Publications by authors named "Xiaojun Huang"

358 Publications

Narcissism and Entrepreneurship: A Systematic Review and an Agenda for Future Research.

Front Psychol 2021 21;12:657681. Epub 2021 Apr 21.

School of Management (School of Tourism/Sino-French College of Tourism), Guangzhou University, Guangzhou, China.

Although narcissism is an important factor influencing entrepreneurial activity and outcomes, not much research has been conducted on the relationship between narcissism and entrepreneurship. To summarize the current literature on this relationship and provide an agenda for further in-depth research, a systematic review was conducted based on the PRISMA guidelines using Web of Science, Elsevier ScienceDirect, and EBSCO host databases. Accordingly, 33 articles have been identified as being eligible for the final synthesis. The findings of the present study showed, in general, that (1) life history theory, person-environment fit theory (P-E theory), and career choice theory were mostly used to explore the topic of narcissism and entrepreneurial intention, social exchange theory was used to analyze narcissistic entrepreneurs' entrepreneurial motives and attitudes, and upper echelons theory (UET) was applied to research on the relationship between narcissism and entrepreneurial outcomes, (2) Narcissistic Personality Inventory (NPI) and narcissistic sub-dimension of the Dark Triad were frequently used self-report scales among 23 identified empirical studies, and (3) narcissism has both bright and dark sides to entrepreneurial activities and outcomes. While narcissism makes potential entrepreneurs have higher entrepreneurial intentions and greater willingness to take risks, it also prevents entrepreneurs from discovering opportunities, acquiring resources, and learning from failure. Besides, results also showed that relations between narcissism and entrepreneurial intentions and performance are more complex. For a deeper understanding of this complex relations and advancing research on narcissism and entrepreneurship, more research is necessary to explore the relations between narcissism and entrepreneurship-related variables from a temporal perspective and at the team level, examine the relationship between narcissism and entrepreneurship ethics, and investigate the interaction effects of narcissism and other personalities.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fpsyg.2021.657681DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8096986PMC
April 2021

Abnormal Large-Scale Network Activation Present in Bipolar Mania and Bipolar Depression Under Resting State.

Front Psychiatry 2021 26;12:634299. Epub 2021 Mar 26.

Medical Psychological Center, The Second Xiangya Hospital, Central South University, Changsha, China.

Previous studies have primarily focused on the neuropathological mechanisms of the emotional circuit present in bipolar mania and bipolar depression. Recent studies applying resting-state functional magnetic resonance imaging (fMRI) have raise the possibility of examining brain-wide networks abnormality between the two oppositional emotion states, thus this study aimed to characterize the different functional architecture represented in mania and depression by employing group-independent component analysis (gICA). Forty-one bipolar depressive patients, 20 bipolar manic patients, and 40 healthy controls (HCs) were recruited and received resting-state fMRI scans. Group-independent component analysis was applied to the brain network functional connectivity analysis. Then, we calculated the correlation between the value of between-group differences and clinical variables. Group-independent component analysis identified 15 components in all subjects, and ANOVA showed that functional connectivity (FC) differed significantly in the default mode network, central executive network, and frontoparietal network across the three groups. Further -tests showed a gradient descent of activity-depression > HC > mania-in all three networks, with the differences between depression and HCs, as well as between depression and mania, surviving after family wise error (FWE) correction. Moreover, central executive network and frontoparietal network activities were positively correlated with Hamilton depression rating scale (HAMD) scores and negatively correlated with Young manic rating scale (YMRS) scores. Three brain networks heighten activity in depression, but not mania; and the discrepancy regions mainly located in prefrontal, which may imply that the differences in cognition and emotion between the two states is associated with top-down regulation in task-independent networks.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fpsyt.2021.634299DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8032940PMC
March 2021

Impact of socio-demographic co-variates on prognosis, tyrosine kinase-inhibitor use and outcomes in persons with newly-diagnosed chronic myeloid leukaemia.

J Cancer Res Clin Oncol 2021 Apr 9. Epub 2021 Apr 9.

National Clinical Research Center for Hematologic Disease, Peking University People's Hospital, Peking University Institute of Hematology, No. 11 Xizhimen South Street, Beijing, 100044, China.

Purpose: Define the impact of socio-demographic co-variates on outcomes of persons with newly-diagnosed chronic phase chronic myeloid leukaemia (CML).

Methods: Data of 961 consecutive subjects with newly-diagnosed CML were integrated for these outcomes in multi-variable Cox regression analyses after adjusting for confounders and interactions.

Results: Elder age was associated with less use of a 2nd generation TKI as initial therapy. Household registration, comorbidity(ies) and education level were associated with use of a generic rather than branded TKI as initial therapy. Subjects with lower education level were more likely to be diagnosed with CML because of leukaemia-related symptoms. Rural registration and lower education level were also associated with a greater likelihood of switching TKI-therapy. Lower education level was associated with lower likelihood of achieving MMR [HR = 0.8 (0.7, 0.9), p = 0.002], MR [HR = 0.8 (0.7, 1.0), p = 0.055], and poor FFS [HR = 1.7 (1.3, 2.5); p < 0.001], PFS [HR = 2.0 (1.1, 5.0); p = 0.014], CML-related survival [HR = 2.5 (1.0, 10.0); p = 0.060] and survival [HR = 2.5 (1.0, 10.0); p = 0.043]. Males had lower rates of MMR and MR and worse FFS, but not survival compared with females. Being married was associated with a higher rate of MR, fewer failures, progressions, and deaths.

Conclusion: Socio-demographic co-variates have a strong impact on therapy choice and responses in persons with newly-diagnosed CML, including circumstances of diagnosis, risk category and prognosis, use of initial TKI, switching TKIs, response to TKI-therapy, and outcomes.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s00432-021-03624-4DOI Listing
April 2021

Clinical risk score for predicting invasive fungal disease after allogeneic hematopoietic stem cell transplantation: Analysis of the China Assessment of Antifungal Therapy in Hematological Diseases (CAESAR) study.

Transpl Infect Dis 2021 Apr 7:e13611. Epub 2021 Apr 7.

Beijing Key Laboratory of Hematopoietic Stem Cell Transplantation, Peking University Institute of Hematology, Peking University, People's Hospital, Beijing, People's Republic of China.

Background And Objective: Invasive fungal disease (IFD) is associated with a high mortality for patients with hematological malignancies undergoing allogeneic hematopoietic stem cell transplantation (allo-HSCT). This study aimed not only to develop a proven/probable IFD risk-scoring model but to identify high-risk populations that would benefit from anti-fungal prophylaxis.

Methods: Data from the China Assessment of Antifungal Therapy in Hematological Diseases (CAESAR) study were retrieved, and all patients (n = 1053) undergoing allo-HSCT were randomly divided into the training set (n = 685) for model development and the validation set (n = 368) for model verification. A weighted risk score for proven or probable IFD was established through multivariate logistic regression analysis.

Results: The study population had a mean age of 28.95 years and the majority underwent myeloablative transplantation in complete remission 1 (53.4%). Five risk factors of IFD were identified, namely neutropenia lasting longer than 14 days, corticosteroid use, diabetes, haploidentical donor, and unrelated donor. Based on the risk score for IFD, the patients were categorized into three groups: low risk (score 0-4, 1.5%-4.0%), intermediate risk (score 5-8, 9.8%), and high risk (score>8, 24.7%-14.0%). Anti-fungal prophylaxis may provide benefits for patients with intermediate (8.5% vs. 18.5%, P = .0085) or high risk (19.4% vs. 30.8%, P = .4651) but not low risk (2.1% vs. 3.8%, P = .6136) of IFD.

Conclusion: A practical weighted risk score for IFD in patients receiving allo-HSCT was established, which can aid decision-making regarding the administration of anti-fungal prophylaxis.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/tid.13611DOI Listing
April 2021

G-CSF-Primed Peripheral Blood Stem Cell Haploidentical Transplantation Could Achieve Satisfactory Clinical Outcomes for Acute Leukemia Patients in the First Complete Remission: A Registered Study.

Front Oncol 2021 15;11:631625. Epub 2021 Mar 15.

Peking University People's Hospital, Peking University Institute of Hematology, National Clinical Research Center for Hematologic Disease, Research Unit of Key Technique for Diagnosis and Treatments of Hematologic Malignancies, Chinese Academy of Medical Sciences, Beijing Key Laboratory of Hematopoietic Stem Cell Transplantation, Beijing, China.

G-CSF-mobilized peripheral blood (G-PB) harvest is the predominant graft for identical sibling donor and unrelated donor allogeneic hematopoietic stem cell transplantation (HSCT) recipients, but it was controversial in haploidentical related donor (HID) HSCT. In this registry study, we aimed to identify the efficacy of HID G-PB HSCT (HID-PBSCT) for acute leukemia (AL) patients in first complete remission (CR1). Also, we reported the outcomes for the use of G-PB grafts in comparison with the combination of G-BM and G-PB grafts in HID HSCT recipients. Sixty-seven AL patients in CR1 who received HID-PBSCT were recruited at Institute of Hematology, Peking University. Patients who received haploidentical HSCT using the combination of G-BM and G-PB harvests in the same period were enrolled as controls (n=392). The median time from HSCT to neutrophil and platelet engraftment was 12 days (range, 9-19 days) and 12 days (range, 8-171 days), respectively. The 28-day cumulative incidence of neutrophil and platelet engraftment after HSCT was 98.5% and 95.5%, respectively. The cumulative incidences of grade II-IV and grade III-IV acute graft-versus-host disease (GVHD) were 29.9% (95%CI 18.8-40.9%) and 7.5% (95%CI 1.1-13.8%), respectively. The cumulative incidences of total and moderate-severe chronic GVHD were 54.9% (95%CI 40.9-68.8%) and 17.4% (95%CI 6.7-28.0%), respectively. The cumulative incidences of relapse and non-relapse mortality were 13.9% (95%CI 5.4-22.5%) and 3.4% (95%CI 0-8.1%), respectively. The probabilities of overall survival (OS) and leukemia-free survival (LFS) were 84.7% (95%CI 74.7-94.7%) and 82.7% (95%CI 73.3-92.1%) respectively. Compared with the HID HSCT recipients using the combination of G-BM and G-PB grafts, the engraftments of neutrophil and platelet were both significantly faster for the G-PB group, and the other clinical outcomes were all comparable between the groups. In multivariate analysis, graft types did not influence the clinical outcomes. Overall, for the patients with AL CR1, G-PB graft could be considered an acceptable graft for HID HSCT recipients. This study was registered at https://clinicaltrials.gov as NCT03756675.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fonc.2021.631625DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8005750PMC
March 2021

A Study of Differences in Penile Dorsal Nerve Somatosensory Evoked Potential Testing Among Healthy Controls and Patients With Primary and Secondary Premature Ejaculation.

J Sex Med 2021 Apr 18;18(4):732-736. Epub 2021 Mar 18.

Department of Urology, The Second Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, China; Andrology Laboratory on Integration of Chinese and Western Medicine, Zhejiang Provincial Key Laboratory of Traditional Chinese Medicine, Hangzhou, China. Electronic address:

Background: Penile dorsal nerve somatosensory evoked potential (DNSEP) is a scientific and objective technique that provides effective and objective data to establish the diagnosis of premature ejaculation (PE).

Aim: To explore differences in DNSEP between patients with primary premature ejaculation (PPE) and those with secondary premature ejaculation (SPE), in order to investigate the clinical value of DNSEP in the diagnosis of PE.

Methods: The participants were divided into a PPE group (34 cases), an SPE group (25 cases) and a healthy control group (18 cases). All participants underwent DNSEP testing, and the latencies and amplitudes of DNSEP were recorded.

Outcomes: Differences in the latencies and amplitudes of DNSEP were compared among the PPE, SPE, and healthy control groups.

Results: The latencies of DNSEP in the PPE and SPE groups were shorter than those in the healthy control group, and these differences were statistically significant (P < 0.01). However, there was no statistically significant difference between the PPE and SPE groups (P > 0.05). The amplitudes of DNSEP in the PPE group were significantly higher than those in the healthy control group (P < 0.01). However, the amplitudes of DNSEP in the SPE group were significantly lower than those in the healthy control group (P < 0.05).

Clinical Implications: PPE and SPE can be differentiated based on differences in the amplitudes of DNSEP, providing an objective basis for treatments and follow-up examinations.

Strengths And Limitations: We evaluated differences in the amplitudes of DNSEP between PPE and SPE patients, which were rare in the published literature. However, specific causes of these differences are still unclear. SEP only reflects afferent pathways in the ejaculatory reflex arc, and role of the brain as a higher center should not be ignored.

Conclusion: Both PPE and SPE patients are characterized by an increased excitability of the penile sensory nerves. Sun Z, Liao Z, Zheng Q, et al. A Study of Differences in Penile Dorsal Nerve Somatosensory Evoked Potential Testing Among Healthy Controls and Patients With Primary and Secondary Premature Ejaculation. J Sex Med Rev 2021;18:732-736.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jsxm.2021.01.186DOI Listing
April 2021

Reprint of "Amorphous nickel titanium alloy film: A new choice for cryo electron microscopy sample preparation".

Prog Biophys Mol Biol 2021 Mar 26;160:5-15. Epub 2021 Feb 26.

Center for Biological Imaging, Core Facilities for Protein Science, Institute of Biophysics, Chinese Academy of Sciences, Beijing, 100101, China; National Key Laboratory of Biomacromolecules, CAS Center for Excellence in Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing, 100101, China; College of Life Science, University of Chinese Academy of Sciences, Beijing, 100049, China. Electronic address:

Cryo-electron microscopy (cryoEM) has become one of the most important approach for structural biology. However, barriers are still there for an increased successful rate, a better resolution and improved efficiency from sample preparation, data collection to image processing. CryoEM sample preparation is one of the bottlenecks with many efforts made recently, including the optimization of supporting substrate (e.g. ultra-thin carbon, graphene, pure gold, 2d crystal of streptavidin, and affinity modification), which was aimed to solve air-water interface problem, or reduce beam induced motion (BIM), or change particle distribution in the grid hole. Here, we report another effort of developing a new supporting substrate, the amorphous nickel-titanium alloy (ANTA) film, for cryoEM sample preparation as a layer of holey supporting film covering on TEM grid. Our investigations showed advantages of ANTA film in comparison with conventional carbon film, including much better electron conductivity and trace non-specific interaction with protein. These advantages yield less BIM and significantly improved particle distribution during cryoEM experiment of human apo-ferritn, thus resulting an improved reconstruction resolution from a reduced number of micrographs and particles. Unlike the pure gold film, the usage of the ANTA film is just same with the carbon film, compatible to conventional automatic cryoEM data collection procedure.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.pbiomolbio.2021.02.001DOI Listing
March 2021

Expanding the clinical spectrum of adult-onset neuronal intranuclear inclusion disease.

Acta Neurol Belg 2021 Feb 24. Epub 2021 Feb 24.

Department of Neurology, Rui Jin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, China.

Neuronal intranuclear inclusion disease (NIID) is a heterogeneous neurodegenerative disease with multiple clinical subtypes. Recent breakthroughs on neuroimaging, skin biopsy and genetic testing have facilitated the diagnosis. We aim to investigate the clinical characteristics of Chinese NIID patients to further refine the spectrum. We analyzed the clinical features of 25 NIID patients from 24 unrelated families and performed skin biopsy and/or sural nerve biopsy on 24 probands. Repeat-primed PCR and fluorescence amplicon length PCR were conducted to detect GGC repeats of NOTCH2NLC. Onset age ranged from 24 to 72 years old, and the disease duration ranged from 12 h to 25 years with the mode of onset characterized as acute, recurrent or chronic progressive type. Tremor was a common phenotype, often observed in the early stages, next to dementia and paroxysmal encephalopathy. Symptoms infrequently reported such as oromandibular dystonia, recurrent vomiting, dizziness and headache of unknown origin, as well as pure peripheral neuropathy were also suggestive of NIID. Reversible leukoencephalopathy following encephalitic episodes and the absence of apparent DWI abnormality were noticed. Two genetically confirmed NIID patients failed to be identified intranuclear inclusions, and one patient was simultaneously found significant mitochondrial swelling and fingerprint profiles depositing in lysosomes. All the patients were identified abnormal GGC repeats of NOTCH2NLC. We identify some atypical clinicopathological features and consider that pathological examinations combined with genetic testing is the gold standard for diagnosis. Whether lysosomal and mitochondrial dysfunction is involved in the pathogenesis of NIID deserves further study.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s13760-021-01622-4DOI Listing
February 2021

Multiomics Approach to Explore the Amelioration Mechanisms of Glucomannans on the Metabolic Disorder of Type 2 Diabetic Rats.

J Agric Food Chem 2021 Mar 19;69(8):2632-2645. Epub 2021 Feb 19.

State Key Laboratory of Food Science and Technology, China-Canada Joint Laboratory of Food Science and Technology (Nanchang), Nanchang University, 235 Nanjing East Road, Nanchang, Jiangxi 330047, People's Republic of China.

Type 2 diabetes (T2D) is a worldwide epidemic associated with metabolic disorders and intestinal microbiota alterations. Polysaccharides have been considered to be beneficial to the prevention and alleviation of T2D. In the present study, ultra-performance liquid chromatography-triple-time-of-flight-based metabolomics and proteomics and 16S rRNA sequencing methods were employed to evaluate the effects of glucomannans from stem, konjac, and leaves on host metabolism and intestinal microbiota regulation in type 2 diabetic rats and potential mechanisms. The metabolism of amino acids was significantly disturbed in the type 2 diabetic rats, especially the upregulated branched-chain amino acid (BCAA) metabolism. Host-derived BCAA metabolism was significantly decreased in type 2 diabetic rats. However, the levels of BCAAs in host circulation and gene abundance of BCAA biosynthesis in gut microbiota were significantly increased in diabetic rats, which suggested that the disturbed intestinal microbiota might be responsible for the increased circulation of BCAAs in T2D. Glucomannan treatment decreased the abundance of microbial BCAA biosynthesis-related genes and ameliorated the host BCAA metabolism. Also, glucomannan with a higher molecular weight and a lower ratio of mannose/glucose possessed better antidiabetic effects. In summary, the antidiabetic effects of glucomannans might be associated with the amelioration of BCAA metabolism by modulating intestinal microbiota.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1021/acs.jafc.0c07871DOI Listing
March 2021

Recommendations for the diagnosis and treatment of paroxysmal kinesigenic dyskinesia: an expert consensus in China.

Transl Neurodegener 2021 Feb 16;10(1). Epub 2021 Feb 16.

Department of Neurology, Affiliated Hospital of Guilin Medical University, Guilin Medical University; Guangxi Key Laboratory of Brain and Cognitive Neuroscience, Guilin Medical University, Guangxi Clinical Research Center for Neurological Diseases, Affiliated Hospital of Guilin Medical University, Guilin Medical University; Guangxi Key Laboratory of Brain and Cognitive Neuroscience, Guilin Medical University, Guilin, China.

Paroxysmal dyskinesias are a group of neurological diseases characterized by intermittent episodes of involuntary movements with different causes. Paroxysmal kinesigenic dyskinesia (PKD) is the most common type of paroxysmal dyskinesia and can be divided into primary and secondary types based on the etiology. Clinically, PKD is characterized by recurrent and transient attacks of involuntary movements precipitated by a sudden voluntary action. The major cause of primary PKD is genetic abnormalities, and the inheritance pattern of PKD is mainly autosomal-dominant with incomplete penetrance. The proline-rich transmembrane protein 2 (PRRT2) was the first identified causative gene of PKD, accounting for the majority of PKD cases worldwide. An increasing number of studies has revealed the clinical and genetic characteristics, as well as the underlying mechanisms of PKD. By seeking the views of domestic experts, we propose an expert consensus regarding the diagnosis and treatment of PKD to help establish standardized clinical evaluation and therapies for PKD. In this consensus, we review the clinical manifestations, etiology, clinical diagnostic criteria and therapeutic recommendations for PKD, and results of genetic analyses in PKD patients performed in domestic hospitals.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s40035-021-00231-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7885391PMC
February 2021

Molecular epidemiology, antimicrobial activity, and virulence gene clustering of Streptococcus agalactiae isolated from dairy cattle with mastitis in China.

J Dairy Sci 2021 Apr 5;104(4):4893-4903. Epub 2021 Feb 5.

College of Veterinary Medicine, Nanjing Agricultural University, Nanjing 210095, China; MOE Joint International Research Laboratory of Animal Health and Food Safety, Nanjing 210095, China. Electronic address:

Streptococcus agalactiae is a contagious pathogen that causes bovine mastitis worldwide, resulting in considerable economic losses. In this study, we isolated 42 S. agalactiae strains in 379 milk samples from cows with subclinical mastitis on 15 dairy farms in 12 Chinese provinces. Analysis based on capsular typing and multilocus sequence typing, combined with patterns of virulence gene scanning and antimicrobial resistance, identified the lineages and populations of the isolates. We grouped the 42 isolates into 7 sequence types belonging to 6 clonal complexes, mainly CC103 (31/42 isolates; 73.8%). We identified an ST-23 strain named Sa 129 for the first time on Chinese dairy farms-this strain is usually associated with human isolates. Capsular types Ia and II were predominant in capsular typing. The prevalence of virulence profile 1 (bibA, cfb, cspA, cylE, fbsA, fbsB, hylB, and pavA) was 64.3%, and represented the main trend in China. With respect to antimicrobial resistance, most isolates were susceptible to β-lactams, rifamycin, glycopeptides, and oxazolidone; resistance to several antimicrobial agents, including lincomycin, clindamycin, and doxycycline, varied in 4 different regions. Our research provides a profile for the molecular epidemiology, multilocus sequence typing, antimicrobial resistance, and virulence gene clustering of S. agalactiae, and may be beneficial for the clinical monitoring, prevention, and control of mastitis in dairy cattle.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3168/jds.2020-19139DOI Listing
April 2021

Both the subtypes of KIT mutation and minimal residual disease are associated with prognosis in core binding factor acute myeloid leukemia: a retrospective clinical cohort study in single center.

Ann Hematol 2021 May 20;100(5):1203-1212. Epub 2021 Jan 20.

Peking University People's Hospital, Peking University Institute of Hematology, National Clinical Research Center for Hematology Disease, Beijing, China.

Core binding factor acute myeloid leukemia (CBF-AML), including cases with KIT mutation, is currently defined as a low-risk AML. However, some patients have poor response to treatment, and the prognostic significance of KIT mutation is still controversial. This study aimed to explore the prognostic significance of different KIT mutation subtypes and minimal residual disease (MRD) in CBF-AML. We retrospectively evaluated continuous patients diagnosed with CBF-AML in our center between January 2014 and April 2019. Of the 215 patients, 147 (68.4%) and 68 (31.6%) patients were RUNX1-RUNX1T1- and CBFB-MYH11 positive, respectively. KIT mutations were found in 71 (33.0%) patients; of them, 38 (53.5%) had D816/D820 mutations. After excluding 10 patients who died or were lost to follow-up within a half year, 42.0% (n = 86) of the remaining 205 patients received allogeneic hematopoietic stem cell transplantation (allo-HSCT). An MRD > 0.1% at the end of two cycles of consolidation predicted relapse (P < 0.001). Multivariate analysis showed that D816 or D820 mutations and MRD > 0.1% at the end of two cycles of consolidation were independent adverse factors affecting relapse-free survival (RFS) and overall survival (OS). Allo-HSCT could improve RFS (74.4% vs. 34.6%, P < 0.001) and OS (78.1% vs. 52.3%, P = 0.002). In conclusion, high-risk CBF-AML patients must be identified before treatment. D816/D820 mutation, MRD > 0.1% at the end of two cycles of consolidation chemotherapy predicted poor survivals, and allo-HSCT can improve the survival of properly identified patients.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s00277-021-04432-zDOI Listing
May 2021

Cryo-EM analysis of the HCoV-229E spike glycoprotein reveals dynamic prefusion conformational changes.

Nat Commun 2021 01 8;12(1):141. Epub 2021 Jan 8.

State Key Laboratory of Agricultural Microbiology, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, China.

Coronaviruses spike (S) glycoproteins mediate viral entry into host cells by binding to host receptors. However, how the S1 subunit undergoes conformational changes for receptor recognition has not been elucidated in Alphacoronavirus. Here, we report the cryo-EM structures of the HCoV-229E S trimer in prefusion state with two conformations. The activated conformation may pose the potential exposure of the S1-RBDs by decreasing of the interaction area between the S1-RBDs and the surrounding S1-NTDs and S1-RBDs compared to the closed conformation. Furthermore, structural comparison of our structures with the previously reported HCoV-229E S structure showed that the S trimers trended to open the S2 subunit from the closed conformation to open conformation, which could promote the transition from pre- to postfusion. Our results provide insights into the mechanisms involved in S glycoprotein-mediated Alphacoronavirus entry and have implications for vaccine and therapeutic antibody design.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41467-020-20401-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7794242PMC
January 2021

Overt gastrointestinal bleeding following haploidentical haematopoietic stem cell transplantation: incidence, outcomes and predictive models.

Bone Marrow Transplant 2021 Jan 7. Epub 2021 Jan 7.

Peking University People's Hospital, Peking University Institute of Haematology, Beijing, China.

Gastrointestinal bleeding (GIB) accounts for a significant proportion of life-threatening bleeding cases occurring after allogeneic haematopoietic stem cell transplantation (allo-HSCT). However, data on GIB after haploidentical HSCT (haplo-HSCT) are not available. A total of 3180 patients received haplo-HSCT at Peking University People's Hospital from January 2015 to November 2019, and GIB occurred in 188 of these patients (incidence of 5.9%). Platelet counts <30 × 10/L, viral hepatitis, acute kidney injury (AKI), gastrointestinal disease or bleeding before HSCT and sinusoidal obstruction syndrome (SOS) were determined to be significant risk factors for the occurrence of GIB after haplo-HSCT. Grade III-IV acute graft-versus-host disease (aGVHD), AKI, thrombotic microangiopathy (TMA), disseminated intravascular coagulation (DIC) and gastrointestinal disease or bleeding before HSCT were significantly related to mortality in patients with GIB after haplo-HSCT. The predictive models developed for the occurrence and mortality of GIB performed well in terms of discrimination, and they might assist clinicians with personalised strategies for GIB prevention and treatment in patients after haplo-HSCT.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41409-020-01187-5DOI Listing
January 2021

Lysosome-Mediated Cytotoxic Autophagy Contributes to Tea Polysaccharide-Induced Colon Cancer Cell Death via mTOR-TFEB Signaling.

J Agric Food Chem 2021 Jan 28;69(2):686-697. Epub 2020 Dec 28.

State Key Laboratory of Food Science and Technology, China-Canada Joint Lab of Food Science and Technology (Nanchang), Nanchang University, 235 Nanjing East Road, Nanchang, Jiangxi 330047, China.

Targeting autophagy and lysosome may serve as a promising strategy for cancer therapy. Tea polysaccharide (TP) has shown promising antitumor effects. However, its mechanism remains elusive. Here, TP was found to have a significant inhibitory effect on the proliferation of colon cancer line HCT116 cells. RNA-seq analysis showed that TP upregulated autophagy and lysosome signal pathways, which was further confirmed through experiments. Immunofluorescence experiments indicated that TP activated transcription factor EB (TFEB), a key nuclear transcription factor modulating autophagy and lysosome biogenesis. In addition, TP inhibited the activity of mTOR, while it increased the expression of Lamp1. Furthermore, TP ameliorated the lysosomal damage and autophagy flux barrier caused by Baf A1 (lysosome inhibitor). Hence, our data suggested that TP repressed the proliferation of HCT116 cells by targeting lysosome to induce cytotoxic autophagy, which might be achieved through mTOR-TFEB signaling. In summary, TP may be used as a potential drug to overcome colon cancer.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1021/acs.jafc.0c07166DOI Listing
January 2021

Preemptive interferon-α treatment could protect against relapse and improve long-term survival of ALL patients after allo-HSCT.

Sci Rep 2020 11 19;10(1):20148. Epub 2020 Nov 19.

Peking University People's Hospital, Peking University Institute of Hematology, National Clinical Research Center for Hematologic Disease, Research Unit of Key Technique for Diagnosis and Treatments of Hematologic Malignancies, Chinese Academy of Medical Sciences, 2019RU029, Beijing Key Laboratory of Hematopoietic Stem Cell Transplantation, No. 11 Xizhimen South Street, Xicheng District, Beijing, 100044, China.

Relapse was the major cause of treatment failure in patients with acute lymphoblastic leukemia (ALL) after allogeneic hematopoietic stem cell transplantation (allo-HSCT). We aimed to identify the efficacy and safety of preemptive interferon-α (IFN-α) treatment in ALL patients who had minimal residual disease (MRD) after allo-HSCT. Multiparameter flow cytometry and polymerase chain reaction assays were applied for MRD monitoring. Recombinant human IFN-α-2b injections were administered subcutaneously twice weekly in every 4 weeks cycle. Twenty-four (35.3%), 5 (7.4%), 6 (8.8%), and 13 (19.1%) patients achieved MRD negativity at 1, 2, 3, and > 3 months, respectively, after treatment. Seven patients showed grade ≥ 3 toxicities after IFN-α treatment. The 4-year cumulative incidence of total acute graft-versus-host disease (aGVHD), severe aGVHD, total chronic GVHD (cGVHD), and severe cGVHD after treatment was 14.7%, 2.9%, 40.0%, and 7.5%, respectively. The 4-year cumulative incidences of relapse and non-relapse mortality after treatment was 31.9% and 6.0%, respectively. The 4-year probabilities of disease-free survival and overall survival after IFN-α treatment were 62.1% and 71.1%, respectively. Thus, preemptive IFN-α treatment could protect against relapse and improve long-term survival for ALL patients who had MRD after allo-HSCT. The study was registered at https://clinicaltrials.gov as #NCT02185261 (09/07/2014).
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41598-020-77186-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7677364PMC
November 2020

Late diagnosis of coarctation of the aorta in a 44-year-old male: a case report.

BMC Cardiovasc Disord 2020 11 3;20(1):470. Epub 2020 Nov 3.

Department of Plastic Surgery, First Affiliated Hospital of Shantou University Medical College, Shantou, 515041, Guangdong, China.

Background: Coarctation of the aorta is a rare congenital disease. In adults, the main manifestations include hypertension, weak or absent femoral pulses, heart failure, and left ventricular hypertrophy.

Case Presentation: We present a case involving a late diagnosis of coarctation of the aorta detected during aortography in a 44-year-old man. The patient underwent stent implantation and aortoplasty. After 2 years of follow-up, the patient was in good condition.

Conclusions: This case shows that coarctation of the aorta can be cured and that hypertension caused by the condition can be controlled to some extent with medication. Based on our findings, we recommend a detailed physical examination for all patients suspected of having coarctation of the aorta; the examination should include blood pressure measurements of both the upper and lower extremities. The case of coarctation of the aorta is not common or easy to be found in medium-aged population. Better BP control, earlier repair, and transcatheter intervention may result in a good outcome in that case.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s12872-020-01753-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7607745PMC
November 2020

A comparative study on nutritive peculiarities of 24 Chinese cowpea cultivars.

Food Chem Toxicol 2020 Dec 1;146:111841. Epub 2020 Nov 1.

State Key Laboratory of Food Science and Technology, China-Canada Joint Lab of Food Science and Technology (Nanchang), Nanchang University, 235 Nanjing East Road, Nanchang, 330047, China. Electronic address:

The nutritive peculiarities and original distribution of 24 Chinese cowpeas cultivars, achieved from Jiangxi, Jilin, Shanxi and Shaanxi provinces in China, were evaluated. Their nutritional components were determined and nutrient characteristics were discussed. Principal component analysis (PCA) was applied to classify the cowpea samples based on their nutrient composition. The results discovered that the proximate composition varied among 24 cowpeas in protein (17.30-27.23%), fat (1.87-3.14%), high level of dietary fiber (29.49-38.54%) and resistant starch (3.18-31.33%). The total tocopherol varied from 74.20 to 187.07 μg/g. PCA results presented that the 24 cowpeas cultivars were automatically grouped with provinces of origin, indicating a relationship between nutrient composition and cultivating religion for cowpeas. The results of this study provide us the information on the nutrients characteristic of current cowpeas in China, and give a guideline on cowpea cultivating optimization and processing.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.fct.2020.111841DOI Listing
December 2020

Production of lentiviral vectors in suspension cells using low proportion of supercoiled circular plasmid DNA.

Cytotechnology 2020 Oct 29. Epub 2020 Oct 29.

Peking University People's Hospital, Peking University Institute of Hematology, National Clinical Research Center for Hematologic Disease, Beijing Key Laboratory of Hematopoietic Stem Cell Transplantation, No. 11 South Street of Xizhimen, Xicheng District, 100044, Beijing, China.

The supercoiled circular (SC) topology form of plasmid DNA has been regarded to be advantageous over open circular or linearized analogue in transfection and expression efficiency, and therefore are largely demanded in the biopharmaceutical manufacturing. However, production of high-purity SC plasmid DNA would result in high manufacturing cost. The effect of SC proportion in plasmid DNA on the quality of packaged lentiviral vectors has never been reported. In this study, we established an efficient system for production of high-titer lentiviral vectors using suspension HEK293SF cells in serum-free media, and the lentiviral titer was not associated with the proportion of SC plasmid DNA. Plasmids DNA with different proportion of SC, open-circular, and linearized forms were prepared using the thermal denaturation method, and were transfected to adherent HEK293T or suspension HEK293SF cells for packaging of lentiviral vectors. The titer of lentiviral vectors from HEK293T cells, but not from HEK293SF cells, was significantly impaired when the proportion of SC plasmid DNA decreased from 60-80% to 30-40%. Further decrease of SC plasmid proportion to 3% led to a dramatic reduction of lentiviral titer no matter the packaging cell line was. However, lentiviral vectors from HEK293SF cells still showed a high titer even when the proportion of SC plasmid DNA was 3%. This study demonstrated that extremely high proportion of SC plasmid DNA was not required for packaging of high-titer lentiviral vector in HEK293SF cells, at least under our manufacturing process.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s10616-020-00433-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7695760PMC
October 2020

Capillary-driven blood separation and in-situ electrochemical detection based on 3D conductive gradient hollow fiber membrane.

Biosens Bioelectron 2021 Jan 14;171:112722. Epub 2020 Oct 14.

Key Laboratory of Macromolecular Synthesis and Functionalization, ERC of Membrane and Water Treatment (MOE), Department of Polymer Science and Engineering, Zhejiang University, Hangzhou, 310027, China. Electronic address:

It is essential to develop portable, versatile, and reliable diagnostic devices in point-of-care testing (POCT). The detection of biomarkers requires selective separation and large specific surface for high sensitivity and accuracy at trace levels in whole blood samples using POCT devices. Herein, a kind of 3D electrochemical biosensors were designed via in-situ synthesizing polyaniline (PANI) and platinum nanoparticles (Pt NPs) on polysulfone hollow fiber membrane (HFM) scaffolds with gradient porous structure. The gradient porous HFMs scaffolds provide uniform capillary flow, self-driven blood separation and sufficient enzyme immobilization sites. Simultaneously, the in-situ deposited materials fulfill interconnected conductive networks, thus ensuring accurate and rapid detection of the sensors without hindering capillary progress. These sensors display ultralow sampling (~3 μL), fast fluid flow (>1 μL/ms), wide linear range (glucose: 0-24 mM, R=0.992; cholesterol: 0-9 mM, R=0.999), high sensitivity and accuracy especially under different hematocrits in POCT applications towards glucose and cholesterol. The innovative integration of POCT biosensors with interconnected conductive nanoparticles, selective blood separation and gradient porous structures can find wide application in resource-limited regions, large population screening, and public health emergencies.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.bios.2020.112722DOI Listing
January 2021

Impact of stopping therapy during the SARS-CoV-2 pandemic in persons with lymphoma.

J Cancer Res Clin Oncol 2021 May 19;147(5):1469-1479. Epub 2020 Oct 19.

Peking University Peoples Hospital, Peking University Institute of Hematology, National Clinical Research Center for Hematologic Disease, No.11, Xizhimen Nan Street, Beijing, 100044, China.

Introduction: The severe acute respiratory syndrome-2 (SARS-CoV-2) pandemic disrupted medical care for persons with cancer including those with lymphoma. Many professional societies recommend postponing, decreasing, or stopping anti-cancer therapy in selected persons during the pandemic. Although seemingly sensible, these recommendations are not evidence-based and their impact on anxiety and health-related quality-of-life (HRQoL) is unknown.

Methods: We surveyed 2532 subjects including 1060 persons with lymphoma, 948 caregivers, and 524 normals using a purposed-designed questionnaire on a patient organization website. Respondents also completed the Zung Self-Rating Anxiety and patient respondents, the EORTC QLQ-C30 instruments to quantify anxiety, and HRQoL. We also evaluated caregiver support and an online education programme of the Chinese Society of Clinical Oncology (CSCO). Data of HRQoL from a 2019 pre-pandemic online survey of 1106 persons with lymphoma were a control.

Results: 33% (95% confidence interval [CI] 30, 36%) of lymphoma patients and 31% (28, 34%) of caregivers but only 21% (17, 24%) of normals had any level of anxiety (both pair-wise P < 0.001). Among lymphoma respondents, physical exercise and better caregiver support were associated with less anxiety, whereas female sex, receiving therapy, and reduced therapy intensity were associated with more anxiety. Paradoxically, lymphoma respondents during the pandemic had better HRQoL than pre-pandemic controls. Reduced therapy intensity was associated with worse HRQoL, whereas respondents who scored caregiver support and the online patient education programme high had better HRQoL.

Conclusion: During the SARS-CoV-2 pandemic, lymphoma patients and their caregivers had significantly higher incidences of anxiety compared with normals. Lymphoma respondents reported better HRQoL compared with pre-pandemic controls. Reduced therapy intensity in persons with cancer may have unanticipated adverse effects on anxiety and HRQoL. Regular and intense support by caregivers and online education programmes alleviate anxiety and improve HRQoL.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s00432-020-03426-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7571863PMC
May 2021

Ethnic and geographic diversity of chronic lymphocytic leukaemia.

Leukemia 2021 02 19;35(2):433-439. Epub 2020 Oct 19.

Haematology Research Centre, Department of Immunology and Inflammation, Imperial College London, London, UK.

East Asians, Asian Indians and Amerindians have a five to ten-fold lower age-adjusted incidence rate (AAIR) of chronic lymphocytic leukaemia (CLL) compared with persons of predominately European descent. The data we review suggest a genetic rather than environmental basis for this discordance. All these populations arose from a common African Black ancestor but different clades have different admixture with archaic hominins including Neanderthals, Denisovans and Homo erectus, which may explain different CLL incidences. There are also some differences in clinical laboratory and molecular co-variates of CLL between these populations. Because the true age-adjusted incidence rate in African Blacks is unknown it is not possible to determine whether modern Europeans acquired susceptibility to CLL or the other populations lost susceptibility and/or developed resistance to developing CLL. We also found other B-cell lymphomas and T- and NK-cell cancers had different incidences in the populations we studied. These data provide clues to determining the cause(s) of CLL.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41375-020-01057-5DOI Listing
February 2021

Transcriptional heterogeneity of clonal plasma cells and immune evasion in immunoglobulin light chain amyloidosis.

Int J Hematol 2021 Feb 10;113(2):231-242. Epub 2020 Oct 10.

Beijing Key Laboratory of Hematopoietic Stem Cell Transplantation, Peking University People's Hospital and Institute of Hematology, Beijing, 100044, China.

Immunoglobulin light chain amyloidosis (AL amyloidosis) is characterized by the presence of B cells producing amyloidogenic immunoglobulin light chains (LCs). The low frequency of aberrant B cells in AL is often masked by a polyclonal B cell background, making it difficult for treatment. We analyzed the single-cell RNA sequencing data from GEO database to compare the plasma cell (PCs) in four individuals with AL amyloidosis, one AL subject after treatment, and six healthy controls. High interindividual variability in AL-derived PCs in their expression pattern of known overexpressed genes in multiple myeloma and their usage of V regions in LCs was demonstrated. We also found overexpression of MHC class I molecules as one of the common features of clonal PCs in individuals with AL amyloidosis. Significantly reduced frequencies of circulating natural killer (NK) cells were also observed in a small cohort of AL patients when compared to healthy controls. These data demonstrate that aberrant PCs in AL has a highly diverse transcriptome, an upregulation of MHC, and a dampened capability of immunosurveillance by reduction of circulating NK frequencies. The analysis of clonal PCs at single cell level may provide a better approach for precise molecular profiling and diagnosis of AL amyloidosis.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s12185-020-03016-3DOI Listing
February 2021

Unmanipulated haploidentical hematopoietic stem cell transplantation for children with myelodysplastic syndrome.

Pediatr Transplant 2020 11 28;24(7):e13864. Epub 2020 Sep 28.

Peking University People's Hospital, Peking University Institute of Hematology, National Clinical Research Center for Hematologic Disease, Research Unit of Key Technique for Diagnosis and Treatments of Hematologic Malignancies, Beijing Key Laboratory of Hematopoietic Stem Cell Transplantation, Beijing, China.

Myelodysplastic syndrome (MDS) is a heterogeneous group of clonal disorders and is rare in children. Allogeneic hematopoietic stem cell transplantation (HSCT) is commonly used in children with MDS with excess blasts and in patients with refractory cytopenia of childhood (RCC) associated with monosomy 7, complex karyotype, severe neutropenia, or transfusion dependence. We recruited 27 children with MDS who received haploidentical hematopoietic stem cell transplantation (haplo-HSCT). At transplantation, 10 patients had RCC, 12 patients had advanced MDS (RAEB and RAEB-T), and 5 patients had myelodysplasia-related acute myeloid leukemia (MDR-AML). All patients received granulocyte colony-stimulating factor (G-CSF)-mobilized bone marrow cells and peripheral blood stem cells. At a median follow-up of 24.1 months (range: 2.0-74.5 months) after HSCT, the estimated probabilities of 3-year disease-free survival (DFS) and overall survival (OS) were both 81.9% (95% CI, 66.8-100.0%). The estimated 3-year incidences of relapse (CIR) and non-relapse mortality (NRM) were both 7.4% (95% CI, 1.2%-21.4%). The 100-day cumulative incidence of grade II-IV aGVHD was 52.6% (95% CI, 42.9-62.3%), while that of grade III-IV aGVHD was 11.1% (95% CI, 5.1-17.1%). The 3-year cumulative incidences of overall and extensive cGVHD were 42.3% (95% CI, 19.8%-57.5%) and 21.1% (95% CI, 2.5%-63.2%), respectively. Univariate analysis showed that chronic GVHD significantly affected OS and DFS. Haploidentical HSCT may be an effective treatment option with easier donor availability for pediatric patients with MDS.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/petr.13864DOI Listing
November 2020

Th2 polarization in target organs is involved in the alleviation of pathological damage mediated by transplanting granulocyte colony-stimulating factor-primed donor T cells.

Sci China Life Sci 2020 Sep 1. Epub 2020 Sep 1.

Peking University People's Hospital, Peking University Institute of Hematology, National Clinical Research Center for Hematologic Disease, Beijing Key Laboratory of HSCT, Peking University, Beijing, 100044, China.

Acute graft-versus-host disease (aGVHD) is caused by allo-activated donor T cells infiltrating target organs. As a regulator of immune function, granulocyte colony-stimulating factor (G-CSF) has been demonstrated to relieve the aGVHD reaction. However, the role of G-CSF-primed donor T cells in specific target organs is still unknown. In this study, we employed a classical MHC-mismatched transplantation mouse model (C57BL/6 into BALB/c) and found that recipient mice transplanted with G-CSF-primed T cells exhibited prolonged survival compared with that of the PBS-treated group. This protective function against GVHD mediated by G-CSF-primed donor T cells was further confirmed by decreased clinical and pathological scores in this aGVHD mouse model, especially in the lung and gut. Moreover, we found that T cells polarized towards Th2 cells and regulatory T cells were increased in specific target organs. In addition, G-CSF treatment inhibited inducible co-stimulator (ICOS) expression and increased the expression of tolerance-related genes in recipient mice. Our study provides new insight into the immune regulatory effects of G-CSF on T cell-mediated aGVHD, especially for its precise regulation in GVHD target organs.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s11427-020-1754-6DOI Listing
September 2020

Gut microbiome alterations and its link to corticosteroid resistance in immune thrombocytopenia.

Sci China Life Sci 2021 May 25;64(5):766-783. Epub 2020 Aug 25.

Peking University People's Hospital, Peking University Institute of Hematology, Beijing Key Laboratory of Hematopoietic Stem Cell Transplantation, Beijing, 100044, China.

Quantitative metagenomic studies have linked the gut microbiota to autoimmune disorders. Here, we performed deep shotgun metagenomic sequencing of fecal samples from 99 immune thrombocytopenia (ITP) patients and 52 healthy controls. Dysbiosis in the gut microbiome of ITP was detected phylogenetically and functionally, and classifier based on species markers distinguished individuals with ITP from healthy controls. In particular, the abundance of Ruminococcus gnavus, Bifidobacterium longum and Akkermansia muciniphila was markedly increased in treatment-naïve ITP patients, and the alterations of microbial species were correlated with clinical indices. Functionally, the secondary bile acid biosynthesis and flagellar assembly were depleted in the gut microbiota of ITP, which may contribute to the onset of ITP by affecting the immune system. Furthermore, we found that corticosteroid treatment affected the gut microbiome of ITP. Compared with corticosteroid-sensitive ITP patients, we identified that the corticosteroid-resistant ITP patients displayed a distinct gut microbiome, which was different from that of the treatment-naïve ITP patients. Together, we provided support for the critical role of gut microbiota in the development of ITP and established a foundation for further research characterizing gut microbiota in relation to corticosteroid resistance of ITP.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s11427-020-1788-2DOI Listing
May 2021

LncRNA UCA1 maintains the low-tumorigenic and nonmetastatic status by stabilizing E-cadherin in primary prostate cancer cells.

Mol Carcinog 2020 10 17;59(10):1174-1187. Epub 2020 Aug 17.

Department of Biochemistry and Molecular Cell Biology, Shanghai Key Laboratory of Tumor Microenvironment and Inflammation, State Key Laboratory of Oncogenes and Related Genes, Shanghai Jiao Tong University School of Medicine, Shanghai, China.

Long noncoding RNAs (LncRNAs) have emerged as important players in cancer biology. Increasing evidence suggests that LncRNAs are frequently dysregulated in cancer and may function as oncogenes or tumor suppressors. Urothelial carcinoma associated 1 (UCA1), a LncRNA, firstly identified in bladder transitional cell carcinoma, seems to act as an oncogene in many different types of human cancers by promoting cell proliferation and migration. In this study, we revealed a novel biological function of UCA1, which was different from that reported by previous studies, was responsible for maintaining the low-tumorigenic, nonmetastatic phenotypes in primary prostate epithelial cells. UCA1 could stabilize E-cadherin protein by preventing the interaction between E-cadherin and its E3 ligase MDM2, which suppressed MDM2-mediated ubiquitination and degradation of E-cadherin. In addition, we also found that UCA1 acted as a sponge of miR-296-3p, which targeted E-cadherin gene CDH1 messenger RNA at the posttranscription level. Taken together, these findings demonstrated that UCA1 had a new important role in effectively keeping E-cadherin at a high level through a dual mechanism, which maintained primary prostate cancer cells at the low-tumorigenic and nonmetastatic status.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/mc.23247DOI Listing
October 2020

Sorafenib maintenance in patients with FLT3-ITD acute myeloid leukaemia undergoing allogeneic haematopoietic stem-cell transplantation: an open-label, multicentre, randomised phase 3 trial.

Lancet Oncol 2020 09 10;21(9):1201-1212. Epub 2020 Aug 10.

Department of Hematology, Nanfang Hospital, Southern Medical University, Guangzhou, China. Electronic address:

Background: Findings of retrospective studies suggest that sorafenib maintenance post-transplantation might reduce relapse in patients with FLT3 internal tandem duplication (FLT3-ITD) acute myeloid leukaemia undergoing allogeneic haematopoietic stem-cell transplantation. We investigated the efficacy and tolerability of sorafenib maintenance post-transplantation in this population.

Methods: We did an open-label, randomised phase 3 trial at seven hospitals in China. Eligible patients (aged 18-60 years) had FLT3-ITD acute myeloid leukaemia, were undergoing allogeneic haematopoietic stem-cell transplantation, had an Eastern Cooperative Oncology Group performance status of 0-2, had composite complete remission before and after transplantation, and had haematopoietic recovery within 60 days post-transplantation. Patients were randomly assigned (1:1) to sorafenib maintenance (400 mg orally twice daily) or non-maintenance (control) at 30-60 days post-transplantation. Randomisation was done with permuted blocks (block size four) and implemented through an interactive web-based randomisation system. The primary endpoint was the 1-year cumulative incidence of relapse in the intention-to-treat population. This trial is registered with ClinicalTrials.gov, NCT02474290; the trial is complete.

Findings: Between June 20, 2015, and July 21, 2018, 202 patients were enrolled and randomly assigned to sorafenib maintenance (n=100) or control (n=102). Median follow-up post-transplantation was 21·3 months (IQR 15·0-37·0). The 1-year cumulative incidence of relapse was 7·0% (95% CI 3·1-13·1) in the sorafenib group and 24·5% (16·6-33·2) in the control group (hazard ratio 0·25, 95% CI 0·11-0·57; p=0·0010). Within 210 days post-transplantation, the most common grade 3 and 4 adverse events were infections (25 [25%] of 100 patients in the sorafenib group vs 24 [24%] of 102 in the control group), acute graft-versus-host-disease (GVHD; 23 [23%] of 100 vs 21 [21%] of 102), chronic GVHD (18 [18%] of 99 vs 17 [17%] of 99), and haematological toxicity (15 [15%] of 100 vs seven [7%] of 102). There were no treatment-related deaths.

Interpretation: Sorafenib maintenance post-transplantation can reduce relapse and is well tolerated in patients with FLT3-ITD acute myeloid leukaemia undergoing allogeneic haematopoietic stem-cell transplantation. This strategy could be a suitable therapeutic option for patients with FLT3-ITD acute myeloid leukaemia.

Funding: None.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/S1470-2045(20)30455-1DOI Listing
September 2020

Dendrobium officinale polysaccharide ameliorates the liver metabolism disorders of type II diabetic rats.

Int J Biol Macromol 2020 Dec 5;164:1939-1948. Epub 2020 Aug 5.

State Key Laboratory of Food Science and Technology, China-Canada Joint Lab of Food Science and Technology (Nanchang), Nanchang University, 235 Nanjing East Road, Nanchang 330047, China. Electronic address:

Type 2 diabetes (T2D) is a complicated endocrine metabolic disease, accompanied with oxidative stress injury and low-grade inflammation. The effects of polysaccharide extracted from Dendrobium officinale stem (DOP) on oxidative stress, inflammation and dysregulated metabolism in the liver of type 2 diabetic rats and its potential mechanism were evaluated in the study. Here, ultra performance liquid chromatography - quadrupole - time - of - flight (UPLC-Q-TOF) mass spectrometry-based lipidomics and metabolomics analysis were carried out to study the amelioration of DOP on the liver metabolism disorders of type 2 diabetic rats. Lipidomics analysis indicated that the disturbed degree of fatty acid, glycerolipid (diacylglycerol and triacylglycerol), and glycerophospholipid (phosphatidylcholine and phosphatidylethanolamine) metabolism were mitigated by the DOP treatment. Metabolomics analysis revealed that the DOP treatment balanced the metabolism of ceramide and bile acids, including deoxycholic acid, taurocholic acid, and cholic acid. In addition, the symptoms of oxidative stress, inflammation, and hepatic lipid accumulation of liver were ameliorated by DOP administration. The above results suggest that the study of functional ingredient application of DOP might be meaningful for the management of T2D.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.ijbiomac.2020.08.007DOI Listing
December 2020

Amorphous nickel titanium alloy film: A new choice for cryo electron microscopy sample preparation.

Prog Biophys Mol Biol 2020 10 3;156:3-13. Epub 2020 Aug 3.

Center for Biological Imaging, Core Facilities for Protein Science, Institute of Biophysics, Chinese Academy of Sciences, Beijing, 100101, China; National Key Laboratory of Biomacromolecules, CAS Center for Excellence in Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing, 100101, China; College of Life Science, University of Chinese Academy of Sciences, Beijing, 100049, China. Electronic address:

Cryo-electron microscopy (cryoEM) has become one of the most important approach for structural biology. However, barriers are still there for an increased successful rate, a better resolution and improved efficiency from sample preparation, data collection to image processing. CryoEM sample preparation is one of the bottlenecks with many efforts made recently, including the optimization of supporting substrate (e.g. ultra-thin carbon, graphene, pure gold, 2d crystal of streptavidin, and affinity modification), which was aimed to solve air-water interface problem, or reduce beam induced motion (BIM), or change particle distribution in the grid hole. Here, we report another effort of developing a new supporting substrate, the amorphous nickel-titanium alloy (ANTA) film, for cryoEM sample preparation as a layer of holey supporting film covering on TEM grid. Our investigations showed advantages of ANTA film in comparison with conventional carbon film, including much better electron conductivity and trace non-specific interaction with protein. These advantages yield less BIM and significantly improved particle distribution during cryoEM experiment of human apo-ferritn, thus resulting an improved reconstruction resolution from a reduced number of micrographs and particles. Unlike the pure gold film, the usage of the ANTA film is just same with the carbon film, compatible to conventional automatic cryoEM data collection procedure.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.pbiomolbio.2020.07.009DOI Listing
October 2020