Publications by authors named "Lei Ye"

600 Publications

Exercise interventions for post-stroke depression: A protocol for systematic review and meta-analysis.

Medicine (Baltimore) 2021 Feb;100(8):e24945

Department of Emergency Medicine, West China Hospital, School of Nursing, and Disaster Medical Center, Sichuan University, Chengdu, China.

Background: Post-stroke depression (PSD) is one of the most common neuropsychiatric complications after stroke and is associated with increased risk of death and poor functional outcomes. Strong evidence shows that exercise has benefits for depression. However, it is not clear whether exercise has benefits specifically for PSD. This study aims to explore the effects of exercise on PSD and to establish safe and effective exercise prescriptions.

Methods And Analysis: The PubMed, Cochrane Library and EMBASE, databases will be searched using prespecified search strategies. Randomized controlled trials and non-randomized prospective controlled cohort studies regarding exercise for PSD will be included. The primary outcomes are depression scale and stroke outcome. The secondary outcomes are the occurrence of adverse events, cognitive function, quality of life indices, and the expression of nerve cell factors. The methodological quality of each study will be evaluated by the physiotherapy evidence database scale. The heterogeneity will be evaluated using the I2 test. If I2 > 50%, random effects models will be used in the analysis; otherwise, fixed effects models will be used to pool the data.

Results: This study will assess the efficacy and safety of exercise for PSD.

Conclusions: Our findings will be helpful for clinicians to re-examine the clinical decision-making in the treatment of PSD, by assessing the efficacy of a promising treatment modality for patients with PSD.

Ethics And Dissemination: Ethical approval is not required because this study is a secondary analysis. The results of this study will be disseminated through journals and academic exchanges.

Systematic Review Registration Number: INPLASY202110100.
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http://dx.doi.org/10.1097/MD.0000000000024945DOI Listing
February 2021

Urinary albumin-to-creatinine ratio levels are associated with subclinical atherosclerosis and predict CVD events and all-cause deaths: a prospective analysis.

BMJ Open 2021 Mar 3;11(3):e040890. Epub 2021 Mar 3.

Department of Endocrine and Metabolic Diseases, Shanghai Institute of Endocrine and Metabolic Diseases, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China

Objective: We aimed to examine the associations of urinary albumin-to-creatinine ratio (ACR) levels with risks of subclinical atherosclerosis, cardiovascular events and all-cause deaths.

Methods: Data from a large population-based cohort were used, which included 9580 participants aged ≥40 years free from cardiovascular diseases. Carotid intima-media thickness, brachial-ankle pulse wave velocity and ankle-brachial index were measured at baseline to assess subclinical atherosclerosis. After a median of 4.53 years' follow-up, 486 cardiovascular events and 230 all-cause deaths were recorded.

Results: The urinary ACR levels were categorised into three groups. Compared with the normal group (0≤ACR <7.82 mg/g), people with low-grade albuminuria (7.82≤ACR <30 mg/g) and albuminuria (ACR ≥30 mg/g) had higher levels of subclinical atherosclerosis. In prospective analysis, people with low-grade albuminuria was not significantly associated with cardiovascular events (HR=1.18; 95% CI 0.95 to 1.46], whereas people with albuminuria had a 50% higher risk of cardiovascular events (HR=1.50; 95% CI 1.11 to 2.03). People with low-grade albuminuria and albuminuria had 43% (HR=1.43; 95% CI 1.05 to 1.93) and 87% (HR=1.87; 95% CI 1.24 to 2.81) higher risks of all-cause deaths during follow-up, respectively. In stratified analysis, the association of higher ACR with risks of cardiovascular events and all-cause deaths was stronger among individuals with concomitant subclinical atherosclerosis, the presence of diabetes and more cardiovascular risk factors, respectively.

Conclusions: ACR levels were positively associated with subclinical atherosclerosis and predicted the risks of cardiovascular events and all-cause deaths. Evaluation of ACR levels should be integrated into risk stratification and prevention of cardiovascular events and all-cause deaths, especially among those with pre-existing subclinical atherosclerosis and cardiometabolic abnormalities.
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http://dx.doi.org/10.1136/bmjopen-2020-040890DOI Listing
March 2021

Functional connectivity density alterations in middle-age retinal detachment patients.

Brain Behav 2021 Mar 1:e01783. Epub 2021 Mar 1.

Department of Ophthalmology, The First Affiliated Hospital of Nanchang University, Nanchang, China.

Objective: Middle-age patients with retinal detachment (RD) exhibit a loss of visual information, and previous studies of functional magnetic resonance imaging (fMRI) have demonstrated abnormal spontaneous activity in the RD brain. Therefore, this study assessed changes in local functional connectivity density (lFCD) and long-range functional connectivity density (longFCD) in middle-age RD patients during resting-state FC.

Methods: In total, 32 middle-age patients with RD (18 men and 14 women), and 32 age-, sex-, and education-matched normal controls (NCs) (18 men and 14 women) were recruited and underwent functional magnetic resonance examination in the resting state. Two-sample t test was performed to compare lFCD and longFCD between groups. Receiver operating characteristic (ROC) curves were generated to distinguish middle-age RD patients from NCs.

Results: Compared with NCs, middle-age RD patients demonstrated increased lFCD values in the right inferior temporal gyrus, and increased longFCD values in the bilateral inferior frontal gyri, left superior and middle frontal gyrus, bilateral inferior temporal gyri, and left cerebellum posterior lobe. Middle-age RD patient exhibited decreased lFCD values in the left cuneus, right lingual gyrus, and left middle frontal gyrus. They also had lower longFCD values in the left lingual gyrus and left inferior occipital gyrus. ROC curve analysis showed excellent accuracy of the specific areas under the curve.

Conclusion: Our results reveal that middle-age RD patients exhibited variations of binarized lFCD and longFCD in specific brain areas, which provides insight into the pathological mechanism of RD patients with acute visual loss.
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http://dx.doi.org/10.1002/brb3.1783DOI Listing
March 2021

Early urinary continence recovery following retzius-sparing robotic-assistant radical prostatectomy with suprapubic catheter: a short-term follow-up outcome.

World J Urol 2021 Feb 27. Epub 2021 Feb 27.

Department of Urology, Xiangya Hospital of Central South University, Changsha, China.

Objective: To evaluate the recovery of early urinary continence in patients with prostate cancer using a suprapubic catheter during Retzius-sparing robotic-assistant laparoscopic prostatectomy.

Patients And Methods: From January 2018 to January 2019, 223 patients diagnosed with prostate cancer who underwent Retzius-sparing robotic-assistant laparoscopic prostatectomy in Diakonie Klinikum Stuttgart were involved in our study. From January 2018 to June 2018, patients (112 cases) only had an indwelling urinary catheter during Retzius-sparing robotic-assistant laparoscopic prostatectomy, while from July 2018 to January 2019, patients (111 cases) were offered an extra suprapubic catheter during operation. The recovery of early urinary continence of patients was mainly investigated one month later.

Results: The overall early urinary continence rate was 81.61%. Patients with suprapubic catheter had better urinary control results, compared to patients with only indwelling urinary catheter (87.39% vs 75.89%, p = 0.027). In addition, International Prostate Symptom Score and irritative subscore in patients with good urinary control were significantly lower than that in patients with urinary incontinence. Suprapubic catheter insertion (OR 0.395; 95% CI 0.190-0.821) and advanced pathological tumor stage (T3a-T4) (OR 2.061; 95% CI 1.008-4.217) were two independent influencing factors for early urinary continence recovery in patients who underwent Retzius-sparing robotic-assistant laparoscopic prostatectomy through multivariate logistic regression analysis.

Conclusion: Suprapubic catheter insertion may be helpful for early urinary continence recovery in patients with Retzius-sparing Robotic-assistant laparoscopic prostatectomy. Advanced pathological tumor stage (T3a-T4) before Retzius-sparing robotic-assistant laparoscopic prostatectomy might be associated with poor urinary control.
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http://dx.doi.org/10.1007/s00345-021-03643-3DOI Listing
February 2021

Prognostic Value of the Nutritional Risk Screening 2002 Scale in Patients With Acute Myocardial Infarction: Insights From the Retrospective Multicenter Study for Early Evaluation of Acute Chest Pain.

J Cardiovasc Nurs 2021 Feb 16. Epub 2021 Feb 16.

Fanghui Li, MBBS Doctor, Department of Emergency Medicine; Staff, Disaster Medical Center; and Doctor, Department of Cardiology, West China Hospital, Sichuan University, Chengdu, China. Dongze Li, MBBS, PhD Doctor, Department of Emergency Medicine; and Staff, Disaster Medical Center, West China Hospital, Sichuan University, Chengdu, China. Jing Yu, MBBS Staff, West China School of Nursing, West China Hospital, Sichuan University, Chengdu, China. Yu Jia, MBBS, PhD Doctor, Department of Emergency Medicine; and Staff, Disaster Medical Center, West China Hospital, Sichuan University, Chengdu, China. Ying Jiang, MBBS Doctor, Department of Cardiology, West China Hospital, Sichuan University, Chengdu, China. Xiaoli Chen, RN, MSc Nurse, Department of Emergency Medicine; and Staff, Disaster Medical Center, West China Hospital, Sichuan University, Chengdu, China. Yongli Gao, RN Nurse, Department of Emergency Medicine; and Committee Member, Disaster Medical Center, West China Hospital, Sichuan University, Chengdu, China. Lei Ye, RN, MSc Nurse, Department of Emergency Medicine; and Staff, Disaster Medical Center, West China Hospital, Sichuan University, Chengdu, China. Zhi Wan, MD Doctor, Department of Emergency Medicine; and Committee Member, Disaster Medical Center, West China Hospital, Sichuan University, Chengdu, China. Yu Cao, MD Doctor, Department of Emergency Medicine; and Committee Member, Disaster Medical Center, West China Hospital, Sichuan University, Chengdu, China. Zhi Zeng, MD Doctor, Department of Emergency Medicine; and Committee Member, Disaster Medical Center, West China Hospital, Sichuan University, Chengdu, China. Rui Zeng, MD Doctor, Department of Emergency Medicine; Committee Member, Disaster Medical Center; and Doctor, Department of Cardiology, West China Hospital, Sichuan University, Chengdu, China.

Background: The Nutritional Risk Screening 2002 (NRS-2002) scale is a rapid and effective screening instrument that assesses nutritional risk among hospitalized patients.

Objective: The present study aimed to explore the prognostic value of the NRS-2002 scale in acute myocardial infarction (AMI) considering its uncertain role in this particular condition.

Methods: Patients with AMI included in the Retrospective Multicenter Study for Early Evaluation of Acute Chest Pain were investigated. Kaplan-Meier survival analysis and Cox proportional hazards models were used to analyze the association between NRS-2002 and mortality in patients with AMI. The primary and secondary endpoints were all-cause and cardiac mortality during the follow-up period.

Results: A total of 2307 patients were enrolled, among whom 246 (10.7%) died within a median follow-up duration of 10.67 (8.04-14.33) months. Kaplan-Meier analysis revealed that patients with an NRS-2002 score of 3 or higher had poorer cumulative survival than those with an NRS-2002 score lower than 3 (P < .001). In the multivariate Cox regression analysis, patients with an NRS-2002 score of 3 or higher had more than double the risk for all-cause mortality (hazard ratio, 2.25; 95% confidence interval, 1.50-3.40; P < .001) and twice the risk for cardiac-related mortality (hazard ratio, 2.01; 95% confidence interval, 1.29-3.13; P = .002) than did patients with lower scores.

Conclusions: Our results showed that the NRS-2002 screening instrument was an independent prognostic predictor for both all-cause and cardiac mortality in patients with AMI. Nutritional risk assessment based on the NRS-2002 scale may provide useful prognostic information of early nutritional risk stratification in patients with AMI.
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http://dx.doi.org/10.1097/JCN.0000000000000786DOI Listing
February 2021

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

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

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

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

Temperature affects substrate-associated bacterial composition during hyphal growth.

Can J Microbiol 2021 Feb 16:1-9. Epub 2021 Feb 16.

Soil and Fertilizer Institute, Sichuan Academy of Agricultural Sciences, Chengdu 610066, China.

The growth of the well-known fungus is influenced by temperature, which has an impact on the associated microbial structure in the substrate. In this study, we analyzed the bacterial diversity of the substrate at different temperatures using next-generation sequencing technology. A total of 513 733 sequences from 15 samples were assigned to 19 bacterial phyla. The samples were dominated by , followed by ; the 2 phyla exhibited opposite changes with elevated temperature. Bacterial genera showed different abundances at different temperatures, in which maintained a stable abundance below 40 °C, while and were enriched with elevated temperature and both showed their highest abundances at 40 °C. Functional prediction uncovered 39 identified KEGG pathways, and bacterial genes involved in the membrane transport pathway exhibited the highest abundance subject to heat (40 °C) during the growth of . . In general, our findings illustrated the influence of temperatures on mycelial morphology and the bacterial community in the substrate, and the results will facilitate cultivation of this fungus.
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http://dx.doi.org/10.1139/cjm-2020-0070DOI Listing
February 2021

Ultrafine CoRu alloy nanoparticles in situ embedded in CoN porous nanosheets as high-efficient hydrogen evolution electrocatalysts.

Dalton Trans 2021 Feb 10;50(8):2973-2980. Epub 2021 Feb 10.

School of Chemical Engineering and Technology, North University of China, Taiyuan, Shanxi 030051, China.

The development of hydrogen evolution reaction (HER) electrocatalysts with outstanding efficiency and favorable stability at all pH values is of great significance but still a dominating challenge toward the development of electrochemical water-splitting technology. Herein, CoRu alloy nanoparticles assembled in CoN porous nanosheets (named as CoRu@CoN) have been successfully achieved from Ru(OH)@Co(OH) through a one-step nitridation process. Benefiting from the unique structure, inherent alloy properties and strong alloy-support interaction derived from the in situ transformation, the resultant hybrids exhibit superior HER activities over a wide pH range, achieving very low overpotentials of 13 mV, 44 mV and 15 mV at 10 mA cm under alkaline, neutral and acidic conditions, respectively. Such activities surpass most reported electrocatalysts and are comparable or even transcendent to commercial Ru/C and Pt/C. Furthermore, CoRu@CoN also exhibits outstanding stability during the accelerated degradation test (ADT) and chronopotentiometry. Our work provides a new approach for designing pH-universal Ru-involved HER electrocatalysts with remarkable efficiency and prominent durability.
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http://dx.doi.org/10.1039/d0dt04248jDOI Listing
February 2021

A Pedestrian Detection Algorithm Based on Score Fusion for Multi-LiDAR Systems.

Sensors (Basel) 2021 Feb 7;21(4). Epub 2021 Feb 7.

Science and Technology on Near-Surface Detection Laboratory, Wuxi 214035, China.

Pedestrian detection plays an essential role in the navigation system of autonomous vehicles. Multisensor fusion-based approaches are usually used to improve detection performance. In this study, we aimed to develop a score fusion-based pedestrian detection algorithm by integrating the data of two light detection and ranging systems (LiDARs). We first evaluated a two-stage object-detection pipeline for each LiDAR, including object proposal and fine classification. The scores from these two different classifiers were then fused to generate the result using the Bayesian rule. To improve proposal performance, we applied two features: the central points density feature, which acts as a filter to speed up the process and reduce false alarms; and the location feature, including the density distribution and height difference distribution of the point cloud, which describes an object's profile and location in a sliding window. Extensive experiments tested in KITTI and the self-built dataset show that our method could produce highly accurate pedestrian detection results in real-time. The proposed method not only considers the accuracy and efficiency but also the flexibility for different modalities.
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http://dx.doi.org/10.3390/s21041159DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7914457PMC
February 2021

Asparanin A inhibits cell migration and invasion in human endometrial cancer via Ras/ERK/MAPK pathway.

Food Chem Toxicol 2021 Feb 6;150:112036. Epub 2021 Feb 6.

School of Food and Biological Engineering, Hefei University of Technology, Hefei, 230009, People's Republic of China; Collaborative Innovation Center for Food Production and Safety, School of Biological Science and Engineering, North Minzu University, Yinchuan, 750021, People's Republic of China. Electronic address:

Asparanin A (AA), a natural compound present in vegetables and medicinal herbs like Asparagus officinalis L., has been investigated extensively for its pharmacological attributes. So far, the effect of AA on endometrial cancer (EC) cell migration and invasion has not been explored. Herein, we elucidated the anti-metastasis mechanism of AA on Ishikawa cells based on miRNA-seq and mRNA-seq integrated analyses. AA treatment led to altered miRNAs expression in Ishikawa cells and inhibited the cell wound healing, cell migration and invasion. Gene Ontology and KEGG enrichment analyses showed that the target genes of different expression miRNAs were significantly enriched in Ras, Rap1 and MAPK signaling pathways. Further verification of these changes via qRT-PCR and Western blot assays in vitro and in vivo demonstrated that AA could suppress human EC cell migration and invasion through Ras/ERK/MAPK pathway. Furthermore, top two miRNAs (miR-6236-p5 and miR-12136_R+8) and top three target genes (KITLG, PDGFD, and NRAS) were identified as functional hub miRNAs and genes through miRNA-target gene network analysis. Our data presented a holistic approach to comprehend the anti-metastatic role of AA in EC after in vitro and in vivo analyses.
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http://dx.doi.org/10.1016/j.fct.2021.112036DOI Listing
February 2021

[Relationship between Changes of Lymphocyte Subsets and Early Hematologic Response in Immunosuppressive Therapy of Severe Aplastic Anemia Patients].

Zhongguo Shi Yan Xue Ye Xue Za Zhi 2021 Feb;29(1):207-212

State Key Laboratory of Experimental Hematology, National Clinical Research Center for Blood Diseases, Institute of Hematology & Blood Disease Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin 300020, China,E-mail:

Objective: To explore the relationship between the change of lymphocyte subsets before and after immunosuppressive therapy (IST) with disease severity of severe aplastic anemia (SAA) and hematologic response to IST.

Methods: The clinical data of 94 patients with SAA/VSAA treated by r-ATG and CsA in our hospital from December 2009 to October 2011 was analyzed retrospectively. Among them, 26 patients who had sequential data of lymphocyte subsets and cytokines before and after treatment were enrolled. The relationship between lymphocyte subsets, cytokine level before IST and disease severity, as well as the relationship between changes if lymphocyte subsets, changes of cytokine and the HR after IST for 6 months was analyzed.

Results: There were no statistical differences in the ratio and absolute count of lymphocyte, the ratio and absolute count of each lymphocyte subsets, including CD3T cells, CD3CD4T cells, CD3CD8T cells, CD3CD161CD56NK cells, and CD19B cells, and the level of cytokines, such as IL-1, IL-2, IL-4, IL-6 and TNF-α before IST between SAA and VSAA groups. Also, there were no statistical difference in the levels of above-motional parameter at 3 and 6 months after IST. The ratio and absolute count of Lym, absolute count of CD3T cells, absolute count of B cells and IL-2 level in response group after IST for 3 and 6 months was significant lower than those before IST. However, only ratio of Lym showed significant decrease after IST for 3 and 6 months in non-response group. After IST for 3 months, the absolute count of CD3T and CD4T cells in response group was significant higher than those in non-response group.

Conclusion: The hematopoietic recovery and early hematologic remission may be affected by the intensity of immune suppression reflected from the changes of lymphocyte subsets and the immune reconstruction reflected from the recovery of lymphocyte subsets. The immune reconstruction is most significant within 3 months after IST.
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http://dx.doi.org/10.19746/j.cnki.issn.1009-2137.2021.01.033DOI Listing
February 2021

ONC201 shows anti-cancer activity against medullary thyroid cancer via transcriptional inhibition of RET, VEGFR2, and IGFBP2.

Mol Cancer Ther 2021 Feb 3. Epub 2021 Feb 3.

Department of Endocrine Neoplasia and Hormonal Disorders, The University of Texas MD Anderson Cancer Center.

Gain-of-function point mutations in the receptor tyrosine kinase RET, a driver oncogene in medullary thyroid carcinoma (MTC), prevent apoptosis through inhibition of ATF4, a critical transcriptional regulator of endoplasmic reticulum stress. However, the critical regulatory mechanisms driving RET-dependent oncogenesis remain elusive, and there is a clinical need to identify a transcriptional RET inhibitor. Here, we found that RET depletion decreased IGFBP2 and VEGFR2 mRNA and protein expression in MTC cells. IGFBP2 knockdown decreased cell survival and migration of MTC cells. In patients, IGFBP2 expression increased in metastatic MTC, and high IGFBP2 associated with poor overall survival. VEGFR2 protein levels were positively associated with RET expression in primary tumors, and VEGF-mediated increased cell viability was RET dependent. The small molecule ONC201 treatment of MTC cells caused apoptotic cell death, decreased transcription of RET, VEGFR2, IGFBP2, increased mRNA levels of ATF4, and ATF4 target genes including DDIT3, BBC3, DUSP8, MKNK2, KLF9, LZTFL1, SESN2. Moreover, IGFBP2 depletion increased ONC201-induced cell death. ONC201 inhibited tumor growth at a well-tolerated dose of 120 mg/kg/week administered by oral gavage and decreased MTC xenografts cell proliferation and angiogenesis. The protein levels of RET, IGFBP2, and VEGFR2 were decreased in ONC201-treated xenografts. Our study uncovered a novel ONC201 mechanism of action through regulation of RET and its targets, VEGFR2 and IGFBP2; this mechanism could be translated into the clinic and represent a promising strategy for the treatment of all MTC patients, including those with TKI-refractory disease and other cancer with RET abnormalities.
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http://dx.doi.org/10.1158/1535-7163.MCT-20-0386DOI Listing
February 2021

Clinical features and outcome of pediatric acute lymphoblastic leukemia with low peripheral blood blast cell count at diagnosis.

Medicine (Baltimore) 2021 Jan;100(4):e24518

Department of Laboratory Medicine, West China Second University Hospital, Sichuan University.

Abstract: Peripheral blood (PB) blast cell count on day 8 of prednisone therapy has been considered one of the strongest predictors of outcome in children with acute lymphoblastic leukemia (ALL). However, little is known about the clinical features and prognostic impact of PB blast cell count at diagnosis in these patients. The aim of this study was to evaluate the relationship between initial PB blast cell count and clinical prognosis of pediatric ALL.The study comprised 367 patients with ALL, aged 0 to 14 years, enrolled and treated using the Chinese Children's Leukemia Group-ALL 2008 protocol between 2011 and 2015. The majority (91.6%) of patients were B-cell precursor ALL (BCP ALL), and 8.4% were T-cell ALL (T-ALL).Patients with BCP ALL in the low PB blast cell count group (<1 × 109/L) had significantly superior survival rates to those in the high count group (≥30 × 109/L). In T-ALL, the low count group showed significantly inferior survival rates compared to both the intermediate count group (1-29.9 × 109/L) and high count group. Multivariate analysis revealed that the initial white blood cell count and minimal residual disease at the end of induction therapy were independently predictive of BCP ALL outcome, while risk stratification was shown to be an independent prognostic factor for T-ALL outcome.These results indicated that low blast cell count in PB at diagnosis was associated with different clinical outcomes in patients with BCP ALL and T-ALL, although it was not an independent outcome predictor by multivariate analysis.
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http://dx.doi.org/10.1097/MD.0000000000024518DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7850651PMC
January 2021

Safety and Efficacy of Filgotinib: Up to 4-Year Results From an Open-Label Extension Study of Phase 2 Rheumatoid Arthritis Programs.

J Rheumatol 2021 Feb 1. Epub 2021 Feb 1.

A. Kavanaugh has received consulting fees from Gilead Sciences. R. R. Westhovens has received consulting fees from Celltrion, Galapagos, Gilead Sciences, Bristol Myers Squibb, and Roche. K. L. Winthrop has received consulting fees from Gilead Sciences, Galapagos, AbbVie, Lilly,and Pfizer. S. J. Lee, Y. Tan, D. An, L. Ye, and J. S. Sundy are employees of Gilead Sciences, Inc. R. Besuyen and L. Meuleners are employees of Galapagos NV. M. Stanislavchuk and A. J. Spindler report no disclosures. M. Greenwald, MD, has received consulting fees from Celgene, Bristol Myers Squibb, Gilead Sciences, Lilly, Pfizer, AbbVie, Fuji, and Novartis. R. Alten has received consulting fees from Gilead Sciences and Galapagos.M. C. Genovese has received consulting fees from Galapagos, AbbVie, Lilly, Pfizer, and Gilead Sciences. A. Kavanaugh, MD, University of California, San Diego, La Jolla, California; R. R. Westhovens, MD, PhD, KU Leuven, Skeletal Biology and Engineering Research Center, Leuven, Belgium; K. L. Winthrop, MD, MPH, Oregon Health and Science University, Portland, Oregon; S. J. Lee, MD, Y. Tan, PhD, D. An, PhD, L. Ye, PhD, J. S. Sundy, MD, PhD, Gilead Sciences, Inc., Foster City, California; R. Besuyen, MD, L. Meuleners, MS, Galapagos NV, Mechelen, Belgium; M. Stanislavchuk, MD, National Pirogov Memorial Medical University, Vinnytsya, Ukraine; A. J. Spindler, MD, Centro Medico Privado de Reumatologia, San Miguel de Tucuman, Argentina; M. Greenwald, MD, Desert Medical Advances, Palm Desert, California; R. Alten, MD, Schlosspark Klinik, University Medicine Berlin, Berlin, Germany; M. C. Genovese, MD, Stanford University School of Medicine, Division of Immunology & Rheumatology, Stanford, California, and Gilead Sciences, Inc., Foster City, California. Address correspondence to: Prof. Arthur Kavanaugh, MD, Center for Innovative Therapy, Division of Rheumatology, Allergy & Immunology, University of California San Diego School of Medicine, 9500 Gilman Drive, #0943, La Jolla, CA 92093, US. E-mail:

Objective: The long-term safety and efficacy of filgotinib (from phase 2 studies), with or without methotrexate (MTX), for the treatment of patients with rheumatoid arthritis was assessed in DARWIN 3, a long-term, open-label extension study (NCT02065700).

Methods: Eligible patients completing the 24-week DARWIN 1 (filgotinib + MTX) and DARWIN 2 (filgotinib monotherapy) studies entered DARWIN 3, where they received filgotinib 200 mg/day, except for 15 men who received filgotinib 100 mg/day. Safety analyses were performed using the safety analysis set and exposure-adjusted incidence rate (EAIR) of treatment-emergent adverse events (TEAEs) was calculated. Efficacy was assessed from baseline in the parent studies.

Results: Of 790 patients completing the phase 2 parent studies, 739 enrolled in the study. Through April 2019, 59.5% of patients had received ≥4 years of study drug. Mean (SD) exposure to filgotinib was 3.55 (1.57) years in the filgotinib + MTX group and 3.38 (1.59) years in the filgotinib monotherapy group. EAIR per 100 patient years of exposure (PYE) for TEAEs was 24.6 in the filgotinib + MTX group and 25.8 in the filgotinib monotherapy group, and for serious TEAEs, the EAIR was 3.1 and 4.3, respectively. ACR20/50/70 responses among patients remaining in the study could be maintained through 4 years, with 89.3%/69.6%/49.1% of filgotinib + MTX group and 91.8%/69.4%/44.4% of monotherapy group maintaining ACR20/50/70 responses based on observed data.

Conclusion: Filgotinib was well tolerated with a 4-year safety profile comparable to that of the parent trials, both in patients receiving combination therapy with MTX or as monotherapy.
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http://dx.doi.org/10.3899/jrheum.201183DOI Listing
February 2021

State-target strategy: a bridge for the integration of Chinese and Western Medicine.

J Tradit Chin Med 2021 02;41(1):1-5

Department of Endocrinology, Guang'anmen Hospital, China Academy of Chinese Medical Sciences, Beijing 10054, China.

The methods ofTraditional Chinese Medicine(TCM)'s diagnosis and treatment have undergone several changes. It is crucial to build a proper model which is capable to modernize TCM into a both standardized and individualized treatment. Tong xiao-lin proposed the state-target strategy to build a bridge for the integration of Chinese and Western medicine. It is a model based on modern medical disease concepts and using the method of TCM to balance the pathological states and adopting the achievements of pharmacology of Chinese medicine to focus on the disease targets, symptom targets, and biochemical indicator targets. The reconstruction of TCM diagnosis and treatment system for diabetes is a good example to demonstrate this theory. It could improve the clinical efficacy, support the scientific research, and reinforce the standardization of TCM.
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http://dx.doi.org/10.19852/j.cnki.jtcm.2021.01.001DOI Listing
February 2021

Research progress in tumor targeted immunotherapy.

Expert Opin Drug Deliv 2021 Jan 28. Epub 2021 Jan 28.

Department of Pharmaceutics, Key Laboratory of Chemical Biology (Ministry of Education), School of Pharmaceutical Sciences, Shandong University , Jinan, 250012, PR China.

Introduction: Compared with traditional cancer treatment methods, tumor-targeted immunotherapy can combine targeted therapy and immunotherapy with long-lasting responses to achieve synergistic therapy, which brings hope to the complete cure of cancer.

Areas Covered: This review summarizes the newest and most up-to-date advances in tumor-targeted immunotherapy, including tumor-associated macrophages (TAMs) targeted immunotherapy, regulatory T (Treg) cells targeted immunotherapy, tumor-associated fibroblasts (TAFs) targeted immunotherapy and immune checkpoints targeted immunotherapy.

Expert Opinion: Immunotherapy can restore anti-tumor immunity in the tumor microenvironment and produce a lasting immune surveillance effect. Smart multifunctional nano delivery system can effectively combine targeted therapy with immunotherapy, which has attracted extensive attention. With the deepening of research, more and more tumor-targeted immunotherapy enter into the clinical trial phases, especially antibodies and inhibitors. Tumor-targeted immunotherapy is a promising approach for conquering cancer and bringing hope for human health.
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http://dx.doi.org/10.1080/17425247.2021.1882992DOI Listing
January 2021

Filgotinib versus placebo or adalimumab in patients with rheumatoid arthritis and inadequate response to methotrexate: a phase III randomised clinical trial.

Ann Rheum Dis 2021 Jan 27. Epub 2021 Jan 27.

Griffith University, Brisbane, Queensland, Australia.

Objective: To evaluate the efficacy and safety of the Janus kinase-1-preferential inhibitor filgotinib versus placebo or tumour necrosis factor-α inhibitor therapy in patients with active rheumatoid arthritis (RA) despite ongoing treatment with methotrexate (MTX).

Methods: This 52-week, multicentre, double-blind, placebo-controlled and active-controlled phase III trial evaluated once-daily oral filgotinib in patients with RA randomised 3:3:2:3 to filgotinib 200 mg (FIL200) or filgotinib 100 mg (FIL100), subcutaneous adalimumab 40 mg biweekly, or placebo (through week 24), all with stable weekly background MTX. The primary endpoint was the proportion of patients achieving 20% improvement in American College of Rheumatology criteria (ACR20) at week 12. Additional efficacy outcomes were assessed sequentially. Safety was assessed from adverse events and laboratory abnormalities.

Results: The proportion of patients (n=1755 randomised and treated) achieving ACR20 at week 12 was significantly higher for FIL200 (76.6%) and FIL100 (69.8%) versus placebo (49.9%; treatment difference (95% CI), 26.7% (20.6% to 32.8%) and 19.9% (13.6% to 26.2%), respectively; both p<0.001). Filgotinib was superior to placebo in key secondary endpoints assessing RA signs and symptoms, physical function and structural damage. FIL200 was non-inferior to adalimumab in terms of Disease Activity Score in 28 joints with C reactive protein ≤3.2 at week 12 (p<0.001); FIL100 did not achieve non-inferiority. Adverse events and laboratory abnormalities were comparable among active treatment arms.

Conclusions: Filgotinib improved RA signs and symptoms, improved physical function, inhibited radiographic progression and was well tolerated in patients with RA with inadequate response to MTX. FIL200 was non-inferior to adalimumab.

Trial Registration Number: NCT02889796.
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http://dx.doi.org/10.1136/annrheumdis-2020-219214DOI Listing
January 2021

Short hairpin RNA attenuates liver fibrosis by regulating the PPAR‑γ and NF‑κB pathways in HBV‑induced liver fibrosis in mice.

Int J Oncol 2020 Nov 22;57(5):1116-1128. Epub 2020 Sep 22.

Shanghai Mabgeek Biotech. Co., Ltd., Shanghai 201203, P.R. China.

Progressive liver fibrosis, caused by chronic viral infection and metabolic disorders, results in the development of cirrhosis and hepatocellular carcinoma. However, no antifibrotic therapies have been approved to date. In our previous study, adeno‑associated virus (AAV) short hairpin RNAs (shRNAs) targeting hepatitis B virus (HBV) and transforming growth factor (TGF)‑β administration could persistently inhibit HBV replication and concomitantly prevent liver fibrosis. However, the differentially expressed proteins and critical regulatory networks of AAV‑shRNA treatment remain unclear. Accordingly, in the present study, we aimed to analyze differentially expressed proteins in the liver of AAV‑shRNA‑treated mice with HBV infection and liver fibrosis using isobaric tags for relative and absolute quantitation (iTRAQ)‑based quantitative proteomics and to elucidate the underlying antifibrotic mechanisms. In total 2,743 proteins were recognized by iTRAQ‑based quantitative proteomics analysis. Gene Ontology analysis revealed that the differentially expressed proteins mostly participated in peptide metabolism in the biological process category, cytosolic ribosomes in the cell component category, and structural constituents of ribosomes in the molecular function category. Kyoto Encyclopedia of Genes and Genomes pathway analysis indicated that oxidative stress and the peroxisome proliferator‑activated receptor (PPAR) signaling pathway were activated after treatment. Verification studies revealed that AAV‑shRNAs inhibited hepatic stellate cell activation and inflammation by suppressing nuclear factor‑κB p65 phosphorylation and α‑smooth muscle actin expression via upregulation of PPAR‑γ. Hepatocytes steatosis was also decreased by activating the PPAR signaling pathway and improving lipid metabolism. The expression level of TGF‑β was decreased due to upregulation of PPAR‑γ expression and direct inhibition using AAV‑shRNA targeting TGF‑β. TGF‑β‑induced oxidative stress was suppressed by increasing glutathione S‑transferase Pi 1 and reducing peroxiredoxin 1. Collectively, the present results indicated that AAV‑shRNAs were effective in modulating liver fibrosis by reducing oxidative stress, inflammation and activating the PPAR signaling pathway.
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http://dx.doi.org/10.3892/ijo.2020.5125DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7549542PMC
November 2020

Antibody-mediated neutralization of IL11 signalling reduces ERK activation and cardiac fibrosis in a mouse model of severe pressure overload.

Clin Exp Pharmacol Physiol 2021 Jan 18. Epub 2021 Jan 18.

National Heart Research Institute Singapore, National Heart Centre Singapore, Singapore, Singapore.

Interleukin-11 (IL11) is important for fibroblast-to-myofibroblast transformations. Here, we examined the signalling and phenotypic effects of inhibiting IL11 signalling using neutralizing antibodies against IL11 or its cognate receptor (IL11RA) in a mouse model of acute and severe pressure overload. C57BL/6J mice underwent ascending aortic constriction (AAC) surgery and were randomized to anti-IL11, anti-IL11RA, or isotype control antibodies (20 mg/kg, bi-weekly for 2 weeks). AAC surgery induced the expression of IL11, IL11RA and extracellular matrix (ECM) genes that was associated with cardiac hypertrophy and aortic remodelling. Inhibition of IL11 signalling reduced AAC-induced cardiac fibrosis and ECM gene expression as well as ERK1/2 phosphorylation but had no effect on cardiac hypertrophy. STAT3 was phosphorylated in the hearts of AAC-treated mice but this was unrelated to IL11 activity, which we confirmed in mouse cardiac fibroblasts in vitro. These data highlight that blocking IL11 signalling reduces cardiac fibrosis due to severe pressure overload and suggests ERK, but not STAT3, activity as the relevant underlying signalling pathway.
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http://dx.doi.org/10.1111/1440-1681.13458DOI Listing
January 2021

Comparative research on nucleocapsid and spike glycoprotein as the rapid immunodetection targets of COVID-19 and establishment of immunoassay strips.

Mol Immunol 2021 03 9;131:6-12. Epub 2021 Jan 9.

Institute of Biopharmaceutical and Health Engineering, Tsinghua Shenzhen International Graduate School, Shenzhen 518055 PR China; School of Life Science, Tsinghua University, Beijing 100084, PR China; Tsinghua-Berkeley Shenzhen Institute (TBSI), Shenzhen International Graduate School, Tsinghua University, Shenzhen, 518055, PR China; Shenzhen Bay Laboratory, Shenzhen, PR China. Electronic address:

The SARS-CoV-2 virus responsible for coronavirus 2019 (COVID-19) poses a significant challenge to healthcare systems worldwide. According to the World Health Organization (WHO), the outbreak of COVID-19 has been a pandemic that infected more than 25.32 million people and caused more than 848.25 thousand deaths worldwide at the time of 1st September 2020. Despite governmental initiatives aimed to contain the spread of the disease, several countries are experiencing unmanageable increases in medical equipment and larger testing capacity. The current diagnosis based on nuclear acid requires specialized instruments, time-consuming, and laborious, the low-cost and convenient technologies were still urgently needed. Both spike and nucleocapsid are key structural proteins of COVID-19 with good immunogenicity, can serve as primary targets for immunoassay. After comparative research, we certified nucleocapsid antigen-monoclonal antibody (mAbs) system was more suitable for the COVID-19 immunodetection. Subsequently, we designed a rapid test strip based on it that can be used in large-scale screening of COVID-19 in population and more suitable for some remote and special needs areas were restricted by a medical condition or for quick and large quantities of screenings.
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http://dx.doi.org/10.1016/j.molimm.2021.01.005DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7833923PMC
March 2021

Semi-Supervised Capsule cGAN for Speckle Noise Reduction in Retinal OCT Images.

IEEE Trans Med Imaging 2021 Jan 4;PP. Epub 2021 Jan 4.

Speckle noise is the main cause of poor optical coherence tomography (OCT) image quality. Convolutional neural networks (CNNs) have shown remarkable performances for speckle noise reduction. However, speckle noise denoising still meets great challenges because the deep learning-based methods need a large amount of labeled data whose acquisition is time-consuming or expensive. Besides, many CNNs-based methods design complex structure based networks with lots of parameters to improve the denoising performance, which consume hardware resources severely and are prone to overfitting. To solve these problems, we propose a novel semi-supervised learning based method for speckle noise denoising in retinal OCT images. First, to improve the model's ability to capture complex and sparse features in OCT images, and avoid the problem of a great increase of parameters, a novel capsule conditional generative adversarial network (Caps-cGAN) with small number of parameters is proposed to construct the semi-supervised learning system. Then, to tackle the problem of retinal structure information loss in OCT images caused by lack of detailed guidance during unsupervised learning, a novel joint semi-supervised loss function composed of unsupervised loss and supervised loss is proposed to train the model. Compared with other state-of-the-art methods, the proposed semi-supervised method is suitable for retinal OCT images collected from different OCT devices and can achieve better performance even only using half of the training data.
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http://dx.doi.org/10.1109/TMI.2020.3048975DOI Listing
January 2021

Preparation of Boronic Acid-Functionalized Cryogels Using Modular and Clickable Building Blocks for Bacterial Separation.

J Agric Food Chem 2021 Jan 28;69(1):135-145. Epub 2020 Dec 28.

Division of Pure and Applied Biochemistry, Department of Chemistry, Lund University, Box 124, 221 00 Lund, Sweden.

Composite cryogels containing boronic acid ligands are synthesized for effective separation and isolation of bacteria. The large and interconnected pores in cryogels enable fast binding and release of microbial cells. To control bacterial binding, an alkyne-tagged boronic acid ligand is conjugated to azide-functionalized cryogel the Cu(I)-catalyzed azide-alkyne cycloaddition reaction. The boronic acid-functionalized cryogel binds Gram-positive and Gram-negative bacteria through reversible boronate ester bonds, which can be controlled by pH and simple monosaccharides. To increase the capacity of affinity separation, a new approach is used to couple the alkyne-tagged phenylboronic acid to cryogel an intermediate polymer layer that provides multiple immobilization sites. The morphology and chemical composition of the composite cryogel are characterized systematically. The capability of the composite cryogel for the separation of Gram-positive and Gram-negative bacteria is investigated. The binding capacities of the composite cryogel for and are 2.15 × 10 and 3.36 × 10 cfu/g, respectively. The bacterial binding of the composite cryogel can be controlled by adjusting pH. The results suggest that the composite cryogel may be used as affinity medium for rapid separation and isolation of bacteria from complex samples.
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http://dx.doi.org/10.1021/acs.jafc.0c06052DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7871328PMC
January 2021

The 287,403 bp Mitochondrial Genome of Ectomycorrhizal Fungus Reveals Intron Expansion, tRNA Loss, and Gene Rearrangement.

Front Microbiol 2020 9;11:591453. Epub 2020 Dec 9.

School of Food and Biological Engineering, Chengdu University, Chengdu, China.

In the present study, the mitogenome of was assembled and analyzed. The mitogenome of comprises 15 conserved protein-coding genes, two rRNA genes, and 14 tRNAs, with a total size of 287,403 bp. Fifty-eight introns with 170 intronic open reading frames were detected in the mitogenome. The intronic region occupied 69.41% of the mitogenome, which contributed to the mitogenome significantly expand relative to most fungal species. Comparative mitogenomic analysis revealed large-scale gene rearrangements occurred in the mitogenome of , involving gene relocations and position exchanges. The mitogenome of was found to have lost several tRNA genes encoding for cysteine, aspartate, histidine, etc. In addition, a pair of fragments with a total length of 32.91 kb in both the nuclear and mitochondrial genomes of was detected, indicating possible gene transfer events. A total of 12.83% intragenomic duplications were detected in the mitogenome. Phylogenetic analysis based on mitochondrial gene datasets obtained well-supported tree topologies, indicating that mitochondrial genes could be reliable molecular markers for phylogenetic analyses of Ascomycota. This study served as the first report on mitogenome in the family Tuberaceae, thereby laying the groundwork for our understanding of the evolution, phylogeny, and population genetics of these important ectomycorrhizal fungi.
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http://dx.doi.org/10.3389/fmicb.2020.591453DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7756005PMC
December 2020

Psychological Impact of the COVID-19 Outbreak on Nurses in China: A Nationwide Survey During the Outbreak.

Front Psychiatry 2020 11;11:598712. Epub 2020 Dec 11.

West China School of Medicine, Sichuan University, Chengdu, China.

The COVID-19 pandemic is a major public health issue and challenge to health professionals. In similar epidemics, nurses experienced more distress than other providers. We surveyed both on-duty nurses caring for infected patients and second-line nurses caring for uninfected patients from Hubei and other provinces throughout China. We received completed surveys from 1,364 nurses from 22 provinces: 658 front-line and 706 second-line nurses. The median (IQR) GHQ-28 score of all nurses was 17 (IQR 11-24). The overall incidence of mild-to-moderate distress (GHQ score > 5) was 28%; that for severe distress (GHQ score > 11) was 6%. The incidence of mild-to-moderate distress in the second-line nurses was higher than that in the front-line nurses (31 vs. 25%; OR, 0.74; 95 CI, 0.58-0.94). Living alone (OR, 0.62; 95% CI, 0.44-0.86) and feeling supported (OR, 0.82, 95% CI, 0.74-0.90) independently predicted lower anxiety. During the COVID-19 pandemic, the psychological problems of all nurses were generally serious. The interviewed second-line nurses face more serious issues than the front-line nurses.
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http://dx.doi.org/10.3389/fpsyt.2020.598712DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7759517PMC
December 2020

Single-Cell Sequencing of Glioblastoma Reveals Central Nervous System Susceptibility to SARS-CoV-2.

Front Oncol 2020 16;10:566599. Epub 2020 Nov 16.

Department of Neurosurgery, The First Affiliated Hospital of Anhui Medical University, Hefei, China.

Background: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) caused the recent global COVID-19 outbreak, which led to a public health emergency. Entry of SARS-CoV-2 into human cells is dependent on the SARS-CoV receptor, angiotensin converting enzyme 2 (ACE2) receptor, and cathepsin. Cathepsin degrades the spike protein (S protein), which results in the entry of viral nucleic acid into the human host cell.

Methods: We explored the susceptibility of the central nervous system (CNS) to SARS-CoV-2 infection using single-cell transcriptome analysis of glioblastoma.

Results: The results showed that ACE2 expression is relatively high in endothelial cells (ECs), bone marrow mesenchymal stem cells (BMSCs), and neural precursor cells (NPCs). Cathepsin B (Cat B) and cathepsin (Cat L) were also strongly expressed in various cell clusters within the glioblastoma microenvironment. Immunofluorescence staining of glioma and normal brain tissue chips further confirmed that ACE2 expression co-localized with CD31, CD73, and nestin, which confirmed the susceptibility to SARS-CoV-2 of nervous system cells, including ECs, BMSCs, and NPCs, from clinical specimens.

Conclusions: These findings reveal the mechanism of SARS-CoV-2 neural invasion and suggest that special attention should be paid to SARS-CoV-2-infected patients with neural symptoms, especially those who suffered a glioma.
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http://dx.doi.org/10.3389/fonc.2020.566599DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7703438PMC
November 2020

Altered brain network centrality in middle-aged patients with retinitis pigmentosa: A resting-state functional magnetic resonance imaging study.

Brain Behav 2021 Feb 9;11(2):e01983. Epub 2020 Dec 9.

Department of Ophthalmology, Jiangxi Province Ocular Disease Clinical Research Center, The First Affiliated Hospital of Nanchang University, Nanchang, China.

Objective: The purpose of this study is to explore the underlying functional network brain activity changes of patients in middle-aged with retinitis pigmentosa (RP) and the relationships with clinical features such as depression scale and visual functioning using voxel-wise degree centrality (DC) method.

Methods: We included 16 patients with RP (11 men, 5 women) and 16 healthy controls (HCs; 11 men, 5 women). Participants were matched in terms of age, weight, gender and handedness (age and weight between the two groups were compared using independent sample t-tests, gender and handedness were compared using chi-square test). We use the voxel-wise DC method to assess spontaneous brain activity. Receiver operating characteristic (ROC) curve analysis was performed to distinguish between RP patients and HCs. Correlation analysis was used to examine the relationships between mean DC values in various brain regions and clinical features (such as depression scale and visual functioning) in RP patients.

Results: Compared with HCs, the DC values of patients with RP were reduced in the right medial frontal gyrus, bilateral cuneus, bilateral precuneus, and bilateral superior frontal gyrus, and increased in the right cerebellum posterior lobe, left inferior temporal gyrus, and right fusiform gyrus. The mean DC values in the bilateral cuneus negatively correlated with the depression scale, and those in the bilateral precuneus positively correlated with the Visual Functioning Questionnaire-25.

Conclusions: Middle-aged patients with RP exhibit abnormal brain network activity in various brain regions, and this may underlie the pathological mechanism of RP.
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http://dx.doi.org/10.1002/brb3.1983DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7882161PMC
February 2021

Molecular Cages Self-Assembled by Imine Condensation in Water.

Angew Chem Int Ed Engl 2021 02 12;60(9):4705-4711. Epub 2021 Jan 12.

Department of Chemistry, Zhejiang University, Hangzhou, 310027, China.

Self-assembly by imine condensation in aqueous media is a formidable task because of the labile nature of imines in the presence of water. Here, by taking advantage of multivalence and ligand preorganization, basket-shaped triscationic cage molecules are self-assembled in high yields in both water and organic solvent, by condensing a hexaformyl and bisamine. These cages, especially the chiral ones, are stable or inert in aqueous solution, that is, no decomposition was observed upon dilution, precipitation, or exposure to competitive amines or aldehydes. Such water-compatibility allows the hosts to take advantage of the hydrophobic effect to accommodate hydrophobic guests. The chiral cage S-2 selectively binds and distinguishes one of two enantiomers, opening up opportunities for applications such as chiral compound separation. Chiral narcissistic self-sorting and sergeants-and-soldiers effects occur during cage formation when two amino precursors are involved in self-assembly.
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http://dx.doi.org/10.1002/anie.202013045DOI Listing
February 2021

BST-2/Tetherin is involved in BAFF-enhanced proliferation and survival via canonical NF-κB signaling in neoplastic B-lymphoid cells.

Exp Cell Res 2021 Jan 24;398(1):112399. Epub 2020 Nov 24.

Department of Oral Surgery, Shanghai Ninth People's Hospital, College of Stomatology, Shanghai Jiao Tong University School of Medicine, Shanghai, China; National Clinical Research Center of Oral Disease, Shanghai, China; Shanghai Key Laboratory of Stomatology & Shanghai Research Institute of Stomatology, Shanghai, China. Electronic address:

The development of Sjögren's syndrome (SS) is accompanied by B cell hyperproliferation and mutation. Our previous study identified aberrant expression of BST-2 (also known as Tetherin/CD317) in B cells from either the peripheral blood or infiltrated salivary glands. However, the roles of BST-2 in the regulation of B cell activation remain unknown. In this study, we identified that BST-2 can respond to BAFF simulation but not to other B cell simulators in neoplastic B cell lines. A CCK-8 assay, an EdU assay and Annexin V/PI staining indicated that BST-2 inhibition attenuated BAFF-enhanced proliferation and survival in both Raji cells and Daudi cells. Screening of BAFF-related signaling in neoplastic B-lymphoid cells indicated that BST-2 was involved in the regulation of NF-κB signaling upon BAFF simulation. However, inhibition of NF-κB by JSH-23 significantly reduced the proliferation and survival of Raji and Daudi cells under both normal and BAFF-simulated conditions. Collectively, our results indicate that BST-2/Tetherin is a BAFF-responsive membrane factor involved in the regulation of NF-κB signaling, thereby assisting in the proliferation and survival of neoplastic B-lymphoid cells. Our study provides a potential molecular mechanism underlying aberrant overactivation of B cells upon SS development.
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http://dx.doi.org/10.1016/j.yexcr.2020.112399DOI Listing
January 2021

Clinical and molecular characterization of thirty Chinese patients with congenital lipoid adrenal hyperplasia.

J Steroid Biochem Mol Biol 2021 Feb 20;206:105788. Epub 2020 Nov 20.

Department of Pediatrics, Ruijin Hospital Affiliated to Shanghai Jiao Tong University, Shanghai, 200025, China. Electronic address:

Congenital lipoid adrenal hyperplasia (LCAH), as the most severe form of congenital adrenal hyperplasia (CAH), is caused by mutations in the steroidogenic acute regulatory protein (STAR). Affected patients were typically characterized by adrenal insufficiency in the first year of life and present with female external genitalia regardless of karyotype. Non-classic LCAH patients usually present from 2 to 4 years old with glucocorticoid deficiency and mild mineralocorticoid deficiency, even develop naturally masculinized external genitalia at birth when they have 46,XY karyotype. We described thirty patients from unrelated Chinese families, including three non-classic LCAH ones. Four novel mutations were reported, including c.556A > G, c.179-15G > T, c.695delG and c.306 + 3_c.306 + 6delAAGT. The c.772C > T is the most common STAR mutation in Chinese population, suggesting a possibility of founder effect. Enzymatic activity assay combined with clinical characteristics showed a good genotype-phenotype correlation in this study. Residual STAR activity more than 20 % may be correlated with non-classic LCAH phenotype. We support the perspective that onset age may be affected by multiple factors and masculinization should be the main weighting factor for diagnosis of non-classic LCAH. Compared with 46,XX LCAH patients, less 46,XY ones were found in our report. A less comprehensive inspection and an easy diagnosis due to classical phenotype both would reduce the possibility of 46,XY LCAH patients to be referred to specialists or geneticists.
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http://dx.doi.org/10.1016/j.jsbmb.2020.105788DOI Listing
February 2021

Missense Variants in PAX4 Are Associated with Early-Onset Diabetes in Chinese.

Diabetes Ther 2021 Jan 20;12(1):289-300. Epub 2020 Nov 20.

Department of Endocrinology and Metabolism, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine (SJTUSM), Shanghai, 200025, China.

Introduction: East Asians are more susceptible to early-onset diabetes than Europeans and exhibit reduced insulin secretion at earlier stages. PAX4 plays a critical role in the development of β-cells. The dysfunction-missense variants PAX4 R192H and PAX4 R192S are common in East Asians but rare in Europeans. Therefore, we aim to investigate the diabetes-associated genes, including PAX4 R192H/S, in East Asians with early-onset diabetes.

Methods: Exome variants of 80 Chinese early-onset diabetes patients (onset age < 35 years) after the exclusion of type 1 diabetes (T1D) were detected by a customized gene panel covering 32 known diabetes-associated genes. Then, 229 subjects with early-onset diabetes (T1D excluded) and 1679 controls from the Chinese population were genotyped to validate the association of PAX4 R192H/S with early-onset diabetes and related phenotypes.

Results: The gene panel detected 11 monogenic diabetes patients with five novel mutations among the 80 early-onset diabetes patients. Asian-specifically enriched PAX4 R192H and R192S were associated with early-onset diabetes (R192H: OR 1.88, 95% CI 1.37-2.60, P = 8.41 × 10; R192S: OR 1.71, 95% CI 1.17-2.51, P = 0.005). In early-onset diabetes patients, PAX4 R192H carriers had higher haemoglobin A1c (HbA1c) levels (P = 0.030) and lower 2 h C-peptide levels in the oral glucose tolerance test (OGTT) (P = 0.040); R192S carriers had lower fasting C-peptide (FCP) (P = 0.011) and 2 h C-peptide levels (P = 0.033) in OGTT than non-variant carriers.

Conclusions: The ethnic-specific enrichment of PAX4 R192H/S predisposing East Asians to early-onset diabetes with decreased C-peptide levels may be one explanation of the discrepancy of diabetes between East Asians and Europeans.

Clinical Trial Registration: ClinicalTrials.gov (NCT01938365).
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http://dx.doi.org/10.1007/s13300-020-00960-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7843779PMC
January 2021