Publications by authors named "Huili Li"

167 Publications

Nkx2.5 Functions as a Conditional Tumor Suppressor Gene in Colorectal Cancer Cells Acting as a Transcriptional Coactivator in p53-Mediated p21 Expression.

Front Oncol 2021 1;11:648045. Epub 2021 Apr 1.

Department of Gastrointestinal Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

NK2 homeobox 5 (Nkx2.5), a homeobox-containing transcription factor, is associated with a spectrum of congenital heart diseases. Recently, Nkx2.5 was also found to be differentially expressed in several kinds of tumors. In colorectal cancer (CRC) tissue and cells, hypermethylation of Nkx2.5 was observed. However, the roles of Nkx2.5 in CRC cells have not been fully elucidated. In the present study, we assessed the relationship between Nkx2.5 and CRC by analyzing the expression pattern of Nkx2.5 in CRC samples and the adjacent normal colonic mucosa (NCM) samples, as well as in CRC cell lines. We found higher expression of Nkx2.5 in CRC compared with NCM samples. CRC cell lines with poorer differentiation also had higher expression of Nkx2.5. Although this expression pattern makes Nkx2.5 seem like an oncogene, and tumor suppressive effects of Nkx2.5 were detected in HCT116 cells by establishing Nkx2.5-overexpressed CRC cells. However, Nkx2.5 overexpression was incapacitated in SW480 cells. To further assess the mechanism, different expression levels and mutational status of p53 were observed in HCT116 and SW480 cells. The expression of p21, a downstream antitumor effector of p53, in CRC cells depends on both expression level and mutational status of p53. Overexpressed Nkx2.5 could elevate the expression of p21 only in CRC cells with wild-type p53 (HCT116), rather than in CRC cells with mutated p53 (SW480). Mechanistically, Nkx2.5 could interact with p53 and increase the transcription of p21 without affecting the expression of p53. In conclusion, our findings demonstrate that Nkx2.5 could act as a conditional tumor suppressor gene in CRC cells with respect to the mutational status of p53. The tumor suppressive effect of Nkx2.5 could be mediated by its role as a transcriptional coactivator in wild-type p53-mediated p21 expression.
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http://dx.doi.org/10.3389/fonc.2021.648045DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8047315PMC
April 2021

Identification of Mitochondrial-Related Prognostic Biomarkers Associated With Primary Bile Acid Biosynthesis and Tumor Microenvironment of Hepatocellular Carcinoma.

Front Oncol 2021 1;11:587479. Epub 2021 Apr 1.

Department of Gastrointestinal Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

Hepatocellular carcinoma (HCC) is one of the leading causes of tumor-associated deaths worldwide. Despite great progress in early diagnosis and multidisciplinary tumor management, the long-term prognosis of HCC remains poor. Currently, metabolic reprogramming during tumor development is widely observed to support rapid growth and proliferation of cancer cells, and several metabolic targets that could be used as cancer biomarkers have been identified. The liver and mitochondria are the two centers of human metabolism at the whole organism and cellular levels, respectively. Thus, identification of prognostic biomarkers based on mitochondrial-related genes (Mito-RGs)-the coding-genes of proteins located in the mitochondria-that reflect metabolic changes associated with HCC could lead to better interventions for HCC patients. In the present study, we used HCC data from The Cancer Genome Atlas (TCGA) database to construct a classifier containing 10 Mito-RGs (ACOT7, ADPRHL2, ATAD3A, BSG, FAM72A, PDK3, PDSS1, RAD51C, TOMM34, and TRMU) for predicting the prognosis of HCC by using 10-fold Least Absolute Shrinkage and Selection Operation (LASSO) cross-validation Cox regression. Based on the risk score calculated by the classifier, the samples were divided into high- and low-risk groups. Gene set enrichment analysis (GSEA), gene set variation analysis (GSVA), t-distributed stochastic neighbor embedding (t-SNE), and consensus clusterPlus algorithms were used to identify metabolic pathways that were significantly different between the high- and low-risk groups. We further investigated the relationship between metabolic status and infiltration of immune cells into HCC tumor samples by using the Cell-type Identification By Estimating Relative Subsets Of RNA Transcripts (CIBERSORT) algorithm combined with the Tumor Immune Estimation Resource (TIMER) database. Our results showed that the classifier based on Mito-RGs could act as an independent biomarker for predicting survival of HCC patients. Repression of primary bile acid biosynthesis plays a vital role in the development and poor prognosis of HCC, which provides a potential approach to treatment. Our study revealed cross-talk between bile acid and infiltration of tumors by immune cells, which may provide novel insight into immunotherapy of HCC. Furthermore, our research may provide a novel method for HCC metabolic therapy based on modulation of mitochondrial function.
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http://dx.doi.org/10.3389/fonc.2021.587479DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8047479PMC
April 2021

Intrathecal Injection of GRIP-siRNA Reduces Postoperative Synaptic Abundance of Kainate Receptor GluK2 Subunits in Rat Dorsal Horns and Pain Hypersensitivity.

Neurochem Res 2021 Apr 13. Epub 2021 Apr 13.

Department of Anesthesiology, Beijing Chaoyang Hospital, Capital Medical University, No. 8, Gongtinan Road, Beijing, 100020, China.

The mechanisms underlying postoperative pain differ from the inflammatory or neuropathic pain. Previous studies have demonstrated that intrathecal α-amino-3-hydroxy-5-methy-4-isoxazole propionate (AMPA) -kainate (KA) receptor antagonist inhibits the guarding pain behavior and mechanical hyperalgesia, indicating a critical role of spinal KA receptors in postoperative pain hypersensitivity. However, how the functional regulations of spinal KA receptor subunits are involved in the postoperative pain hypersensitivity remains elusive. Therefore, in the current study, we investigated the synaptic delivery of spinal KA receptor subunits and the interaction between KA receptor subunits and glutamate receptor-interacting protein (GRIP) during the postoperative pain. Our data indicated that plantar incision induced the synaptic delivery of GluK2, but not GluK1 or GluK3 in ipsilateral spinal cord dorsal horns. The co-immunoprecipitation showed an increased GluK2 -GRIP interaction in ipsilateral dorsal horn neurons at 6 h post-incision. Interestingly, Intrathecal pretreatment of GRIP siRNA increased the paw withdrawal thresholds to mechanical stimuli and decreased the cumulative pain scores in the paws ipsilateral to the incision at 6 h post-incision. Additionally, Intrathecal pretreatment of GRIP siRNA reduced the synaptic abundance of GluK2 in ipsilateral spinal dorsal horn at 6 h after plantar incision. In general, our data have demonstrated that the GluK2- GRIP interaction-mediated synaptic abundance of GluK2 in dorsal horn neurons plays an important role in the postoperative pain hypersensitivity. Disrupting the GluK2- GRIP interaction may provide a new approach for relieving postoperative pain.
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http://dx.doi.org/10.1007/s11064-021-03323-zDOI Listing
April 2021

Retraction of "Synthesis of near-Infrared Quantum Dots in Cultured Cancer Cells".

ACS Appl Mater Interfaces 2021 Apr 13. Epub 2021 Apr 13.

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http://dx.doi.org/10.1021/acsami.1c05347DOI Listing
April 2021

Cervical erector spinae plane block as a perioperative analgesia method for shoulder arthroscopy: a case series.

J Anesth 2021 Mar 8. Epub 2021 Mar 8.

Department of Anesthesiology, Beijing Chaoyang Hospital, Capital Medical University, Beijing, 100020, China.

Shoulder arthroscopy, a common intervention for severe rotator cuff injuries, is associated with severe postoperative pain. Upon performing cervical erector spinae plane (ESP) blocks at the C7 TP (tip or posterior tip) or the posterior tip of the C6 TP posterior tubercle in six patients undergoing shoulder arthroscopy, sensory block was detectable in congruent cervico-thoracic dermatomes. Effective intraoperative and postoperative analgesia were consistently obtained for all six patients. This preliminary study illustrated that the cervical ESP block can be considered a potential simple regional anesthesia method for providing analgesia during shoulder arthroscopy with low risks of diaphragmatic paresis, upper extremity motor paresis, nerve injury and persistent hypotension.
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http://dx.doi.org/10.1007/s00540-021-02907-xDOI Listing
March 2021

Association between Dexamethasone and Delirium in Critically Ill Patients: A Retrospective Cohort Study of a Large Clinical Database.

J Surg Res 2021 Feb 24;263:89-101. Epub 2021 Feb 24.

Department of Anesthesiology, Beijing Chaoyang Hospital, Capital Medical University, Beijing, China. Electronic address:

Background: Delirium is a common complication in intensive care unit (ICU) patients, and it can significantly increase the length of hospital stay and cost. Dexamethasone is widely used in various inflammatory diseases and must be used with caution in critically ill patients. Previous studies have shown that the effect of corticosteroid use on the development of delirium in critically ill patients is still controversial, and there is inconclusive conclusion about the effect of dexamethasone on delirium in such patients. Therefore, this study aimed to confirm the effect of dexamethasone use and the dose on the incidence of delirium and patient prognosis in critically ill patients through a large cohort study.

Methods: A retrospective cohort study was conducted using data extracted from the Medical Information Mart for Intensive Care III database, which is a large and freely available database of all 46,476 patients who visited Beth Israel Deaconess Medical Center in Boston, Massachusetts, USA and were admitted to the ICU between 2001 and 2012. The primary outcome was the development of delirium, using multivariate logistic regression analysis to reveal the relationship between dexamethasone and delirium. Secondary endpoints were in-hospital mortality, ICU mortality, total length of stay, and length of ICU stay, and the relationship between dexamethasone and prognosis was assessed with Cox proportional hazards models. Propensity score matching with 1:1 grouping was used to eliminate the effect of confounders on both cohorts. The locally weighted scatter plot smoothing technique was used to investigate the dose correlation between dexamethasone and outcomes, subgroup analysis was used to account for heterogeneity, and different correction models and propensity matching analysis were used to eliminate potential confounders.

Results: Finally, 38,509 patients were included, and 2204 (5.7%) used dexamethasone. No significant statistical difference was observed in basic demographic information after propensity score matching between the two study groups. A significantly higher incidence of delirium (5.0% versus 3.4%, P < 0.001), increased in-hospital mortality (14.9% versus 10.3%, P < 0.001), ICU mortality (9.0% versus 7.5%, P = 0.008), and longer length of stay and ICU stay were observed in patients taking dexamethasone compared with those not taking dexamethasone. Multivariate logistic and Cox regression analyses confirmed that dexamethasone was significantly associated with delirium (adjusted odds ratio = 1.48, 95% confidence interval [CI] = 1.09-2.00, P = 0.012), in-hospital mortality (adjusted hazard ratio = 1.19, 95% CI = 1.02-1.40, P = 0.032), and ICU mortality (adjusted hazard ratio = 1.62, 95% CI = 1.22-2.15, P = 0.001). Compared with critically ill patients using high-dose dexamethasone, the risk of delirium was lower in the dose less than the 10 mg group, and patients using 10-14 mg may be associated with a lower risk of in-hospital death and the least ICU mortality, length of hospital stay, and ICU stay.

Conclusions: This study demonstrated that the use of dexamethasone in critically ill patients exacerbated the occurrence of delirium while increasing the risk of in-hospital death, ICU death, and length of hospital stay, with a lower risk of delirium and a shorter total length of hospital stay with low-dose dexamethasone than with larger doses.
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http://dx.doi.org/10.1016/j.jss.2021.01.027DOI Listing
February 2021

Use of transmuscular quadratus lumborum block for postoperative analgesia after laparoscopic nephrectomy.

Reg Anesth Pain Med 2021 Feb 25. Epub 2021 Feb 25.

Department of Anesthesia and Pain Medicine, Beijing Chaoyang Hospital, Capital Medical University, Beijing, China

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http://dx.doi.org/10.1136/rapm-2021-102478DOI Listing
February 2021

The Role of Dyslipidemia in Colitis-Associated Colorectal Cancer.

J Oncol 2021 12;2021:6640384. Epub 2021 Feb 12.

Department of Gastrointestinal Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China.

Dyslipidemia, characterized by metabolic abnormalities, has become an important participant in colorectal cancer (CRC). Dyslipidemia aggravates intestinal inflammation, destroys the protective mucous layer, and disrupts the balance between injury and recovery. On the other hand, antioxidants induced by oxidative stress enhance glycolysis to maintain the acquisition of ATP allowing epithelial cells with damaged genomes to survive. In the repetitive phase of colitis, survival factors enable these epithelial cells to continuously proliferate. The main purpose is to restore and rebuild damaged mucosa, mainly aiming to recover mucosal damage and reconstruct mucosa, but it is also implicated in the occurrence and malignancy of CRC. The metabolic reprogramming of aerobic glycolysis and lipid synthesis enables these transformed epithelial cells to convert raw carbohydrate and amino acid substrates, thereby synthesizing protein and phospholipid biomass. Stearoyl-CoA desaturase, responsible for the fatty acid desaturation, improves the fluidity and permeability of cell membranes, which is one of the key factors affecting metabolic rate. In response to available fat, tumor cells reprogram their metabolism to better plunder energy-rich lipids and rapidly scavenge these lipids through continuous proliferation. However, lipid metabolic disorders inhibit the function of immune-infiltrating cells in the tumor microenvironment through the cross-talk between tumor cells and immunosuppressive stromal cells, thereby providing opportunities for tumor progress. Nonsteroidal anti-inflammatory drugs and lipid-lowering drugs can decrease the formation of aberrant crypt foci, lower the burden of the adenomatous polyp, and reduce the incidence of CRC. This review provides a comprehensive understanding of dyslipidemia on tumorigenesis and tumor progression and a development prospect of lipid disorders on tumor immunity.
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http://dx.doi.org/10.1155/2021/6640384DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7895570PMC
February 2021

Reviewing the world's edible mushroom species: A new evidence-based classification system.

Compr Rev Food Sci Food Saf 2021 Mar 18;20(2):1982-2014. Epub 2021 Feb 18.

CAS Key Laboratory for Plant Diversity and Biogeography of East Asia, Kunming Institute of Botany, Chinese Academy of Sciences, Kunming, Yunnan, China.

Wild mushrooms are a vital source of income and nutrition for many poor communities and of value to recreational foragers. Literature relating to the edibility of mushroom species continues to expand, driven by an increasing demand for wild mushrooms, a wider interest in foraging, and the study of traditional foods. Although numerous case reports have been published on edible mushrooms, doubt and confusion persist regarding which species are safe and suitable to consume. Case reports often differ, and the evidence supporting the stated properties of mushrooms can be incomplete or ambiguous. The need for greater clarity on edible species is further underlined by increases in mushroom-related poisonings. We propose a system for categorizing mushroom species and assigning a final edibility status. Using this system, we reviewed 2,786 mushroom species from 99 countries, accessing 9,783 case reports, from over 1,100 sources. We identified 2,189 edible species, of which 2,006 can be consumed safely, and a further 183 species which required some form of pretreatment prior to safe consumption or were associated with allergic reactions by some. We identified 471 species of uncertain edibility because of missing or incomplete evidence of consumption, and 76 unconfirmed species because of unresolved, differing opinions on edibility and toxicity. This is the most comprehensive list of edible mushrooms available to date, demonstrating the huge number of mushrooms species consumed. Our review highlights the need for further information on uncertain and clash species, and the need to present evidence in a clear, unambiguous, and consistent manner.
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http://dx.doi.org/10.1111/1541-4337.12708DOI Listing
March 2021

Arrhythmias in patients with coronavirus disease 2019 (COVID-19) in Wuhan, China: Incidences and implications.

J Electrocardiol 2021 Mar-Apr;65:96-101. Epub 2021 Jan 24.

Department of Cardiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China. Electronic address:

Background: Coronavirus disease 2019 (COVID-19) continues to impact populations around the globe. Information regarding the incidences and implications of arrhythmias in COVID-19 is limited.

Methods: A total of 463 patients with COVID-19 and who had at least one electrocardiogram recording from February 1 to March 19, 2020, in Wuhan Union Hospital were enrolled in the study.

Results: Arrhythmias occurred in 85 of 463 (18.4%) patients: atrial arrhythmias in 10.2%, junctional arrhythmias in 0.2%, ventricular arrhythmias in 3.5%, and conduction block in 7.3%. Compared with patients without arrhythmias, those with arrhythmias had higher mortality, both during the time from symptom onset (p < 0.001) and from admission to follow-up (p < 0.001). The frequencies of severe COVID-19 (44.7% vs. 21.2%; p < 0.001) and death (25.9% vs. 10.1%; p < 0.001) were higher in patients with arrhythmias than in those without arrhythmias. Atrial arrhythmias and ventricular arrhythmias could predict severity and mortality, their odds ratios (OR) were 4.45 (95% confidence interval [CI] 2.35 to 8.40), 5.80 (95% CI 1.89 to 17.76) respectively for severity, and were 3.51 (95% CI 1.74 to 7.08), 3.41 (95% CI 1.13 to 10.24) respectively for mortality. High levels of interleukin-6 (IL-6) and IL-10 were associated with the occurrence of arrhythmias (all p < 0.05).

Conclusion: Arrhythmias were significantly associated with COVID-19 severity and mortality. Atrial arrhythmia was the most frequent arrhythmia type. IL-6 and IL-10 levels can predict the risk of arrhythmias in COVID-19 patients.
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http://dx.doi.org/10.1016/j.jelectrocard.2021.01.012DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7830267PMC
January 2021

The emerging role of kainate receptor functional dysregulation in pain.

Mol Pain 2021 Jan-Dec;17:1744806921990944

Department of Anesthesiology, Beijing Chaoyang Hospital, Capital Medical University, Beijing, China.

Pain is a serious clinical challenge, and is associated with a significant reduction in quality of life and high financial costs for affected patients. Research efforts have been made to explore the etiological basis of pain to guide the future treatment of patients suffering from pain conditions. Findings from studies using KA (kainate) receptor agonist, antagonists and receptor knockout mice suggested that KA receptor dysregulation and dysfunction may govern both peripheral and central sensitization in the context of pain. Additional evidence showed that KA receptor dysfunction may disrupt the finely-tuned process of glutamic acid transmission, thereby contributing to the onset of a range of pathological contexts. In the present review, we summarized major findings in recent studies which examined the roles of KA receptor dysregulation in nociceptive transmission and in pain. This timely overview of current knowledge will help to provide a framework for future developing novel therapeutic strategies to manage pain.
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http://dx.doi.org/10.1177/1744806921990944DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7883153PMC
February 2021

Coexistence of TDP-43 and C5b-9 staining of muscle in a patient with inclusion body myositis.

BMJ Case Rep 2021 Feb 9;14(2). Epub 2021 Feb 9.

Neurology, Penn State Health Milton S Hershey Medical Center, Hershey, Pennsylvania, USA

While sporadic inclusion body myositis (sIBM) is the most commonly acquired inflammatory myopathy above 50 years of age, its refractory response to conventional immunosuppressive treatments raises questions about its perplexing pathogenesis. Muscle biopsy typically reveals major histocompatibility complex I antigens and CD8+ T cell endomysial infiltrates invading non-necrotic muscle fibres early in the disease course with rimmed vacuoles, protein aggregates and amyloid inclusions later in the disease. Transactive response DNA-binding protein-43 (TDP-43), a protein implicated in transcriptional repression in neurodegenerative diseases, is also found in sIBM. C5b-9 membrane attack complex, an effector protein involved in the complement cascade of the immune response, is commonly found in dermatomyositis, but has rarely been reported in IBM. We describe a novel case of IBM with simultaneous C5b-9 and TDP-43 staining on quadriceps biopsy, raising the question of a possibility of concurrent immune-mediated inflammatory and myodegenerative pathogenesis.
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http://dx.doi.org/10.1136/bcr-2020-238312DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7875291PMC
February 2021

Dermatomal coverage of single-injection ultrasound-guided parasagittal approach to anterior quadratus lumborum block at the lateral supra-arcuate ligament.

J Anesth 2021 04 7;35(2):307-310. Epub 2021 Feb 7.

Department of Anesthesiology, Beijing Chaoyang Hospital, Capital Medical University, Beijing, 100020, China.

The subcostal quadratus lumborum (QL) block is used in postoperative analgesia for abdominal surgery. However, only a small portion of local anesthetic can spread into the thoracic paravertebral space from the injection site via the lateral arcuate ligament, due to the barrier action of the ligament. In this study, we determined the effectiveness of a new ultrasound-guided parasagittal approach to anterior QL block at the lateral supra-arcuate ligament. Twenty six patients scheduled for laparoscopic renal surgery were enrolled. The parasagittal approach to the anterior QL block at the lateral supra-arcuate ligament was carried out preoperatively. Our data showed that at 5 and 10 min after injection, the patients achieved the sensory block of dermatomes T9-T12 and T7-L1, respectively. Some patients achieved coverage as cephalad as T5 and as caudal as L3. Four patients (16.7%) developed quadriceps weakness after the blocks. The parasagittal technique provides a new choice for postoperative analgesia of abdominal surgery with rapid onset and reliable dermatomal coverage.Trial registration: Chinese Clinical Trial Registry: ChiCTR2000029211.
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http://dx.doi.org/10.1007/s00540-021-02903-1DOI Listing
April 2021

The specific DNA barcodes based on chloroplast genes for species identification of Orchidaceae plants.

Sci Rep 2021 Jan 14;11(1):1424. Epub 2021 Jan 14.

College of Biology, Hunan University, Changsha, 410082, China.

DNA barcoding is currently an effective and widely used tool that enables rapid and accurate identification of plant species. The Orchidaceae is the second largest family of flowering plants, with more than 700 genera and 20,000 species distributed nearly worldwide. The accurate identification of Orchids not only contributes to the safe utilization of these plants, but also it is essential to the protection and utilization of germplasm resources. In this study, the DNA barcoding of 4 chloroplast genes (matK, rbcL, ndhF and ycf1) were used to provide theoretical basis for species identification, germplasm conservation and innovative utilization of orchids. By comparing the nucleotide replacement saturation of the single or combined sequences among the 4 genes, we found that these sequences reached a saturation state and were suitable for phylogenetic relationship analysis. The phylogenetic analyses based on genetic distance indicated that ndhF and ycf1 sequences were competent to identification at genus and species level of orchids in a single gene. In the combined sequences, matK + ycf1 and ndhF + ycf1 were qualified for identification at the genera and species levels, suggesting the potential roles of ndhF, ycf1, matK + ycf1 and ndhF + ycf1 as candidate barcodes for orchids. Based on the SNP sites, candidate genes were used to obtain the specific barcode of orchid plant species and generated the corresponding DNA QR code ID card that could be immediately recognized by electronic devices. This study provides innovative research methods for efficient species identification of orchids. The standardized and accurate barcode information of Orchids is provided for researchers. It lays the foundation for the conservation, evaluation, innovative utilization and protection of Orchidaceae germplasm resources.
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http://dx.doi.org/10.1038/s41598-021-81087-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7809279PMC
January 2021

Transincisional Ultrasound-Guided Quadratus Lumborum Block in Open Renal Surgeries.

Pain Physician 2021 Jan;24(1):E127-E128

Department of Anesthesiology, Beijing Chaoyang Hospital, Capital Medical University, Beijing, China.

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January 2021

Corrigendum: Identification of Immune-Related Prognostic Genes and LncRNAs Biomarkers Associated With Osteosarcoma Microenvironment.

Front Oncol 2020 30;10:620320. Epub 2020 Nov 30.

Department of Gastrointestinal Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

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http://dx.doi.org/10.3389/fonc.2020.620320DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7735646PMC
November 2020

Ultrasound-Guided Lumbar Paravertebral Block After Pre-Designed Route on X-Ray Film for Radicular Pain Following Failed Back Surgery Syndrome: A Case Report.

J Pain Res 2020 8;13:3331-3336. Epub 2020 Dec 8.

Department of Anesthesiology, Beijing Chaoyang Hospital, Capital Medical University, Beijing, People's Republic of China.

Background: Persistent or recurring radicular pain after lumbar surgery is a clinical condition of failed back surgery syndrome (FBSS) that seriously affects the life quality of patients. Conventional medication and physiotherapy do not fully relieve this pain. A simpler, safer, and less invasive option is lumbar selective nerve root block or paravertebral block. Here, we share our experience regarding lumbar paravertebral block for a patient with FBSS, which successfully alleviated radicular pain after lumbar surgery.

Case Presentation: An 80-year-old man with left lower limb radicular pain diagnosed as L4-5, L5-S1 intervertebral disc protrusion, spinal canal stenosis, and degenerative scoliosis underwent lumbar surgery. Four months after surgery, he experienced left lower limb radicular pain. After designing the puncture route based on X-ray film, we performed a combined ultrasound-guided L4 and L5 paravertebral block. With his improved pain control, his functional status and ability to perform daily activities also markedly improved.

Conclusion: Real-time ultrasound-guided lumbar paravertebral block performed with a pre-designed route on X-ray film can provide a simple and safe way to relieve radicular pain in FBSS.
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http://dx.doi.org/10.2147/JPR.S280541DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7733463PMC
December 2020

eRNAs and Superenhancer lncRNAs Are Functional in Human Prostate Cancer.

Dis Markers 2020 22;2020:8847986. Epub 2020 Sep 22.

National Engineering Center for Biochip at Shanghai, Shanghai, China.

Prostate cancer (PCa) is one of the most commonly diagnosed cancers in males worldwide. lncRNAs (long noncoding RNAs) play a significant role in the occurrence and development of PCa. eRNAs (enhancer RNAs) and SE-lncRNAs (superenhancer lncRNAs) are important elements of lncRNAs, but the role of eRNAs and SE-lncRNAs in PCa remains largely unclear. In this work, we identified 681 eRNAs and 292 SE-lncRNAs that were expressed differentially in PCa using a microarray. We also found that eRNAs transcribed from active open chromatin had significantly higher expression than those from active closed chromatin, and SE-lncRNAs had a little higher expression than eRNAs. Next, we constructed a transcriptional regulation network that eRNA-related enhancer and the target genes shared the same TF-binding motifs. Further, we investigated whether CTCF played a role in mediating the transcriptional regulation network. eRNAs, especially those that regulate androgen response genes, may be candidates for prognostic biomarkers and therapy targets. Our work provides a new perspective for developing medical treatments and therapies for prostate cancer.
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http://dx.doi.org/10.1155/2020/8847986DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7532396PMC
September 2020

Carbon phosphide nanosheets and nanoribbons: insights on modulating their electronic properties by first principles calculations.

Phys Chem Chem Phys 2020 Oct;22(39):22520-22528

School of Energy and Mechanical Engineering, Jiangxi University of Science and Technology, Nanchang 330013, China.

A carbon phosphide (CP) monolayer, a 2D structure derived from the same 3-fold coordination found both in graphene and phosphorene, has been successfully synthesized in an experiment recently. In this paper, we investigated the modulation of electronic structures and transport characteristics of 2D nanosheets and quasi-1D nanoribbons of CP nanomaterials in the α-phase by using first-principles density functional theory simulation. The calculated band structures show that the band gap of 2D CP nanosheets progressively increases as the uniform biaxial strain changes from compression to stretching. However, the biaxial strain cannot change the indirect band gap behavior of the original 2D CP nanosheet. In addition, the band structures of quasi-1D nanoribbons with different styles of H-passivated zigzag edges have also been studied. The results show that the H-passivated zigzag PC ribbons with two P edges are semiconductors with indirect band gaps, and the gaps decrease with increasing width of ribbons. However, the H-passivated CP nanoribbons with one P-atom terminated edge in combination with one P-atom edge, and H-passivated CC nanoribbons with two C-atom terminated edges display metallic behaviors. The semi-conductive or metallic behaviors of zigzag CP nanoribbons can be explained by presenting the wave function of their energy band around the Fermi level. Finally, the electronic transport properties of different CP nanoribbon based nanojunctions are studied in which arise the interesting negative differential resistance or rectification effects in their current-voltage characteristic curves.
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http://dx.doi.org/10.1039/d0cp03615cDOI Listing
October 2020

Calpain activation mediates microgravity-induced myocardial abnormalities in mice via p38 and ERK1/2 MAPK pathways.

J Biol Chem 2020 12 28;295(49):16840-16851. Epub 2020 Sep 28.

Institutes of Biology and Medical Sciences, Soochow University, Suzhou, China; Department of Pathology and Laboratory Medicine, Western University, London, Ontario, Canada; Lawson Health Research Institute of London Health Sciences Centre, London, Ontario, Canada; Department of Medicine, Western University, London, Ontario, Canada. Electronic address:

The human cardiovascular system has adapted to function optimally in Earth's 1G gravity, and microgravity conditions cause myocardial abnormalities, including atrophy and dysfunction. However, the underlying mechanisms linking microgravity and cardiac anomalies are incompletely understood. In this study, we investigated whether and how calpain activation promotes myocardial abnormalities under simulated microgravity conditions. Simulated microgravity was induced by tail suspension in mice with cardiomyocyte-specific deletion of , which disrupts activity and stability of calpain-1 and calpain-2, and their WT littermates. Tail suspension time-dependently reduced cardiomyocyte size, heart weight, and myocardial function in WT mice, and these changes were accompanied by calpain activation, NADPH oxidase activation, and oxidative stress in heart tissues. The effects of tail suspension were attenuated by deletion of Notably, the protective effects of deletion were associated with the prevention of phosphorylation of Ser-345 on p47 and attenuation of ERK1/2 and p38 activation in hearts of tail-suspended mice. Using a rotary cell culture system, we simulated microgravity in cultured neonatal mouse cardiomyocytes and observed decreased total protein/DNA ratio and induced calpain activation, phosphorylation of Ser-345 on p47 , and activation of ERK1/2 and p38, all of which were prevented by calpain inhibitor-III. Furthermore, inhibition of ERK1/2 or p38 attenuated phosphorylation of Ser-345 on p47 in cardiomyocytes under simulated microgravity. This study demonstrates for the first time that calpain promotes NADPH oxidase activation and myocardial abnormalities under microgravity by facilitating p47 phosphorylation via ERK1/2 and p38 pathways. Thus, calpain inhibition may be an effective therapeutic approach to reduce microgravity-induced myocardial abnormalities.
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http://dx.doi.org/10.1074/jbc.RA119.011890DOI Listing
December 2020

Rescue of Hepatic Phospholipid Remodeling Defectin iPLA2β-Null Mice Attenuates Obese but Not Non-Obese Fatty Liver.

Biomolecules 2020 09 17;10(9). Epub 2020 Sep 17.

Institute of Clinical Chemistry and Laboratory Medicine, University of Regensburg,Franz-Josef-Strauss-Allee 11, 93053 Regensburg, Germany.

Polymorphisms of group VIA calcium-independent phospholipase A2 (iPLA2β orPLA2G6) are positively associated with adiposity, blood lipids, and Type-2 diabetes. Theubiquitously expressed iPLA2β catalyzes the hydrolysis of phospholipids (PLs) to generate a fattyacid and a lysoPL. We studied the role of iPLA2β on PL metabolism in non-alcoholic fatty liverdisease (NAFLD). By using global deletion iPLA2β-null mice, we investigated three NAFLD mousemodels; genetic Ob/Ob and long-term high-fat-diet (HFD) feeding (representing obese NAFLD) aswell as feeding with methionine- and choline-deficient (MCD) diet (representing non-obeseNAFLD). A decrease of hepatic PLs containing monounsaturated- and polyunsaturated fatty acidsand a decrease of the ratio between PLs and cholesterol esters were observed in all three NAFLDmodels. iPLA2β deficiency rescued these decreases in obese, but not in non-obese, NAFLD models.iPLA2β deficiency elicited protection against fatty liver and obesity in the order of Ob/Ob › HFD »MCD. Liver inflammation was not protected in HFD NAFLD, and that liver fibrosis was evenexaggerated in non-obese MCD model. Thus, the rescue of hepatic PL remodeling defect observedin iPLA2β-null mice was critical for the protection against NAFLD and obesity. However, iPLA2βdeletion in specific cell types such as macrophages may render liver inflammation and fibrosis,independent of steatosis protection.
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http://dx.doi.org/10.3390/biom10091332DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7565968PMC
September 2020

DVL mutations identified from human neural tube defects and Dandy-Walker malformation obstruct the Wnt signaling pathway.

J Genet Genomics 2020 06 27;47(6):301-310. Epub 2020 Jun 27.

Obstetrics and Gynecology Hospital, State Key Laboratory of Genetic Engineering at School of Life Sciences, Fudan University, Shanghai, 200011, China; NHC Key Lab of Reproduction (Shanghai Institute of Planned Parenthood Research), Institute of Reproduction and Development, Fudan University, Shanghai, 200032, China; Children's Hospital and Institutes of Biomedical Sciences, Fudan University, Shanghai, 200032, China. Electronic address:

Wnt signaling pathways, including the canonical Wnt/β-catenin pathway, planar cell polarity pathway, and Wnt/Ca signaling pathway, play important roles in neural development during embryonic stages. The DVL genes encode the hub proteins for Wnt signaling pathways. The mutations in DVL2 and DVL3 were identified from patients with neural tube defects (NTDs), but their functions in the pathogenesis of human neural diseases remain elusive. Here, we sequenced the coding regions of three DVL genes in 176 stillborn or miscarried fetuses with NTDs or Dandy-Walker malformation (DWM) and 480 adult controls from a Han Chinese population. Four rare mutations were identified: DVL1 p.R558H, DVL1 p.R606C, DVL2 p.R633W, and DVL3 p.R222Q. To assess the effect of these mutations on NTDs and DWM, various functional analyses such as luciferase reporter assay, stress fiber formation, and in vivo teratogenic assay were performed. The results showed that the DVL2 p.R633W mutation destabilized DVL2 protein and upregulated activities for all three Wnt signalings (Wnt/β-catenin signaling, Wnt/planar cell polarity signaling, and Wnt/Ca signaling) in mammalian cells. In contrast, DVL1 mutants (DVL1 p.R558H and DVL1 p.R606C) decreased canonical Wnt/β-catenin signaling but increased the activity of Wnt/Ca signaling, and DVL3 p.R222Q only decreased the activity of Wnt/Ca signaling. We also found that only the DVL2 p.R633W mutant displayed more severe teratogenicity in zebrafish embryos than wild-type DVL2. Our study demonstrates that these four rare DVL mutations, especially DVL2 p.R633W, may contribute to human neural diseases such as NTDs and DWM by obstructing Wnt signaling pathways.
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http://dx.doi.org/10.1016/j.jgg.2020.06.003DOI Listing
June 2020

Identification of Immune-Related Prognostic Genes and LncRNAs Biomarkers Associated With Osteosarcoma Microenvironment.

Front Oncol 2020 24;10:1109. Epub 2020 Jul 24.

Department of Gastrointestinal Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

Osteosarcoma (OS) is the most common malignancy of the bone that occurs majorly in young people and adolescents. Although the survival of OS patients markedly improved by complete surgical resection and chemotherapy, the outcome is still poor in patients with recurrent and/or metastasized OS. Thus, identifying prognostic biomarkers that reflect the biological heterogeneity of OS could lead to better interventions for OS patients. Increasing studies have indicated the association between immune-related genes (IRGs) and cancer prognosis. In the present study, based on the data concerning OS obtained from TARGET (Therapeutically Applicable Research to Generate Effective Treatments) database, we constructed a classifier containing 12 immune-related (IR) long non-coding RNAs (lncRNAs) and 3 IRGs for predicting the prognosis of OS by using the least absolute shrinkage and selection operation Cox regression. Besides, based on the risk score calculated by the classifier, the samples were divided into high- and low-risk groups. We further investigated the tumor microenvironment of the OS samples by ESTIMATE and CIBERSORT algorithms between the two groups. Finally, we identified three small molecular drugs with potential therapeutic value for OS patients with high-risk score. Our results suggest that the IRGs and IR-lncRNAs-based classifier could be used as a reliable prognostic predictor for OS survival.
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http://dx.doi.org/10.3389/fonc.2020.01109DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7393189PMC
July 2020

Ultrasound and pressure-guided thoracic paravertebral block: A preliminary investigation.

Eur J Anaesthesiol 2020 09;37(9):824-826

From the Department of Anaesthesiology, Beijing Chaoyang Hospital, Capital Medical University, Beijing (HL, DM, YW) and Department of Anaesthesiology, Shiyan Taihe Hospital, Affiliated Hospital of Hubei University of Medicine, Hubei, Shiyan, China (HW).

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http://dx.doi.org/10.1097/EJA.0000000000001198DOI Listing
September 2020

Association between rare variants in specific functional pathways and human neural tube defects multiple subphenotypes.

Neural Dev 2020 07 10;15(1). Epub 2020 Jul 10.

Beijing Municipal Key Laboratory of Child Development and Nutriomics, Capital Institute of Pediatrics, Beijing, 100020, China.

Background: Neural tube defects (NTDs) are failure of neural tube closure, which includes multiple central nervous system phenotypes. More than 300 mouse mutant strains exhibits NTDs phenotypes and give us some clues to establish association between biological functions and subphenotypes. However, the knowledge about association in human remains still very poor.

Methods: High throughput targeted genome DNA sequencing were performed on 280 neural tube closure-related genes in 355 NTDs cases and 225 ethnicity matched controls, RESULTS: We explored that potential damaging rare variants in genes functioning in chromatin modification, apoptosis, retinoid metabolism and lipid metabolism are associated with human NTDs. Importantly, our data indicate that except for planar cell polarity pathway, craniorachischisis is also genetically related with chromatin modification and retinoid metabolism. Furthermore, single phenotype in cranial or spinal regions displays significant association with specific biological function, such as anencephaly is associated with potentially damaging rare variants in genes functioning in chromatin modification, encephalocele is associated with apoptosis, retinoid metabolism and one carbon metabolism, spina bifida aperta and spina bifida cystica are associated with apoptosis; lumbar sacral spina bifida aperta and spina bifida occulta are associated with lipid metabolism. By contrast, complex phenotypes in both cranial and spinal regions display association with various biological functions given the different phenotypes.

Conclusions: Our study links genetic variant to subphenotypes of human NTDs and provides a preliminary but direct clue to investigate pathogenic mechanism for human NTDs.
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http://dx.doi.org/10.1186/s13064-020-00145-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7353782PMC
July 2020

Persistent proliferation of keratinocytes and prolonged expression of pronociceptive inflammatory mediators might be associated with the postoperative pain in KK mice.

Mol Pain 2020 Jan-Dec;16:1744806920927284

Department of Anesthesiology, Beijing Chaoyang Hospital, Capital Medical University, Beijing, China.

Epidermal keratinocytes play a vital role in restoration of the intact skin barrier during wound healing. The negative effect of hyperglycemia may prolong the wound healing process. Epidermal keratinocytes have been demonstrated to modulate and directly initiate nociceptive responses in rat models of fractures and chemotherapy-induced neuropathic pain. However, it is unclear whether epidermal keratinocytes are involved in the development and maintenance of incisional pain in nondiabetic or diabetic animals. In the current study, using behavioral tests and immunohistochemistry, we investigated the differential keratinocytes proliferation and expression of pronociceptive inflammatory mediators in keratinocytes in C57BL/6J mice and diabetic KK mice. Our data showed that plantar incision induced postoperative pain hypersensitivity in both C57BL/6J mice and KK mice, while the duration of postoperative pain hypersensitivity in KK mice was longer than that in C57BL/6J mice. Moreover, plantar incision induced the keratinocytes proliferation and expression of IL-1β and TNF-α in keratinocytes in both C57BL/6J mice and KK mice. Interestingly, compared to C57BL/6J mice, the slower and more persistent proliferation of keratinocytes and expression of IL-1β and TNF-α in keratinocytes were observed in KK mice. Together, our study suggested that plantar incision may induce the differential keratinocytes proliferation and expression of IL-1β and TNF-α in kertinocytes in diabetic and nondiabetic animals, which might be associated with the development and maintenance differences in diabetic and nondiabetic postoperative pain.
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http://dx.doi.org/10.1177/1744806920927284DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7252385PMC
May 2020

PINK1 Activation and Translocation to Mitochondria-Associated Membranes Mediates Mitophagy and Protects Against Hepatic Ischemia/Reperfusion Injury.

Shock 2020 12;54(6):783-793

Department of Gastrointestinal Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

Hepatic ischemia/reperfusion (I/R) injury is a major concern in liver surgery settings. Mitochondria are critical targets or the origin of tissue injury, particularly I/R injury. Mitophagy, a selective form of autophagy, is a fundamental process that removes damaged or unwanted mitochondria for mitochondrial quality control, but its role in hepatic I/R remains unclear. In the present study, we investigated the role of mitophagy in hepatic I/R by focusing on PTEN-induced putative kinase 1 (PINK1). Livers from 10-week-old mice and primary hepatocytes were subjected to in vivo hepatic I/R and in vitro hypoxia-reoxygenation (H/R), respectively. Analyses of oxidative stress, immunoblotting, and ATP generation showed that hepatic I/R leads to mitochondrial damage. Dysfunctional mitochondria promoted reactive oxygen species (ROS) production and apoptosis. Hepatic I/R led to decreases in the mitochondrial proteins COX4 and TOM20 and mitochondrial DNA and increases in the autophagy-related indicators LC3 and P62, which indicates that hepatic I/R promotes mitophagy. We found that I/R also leads to endoplasmic reticulum stress, which has frequent signal communication with mitochondria through the mitochondria-associated membranes (MAMs). We showed that the mitophagy-related proteins Parkin, Beclin, optineurin were enhanced in hepatic I/R. No significant change is in PINK1 but it translocated to MAMs region to initiate mitophagy. The silencing PINK1 by shRNA in cultured primary hepatocytes reduced the level of H/R-induced mitophagy, leading to the accumulation of dysfunctional mitochondria during H/R, increased production of ROS, mitochondria-induced apoptosis, and eventually hepatocyte death. Taken together, these findings indicate that PINK1-mediated mitophagy plays a key role in mitochondrial quality control and liver cell survival during I/R.
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http://dx.doi.org/10.1097/SHK.0000000000001534DOI Listing
December 2020