Publications by authors named "Ju Gao"

202 Publications

Mechanosensitive cation channel Piezo1 contributes to ventilator-induced lung injury by activating RhoA/ROCK1 in rats.

Respir Res 2021 Sep 21;22(1):250. Epub 2021 Sep 21.

Department of Anesthesiology, Institute of Anesthesia, Emergency and Critical Care, Yangzhou University Affiliated Northern Jiangsu People's Hospital, 98 Nan Tong Western Road, Yangzhou, 225001, Jiangsu, China.

Background: Mechanical ventilation can induce or aggravate lung injury, which is termed ventilator-induced lung injury (VILI). Piezo1 is a key element of the mechanotransduction process and can transduce mechanical signals into biological signals by mediating Ca influx, which in turn regulates cytoskeletal remodeling and stress alterations. We hypothesized that it plays an important role in the occurrence of VILI, and investigated the underlying mechanisms.

Methods: High tidal volume mechanical ventilation and high magnitude cyclic stretch were performed on Sprague-Dawley rats, and A549 and human pulmonary microvascular endothelial cells, respectively, to establish VILI models. Immunohistochemical staining, flow cytometry, histological examination, enzyme-linked immunosorbent assay, western blotting, quantitative real-time polymerase chain reaction and survival curves were used to assess the effect of Piezo1 on induction of lung injury, as well as the signaling pathways involved.

Results: We observed that Piezo1 expression increased in the lungs after high tidal volume mechanical ventilation and in cyclic stretch-treated cells. Mechanistically, we observed the enhanced expression of RhoA/ROCK1 in both cyclic stretch and Yoda1-treated cells, while the deficiency or inhibition of Piezo1 dramatically antagonized RhoA/ROCK1 expression. Furthermore, blockade of RhoA/ROCK1 signaling using an inhibitor did not affect Piezo1 expression. GSMTx4 was used to inhibit Piezo1, which alleviated VILI-induced pathologic changes, water content and protein leakage in the lungs, and the induction of systemic inflammatory mediators, and improved the 7-day mortality rate in the model rats.

Conclusions: These findings indicate that Piezo1 affects the development and progression of VILI through promotion of RhoA/ROCK1 signaling.
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http://dx.doi.org/10.1186/s12931-021-01844-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8456630PMC
September 2021

Clinical and prognostic characteristics of 95 cases of Langerhans cell histiocytosis in children: a single-institute experience from 2013 to 2020.

Ann Med 2021 12;53(1):1537-1546

Department of Pediatrics, West China Second University Hospital, Sichuan University, Chengdu, China.

Background: This study aimed to understand the clinical characteristics and outcomes of children with Langerhans cell histiocytosis (LCH) in China.

Methods: We conducted a retrospective study of 95 paediatric patients with LCH in West China Second University Hospital of Sichuan University between July 2013 and August 2020.

Results: The onset age of multisystem LCH (MS-LCH) patients with risk organ (RO) involvement was younger than that of MS-LCH without RO involvement ( = .002) and single system LCH ( < .001) patients; bone was the most frequently involved organ, followed by the skin. Of all, the mutation was detected in 48 out of 84 patients who underwent gene analysis. Additionally, in our study, , , , and were known mutations in the mitogen-activated protein kinase () pathway. The genotype in the tissue and plasma prior to therapy were detected in 16 patients, and the concordance was only 37.5% (6/16). According to the modified LCH-III-based-protocol, JLSG-02 protocol chemotherapy, and vemurafenib, the estimated five-year overall survival, event-free survival (EFS) and cumulative reactivation rates of 95 patients were 98.8%, 74.6% and 24.5%, respectively. The EFS rate in good responders was better than that in poor responders at 12-week (HR = 0.022, 95%CI 0.002-0.231,  = .002), and EFS was not affected by age, RO involvement or mutation. Regarding sequelae, nine patients had central diabetes insipidus and two had growth retardation.

Conclusions: In this study, LCH was a highly heterogeneous disease characterized molecularly by MAPK-pathway activating mutations. Vincristine, prednisone and cytarabine-based chemotherapy combined with vemurafenib improved the prognosis of childhood LCH. In future, prospective clinical trials and novel therapeutic strategies should be developed to improve outcomes in paediatric patients with LCH.KEY MESSAGEChildren with Langerhans cell histiocytosis in China present highly heterogeneous clinical characteristics, with up to 60% of cases harbouring mutations in pathway.Treatment response at 12-week is associated with EFS in our study.Vincristine, prednisone and cytarabine-based chemotherapy combined with vemurafenib improved the prognosis of Chinese childhood LCH, but the reactivation rate is still high.
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http://dx.doi.org/10.1080/07853890.2021.1966085DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8409935PMC
December 2021

Hypoxia induces inflammatory microenvironment by priming specific macrophage polarization and modifies LSC behaviour via VEGF-HIF1α signalling.

Transl Pediatr 2021 Jul;10(7):1792-1804

Department of Pediatric Hematology and Oncology, West China Second University Hospital of Sichuan University, Chengdu, China.

Background: Leukemia stem cells (LSCs) play pivotal roles in leukemogenesis, and are closely implicated in leukemia relapse and chemoresistance. LSCs are tightly modulated by hypoxic exposure and macrophage-conditioned microenvironment. Nevertheless, the impacts on the biology of LSCs imposed by the interaction of hypoxia and macrophage polarization remain elusive.

Methods: In the study, LSCs characterized by CD34+CD38- immunophenotype sorted from KG1α and primary AML cells were employed as and cell models. mRNA and protein expressions of cytokine/chemokine of cells under normoxic and hypoxic conditions were determined by RT-PCR and western blot. Macrophage polarization, cell cycle and apoptosis were determined by flowcytometry. Cell viability was assayed by CCK-8.

Results: Macrophages preferentially presented with M2 polarization phenotype characterized by upregulated VEGF and CCL17 cytokine/chemokine profile, when stimulated by specific set of cytokines under hypoxic exposure, and induced an anti-inflammatory microenvironment. LSCs exhibited significantly increased cell viability, colony-forming capacity and chemoresistance when co-incubated in hypoxic conditioned medium (H-CM) primed by polarized M1 macrophages. VEGF expression was upregulated in LSCs which in turn activated survivin expression. VEGF-mediated upregulation of survivin could be abolished by inhibition of VEGF receptor, but not blocked by survivin-targeting siRNA. In addition, survivin upregulation exerted antiapoptotic effects and was associated with increased chemoresistance. Finally, VEGF mediated transcriptional induction of HIF-1α of LSCs coincubated in H-CM, and HIF-1α induction in turn enhanced chemoresistance and reduced cell apoptosis.

Conclusions: To our best knowledge, this is the first study that focus to explore molecule players and interacting signal pathways regulating LSC biology under hypoxic exposure. It reveals that hypoxia preferentially skew macrophage M2 polarization with specific cytokine profile and proinflammatory microenvironment, which impacts malignant behavior of LSCs. VEGF-HIF-1α interaction is closely implicated in sustaining LSCs survival under hypoxic exposure and might be of potential target of novel therapy.
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http://dx.doi.org/10.21037/tp-21-86DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8349958PMC
July 2021

Translational regulation in the brain by TDP-43 phase separation.

J Cell Biol 2021 Oct 24;220(10). Epub 2021 Aug 24.

Department of Pharmacology and Experimental Neurosciences, University of Nebraska Medical Center, Omaha, NE.

The in vivo physiological function of liquid-liquid phase separation (LLPS) that governs non-membrane-bound structures remains elusive. Among LLPS-prone proteins, TAR DNA-binding protein of 43 kD (TDP-43) is under intense investigation because of its close association with neurological disorders. Here, we generated mice expressing endogenous LLPS-deficient murine TDP-43. LLPS-deficient TDP-43 mice demonstrate impaired neuronal function and behavioral abnormalities specifically related to brain function. Brain neurons of these mice, however, did not show TDP-43 proteinopathy or neurodegeneration. Instead, the global rate of protein synthesis was found to be greatly enhanced by TDP-43 LLPS loss. Mechanistically, TDP-43 LLPS ablation increased its association with PABPC4, RPS6, RPL7, and other translational factors. The physical interactions between TDP-43 and translational factors relies on a motif, the deletion of which abolished the impact of LLPS-deficient TDP-43 on translation. Our findings show a specific physiological role for TDP-43 LLPS in the regulation of brain function and uncover an intriguing novel molecular mechanism of translational control by LLPS.
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http://dx.doi.org/10.1083/jcb.202101019DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8404466PMC
October 2021

Pulse therapy with vincristine and dexamethasone for childhood acute lymphoblastic leukaemia (CCCG-ALL-2015): an open-label, multicentre, randomised, phase 3, non-inferiority trial.

Lancet Oncol 2021 09 27;22(9):1322-1332. Epub 2021 Jul 27.

Department of Hematology/Oncology, Shanghai Children's Medical Center, School of Medicine, Shanghai Jiao Tong University, National Health Committee Key Laboratory of Pediatric Hematology & Oncology, Shanghai, China.

Background: Vincristine plus dexamethasone pulses are generally used throughout maintenance treatment for childhood acute lymphoblastic leukaemia. However, previous studies remain inconclusive about the benefit of this maintenance therapy and the absence of randomised, controlled trials in patients with low-risk or high-risk acute lymphoblastic leukaemia provides uncertainty. We therefore aimed to determine if this therapy could be safely omitted beyond 1 year of treatment without leading to an inferior outcome in any risk subgroup of childhood acute lymphoblastic leukaemia.

Methods: This open-label, multicentre, randomised, phase 3, non-inferiority trial involved 20 major medical centres across China. We enrolled patients who were aged 0-18 years with newly diagnosed acute lymphoblastic leukaemia that was subsequently in continuous remission for 1 year after initial treatment. Patients with secondary malignancy or primary immunodeficiency were excluded. Eligible patients were classified as having low-risk, intermediate-risk, or high-risk acute lymphoblastic leukaemia based on minimal residual disease and immunophenotypic and genetic features of leukaemic cells. Randomisation and analyses were done separately for the low-risk and intermediate-to-high-risk cohorts. Randomisation was generated by the study biostatistician with a block size of six. Stratification factors included participating centre, sex, and age at diagnosis; the low-risk cohort was additionally stratified for ETV6-RUNX1 status, and the intermediate-to-high-risk cohort for cell lineage. Patients in each risk cohort were randomly assigned (1:1) to either receive (ie, the control group) or not receive (ie, the experimental group) seven pulses of intravenous vincristine (1·5 mg/m) plus oral dexamethasone (6 mg/m per day for 7 days) during the second year of treatment. The primary endpoint was difference in 5-year event-free survival between the experimental group and the control group for both the low-risk and intermediate-to-high-risk cohorts, with a non-inferiority margin of 0·05 (5%). The analysis was by intention to treat. This trial is registered with the Chinese Clinical Trial Registry, ChiCTR-IPR-14005706.

Findings: Between Jan 1, 2015, and Feb 20, 2020, 6141 paediatric patients with newly diagnosed acute lymphoblastic leukaemia were registered to this study. Approximately 1 year after diagnosis and treatment, 5054 patients in continuous remission were randomly assigned, including 2923 (1442 in the control group and 1481 in the experimental group) with low-risk acute lymphoblastic leukaemia and 2131 (1071 control, 1060 experimental) with intermediate-to-high risk acute lymphoblastic leukaemia. Median follow-up for patients who were alive at the time of analysis was 3·7 years (IQR 2·8-4·7). Among patients with low-risk acute lymphoblastic leukaemia, no difference was observed in 5-year event-free survival between the control group and the experimental group (90·3% [95% CI 88·4-92·2] vs 90·2% [88·2-92·2]; p=0·90). The one-sided 95% upper confidence bound for the difference in 5-year event-free survival probability was 0·024, establishing non-inferiority. Among patients with intermediate-to-high-risk acute lymphoblastic leukaemia, no difference was observed in 5-year event-free survival between the control group and the experimental group (82·8% [95% CI 80·0-85·7] vs 80·8% [77·7-84·0]; p=0·90), but the one-sided 95% upper confidence bound for the difference in 5-year event-free survival probability was 0·055, giving a borderline inferior result for those in the experimental group. In the low-risk cohort, we found no differences in the rates of infections, symptomatic osteonecrosis, or other complications during the second year of maintenance treatment between patients in the control and experimental groups. Patients with intermediate-to-high-risk acute lymphoblastic leukaemia in the control group were more likely to develop grade 3-4 pneumonia (26 [2·4%] of 1071 vs ten [0·9%] of 1060) and vincristine-related peripheral neuropathy (17 [1·6%] vs six [0·6%]) compared with the experimental group. Incidence of grade 5 fatal infection was similar between the control group and the experimental group in both the low-risk cohort (two [0·1%] of 1442 vs five [0·3%] of 1481) and intermediate-to-high risk cohort (six [0·6%] of 1071 vs five [0·5%] of 1060).

Interpretation: Vincristine plus dexamethasone pulses might be omitted beyond 1 year of treatment for children with low-risk acute lymphoblastic leukaemia. Additional studies are needed for intermediate-to-high-risk acute lymphoblastic leukaemia.

Funding: VIVA China Children's Cancer Foundation, the National Natural Science Foundation of China, the China fourth round of Three-Year Public Health Action Plan (2015-2017), Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences, US National Cancer Institute, St Baldrick's Foundation, and the American Lebanese Syrian Associated Charities.

Translation: For the Chinese translation of the abstract see Supplementary Materials section.
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http://dx.doi.org/10.1016/S1470-2045(21)00328-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8416799PMC
September 2021

Case Report: Coexistence of Anti-AMPA Receptor Encephalitis and Positive Biomarkers of Alzheimer's Disease.

Front Neurol 2021 2;12:673347. Epub 2021 Jul 2.

Institute of Neuropsychiatry, The Affiliated Brain Hospital of Nanjing Medical University, Nanjing, China.

Anti-α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor encephalitis is a rare autoimmune disease that is characterized by acute cognitive impairment, mental symptoms, and seizures. The high comorbidity rate between anti-AMPA receptor (AMPAR) encephalitis and other somatic diseases, such as malignancy, has revealed the possibility of potential copathogenesis. However, there have not yet been reports about anti-AMPAR encephalitis with concomitant cerebrospinal fluid (CSF) biomarkers consistent with Alzheimer disease (AD). Herein, we present the case of an elderly male patient with autoimmune encephalitis (AE) presenting with anti-AMPA1-R and anti-AMPA2-R antibodies, as well as CSF biomarkers of AD. The patient was hospitalized with acute memory decline for 1 week. Anti-AMPA1-R and anti-AMPA2-R antibodies were positively detected in CSF, and the anti-AMPA2-R antibody was also present in the serum. Additionally, the biomarkers of AD were concurrently present in CSF (Aβ = 245.70 pg/mL, t-Tau = 894.48 pg/mL, p-Tau = 78.66 pg/mL). After administering a combined treatment of intravenous immunoglobulin and glucocorticoids, the patient recovered significantly, and his cognitive function achieved a sustained remission during 2 months' follow-up. This case raises the awareness of a possible interaction between AE and changes of CSF biomarkers. We speculated that the existence of AMPAR antibodies can induce changes of CSF, and other pathological alterations. This present report highlights that a potential relationship exists among AE and provides a warning when making the diagnosis of AD.
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http://dx.doi.org/10.3389/fneur.2021.673347DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8283122PMC
July 2021

Impaired Memory Awareness and Loss Integration in Self-Referential Network Across the Progression of Alzheimer's Disease Spectrum.

J Alzheimers Dis 2021 ;83(1):111-126

Institute of Neuropsychiatry, the Affiliated Brain Hospital of Nanjing Medical University, Nanjing, Jiangsu, China.

Background: Anosognosia, or unawareness of memory deficits, is a common manifestation of Alzheimer's disease (AD), but greatly variable in subjective cognitive decline (SCD) and amnestic mild cognitive impairment (aMCI) subjects. Self-referential network (SRN) is responsible for self-referential processing and considered to be related to AD progression.

Objective: Our aim is to explore connectivity changes of SRN and its interaction with memory-related network and primary sensorimotor network (SMN) in the AD spectrum.

Methods: About 444 Alzheimer's Disease Neuroimaging Initiative subjects (86 cognitively normal [CN]; 156 SCD; 146 aMCI; 56 AD) were enrolled in our study. The independent component analysis (ICA) method was used to extract the SRN, SMN, and memory-related network from all subjects. The alteration of functional connectivity (FC) within SRN and its connectivity with memory-related network/SMN were compared among four groups and further correlation analysis between altered FC and memory awareness index as well as episodic memory score were performed.

Results: Compared with CN group, individuals with SCD exhibited hyperconnectivity within SRN, while aMCI and AD patients showed hypoconnectivity. Furthermore, aMCI patients and AD patients both showed the interruption of the FC between the SRN and memory-related network compared to CN group. Pearson correlation analysis showed that disruptive FC within SRN and its interaction with memory-related network were related to memory awareness index and episodic memory scores.

Conclusion: In conclusion, impaired memory awareness and episodic memory in the AD spectrum are correlated to the disconnection within SRN and its interaction with memory-related network.
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http://dx.doi.org/10.3233/JAD-210541DOI Listing
January 2021

Effects of intraoperative lung-protective ventilation on clinical outcomes in patients with traumatic brain injury: a randomized controlled trial.

BMC Anesthesiol 2021 06 28;21(1):182. Epub 2021 Jun 28.

Department of Anesthesiology, Northern Jiangsu People's Hospital, Clinical Medical School, Yangzhou University, 98# Nantong West Road, 225001, Yangzhou, China.

Background: Secondary lung injury is the most common non-neurological complication after traumatic brain injury (TBI). Lung-protective ventilation (LPV) has been proven to improve perioperative oxygenation and lung compliance in some critical patients. This study aimed to investigate whether intraoperative LPV could improve respiratory function and prevent postoperative complications in emergency TBI patients.

Methods: Ninety TBI patients were randomly allocated to three groups (1:1:1): Group A, conventional mechanical ventilation [tidal volume (VT) 10 mL/kg only]; Group B, small VT (8 mL/kg) + positive end-expiratory pressure (PEEP) (5 cmHO); and Group C, small VT (8 mL/kg) + PEEP (5 cmHO) + recruitment maneuvers (RMs). The primary outcome was the incidence of total postoperative pulmonary complications; Secondary outcomes were intraoperative respiratory mechanics parameters and serum levels of brain injury markers, and the incidence of each postoperative pulmonary and neurological complication.

Results: Seventy-nine patients completed the final analysis. The intraoperative PaO and dynamic pulmonary compliance of Groups B and C were higher than those of Group A (P = 0.028; P = 0.005), while their airway peak pressure and plateau pressure were lower than those of group A (P = 0.004; P = 0.005). Compared to Group A, Groups B and C had decreased 30-day postoperative incidences of total pulmonary complications, hypoxemia, pulmonary infection, and atelectasis (84.0 % vs. 57.1 % vs. 53.8 %, P = 0.047; 52.0 % vs. 14.3 % vs. 19.2 %, P = 0.005; 84.0 % vs. 50.0 % vs. 42.3 %, P = 0.006; 24.0 % vs. 3.6 % vs. 0.0 %, P = 0.004). Moreover, intraoperative hypotension was more frequent in Group C than in Groups A and B (P = 0.007). At the end of surgery, the serum levels of glial fibrillary acidic protein and ubiquitin carboxyl-terminal hydrolase isozyme L1 in Group B were lower than those in Groups A and C (P = 0.002; P < 0.001). The postoperative incidences of neurological complications among the three groups were comparable.

Conclusions: Continuous intraoperative administration of small VT + PEEP is beneficial to TBI patients. Additional RMs can be performed with caution to prevent disturbances in the stability of cerebral hemodynamics.

Trial Registration: Chinese Clinical Trial Registry (ChiCTR2000038314), retrospectively registered on September 17, 2020.
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http://dx.doi.org/10.1186/s12871-021-01402-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8236740PMC
June 2021

Overexpression of ferroptosis defense enzyme Gpx4 retards motor neuron disease of SOD1G93A mice.

Sci Rep 2021 Jun 18;11(1):12890. Epub 2021 Jun 18.

Department of Cell Systems & Anatomy, University of Texas Health San Antonio, 7703 Floyd Curl Dr., San Antonio, TX, 78229, USA.

Degeneration and death of motor neurons in Amyotrophic Lateral Sclerosis (ALS) are associated with increased lipid peroxidation. Lipid peroxidation is the driver of ferroptosis, an iron-dependent oxidative mode of cell death. However, the importance of ferroptosis in motor neuron degeneration of ALS remains unclear. Glutathione peroxidase 4 (Gpx4) is a key enzyme in suppressing ferroptosis by reducing phospholipid hydroperoxides in membranes. To assess the effect of increased protection against ferroptosis on motor neuron disease, we generated SOD1GPX4 double transgenic mice by cross-breeding GPX4 transgenic mice with SOD1 mice, a widely used ALS mouse model. Compared with control SOD1 mice, both male and female SOD1GPX4 mice had extended lifespans. SOD1GPX4 mice also showed delayed disease onset and increased motor function, which were correlated with ameliorated spinal motor neuron degeneration and reduced lipid peroxidation. Moreover, cell toxicity induced by SOD1 was ameliorated by Gpx4 overexpression and by chemical inhibitors of ferroptosis in vitro. We further found that the anti-ferroptosis defense system in spinal cord tissues of symptomatic SOD1 mice and sporadic ALS patients might be compromised due to deficiency of Gpx4. Thus, our results suggest that ferroptosis plays a key role in motor neuron degeneration of ALS.
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http://dx.doi.org/10.1038/s41598-021-92369-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8213805PMC
June 2021

Hemophagocytic Lymphohistiocytosis in Langerhans Cell Histiocytosis: A Case Series and Literature Review.

J Pediatr Hematol Oncol 2021 Jun 16. Epub 2021 Jun 16.

Department of Pediatrics, West China Second University Hospital, Sichuan University Key Laboratory of Birth Defects and Related Diseases of Women and Children, Sichuan University, Ministry of Education, Chengdu, Sichuan Province, China.

Langerhans cell histiocytosis (LCH) is characterized pathologically by langerin-positive (CD207+) dendritic cell proliferation and is considered by some as a myeloid neoplastic disorder. Hemophagocytic lymphohistiocytosis (HLH) is associated with immune dysregulation characterized by the accumulation of activated macrophages and hypercytokinemia. However, these 2 histiocytosis rarely coexist. Currently, the etiology, risk factors, optimal therapy, and outcomes of LCH-HLH remain unclear. We reviewed the medical records of 7 LCH-HLH patients from our hospital and analyzed 50 LCH-HLH patients reported in scientific literature. The median age of LCH onset of these 57 LCH-HLH patients was 1 year, and 91% (52/57) of patients diagnosed as LCH were less than 2 years old. Fifty-six LCH-HLH patients belonged to the multisystem LCH category and 84% (47/56) patients had risk-organ involvement. Twenty-three LCH-HLH patients were complicated with infection and 3 patients had a primary pathogenic mutation of HLH. Overall, 90% of LCH patients developed HLH at the diagnosis or during chemotherapy. Of the 57 LCH-HLH patients, 15 died. Multisystem LCH patients with risk-organ involvement under 2 years old were most likely to develop HLH when complicated with infection at diagnosis or during chemotherapy. Identifying LCH-HLH patients during early stages and treating them with prompt chemotherapy, hematopoietic stem cell transplantation, or supportive therapies are important for better survival.
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http://dx.doi.org/10.1097/MPH.0000000000002212DOI Listing
June 2021

Clinical characteristics of tumor lysis syndrome in childhood acute lymphoblastic leukemia.

Sci Rep 2021 05 6;11(1):9656. Epub 2021 May 6.

Department of Hematology and Oncology, Children's Hospital of Nanjing Medical University, Nanjing, China.

Tumor lysis syndrome (TLS) is a common and fatal complication of childhood hematologic malignancies, especially acute lymphoblastic leukemia (ALL). The clinical features, therapeutic regimens, and outcomes of TLS have not been comprehensively analyzed in Chinese children with ALL. A total of 5537 children with ALL were recruited from the Chinese Children's Cancer Group, including 79 diagnosed with TLS. The clinical characteristics, treatment regimens, and survival of TLS patients were analyzed. Age distribution of children with TLS was remarkably different from those without TLS. White blood cells (WBC) count ≥ 50 × 10/L was associated with a higher risk of TLS [odds ratio (OR) = 2.6, 95% CI = 1.6-4.5]. The incidence of T-ALL in TLS children was significantly higher than that in non-TLS controls (OR = 4.7, 95% CI = 2.6-8.8). Hyperphosphatemia and hypocalcemia were more common in TLS children with hyperleukocytosis (OR = 2.6, 95% CI = 1.0-6.9 and OR = 5.4, 95% CI = 2.0-14.2, respectively). Significant differences in levels of potassium (P = 0.004), calcium (P < 0.001), phosphorus (P < 0.001) and uric acid (P < 0.001) were observed between groups of TLS patients with and without increased creatinine. Laboratory analysis showed that older age was associated with a higher level of creatinine. Calcium level was notably lower in males. WBC count, lactate dehydrogenase, and creatinine levels were significantly higher in T-ALL subgroup, whereas procalcitonin level was higher in B-ALL children. Older age, infant, a higher level of WBC and T-ALL were risk factors TLS occurrence. Hyperleukocytosis has an impact on the severity of TLS, while renal injury may be an important feature in the process of TLS.
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http://dx.doi.org/10.1038/s41598-021-88912-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8102476PMC
May 2021

Age-related differences of genetic susceptibility to patients with acute lymphoblastic leukemia.

Aging (Albany NY) 2021 04 23;13(9):12456-12465. Epub 2021 Apr 23.

Department of Hematology/Oncology, West China Second Hospital, Sichuan University, Chengdu, China.

Inherited predispositions to acute lymphoblastic leukemia have been well investigated in pediatric patients, but studies on adults, particularly Chinese patients, are limited. In this study, we conducted a genome-wide association study in 466 all-age Chinese patients with Acute lymphoblastic leukemia (ALL) and 1,466 non-ALL controls to estimate the impact of age on ALL susceptibility in the Chinese population. Among the 17 reported loci, 8 have been validated in pediatric and 1 in adult patients. The strongest association signal was identified at locus and gradually decreased with age, while the signal at exhibited the opposite trend and significantly impact on adult patients. With genome-wide approaches, germline variants at 2q14.3 rank as the top inherited predisposition to adult patients (e.g., rs73956024, = 4.3 × 10) and separate the genetic risk of pediatric vs. adult patients ( = 3.6 × 10), whereas variants at 15q25.3 (e.g., rs11638062) have a similar impact on patients in different age groups (overall = 2.9 × 10). Our analysis highlights the impact of age on genetic susceptibility to ALL in Chinese patients.
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http://dx.doi.org/10.18632/aging.202903DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8148462PMC
April 2021

Mechanosensitive Piezo1 channel activation promotes ventilator-induced lung injury via disruption of endothelial junctions in ARDS rats.

Biochem Biophys Res Commun 2021 06 8;556:79-86. Epub 2021 Apr 8.

Department of Anesthesiology, Northern Jiangsu People's Hospital, Clinical Medical School, Yangzhou University, Yangzhou, 225001, China. Electronic address:

Objective: This study aimed to investigate the role of endothelial Piezo1 in mediating ventilator-induced lung injury secondary to acute respiratory distress syndrome (ARDS).

Methods: Rats and lung endothelial cells (ECs) were transfected with Piezo1 shRNA (shPiezo1) and Piezo1 siRNA, respectively, to knock down Piezo1. Intratracheal instillation or incubation with lipopolysaccharide (LPS) was used to establish an ARDS model, and high tidal volume (HVT) ventilation or 20% cyclic stretch (CS) was administered to simulate a two-hit injury. Lung injury, alterations in lung endothelial barrier, disruption of adherens junctions (AJs), and Ca influx were assessed.

Results: Lung vascular hyperpermeability was further increased in ARDS rats following HVT ventilation, which was abrogated in shPiezo1-treated rats. 20% CS led to severer rupture of AJs following LPS stimulation as indicated by immunofluorescence staining. The internalization and degradation of VE-cadherin were blocked by knockdown of Piezo1. Additionally, 20% CS induced Piezo1 activation, manifesting as elevated intracellular Ca concentration in LPS-treated ECs, and subsequently increased calcium-dependent calpain activity. Pharmacological inhibition of calpain or Piezo1 knockdown prevented the loss of VE-cadherin, p120-catenin, and β-catenin in ARDS rats undergoing HVT ventilation and LPS-treated ECs exposed to 20% CS.

Conclusion: Excessive mechanical stretch during ARDS induces the activation of Piezo1 channel and its downstream target, calpain, via Ca influx. This results in the disassembly of endothelial AJs and further facilitates lung endothelial barrier breakdown and vascular hyperpermeability.
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http://dx.doi.org/10.1016/j.bbrc.2021.03.163DOI Listing
June 2021

Effect of perioperative mechanical ventilation strategies on postoperative pulmonary complications in patients undergoing thoracic surgery:a Meta-analysis.

Asian J Surg 2021 May 20;44(5):776-777. Epub 2021 Mar 20.

Department of Anesthesiology, Northern Jiangsu People's Hospital, Clinical Medical College, Yangzhou University, China. Electronic address:

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http://dx.doi.org/10.1016/j.asjsur.2021.02.015DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7979445PMC
May 2021

Prognostic factors for CNS control in children with acute lymphoblastic leukemia treated without cranial irradiation.

Blood 2021 Jul;138(4):331-343

Departments of Oncology, Global Pediatric Medicine, Biostatistics and Pharmaceutical Sciences, St. Jude Children's Research Hospital, Memphis, TN.

To identify the prognostic factors that are useful to improve central nervous system (CNS) control in children with acute lymphoblastic leukemia (ALL), we analyzed the outcome of 7640 consecutive patients treated on Chinese Children's Cancer Group ALL-2015 protocol between 2015 and 2019. This protocol featured prephase dexamethasone treatment before conventional remission induction and subsequent risk-directed therapy, including 16 to 22 triple intrathecal treatments, without prophylactic cranial irradiation. The 5-year event-free survival was 80.3% (95% confidence interval [CI], 78.9-81.7), and overall survival 91.1% (95% CI, 90.1-92.1). The cumulative risk of isolated CNS relapse was 1.9% (95% CI, 1.5-2.3), and any CNS relapse 2.7% (95% CI, 2.2-3.2). The isolated CNS relapse rate was significantly lower in patients with B-cell ALL (B-ALL) than in those with T-cell ALL (T-ALL) (1.6%; 95% CI, 1.2-2.0 vs 4.6%; 95% CI, 2.9-6.3; P < .001). Independent risk factors for isolated CNS relapse included male sex (hazard ratio [HR], 1.8; 95% CI, 1.1-3.0; P = .03), the presence of BCR-ABL1 fusion (HR, 3.8; 95% CI, 2.0-7.3; P < .001) in B-ALL, and presenting leukocyte count ≥50×109/L (HR, 4.3; 95% CI, 1.5-12.2; P = .007) in T-ALL. Significantly lower isolated CNS relapse was associated with the use of total intravenous anesthesia during intrathecal therapy (HR, 0.2; 95% CI, 0.04-0.7; P = .02) and flow cytometry examination of diagnostic cerebrospinal fluid (CSF) (HR, 0.2; 95% CI, 0.06-0.6; P = .006) among patients with B-ALL. Prephase dexamethasone treatment, delayed intrathecal therapy, use of total intravenous anesthesia during intrathecal therapy, and flow cytometry examination of diagnostic CSF may improve CNS control in childhood ALL. This trial was registered with the Chinese Clinical Trial Registry (ChiCTR-IPR-14005706).
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http://dx.doi.org/10.1182/blood.2020010438DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8323972PMC
July 2021

Co-occurrence of TCF3-PBX1 gene fusion, and chromosomal aberration in a pediatric pre-B cell acute lymphoblastic leukemia with clitoris swelling: A case report and literature review.

Medicine (Baltimore) 2021 Feb;100(8):e24802

Key Laboratory of Birth Defects and Related Diseases of Women and Children, Ministry of Education.

Rationale: Clitoris swelling as the initial clinical presentation of acute lymphoblastic leukemia (ALL) is extremely rare. These patients may be misdiagnosed with acute myeloid leukemia or solid tumor, and the main treatment can also be delayed.

Patient Concerns: A 2.10-year-old girl was referred to the pediatric surgery clinic with a worsening onset of clitoris swellings. The patient was afebrile and well appearing. Multiple retroperitoneal mass were confirmed by computed tomography (CT) and high serum neuron-specific enolase level was high. She was scheduled for an abdominal biopsy from the retroperitoneal mass suspicious of neuroblastoma.

Diagnoses: The child was eventually diagnosed as having precursor B cell ALL with central nervous system involved, with TCF3-PBX1 fusion gene and additional chromosomal aberrations, based on examinations of the bone marrow and brain magnetic resonance imaging.

Interventions: Before the diagnosis of leukemia, the patient was given symptomatic treatment for 1 week. She was treated with chemotherapy in accordance with the Chinese Children's Cancer Group protocol 2015 after confirmed diagnosis.

Outcomes: After induction chemotherapy for ALL, although the girl had transiently clinical remission, the bone marrow aspirate indicated a poor outcome. Our patient discontinued treatment and discharged. From literature review, there was only 1 case of in acute myeloid leukemia with clitoris swelling as the initial symptom.

Lessons: The clinical symptoms of ALL with clitoris swelling are not typical, with a high rate of misdiagnosis. When the cause of clitoris swelling is unknown, ALL should be considered. Bone marrow aspiration must be done before doing a more invasive investigation like biopsy.
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http://dx.doi.org/10.1097/MD.0000000000024802DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7909158PMC
February 2021

Effects of melatonin on protecting against lung injury (Review).

Authors:
Weiwei Wang Ju Gao

Exp Ther Med 2021 Mar 20;21(3):228. Epub 2021 Jan 20.

Department of Anesthesiology, Clinical Medical College of Yangzhou University, Northern Jiangsu People's Hospital Affiliated to Yangzhou University, Yangzhou, Jiangsu 225001, P.R. China.

Melatonin (MT; N-acetyl-5-methoxy-tryptamine), which has multiple effects and roles, is secreted from the pineal gland at night according to the daily rhythm. In addition to circadian regulation, MT has anti-inflammatory, antioxidant and anticancer functions. Recent studies postulated that MT serves a critical role in apoptosis, anti-ischemic reperfusion injury and anti-proliferative effects on various cells. The current review reported on the underlying mechanism behind the protective effect of MT on lung diseases, such as acute lung injury, acute respiratory distress syndrome, chronic obstructive pulmonary disease, lung ischemia-reperfusion injury, sepsis-induced lung injury and ventilator-induced lung injury. MT is considered an adjuvant with therapeutic drugs for preventing inflammation and is responsible for regulating patient sleep cycles in the intensive care unit. The current review described the anti-inflammatory and antioxidant efficiency of MT with a focus on the molecular mechanisms of action in various lung injuries.
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http://dx.doi.org/10.3892/etm.2021.9659DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7851611PMC
March 2021

Current antipsychotic agent use and risk of venous thromboembolism and pulmonary embolism: a systematic review and meta-analysis of observational studies.

Ther Adv Psychopharmacol 2021 14;11:2045125320982720. Epub 2021 Jan 14.

Department of Psychiatry, Huai'an No. 3 People's Hospital, Huai'an 223001, Jiangsu, China.

Background: Antipsychotic agents (APS) are widely used drugs to treat psychotic symptoms and can effectively reduce both positive and negative symptoms of schizophrenia. For decades, some studies suggested that there is a relationship between using APS and the risk of venous thromboembolism (VTE) and pulmonary embolism (PE). However, results remain inconclusive.

Method: This review has been registered in International Prospective Register of Systematic Reviews (PROSPERO, ID: CDR42020155620). Relevant studies were identified among observational studies published up to 1 October 2019 in the databases MEDLINE, EMBASE, and Cochrane Library. Random or fixed-effects models were used to calculate the pooled odds ratio (OR).

Results: In total, 28 observational studies were included. The results showed that compared with non-users, current APS users have significantly increased risks of VTE [OR 1.55 95% confidence interval (CI) 1.36, 1.76] and PE (OR 3.68, 95% CI 1.23, 11.05). Subgroup analyses suggested that new users were associated with a higher risk of VTE (OR 2.06, 95% CI 1.81, 2.35). For individual drugs, increased risk of VTE and PE was observed in taking haloperidol, risperidone, olanzapine, prochlorperazine but not in chlorpromazine, quetiapine or aripiprazole. However, careful interpretation is needed because of high heterogeneity among studies and scarce data.

Conclusion: The present comprehensive meta-analysis further indicates a significantly increased risk of VTE and PE in current APS users compared with non-users. Subgroup analyses suggest that new users are more likely to develop VTE. However, due to significant heterogeneity among studies, conclusions should be considered with caution.
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http://dx.doi.org/10.1177/2045125320982720DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7812411PMC
January 2021

Influences Morphology and Grain Size in Rice.

J Plant Biol 2021 Jan 4:1-14. Epub 2021 Jan 4.

Guangxi Academy of Agricultural Sciences/Guangxi Crop Genetic Improvement and Biotechnology Laboratory, Nanning, 530007 China.

Although morphology and grain size are important to rice growth and yield, the identity of abundant natural allelic variations that determine agronomically important differences in crops is unknown. Here, we characterized the function of mitogen-activated protein kinase 3 from Wall. ex Watt encoded by . Different alternative splicing variants occurred in . Green fluorescent protein (GFP)- fusion proteins localized to the cell membrane and nuclei of rice protoplasts. Overexpression of influenced the expression levels of the grain size-related genes , , , , and Phylogenetic analysis showed that is well conserved in plants while showing large amounts of variation between , , and wild rice. In addition, slightly influenced brassinosteroid (BR) responses and the expression levels of BR-related genes. Our findings thus identify a new gene, , influencing morphology and grain size and that represents a possible link between mitogen-activated protein kinase and BR response pathways in grain growth.

Supplementary Information: The online version contains supplementary material available at 10.1007/s12374-020-09290-2.
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http://dx.doi.org/10.1007/s12374-020-09290-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7780602PMC
January 2021

Hypoxic exposure activates the B cell-specific Moloney murine leukaemia virus integration site 1/PI3K/Akt axis and promotes EMT in leukaemia stem cells.

Oncol Lett 2021 Feb 8;21(2):98. Epub 2020 Dec 8.

Department of Pediatric Hematology and Oncology, West China Second University Hospital of Sichuan University, Chengdu, Sichuan 610041, P.R. China.

Acute myeloid leukemia (AML) is a malignant tumor of the immature myeloid hematopoietic cells in the bone marrow. Disease recurrence driven by leukaemia stem cells (LSCs), a sub-population of leukaemia cells presenting self-renewal capacity and differentiation potential, is a major problem in the treatment of AML. Although a hypoxic microenvironment is considered to promote AML malignant behaviours and is considered a potential therapeutic target, the effect of hypoxic stimulation of LSCs is still largely unknown. Therefore, the present study analysed the effects of hypoxia on the malignant behaviours of LSCs. Hypoxia exposure upregulated hypoxia-inducible factor (HIF)-1α, which upregulated the transcription of B cell-specific Moloney murine leukaemia virus integration site 1 (BMI-1). Hypoxia exposure also activated the PI3K/Akt pathway and promoted the epithelial mesenchymal transition (EMT) in LSCs via hypoxia-mediated activation of HIF-1α. BMI-1 served an important role in the hypoxia-induced activation of the PI3K/Akt pathway and the promotion of EMT. Hypoxia exposure promoted chemoresistance against cytarabine arabinoside by inducing HIF-1α, thus activating the transcriptional activity of HIF-1α. Knockdown of BMI-1 disrupted hypoxia-induced chemoresistance in LSCs, indicating that HIF-1α-induced BMI-1 has a role in hypoxia-promoted malignant behaviours. Furthermore, it was demonstrated that induced BMI-1 inhibits the self-renewal capacity in LSCs under hypoxic conditions. The present study provides evidence demonstrating that hypoxia exposure regulates LSCs by activating HIF-1α/BMI-1 signalling, in turn modulating PI3K/Akt signalling and EMT. These results highlight potentially novel therapeutic targets of LSCs to improve the treatment of AML.
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http://dx.doi.org/10.3892/ol.2020.12359DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7751341PMC
February 2021

Cytosolic PINK1 orchestrates protein translation during proteasomal stress by phosphorylating the translation elongation factor eEF1A1.

FEBS Lett 2021 02 6;595(4):507-520. Epub 2021 Jan 6.

The United Innovation of Mengchao Hepatobiliary Technology Key Laboratory of Fujian Province, Mengchao Hepatobiliary Hospital of Fujian Medical University, Fuzhou, China.

Mutations in PINK1 (PTEN-induced putative kinase 1) are associated with autosomal recessive early-onset Parkinson's disease. Full-length PINK1 (PINK1-l) has been extensively studied in mitophagy; however, the functions of the short form of PINK1 (PINK1-s) remain poorly understood. Here, we report that PINK1-s is recruited to ribosome fractions after short-term inhibition of proteasomes. The expression of PINK1-s greatly inhibits protein synthesis even without proteasomal stress. Mechanistically, PINK1-s phosphorylates the translation elongation factor eEF1A1 during proteasome inhibition. The expression of the phosphorylation mimic mutation eEF1A1S396E rescues protein synthesis defects and cell viability caused by PINK1 knockout. These findings implicate an important role for PINK1-s in protecting cells against proteasome stress through inhibiting protein synthesis.
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http://dx.doi.org/10.1002/1873-3468.14030DOI Listing
February 2021

Insight into the heavy metal binding properties of dissolved organic matter in mine water affected by water-rock interaction of coal seam goaf.

Chemosphere 2021 Feb 28;265:129134. Epub 2020 Nov 28.

School of Chemical & Environment Engineering, China University of Mining and Technology (Beijing), Beijing, 100083, China.

The water-rock interaction has a significant effect on the binding characteristics of dissolved organic matter and heavy metals when mine water flows in goaf. This study used fluorescence excitation-emission matrix (EEM) quenching combined with parallel factor (PARAFAC) analysis to characterize the binding properties of DOM with Fe (Ⅲ), Fe (Ⅱ+Ⅲ) and Mn (Ⅱ) in mine water under rock-influenced conditions. Two protein-like components and two humic-like components were identified by PARAFAC, in which protein-like components dominated (75.9%). The fluorescence intensity of each component can all be weakened, especially the stability constant (logK) value of Fe (Ⅱ+Ⅲ) with fulvic-like acid and humic-like acid was the largest and the binding was more stable. Clay minerals and iron-bearing minerals in rocks had significant effects on the binding characteristics of DOM and metal ions under water-rock interaction. Iron ions released by the oxidation of pyrite and siderite in sandstone can reduce the fluorescence intensity of the derived components. The competitive adsorption effect of clay minerals on metal ions made the fluorescence intensity of the derived components under the action of sandstone containing less clay minerals (19.5%) be lower than that of mudstone (31.3%). Meanwhile, the process of water-rock interaction was accompanied by microbial activities to convert protein-like components into fulvic-like and humic-like components, or higher levels of stable substances. This study shows that when assessing the potential ability of mine water DOM and metal ions binding and migration during the flow of water in goaf it is crucial to take into account the presence of water-rock interaction.
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http://dx.doi.org/10.1016/j.chemosphere.2020.129134DOI Listing
February 2021

Validations of Top and Novel Susceptibility Variants in All-Age Chinese Patients With Acute Lymphoblastic Leukemia.

Front Genet 2020 25;11:1004. Epub 2020 Aug 25.

Key Laboratory of Birth Defects and Related Diseases of Women and Children, Department of Pediatric Hematology/Oncology, West China Second Hospital, Sichuan University, Ministry of Education, Chengdu, China.

Through genome-wide association studies (GWAS), multiple inherited predispositions to acute lymphoblastic leukemia (ALL) have been identified in children. Most recently, a novel susceptibility locus at was localized, exhibiting Hispanic-specific manner. In this study, we conducted a replication study to in all-age Chinese patients ( = 451), not only validating the novel locus, but also systematically determining the impact of age on association status of the top GWAS signals. We found that single nucleotide polymorphisms at , , , were only significantly associated with ALL susceptibility in childhood patients with no fusion, while signal exhibited its significance in adults no matter carrying fusion or not. Moreover, the novel SNP can be validated in pediatric patients without both and fusion. Our finding suggests the modifying effects of age on genetic predisposition to ALL, and highlights the impact of SNP in Chinese patients.
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http://dx.doi.org/10.3389/fgene.2020.01004DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7477633PMC
August 2020

Fgr contributes to hemorrhage-induced thalamic pain by activating NF-κB/ERK1/2 pathways.

JCI Insight 2020 10 15;5(20). Epub 2020 Oct 15.

Department of Anesthesiology.

Thalamic pain, a type of central poststroke pain, frequently occurs following ischemia/hemorrhage in the thalamus. Current treatment of this disorder is often ineffective, at least in part due to largely unknown mechanisms that underlie thalamic pain genesis. Here, we report that hemorrhage caused by microinjection of type IV collagenase or autologous whole blood into unilateral ventral posterior lateral nucleus and ventral posterior medial nucleus of the thalamus increased the expression of Fgr, a member of the Src family nonreceptor tyrosine kinases, at both mRNA and protein levels in thalamic microglia. Pharmacological inhibition or genetic knockdown of thalamic Fgr attenuated the hemorrhage-induced thalamic injury on the ipsilateral side and the development and maintenance of mechanical, heat, and cold pain hypersensitivities on the contralateral side. Mechanistically, the increased Fgr participated in hemorrhage-induced microglial activation and subsequent production of TNF-α likely through activation of both NF-κB and ERK1/2 pathways in thalamic microglia. Our findings suggest that Fgr is a key player in thalamic pain and a potential target for the therapeutic management of this disorder.
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http://dx.doi.org/10.1172/jci.insight.139987DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7605540PMC
October 2020

Hereditary Thrombotic Thrombocytopenic Purpura in a Chinese Boy With a Novel Compound Heterozygous Mutation of the Gene.

Front Pediatr 2020 10;8:554. Epub 2020 Sep 10.

Department of Pediatrics, West China Second University Hospital, Sichuan University, Sichuan, China.

Hereditary thrombotic thrombocytopenic purpura (TTP) is caused by mutations with autosomal recessive inheritance. It typically presents during childhood and is frequently misdiagnosed as immune thrombocytopenia. We present a case of hereditary TTP with an undescribed compound heterozygous mutation in a Chinese boy. A 12-year-old boy with a history of intermittent thrombocytopenia in the prior 6 years had severe deficiency of plasma ADAMTS13 and harbored a novel compound heterozygous mutation which was also identified in his sister. The c.577C>T was a pathogenic variant reported exclusively in Japanese cases. The undescribed c.2397C>A non-sense mutation was predicted to encode a truncated protein. Identification of the specific novel heterozygous mutation in the Chinese family, consisting a variant restricted to Asian individuals and an undescribed c.2397C>A non-sense mutation, demonstrates genetic diversity underlying hereditary TTP, and possibly ethnic skewed mutation profiles.
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http://dx.doi.org/10.3389/fped.2020.00554DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7511713PMC
September 2020

Corrigendum: DNA Methylation and Gene Expression of Matrix Metalloproteinase 9 Gene in Deficit and Non-deficit Schizophrenia.

Front Genet 2020 14;11:823. Epub 2020 Aug 14.

Department of Geriatric Psychiatry, Nanjing Brain Hospital, Affiliated to Nanjing Medical University, Nanjing, China.

[This corrects the article DOI: 10.3389/fgene.2018.00646.].
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http://dx.doi.org/10.3389/fgene.2020.00823DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7456980PMC
August 2020

[New advances in molecular mechanisms of ventilator induced lung injury].

Authors:
Lulu Jiang Ju Gao

Zhonghua Wei Zhong Bing Ji Jiu Yi Xue 2020 Jul;32(7):890-893

Department of Anesthesiology, Northern Jiangsu People's Hospital, Yangzhou 225001, Jiangsu, China. Corresponding author: Gao Ju, Email:

Mechanical ventilation (MV) is a common way of respiratory support during general anesthesia and in critically ill patients. Recently people gradually realize that MV is a double-edged sword, which itself can also induce or aggravate lung injury as a damage factor, that is, ventilator induced lung injury (VILI). Current researches on the mechanisms of VILI have changed from traditional barotrauma/volutrauma/atelectasis to biotrauma. In particular, it should be noted that MV can not only cause damage to the lung, but also to the distant organs. This article reviews current researches on the molecular mechanisms of VILI, updates our understanding of them, and provides a theoretical basis for the prevention and treatment of VILI and distant organ damage.
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http://dx.doi.org/10.3760/cma.j.cn121430-20200324-00099DOI Listing
July 2020

Transcriptomic profiling of germinating seeds under cold stress and characterization of the cold-tolerant gene LTG5 in rice.

BMC Plant Biol 2020 Aug 6;20(1):371. Epub 2020 Aug 6.

Rice Research Institute, Guangxi Academy of Agricultural Sciences/Guangxi Key Laboratory of Rice Genetics and Breeding, Nanning, China.

Background: Low temperature is a limiting factor of rice productivity and geographical distribution. Wild rice (Oryza rufipogon Griff.) is an important germplasm resource for rice improvement. It has superior tolerance to many abiotic stresses, including cold stress, but little is known about the mechanism underlying its resistance to cold.

Results: This study elucidated the molecular genetic mechanisms of wild rice in tolerating low temperature. Comprehensive transcriptome profiles of two rice genotypes (cold-sensitive ce 253 and cold-tolerant Y12-4) at the germinating stage under cold stress were comparatively analyzed. A total of 42.44-68.71 million readings were obtained, resulting in the alignment of 29,128 and 30,131 genes in genotypes 253 and Y12-4, respectively. Many common and differentially expressed genes (DEGs) were analyzed in the cold-sensitive and cold-tolerant genotypes. Results showed more upregulated DEGs in the cold-tolerant genotype than in the cold-sensitive genotype at four stages under cold stress. Gene ontology enrichment analyses based on cellular process, metabolic process, response stimulus, membrane part, and catalytic activity indicated more upregulated genes than downregulated ones in the cold-tolerant genotype than in the cold-sensitive genotype. Quantitative real-time polymerase chain reaction was performed on seven randomly selected DEGs to confirm the RNA Sequencing (RNA-seq) data. These genes showed similar expression patterns corresponding with the RNA-Seq method. Weighted gene co-expression network analysis (WGCNA) revealed Y12-4 showed more positive genes than 253 under cold stress. We also explored the cold tolerance gene LTG5 (Low Temperature Growth 5) encoding a UDP-glucosyltransferase. The overexpression of the LTG5 gene conferred cold tolerance to indica rice.

Conclusion: Gene resources related to cold stress from wild rice can be valuable for improving the cold tolerance of crops.
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http://dx.doi.org/10.1186/s12870-020-02569-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7409433PMC
August 2020

Graphene-bridged topological network metamaterials with perfect modulation applied to dynamic cloaking and meta-sensing.

Opt Express 2020 Jul;28(15):22064-22075

Perfect state transfer of the bus topological system enables the sharing of information or excitation between nodes. Herein we report groundbreaking research on the transfer of the graphene-bridged bus topological network structure to an electromagnetic metamaterial setting, named "bus topological network metamaterials (TNMMs)." Correspondingly, the electromagnetic response imprints onto the topological excitation. We find that the bus-TNMMs display a perfect modulation of the terahertz response. The blue-shift of resonance frequency could increase to as large as 1075 GHz. The modulation sensitivity of the bus-TNMMs reaches 1027 GHz/Fermi level unit (FLU). Meanwhile, with the enhancement of modulation, the line shape of the reflection keeps underformed. Parabola, ExpDec1, and Asymptotic models are used to estimate the modulation of the resonance frequency. Besides, the bus-TNMMs system provides a fascinating platform for dynamic cloaking. By governing the Fermi level of graphene, the bus-TNMMs can decide whether it is cloaking or not in a bandwidth of 500 GHz. Also, the bus-TNMMs exhibit the immense potential for dynamically detecting the vibrational fingerprinting of an analyte. These results give a far-reaching outlook for steering dynamically the terahertz response with the bus-TNMMs. Therefore, we believe that the discovery of bus-TNMMs will revolutionize our understanding of the modulation of the electromagnetic response.
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http://dx.doi.org/10.1364/OE.396976DOI Listing
July 2020

X-linked chronic granulomatous disease misdiagnosed as non-Langerhans cell histiocytosis: A case report.

Scand J Immunol 2021 Jan 5;93(1):e12948. Epub 2020 Aug 5.

Department of Pediatrics, West China Second University Hospital, Sichuan University, Chengdu, China.

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http://dx.doi.org/10.1111/sji.12948DOI Listing
January 2021
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