Publications by authors named "Wei Lian"

172 Publications

[Corrigendum] Identification of microRNAs associated with the aggressiveness of prolactin pituitary tumors using bioinformatic analysis.

Oncol Rep 2021 Jul 20;46(1). Epub 2021 May 20.

Department of Neurosurgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Dongcheng, Beijing 100730, P.R. China.

Following the publication of this article, an interested reader contacted the authors about some possible anomalies in the presentation of the data in Table I, and they have realized that this Table contained some errors. Two different entries for the miRNA hsa‑miR‑886‑3p were inadvertently included in the Table, due to there being two different microarray IDs for this miRNA when performing differential analysis by GEO2R (Owing to an oversight, the repeated miRNA was not deleted; therefore, the row of data for the second has‑miR‑886‑3p entry, comprising P‑value 0.00235, t‑value, 3.82, B‑value, ‑4.58 and logFC, 3.2 has been deleted, and the correct data row for the miRNA hsa‑miR‑513a‑5p has been inserted.) A corrected version of the Table is shown opposite (the corrected data row entry is highlighted in bold). The authors sincerely apologize for the errors that were introduced during the preparation of this Table, and thank the reader of their article who drew this matter to their attention. Furthermore, they regret any inconvenience that this mistake has caused. [the original article was published in Oncology Reports 42: 533‑548, 2019; DOI: /10.3892/or.2019.7173].
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http://dx.doi.org/10.3892/or.2021.8081DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8144937PMC
July 2021

DDIT4 Novel Mutations in Pancreatic Cancer.

Gastroenterol Res Pract 2021 30;2021:6674404. Epub 2021 Apr 30.

Department of Pathology, 1st Affiliated Hospital, Fujian Medical University, 20 Chazhong Road, Fuzhou 350005, China.

Pancreatic cancer is one of the most common malignancies worldwide. This study is aimed at searching the possible genetic mutations and the value of novel gene mutation in the DNA damage-inducible transcript 4 (DDIT4) and signaling pathway in pancreatic cancer. Polymerase chain reaction (PCR) was performed to amplify the DNA sequences of DDIT4 from patients with pancreatic ductal adenocarcinoma. In addition, we used IHC to detect the expression level of DDIT4 in patients with pancreatic cancer in different types of gene mutation. Double-labeled immunofluorescence was employed to explore the expression levels of DDIT4/LC3 and their potential correlation. Our work indicated the two novel stable gene mutations in DDIT4 mRNA 3'-untranslated region (m.990 U>A and m.1246 C>U). Thirteen samples were found to have mutation in the DDIT4 3'-untranslated regions (UTR). To further verify the influence of gene mutation on protein expression, we performed immunohistochemistry on different gene mutation types, and we found a correlation between DDIT4 expression and gene mutation, which is accompanied by nuclear staining deepening. In order to further discuss the clinical value of DDIT4 gene mutation, immunofluorescence suggested that the expression of DDIT4 colocated with LC3; thus, we speculated that DDIT4 mutation may be involved in autophagy in pancreatic cancer cell. In this study, we found mutation in the 3'-UTR region of DDIT4, which may be associated with DDIT4 expression and tumor autophagy in pancreatic cancer tissues.
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http://dx.doi.org/10.1155/2021/6674404DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8110378PMC
April 2021

The PLGA nanoparticles for sustainable release of CGRP to ameliorate the inflammatory and vascular disorders in the lung of CGRP-deficient rats.

Drug Deliv 2021 Dec;28(1):865-872

Higher Educational Key Laboratory for Nano Biomedical Technology of Fujian Province, School of Pharmacy, Nano Medical Technology Research Institute, Fujian Medical University, Fuzhou, China.

The calcitonin gene-related peptide (CGRP) has been demonstrated relating to vascular and inflammatory regulations not only the nerve systems. As the anti-inflammation factor and the most potent vasodilator, the CGRP holds therapeutic potentials for the treatment of cardiovascular diseases which was, however, limited by its peptide nature and short half-life. With advantages in improving the stability, circulation time and protection from degradation, the nanoparticles were promising as delivery carriers for the peptide. Nevertheless, few nanoparticulate systems were developed to deliver the CGRP peptide for the modulation of vascular or inflammatory functions instead of neural regulation. In this study, the CGRP was encapsulated into the poly (lactic-co-glycolic acid) (PLGA) nanoparticle for sustained release of CGRP . The nanoparticles recovered the systemic level of CGRP and the vascular inflammatory factors in the CGRP rats comparing to the administration of (Dulbecco's Phosphate Buffered Saline) DPBS or peptide only. With the decrease of vascular wall thickness and the attenuation of the T cell infiltration in the lung, the polymer based CGRP delivery system showed potentials to facilitate the therapeutic effects of the CGRP which may help for the development of CGRP-based therapy in vascular and inflammatory disorder related diseases.
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http://dx.doi.org/10.1080/10717544.2021.1902021DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8118460PMC
December 2021

Comprehensive Analysis of a Novel Serum Exosome-Derived Competitive Endogenous RNA Network for Constructing a Prognostic Model for Glioblastoma.

Front Oncol 2021 5;11:553594. Epub 2021 Mar 5.

Department of Neurosurgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.

Purpose: Glioblastoma (GBM) is one of the most aggressive brain tumors with high mortality, and tumor-derived exosomes provide new insight into the mechanisms of GBM tumorigenesis, metastasis and therapeutic resistance. We aimed to establish an exosome-derived competitive endogenous RNA (ceRNA) network for constructing a prognostic model for GBM.

Methods: We obtained the expression profiles of long noncoding RNAs (lncRNAs), miRNAs, and mRNAs from the GEO and TCGA databases and identified differentially expressed RNAs in GBM to construct a ceRNA network. By performing lasso and multivariate Cox regression analyses, we identified optimal prognosis-related differentially expressed lncRNAs (DElncRNAs) and generated a risk score model termed the exosomal lncRNA (exo-lncRNA) signature. The exo-lncRNA signature was subsequently validated in the CGGA GBM cohort. Finally, a novel prognostic nomogram was constructed based on the exo-lncRNA signature and clinicopathological parameters and validated in the CGGA external cohort. Based on the ceRNA hypothesis, oncocers were identified based on highly positive correlations between lncRNAs and mRNAs mediated by the same miRNAs. Furthermore, regression analyses were performed to assess correlations between the expression abundances of lncRNAs in tumors and exosomes.

Results: A total of 45 DElncRNAs, six DEmiRNAs, and 38 DEmRNAs were identified, and an exosome-derived ceRNA network was built. Three optimal prognostic-related DElncRNAs, HOTAIR (HR=0.341, P<0.001), SOX21-AS1 (HR=0.30, P<0.001), and STEAP3-AS1 (HR=2.47, P<0.001), were included to construct the exo-lncRNA signature, which was further proven to be an independent prognostic factor. The novel prognostic nomogram was constructed based on the exo-lncRNA signature, patient age, pharmacotherapy, radiotherapy, IDH mutation status, and MGMT promoter status, with a concordance index of 0.878. ROC and calibration plots both suggested that the nomogram had beneficial discrimination and predictive abilities. A total of 11 pairs of prognostic oncocers were identified. Regression analysis suggested excellent consistency of the expression abundance of the three exosomal lncRNAs between exosomes and tumor tissues.

Conclusions: Exosomal lncRNAs may serve as promising prognostic predictors and therapeutic targets. The prognostic nomogram based on the exo-lncRNA signature might provide an intuitive method for individualized survival prediction and facilitate better treatment strategies.
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http://dx.doi.org/10.3389/fonc.2021.553594DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7973265PMC
March 2021

Identification and expression analysis of the WRKY gene family in Isatis indigotica.

Gene 2021 May 9;783:145561. Epub 2021 Mar 9.

College of Horticulture, Nanjing Agricultural University, Nanjing 210095, China. Electronic address:

The WRKY proteins, which represent one of the largest families of transcriptional regulators in plants, play pivotal roles in regulating multiple processes of growth and development, particularly in diverse stress responses. Isatis indigotica is widely used in Traditional Chinese Medicine and is famous for its use as a dye for the color indigo. However, reports of the WRKY gene family in I. indigotica are limited. In this study, 64 IiWRKY genes encoding proteins with the complete WRKY domain were identified from genome of I. indigotica. Based on their structure and phylogenetic relationships of this gene family in I. indigotica, the IiWRKY genes were classified into three groups: Group I (n = 13), Group II (n = 35) and Group III (n = 16). Sequence alignment revealed that IiWRKY proteins harbored two variants, WRKYRQK and WRKYGKK, of the highly conserved WRKYGQK motif. The number of exons in IiWRKY genes varied from two to 14, with most of IiWRKY genes containing three exons. Investigation of gene duplication demonstrated that 10 and 14 IiWRKY genes were incorporated in tandem and segmental duplication events, respectively. Finally, the expression profiles derived from transcriptome data and quantitative real-time PCR analysis showed distinct expression patterns of these IiWRKY gene in five different organs or in response to four abiotic stresses. Taken together, our results will contribute to functional analysis of IiWRKY genes, and also provide a basis for further clarification of the molecular mechanism of stress responses in this important herb.
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http://dx.doi.org/10.1016/j.gene.2021.145561DOI Listing
May 2021

Anatomic relationship between S2 sacroiliac screws' entry points and pelvic external branches of superior gluteal artery.

Eur J Trauma Emerg Surg 2021 Mar 6. Epub 2021 Mar 6.

Orthopaedics Department, Yantai Shan Hospital, 91#, Jiefang Road, Yantai, 264008, People's Republic of China.

Objective: To study the relationship between the pelvic external branches of the superior gluteal artery and the entry area of the S2 sacroiliac screw to provide the anatomical basis and technical reference for avoiding the superior gluteal artery injury during the clinical screw placement.

Methods: CTA imaging of superior gluteal artery of 74 healthy adults (37 males and 37 females) was randomly selected. The safe bony entry area ('safe area' for abbreviation) of S2 sacroiliac screw in the standard lateral view of the pelvis three-dimensional reconstruction CT image was determined by the CT auxiliary measurement software. The relationship between the pelvic external branches of the superior gluteal artery and the safe area of S2 sacroiliac screw was observed, and the cases in which the artery intersected the safe area were counted. The distance between the safe area and the superior gluteal artery branches closest to it was measured for the cases in which the artery and the safe area did not intersect.

Results: 21 of the 74 cases did not have a bone channel of horizontal S2 sacroiliac screw, so they were excluded from this study. In the remaining 53 cases, 12 cases had the deep superior branch of the superior gluteal artery through the safe area of S2 screw (22.6%), and 16 cases had the superficial branch of the superior gluteal artery through the safe area of S2 screw (30.2%). There was no obvious overlap feature and law between the safe area and the superficial and deep superior branches. In 20 cases of the 53 cases, the safe area of S2 screw was located between the deep superior branch and the superficial branch of superior gluteal artery (37.7%), and in 5 cases, the safe area of S2 screw was located behind the superficial branch of superior gluteal artery (9.4%). In the cases where the superior gluteal artery did not intersect the screw entry bony safe area, the part of superior gluteal artery closest to the safe area was located in front or back of the widest part of the safe area.

Conclusion: The risk of accidental injury of the deep superior branch and superficial branch of the superior gluteal artery is high during the process of S2 sacroiliac screw placement. Even if the screw entry point is located in the bony safe area, the absolute safety of screw placement cannot be guaranteed. We strongly suggest that a careful and thorough plan is needed before surgery.
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http://dx.doi.org/10.1007/s00068-021-01622-2DOI Listing
March 2021

[Comparison of the composition and content of pulmonary surfactant among plateau zokors, plateau pikas and rats].

Sheng Li Xue Bao 2021 Feb;73(1):51-61

College of Ecological Environment Engineering, Qinghai University, Xining 810016, China.

In the present study, the composition and content of pulmonary surfactant (PS) were analyzed to explore the hypoxia adaptation mechanism in plateau zokors (Myospalax baileyi) and plateau pikas (Ochotona curzoniae). 36 plateau zokors and plateau pikas were trapped alive at the Laji Mountain in Guide County, Qinghai Province (at the altitude of about 3 600 m), and 36 Sprague-Dawley (SD) rats were purchased from the experimental animal center of Lanzhou University (at the altitude of about 1 500 m). All animals were lavaged after laboratory anesthesia, the blood in lung tissues was fully washed out and the lung tissues were then taken out to obtain the bronchoalveolar lavage fluid by bronchoalveolar lavage. The composition and content of phospholipids in the PS of three different kinds of animals were analyzed by using high performance liquid chromatography; the protein composition, content and types in the PS were analyzed by G-250 Coomassie brilliant blue method, polyacrylamide gel electrophoresis (PAGE) and mass spectrometry; the dissolved oxygen in the PS solutions were determined by using dissolved oxygen electrode. The results showed that the total contents of phospholipids in the PS were successively increased among plateau zokors, plateau pikas and SD rats (P < 0.05), while the total content of proteins successively decreased (P < 0.05). There were five phospholipids identified in the PS, including linoleic palmitoylphosphatidylcholine (LPPC), dipalmitoylphosphatidylcholine (DPPC), phosphatidylglyerol (PG), phosphatidylinositol (PI) and phosphatidylserine (PSe), but the relative contents of these phospholipids were different. The relative content of LPPC was successively increased among plateau zokors, plateau pikas and SD rats (P < 0.01). The relative contents of DPPC, PG and PI in the PS of plateau zokors were significantly higher than those of plateau pikas (P < 0.01), while insignificant differences between plateau pikas and SD rats (P > 0.05). The relative content of PSe had no significant differences between plateau zokors and plateau pikas (P > 0.05), but both were significantly higher than that of SD rats (P < 0.01). The serum albumin (SA) was identified in the PS of three kinds of animals, including homologous tetramer protein containing heme, which is composed of hemoglobin β subunit, in plateau zokors and plateau pikas. Immunoglobulin (Ig) heavy chain was found in PS of plateau zokors and SD rats. The content of Ig heavy chain in plateau zokor was significantly higher than that in SD rats (P < 0.01), and the content of protein containing heme was significantly higher than that in plateau pikas (P < 0.05). The amount of dissolved oxygen was successively decreased in the PS among plateau zokors, plateau pikas and SD rats (P < 0.01), but it was significantly higher than that in saline (P < 0.01). These results suggest that the total content of proteins in the PS of plateau zokors and plateau pikas was significantly higher, while the total content of phospholipids was significantly decreased. There were high content of homologous tetramer protein containing heme in the PS of plateau zokors and plateau pikas. The relative content of DPPC, the main component of phospholipids, was significantly increased in plateau zokors. The changes of PS component and content improve the adaptability of the two plateau animals in hypoxia environment.
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February 2021

Clinical profiles of silent corticotroph adenomas compared with silent gonadotroph adenomas after adopting the 2017 WHO pituitary classification system.

Pituitary 2021 Mar 2. Epub 2021 Mar 2.

Department of Neurosurgery, Pituitary Center, Peking Union Medical College Hospital, Chinese Academy of Medical Science and Peking Union Medical College, No.1 Shuaifuyuan, Dongcheng District, Beijing, 100730, China.

Purpose: Silent corticotroph adenomas (SCAs) can be redefined according to the 2017 World Health Organization pituitary classification system with the introduction of T‑PIT, a transcription factor. We studied the clinical features of these redefined SCAs.

Methods: We compared 112 patients with SCAs and 198 patients with silent gonadotroph adenomas (SGAs) who underwent surgery from January 2019 to May 2020.

Results: The prevalence of SCAs increased from 21.3 to 30.2% under the new classification rules. T-PIT-positive, adrenocorticotropic hormone-negative SCAs and T-PIT-positive, adrenocorticotropic hormone-positive SCAs exhibited similar clinical features. SCAs exhibited significant female preponderance (90.2% vs. 29.8%, P < 0.0001); more frequent invasion (36.6% vs. 7.6%, P < 0.0001), especially multiple-site invasion (P < 0.0001); and marked cystic changes on imaging compared with SGAs (54.5% vs. 19.2%, P < 0.0001). SCAs had a softer tumor consistency (89.2% vs. 61.1%, P < 0.0001). Gross total resection was achieved in 66.1% of SCAs and 66.2% of SGAs (P > 0.9999). The overall recurrence/progression rates of SCAs and SGAs were 9.8% and 6.6% at 14.1 and 13.5 months of follow-up, respectively (P = 0.3765). The proportion of patients with more than two recurrences requiring multiple surgeries and radiation was similar between SCAs and SGAs (7.1% vs. 3.0%, P = 0.1514). However, multiple recurrences of SCAs affected younger patients than SGAs (39.0 vs. 53.5 years, P = 0.0433).

Conclusions: The prevalence of SCAs increased with the introduction of T-PIT. SCAs and SGAs exhibited comparable size and recurrence/progression rates, but SCAs showed increased invasion and more marked cystic change. Aggressive SCAs tended to affect younger patients. Close long-term monitoring for SCA recurrence/progression is required.
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http://dx.doi.org/10.1007/s11102-021-01133-8DOI Listing
March 2021

Fermented cottonseed meal improves production performance and reduces fat deposition in broiler chickens.

Anim Biosci 2021 Apr 25;34(4):680-691. Epub 2020 Nov 25.

College of Animal Science and Technology, Shihezi University, Xinjiang 832000, China.

Objective: This study was conducted to investigate the effect of fermented cottonseed meal (FCSM) on growth performance, carcass traits, and fat deposition in white-feather broiler chickens.

Methods: A total of 480 male one-day-old white-feather broiler chickens were selected randomly and divided into four groups with six replicates of 20 chickens in each. The experimental chickens were fed diets including 3%, 6%, or 9% FCSM fermented by Candida tropicalis until 42 days old. In the experiment, the chickens of the control group were fed soybean meal.

Results: FCSM supplementation linearly decreased the feed conversion ratio from d 15 to 21 and d 36 to 42, respectively (p<0.05). The percentage of carcass and semi-eviscerate increased in response to dietary FCSM supplementation at d 21 (p<0.05). The percentage of eviscerated and semi-eviscerate of 3FCSM was higher than that in other groups at d 35 (p<0.05). At the age of 42 d, the percentage of carcass increased in a quadratic way among increasing FCSM in diets (p<0.05). The subcutaneous fat thickness linearly decreased with the increasing levels of FCSM at d 21 (p<0.05). Gompertz and Logistic functions provided a better fit on abdominal fat and subcutaneous fat, respectively. The best fitted equation predicted that the maximum growth rate of abdominal fat weight and subcutaneous fat thickness occurred at d 28. FCSM had no significant effects on the shape of growth curve of abdominal fat weight and subcutaneous fat thickness, but reduced the height of the curve. Birds receiving the 6FCSM diet for 21 d had smaller adipocyte surface and lower serum glucose as well as triglyceride concentration.

Conclusion: FCSM is beneficial for broiler chickens as it positively affects their growth and carcass in addition to altering their fat deposition.
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http://dx.doi.org/10.5713/ajas.20.0571DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7961297PMC
April 2021

Lung injury induced by pyrrolizidine alkaloids depends on metabolism by hepatic cytochrome P450s and blood transport of reactive metabolites.

Arch Toxicol 2021 01 8;95(1):103-116. Epub 2020 Oct 8.

School of Biomedical Sciences, Faculty of Medicine, The Chinese University of Hong Kong, Shatin, New Territories, Hong Kong SAR, People's Republic of China.

Pyrrolizidine alkaloids (PAs) are common phytotoxins with both hepatotoxicity and pneumotoxicity. Hepatic cytochrome P450 enzymes are known to bioactivate PAs into reactive metabolites, which can interact with proteins to form pyrrole-protein adducts and cause intrahepatic cytotoxicity. However, the metabolic and initiation biochemical mechanisms underlying PA-induced pneumotoxicity remain unclear. To investigate the in vivo metabolism basis for PA-induced lung injury, this study used mice with conditional deletion of the cytochrome P450 reductase (Cpr) gene and resultant tissue-selective ablation of microsomal P450 enzyme activities. After oral exposure to monocrotaline (MCT), a pneumotoxic PA widely used to establish animal lung injury models, liver-specific Cpr-null (LCN) mice, but not extrahepatic Cpr-low (xh-CL) mice, had significantly lower level of pyrrole-protein adducts in the serum, liver and lungs compared with wild-type (WT) mice. While MCT-exposed LCN mice had significantly higher blood concentration of intact MCT, compared to MCT-exposed WT or xh-CL mice. Consistent with the MCT in vivo bioactivation data, MCT-induced lung injury, represented by vasculature damage, in WT and xh-CL mice but not LCN mice. Furthermore, reactive metabolites of MCT were confirmed to exist in the blood efflux from the hepatic veins of MCT-exposed rats. Our results provide the first mode-of-action evidence that hepatic P450s are essential for the bioactivation of MCT, and blood circulating reactive metabolites of MCT to the lung causes pneumotoxicity. Collectively, this study presents the scientific basis for the application of MCT in animal lung injury models, and more importantly, warrants public awareness and further investigations of lung diseases associated with exposure to not only MCT but also different PAs.
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http://dx.doi.org/10.1007/s00204-020-02921-0DOI Listing
January 2021

UPLC-MS/MS-based Lipidomic Profiles Revealed Aberrant Lipids Associated with Invasiveness of Silent Corticotroph Adenoma.

J Clin Endocrinol Metab 2021 Jan;106(1):e273-e287

Department of Neurosurgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, P.R. China.

Context: The accumulation of aberrant lipids and abnormal lipid metabolism in silent corticotroph adenomas (SCAs) could contribute to changes in clinical phenotypes, especially sphenoid sinus invasion.

Objective: To systematically investigate lipidomic and transcriptomic alterations associated with invasiveness and their potential molecular mechanisms in SCAs and to provide candidate biomarkers for predicting invasiveness and novel treatment options for invasive SCAs by targeting lipids.

Methods: Fifty-four SCAs (34 invasive/20 noninvasive) were subjected to lipidomic analysis based on ultraperformance liquid chromatography mass spectrometry, and 42 clinically nonfunctioning pituitary adenomas (23 invasive/19 noninvasive) were subjected to transcriptomic analysis. Differential analysis was performed to determine differential lipids and genes between invasive and noninvasive tumors. A functionally connected network was constructed with the molecular pathways as cores. Multiple machine learning methods were applied to identify the most critical lipids, which were further used to construct a lipidomic signature to predict invasive SCAs by multivariate logistic regression, and its performance was evaluated by receiver operating characteristic analysis.

Results: Twenty-eight differential lipids were identified, and a functionally connected network was constructed with 2 lipids, 17 genes, and 4 molecular pathways. Connectivity Map (CMap) analysis further revealed 32 potential drugs targeting 4 genes and related pathways. The 4 most critical lipids were identified as risk factors contributing to the invasive phenotype. A lipidomic signature was constructed and showed excellent performance in discriminating invasive and noninvasive SCAs.

Conclusions: The lipidomic signature could serve as a promising predictor for the invasive SCA phenotype and provide potential therapeutic targets for SCAs.
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http://dx.doi.org/10.1210/clinem/dgaa708DOI Listing
January 2021

Development and Validation of a Novel DNA Methylation-Driven Gene Based Molecular Classification and Predictive Model for Overall Survival and Immunotherapy Response in Patients With Glioblastoma: A Multiomic Analysis.

Front Cell Dev Biol 2020 3;8:576996. Epub 2020 Sep 3.

Department of Neurosurgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.

Purpose: Glioblastoma (GBM) is the most common primary malignant tumor of the central nervous system, with a 5-year overall survival (OS) rate of only 5.6%. This study aimed to develop a novel DNA methylation-driven gene (MDG)-based molecular classification and risk model for individualized prognosis prediction for GBM patients.

Methods: The DNA methylation profiles (458 samples) and gene expression profiles (376 samples) of patients were enrolled to identify MDGs using the MethylMix algorithm. Unsupervised consensus clustering was performed to develop the MDG-based molecular classification. By performing the univariate, least absolute shrinkage and selection operator (LASSO), and multivariate Cox regression analysis, a MDG-based prognostic model was developed and validated. Then, Bisulfite Amplicon Sequencing (BSAS) and quantitative real-time polymerase chain reaction (qPCR) were performed to verify the methylation and expressions of MDGs in GBM cell lines.

Results: A total of 199 MDGs were identified, the expression patterns of which enabled TCGA and CGGA GBM patients to be divided into 2 clusters by unsupervised consensus clustering. Cluster 1 patients commonly exhibited a poor prognosis, were older in age, and were more sensitive to immunotherapies. Then, six MDGs (ANKRD10, BMP2, LOXL1, RPL39L, TMEM52, and VILL) were further selected to construct the prognostic risk score model, which was validated in the CGGA cohort. Kaplan-Meier survival analysis demonstrated that high-risk patients had significantly poorer OS than low-risk patients (logrank = 3.338 × 10-6). Then, a prognostic nomogram was constructed and validated. Calibration plots, receiver operating characteristic curves, and decision curve analysis indicated excellent predictive performance for the nomogram in both the TCGA training and CGGA validation cohorts. Finally, BSAS and qPCR analysis validated that the expressions of the MDGs were negatively regulated by methylations of target genes, especially promoter region methylation.

Conclusion: The MDG-based prognostic model could serve as a promising prognostic indicator and potential therapeutic target to facilitate individualized survival prediction and better treatment options for GBM patients.
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http://dx.doi.org/10.3389/fcell.2020.576996DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7494802PMC
September 2020

Cyanidin-3-O-Glucoside Improves Colonic Motility During Severe Acute Pancreatitis by Inhibiting the HS-Regulated AMPK/mTOR Pathway.

Drug Des Devel Ther 2020 19;14:3385-3391. Epub 2020 Aug 19.

Department of Gastroenterology, Southwest Hospital of Army Medical University, Chongqing, People's Republic of China.

Background: Cyanidin-3-O-glucoside (C3G) is an important anthocyanin that can modulate digestive system functioning. Inflammation associated with severe acute pancreatitis (SAP) induces HS production, which impairs the gastrointestinal (GI) system. We investigated the effects of C3G in attenuating SAP-associated colonic motility loss by examining the HS level and activity of AMP-activated protein kinase (AMPK)/mammalian target of rapamycin (mTOR) pathway.

Methods: A rat model of SAP was induced using sodium taurocholate, and the effect of C3G on colonic mobility, HS production, and the inflammatory response was investigated. AMPK/mTOR pathway changes were detected to assess the pathways by which HS influences colonic mobility in SAP-model rats. The mechanism underlying HS function was further examined by subjecting colonic muscle cells (CMCs) to C3G, SAP plasma and an AMPK activator.

Results: Administering C3G improved colonic motility but suppressed the inflammatory response and HS production in the SAP-model rats, which was associated with inhibiting the AMPK/mTOR pathway. Furthermore, activating the AMPK/mTOR pathway in CMCs promoted inflammation but suppressed Ca2+ levels, even after administering C3G.

Conclusion: Administering C3G may improve SAP-associated colonic mobility by inhibiting the HS-mediated AMPK/mTOR pathway.
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http://dx.doi.org/10.2147/DDDT.S256450DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7468407PMC
August 2020

Biomechanical comparison of three minimally invasive fixations for unilateral pubic rami fractures.

BMC Musculoskelet Disord 2020 Sep 4;21(1):594. Epub 2020 Sep 4.

Orthopaedics Department, Yantai Shan Hospital, 91#, Jiefang Road, Yantai, 264008, Shandong Province, People's Republic of China.

Background: To compare the mechanical characteristics of a percutaneous superior pubic intramedullary screw, percutaneous bridging plate and percutaneous screw-rod system of the anterior ring for the treatment of unilateral vertical pubic fractures to provide a reference for clinical application.

Methods: A finite element model of pelvic anterior ring injury (unilateral vertical pubic fracture) was produced. The fractures were fixed with a percutaneous superior pubic intramedullary screw, percutaneous bridging plate and percutaneous screw-rod system of the anterior ring and their combinations in 5 types of models. The fracture stabilities under vertical, bilateral and anterior-posterior load were quantified and compared based on the displacement of the hip joints' midpoint as quantificational index of fracture stability.

Results: In the condition of bilateral and anterior-posterior load, the vertical, bilateral and anterior-posterior displacements of the hip joints' midpoint of different models were significantly different respectively. In general, the displacements of the 5 pelvic anterior ring fixations were ranked from maximum to minimum as follows: bridging plate, pelvic anterior screw-rod system, combination of bridging plate and pelvic anterior screw-rod system, superior pubic intramedullary screw and combination of superior pubic intramedullary screw and pelvic anterior screw-rod system.

Conclusion: For the fixation in unilateral pubic fractures of pelvic ring injury, the percutaneous superior pubic intramedullary screw is optimal, the percutaneous pelvic anterior screw-rod system is the second choice, and percutaneous bridging plate ranks the third. The percutaneous pelvic anterior screw-rod system can significantly increase fixation stability of the percutaneous superior pubic intramedullary screw and the percutaneous bridging plate.
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http://dx.doi.org/10.1186/s12891-020-03604-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7487546PMC
September 2020

Identifying Facial Features and Predicting Patients of Acromegaly Using Three-Dimensional Imaging Techniques and Machine Learning.

Front Endocrinol (Lausanne) 2020 29;11:492. Epub 2020 Jul 29.

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

Facial changes are common among nearly all acromegalic patients. As they develop slowly, patients often fail to notice such changes before they become obvious. Consequently, diagnosis and treatment are often delayed. So far, convenient and accurate early detection of this disease is still unavailable. This study is designed to combine the use of 3D imaging and machine learning techniques in facial feature analysis and identification of acromegalic patients, in an effort to ascertain how both techniques performed in terms of applicability and value in the early detection of the disease. One hundred and twenty-four participants including 62 patients with acromegaly and 62 matched controls were enrolled. Using three-dimensional imaging techniques, 58 facial parameters were measured on each face. A two-way analysis of variance (ANOVA) and a -tests were conducted to examine the variations of these parameters with disease status and gender. Using linear discriminant analysis (LDA), we further distinguished patients from controls, characterized what combinations of the parameters could best predict disease state and their relative contributions. Patients are significantly different from normal subjects in many variables, and facial changes of male patients are more significant than female ones. Both male and female patients present following major changes: the increase of facial length and breadth, the widening and elevation of the nose, the thickening of vermilion and the enlargement of the mandible. Facial variables which strongly related to the pathological states can be used to predict the morbid state with high accuracy (prediction accuracies 92.86% in females, < 0.0001 and 75% in males, < 0.001). We have further testified that only a few variables play a vital role in disease prediction and the vital combination of variables vary with gender. Three-dimensional imaging enables comprehensive and accurate quantification of facial characteristics, which makes it a promising technique to investigate facial features of acromegalic patients. In combination with machine learning technique, patients can be accurately identified and predicted by their facial variables. This approach might be beneficial for the early detection of acromegalic patients and timely consultation to improve their outcomes.
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http://dx.doi.org/10.3389/fendo.2020.00492DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7403213PMC
June 2021

Sealing Failure Mechanism and Control Method for Cement Sheath during Hydraulic Fracturing.

ACS Omega 2020 Aug 6;5(32):19978-19994. Epub 2020 Aug 6.

Engineering Technology Research Institute, Tuha Oilfield, Xinjiang 838202, China.

This study focused on the sealing failure mechanism and control method for a cement sheath during hydraulic fracturing. Taking a shale gas well as an example, whole wellbore numerical models of the casing-cement sheath-formation assembly were established, failure modes of the cement sheath at different depths were clarified, and control methods were proposed based on the calculation results. The following conclusions were drawn. (1) The maximum radial/tangential stress of the cement sheath increased/decreased with an increase in the depth, and the cement sheath above the intermediate casing shoe posed the risk of tangential tensile failure, resulting in tensile cracks. The cement sheath below the intermediate casing shoe produced a micro-annulus under a cyclic casing pressure, and the tensile cracks and micro-annulus constituted passages for the sustained casing pressure. (2) The swelling stress of the expansion cement slurry could offset the circumferential tensile stress and increase the radial compressive stress. Because a cement sheath with a high Young's modulus usually exhibits high tensile and compressive strengths, it is recommended to use a high Young's modulus cement slurry system above the intermediate casing shoe and optimize the free expansion ratio. (3) In comparison with ordinary cement stone, low residual strain cement stone exhibited a larger elastic deformation interval. The cumulative residual strain caused by cyclic loading was smaller, and the Young's modulus demonstrated a lesser decrease. The results of an equivalent physical experiment demonstrated that an ordinary cement sheath lost its integrity after 13 loading cycles with a maximum casing pressure of 60 MPa. A low residual strain cement sheath could guarantee integrity after 30 loading cycles when the maximum casing pressure was 90 MPa, and sealing failure occurred after 11 loading cycles when the maximum casing pressure was 130 MPa. It is recommended to use a low residual strain cement slurry below the intermediate casing shoe to prevent a micro-annulus.
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http://dx.doi.org/10.1021/acsomega.0c01326DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7439274PMC
August 2020

Development of a Nomogram With Alternative Splicing Signatures for Predicting the Prognosis of Glioblastoma: A Study Based on Large-Scale Sequencing Data.

Front Oncol 2020 22;10:1257. Epub 2020 Jul 22.

Department of Neurosurgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.

Alternative splicing (AS) was reported to play a vital role in development and progression of glioblastoma (GBM), the most common and fatal brain tumor. Systematic analysis of survival-associated AS event profiles and prognostic prediction model based on multiple AS events in GBM was needed. Genome-wide AS and RNA sequencing profiles were generated in 152 patients with GBM in the cancer genome atlas (TCGA). Prognosis-associated AS events were screened by integrated Cox regression analysis to construct the prognostic risk score model in the training cohort ( = 101). The AS-based signature and clinicopathologic parameters were applied to construct a prognostic nomogram for 0.5-, 1-, and 3-year OS prediction. Finally, the regulatory networks between prognostic AS events and splicing factors (SFs) were constructed. A total of 1,598 prognosis-related AS events from 1,183 source genes were determined. Eight prognostic risk score model based on integrated AS events and 7 AS types were established, respectively. Concordance index (C-index) and receiver operating characteristic (ROC) curve analysis demonstrated powerful ability in distinguishing patients' outcomes. Only Alternate Donor site (AD) and Exon Skip (ES) signature out of the eight types of AS signature were identified as independent prognostic factors for GBM, which was validated in the internal validation cohort. The nomogram with age, new event, pharmaceutical therapy, radiation therapy, AD signature and ES signature were constructed, with C-index of 0.892 (95% CI, 0.853-0.931; = 5.13 × 10). Calibration plots, ROC, and decision curve analysis suggested excellent predictive performance for the nomogram in both TCGA training cohort and validation cohort. Splicing network indicated distinguished correlations between prognostic AS events and SFs in GBM patients. AS-based prediction model could serve as a promising prognostic predictor and potential therapeutic target for GBM, facilitating better treatment strategies in clinical practice.
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http://dx.doi.org/10.3389/fonc.2020.01257DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7387698PMC
July 2020

The Immune Profile of Pituitary Adenomas and a Novel Immune Classification for Predicting Immunotherapy Responsiveness.

J Clin Endocrinol Metab 2020 09;105(9)

Department of Neurosurgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, P. R. China.

Context: The tumor immune microenvironment is associated with clinical outcomes and immunotherapy responsiveness.

Objective: To investigate the intratumoral immune profile of pituitary adenomas (PAs) and its clinical relevance and to explore a novel immune classification for predicting immunotherapy responsiveness.

Design, Patients, And Methods: The transcriptomic data from 259 PAs and 20 normal pituitaries were included for analysis. The ImmuCellAI algorithm was used to estimate the abundance of 24 types of tumor-infiltrating immune cells (TIICs) and the expression of immune checkpoint molecules (ICMs).

Results: The distributions of TIICs differed between PAs and normal pituitaries and varied among PA subtypes. T cells dominated the immune microenvironment across all subtypes of PAs. The tumor size and patient age were correlated with the TIIC abundance, and the ubiquitin-specific protease 8 (USP8) mutation in corticotroph adenomas influenced the intratumoral TIIC distributions. Three immune clusters were identified across PAs based on the TIIC distributions. Each cluster of PAs showed unique features of ICM expression that were correlated with distinct pathways related to tumor development and progression. CTLA4/CD86 expression was upregulated in cluster 1, whereas programmed cell death protein 1/programmed cell death 1 ligand 2 (PD1/PD-L2) expression was upregulated in cluster 2. Clusters 1 and 2 exhibited a "hot" immune microenvironment and were predicted to exhibit higher immunotherapy responsiveness than cluster 3, which exhibited an overall "cold" immune microenvironment.

Conclusions: We summarized the immune profile of PAs and identified 3 novel immune clusters. These findings establish a foundation for further immune studies on PAs and provide new insights into immunotherapy strategies for PAs.
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http://dx.doi.org/10.1210/clinem/dgaa449DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7413599PMC
September 2020

Comprehensive identification of a two-genesignature as a novel potential prognostic model for patients with medulloblastoma.

Am J Transl Res 2020 15;12(5):1600-1613. Epub 2020 May 15.

Department of Neurosurgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College Dongcheng District, Beijing, P. R. China.

Medulloblastoma is one of the most common malignant pediatric brain tumors and has a poor prognosis and high mortality. We investigated the prognostic significance of specific gene signatures and established a novel prognostic model for medulloblastoma patients. Ninety-seven differentially expressed genes between 69 medulloblastoma samples and 4 normal cerebellum samples were identified using the GSE68956 dataset. Univariate and multivariate Cox regression analyses revealed optimal prognosis-related genes, of which PFKP and STXBP1 exhibited significant prognostic values. A risk score model was then established to assess the prognostic value of the gene signature. Kaplan-Meier survival analysis demonstrated that patients with a high risk score had significantly poorer overall survival (OS, log-rank P = 0.003308). The concordance index (C-index) of the two-gene prognostic model for OS prediction was 0.752 (95% CI, 0.740-0.764). The area under the receiver operating characteristic curve (AUC) values for predicting 3-year and 5-year survival were 0.726 and 0.730, respectively. The risk score model was further validated in the ICGC cohort and PUMCH cohort using quantitative real-time polymerase chain reaction (qRT-PCR). Cox regression analyses were performed to assess the two-gene risk score model, metastasis stage, and chemotherapy as independent prognostic factors for medulloblastoma. The C-index of the comprehensive prognostic model composed of the two-gene signature integrated with clinicopathological features for predicting OS was 0.823 (95% CI, 0.739-0.907). The AUCs of the comprehensive prognostic model for predicting 3-year and 5-year survival were 0.774 and 0.759, respectively. Thus, the two-gene risk score model is a promising prognostic biomarker for medulloblastoma.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7270006PMC
May 2020

Imaging Features of Coronavirus disease 2019 (COVID-19): Evaluation on Thin-Section CT.

Acad Radiol 2020 May 20;27(5):609-613. Epub 2020 Mar 20.

Department of Radiology, Beijing Ditan Hospital, Capital Medical University, No. 8 Jingshun East Street, Chaoyang District, Beijing, China. Electronic address:

Rationale And Objectives: To retrospectively analyze the chest imaging findings in patients with coronavirus disease 2019 (COVID-19) on thin-section CT.

Materials And Methods: Fifty-three patients with confirmed COVID-19 infection underwent thin-section CT examination. Two chest radiologists independently evaluated the imaging in terms of distribution, ground-glass opacity (GGO), consolidation, air bronchogram, stripe, enlarged mediastinal lymph node, and pleural effusion.

Results: Fourty-seven cases (88.7%) had findings of COVID-19 infection, and the other six (11.3%) were normal. Among the 47 cases, 78.7% involved both lungs, and 93.6% had peripheral infiltrates distributed along the subpleural area. All cases showed GGO, 59.6% of which were round and 40.4% patchy. Other imaging features included "crazy-paving pattern" (89.4%), consolidation (63.8%), and air bronchogram (76.6%). Air bronchograms were observed within GGO (61.7%) and consolidation (70.3%). Neither enlarged mediastinal lymph nodes nor pleural effusion were present. Thirty-three patients (62.3%) were followed an average interval of 6.2 ± 2.9 days. The lesions increased in 75.8% and resorbed in 24.2% of patients.

Conclusion: COVID-19 showed the pulmonary lesions in patients infected with COVID-19 were predominantly distributed peripherally in the subpleural area.
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http://dx.doi.org/10.1016/j.acra.2020.03.002DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7156158PMC
May 2020

Chemical-defined medium supporting the expansion of human mesenchymal stem cells.

Stem Cell Res Ther 2020 03 19;11(1):125. Epub 2020 Mar 19.

Guangdong Provincial Key Laboratory of Regional Immunity and Diseases, Department of Immunology, School of Medicine, Shenzhen University, Nanhai Avenue 3688, Shenzhen, 518060, Guangdong, People's Republic of China.

Objectives: Mesenchymal stem cells (MSCs) have been intensively investigated as to their therapeutic potentials. However, the full chemical-defined medium supporting the isolation and expansion of human MSCs has not been developed yet.

Materials And Methods: Here, we developed the full chemical-defined medium, NBVbe medium, via RNA sequencing, bioinformatic analysis, and growth factor screening.

Results: The NBVbe medium contains N2B27 medium with the BSA (bovine serum albumin) replaced by the recombinant human albumin, bFGF (basic fibroblast growth factor), vitamin C, and EGF (epidermal growth factor). The NBVbe medium could support the isolation and expansion of human MSCs from the umbilical cords.

Conclusions: The full chemical-defined medium supporting the isolation and expansion of human MSCs has been developed. This would be helpful for further optimization of the MSC medium, their clinical applications, and molecular characterization.
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http://dx.doi.org/10.1186/s13287-020-01641-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7083066PMC
March 2020

Clinical Characteristics of Pediatric Patients With Sellar and Suprasellar Lesions Who Initially Present With Central Diabetes Insipidus: A Retrospective Study of 55 Cases From a Large Pituitary Center in China.

Front Endocrinol (Lausanne) 2020 20;11:76. Epub 2020 Feb 20.

Department of Neurosurgery, Chinese Academy of Medical Sciences and Peking Union Medical College, Peking Union Medical College Hospital, Beijing, China.

To increase knowledge for the early differential diagnosis and accurate therapeutic strategies for pediatric patients with sellar or suprasellar region (SSR) lesions who initially present with central diabetes insipidus (CDI). This is a retrospective review of 55 pediatric patients (≤14 years old) with identified lesions in the SSR who initially presented with CDI at a large pituitary center between 2012 and 2018. The following data were summarized: demographic, clinical, endocrine, and neuroimaging data, intraoperative findings, histopathological findings, treatments, and prognosis. In our group, the etiologies of the SSR lesions included germ cell tumors (GCTs, 74.5%), Langerhans cell histiocytosis (LCH, 18.2%), and craniopharyngioma (CP, 7.3%). Almost all patients (50/55, 90.9%) showed anterior pituitary dysfunction [multiple axes dysfunction (38), and isolated axis dysfunction (14)], while the GH/IGF-I axis was the most affected. Most GCT patients presented with various clinical manifestations besides CDI and had elevated β-HCG, whereas LCH and CP patients mostly presented few non-specific symptoms besides CDI and most had normal level tumor markers. Sellar MRI demonstrated that posterior pituitary bright spot disappearance occurred in all patients, and pituitary stalk thickening was observed in 96.7% of patients. Treatment varied due to the different etiologies of the SSR lesions. After follow-up for 35.4 ± 20.2 months, the proportions of patients who needed AVP (arginine vasopressin) for GCT, LCH, and CP were 86.5, 100, and 75%, respectively, and the proportions of patients who needed HRT were 89.2, 50, and 75%, respectively. For pediatric SSR lesions that first manifest as CDI, we should comprehensively consider clinical characteristics and imaging features to aid in their early differential diagnosis. Tumor markers and surgical histopathology are also great complements for the differential diagnosis. Additionally, various treatment strategies should be adopted according to different causes to improve the child's prognosis and quality of life.
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http://dx.doi.org/10.3389/fendo.2020.00076DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7044264PMC
March 2021

Improved therapeutic consistency and efficacy of mesenchymal stem cells expanded with chemically defined medium for systemic lupus erythematosus.

Cell Mol Immunol 2020 10 5;17(10):1104-1106. Epub 2020 Feb 5.

Guangdong Provincial Key Laboratory of Regional Immunity and Diseases, Department of Immunology, Health Science Center, Shenzhen University, Shenzhen, 518055, P. R. China.

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http://dx.doi.org/10.1038/s41423-020-0364-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7608228PMC
October 2020

Sleep quality in acromegaly and changes after transsphenoidal surgery: a prospective longitudinal study.

Sleep Med 2020 03 12;67:164-170. Epub 2019 Dec 12.

Neurosurgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100730, PR China; Key Laboratory of Endocrinology of Ministry of Health, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100730, PR China; China Pituitary Disease Registry Center, Beijing, 100730, PR China; China Pituitary Adenoma Specialist Council, Beijing, 100730, PR China. Electronic address:

Objective: To elucidate the sleep quality characteristics and factors related to either good or poor sleep quality in acromegaly patients before surgery and to explore sleep quality changes after transsphenoidal surgery and the factors related to these changes.

Methods: We prospectively enrolled 39 acromegaly patients and 78 patients with nonfunctioning pituitary adenomas. Scales for anxiety, depression, disease stigma and nasal condition were evaluated. The Pittsburgh Sleep Quality Index (PSQI) questionnaire was administered before surgery as well as one month and three months after surgery.

Results: A higher percentage of acromegaly patients had poor sleep quality compared to controls (35.9% vs. 5.1%, p < 0.001). In addition, acromegaly patients experienced worse subjective sleep quality, extended sleep latency, increased sleep disturbance and decreased daytime functioning. Higher scores for anxiety, disease stigma and sinonasal outcomes were correlated with worse sleep quality in acromegaly patients. At one month after transsphenoidal surgery, we found worse subjective sleep quality, extended sleep latency, shortened sleep duration, impaired sleep efficiency and increased sleep disturbance in acromegaly patients. At three months postoperatively, most impaired PSQI domains in acromegaly patients recovered to preoperative levels. The use of soluble gauze was related to decreased sleep quality at one month after surgery and severe anxiety and depression were related to improved sleep quality at three months after surgery.

Conclusions: Sleep quality was reduced in acromegaly patients. Moreover, sleep quality initially worsened after surgery but later recovered. Emotional problems and the use of soluble gauze were related factors.

Clinical Trial Registration: None.
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http://dx.doi.org/10.1016/j.sleep.2019.11.1256DOI Listing
March 2020

Development and validation of a nomogram with an autophagy-related gene signature for predicting survival in patients with glioblastoma.

Aging (Albany NY) 2019 12 17;11(24):12246-12269. Epub 2019 Dec 17.

Department of Neurosurgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Dongcheng, Beijing 100730, P.R. China.

Glioblastoma (GBM) is the most common brain tumor with significant morbidity and mortality. Autophagy plays a vital role in GBM development and progression. We aimed to establish an autophagy-related multigene expression signature for individualized prognosis prediction in patients with GBM. Differentially expressed autophagy-related genes (DE-ATGs) in GBM and normal samples were screened using TCGA. Univariate and multivariate Cox regression analyses were performed on DE-ATGs to identify the optimal prognosis-related genes. Consequently, NRG1 (HR=1.142, P=0.008), ITGA3 (HR=1.149, P=0.043), and MAP1LC3A (HR=1.308, P=0.014) were selected to establish the prognostic risk score model and validated in the CGGA validation cohort. GSEA revealed that these genes were mainly enriched in cancer- and autophagy-related KEGG pathways. Kaplan-Meier survival analysis demonstrated that patients with high risk scores had significantly poorer overall survival (OS, log-rank P= 6.955×10). The autophagy signature was identified as an independent prognostic factor. Finally, a prognostic nomogram including the autophagy signature, age, pharmacotherapy, radiotherapy, and IDH mutation status was constructed, and TCGA/CGGA-based calibration plots indicated its excellent predictive performance. The autophagy-related three-gene risk score model could be a prognostic biomarker and suggest therapeutic targets for GBM. The prognostic nomogram could assist individualized survival prediction and improve treatment strategies.
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http://dx.doi.org/10.18632/aging.102566DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6949068PMC
December 2019

Preoperative and Postoperative Bone Mineral Density Change and Risk Factor Analysis in Patients with a GH-Secreting Pituitary Adenoma.

Int J Endocrinol 2019 3;2019:2102616. Epub 2019 Nov 3.

Department of Neurosurgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100730, China.

Purpose: This study analysed changes in bone mineral density (BMD) at different sites in patients with acromegaly and postoperative BMD changes and explored risk factors associated with BMD.

Methods: Clinical data of 39 patients with growth hormone- (GH-) secreting pituitary adenomas and 29 patients with nonfunctioning pituitary adenomas who were newly diagnosed in neurosurgery from January 2016 to December 2018 were retrospectively analysed, including measurements of preoperative and postoperative BMD, serum GH glucose inhibition, random GH and IGF-1, and other anterior pituitary hormones.

Results: The average patient age and disease duration were 43.74 (33.41-54.07) years and 72.15 (22.82-121.48) months, respectively. Compared with patients with nonfunctioning adenomas, patients with GH-secreting pituitary adenomas had significantly higher BMDs at L1, L2, femoral neck, Ward triangle, trochanter, femoral shaft, and total hip sites ( < 0.05). The BMD score at L1 and femoral neck sites significantly increased ( < 0.05). Thirteen patients underwent re-examination of BMD 1 year postsurgery, and the BMD score was reduced to normal levels at L1, L2, L3, L4, L1-L4, and L2-L4 compared with preoperative levels ( < 0.05). Postoperative BMD scores in the femoral neck and total hip were significantly increased ( < 0.05). Disease duration was negatively correlated with the lumbar-spine BMD score. IGF-1 burden was negatively correlated with the BMD score at L1 and L1-L4. Multiple regression analysis showed that IGF-1 burden was a risk factor for a BMD score decrease at L1 and L1-L4.

Conclusion: BMD in patients with GH-secreting pituitary adenomas (compared with nonfunctional adenomas) increased at L1, L2, femoral neck, Ward triangle, trochanter, femoral shaft, and total hip sites. Lumbar-spine BMD score recovered to normal levels postsurgically when GH and IGF-1 levels were controlled. BMD score was negatively correlated with disease duration and IGF-1 burden in patients with GH-secreting pituitary adenomas, and IGF-1 burden was an independent risk factor for reduced lumbar-spine BMD score.
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http://dx.doi.org/10.1155/2019/2102616DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6875336PMC
November 2019

Effects of a Modified Tai Chi Program on Older People with Mild Dementia: A Randomized Controlled Trial.

J Alzheimers Dis 2019 ;72(3):947-956

Center for Cognitive Disorders, Beijing Geriatric Hospital, Beijing, China.

Background: Tai Chi exercise is a non-pharmacological therapy that has received increased attention in recent years. A Tai Chi program has been specifically modified for older people with cognitive impairments by the research team.

Objective: We aim to assess the effects of this Tai Chi program on mild dementia.

Methods: Eighty older people with mild dementia were recruited and randomly assigned to a Tai Chi group or a control group. The Tai Chi group practiced the Tai Chi program three times a week for 10 months, while the control group continued receiving routine treatments. All participants were assessed for cognitive function, behavior/mood, and activities of daily living at baseline, 5 months, and 10 months.

Results: The Tai Chi group performed better than the control group. Repeated measures ANOVA revealed a significant group×time interaction in the Montreal Cognitive Assessment (MoCA). Further analysis of sub-items of the MoCA showed a significant time effect in naming and abstraction. It was statistically significant in both main effect of time and group×time interaction in the Neuropsychiatric Inventory (NPI) and Geriatric Depression Scale (GDS). Paired sample t test showed the Tai Chi group scored lower at 5 and 10 months in the NPI and at 10 months in the GDS compared with baseline. The Tai Chi group scored lower than the control group at 10 months in the NPI and GDS.

Conclusion: The results suggest this Tai Chi program may help improve cognitive function and mental well-being for older adults with mild dementia.
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http://dx.doi.org/10.3233/JAD-190487DOI Listing
November 2020

Preoperative Fasting C-Peptide Acts as a Promising Predictor of Improved Glucose Tolerance in Patients With Acromegaly After Transsphenoidal Surgery: A Retrospective Study of 64 Cases From a Large Pituitary Center in China.

Front Endocrinol (Lausanne) 2019 1;10:736. Epub 2019 Nov 1.

Department of Neurosurgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.

Abnormal glucose metabolism is one of the most frequent acromegaly complications. Improvement of glucose metabolism can be observed only in half of acromegaly patients after surgery. We aimed to investigate the risk factors for determining abnormal glucose metabolism before surgery in patients with acromegaly, and to explore the predictors of improved preoperative glucose intolerance after surgery. We retrospectively reviewed 64 patients who received transsphenoidal surgery for acromegaly. Growth hormone (GH), insulin-like growth factor-1 (IGF-1) and glucose metabolism were assessed before, immediately after, and 3 months after surgery. Glucose metabolic parameters included glycosylated hemoglobin (HbA1c), plasma glucose (PG), C-peptide (CP), insulin (INS), and the indices of β-cell function, insulin sensitivity, and insulin resistance (IR). Preoperatively, 18 patients (28.1%) had diabetes (DM), 34 (53.1%) had prediabetes (PreDM), and 12 (18.8%) had normal glucose tolerance (NGT). All the indices of pancreatic β-cell function were significantly lower in patients with DM than those with PreDM and NGT (all < 0.005). IGF-1 was significantly positively correlated with insulin sensitivity and IR ( < 0.05), while GH was not. Postoperatively, glucose tolerance was improved in 71.2% of patients (37/52) with preoperative glucose intolerance. Insulin sensitivity was increased, while β-cell function and IR were decreased in most patients after surgery, regardless of whether their acromegaly achieved remission. A multivariate logistic regression analysis revealed that preoperative fasting C-peptide (FCP, OR = 2.639, = 0.022), disposition index (DI, OR = 1.397, = 0.043) and Predictor-2 (OR = 0.578, = 0.035) were determined to be the predictors for improved glucose tolerance status after surgery. Afterwards, through Receiver operating characteristic (ROC) analyses, FCP >2.445 ng/ml was the best independent predictor, with an 86.6% PPV (positive predictive value) and a 74.5% NPV (negative predictive value). Preoperative high FCP is a promising postsurgical predictor of improved glucose tolerance in patients with acromegaly. Oral glucose tolerance testing (OGTT) and HbA1c should be monitored regularly after surgery, and diabetes management should be adjusted based on the patient's latest glucose tolerance status.
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http://dx.doi.org/10.3389/fendo.2019.00736DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6838023PMC
November 2019

Three acquired immunodeficiency syndrome patients with central nervous system infection: diagnostic approach and outcome of treatment.

Chin Med J (Engl) 2019 Nov;132(22):2754-2756

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

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http://dx.doi.org/10.1097/CM9.0000000000000507DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6940090PMC
November 2019

The urinary levels of CTX-II, C2C, PYD, and Helix-II increased among adults with KBD: a cross-sectional study.

J Orthop Surg Res 2019 Oct 21;14(1):328. Epub 2019 Oct 21.

Institute for Kashin-Beck Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Harbin Medical University, Harbin, 150081, Heilongjiang, China.

Background: Kashin-Beck disease (KBD) is an endemic osteoarthropathy, and its pathogenesis is still not entirely clear. Pathologically, many KBD changes are similar to those of osteoarthritis (OA). Therefore, this study aimed to identify changes in the levels of potential urinary biomarkers for OA, including C-telopeptide of type II collagen (uCTX-II), type II collagen cleavage neoepitope (uC2C), pyridinoline (uPYD), and uHelix-II, among adults with KBD.

Methods: Urinary samples of 83 external control (EC) subjects, 91 KBD patients, and 86 internal control (IC) subjects were tested by ELISA after the subjects completed a questionnaire and X-ray examination.

Results: The medians of the four markers in the KBD group were higher than those in the EC group and those in the IC group. The medians in the grade II KBD group were higher than those in the grade I group but were not statistically significant (P = 0.301, P = 0.408, P = 0.204, and P = 0.898 for uCTX-II, uC2C, uPYD, and uHelix-II, respectively). The area under the curve (AUC) of uCTX-II (0.775) was higher than that of the others (0.672, 0.639, and 0.628 for uC2C, uPYD, and uHelix-II, respectively).

Conclusion: The levels of uCTX-II, uC2C, uPYD, and uHelix-II were elevated in adults with KBD and showed an increasing trend as the severity of KBD increased. The prediction accuracy of uCTX-II was more useful than that of the others for assisting in the diagnosis of KBD.
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http://dx.doi.org/10.1186/s13018-019-1392-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6805615PMC
October 2019