Publications by authors named "Xun Wu"

145 Publications

Long-term outcome of stereotactic aspiration, endoscopic evacuation, and open craniotomy for the treatment of spontaneous basal ganglia hemorrhage: a propensity score study of 703 cases.

Ann Transl Med 2021 Aug;9(16):1289

Department of Neurosurgery, Tangdu Hospital, the Fourth Military Medical University, Xi'an, China.

Background: To compare the long-term therapeutic effects of stereotactic aspiration (SA), endoscopic evacuation (EE), and open craniotomy (OC) in the surgical treatment of spontaneous basal ganglia hemorrhage and explore the appropriate clinical indications for each technique.

Methods: Multiple-treatment inverse probability of treatment weighting (IPTW)-adjusted logistic regression analysis was performed to evaluate the therapeutic effects of these techniques. The primary and secondary outcomes were 6-month modified Rankin Scale (mRS) and mortality rates, respectively.

Results: A total of 703 patients were ultimately enrolled. For the entire cohort, the 6-month mortality rate was significantly higher (OR 2.396, 95% CI: 1.865-3.080), and the 6-month functional outcome was significantly worse (OR 1.359, 95% CI: 1.091-1.692) for SA than that of EE. The 6-month mortality rate for OC was significantly higher (OR 1.395, 95% CI: 1.059-1.837) than that of EE. Further subgroup analysis was stratified by initial hematoma volume and Glasgow Coma Scale (GCS) score. The mortality rate for SA was significantly higher for patients with hematoma volume of 20-40 mL (OR 6.226, 95% CI: 3.848-10.075), 40-80 mL (OR 2.121, 95% CI: 1.492-3.016), and ≥80 mL (OR 5.544, 95% CI: 3.315-9.269) than in the same subgroups of EE. The functional outcomes for SA were significantly worse than that of EE for hematoma volume subgroups of 40-80 mL (OR 1.424, 95% CI: 1.039-1.951) and ≥80 mL (OR 4.224, 95% CI: 1.655-10.776). The mortality rate for SA was significantly higher than that of EE for the GCS score subgroups of 6-8 (OR 2.082, 95% CI: 1.410-3.076) and 3-5 (OR 2.985, 95% CI: 1.904-4.678). The mortality rate for OC was significantly higher for the GCS score of 3-5 subgroup (OR 1.718, 95% CI: 1.115-2.648), and a tendency for a higher mortality rate of 6-8 subgroup (OR 1.442, 95% CI: 0.965-2.156) than that of EE.

Conclusions: EE can decrease the 6-month mortality rate and improve the 6-month functional outcomes of spontaneous basal ganglia hemorrhage in patients with a hematoma volume ≥40 mL. EE can decrease the 6-month mortality rate of spontaneous basal ganglia hemorrhage in patients with a GCS score of 3-8.
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http://dx.doi.org/10.21037/atm-21-1612DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8422088PMC
August 2021

Epilepsy centers in China: Current status and ways forward.

Epilepsia 2021 Sep 12. Epub 2021 Sep 12.

Department of Neurology, Xuanwu Hospital, Capital Medical University, Beijing, China.

Objective: China has the largest population of patients with epilepsy worldwide, which imposes a heavy burden on the public and health care systems. Several epidemiological surveys on epilepsy have been performed in China. Although these surveys grossly describe the prevalence and gap in treatment of epilepsy, the status of epilepsy centers is unclear. The number of epilepsy centers has increased substantially in recent decades. Therefore, a nationwide investigation of the scale and distribution, personnel, equipment, and epilepsy care capacity of each epilepsy center is of great value.

Methods: In 2017-2018, a multicenter cross-sectional survey was performed by the Commission on Standardized Development of Epilepsy Centers, China Association Against Epilepsy in 31 provinces, autonomous regions, and municipalities. The survey consisted of 74 questions divided into four sections: (1) overview, (2) personnel, (3) essential equipment and facilities, and (4) epilepsy care service capacity. The questions ranged from January 1, 2016 to December 31, 2016. The data were analyzed using descriptive statistics.

Results: There were 358 epilepsy centers for the 1.38 billion national population in 2016. Three quarters were in the eastern and western regions, and >90% were in tertiary hospitals. There were 9688 doctors engaged in epilepsy care, and 4.8% of doctors and electrophysiological physicians/technicians passed the national test for electroencephalography technical accreditation. A total of 9667 patients underwent resective surgeries in 2016. There were 888 vagus nerve stimulation procedures and 275 deep brain stimulation procedures.

Significance: This study is the first unique survey of epilepsy centers in China. Despite their rapid development, epilepsy centers cannot meet patients' needs at this stage. The results provide data-based evidence for the formulation of policies related to epilepsy service planning.
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http://dx.doi.org/10.1111/epi.17058DOI Listing
September 2021

Effect of red light on the composition of metabolites in tea leaves during the withering process using untargeted metabolomics.

J Sci Food Agric 2021 Aug 21. Epub 2021 Aug 21.

Tea Research Institute, Chinese Academy of Agricultural Sciences, Hangzhou, China.

Background: Red light withering significantly improves the sensory flavor qualities of tea, although changes in metabolites during this process have not been systematically studied until now. The present study comprehensively analyzes metabolites in withered tea leaves at 2-h intervals up to 12 h under red light (630 nm) and dark conditions using ultra performance liquid chromatography-high resolution mass spectrometry (untargeted metabolomics).

Results: Ninety-four non-volatile compounds are identified and relatively quantified, including amino acids, catechins, dimeric catechins, flavonol glycosides, glycosidically-bound volatiles, phenolic acids and nucleosides. The results show that amino acids, catechins and dimeric catechins are most affected by red light treatment. Ten free amino acids, theaflavins and theasinensin A increase after red light irradiation, whereas epigallocatechin gallate and catechin fall.

Conclusion: The present study provides a comprehensive and systematic profile of the dynamic effects of red light on withering tea and a rationale for its use in tea processing quality control. © 2021 Society of Chemical Industry.
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http://dx.doi.org/10.1002/jsfa.11500DOI Listing
August 2021

Association between Growth Differentiation Factor-15 and Risk of Cardiovascular Diseases in Patients with Adult Growth Hormone Deficiency.

Int J Endocrinol 2021 6;2021:5921863. Epub 2021 Aug 6.

Department of Endocrinology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China.

Objective: Patients with adult growth hormone deficiency (AGHD) confer a heightened risk of cardiovascular disease and increased mortality because of metabolic disorders. Growth differentiation factor-15 (GDF-15) plays an important role in predicting metabolic abnormalities. We sought to investigate the correlation between GDF-15 and cardiovascular risk in AGHD patients.

Methods: The study enrolled 80 AGHD patients and 80 healthy subjects. We analyzed the association between GDF-15 and some major biochemical indicators. The potential association between GDF-15 and cardiovascular disease risk was analyzed.

Results: The AGHD group exhibited increased waist-hip ratio and high-sensitivity C-reactive protein (hs-CRP) and lipid levels compared with the healthy control group. Serum GDF-15 levels in AGHD group were elevated significantly compared with the control group ( < 0.001). GDF-15 levels were negatively associated with insulin-like growth factor-1 in AGHD group (=0.006) and positively correlated with waist-to-hip ratio (=0.018), triglycerides (=0.007), and hs-CRP (=0.046). In addition, GDF-15 was positively correlated with Framingham risk score significantly after adjustment for other factors ( = 0.497, < 0.001). Moreover, GDF-15 was an independent risk factor for cardiovascular disease in AGHD patients after adjusting for traditional cardiovascular risk factors.

Conclusion: Elevated GDF-15 levels were significantly associated with cardiovascular risk factors and can be considered as a predictive biomarker of cardiovascular risk in AGHD patients.
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http://dx.doi.org/10.1155/2021/5921863DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8363436PMC
August 2021

Development of recombinase polymerase amplification combined with lateral flow detection assay for rapid and visual detection of Ralstonia solanacearum in tobacco.

Plant Dis 2021 Jul 8. Epub 2021 Jul 8.

College of Plant Protection, Anhui Agricultural University, Department of Plant Pathology, Hefei, Anhui, China, Hefei, Anhui, China, 230036;

Bacterial wilt caused by Ralstonia solanacearum is a serious soil-borne disease that results in severe losses to tobacco (Nicotiana tabacum) production in China. In this study, a novel RPA-LFD assay for the rapid visual detection of R. solanacearum was established using recombinase polymerase amplification (RPA) and lateral-flow dipstick (LFD). The RPA-LFD assay was performed at 37°C in 30 min without complex equipment. Targeting the sequence of the RipTALI-9 gene, we designed RPA primers (Rs-rpa-F/R) and an LF probe (Rs-LF-probe) that showed high specificity to R. solanacearum. The sensitivity of RPA-LFD assay to R. solanacearum was the same as that in conventional PCR at 1 pg genomic DNA, 102 CFU/g artificially inoculated tobacco stem, and 103 CFU/g artificially inoculated soil. The RPA-LFD assay could also detect R. solanacearum from plant and soil samples collected from naturally infested tobacco fields. These results suggest that the RPA-LFD assay developed in this study is a rapid, accurate molecular diagnostic tool with high sensitivity for the detection of R. solanacearum.
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http://dx.doi.org/10.1094/PDIS-04-21-0688-REDOI Listing
July 2021

Correlation of Significantly Decreased Serum Circulating Mesencephalic Astrocyte-Derived Neurotrophic Factor Level With an Increased Risk of Future Cardiovascular Disease in Adult Patients With Growth Hormone Deficiency.

Front Endocrinol (Lausanne) 2021 16;12:671126. Epub 2021 Jun 16.

Department of Endocrinology and Metabolism, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China.

Objective: Adult growth hormone deficiency (AGHD) is a rare chronic inflammatory disease caused by damage to the pituitary gland and is accompanied by disorders of multiple metabolic pathways. By examining the correlation between the serum mesencephalic astrocyte-derived neurotrophic factor (MANF) levels of AGHD patients and those of normal controls, we hope to elucidate the close relationship among MANF, lipid metabolism and insulin resistance in AGHD and discuss the potential therapeutic value of MANF.

Methods: This study included 101 AGHD patients and 100 healthy subjects matched for sex, age, height, and weight. Anthropometric parameters and biochemical indicators such as body mass index, waist circumference, hip circumference, serum MANF level, blood lipids and insulin level were measured. The above patients were also divided into several subgroups for correlation analysis based on indicators such as insulin resistance and BMI.

Results: The serum circulating MANF content of AGHD patients was significantly lower than that of the normal control group (5.235 (0.507-17.62) ng/ml (n=101) 10.30 (1.84-16.65) ng/ml (n=100); p<0.0001), and circulating MANF levels were linearly correlated with HOMA-IR in the AGHD population (R=0.481, P=0.0041). When MANF was at pathological concentrations (lower than the mean circulating MANF of normal controls), the lowest concentration tertile (OR=21.429 p<0.0001) had a significantly higher disease odds ratio, Framingham risk score and 10-year risk of atherosclerotic cardiovascular disease than the highest concentration tertile.

Conclusions: MANF has a significant correlation with insulin resistance in the AGHD state. There is a strong correlation with abnormal glucose and lipid metabolism in the obese AGHD population. MANF is also a good assessment factor for the risk of cardiovascular disease in AGHD patients and has excellent therapeutic potential.
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http://dx.doi.org/10.3389/fendo.2021.671126DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8242342PMC
June 2021

Cell Death and Exosomes Regulation After Myocardial Infarction and Ischemia-Reperfusion.

Front Cell Dev Biol 2021 9;9:673677. Epub 2021 Jun 9.

Department of Cardiovascular Surgery, The Second Xiangya Hospital, Central South University, Changsha, China.

Cardiovascular disease (CVD) is the leading cause of death in the global population, accounting for about one-third of all deaths each year. Notably, with CVDs, myocardial damages result from myocardial infarction (MI) or cardiac arrhythmias caused by interrupted blood flow. Significantly, in the process of MI or myocardial ischemic-reperfusion (I/R) injury, both regulated and non-regulated cell death methods are involved. The critical factor for patients' prognosis is the infarct area's size, which determines the myocardial cells' survival. Cell therapy for MI has been a research hotspot in recent years; however, exosomes secreted by cells have attracted much attention following shortcomings concerning immunogens. Exosomes are extracellular vesicles containing several biologically active substances such as lipids, nucleic acids, and proteins. New evidence suggests that exosomes play a crucial role in regulating cell death after MI as exosomes of various stem cells can participate in the cell damage process after MI. Hence, in the review herein, we focused on introducing various cell-derived exosomes to reduce cell death after MI by regulating the cell death pathway to understand myocardial repair mechanisms better and provide a reference for clinical treatment.
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http://dx.doi.org/10.3389/fcell.2021.673677DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8220218PMC
June 2021

A re-irradiation dose of 55-60 Gy improves the survival rate of patients with local recurrent esophageal squamous cell carcinoma after radiotherapy.

Radiat Oncol 2021 Jun 8;16(1):100. Epub 2021 Jun 8.

Department of Oncology, Chengdu Fifth People's Hospital, No 33, Mashi Street, Wenjiang District, Chengdu, 611130, Sichuan, People's Republic of China.

Introduction: Local recurrence (LR) is clinical challenge in the treatment of esophageal squamous cell carcinoma (ESCC). The current study aimed to determine the optimal re-irradiation dose for local recurrent esophageal squamous cell carcinoma (LRESCC) following radical (chemo) radiotherapy.

Methods: We retrospectively analyzed 125 patients with LRESCC after receiving initial radiotherapy. For radiotherapy treatment, 58 patients were assigned to low-dose (LD) group (50-54 Gy) and 67 were assigned to the high-dose (HD) group (55-60 Gy). The response rate (complete + partial response), 1-, 2- and 3-year survival rate, and toxicity were recorded. We then analyzed the impact of different radiotherapy doses and combination chemotherapy on the survival of patients with LRESCC.

Results: After re-irradiation, the 1-, 2- and 3-year survival rates in the LD and HD groups were 48.3%, 24.1% and 10.3% and 61.2%, 34.3% and 19.4% in the HD group, respectively, and the difference in overall survival rate between the two groups were significant (P < 0.05). The median survival time of patients receiving radiotherapy alone was 9 months in the LD group and 15 months in the HD group (P < 0.05). The survival rate of patients treated with chemoradiotherapy was higher than that of patients treated with radiotherapy alone in the LD group. However, chemoradiotherapy showed no advantage over radiotherapy alone in the HD group. In addition, the incidence of radiation esophagitis, the most common toxicity, was higher in the HD group compared to the LD group (68.7% vs 58.6%). Multivariate analysis demonstrated that re-irradiation dose was an independent favorable prognostic factor in patients with LRESCC.

Conclusion: Higher re-irradiation dose (55-60 Gy) can improve the long-term survival of patients with LRESCC after radiotherapy, with tolerable toxicity.
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http://dx.doi.org/10.1186/s13014-021-01828-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8186078PMC
June 2021

Altered T Follicular Helper Cell Subsets and Function in Chronic Lymphocytic Leukemia.

Front Oncol 2021 28;11:674492. Epub 2021 Apr 28.

Department of Immunology, Max Rady College of Medicine, Rady Faculty of Health Sciences, University of Manitoba, Winnipeg, MB, Canada.

Follicular helper T cells (T) have specialized properties in promoting normal B cell activation but their role in chronic lymphocytic leukemia (CLL) is unknown. We find that T cells are elevated in CLL patients and are phenotypically abnormal, expressing higher levels of PD-1, TIGIT, CD40L, IFNγ and IL-21, and exhibiting abnormal composition of T1, T2 and T17 subsets. Frequencies of CD4-positive T cells expressing T1 markers and IL-21 were positively correlated with patient lymphocyte counts and RAI stage, suggesting that accumulation of abnormal T cells is concomitant with expansion of the leukemic B cell clone. Treatment with ibrutinib led to normalization of T frequencies and phenotype. T cells identified in CLL bone marrow display elevated expression of several functional markers compared to blood T cells. CLL T cell-B cell co-culture experiments revealed a correlation of patient T frequencies with functional ability of their CD4-positive T cells to promote CLL proliferation. Conversely, CLL cells can preferentially activate the T cell subset in co-culture. Together our results indicate that CLL development is associated with expansion of abnormal T populations that produce elevated levels of cytokines and costimulatory molecules which may help support CLL proliferation.
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http://dx.doi.org/10.3389/fonc.2021.674492DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8113764PMC
April 2021

Simulation of gas transport in a landfill with layered new and old municipal solid waste.

Sci Rep 2021 05 3;11(1):9436. Epub 2021 May 3.

College of Hohai, Chongqing Jiaotong University, Chongqing, 400074, China.

Average biodegradation rate of newly filled municipal solid waste (MSW) in landfills is relatively fast, and the landfill gas produced by the new MSW biodegradation can cause great variations in gas pressure. To predict the gas pressure distribution in the MSW layer, a one-dimensional gas transport model is established in this study. The following factors are considered in this model: (1) the variation of gas permeability with depth; (2) the anisotropy ratio of gas permeability; (3) the settlement caused by waste biodegradation. Furthermore, a single peak model for gas production is applied as the source term of gas production. The equation for settlement caused by waste biodegradation is presented, and the time of peak gas production rate is obtained by fitting the settlement of the newly filled layer. The stratification of the unsaturated and saturated regions is taken into account by distinguishing the difference in gas saturation. The layering of the new and old waste layers is considered by distinguishing the difference in the length of time that waste has been degraded to produce gas. Based on the method of numerical calculation, the gas pressure distribution in the landfill with layered new and old MSW is well simulated. The position where the maximum gas pressure occurs is found. The sensitivity analysis shows that the influence of the anisotropy ratio on gas pressure distribution is more significant.
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http://dx.doi.org/10.1038/s41598-021-88858-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8093249PMC
May 2021

Acrolein Induces Systemic Coagulopathy via Autophagy-dependent Secretion of von Willebrand Factor in Mice after Traumatic Brain Injury.

Neurosci Bull 2021 Aug 3;37(8):1160-1175. Epub 2021 May 3.

Department of Neurosurgery, Tangdu Hospital, Fourth Military Medical University, Xi'an, 710038, China.

Traumatic brain injury (TBI)-induced coagulopathy has increasingly been recognized as a significant risk factor for poor outcomes, but the pathogenesis remains poorly understood. In this study, we aimed to investigate the causal role of acrolein, a typical lipid peroxidation product, in TBI-induced coagulopathy, and further explore the underlying molecular mechanisms. We found that the level of plasma acrolein in TBI patients suffering from coagulopathy was higher than that in those without coagulopathy. Using a controlled cortical impact mouse model, we demonstrated that the acrolein scavenger phenelzine prevented TBI-induced coagulopathy and recombinant ADAMTS-13 prevented acrolein-induced coagulopathy by cleaving von Willebrand factor (VWF). Our results showed that acrolein may contribute to an early hypercoagulable state after TBI by regulating VWF secretion. mRNA sequencing (mRNA-seq) and transcriptome analysis indicated that acrolein over-activated autophagy, and subsequent experiments revealed that acrolein activated autophagy partly by regulating the Akt/mTOR pathway. In addition, we demonstrated that acrolein was produced in the perilesional cortex, affected endothelial cell integrity, and disrupted the blood-brain barrier. In conclusion, in this study we uncovered a novel pro-coagulant effect of acrolein that may contribute to TBI-induced coagulopathy and vascular leakage, providing an alternative therapeutic target.
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http://dx.doi.org/10.1007/s12264-021-00681-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8353051PMC
August 2021

Superhydrophobic Nanocoatings as Intervention against Biofilm-Associated Bacterial Infections.

Nanomaterials (Basel) 2021 Apr 19;11(4). Epub 2021 Apr 19.

Department of Pharmaceutical Chemistry, School of Pharmacy, International Medical University (IMU), Bukit Jalil, Kuala Lumpur 57000, Malaysia.

Biofilm formation represents a significant cause of concern as it has been associated with increased morbidity and mortality, thereby imposing a huge burden on public healthcare system throughout the world. As biofilms are usually resistant to various conventional antimicrobial interventions, they may result in severe and persistent infections, which necessitates the development of novel therapeutic strategies to combat biofilm-based infections. Physicochemical modification of the biomaterials utilized in medical devices to mitigate initial microbial attachment has been proposed as a promising strategy in combating polymicrobial infections, as the adhesion of microorganisms is typically the first step for the formation of biofilms. For instance, superhydrophobic surfaces have been shown to possess substantial anti-biofilm properties attributed to the presence of nanostructures. In this article, we provide an insight into the mechanisms underlying biofilm formation and their composition, as well as the applications of nanomaterials as superhydrophobic nanocoatings for the development of novel anti-biofilm therapies.
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http://dx.doi.org/10.3390/nano11041046DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8073257PMC
April 2021

Design and Fabrication of Wideband Air-Coupled Capacitive Micromachined Ultrasonic Transducers With Varying Width Annular-Ring and Spiral Cell Structures.

IEEE Trans Ultrason Ferroelectr Freq Control 2021 Aug 26;68(8):2749-2759. Epub 2021 Jul 26.

Air-coupled transducers with broad bandwidth are desired for many airborne applications, such as obstacle detection, haptic feedback, and flow metering. In this article, we present a design strategy and demonstrate a fabrication process for developing improved concentric annular- and novel spiral-shaped capacitive micromachined ultrasonic transducers (CMUTs) that can generate high output pressure and provide wide bandwidth in air. We explore the ability to implement complex geometries by photolithographic definition to improve the bandwidth of air-coupled CMUTs. The ring widths in the annular design were varied so that the device can be improved in terms of bandwidth when these rings resonate in parallel. Using the same ring width parameters for the spiral-shaped design but with a smoother transition between the ring widths along the spiral, the bandwidth of the spiral-shaped device is improved. With the reduced process complexity associated with the anodic-bonding-based fabrication process, a 25- [Formula: see text] vibrating silicon plate was bonded to a borosilicate glass wafer with up to 15- [Formula: see text] deep cavities. The fabricated devices show an atmospheric deflection profile that is in agreement with the FEM results to verify the vacuum sealing of the devices. The devices show a 3-dB fractional bandwidth (FBW) of 12% and 15% for spiral- and annular-shaped CMUTs, respectively. We measured a 127-dB sound pressure level at the surface of the transducers. The angular response of the fabricated CMUTs was also characterized. The results demonstrated in this article show the possibility of improving the bandwidth of air-coupled devices by exploring the flexibility in the design process associated with CMUT technology.
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http://dx.doi.org/10.1109/TUFFC.2021.3076143DOI Listing
August 2021

Death after discharge: prognostic model of 1-year mortality in traumatic brain injury patients undergoing decompressive craniectomy.

Chin Neurosurg J 2021 Apr 21;7(1):24. Epub 2021 Apr 21.

Department of Neurosurgery, Tangdu Hospital, No. 569 Xin Si Road, Xi'an, 710038, Shaanxi Province, China.

Background: Despite advances in decompressive craniectomy (DC) for the treatment of traumatic brain injury (TBI), these patients are at risk of having a poor long-term prognosis. The aim of this study was to predict 1-year mortality in TBI patients undergoing DC using logistic regression and random tree models.

Methods: This was a retrospective analysis of TBI patients undergoing DC from January 1, 2015, to April 25, 2019. Patient demographic characteristics, biochemical tests, and intraoperative factors were collected. One-year mortality prognostic models were developed using multivariate logistic regression and random tree algorithms. The overall accuracy, sensitivity, specificity, and area under the receiver operating characteristic curves (AUCs) were used to evaluate model performance.

Results: Of the 230 patients, 70 (30.4%) died within 1 year. Older age (OR, 1.066; 95% CI, 1.045-1.087; P < 0.001), higher Glasgow Coma Score (GCS) (OR, 0.737; 95% CI, 0.660-0.824; P < 0.001), higher D-dimer (OR, 1.005; 95% CI, 1.001-1.009; P = 0.015), coagulopathy (OR, 2.965; 95% CI, 1.808-4.864; P < 0.001), hypotension (OR, 3.862; 95% CI, 2.176-6.855; P < 0.001), and completely effaced basal cisterns (OR, 3.766; 95% CI, 2.255-6.290; P < 0.001) were independent predictors of 1-year mortality. Random forest demonstrated better performance for 1-year mortality prediction, which achieved an overall accuracy of 0.810, sensitivity of 0.833, specificity of 0.800, and AUC of 0.830 on the testing data compared to the logistic regression model.

Conclusions: The random forest model showed relatively good predictive performance for 1-year mortality in TBI patients undergoing DC. Further external tests are required to verify our prognostic model.
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http://dx.doi.org/10.1186/s41016-021-00242-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8058982PMC
April 2021

Potential of Superhydrophobic Surface for Blood-Contacting Medical Devices.

Int J Mol Sci 2021 Mar 24;22(7). Epub 2021 Mar 24.

Department of Pharmaceutical Chemistry, School of Pharmacy, International Medical University, Kuala Lumpur 57000, Malaysia.

Medical devices are indispensable in the healthcare setting, ranging from diagnostic tools to therapeutic instruments, and even supporting equipment. However, these medical devices may be associated with life-threatening complications when exposed to blood. To date, medical device-related infections have been a major drawback causing high mortality. Device-induced hemolysis, albeit often neglected, results in negative impacts, including thrombotic events. Various strategies have been approached to overcome these issues, but the outcomes are yet to be considered as successful. Recently, superhydrophobic materials or coatings have been brought to attention in various fields. Superhydrophobic surfaces are proposed to be ideal blood-compatible biomaterials attributed to their beneficial characteristics. Reports have substantiated the blood repellence of a superhydrophobic surface, which helps to prevent damage on blood cells upon cell-surface interaction, thereby alleviating subsequent complications. The anti-biofouling effect of superhydrophobic surfaces is also desired in medical devices as it resists the adhesion of organic substances, such as blood cells and microorganisms. In this review, we will focus on the discussion about the potential contribution of superhydrophobic surfaces on enhancing the hemocompatibility of blood-contacting medical devices.
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http://dx.doi.org/10.3390/ijms22073341DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8036518PMC
March 2021

Topochemical Deintercalation of Li from Layered LiNiB: toward 2D MBene.

J Am Chem Soc 2021 Mar 15;143(11):4213-4223. Epub 2021 Mar 15.

Department of Chemistry, Iowa State University, Ames, Iowa 50011, United States.

The pursuit of two-dimensional (2D) borides, MBenes, has proven to be challenging, not the least because of the lack of a suitable precursor prone to the deintercalation. Here, we studied room-temperature topochemical deintercalation of lithium from the layered polymorphs of the LiNiB compound with a considerable amount of Li stored in between [NiB] layers (33 at. % Li). Deintercalation of Li leads to novel metastable borides (LiNiB) with unique crystal structures. Partial removal of Li is accomplished by exposing the parent phases to air, water, or dilute HCl under ambient conditions. Scanning transmission electron microscopy and solid-state Li and B NMR spectroscopy, combined with X-ray pair distribution function (PDF) analysis and DFT calculations, were utilized to elucidate the novel structures of LiNiB and the mechanism of Li-deintercalation. We have shown that the deintercalation of Li proceeds via a "zip-lock" mechanism, leading to the condensation of single [NiB] layers into double or triple layers bound via covalent bonds, resulting in structural fragments with Li[NiB] and Li[NiB] compositions. The crystal structure of LiNiB is best described as an intergrowth of the ordered single [NiB], double [NiB], or triple [NiB] layers alternating with single Li layers; this explains its structural complexity. The formation of double or triple [NiB] layers induces a change in the magnetic behavior from temperature-independent paramagnets in the parent LiNiB compounds to the spin-glassiness in the deintercalated LiNiB counterparts. LiNiB compounds showcase the potential to access a plethora of unique materials, including 2D MBenes (NiB).
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http://dx.doi.org/10.1021/jacs.0c11397DOI Listing
March 2021

Single-Cell RNA Sequencing With Combined Use of Bulk RNA Sequencing to Reveal Cell Heterogeneity and Molecular Changes at Acute Stage of Ischemic Stroke in Mouse Cortex Penumbra Area.

Front Cell Dev Biol 2021 22;9:624711. Epub 2021 Feb 22.

Department of Neurosurgery, Tangdu Hospital, Fourth Military Medical University, Xi'an, China.

Stroke has been the leading cause of adult morbidity and mortality over the past several years. After an ischemic stroke attack, many dormant or reversibly injured brain cells exist in the penumbra area. However, the pathological processes and unique cell information in the penumbra area of an acute ischemic stroke remain elusive. We applied unbiased single cell sequencing in combination with bulk RNA-seq analysis to investigate the heterogeneity of each cell type in the early stages of ischemic stroke and to detect early possible therapeutic targets to help cell survival. We used these analyses to study the mouse brain penumbra during this phase. Our results reveal the impact of ischemic stroke on specific genes and pathways of different cell types and the alterations of cell differentiation trajectories, suggesting potential pathological mechanisms and therapeutic targets. In addition to classical gene markers, single-cell genomics demonstrates unique information on subclusters of several cell types and metabolism changes in an ischemic stroke. These findings suggest that in microglia, in astrocytes, and in oligodendrocytes may play a subcluster-specific role in cell death or survival in the early stages of ischemic stroke. Moreover, RNA-scope multiplex hybridization and immunofluorescence staining were applied to selected target gene markers to validate and confirm the existence of these cell subtypes and molecular changes during acute stage of ischemic stroke.
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http://dx.doi.org/10.3389/fcell.2021.624711DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7937629PMC
February 2021

Structure evolution of single-site Pt in a metal-organic framework.

J Chem Phys 2021 Mar;154(9):094710

Department of Chemistry, Iowa State University, Ames, Iowa 50011, USA.

Heterogeneous single-metal-site catalyst or single-atom catalyst research has grown rapidly due to the accessibility of modern characterization techniques that can provide invaluable information at the atomic-scale. Herein, we study the structural evolution of isolated single Pt sites incorporated in a metal-organic framework containing bipyridine functional groups using in situ diffuse reflectance infrared Fourier transform spectroscopy with CO as the probe molecule. The structure and electronic properties of the isolated Pt sites are further corroborated by x-ray photoelectron spectroscopy and aberration-corrected scanning transmission electron microscopy. We find the prerequisite of high temperature He treatment for Pt activation and CO insertion and inquire into the structural transformation of Pt site process by dynamic nuclear polarization-enhanced solid-state nuclear magnetic resonance spectroscopy.
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http://dx.doi.org/10.1063/5.0041904DOI Listing
March 2021

Individualized Surgical Reconstruction of the Right Ventricle Outflow Tract in Double Outlet Right Ventricle With Mirror Image-Dextrocardia.

Front Pediatr 2021 19;9:611007. Epub 2021 Feb 19.

Department of Cardiovascular Surgery, The Second Xiangya Hospital of Central South University, Changsha, China.

The purpose of this study was to report our experience in the surgical reconstruction of the right ventricular outflow tract in double outlet right ventricle with a major coronary artery crossing the right ventricular outflow tract in the presence of mirror image-dextrocardia. From January 2005 to December 2019, 19 double outlet right ventricle patients (median age 4 years) with mirror image-dextrocardia and a major coronary artery crossing the right ventricular outflow tract received surgical repair. An autologous pericardial patch was used to enlarge the right ventricular outflow tract in four patients without pulmonary stenosis and three patients with mild pulmonary stenosis. A valved bovine jugular venous conduit was added to a hypoplastic native pathway in nine patients, among which six patients with moderate pulmonary stenosis received small-sized bovine jugular venous conduit implantation (diameter ≤ 16 mm). In comparison, a large-sized bovine jugular venous conduit (diameter >16 mm) was adopted in a total of three patients with severe pulmonary stenosis. Finally, three patients with preoperative pulmonary hypertension (mean pulmonary artery pressure ≥40 mmHg) did not undergo further intervention of right ventricular outflow tract due to the adequate outflow tract blood flow. There was no hospital mortality. One patient with sub-pulmonary ventricular septal defect and concomitant severe pulmonary hypertension died from respiratory failure 11 months after the operation. Kaplan-Meier survival was 94% at 5, 10 years. Within a mean echocardiographic follow-up of 6.9 ± 3.6 years, a total of two patients received reintervention due to valvular stenosis of the bovine jugular venous conduit (pressure gradient > 50 mmHg at 4 and 9 years) after surgical operation. Actuarial freedom from reoperation was 90 and 72% at 5 and 10 years, respectively. During the last echocardiographic follow-up phase, all the survivors were in NYHA class I. Double outlet right ventricle with mirror image-dextrocardia is a rare and complicated congenital cardiac malformation. Surgical reconstruction of the right ventricular outflow tract should be individualized based on the degree of pulmonary stenosis and the specific anatomical features of each patient. Reconstructing the pulmonary artery using the various sizes of valved bovine jugular venous conduit is a safe and effective surgical method.
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http://dx.doi.org/10.3389/fped.2021.611007DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7933223PMC
February 2021

Down-regulation of the tumor suppressor miR-34a contributes to head and neck cancer by up-regulating the MET oncogene and modulating tumor immune evasion.

J Exp Clin Cancer Res 2021 Feb 17;40(1):70. Epub 2021 Feb 17.

Cancer Biology and Immunology Laboratory, College of Dental Medicine, Columbia University Irving Medical Center, New York, NY, USA.

Background: MicroRNAs (miRs) have been shown to play an important role in tumorigenesis, including in head and neck squamous cell carcinoma (HNSCC). The miR-34 family is thought to play a role in tumor suppression, but the exact mechanism of their action in HNSCC is not well understood. Moreover, the impact of chromosomal changes and mutation status on miR-34a expression remains unknown.

Methods: Differential expression of miR-34a, MET, and genomic alterations were assessed in the Cancer Genome Atlas (TCGA) datasets as well as in primary HNSCC and adjacent normal tissue. The biological functions of miR-34a in HNSCC were investigated in samples derived from primary human tumors and HNSCC cell lines. The expression of MET was evaluated using immunohistochemistry, and the molecular interaction of miR-34a and MET were demonstrated by RNA pulldown, RNA immunoprecipitation, luciferase reporter assay, and rescue experiments. Lastly, locked nucleic acid (LNA) miRs in mouse xenograft models were used to evaluate the clinical relevance of miR-34a in HNSCC tumor growth and modulation of the tumor microenvironment in vivo.

Results: Chromosome arm 1p loss and P53 mutations are both associated with lower levels of miR-34a. In HNSCC, miR-34a acts as a tumor suppressor and physically interacts with and functionally targets the proto-oncogene MET. Our studies found that miR-34a suppresses HNSCC carcinogenesis, at least in part, by downregulating MET, consequently inhibiting HNSCC proliferation. Consistent with these findings, administration of LNA-miR-34a in an in vivo model of HNSCC leads to diminished HNSCC cell proliferation and tumor burden in vitro and in vivo, represses expression of genes involved in epithelial-mesenchymal transition, and negates the oncogenic effect of MET in mouse tumors. Consistently, LNA-miR-34a induced a decreased number of immunosuppressive PDL1-expressing tumor-associated macrophages in the tumor microenvironment. In HNSCC patient samples, higher levels of miR-34a are significantly associated with a higher frequency of Th1 cells and CD8 naïve T cells.

Conclusions: Our results demonstrate that miR-34a directly targets MET and maintains anti-tumor immune activity. We propose miR-34a as a potential new therapeutic approach for HNSCC.
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http://dx.doi.org/10.1186/s13046-021-01865-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7890893PMC
February 2021

Human Genetic Variation Influences Enteric Fever Progression.

Cells 2021 02 6;10(2). Epub 2021 Feb 6.

Department of Life Sciences, International Medical University, Kuala Lumpur 57000, Malaysia.

In the 21st century, enteric fever is still causing a significant number of mortalities, especially in high-risk regions of the world. Genetic studies involving the genome and transcriptome have revealed a broad set of candidate genetic polymorphisms associated with susceptibility to and the severity of enteric fever. This review attempted to explain and discuss the past and the most recent findings on human genetic variants affecting the progression of typhoidal species infection, particularly toll-like receptor (TLR) 4, TLR5, interleukin (IL-) 4, natural resistance-associated macrophage protein 1 (NRAMP1), VAC14, PARK2/PACRG, cystic fibrosis transmembrane conductance regulator (CFTR), major-histocompatibility-complex (MHC) class II and class III. These polymorphisms on disease susceptibility or progression in patients could be related to multiple mechanisms in eliminating both intracellular and extracellular typhoidal species. Here, we also highlighted the limitations in the studies reported, which led to inconclusive results in association studies. Nevertheless, the knowledge obtained through this review may shed some light on the development of risk prediction tools, novel therapies as well as strategies towards developing a personalised typhoid vaccine.
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http://dx.doi.org/10.3390/cells10020345DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7915608PMC
February 2021

[Corrigendum] Downregulation of nucleolar and spindle‑associated protein 1 expression suppresses cell migration, proliferation and invasion in renal cell carcinoma.

Oncol Rep 2021 02 30;45(2):793. Epub 2020 Nov 30.

Department of Urology, Shenzhen Second People's Hospital, The First Affiliated Hospital of Shenzhen University, Shenzhen, Guangdong 518037, P.R. China.

Following the publication of the above article, the authors have realized that Fig. 5A was published with certain errors; essentially, the authors needed to perform further experiments to validate certain of their results, and the Blank and si‑NC control data in Fig. 5A were included from an incorrect set of experiments (the intended si‑NUSAP1 experimental data from the flow cytometric analyses, however, were presented correctly in the published Figure). The corrected version of Fig. 5, featuring the panels for the Blank and si‑NC control data in Fig. 5A from the same set of experiments, is shown opposite. The authors have confirmed that the errors associated with this figure did not have any significant impact on either the results or the conclusions reported in this study, and are grateful to the Editor of Oncology Reports for allowing them the opportunity to publish this Corrigendum. Furthermore, they apologize to the readership of the Journal for any inconvenience caused. [the original article was published in Oncology Reports 36: 1506-1516, 2016; DOI: 10.3892/or.2016.4955].
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http://dx.doi.org/10.3892/or.2020.7875DOI Listing
February 2021

20-HETE synthesis inhibition attenuates traumatic brain injury-induced mitochondrial dysfunction and neuronal apoptosis via the SIRT1/PGC-1α pathway: A translational study.

Cell Prolif 2021 Feb 13;54(2):e12964. Epub 2020 Dec 13.

Department of Neurosurgery, Tangdu Hospital, The Fourth Military Medical University, Xi'an, China.

Objectives: 20-hydroxyeicosatetraenoic acid (20-HETE) is a metabolite of arachidonic acid catalysed by cytochrome P450 enzymes and plays an important role in cell death and proliferation. We hypothesized that 20-HETE synthesis inhibition may have protective effects in traumatic brain injury (TBI) and investigated possible underlying molecular mechanisms.

Materials And Methods: Neurologic deficits, and lesion volume, reactive oxygen species (ROS) levels and cell death as assessed using immunofluorescence staining, transmission electron microscopy and Western blotting were used to determine post-TBI effects of HET0016, an inhibitor of 20-HETE synthesis, and their underlying mechanisms.

Results: The level of 20-HETE was found to be increased significantly after TBI in mice. 20-HETE synthesis inhibition reduced neuronal apoptosis, ROS production and damage to mitochondrial structures after TBI. Mechanistically, HET0016 decreased the Drp1 level and increased the expression of Mfn1 and Mfn2 after TBI, indicating a reversal of the abnormal post-TBI mitochondrial dynamics. HET0016 also promoted the restoration of SIRT1 and PGC-1α in vivo, and a SIRT1 activator (SRT1720) reversed the downregulation of SIRT1 and PGC-1α and the abnormal mitochondrial dynamics induced by 20-HETE in vitro. Furthermore, plasma 20-HETE levels were found to be higher in TBI patients with unfavourable neurological outcomes and were correlated with the GOS score.

Conclusions: The inhibition of 20-HETE synthesis represents a novel strategy to mitigate TBI-induced mitochondrial dysfunction and neuronal apoptosis by regulating the SIRT1/PGC-1α pathway.
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http://dx.doi.org/10.1111/cpr.12964DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7848954PMC
February 2021

Thermoelectric Converters Based on Ionic Conductors.

Chem Asian J 2021 Jan 22;16(2):129-141. Epub 2020 Dec 22.

Department of Chemistry, Renmin University of China, Beijing, 100872, P. R. China.

Thermoelectric materials represent a new paradigm for harvesting low-grade heat, which would otherwise be dissipated to the environment uselessly. Relative to conventional thermoelectric materials generally composed of semiconductors or semi-metals, ionic thermoelectric materials are rising as an alternative choice which exhibit higher Seebeck coefficient and lower thermal conductivity. The ionic thermoelectric materials own a completely different thermoelectric conversion mechanism, in which the ions do not enter the electrode but rearrange on the electrode surface to generate a voltage difference between the hot and cold electrodes. This unique character has inspired worldwide interests on the design of ionic-type thermoelectric converters with attractive advantages of high flexibility, low cost, limited environmental pollution, and self-healing capability. Referring to the categories of ionic thermoelectric conversion, some representative ionic thermoelectric materials with their respective characteristics are summarized in this minireview. In addition, examples of applying ionic thermoelectric materials in supercapacitors, wearable devices, and fire warning system are also discussed. Insight into the challenges for the further development of ionic thermoelectric materials is finally provided.
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http://dx.doi.org/10.1002/asia.202001331DOI Listing
January 2021

Body fat distribution and circulating adipsin are related to metabolic risks in adult patients with newly diagnosed growth hormone deficiency and improve after treatment.

Biomed Pharmacother 2020 Dec 3;132:110875. Epub 2020 Nov 3.

Department of Endocrinology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China. Electronic address:

Objective: The relationships between body fat distribution, the adipokine adipsin and metabolic risks were assessed in patients with adult growth hormone deficiency (AGHD) before and after growth hormone (GH) treatment.

Methods: Sixty newly diagnosed AGHD patients were included in our study, 24 of whom were evaluated after at least one year of GH treatment. Anthropometric parameters, glucolipid metabolism and the adipokine adipsin were measured. Visceral adipose tissue (VAT) and body composition were evaluated using a dual-energy X-ray-absorptiometry (DXA) scanner.

Results: At baseline, the higher VAT group had worse glucolipid metabolism parameters. Basal GH was negatively associated with VAT (r=-0.277, p = 0.045), while minimal correlations were found with fat mass depots, such as limbs and trunk fat (all p > 0.05). Adipsin was correlated with total body fat (r = 0.543, p < 0.001), VAT (r = 0.563, p < 0.001) and insulin resistance (r = 0.353, p = 0.006). The effect of GH administration on fat distribution was mainly reflected in the reduction in VAT. Partial improvements were found in lipid profiles, including increased high-density lipoprotein (HDL) and decreases in triglycerides (TGs) and lipoprotein(a), while glucose metabolism showed little change. The adipsin level also decreased significantly. The best predictors of VAT at baseline were trunk fat and IGF-I, and after treatment, VAT was predicted by decreased adipsin and an increase in lean mass.

Conclusions: (1) VAT is an important metabolic risk factor for AGHD patients. (2) GH treatment decreased body fat predominantly in the visceral and central fat depots. (3) The lipid profiles partially improved after treatment, while glucose metabolism showed little change.
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http://dx.doi.org/10.1016/j.biopha.2020.110875DOI Listing
December 2020

LncRNA-IUR Sponges miR-24 to Upregulate P53 in Laryngeal Squamous Cell Carcinoma.

Cancer Manag Res 2020 16;12:11639-11647. Epub 2020 Nov 16.

Department of Maxillofacial Surgery, Guangxi Medical University College of Stomatology, Nanning 530021, People's Republic of China.

Objective: The functions of lncRNA-IUR in laryngeal squamous cell carcinoma (LSCC) were investigated in this study.

Methods: RT-qPCR and paired -test were used to measure and compare expression levels of IUR, miR-24 and p53 in LSCC and non-tumor tissues. Human LSCC cell line UM-SCC-17A was used and transfected by pcDNA3.1 vector to overexpress IUR and miR-24. The transwell assay and wound healing assay illustrated the effect of overexpression of IUR or miR-24 in the cell invasion and migration of LSCC. Subcutaneous tumor model in nude mice was carried out to demonstrate the mechanism between IUR and miR-24 in regulating tumor growth.

Results: We found that IUR was downregulated in LSCC. Low expression levels of IUR were correlated with the poor survival of LSCC patients. Overexpression experiments showed that overexpression of IUR led to increased, while overexpression of miR-24 led to decreased expression levels of p53 in LSCC cells. And bioinformatics analysis showed that IUR may sponge miR-24. Cell proliferation assay showed that overexpression of IUR and p53 led to decreased proliferation rate of LSCC cells, while overexpression of miR-24 led to increased proliferation rate of LSCC cells. We also illustrated that overexpression of IUR promoted cell migration and invasion while miR-24 had opposite effects. In addition, subcutaneous tumor model in nude mice showed that overexpression of miR-24 attenuated the effects of overexpression of IUR on the expression of p53 and cancer cell proliferation.

Conclusion: IUR sponges miR-24 to upregulate p53 in LSCC, thereby inhibiting cancer cell proliferation.
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http://dx.doi.org/10.2147/CMAR.S236188DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7678708PMC
November 2020

Evaluating the cost-effectiveness of catheter ablation of atrial fibrillation.

Cardiovasc Diagn Ther 2020 Oct;10(5):1200-1215

Department of Cardiovascular Surgery, Second Xiangya Hospital, Central South University, Changsha, China.

Background: The pursuit of a clearer understanding of the pathogenesis of atrial fibrillation (AFib) and the development of new technology has resulted in a surge of interest in the surgical ablation for AFib. Here, we report our 8-year experience in the surgical treatment and management of AFib alongside, evaluating the cost-effectiveness in southern Mainland China over a 1-year follow-up.

Methods: Data of 3,068 patients from March 2011 through June 2019 was retrospectively extracted from The Provincial National Cardiac Database of Xiangya Second Hospital. The activities considered (and costs calculated) were outpatient consultations, hospital admissions, and drug treatment. Quality of life (QoL) questionnaires were also carried out to assess whether concomitant AFib correction procedures increase risk in patients, or improve patient's QoL.

Results: A total of 3,068 patients completed the questionnaires at a minimum of one time-point during the follow-up. The total cost was combined to obtain incremental costs per quality-adjusted life-years (QALYs). The total costs of the AFib catheter ablation group were remarkably higher compared to surgery as usual group. The incremental cost-effectiveness ratio was $76,513,227 (¥542,287,667) per QALY, with an acceptability line graph for cost at 43%.

Conclusions: AFib is an extraordinarily costly and worrisome public health problem. Precision medicine is vital as it provides a platform for the clinical translation of targeted interventions that are designed to help treat and prevent AFib. Thus, to improve the QoL expectancy outcome(s), both therapeutic and surgical interventions should be aimed at addressing the underlying heart disease rather than restoring sinus rhythm.
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http://dx.doi.org/10.21037/cdt-20-574DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7666964PMC
October 2020

Antagonism of Protease-Activated Receptor 4 Protects Against Traumatic Brain Injury by Suppressing Neuroinflammation via Inhibition of Tab2/NF-κB Signaling.

Neurosci Bull 2021 Feb 27;37(2):242-254. Epub 2020 Oct 27.

Department of Neurosurgery, Tangdu Hospital, The Fourth Military Medical University, Xi'an, 710038, China.

Traumatic brain injury (TBI) triggers the activation of the endogenous coagulation mechanism, and a large amount of thrombin is released to curb uncontrollable bleeding through thrombin receptors, also known as protease-activated receptors (PARs). However, thrombin is one of the most critical factors in secondary brain injury. Thus, the PARs may be effective targets against hemorrhagic brain injury. Since the PAR1 antagonist has an increased bleeding risk in clinical practice, PAR4 blockade has been suggested as a more promising treatment. Here, we explored the expression pattern of PAR4 in the brain of mice after TBI, and explored the effect and possible mechanism of BMS-986120 (BMS), a novel selective and reversible PAR4 antagonist on secondary brain injury. Treatment with BMS protected against TBI in mice. mRNA-seq analysis, Western blot, and qRT-PCR verification in vitro showed that BMS significantly inhibited thrombin-induced inflammation in astrocytes, and suggested that the Tab2/ERK/NF-κB signaling pathway plays a key role in this process. Our findings provide reliable evidence that blocking PAR4 is a safe and effective intervention for TBI, and suggest that BMS has a potential clinical application in the management of TBI.
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http://dx.doi.org/10.1007/s12264-020-00601-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7870748PMC
February 2021

Homocysteine promotes hepatic steatosis by activating the adipocyte lipolysis in a HIF1α-ERO1α-dependent oxidative stress manner.

Redox Biol 2020 10 1;37:101742. Epub 2020 Oct 1.

Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Peking University, Key Laboratory of Molecular Cardiovascular Science, Ministry of Education, Beijing, 100191, PR China; Center of Basic Medical Research, Institute of Medical Innovation and Research, Third Hospital, Peking University, Beijing, 100191, PR China; Center for Obesity and Metabolic Disease Research, School of Basic Medical Sciences, Peking University, Beijing, 100191, PR China. Electronic address:

Hyperhomocysteinemia (HHcy) is related to liver diseases, such as nonalcoholic fatty liver (NAFL). Although the precise pathogenesis of NAFL is still largely unknown, the links between organs seem to play a vital role. The current study aimed to explore the role of white adipose tissue in homocysteine (Hcy)-induced NAFL. Blood samples from nonhyperhomocysteinemia or hyperhomocysteinemia individuals were collected to assess correlation between Hcy and triglyceride (TG) or free fatty acids (FFAs) levels. C57BL/6 mice were maintained on a high-methionine diet or administered with Hcy (1.8 g/L) in the drinking water to establish an HHcy mouse model. We demonstrated that Hcy activated adipocyte lipolysis and that this change was accompanied by an increased release of FFAs and glycerol. Excessive FFAs were taken up by hepatocyte, which resulted in lipid accumulation in the liver. Treatment with acipimox (0.08 g kg day ), a potent chemical inhibitor of lipolysis, markedly decreased Hcy-induced NAFL. Mechanistically, hypoxia-inducible factor 1α (HIF1α)-endoplasmic reticulum oxidoreductin 1α (ERO1α) mediated pathway promoted HO accumulation and induced endoplasmic reticulum (ER) overoxidation, ER stress and more closed ER-lipid droplet interactions, which were responsible for activating the lipolytic response. In conclusion, this study reveals that Hcy activates adipocyte lipolysis and suggests the potential utility of targeted ER redox homeostasis for treating Hcy-induced NAFL.
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http://dx.doi.org/10.1016/j.redox.2020.101742DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7559542PMC
October 2020

SIRT3 protects against early brain injury following subarachnoid hemorrhage promoting mitochondrial fusion in an AMPK dependent manner.

Chin Neurosurg J 2020 3;6. Epub 2020 Jan 3.

Department of Neurosurgery, Tangdu Hospital, the Fourth Military Medical University, Xi'an, 710038 Shaanxi China.

Background: Subarachnoid hemorrhage (SAH), an acute cerebrovascular accident, features with its high death and disability rate. Sirtuin3 (SIRT3) is a NAD+ dependent deacetylase which mainly located in mitochondria. Reduced SIRT3 function was indicated to involve in many disorders of central nervous system. Herein, we aimed to explore the neuroprotective effects of SIRT3 on SAH and to furtherly explore the underlying mechanisms.

Methods: Adult C57BL/6 J male mice (8-10 weeks) were used to establish SAH models. The pharmacological agonist of SIRT3, Honokiol (HKL), was injected in an intraperitoneal manner (10 mg/kg) immediately after the operation. Brain edema and neurobehavioral score were assessed. Nissl staining and FJC staining were used to evaluate the extent of neuronal damage. The changes of mitochondria morphology were observed with transmission electron microscopy. Western blot was used for analyzing the protein level of SIRT3 and the downstream signaling molecules.

Result: SIRT3 was downregulated after SAH, and additional treatment of SIRT3 agonist HKL alleviated brain edema and neurobehavioral deficits after SAH. Additionally, electron microscopy showed that HKL significantly alleviated the morphological damage of mitochondria induced by SAH. Further studies showed that HKL could increase the level of mitochondrial fusion protein Mfn1 and Mfn2, thus maintaining (mitochondrial morphology), protecting mitochondrial function and promoting neural survival. While, additional Compound C (CC) treatment, a selective AMPK inhibitor, abolished these protective effects.

Conclusions: Activation of SIRT3 protects against SAH injury through improving mitochondrial fusion in an AMPK dependent manner.
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http://dx.doi.org/10.1186/s41016-019-0182-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7398350PMC
January 2020
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