subunits negatively regulate lifespan. Our study reveals detailed functional insights into longevity.
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http://dx.doi.org/10.1038/s41467-021-24816-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8316574PMC
July 2021

Epidemiology of Takayasu arteritis in Shanghai: A hospital-based study and systematic review.

Int J Rheum Dis 2021 Oct 27;24(10):1247-1256. Epub 2021 Jul 27.

Department of Renal and Rheumatology, Xinhua Hospital Affiliated To Shanghai JiaoTong University School of Medicine, Shanghai, China.

Background: Takayasu arteritis (TAK) is a rare large vessel vasculitis, and epidemiological data on TAK are lacking in China. Thus, we designed this study to estimate the TAK prevalence and incidence in residential Shanghai, China.

Methods: Data on diagnosed TAK cases aged over 16 years were retrieved from 22 tertiary hospitals in Shanghai through hospital electronic medical record systems between January 1, 2015 and December 31, 2017 to estimate the prevalence and incidence. A systematic literature review based on searches in PubMed, Ovid-Medline, Excerpta Medica Database (EMBASE), Web of Science, and China National Knowledge Infrastructure (CNKI) was performed to summarize TAK distribution across the world.

Results: In total 102 TAK patients, with 64% female, were identified. The point prevalence (2015-2017) was 7.01 (95% CI 5.65-8.37) cases per million, and the mean annual incidence was 2.33 (1.97-3.21) cases per million. The average age of TAK patients was 44 ± 16 years, with the highest prevalence (11.59 [9.23-19.50] cases per million) and incidence (3.55 [0.72 3.74] cases per million) in the 16 to 34 years population. Seventeen reports were included in the system review, showing that the epidemiology of TAK varied greatly across the world. The incidence and prevalence were both relatively higher in Asian countries, with the prevalence ranging 3.3-40 cases per million and annual incidence ranging 0.34-2.4 cases per million.

Conclusions: The prevalence and incidence of TAK in Shanghai was at moderate to high levels among the previous reports. The disease burden varied globally among racial populations.
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http://dx.doi.org/10.1111/1756-185X.14183DOI Listing
October 2021

A Multi-Objective Evolutionary Approach Based on Graph-in-Graph for Neural Architecture Search of Convolutional Neural Networks.

Int J Neural Syst 2021 Sep 24;31(9):2150035. Epub 2021 Jul 24.

Tianjin Key Laboratory of Autonomous Intelligent Technology and System, Tiangong University, Tianjin, P. R. China.

With the development of deep learning, the design of an appropriate network structure becomes fundamental. In recent years, the successful practice of Neural Architecture Search (NAS) has indicated that an automated design of the network structure can efficiently replace the design performed by human experts. Most NAS algorithms make the assumption that the overall structure of the network is linear and focus solely on accuracy to assess the performance of candidate networks. This paper introduces a novel NAS algorithm based on a multi-objective modeling of the network design problem to design accurate Convolutional Neural Networks (CNNs) with a small structure. The proposed algorithm makes use of a graph-based representation of the solutions which enables a high flexibility in the automatic design. Furthermore, the proposed algorithm includes novel ad-hoc crossover and mutation operators. We also propose a mechanism to accelerate the evaluation of the candidate solutions. Experimental results demonstrate that the proposed NAS approach can design accurate neural networks with limited size.
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http://dx.doi.org/10.1142/S0129065721500350DOI Listing
September 2021

[Analysis of related factors of poor prognosis in children with parenteral nutrition-associated cholestasis].

Zhonghua Wei Zhong Bing Ji Jiu Yi Xue 2021 Jun;33(6):731-735

Department of Integrated Traditional Chinese Medicine and Western Medicine, Wuhan Children's Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430016, Hubei, China.

Objective: To explore the related factors affecting the prognosis of children with parenteral nutrition-associated cholestasis (PNAC).

Methods: Twenty children with PNAC admitted to Wuhan Children's Hospital, Tongji Medical College, Huazhong University of Science and Technology from January 2014 to December 2020 were selected as research objects by retrospective study. According to prognosis,children were divided into good (15 cases) and poor prognosis group (5 cases). Clinical data such as general condition, intravenous nutrition duration, related biochemical examination indexes and main treatment methods of children in the two groups were collected. Spearman correlation analysis was used to quantify the correlation between alanine aminotransferase (ALT) and poor prognosis. Univariate analysis was used to analyze the risk factors affecting the prognosis of children with PNAC, and receiver operating characteristic curve (ROC curve) was drawn to evaluate the predictive value of ALT on the prognosis of children.

Results: There were no significant differences in gender, body weight, gestational age, age, feeding mode, duration of intravenous nutrition, direct bilirubin (DBil), aspartate aminotransferase (AST), γ-glutamyltranspeptidase (GGT), total protein (TP), serum albumin (Alb), globulin (GLB), alkaline phosphatase (ALP), platelet count (PLT), white blood cell count (WBC), red blood cell count (RBC), hemoglobin (Hb), lymphocyte count (LYM), urine culture, AST/PLT ratio (APRI) and main treatment methods between the two groups. Total bilirubin (TBil), ALT, neutrophil count (NEU) and monocyte count (MONO) in the good prognosis group were significantly lower than those in the poor prognosis group [TBil (μmol/L): 120.00±48.63 vs. 175.26±29.14, ALT (U/L): 73.25±44.29 vs. 145.30±74.33, NEU (×10/L): 2.55±1.29 vs. 5.08±4.10, MONO (×10/L): 1.23±0.87 vs. 2.13±0.60, all P < 0.05]. Logistic regression analysis showed that ALT was the risk factor affecting the prognosis of children with PNAC, when ALT increased by 1 U/L, the probability of poor prognosis increased by 3.6% [odds ratio (OR) = 1.04, 95% confidence interval (95%CI) was 1.00-1.07, P = 0.04]. Spearman correlation analysis showed that the incidence of poor prognosis was positively correlated with ALT (r = 0.49, P = 0.03). ROC analysis showed that ALT had certain predictive value for the prognosis of children with PNAC [area under ROC cure (AUC) = 0.83, 95%CI was 0.00-1.00, P = 0.03]; when the cut-off value was 121.50 U/L, its sensitivity was 80% and specificity was 93%, suggesting that ALT could be used as the main indicator for clinical prediction of poor prognosis for PNAC.

Conclusions: ALT is an independent risk factor of poor prognosis in children with PNAC.
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http://dx.doi.org/10.3760/cma.j.cn121430-20210322-00416DOI Listing
June 2021

Metformin activates chaperone-mediated autophagy and improves disease pathologies in an Alzheimer disease mouse model.

Protein Cell 2021 Oct 21;12(10):769-787. Epub 2021 Jul 21.

Department of Biochemistry & Research Center of Clinical Pharmacy of The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, 310058, China.

Chaperone-mediated autophagy (CMA) is a lysosome-dependent selective degradation pathway implicated in the pathogenesis of cancer and neurodegenerative diseases. However, the mechanisms that regulate CMA are not fully understood. Here, using unbiased drug screening approaches, we discover Metformin, a drug that is commonly the first medication prescribed for type 2 diabetes, can induce CMA. We delineate the mechanism of CMA induction by Metformin to be via activation of TAK1-IKKα/β signaling that leads to phosphorylation of Ser85 of the key mediator of CMA, Hsc70, and its activation. Notably, we find that amyloid-beta precursor protein (APP) is a CMA substrate and that it binds to Hsc70 in an IKKα/β-dependent manner. The inhibition of CMA-mediated degradation of APP enhances its cytotoxicity. Importantly, we find that in the APP/PS1 mouse model of Alzheimer's disease (AD), activation of CMA by Hsc70 overexpression or Metformin potently reduces the accumulated brain Aβ plaque levels and reverses the molecular and behavioral AD phenotypes. Our study elucidates a novel mechanism of CMA regulation via Metformin-TAK1-IKKα/β-Hsc70 signaling and suggests Metformin as a new activator of CMA for diseases, such as AD, where such therapeutic intervention could be beneficial.
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http://dx.doi.org/10.1007/s13238-021-00858-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8464644PMC
October 2021

Broadband, Enhanced, and Antithermally Quenched Near-Infrared Phosphors via a Cosubstitution Approach.

Inorg Chem 2021 Aug 20;60(15):11616-11625. Epub 2021 Jul 20.

College of Materials Science and Engineering, Kunming University of Science and Technology, Kunming 650093, China.

Wearable biosensing and food safety inspection devices with high thermal stability, high brightness, and broad near-infrared (NIR) phosphor-converted light-emitting diodes (pc-LEDs) could accelerate the next-generation NIR light applications. In this work, NIR LaGdGaGeO:Cr ( = 0 to 1.5) phosphors were successfully fabricated by a high-temperature solid-state method. Here, by doping Gd ions into the La sites in the LaGaGeO matrix, a 7.9-fold increase in the photoluminescence (PL) intensity of the Cr ions, as well as a remarkably broadened full width at half-maximum (FWHM) of the corresponding PL spectra, is achieved. The enhancements in the PL, PLE intensity, and FWHM are attributed to the suppression of the nonradiative transition process of Cr when Gd ions are doped into the host, which can be demonstrated by the decay curves. Moreover, the LaGdGaGeO:Cr phosphor displays an abnormally negative thermal phenomenon that the integral PL intensity reaches 131% of the initial intensity when the ambient temperature increases to 160 °C. Finally, the broadband NIR pc-LED was fabricated based on the as-explored LaGdGaGeO:Cr phosphors combined with a 460 nm chip, and the potential applications for the broadband NIR pc-LEDs were discussed in detail.
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http://dx.doi.org/10.1021/acs.inorgchem.1c01588DOI Listing
August 2021

Bioinformatics Technologies in Autophagy Research.

Adv Exp Med Biol 2021 ;1208:387-453

Key Laboratory of Molecular Biophysics of Ministry of Education, Hubei Bioinformatics and Molecular Imaging Key Laboratory, Center for Artificial Intelligence Biology, College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan, China.

Autophagy is an important and dynamic biological process, and provides an ideal application scenario for bioinformatics to develop new data resources, algorithms, tools and computational or mathematic models for a better understanding of complex regulatory mechanisms in cells. In the past decade, great efforts have been taken on the development of numerous bioinformatics technologies in autophagy research, and a comprehensive summarization of these important studies will provide a timely reference for both biologists and bioinformaticians who are working in the field of autophagy. In this book chapter, we first introduce bioinformatics technologies that allow sequence analysis of autophagy genes. We briefly summarize the mainstream algorithms in sequence alignment for the identification of homologous autophagy genes and emphasize the computational identification of potential orthologs and paralogs, as well as the evolutionary analysis of autophagy gene families. Three methods for the recognition of autophagy-related sequence motifs are introduced: regular expression, position-specific scoring matrix (PSSM) and group-based prediction system (GPS). Second, we carefully summarize recent progress in the analysis of autophagy-related omics data. We discuss how two major types of computational methods, enrichment analysis and network analysis can be used to analyze omics data, including transcriptomics, non-coding RNAomics, epigenomics, proteomics, phosphoproteomics and protein lysine modification (PLM) omics data. Finally, we summarize several important autophagy-related data resources, including both autophagy gene databases and autophagy-related RNA databases. We anticipate that more useful bioinformatics technologies will be developed and play an ever-more-important role in the analysis of autophagy.
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http://dx.doi.org/10.1007/978-981-16-2830-6_18DOI Listing
July 2021

Recurrent Myocardial Infarction and Catecholamine-Induced Cardiomyopathy: A Case Report.

Chin Med Sci J 2021 Jun;36(2):158-160

Department of Anesthesiology, Peking Union Medical College Hospital,Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100730, China.

Pheochromocytomas or paragangliomas are rare and the diagnosis remains a challenge for clinicians. We present a woman suffering from recurrent myocardial infarction and cardiomyopathy, who was finally diagnosed with paraganglioma. Pheochromocytomas or paraganglioma should be considered in the differential diagnosis of a patient with symptoms possibly referring to acute coronary syndrome and cardiomyopathy.
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http://dx.doi.org/10.24920/003768DOI Listing
June 2021

Assessing Empathy in Anesthesia Residents with the Chinese Version of the Consultation and Relational Empathy: A Pilot Standardized Patient Program.

Chin Med Sci J 2021 Jun;36(2):79-84

Department of Anesthesiology, Peking Union Medical College Hospital,Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100730, China.

Objectives To validate the reliability of the Chinese version of the Consultation and Relational Empathy (CARE) in physician-standardized patient (SP) encounter. We also tried to examine the agreement between video-based ratings and in-room ratings, as well as the agreement between the faculty ratings and SP ratings. Methods The CARE was translated into Chinese. Forty-eight anesthesia residents were recruited to make preoperative interview in SP-counter. Performance of each resident was graded by in-room raters, video raters and SP raters. Consistency between different raters was examined. Results The Chinese-CARE measure demonstrated high scale reliability with a Cronbach's alpha value of 0.95 and high consistency in the in-room ratings in intraclass correlation (coefficient=0.888,<0.001). Despite a good consistency in intraclass correlation, video ratings were significantly higher than in-room ratings (39.6±7.1. 24.0±10.0,<0.001), and Wilcoxon signed-rank test indicated that the pass/fail rate was significantly higher based on video ratings than based on in-room ratings (45/48. 22/48, <0.001). SP ratings had a moderate consistency with in-room faculty ratings (coefficient=0.568,<0.001), and there was no significant difference between the pass/fail rates based on the in-room ratings and SP ratings (22/48. 28/48, =0.12). Conclusions The Chinese-CARE measure is reliable in the assessment of empathy during preoperative anesthesia interview. In-room and video ratings are not equivalent, while SP may provide a feasible alternative for the faculty rater in the assessment of communication skills with an appropriate measure.
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http://dx.doi.org/10.24920/003741DOI Listing
June 2021

iCAL: a new pipeline to investigate autophagy selectivity and cancer.

Autophagy 2021 07 28;17(7):1799-1801. Epub 2021 Jun 28.

Key Laboratory of Birth Defects and Related Diseases of Women and Children, Department of Paediatrics, West China Second University Hospital, State Key Laboratory of Biotherapy and Collaborative Innovation Center of Biotherapy, Sichuan University, Chengdu, China.

Macroautophagy/autophagy can selectively degrade misfolded proteins, damaged organelles and other cargoes. It is conceivable that alteration of the degradation processes could disrupt normal cellular signaling and contribute to human diseases such as cancer. To explore the link between aberrant autophagy selectivity and human cancer, we have developed a pipeline called "nference of ancer-ssociated C3-interacting region-containing proteins" (iCAL), which integrates a sequence-based predictor, a model-based computational method, publicly available cancer mutations, and multiple experimental approaches. Using iCAL, we have identified 222 LIR motif-associated mutations (LAMs) in 148 LIR-containing proteins (LIRCPs), and validated that LAMs in ATG4B, STBD1, EHMT2 and BRAF impair their interactions with LC3 and/or autophagy activities. Moreover, we uncovered that STBD1, a previously poorly-characterized protein, inhibits tumor growth via metabolism reprogramming in cancer cells. A patient-derived mutation in STBD1 (W203C) disrupts the interaction with LC3 and promotes tumor growth. Taken together, iCAL provides an exciting new avenue to discover novel autophagy pathways that contribute to carcinogenesis.
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http://dx.doi.org/10.1080/15548627.2021.1939972DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8354658PMC
July 2021

Lipidomics study of the therapeutic mechanism of Plantaginis Semen in potassium oxonate-induced hyperuricemia rat.

BMC Complement Med Ther 2021 Jun 25;21(1):175. Epub 2021 Jun 25.

School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing, 102488, China.

Background: Plantaginis Semen has been widely used as folk medicine and health care food against hyperuricemia (HUA) and gout, but its pharmacological mechanism remains unclear. This study investigated the therapeutic mechanism of Plantaginis Semen extract on potassium oxonate -induced HUA rats based on a lipidomics approach.

Methods: A model of HUA was established by potassium oxonate intragastric administration. 42 Sprague-Dawley (SD) male rats were randomly divided into the control group, model group, benzbromarone group (10 mg/kg) and three Plantaginis Semen groups (n = 7). The Plantaginis Semen groups were treated orally with Plantaginis Semen, 0.9375, 1.875  or 3.75 g/kg for 28 days. The levels of serum uric acid (UA), creatinine (Cr), triacylglycerol (TG) and tumor necrosis factor-α (TNF-α) were  measured using enzyme-linked immunosorbent assay kits. Ultra performance liquid chromatography quadrupole time of flight mass spectrometry (UPLC-Q-TOF/MS) was used for the serum lipidomics analysis, multivariate statistical analysis and independent samples t-test were carried out for the pattern recognition and characteristic metabolites identification. The relative levels of critical regulatory factors were determined by quantitative real-time polymerase chain reaction (RT-qPCR).

Results: Compared with the model group, the levels of serum UA, Cr, TG and TNF-α were significantly (p < 0.05) decreased in benzbromarone and three Plantaginis Semen groups. With lipidomics analysis, significant lipid metabolic perturbations were observed in HUA rats, 13 metabolites were identified as potential biomarkers and glycerophospholipid metabolism pathway was  most affected. These perturbations  were partially restored via treatment of benzbromarone and Plantaginis Semen. Additionally, the mRNA expression levels of urate anion transporter 1 (URAT1) and phosphatidylinositol 3-kinase/protein kinases B (PI3K/Akt) were significantly decreased (p < 0.01) after treatment with benzbromarone and high dose of Plantaginis Semen.

Conclusions: Plantaginis Semen had significant effects on anti-HUA, anti-inflammatory and renal protection. It attenuated potassium oxonate-induced HUA through regulation of lipid metabolism disorder.
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http://dx.doi.org/10.1186/s12906-021-03350-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8235650PMC
June 2021
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