Publications by authors named "Chao Lv"

154 Publications

Ascorbic Acid Inhibits Liver Cancer Growth and Metastasis and , Independent of Stemness Gene Regulation.

Front Pharmacol 2021 24;12:726015. Epub 2021 Aug 24.

School of Pharmacy, Shanghai Jiao Tong University, Shanghai, China.

Experimental and clinical evidence has indicated that the natural product ascorbic acid (AA) is effective in preventing and treating various types of cancers. However, the effect of AA on liver cancer metastasis has not yet been reported. Cancer stem cells (CSCs) play pivotal roles in cancer metastasis. Here, we demonstrated that AA selectively inhibited the viability of both liver cancer cells and CSCs, reduced the formation of cancer cell colonies and CSC spheres, and inhibited tumor growth . Additionally, AA prevented liver cancer metastasis in a xenotransplantation model without suppressing stemness gene expression in liver CSCs. Further study indicated that AA increased the concentration of HO and induced apoptosis in liver CSCs. Catalase attenuated the inhibitory effects of AA on liver CSC viability. In conclusion, AA inhibited the viability of liver CSCs and the growth and metastasis of liver cancer cells and by increasing the production of HO and inducing apoptosis. Our findings provide evidence that AA exerts its anti-liver cancer efficacy and , in a manner that is independent of stemness gene regulation.
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http://dx.doi.org/10.3389/fphar.2021.726015DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8422961PMC
August 2021

Hu-Zhang-Qing-Mai-Yin Inhibits Proliferation of Human Retinal Capillary Endothelial Cells Exposed to High Glucose.

Front Pharmacol 2021 6;12:732655. Epub 2021 Aug 6.

Institute of Interdisciplinary Integrative Medicine Research, Shanghai University of Traditional Chinese Medicine, Shanghai, China.

Background: Diabetic retinopathy (DR) is one of the serious complications of diabetes and an important cause of blindness. Despite much research on the pathogenesis of DR, there is still a lack of safe and effective treatment methods. Hu-zhang-qing-mai-yin (HZQMY), a Chinese medicine formula, has been clinically used in the safe and effective treatment of DR for many years. However, the systematic pharmacological research is lacking. The aim of this study was to evaluate the anti-DR effects of HZQMY and explore the possible mechanism involved.

Methods: The constituents of HZQMY were analyzed by LC-MS/MS. DR model was established by high glucose simulation on human retinal capillary endothelial cells (HRCECs) . The cell viability, cell proliferation, cell apoptosis, and tube formation were assessed. Subsequently the related mechanisms were analyzed by assays for JC-1 mitochondrial membrane potential (MMP), intracellular ROS, ATP, western blot and proteomics.

Results: 27 main chemical components contained in HZQMY were identified. HZQMY significantly inhibited the viability and proliferation of HRCECs exposed to high glucose, and promoted the apoptosis. In addition, HZQMY also boosted the release of ROS and suppressed tube formation of HRCECs under high glucose exposure. Meanwhile, HRCECs treated with high glucose released more ROS than normal cells, which could be markedly inhibited by HZQMY in a dose-dependent manner. Additionally, western blot assay indicated that HZQMY increased the expression of proteins related to the P38 signaling pathway and inhibited nuclear factor kappa-B (NF-κB) pathway. Proteomic analysis predicted that HSPA4, MAPK3, ENO1, EEF2 and ERPS may be the candidate targets of HZQMY in HRCECs.

Conclusions: HZQMY inhibited the proliferation and promoted the Mitochondria related apoptosis of HRCECs exposed to high glucose possibly through regulating P38 and NF-κB signaling pathway.
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http://dx.doi.org/10.3389/fphar.2021.732655DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8377758PMC
August 2021

Application of omics- and multi-omics-based techniques for natural product target discovery.

Biomed Pharmacother 2021 Sep 25;141:111833. Epub 2021 Jun 25.

Institute of Interdisciplinary Integrative Medicine Research, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China. Electronic address:

Natural products continue to be an unparalleled source of pharmacologically active lead compounds because of their unprecedented structures and unique biological activities. Natural product target discovery is a vital component of natural product-based medicine translation and development and is required to understand and potentially reduce mechanisms that may be associated with off-target side effects and toxicity. Omics-based techniques, including genomics, transcriptomics, proteomics, metabolomics, and bioinformatics, have become recognized as effective tools needed to construct innovative strategies to discover natural product targets. Although considerable progress has been made, the successful discovery of natural product targets remains a challenging time-consuming process that has come to increasingly rely on the effective integration of multi-omics-based technologies to create emerging panomics (a.k.a., integrative omics, pan-omics, multiomics)-based strategies. This review summarizes a series of successful studies regarding the application of integrative omics-based methods in natural product target discovery. The advantages and disadvantages of each technique are discussed, with a particular focus on the systematic integration of multi-omics strategies. Further, emerging micro-scale single-cell-based techniques are introduced, especially to deal with minute natural product samples.
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http://dx.doi.org/10.1016/j.biopha.2021.111833DOI Listing
September 2021

The regulation of miR-320a/XBP1 axis through LINC00963 for endoplasmic reticulum stress and autophagy in diffuse large B-cell lymphoma.

Cancer Cell Int 2021 Jun 10;21(1):305. Epub 2021 Jun 10.

School of Basic Medicine, Jiamusi University, Jiamusi, 154007, Heilongjiang, China.

Background: This study incorporates fundamental research referring to considerable amounts of gene-sequencing data and bioinformatics tools to analyze the pathological mechanisms of diffuse large B-cell lymphoma (DLBCL).

Methods: A lncRNA-miRNA-mRNA ceRNA network of DLBCL was constructed through database analysis combining GTEx and TCGA. qPCR was used to detect the expression of LINC00963 and miR-320a in DLBCL cell lines. After LINC00963 or miR-320a overexpression in vitro, western blot was performed to assess the protein levels of UPR sensors (GRP78, p-IRE1, IRE1, active ATF6, ATF4 and XBP1), along with apoptosis markers (Bcl-2, Bax, caspase 3) and autophagy indicators (Beclin1, LC3II, LC3I and p62). Additionally, the expression of LC3 was analyzed through immunofluorescence (IF) assay.  RESULTS: Following LINC00963 overexpression in vitro, SUDHL4 cell line showed a marked increase in the level of UPR-related GRP78, p-IRE1 and spliced XBP-1/XBP-1(s), apoptosis-related Bax and cleaved caspase 3, as well as autophagy-related Beclin1 and LC3II, whereas miR-320a mimic greatly diminished the effects of LINC00963 overexpression. Moreover, LINC00963 targeted miR-320a while miR-320a bound to the 3'UTR of XBP1. It was also found that LINC00963 overexpression resulted in significantly delayed tumor growth in a xenograft model of DLBCL.  CONCLUSION: Mechanistically, LINC00963/miR-320a regulated XBP1-apoptosis pathway and autophagy, implying the therapeutic potential of this pathway for selective targeting. The data presented here illustrated the mechanism of LINC00963/miR-320a/XBP1 in DLBCL for the first time.
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http://dx.doi.org/10.1186/s12935-021-01992-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8194177PMC
June 2021

Risk Factors for Death Among the First 80 543 COVID-19 Cases in China: Relationships Between Age, Underlying Disease, Case Severity, and Region.

Clin Infect Dis 2021 May 27. Epub 2021 May 27.

Hubei Center for Disease Control and Prevention, 6 North Zuodaoquan, Hongshan District, Wuhan 430079, China.

Background: Knowledge of COVID-19 epidemiology remains incomplete and crucial questions persist. We aimed to examine risk factors for COVID-19 death.

Methods: A total of 80 543 COVID-19 cases reported in China, nationwide, through April 8, 2020 were included. Risk factors for death were investigated by Cox proportional hazards regression and stratified analyses.

Results: Overall national case fatality ratio (CFR) was 5.64%. Risk factors for death were older age (≥80: adjusted hazard ratio [aHR]=12.58, 95% confidence interval [CI]=6.78-23.33), presence of underlying disease (aHR=1.33, CI=1.19-1.49), worse case severity (severe: aHR=3.86, CI=3.15-4.73; critical: aHR=11.34, CI=9.22-13.95), and near-epicenter region (Hubei: aHR=2.64, CI=2.11-3.30; Wuhan: aHR=6.35, CI=5.04-8.00). CFR increased from 0.35% (30-39 years) to 18.21% (≥70 years) without underlying disease. Regardless of age, CFR increased from 2.50% for no underlying disease to 7.72% for 1, 13.99% for 2, and 21.99% for ≥3. CFR increased with worse case severity from 2.80% (mild), to 12.51% (severe) and 48.60% (critical) regardless of region. Compared to other regions, CFR was much higher in Wuhan regardless of case severity (mild: 3.83% versus 0.14% in Hubei and 0.03% elsewhere; moderate: 4.60% versus 0.21% and 0.06%; severe: 15.92% versus 5.84% and 1.86%; and critical: 58.57% versus 49.80% and 18.39%).

Conclusions: Older patients regardless of underlying disease and patients with underlying disease regardless of age were at elevated risk of death. Higher death rates near the outbreak epicenter and during the surge of cases reflect the deleterious effects of allowing health systems to become overwhelmed.
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http://dx.doi.org/10.1093/cid/ciab493DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8244662PMC
May 2021

Targeting inflammation-associated AMPK//Mfn-2/MAPKs signaling pathways by baicalein exerts anti-atherosclerotic action.

Phytother Res 2021 Aug 18;35(8):4442-4455. Epub 2021 May 18.

Department of Cardiology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

Inflammatory responses in macrophages, endothelial cells, and vascular smooth muscle cells play crucial roles in the development of atherosclerosis. Baicalein, a flavonoid phytochemical, possesses anti-inflammatory properties, but the underlying mechanisms of its action are not fully understood. The aim of this study was to explore whether baicalein inhibited inflammatory activities in RAW264.7, HUVEC, and MOVAS cells and to analyze its underlying mechanisms. Our results showed that baicalein treatment effectively reduced the levels of IL-6, TNF-α, PAI-1, and MMP-9 released by these cells upon stimulation with Ang II or ox-LDL. We discovered that the molecular mechanisms underlying baicalein suppression of the generation of proinflammatory cytokines were associated with the inhibition of MAPK/NF-κB pathway activity. Moreover, Ang II and ox-LDL intervention decreased the content of Mfn-2 in the three types of cells, but incubation of baicalein alleviated the Ang II/ox-LDL-induced reduction of Mfn-2 levels. Adv-Mfn2 treatment not only increased the expression of Mfn-2 but also reduced the levels of phosphorylated ERK1/2, p38, JNK, and NF-κB, followed by a decrease in the concentrations of IL-6, TNF-α, PAI-1, and MMP-9 in the supernatant. Furthermore, our findings indicated that baicalein treatment markedly suppressed the decrease in AMPK activity induced with Ang II and ox-LDL, and incubation with Compound C reversed the effects of baicalein on AMPK activation and Mfn-2 expression. In conclusion, our data suggest that baicalein shows anti-inflammatory properties, probably by activating the AMPK/Mfn-2 axis, accompanied by inhibition of downstream MAPKs/NF-κB signaling transduction.
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http://dx.doi.org/10.1002/ptr.7149DOI Listing
August 2021

Double minute chromosomes in acute myeloid leukemia and myelodysplastic syndromes are associated with complex karyotype, monosomal karyotype, deletion, and mutations.

Leuk Lymphoma 2021 Apr 27:1-9. Epub 2021 Apr 27.

Department of Hematology, Chinese PLA General Hospital, Beijing, China.

Double minute chromosomes (DMs) are rare in hematologic malignancies. We presented the cytogenetic characteristics and clinical features of the largest single-center cohort of acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS) patients with DMs. A total of 2576 AML patients and 1642 MDS patients were investigated, and 30 patients (AML = 19; MDS = 11) who had DMs were followed up. DMs were more common in primary AML (94.7%) and MDS (90.9%). Monosomal karyotypes (MK) were also the main cytogenetic characteristics, like complex karyotypes (CK). AML with myelodysplasia-related changes (AML-MRC) and MDS-refractory anemia with excess blasts (MDS-RAEB) was common in this cohort. We conclude that DMs-positive AML and DMs-positive MDS are associated with older age, complex karyotypes, monosomal karyotypes, deletion and mutations. DMs are a type of chromothripsis, which can be observed by the karyotype analysis. and were the most commonly amplified genes in DMs. Most patients with DMs presented an extremely poor prognosis.
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http://dx.doi.org/10.1080/10428194.2021.1919663DOI Listing
April 2021

High-risk-pattern lung adenocarcinoma with epidermal growth factor receptor mutation is associated with distant metastasis risk and may benefit from adjuvant targeted therapy.

Interact Cardiovasc Thorac Surg 2021 Aug;33(3):395-401

Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Thoracic Surgery II, Peking University Cancer Hospital & Institute, Beijing, China.

:

Objectives: This study aimed to evaluate the value of the high-risk-pattern histology (micropapillary and solid components) for predicting distant metastasis in lung adenocarcinoma and to determine the survival benefit with adjuvant targeted therapy for resected non-small cell lung cancer with high-risk-pattern histology.

Methods: Patients receiving surgery for non-small cell lung cancer were included in this retrospective study. Histological classification was performed according to 2015 World Health Organization classification. Tumours with micropapillary and solid components were defined as high-risk-pattern tumours. Univariable and multivariable Cox regression analyses were used for survival analysis. Adjuvant targeted therapy was alternative for patients with epidermal growth factor receptor (EGFR)-mutation and refusing adjuvant chemotherapy, and outcome was evaluated between 2 groups.

Results: The 514 patients (78 in high-risk group and 436 in low-risk group) were followed up for a median of 64 months. High-risk-pattern adenocarcinoma was significantly more common in male patients (P < 0.001) and in smokers (P < 0.001). Among patients with EGFR mutation (n = 164), the high-risk pattern was significantly associated with distant metastasis (P = 0.028) including brain metastasis (P = 0.022). In the 42 patients with high-risk pattern plus EGFR mutation, survival was significantly better after treatment with adjuvant targeted therapy than with chemotherapy (5-year overall survival: 56.4 ± 2.6 vs 44.7 ± 3.7 months, P = 0.011; 5-year disease-free survival: 54.0 ± 3.3 vs 41.9 ± 4.5 months, P = 0.006).

Conclusions: High-risk pattern is associated with distant metastasis in non-small cell lung cancer after surgery. Adjuvant targeted therapy may be superior to chemotherapy for treatment of patients with high-risk pattern and EGFR mutation.
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http://dx.doi.org/10.1093/icvts/ivab099DOI Listing
August 2021

Dsk2 involves in conidiation, multi-stress tolerance and thermal adaptation in Beauveria bassiana.

Environ Microbiol Rep 2021 Jun 18;13(3):384-393. Epub 2021 Apr 18.

Key Laboratory for Humid Subtropical Eco-Geographical Processes of the Ministry of Education, School of Geographical Sciences, Fujian Normal University, Fuzhou, 350007, China.

Dsk2 is a nuclear-enriched ubiquitin-like polyubiquitin-binding protein that regulates protein degradation in yeast but has not been explored yet in filamentous fungi, such as Beauveria bassiana. Here, we report Beauveria bassiana Dsk2 located both in the nucleus and in cytoplasm of hyphal cells. Deletion of Dsk2 resulted in mild growth defect on scant media with various carbon/nitrogen sources and dramatic attenuation in conidiation capability at optimal condition. Compared to the wild-type, ΔDsk2 strains are much more sensitive to high osmotic and oxidative pressure during vegetative growth. Meanwhile, the mutant strains showed an increased chemical tolerance to Congo red and calcofluor white, two cell wall perturbing agents. The transcriptional changes of genes involved in central development, superoxide dismutase and chitin synthesis pathway indicate that Dsk2 acts as a multi-functional regulator in adapting to environmental changes. Importantly, Dsk2 negatively regulated the ability of thermal resistance in B. bassiana, which makes it a potential target gene for constructing engineering anti-thermal strains in the circumstance of global warming. Altogether, our finding highlights novel roles of Dsk2 involved in the asexual cycle, multi-stress tolerance and pest control potential of B. bassiana.
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http://dx.doi.org/10.1111/1758-2229.12946DOI Listing
June 2021

[Clinical Recommendations for Perioperative Immunotherapy-induced Adverse Events in Patients with Non-small Cell Lung Cancer].

Zhongguo Fei Ai Za Zhi 2021 Mar;24(3):141-160

Department of Thoracic Surgery, Peking University Cancer Hospital, Beijing 100142, China.

Background: Perioperative treatment has become an increasingly important aspect of the management of patients with non-small cell lung cancer (NSCLC). Small-scale clinical studies performed in recent years have shown improvements in the major pathological remission rate after neoadjuvant therapy, suggesting that it will soon become an important part of NSCLC treatment. Nevertheless, neoadjuvant immunotherapy may be accompanied by serious adverse reactions that lead to delay or cancelation of surgery, additional illness, and even death, and have therefore attracted much attention. The purpose of the clinical recommendations is to form a diagnosis and treatment plan suitable for the current domestic medical situation for the immune-related adverse event (irAE).

Methods: This recommendation is composed of experts in thoracic surgery, oncologists, thoracic medicine and irAE related departments (gastroenterology, respirology, cardiology, infectious medicine, hematology, endocrinology, rheumatology, neurology, dermatology, emergency section) to jointly complete the formulation. Experts make full reference to the irAE guidelines, large-scale clinical research data published by thoracic surgery, and the clinical experience of domestic doctors and publicly published cases, and repeated discussions in multiple disciplines to form this recommendation for perioperative irAE.

Results: This clinical recommendation covers the whole process of prevention, evaluation, examination, treatment and monitoring related to irAE, so as to guide the clinical work comprehensively and effectively.

Conclusions: Perioperative irAE management is an important part of immune perioperative treatment of lung cancer. With the continuous development of immune perioperative treatment, more research is needed in the future to optimize the diagnosis and treatment of perioperative irAE.
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http://dx.doi.org/10.3779/j.issn.1009-3419.2021.101.06DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8143963PMC
March 2021

Investigation of doping effects of different noble metals for ethanol gas sensors based on mesoporous InO.

Nanotechnology 2021 May 7;32(30). Epub 2021 May 7.

State Key Laboratory on Integrated Optoelectronics, College of Electronic Science and Engineering, Jilin University, Changchun 130012, People's Republic of China.

Elaborating the sensitization effects of different noble metals on InOhas great significance in providing an optimum method to improve ethanol sensing performance. In this study, long-range ordered mesoporous InOhas been fabricated through replicating the structure of SBA-15. Different noble metals (Au, Ag, Pt and Pd) with the same doping amount (1 at%) have been introduced by andoping routine. The results of the gas sensing investigation indicate that the gas responses towards ethanol can be obviously increased by doping different noble metals. In particular, the best sensing performance towards ethanol detection can be achieved through Pd doping, and the sensors based on Pd-doped InOnot only possess the highest response (39.0-100 ppm ethanol) but also have the shortest response and recovery times at the optimal operating temperature of 250 °C. The sensing mechanism of noble metal doped materials can be attributed to the synergetic effect combining 'catalysis' and 'electronic and chemical sensitization' of noble metals. In particular, the chemical state of the noble metal also has a great influence on the gas sensing mechanism. A detailed explanation of the enhancement of gas sensing performance through noble metal doping is presented in the gas sensing mechanism part of the manuscript.
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http://dx.doi.org/10.1088/1361-6528/abf453DOI Listing
May 2021

Clinical recommendations for perioperative immunotherapy-induced adverse events in patients with non-small cell lung cancer.

Thorac Cancer 2021 05 30;12(9):1469-1488. Epub 2021 Mar 30.

Peking University Cancer Hospital, Beijing, China.

Perioperative adjuvant treatment has become an increasingly important aspect of the management of patients with non-small cell lung cancer (NSCLC). In particular, the success of immune checkpoint inhibitors, such as antibodies against PD-1 and PD-L1, in patients with lung cancer has increased our expectations for the success of these therapeutics as neoadjuvant immunotherapy. Neoadjuvant therapy is widely used in patients with resectable stage IIIA NSCLC and can reduce primary tumor and lymph node stage, improve the complete resection rate, and eliminate microsatellite foci; however, complete pathological response is rare. Moreover, because the clinical benefit of neoadjuvant therapy is not obvious and may complicate surgery, it has not yet entered the mainstream of clinical treatment. Small-scale clinical studies performed in recent years have shown improvements in the major pathological remission rate after neoadjuvant therapy, suggesting that it will soon become an important part of NSCLC treatment. Nevertheless, neoadjuvant immunotherapy may be accompanied by serious adverse reactions that lead to delay or cancellation of surgery, additional illness, and even death, and have therefore attracted much attention. In this article, we draw on several sources of information, including (i) guidelines on adverse reactions related to immune checkpoint inhibitors, (ii) published data from large-scale clinical studies in thoracic surgery, and (iii) practical experience and published cases, to provide clinical recommendations on adverse events in NSCLC patients induced by perioperative immunotherapy.
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http://dx.doi.org/10.1111/1759-7714.13942DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8088961PMC
May 2021

Effects of sevoflurane general anesthesia during early pregnancy on AIM2 expression in the hippocampus and parietal cortex of Sprague-Dawley offspring rats.

Exp Ther Med 2021 May 8;21(5):469. Epub 2021 Mar 8.

Department of Anesthesiology, Taian City Central Hospital, Taishan, Taian, Shandong 271000, P.R. China.

The aim of the present study was to investigate the effect of exposure to sevoflurane general anesthesia during early pregnancy on interferon-inducible protein AIM2 (AIM2) expression in the hippocampus and parietal cortex of the offspring Sprague-Dawley (SD) rats. A total of 18 SD rats at a gestational age of 5-7 days were randomly divided into three groups: i) A control group (control); ii) 2-h sevoflurane general anesthesia, group 1 (S1); and iii) 4-h sevoflurane general anesthesia, group 2 (S2). The six offspring rats in each group were maintained for 30 days and assessed by Morris water maze testing. Brain specimens were collected from offspring rats 30 days after birth. Changes in the structural morphology of neurons in the hippocampus and parietal cortex were observed using hematoxylin and eosin staining. Nissl bodies in the hippocampus and parietal cortex were observed by Nissl staining. The expression of glial fibrillary acidic protein (GFAP), AIM2, CD45 and IL-1β was detected by immunohistochemistry and the protein levels of CD45, IL-1β, pro-caspase-1 and caspase-1 p10 were detected by western blotting. Compared with the control group, offspring rats in the S1 and S2 groups exhibited poor long-term learning and memory ability and experienced different degrees of damage to both the hippocampus and parietal cortex. The expression levels of GFAP, AIM2, CD45, IL-1β, caspase-1 and caspase-1 p10 in the offspring of both the S1 and the S2 groups were significantly increased (P<0.05) compared with offspring of the control group. Moreover, compared with the offspring of the S1 group, hippocampal and parietal cortex injury in the offspring of the S2 group was further aggravated, and the expression of GFAP, AIM2, CD45, IL-1β, pro-caspase-1 and cleaved-caspase-1 was significantly increased (P<0.05). In conclusion, sevoflurane general anesthesia in SD rat early pregnancy promoted the expression of AIM2 and the inflammatory response in the hippocampus and parietal cortex of offspring rats.
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http://dx.doi.org/10.3892/etm.2021.9900DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7976445PMC
May 2021

Small Cell Size Circulating Aneuploid Cells as a Biomarker of Prognosis in Resectable Non-Small Cell Lung Cancer.

Front Oncol 2021 3;11:590952. Epub 2021 Mar 3.

Department of Thoracic Surgery II, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Peking University Cancer Hospital and Institute, Beijing, China.

Objective: The size distribution of circulating aneuploid cells (CACs) and its clinical significance were investigated in resectable non-small cell lung cancer (NSCLC).

Patients And Methods: A total of 50 patients with resectable NSCLC were enrolled in this study. Blood samples (50 pre-surgery and 35 post-surgery) were collected and used for the detection of CAC chromosome 8 heteroploidy through the subtraction enrichment and immunostaining fluorescence hybridization (SE-iFISH) method.

Results: Less than 20% small cell size and more than 80% large cell size CACs were detected. Karyotypes, including triploid, tetraploid, and multiploid, had varying distributions. The triploid subtype accounted for the majority of small cell size CACs, whereas the multiploid subtype accounted for the majority of large cell size CACs. We found that total small cell size and triploid small cell size CACs, but not large cell size CACs, derived from pre-surgery samples, were associated with shorter disease-free survival. Moreover, total small cell size and triploid small cell size CACs were associated with higher TNM stage and recurrence. Nevertheless, the variation between pre- and post-surgery CACs was not related to survival among patients with resectable NSCLC.

Conclusions: Pre-surgery small cell size CACs, especially the triploid subtype, could be regarded as a potential prognostic biomarker for patients with resectable NSCLC.
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http://dx.doi.org/10.3389/fonc.2021.590952DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7968455PMC
March 2021

Zp4 is completely dispensable for fertility in female rats†.

Biol Reprod 2021 06;104(6):1282-1291

Institute of Reproductive & Stem Cell Engineering, School of Basic Medical Science, Central South University, Changsha, China.

Zona pellucida (ZP), which is composed of at most four extracellular glycoproteins (ZP1, ZP2, ZP3, and ZP4) in mammals, shelters the oocytes and is vital in female fertility. Several studies have identified the indispensable roles of ZP1-3 in maintaining normal female fertility. However, the understanding of ZP4 is still very poor because only one study on ZP4-associated infertility performed in rabbits has been reported up to date. Here we investigated the function of mammalian Zp4 by creating a knockout (KO) rat strain (Zp4-/- rat) using CRISPR-Cas9-mediated DNA-editing method. The influence of Zp4 KO on ZP morphology and some pivotal processes of reproduction, including oogenesis, ovulation, fertilization, and pup production, were studied using periodic acid-Schiff's staining, superovulation, in vitro fertilization, and natural mating. The ZP morphology in Zp4-/- rats was normal, and none of these pivotal processes was affected. This study renewed the knowledge of mammalian Zp4 by suggesting that Zp4 was completely dispensable for female fertility.
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http://dx.doi.org/10.1093/biolre/ioab047DOI Listing
June 2021

Mutant Zp1 impedes incorporation of ZP3 and ZP4 in the zona pellucida, resulting in zona absence and female infertility in rats†.

Biol Reprod 2021 06;104(6):1262-1270

School of Basic Medical Science, Institute of Reproductive & Stem Cell Engineering, Central South University, Changsha, China.

The zona pellucida (ZP) plays vital roles in reproductive processes including oogenesis, fertilization, and preimplantation development. Both human and rat ZP consist of four glycoproteins, called ZP1, ZP2, ZP3, and ZP4. Our previous research reported a novel Zp1 mutation in cases of human infertility, associated with an abnormal phenotype involving the absence of the ZP. Here, we developed a homologous rat strain to investigate the pathogenic effect. The ovaries of homozygous (Zp1MT/MT) females possessed both growing and fully grown oocytes; the oocytes completely lacked a ZP, but ZP1 was detectable inside the cytoplasm. Only 1-2 eggs were recovered from oviducts of superovulated Zp1MT/MT females, while an average of 21 eggs were recovered from superovulated Zp1WT/WT per female. The eggs of Zp1MT/MT females were not surrounded by a ZP and lost their fertilization capacity in vitro. Zp1MT/MT females mated with wild-type males failed to become pregnant. Studies in 293T cells showed that mutant Zp1 resulted in a truncated ZP1 protein, which might be intracellularly sequestered and interacted with wild-type ZP3 or ZP4. Our results suggest that the Zp1 point mutation led to infertility and loss of the ZP in oocytes in rats.
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http://dx.doi.org/10.1093/biolre/ioab025DOI Listing
June 2021

Molecular dynamics simulation studies on the specific regulation of PTPN18 to the HER2 phospho-peptides.

J Mol Recognit 2021 Jul 23;34(7):e2890. Epub 2021 Feb 23.

Key Laboratory of Theoretical and Computational Photochemistry, Ministry of Education, College of Chemistry, Beijing Normal University, Beijing, China.

The specific regulation of PTPN18 protein to three HER2 phospho-peptides has been studied by molecular dynamics simulations and free energy calculations. The results revealed that the three HER2 phospho-peptides binding to the PTPN18 catalytic domain is energetically favorable due to substrate specificity of PTPN18, and moreover, the PTPN18 protein have significantly higher affinity to pY1248 peptide (-45.22 kcal/mol) than that of pY1112 (-25.3 kcal/mol) and pY1196 (-31.86 kcal/mol) peptides. Further, the binding of HER2 phospho-peptides to PTPN18 have also caused the closure of WPD-loop with the decrease of the centroid distances between the P-loop and the WPD loop. The WPD-loop closure of PTPN18 relates directly to the new hydrogen bond and hydrophobic interaction formations between the residues Tyr62, Asp64, Val65, Ala231, Arg235, and Ala273 in PTPN18 and Tyr(PO3) in the HER2 phospho-peptides, which suggests that these key residues would contribute to the specific regulation of PTPN18 to the substrates. The correlation analysis revealed the allosteric communication networks from the pY binding loop to the WPD loop through the structural change and the residue interactions in PTPN18. These results will be helpful to understand the specific regulation through the allosteric communication network in the PTPN18 catalytic domain.
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http://dx.doi.org/10.1002/jmr.2890DOI Listing
July 2021

Efficacy and Safety of PD-1/PD-L1 Inhibitors Plus Chemotherapy Versus PD-1/PD-L1 Inhibitors in Advanced Non-Small Cell Lung Cancer: A Network Analysis of Randomized Controlled Trials.

Front Oncol 2020 11;10:574752. Epub 2021 Jan 11.

Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Thoracic Surgery II, Peking University Cancer Hospital & Institute, Beijing, China.

Immune checkpoint inhibitors (ICIs) are recommended as first-line treatment for late-stage non-small cell lung cancer (NSCLC), either as monotherapy or in combination with chemotherapy. However, efficacy and safety comparisons between ICIs as monotherapy and ICIs with chemotherapy are lacking. We searched PubMed, Embase, and Cochrane Library for randomized controlled trials published before February 29th, 2020, with the search terms "immunotherapy" and "chemotherapy". 10 eligible trials were identified with a total of 5,956 patients. Of these patients, 3,204 received immune therapy and 2,752 received chemotherapy. PD-1 inhibitors with chemotherapy improved OS (HR 0.84, 0.77-0.92), PFS (HR 0.80, 0.75-0.85), and objective response rate (ORR) (odds ratio (OR) 2.55, 1.20-5.28) compared to PD-1 inhibitors as monotherapy. In contrast, PD-L1 inhibitors plus chemotherapy showed no significant differences in OS, PFS, or ORR compared with PD-L1 inhibitors as monotherapy. When patients were stratified according to PD-L1 expression level, patients with high PD-L1 expression (≥ 50%) receiving PD-1 inhibitors plus chemotherapy had improved PFS, but not other outcomes, compared to PD-1 inhibitors as monotherapy. In these patients, PD-L1 inhibitors plus chemotherapy showed no significant difference in survival compared with PD-L1 inhibitors. In the low PD-L1 expression group (1%-49%), PD-1 inhibitors plus chemotherapy improved OS and PFS, but no advantage was observed in PD-L1 inhibitors plus chemotherapy in OS, PFS, or ORR compared with PD-L1 inhibitor monotherapy. When comparing PD-1/PD-L1 inhibitors plus chemotherapy with PD-1/PD-L1 inhibitors monotherapy, no significant differences were observed in the rate of immune-related adverse events (AEs). In summary, for treating patients with late-stage NSCLC, PD-1 inhibitors plus chemotherapy have improved efficacy compared with PD-1 inhibitor monotherapy, but PD-L1 inhibitors plus chemotherapy have similar efficacy as PD-L1 monotherapy. Survival benefits of PD-1/PD-L1 inhibitors combined with chemotherapy were particularly significant in patients with low PD-L1 expression levels.

Systematic Review Registration: PROSPERO, identifier CRD42020166678 (https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=166678).
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http://dx.doi.org/10.3389/fonc.2020.574752DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7873939PMC
January 2021

Rosuvastatin exerts anti-atherosclerotic effects by improving macrophage-related foam cell formation and polarization conversion via mediating autophagic activities.

J Transl Med 2021 02 10;19(1):62. Epub 2021 Feb 10.

Department of Cardiology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China.

Background: Atherosclerosis is a chronic vascular disease posing a great threat to public health. We investigated whether rosuvastatin (RVS) enhanced autophagic activities to inhibit lipid accumulation and polarization conversion of macrophages and then attenuate atherosclerotic lesions.

Methods: All male Apolipoprotein E-deficient (ApoE) mice were fed high-fat diet supplemented with RVS (10 mg/kg/day) or the same volume of normal saline gavage for 20 weeks. The burden of plaques in mice were determined by histopathological staining. Biochemical kits were used to examine the levels of lipid profiles and inflammatory cytokines. The potential mechanisms by which RVS mediated atherosclerosis were explored by western blot, real-time PCR assay, and immunofluorescence staining in mice and RAW264.7 macrophages.

Results: Our data showed that RVS treatment reduced plaque areas in the aorta inner surface and the aortic sinus of ApoE mice with high-fat diet. RVS markedly improved lipid profiles and reduced contents of inflammatory cytokines in the circulation. Then, results of Western blot showed that RVS increased the ratio LC3II/I and level of Beclin 1 and decreased the expression of p62 in aortic tissues, which might be attributed to suppression of PI3K/Akt/mTOR pathway, hinting that autophagy cascades were activated by RVS. Moreover, RVS raised the contents of ABCA1, ABCG1, Arg-1, CD206 and reduced iNOS expression of arterial wall, indicating that RVS promoted cholesterol efflux and M2 macrophage polarization. Similarly, we observed that RVS decreased lipids contents and inflammatory factors expressions in RAW264.7 cells stimulated by ox-LDL, accompanied by levels elevation of ABCA1, ABCG1, Arg-1, CD206 and content reduction of iNOS. These anti-atherosclerotic effects of RVS were abolished by 3-methyladenine intervention. Moreover, RVS could reverse the impaired autophagy flux in macrophages insulted by chloroquine. We further found that PI3K inhibitor LY294002 enhanced and agonist 740 Y-P weakened the autophagy-promoting roles of RVS, respectively.

Conclusions: Our study indicated that RVS exhibits atheroprotective effects involving regulation lipid accumulation and polarization conversion by improving autophagy initiation and development via suppressing PI3K/Akt/mTOR axis and enhancing autophagic flux in macrophages.
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http://dx.doi.org/10.1186/s12967-021-02727-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7877030PMC
February 2021

A facile synthesis of isotope labeled acylcarnitines.

J Labelled Comp Radiopharm 2021 May 22;64(5):217-224. Epub 2021 Feb 22.

Department of Research and Development, Nanjing Apollomics Biotech, Inc., Nanjing, China.

Acylcarnitines are a big family of small molecule metabolites with various acyl groups attached to the hydroxyl moiety of l-carnitine. They are good indicators of multiple metabolic disorders. For instance, the newborn screening panel uses flow injection tandem mass spectrometry to analyze more than 30 different acylcarnitines and amino acids extracted from dried blood spots. A facile approach has been developed for the synthesis of isotope labeled acylcarnitines whose mass shift over their unlabeled counterparts can be any number in the range of 3 to 12 Da. This strategy makes it more convenient to provide authentic internal standards for acylcarnitines profiling analyses, thereby expanding their clinical applications.
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http://dx.doi.org/10.1002/jlcr.3904DOI Listing
May 2021

Combined Effects of Plant Sterols with Low Ratio of n-6/n-3 Polyunsaturated Fatty Acids against Atherosclerosis in ApoE Mice.

Curr Med Sci 2020 Dec 11;40(6):1099-1106. Epub 2021 Jan 11.

Department of Cardiology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China.

The effects of low ratio of n-6/n-3 polyunsaturated fatty acids (PUFA) have been clarified against atherosclerosis. Increasing evidence indicated that plant sterols (PS) have a significant cholesterol-lowering effect. This study explored the effects of PS combined with n-6/n-3 (2:1) PUFA on atherosclerosis and investigated the possible mechanism. In ApoE mice, the milk fat in high fat diets was replaced with n-6/n-3 (2:1) PUFA alone or supplemented with 6% PS for 16 weeks. Results demonstrated that PS combined with PUFA exerted commentary and synergistic effects on ameliorating atherosclerosis, improving lipid metabolism and lipid deposition in liver, and alleviating inflammatory response. These changes were accompanied with decreased serum TC, TG, LDL-C and increased fecal cholesterol efflux, as well as the lower inflammatory cytokine CRP, IL-6, TNF-α. It is suggested that the underlying mechanism of PS combined with n-6/n-3 (2:1) PUFA promoting the fecal cholesterol efflux may be mediated by liver X receptor α/ATP-binding cassette transporter A1 pathway.
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http://dx.doi.org/10.1007/s11596-020-2292-zDOI Listing
December 2020

Validation of the 8th Edition Nodal Staging and Proposal of New Nodal Categories for Future Editions of the TNM Classification of Non-Small Cell Lung Cancer.

Ann Surg Oncol 2021 Aug 2;28(8):4510-4516. Epub 2021 Jan 2.

Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Thoracic Surgery II, Peking University Cancer Hospital and Institute, Beijing, China.

Background: The International Association for the Study of Lung Cancer (IASLC) N classifications, which depend on the location and involvement of the lymph nodes, provide accurate prognoses. This study validated the efficiency of classifications using a single-institution dataset and proposed a modified system based on 5-level N1 node dissection.

Methods: From January 2005 to December 2014, 1851 patients with completely resected non-small cell lung cancer were reviewed. According to the IASLC recommendations, N1 is further subdivided into N1a (single) and N1b (multiple), N2 is divided into N2a1 (single station without N1), N2a2 (single station with N1), and N2b (multiple station). Additionally, we evaluated dividing N0 into N0a (with level 13/14 examination) and N0b (without level 13/14 examination), and N1 into N1a* (only level 13/14 positive) and N1b* (level 10-12 positive). Overall survival was also compared.

Results: Multivariate analysis showed that the N classifications recommended by the IASLC and those proposed and evaluated by this study could both significantly predict the prognoses of patients (p < 0.001, respectively). There was no significant difference in survival between N1b and N1a (hazard ratio [HR] 1.049, p = 0.83) and N2a1 and N1b (HR 1.314, p = 0.261); however, there were significant differences between N0a and N0b (HR 1.778, p < 0.001) and N1a* and N1b* (HR 2.014, p = 0.019). The survival curve of N1a* overlapped N0b (HR 0.997, p = 0.991), and N2a1 overlapped N1b* (HR 0.842, p = 0.444).

Conclusion: More detailed nodal information is required to facilitate future revisions of N staging.
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http://dx.doi.org/10.1245/s10434-020-09461-yDOI Listing
August 2021

Does neoadjuvant targeted therapy provide an opportunity for resectable EGFR-mutant lung cancer: a real-world retrospective study.

J Thorac Dis 2020 Oct;12(10):5324-5335

Department of Thoracic Surgery II, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Peking University Cancer Hospital & Institute, Beijing, China.

Background: Although neoadjuvant chemotherapy could improve survival outcome in resectable non-small cell lung cancer (NSCLC), the efficacy of neoadjuvant targeted therapy is still unclear.

Methods: We retrospectively reviewed clinical records of stage I-IIIA lung adenocarcinoma patients treated with neoadjuvant targeted therapy or chemotherapy prior to surgery. The collected data were compared between the two groups. Tumor samples were collected and analyzed by sequencing to explore the epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) resistance mechanisms.

Results: A total of 134 patients were enrolled; of these, 119 (88.8%) had clinical stage II-IIIA disease. Radiographic response rate was significantly higher with neoadjuvant targeted therapy than with chemotherapy among patients harboring EGFR mutation [objective response rate (ORR): 55.8% 32.6%; P=0.030]. EGFR exon 19 deletion achieved better tumor response than those with exon 21 L858R mutation (ORR: 70.0% 40.0%; P=0.057). Postoperative complications, operation time, drainage volume, and postoperative hospital length of stay were comparable between two groups. There was no difference on disease free survival (DFS) between patients receiving neoadjuvant targeted therapy and chemotherapy (P=0.871), but those who continued long-term adjuvant targeted therapy had significantly longer DFS than those only treated with adjuvant chemotherapy postoperatively (P=0.011). A series of potential molecular mechanisms of EGFR-TKI primary resistance were detected; these included BIM deletion polymorphisms, T790M mutation, and , , , or mutations. Patients who presented stable disease (SD) response after TKI therapy had significantly lower EGFR mutation abundance than PR response (P=0.032).

Conclusions: Neoadjuvant EGFR-TKI appears to be more effective than conventional chemotherapy for EGFR-mutant NSCLC patients. This study provides evidence that needs to be investigated further in randomized controlled trials (RCT).
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http://dx.doi.org/10.21037/jtd-20-1265DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7656393PMC
October 2020

Self-Assembly of Linear Amphiphilic Pentablock Terpolymer PAA-PS-PEO-PS-PAAin Dilute Aqueous Solution.

Polymers (Basel) 2020 Sep 24;12(10). Epub 2020 Sep 24.

MOE Key Laboratory of Macromolecular Synthesis and Functionalization, Department of Polymer Science & Engineering, Zhejiang University, Hangzhou 310027, China.

A series of linear amphiphilic pentablock terpolymer PAA--PS--PEO--PS--PAA (ASOSA) with various lengths of the PAA block ( = 15, 40, 60, and 90) were synthesized via a two-step atom transfer radical polymerization (ATRP) using Br-poly(ethylene oxide)-Br (Br-PEO-Br) as the macroinitiator, styrene (St) as the first monomer, and ert-butyl acrylate (BA) as the second monomer, followed with the hydrolysis of PBA blocks. The ASOSA pentablock terpolymers formed micelles in dilute aqueous solution, of which the morphologies were dependent on the length of the PAA block. Cryogenic transmission electron microscopy (cryo-TEM), dynamic light scattering (DLS), and zeta potential measurement were employed to investigate the morphologies, chain structures, size, and size distribution of the obtained micelles. The morphology of ASOSA micelles changed from spherical vesicles with ordered porous membranes to long double nanotubes, then to long nanotubes with inner modulated nanotubes or short nanotubes, and finally, to spherical micelles or large compound vesicles with spherical micelles inside when increased from 15 to 90. The hydrophobic PS blocks formed the walls of vesicles and nanotubes as well as the core of spherical micelles. The hydrophilic PEO and PAA block chains were located on the surfaces of vesicle membranes, nanotubes, and spherical micelles. The PAA block chains were partially ionized, leading to the negative zeta potential of ASOSA micelles in dilute aqueous solutions.
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http://dx.doi.org/10.3390/polym12102183DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7598608PMC
September 2020

Trimetazidine Ameliorates Myocardial Metabolic Remodeling in Isoproterenol-Induced Rats Through Regulating Ketone Body Metabolism Activating AMPK and PPAR α.

Front Pharmacol 2020 14;11:1255. Epub 2020 Aug 14.

Department of Cardiology, Tianjin Union Medical Center, Tianjin, China.

Background: Metabolic remodeling plays a vital role in the development of heart failure. The trimetazidine can optimize fatty acid and glucose oxidation inhibition of long-chain 3-ketoacyl CoA thiolase in the heart. So, trimetazidine commonly used in cardiovascular therapy as a myocardial metabolic drug. This study was conducted to assess the effects and mechanisms of trimetazidine on ketone body metabolism in heart failure rats.

Methods: A rat model of heart failure was established by continuous subcutaneous injection of isoproterenol in 10 mg/kg/d. We examined body weight, heart weight index, and tested B-type natriuretic peptide by kit. We detected the structure and function of the heart. Hematoxylin-eosin staining and Masson's trichrome staining was performed to assess myocardial tissue morphology. To evaluate apoptosis, we used Tunel staining. Metabolic substrate contents of glucose, free fatty acid, ketone bodies, lactic acid, and pyruvate and ATP levels in myocardial tissues were measured with the corresponding kit. We detected the levels of protein expressions related to myocardial substrate uptake and utilization by Western blot.

Results: Trimetazidine remarkably reduced the heart weight index and B-type natriuretic peptide levels. Besides, trimetazidine increased the level of blood pressure and decreased heart rate. Moreover, trimetazidine inhibited decreases in left ventricular ejection fraction and left ventricular fractional shortening. Further, trimetazidine decreased the levels of collagen volume fraction and promoted ATP production in myocardial tissues. Trimetazidine also reduced the levels of free fatty acid, ketone bodies, lactic acid, and increased glucose and pyruvate levels in myocardial tissues. Furthermore, trimetazidine markedly inhibited apoptosis. More importantly, the protein expression levels related to myocardial substrate uptake and utilization increased dramatically in the trimetazidine group. In particular, the protein expressions related to ketone body utilization were prominent.

Conclusions: Trimetazidine could attenuate metabolic remodeling and improve cardiac function in heart failure rats. The potential mechanism for the cardioprotective effect of trimetazidine may be highly associated with its regulation of adenosine monophosphate-activated protein kinase, and peroxisome proliferator activated receptor α expressions. Along with the regulation, myocardial substrate utilization was improved, especially the utilization of ketone bodies.
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http://dx.doi.org/10.3389/fphar.2020.01255DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7457052PMC
August 2020

Contributions and achievements on schistosomiasis control and elimination in China by NIPD-CTDR.

Adv Parasitol 2020 10;110:1-62. Epub 2020 Jun 10.

National Institute of Parasitic Diseases, Chinese Center for Disease Control and Prevention; Chinese Center for Tropical Diseases Research, Shanghai, People's Republic of China; WHO Collaborating Centre for Tropical Diseases; National Center for International Research on Tropical Diseases, Ministry of Science and Technology; Key Laboratory of Parasite and Vector Biology, Ministry of Health, Shanghai, People's Republic of China; School of Global Health, Chinese Center for Tropical Diseases Research, Shanghai Jiao Tong University School of Medicine, Shanghai, People's Republic of China. Electronic address:

Being a zoonotic parasitic disease, schistosomiasis was widely spread in 12 provinces of Southern China in the 1950s, severly harming human health and hindering economic development. The National Institute of Parasitic Diseases at the Chinese Center for Diseases Control and Prevention, and Chinese Center for Tropical Diseases Research (NIPD-CTDR), as the only professional institution focussing on parasitic diseases at the national level, has played an important role in schistosomiasis control in the country. In this article, we look back at the changes of schistosomiasis endemicity and the contribution of NIPD-CTDR to the national schistosomiasis control programme. We review NIPD-CTDR's activities, including field investigations, design of control strategies and measures, development of diagnostics and drugs, surveillance-response of endemic situation, and monitoring & evaluation of the programme. The NIPD-CTDR has mastered the transmission status of schistosomiasis, mapped the snail distribution, and explored strategies and measures suitable for different types of endemic areas in China. With a good understanding of the life cycle of Schistosoma japonicum and transmission patterns of the disease, advanced research carried out in the NIPD-CTDR based on genomics and modern technology has made it possible to explore highly efficient and soft therapeutic drugs and molluscicides, making it possible to develop new diagnostic tools and produce vaccine candidates. In the field, epidemiological studies, updated strategies and targeted intervention measures developed by scientists from the NIPD-CTDR have contributed significantly to the national schistosomiasis control programme. This all adds up to a strong foundation for eliminating schistosomiasis in China in the near future, and recommendations have been put forward how to reach this goal.
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http://dx.doi.org/10.1016/bs.apar.2020.04.002DOI Listing
June 2021

The association between severe COVID-19 and low platelet count: evidence from 31 observational studies involving 7613 participants.

Br J Haematol 2020 Jul 9;190(1):e29-e33. Epub 2020 Jun 9.

Department of General Practice, Shenzhen Longhua District Central Hospital, Shenzhen, China.

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http://dx.doi.org/10.1111/bjh.16817DOI Listing
July 2020

Correction to: Screening of pectinase-producing bacteria from citrus peel and characterization of a recombinant pectate lyase with applied potential.

Arch Microbiol 2020 09;202(7):2021

Fujian Key Laboratory of Marine Enzyme Engineering, Fuzhou University, Fuzhou, 350116, People's Republic of China.

In the original article.
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http://dx.doi.org/10.1007/s00203-020-01893-0DOI Listing
September 2020

Characterization of the Nitrate Transporter gene family and functional identification of HvNRT2.1 in barley (Hordeum vulgare L.).

PLoS One 2020 23;15(4):e0232056. Epub 2020 Apr 23.

Jiangsu Key Laboratory of Crop Genetics and Physiology/ Key Laboratory of Plant Functional Genomics of the Ministry of Education/ Jiangsu Key Laboratory of Crop Genomics and Molecular Breeding, Agricultural College of Yangzhou University, Yangzhou, China.

Nitrogen use efficiency (NUE) is the efficiency with which plants acquire and use nitrogen. Plants have high-affinity nitrate transport systems, which involve certain nitrate transporter (NRT) genes. However, limited data are available on the contribution of the NRT2/3 gene family in barley nitrate transport. In the present study, ten putative NRT2 and three putative NRT3 genes were identified using bioinformatics methods. All the HvNRT2/3 genes were located on chromosomes 3H, 5H, 6H or 7H. Remarkably, the presence of tandem repeats indicated that duplication events contributed to the expansion of the NRT2 gene family in barley. In addition, the HvNRT2/3 genes displayed various expression patterns at selected developmental stages and were induced in the roots by both low and high nitrogen levels. Furthermore, the overexpression of HvNRT2.1 improved the yield related traits in Arabidopsis. Taken together, the data generated in the present study will be useful for genome-wide analyses to determine the precise role of the HvNRT2/3 genes during barley development, with the ultimate goal of improving NUE and crop production.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0232056PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7179922PMC
July 2020

Single‑cell RNA sequencing of t(8;21) acute myeloid leukemia for risk prediction.

Oncol Rep 2020 Apr 18;43(4):1278-1288. Epub 2020 Feb 18.

Department of Hematology and BMT Center, Chinese PLA General Hospital, Beijing 100853, P.R. China.

Single‑cell RNA sequencing (scRNA‑seq) of bone marrow or peripheral blood samples from patients with acute myeloid leukemia (AML) enables the characterization of heterogeneous malignant cells. A total of 87 cells from two patients with t(8;21) AML were analyzed using scRNA‑seq. Clustering methods were used to separate leukemia cells into different sub‑populations, and the expression patterns of specific marker genes were used to annotate these populations. Among the 31 differentially expressed genes in the cells of a patient who relapsed after hematopoietic stem cell transplantation, 13 genes were identified to be associated with leukemia. Furthermore, three genes, namely AT‑rich interaction domain 2, lysine methyltransferase 2A and synaptotagmin binding cytoplasmic RNA interacting protein were validated as possible prognostic biomarkers using two bulk expression datasets. Taking advantage of scRNA‑seq, the results of the present study may provide clinicians with several possible biomarkers to predict the prognostic outcomes of t(8;21) AML.
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http://dx.doi.org/10.3892/or.2020.7507DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7057921PMC
April 2020
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