Publications by authors named "Lin Jin"

528 Publications

The Leptinotarsa forkhead transcription factor O exerts a key function during larval-pupal-adult transition.

J Insect Physiol 2021 Jun 11:104266. Epub 2021 Jun 11.

Education Ministry Key Laboratory of Integrated Management of Crop Diseases and Pests, College of Plant Protection, Nanjing Agricultural University, Nanjing 210095, China. Electronic address:

Forkhead box O (FoxO) protein, a major downstream transcription factor of insulin/insulin-like growth factor signaling/target of rapamycin pathway (IIS/TOR), is involved in the regulation of larval growth and the determination of organ size. FoxO also interacts with 20-hydroxyecdysone (20E) and juvenile hormone (JH) signal transduction pathways, and hence is critical for larval development in holometabolans. However, whether FoxO plays a critical role during larval metamorphosis needs to be further determined in Leptinotarsa decemlineata. We found that 20E stimulated the expression of LdFoxO. RNA interference (RNAi)-aided knockdown of LdFoxO at the third-instar stage repressed 20E signaling and reduced larval weight. Although the resultant larvae survived through the third-fourth instar ecdysis, around 70% of the LdFoxO depleted moribund beetles developmentally arrested at prepupae stage. These LdFoxO depleted beetles were completely wrapped in the larval exuviae, gradually darkened and finally died. Moreover, approximately 12% of the LdFoxO RNAi beetles died as pharate adults. Ingestion of either 20E or JH by the LdFoxO depletion beetles excessively rescued the corresponding hormonal signals, but could not alleviate larval performance and restore defective phenotypes. Therefore, FoxO plays an important role in regulation of larval-pupal-adult transformation in L. decemlineata, in addition to mediation of IIS/TOR pathway and stimulation of ecdysteroidogenesis.
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http://dx.doi.org/10.1016/j.jinsphys.2021.104266DOI Listing
June 2021

Local Efficacy of Corticosteroids as an Adjuvant for Periarticular Cocktail Injection in Simultaneous Bilateral Total Knee Arthroplasty: A Prospective Randomized Double-Blind Controlled Trial.

Pain Res Manag 2021 19;2021:5595095. Epub 2021 May 19.

Department of Orthopaedic Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100730, China.

Multimodal cocktail periarticular injections comprising corticosteroids are the most suggested therapy for postoperative discomfort and swelling following total knee arthroplasty (TKA). Nevertheless, previous findings cannot be applied to instances of unilateral total knee arthroplasty on bilateral knees. This randomized, prospective, double-blind, controlled clinical study examines the efficacy as well as safety of periarticular multimodal cocktail injection along or sans corticosteroids in certain situations. The 60 patients (120 knees) that experienced concurrent bilateral total knee arthroplasty were provided periarticular injections along additional betamethasone (7 mg) in the randomized knee, as well as the other knee, where corticosteroid was not administered. Key results were "pain scores at rest as well as in action" on a visual analogue scale of 11 pt. Other results included motion range, swelling of the thigh, Hospital for Special Surgery score (HSS score), and adverse effects were measured between the two sides. No statistically promising variations were found in the visual analogue scale ranking, motion range, girth of the thigh, and HSS score, as well as complications between the two sides. The impact on treatment outcomes was maintained between the knees on postoperative day 3 or at 3 months of follow-up. Multimodal periarticular injection without corticosteroid will alleviate postoperative swelling and pain. More studies are needed for the use of betamethasone as a corticosteroid in periarticular multimodal cocktail injections. This Chinese Clinical Trial Registry is registered with ChiCTR-OPC-17013503, dated 2017-11-23, available from http://www.chictr.org.cn/showproj.aspxproj=23146.
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http://dx.doi.org/10.1155/2021/5595095DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8154299PMC
May 2021

SARS-CoV-2 envelope protein causes acute respiratory distress syndrome (ARDS)-like pathological damages and constitutes an antiviral target.

Cell Res 2021 Jun 10. Epub 2021 Jun 10.

Key Laboratory of Animal Models and Human Disease Mechanisms of the Chinese Academy of Sciences/Key Laboratory of Bioactive Peptides of Yunnan Province, KIZ-CUHK Joint Laboratory of Bioresources and Molecular Research in Common Diseases, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, Yunnan, China.

Cytokine storm and multi-organ failure are the main causes of SARS-CoV-2-related death. However, the origin of excessive damages caused by SARS-CoV-2 remains largely unknown. Here we show that the SARS-CoV-2 envelope (2-E) protein alone is able to cause acute respiratory distress syndrome (ARDS)-like damages in vitro and in vivo. 2-E proteins were found to form a type of pH-sensitive cation channels in bilayer lipid membranes. As observed in SARS-CoV-2-infected cells, heterologous expression of 2-E channels induced rapid cell death in various susceptible cell types and robust secretion of cytokines and chemokines in macrophages. Intravenous administration of purified 2-E protein into mice caused ARDS-like pathological damages in lung and spleen. A dominant negative mutation lowering 2-E channel activity attenuated cell death and SARS-CoV-2 production. Newly identified channel inhibitors exhibited potent anti-SARS-CoV-2 activity and excellent cell protective activity in vitro and these activities were positively correlated with inhibition of 2-E channel. Importantly, prophylactic and therapeutic administration of the channel inhibitor effectively reduced both the viral load and secretion of inflammation cytokines in lungs of SARS-CoV-2-infected transgenic mice expressing human angiotensin-converting enzyme 2 (hACE-2). Our study supports that 2-E is a promising drug target against SARS-CoV-2.
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http://dx.doi.org/10.1038/s41422-021-00519-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8190750PMC
June 2021

RNAi of vacuolar-type H-ATPase genes causes growth delay and molting defect in .

Bull Entomol Res 2021 Jun 11:1-10. Epub 2021 Jun 11.

Education Ministry Key Laboratory of Integrated Management of Crop Diseases and Pests, College of Plant Protection, Nanjing Agricultural University, Nanjing210095, China.

Henosepilachna vigintioctopunctata is one of the most serious insect pests to a large number of nightshades and cucurbits. RNA interference (RNAi) triggered by double-stranded RNA (dsRNA) offers a reduced risk approach to control the beetle. Identification of amenable target genes and determination of appropriate life stage for dsRNA treatment are two critical steps in order to improve RNAi efficiency. In the present paper, we identified three vATPase genes, namely HvvATPaseC, HvvATPaseE and HvvATPaseH. We found that the three transcripts were widely expressed in the eggs, first- to fourth-instar larvae, prepupae, pupae and adults. They were abundantly transcribed in the hindgut and Malpighian tubules, in contrast to the epidermis and fat body. Three days' ingestion of dsvATPaseC, dsvATPaseE and dsvATPaseH by the fourth-instar larvae significantly decreased corresponding transcript level by 90.1, 88.9 and 97.2%, greatly reduced larval fresh weight by 28.0, 29.9 and 28.0%, and caused 66.7, 100 and 78.7% larval lethality respectively. Comparably, 3 days' exposure of the third-instar larvae to dsvATPaseC significantly reduced HvvATPaseC mRNA level by 89.5%, decreased approximately 80% of the larval fresh weight, and killed 100% of the treated larvae. Therefore, the three vATPase genes, especially HvvATPaseE, are potential amenable target genes and young larvae are more susceptible to dsRNA. Our findings will enable the development of the dsRNA-based pesticide to control H. vigintioctopunctata.
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http://dx.doi.org/10.1017/S0007485321000420DOI Listing
June 2021

Efficient Synthesis and Biological Evaluation of 6-Trifluoroethoxy Functionalized Pteridine Derivatives as EGFR Inhibitors.

Med Chem 2021 Jun 3. Epub 2021 Jun 3.

Fujian Key Laboratory of Drug Target Discovery and Structural and Functional Research, Fujian Medical University, Fuzhou, China.

Background: Pteridine-based scaffolds have been widely prevalent in pharmaceuticals, such as kinase inhibitors targeting EGFR, FLT3 and PI3K/mTOR, which are attractive targets for anticancer therapy.

Objective: This work aimed to design and synthesize 6-2,2,2-trifluoroethoxy functionalized pteridine-based derivatives for investigation of their anti-cancer activities as EGFR inhibitor.

Method: Pteridine-based derivatives were synthesized in 6 steps involving amination, bromination, cyclization, alkoxylation, chlorination and coupling reactions. Cellular anti-proliferative activities and inhibition activities on EGFR signaling of these pteridine derivatives in vitro were determined by the MTT assay and western blot analysis, respectively. Molecular docking simulation studies were carried out by the crystallographic structure of the erlotinib/EGFR kinase domain [Protein Data Bank (PDB) code: 1M17].

Results: The compound 7m, with IC50 values of 27.40 μM on A549 cell line, exhibited comparable anti-proliferative activity relative to the positive control. Besides western blots showed its obvious down-regulation of p-EGFR and p-ERK expression at 0.8 μM. Molecular docking model displayed a hydrogen bond between Met-769 amide nitrogen and N-1 in pteridine motif of 7m which lay at the ATP binding site of EGFR kinase domain.

Conclusion: The inhibition of 7m on cellular growth was comparable to that of the positive control. The inhibitory activities of 7m on EGFR phosphorylation and ERK phosphorylation in A549 cell line were relatively superior to that of the positive control. Both results suggested that the anti-proliferative activity of 7m against A549 cell line was caused by inhibition of EGFR signaling pathway, providing a new perspective for modification on pteridine-based derivatives as EGFR inhibitor.
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http://dx.doi.org/10.2174/1573406417666210604105923DOI Listing
June 2021

Disruption of kynurenine pathway reveals physiological importance of tryptophan catabolism in Henosepilachna vigintioctopunctata.

Amino Acids 2021 Jun 5. Epub 2021 Jun 5.

Education Ministry Key Laboratory of Integrated Management of Crop Diseases and Pests, College of Plant Protection, Nanjing Agricultural University, Nanjing, 210095, China.

Kynurenine pathway is critically important to catabolize tryptophan, to produce eye chromes, and to protect nervous system in insects. However, several issues related to tryptophan degradation remain to be clarified. In the present paper, we identified three genes (karmoisin, vermilion and cardinal) involved in kynurenine pathway in Henosepilachna vigintioctopunctata. The karmoisin and cardinal were highly expressed in the pupae and adults having compound eyes. Consistently, high-performance liquid chromatography result showed that three ommochrome peaks were present in adult heads rather than bodies (thoraces, legs, wings and abdomens). RNA interference (RNAi)-aided knockdown of vermilion caused accumulation of tryptophan in both adult heads and bodies, disappearance of ommochromes in the heads and a complete loss of eye color in both pupae and adults. Depletion of cardinal brought about excess of 3-hydroxykynurenine and insufficient ommochromes in the heads and decolored eyes. RNAi of karmoisin resulted in a decrease in ommochromes in the heads, and a partial loss of eye color. Moreover, a portion of karmoisin-, vermilion- or cardinal-silenced adults exhibited negative phototaxis, whereas control beetles showed positive phototaxis. Furthermore, dysfunctions of tryptophan catabolism impaired climbing ability. Our findings clearly illustrated several issues related to kynurenine pathway and provided a new insight into the physiological importance of tryptophan catabolism in H. vigintioctopunctata.
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http://dx.doi.org/10.1007/s00726-021-03009-4DOI Listing
June 2021

A flexible multiplexed immunosensor for point-of-care in situ wound monitoring.

Sci Adv 2021 May 21;7(21). Epub 2021 May 21.

Institute for Health Innovation & Technology (iHealthtech), National University of Singapore, Singapore 117599, Singapore.

Chronic wounds arise from interruption of normal healing due to many potential pathophysiological factors. Monitoring these multivariate factors can provide personalized diagnostic information for wound management, but current sensing technologies use complex laboratory tests or track a limited number of wound parameters. We report a flexible biosensing platform for multiplexed profiling of the wound microenvironment, inflammation, and infection state at the point of care. This platform integrates a sensor array for measuring inflammatory mediators [tumor necrosis factor-α, interleukin-6 (IL-6), IL-8, and transforming growth factor-β1], microbial burden (), and physicochemical parameters (temperature and pH) with a microfluidic wound exudate collector and flexible electronics for wireless, smartphone-based data readout. We demonstrate in situ multiplexed monitoring in a mouse wound model and also profile wound exudates from patients with venous leg ulcers. This technology may facilitate more timely and personalized wound management to improve chronic wound healing outcomes.
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http://dx.doi.org/10.1126/sciadv.abg9614DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8139589PMC
May 2021

Northern pig-tailed macaques ( ) infected with SARS-CoV-2 show rapid viral clearance and persistent immune response.

Zool Res 2021 May;42(3):350-353

Key Laboratory of Animal Models and Human Disease Mechanisms of the Chinese Academy of Sciences/Key Laboratory of Bioactive Peptides of Yunnan Province, KIZ-CUHK Joint Laboratory of Bioresources and Molecular Research in Common Diseases, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, Yunnan 650223, China.

Coronavirus disease 2019 (COVID-19), which is caused by severe acute respiratory syndrome coronavirus (SARS-CoV-2), has become an unprecedented global health emergency. At present, SARS-CoV-2-infected nonhuman primates are considered the gold standard animal model for COVID-19 research. Here, we showed that northern pig-tailed macaques ( , NPMs) supported SARS-CoV-2 replication. Furthermore, compared with rhesus macaques, NPMs showed rapid viral clearance in lung tissues, nose swabs, throat swabs, and rectal swabs, which may be due to higher expression of interferon (IFN)-α in lung tissue. However, the rapid viral clearance was not associated with good outcome. In the second week post infection, NPMs developed persistent or even more severe inflammation and body injury compared with rhesus macaques. These results suggest that viral clearance may have no relationship with COVID-19 progression and SARS-CoV-2-infected NPMs could be considered as a critically ill animal model in COVID-19 research.
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http://dx.doi.org/10.24272/j.issn.2095-8137.2020.334DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8175946PMC
May 2021

Particulate matter exposure exacerbates susceptibility to SARS-CoV-2 infection in humanized ACE2 mice.

Zool Res 2021 May;42(3):335-338

Key Laboratory of Animal Models and Human Disease Mechanisms of Chinese Academy of Sciences/Key Laboratory of Bioactive Peptides of Yunnan Province, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, Yunnan 650223, China.

The global outbreak of coronavirus disease 2019 (COVID-19), which is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), as of 8 May 2021, has surpassed 150 700 000 infections and 3 279 000 deaths worldwide. Evidence indicates that SARS-CoV-2 RNA can be detected on particulate matter (PM), and COVID-19 cases are correlated with levels of air pollutants. However, the mechanisms of PM involvement in the spread of SARS-CoV-2 remain poorly understood. Here, we found that PM exposure increased the expression level of angiotensin-converting enzyme 2 (ACE2) and transmembrane serine protease 2 (TMPRSS2) in several epithelial cells and increased the adsorption of the SARS-CoV-2 spike protein. Instillation of PM in a hACE2 mouse model significantly increased the expression of and and viral replication in the lungs. Furthermore, PM exacerbated the pulmonary lesions caused by SARS-CoV-2 infection in the hACE2 mice. In conclusion, our study demonstrated that PM is an epidemiological factor of COVID-19, emphasizing the necessity of wearing anti-PM masks to cope with this global pandemic.
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http://dx.doi.org/10.24272/j.issn.2095-8137.2021.088DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8175951PMC
May 2021

Ca-supplying black phosphorus-based scaffolds fabricated with microfluidic technology for osteogenesis.

Bioact Mater 2021 Nov 20;6(11):4053-4064. Epub 2021 Apr 20.

Henan Provincial People's Hospital, Zhengzhou University People's Hospital, Zhengzhou, 450003, People's Republic of China.

Effective osteogenesis remains a challenge in the treatment of bone defects. The emergence of artificial bone scaffolds provides an attractive solution. In this work, a new biomineralization strategy is proposed to facilitate osteogenesis through sustaining supply of nutrients including phosphorus (P), calcium (Ca), and silicon (Si). We developed black phosphorus (BP)-based, three-dimensional nanocomposite fibrous scaffolds via microfluidic technology to provide a wealth of essential ions for bone defect treatment. The fibrous scaffolds were fabricated from 3D poly (l-lactic acid) (PLLA) nanofibers (3D NFs), BP nanosheets, and hydroxyapatite (HA)-porous SiO nanoparticles. The 3D [email protected] NFs possess three advantages: i) stably connected pores allow the easy entrance of bone marrow-derived mesenchymal stem cells (BMSCs) into the interior of the 3D fibrous scaffolds for bone repair and osteogenesis; ii) plentiful nutrients in the NFs strongly improve osteogenic differentiation in the bone repair area; iii) the photothermal effect of fibrous scaffolds promotes the release of elements necessary for bone formation, thus achieving accelerated osteogenesis. Both in vitro and results demonstrated that the 3D [email protected] NFs, with the assistance of NIR laser, exhibited good performance in promoting bone regeneration. Furthermore, microfluidic technology makes it possible to obtain high-quality 3D [email protected] NFs with low costs, rapid processing, high throughput and mass production, greatly improving the prospects for clinical application. This is also the first BP-based bone scaffold platform that can self-supply Ca, which may be the blessedness for older patients with bone defects or patients with damaged bones as a result of calcium loss.
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http://dx.doi.org/10.1016/j.bioactmat.2021.04.014DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8089774PMC
November 2021

Crustacean cardioactive peptide as a stimulator of feeding and a regulator of ecdysis in Leptinotarsa decemlineata.

Pestic Biochem Physiol 2021 Jun 3;175:104838. Epub 2021 Apr 3.

Education Ministry Key Laboratory of Integrated Management of Crop Diseases and Pests, College of Plant Protection, Nanjing Agricultural University, Nanjing 210095, China. Electronic address:

Crustacean cardioactive peptide (CCAP), a highly conserved amidated neuropeptide, stimulates feeding in Drosophila melanogaster and Periplaneta americana, and regulates pupa-adult transition in Tribolium castaneum and Manduca sexta. In the present paper, we intended to address whether CCAP plays the dual roles in the Colorado potato beetle Leptinotarsa decemlineata. We found that the levels of Ldccap were high in the dissected samples of brain-corpora cardiaca-corpora allata complex and ventral nerve cord, midgut and hindgut in the final (fourth)-instar larvae. A pulse of 20-hydroxyecdysone triggered the expression of Ldccap in the central nervous system but decreased the transcription in the midgut. In contrast, juvenile hormone intensified the expression of Ldccap in the midgut. RNA interference (RNAi)-aided knockdown of Ldccap at the penultimate instar stage inhibited foliage consumption, reduced the contents of trehalose and chitin, and lowered the mRNA levels of two chitin biosynthesis genes (LdUAP1 and LdChSAb). Moreover, around 70% of the Ldccap RNAi larvae remained as prepupae, completely wrapped in the old larval exuviae, and finally died. The remaining RNAi beetles continually developed to severely-deformed adults: most having wrinkled and smaller elytra and hindwings, and shortened legs. Therefore, CCAP plays three distinct roles, stimulating feeding in foraging larval stage, regulating ecdysis, and facilitating wing expansion and appendage elongation in a coleopteran. In addition, Ldccap can be used as a potential target gene for developing novel management strategies against this coleopteran pest.
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http://dx.doi.org/10.1016/j.pestbp.2021.104838DOI Listing
June 2021

Xuebijing injection in septic rats mitigates kidney injury, reduces cortical microcirculatory disorders, and suppresses activation of local inflammation.

J Ethnopharmacol 2021 Aug 12;276:114199. Epub 2021 May 12.

Department of Critical Care Medicine, Beijing Friendship Hospital, Capital Medical University, Beijing, 100050, China. Electronic address:

Ethnopharmacological Relevance: Xuebijing injections originate from the traditional Chinese medicine (TCM) prescription XuefuZhuyu Decoction. It is composed of five Chinese herbal extracts; Carthami flos, Paeoniae radix rubra, Chuanxiong rhizoma, Salviae miltiorrhizae, and Angelicae Sinensis radix. The China Food and Drug Administration approved Xuebijing injections as a TCM preparation for the adjuvant treatment of sepsis.

Aim Of The Study: This study aims to determine the effects of Xuebijing injections as an adjuvant to antibiotics for the treatment of renal microcirculatory dysfunction and renal inflammation in rats with sepsis.

Materials And Methods: The rats received a sham operation (Sham), sham operation followed by Xuebijign injection (Sxbj), cecal ligation and puncture (CLP), or CLP followed by Xuebijing injection (Cxbj). Renal microvascular perfusion in the cortex and oxygenation were assessed at different times after sepsis induction. Renal levels of interleukin (IL)-1β, IL-6, tumor necrosis factor (TNF)-α, and high mobility group box (HMGB)-1 were measured. Urinary TIMP-2 × IGFBP-7 and neutrophil gelatinase-associated lipocalin (NGAL) were measured as kidney biomarkers, and serum creatinine (SCr) was used to assess kidney injury. Tissue samples were stained for histologic evaluation.

Results: The induction of sepsis increased local inflammation and decreased renal microvascular perfusion and oxygenation. Compared with the CLP group, the Cxbj group displayed improvements in microvascular perfusion and oxygenation (p < 0.05). The CLP group had significant increases in renal inflammatory biomarkers (IL-1β, IL-6, TNF-α, and HMGB-1; p < 0.05) and Xuebijing injection reduced the levels of these markers. The levels of urinary TIMP-2 × IGFBP-7, NAGL, and SCr were lower in the Cxbj group than in the CLP group (p < 0.05), and the CLP group had a higher Paller score than the Cxbj group (p < 0.05). However, the CLP and Cxbj groups had no significant difference in mortality.

Conclusions: This study into the early stages of sepsis in a rat model indicated that as an adjuvant therapy to antibiotics, Xuebijing injection improved renal perfusion and oxygenation, suppressed renal inflammation, and ameliorated kidney dysfunction. However, Xuebijing injection had no impact on mortality.
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http://dx.doi.org/10.1016/j.jep.2021.114199DOI Listing
August 2021

Pannexin-1 Contributes to the Apoptosis of Spinal Neurocytes in Spinal Cord Injury.

Front Physiol 2021 27;12:656647. Epub 2021 Apr 27.

Department of Spine Surgery, The First Affiliated Hospital of Fujian Medical University, Fuzhou, China.

Currently, the role of Pannexin-1, a homomeric membrane hemichannel on the neuron cell membrane, in the development of spinal cord injury (SCI) is largely unknown. Herein, we assessed the contribution of Panx1 in the development of SCI. The SCI model was established using rat primary spinal neurocytes treated with hydrogen peroxide (HO). Effects of Panx1 overexpression or depletion in spinal neurocytes were analyzed by lentivirus-mediated transfection of Panx1 and interference sh-Panx1. Decreased cell viability was seen in SCI cells, which was further enhanced under Panx1 overexpression and mitigated by Panx1 deficiency. HO induced an increase of intracellular Ca signal and upregulated level of the proapoptotic protein Bax, and apoptosis pathway proteins including cleaved Caspase-3 and PARP1, which was enhanced by Panx1 overexpression or attenuated by Panx1 depletion. On the other hand, HO treatment suppressed the level of antiapoptotic protein Bcl-2, which was further decreased by Panx1 overexpression or mitigated by Panx1 depletion. The results indicate that Panx1 was involved in the intracellular Ca overload of SCI cells by accelerating extracellular Ca influx, which promoted the apoptosis of spinal neurocytes through Ca dependent pathways, thus aggravating the secondary injury of SCI.
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http://dx.doi.org/10.3389/fphys.2021.656647DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8112589PMC
April 2021

Wedelolactone improves the renal injury induced by lipopolysaccharide in HK-2 cells by upregulation of protein tyrosine phosphatase non-receptor type 2.

J Int Med Res 2021 May;49(5):3000605211012665

Department of Critical Care Medicine, Beijing Friendship Hospital Affiliated to Capital Medical University, Beijing, China.

Objective: To explore the effects of wedelolactone (WEL) on sepsis-induced renal injury in the human renal proximal tubular epithelial cell line HK-2.

Methods: HK-2 cells were stimulated by 1 µg/ml lipopolysaccharide (LPS) to trigger renal injury . HK-2 cells were pretreated with or without WEL (0.1, 1 and 10 µM) before LPS stimulation. Protein and mRNA analyses were performed using enzyme-linked immunosorbent assays, Western blot analysis and quantitative reverse transcription-polymerase chain reaction. The MTT assay and flow cytometry were used to measure cell viability and the rate of cell apoptosis. Protein tyrosine phosphatase non-receptor type 2 (PTPN2) knockdown was induced by the transection of HK-2 cells with short hairpin RNA.

Results: Cell viability was significantly increased in a dose-dependent manner by WEL in LPS-induced HK-2 cells. WEL also decreased the levels of four inflammatory cytokines and cell apoptosis in LPS-induced HK-2 cells. The level of PTPN2 was increased after WEL treatment. PTPN2 knockdown partly abolished the inhibitory effects of WEL on cell apoptosis, the levels of inflammatory cytokines and on p38 mitogen-activated protein kinase/nuclear factor-kappaB signalling in LPS-induced HK-2 cells.

Conclusion: WEL improved renal injury by suppressing inflammation and cell apoptosis through upregulating PTPN2 in HK-2 cells. PTPN2 might be used as a potential therapeutic target for LPS-induced sepsis.
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http://dx.doi.org/10.1177/03000605211012665DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8127797PMC
May 2021

Risk predictive role of hypernatremia for occurrence of sepsis-induced acute kidney injury.

Ann Palliat Med 2021 Apr;10(4):4705-4715

Department of Critical Care Medicine, Beijing Friendship Hospital, Capital Medical University, Beijing, China.

Background: Septic acute kidney injury (AKI), identified when sepsis and AKI present concurrently, is a syndrome of acute function impairment and organ damage, which accounts for ~50% AKI in the intensive care unit (ICU).

Methods: This study retrospectively reviewed 591 patients who were diagnosed with sepsis and admitted to the ICU of Beijing Friendship Hospital from January 2009 to December 2014. According to the concentration of serum sodium, the 591 patients were further divided into 3 groups: normal group, hyponatremia group, and hypernatremia group.

Results: The arterial partial pressure of carbon dioxide (PaCO2, P=0.014), concentration of sodium (Na+, P<0.001), and chloride ion (Cl-, P<0.001), blood urea nitrogen (BUN, P<0.001), acute physiology and chronic health evaluation (APACHE) score (P<0.001), sequential organ failure assessment (SOFA) score (P<0.001), and Glasgow score (P<0.001) showed significant differences. The SOFA score [P=0.040; odds ratio (OR) =1.261], body mass index (BMI, P=0.041; OR =1.229), P content (P=0.032; OR =7.180) and creatine kinase myocardial band (CK-MB, P=0.006; OR =1.168) may be risk factors for occurrence of AKI in patients with hypernatremia. The AKI (P<0.001; OR =6.850) and P content (P=0.027; OR =3.676) may be risk factors for death in patients with hypernatremia. The Na+ suggested a predictive ability for AKI (P<0.001; area under the curve (AUC): 0.586) but not for death (P=0.104).

Conclusions: Hypernatremia is independently associated with an increased risk and has a predictive ability of AKI in patients with sepsis.
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http://dx.doi.org/10.21037/apm-21-792DOI Listing
April 2021

Different diagnostic performance of plasma fibrinogen and D-dimer in periprosthetic joint infection: a propensity score matched study.

BMC Musculoskelet Disord 2021 May 7;22(1):422. Epub 2021 May 7.

Department of Orthopedic Surgery, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Science, Beijing, China.

Background: Fibrinogen (Fbg) and D-dimer have been used as biomarkers for the diagnosis of periprosthetic joint infection (PJI). However, previous research has reported conflicting results on the diagnostic value of D-dimer in comparison to Fbg, C-reactive protein (CRP), and erythrocyte sedimentation rate (ESR).

Aim: This study aimed to: (1) determine the optimal threshold of plasma Fbg and D-dimer in the diagnosis of PJI and compare their diagnostic value to that of CRP and ESR; and (2) investigate whether Fbg and D-dimer perform differently than CRP and ESR as diagnostic indicators for different types of PJI.

Methods: A total of 115 revision cases after total hip arthroplasty (THA) and total knee arthroplasty (TKA) were identified. Based on demographic characteristics, 25 culture-positive cases were matched to 50 culture-negative cases using propensity score matching. Sensitivity, specificity, receiver operating characteristics (ROC), negative predictive value (NPV), and positive predictive value (PPV) were calculated and compared.

Results: The optimal thresholds were 2.72 mg/L for D-dimer, 3.655 g/L for Fbg, 12.64 mg/L for CRP, and 27 mm/h for ESR. Levels of plasma Fbg, D-dimer, CRP, and ESR were significantly higher in the culture-positive group than the culture-negative group. Fbg, D-dimer, CRP, and ESR showed sensitivity of 0.92, 0.56, 0.92, and 0.88, respectively, and showed specificity of 0.84, 0.96, 0.94, and 0.80, respectively. The ROC curve showed that CRP has the highest area under the curve (AUC) (0.94), followed by Fbg (0.90), ESR (0.87), and D-dimer (0.81).

Conclusions: Plasma Fbg exhibited a similar diagnostic performance compared to CRP and ESR in predicting culture-positive results in PJI. Plasma D-dimer showed high specificity but low sensitivity. In our study, Fbg and D-dimer did not show better diagnostic performance with different pathogens and different types of PJI. Further studies are required to investigate the difference between serum D-dimer and plasma D-dimer in the arthroplasty population.
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http://dx.doi.org/10.1186/s12891-021-04282-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8106205PMC
May 2021

Quantum walks on a programmable two-dimensional 62-qubit superconducting processor.

Science 2021 05 6;372(6545):948-952. Epub 2021 May 6.

National Institute of Informatics, 2-1-2 Hitotsubashi, Chiyoda-ku, Tokyo 101-8430, Japan.

Quantum walks are the quantum mechanical analog of classical random walks and an extremely powerful tool in quantum simulations, quantum search algorithms, and even for universal quantum computing. In our work, we have designed and fabricated an 8-by-8 two-dimensional square superconducting qubit array composed of 62 functional qubits. We used this device to demonstrate high-fidelity single- and two-particle quantum walks. Furthermore, with the high programmability of the quantum processor, we implemented a Mach-Zehnder interferometer where the quantum walker coherently traverses in two paths before interfering and exiting. By tuning the disorders on the evolution paths, we observed interference fringes with single and double walkers. Our work is a milestone in the field, bringing future larger-scale quantum applications closer to realization for noisy intermediate-scale quantum processors.
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http://dx.doi.org/10.1126/science.abg7812DOI Listing
May 2021

Ecotoxicological effects of pyraclostrobin on tilapia (Oreochromis niloticus) via various exposure routes.

Environ Pollut 2021 Apr 28;285:117188. Epub 2021 Apr 28.

Shandong Provincial Key Laboratory for Biology of Vegetable Diseases and Insect Pests, Shandong Agricultural University, Tai'an, Shandong, 271018, PR China; College of Plant Protection, Shandong Agricultural University, Tai'an, Shandong, 271018, PR China. Electronic address:

Pyraclostrobin is a widely used and highly efficient fungicide that also has high toxicity to aquatic organisms, especially fish. Although some research has reported the toxic effects of pyraclostrobin on fish, the main toxic pathways of pyraclostrobin in fish remain unclear. The present study has integrated histopathological, biochemical and hematological techniques to reveal the main toxic pathways and mechanisms of pyraclostrobin under different exposure routes. Our results indicated that pyraclostrobin entered fish mainly through the gills. The highest accumulation of pyraclostrobin was observed in the gills and heart compared with accumulation in other tissues and gill tissue showed the most severe damage. Hypoxia symptoms (water jacking, tummy turning and cartwheel formation) in fish were observed throughout the experiment. Taken together, our results suggested that the gills are important target organs. The high pyraclostrobin toxicity to gills might be associated with oxidative damage to the gills, inducing alterations in ventilation frequency, oxygen-carrying substances in blood and disorders of energy metabolism. Our research facilitates a better understanding of the toxic mechanisms of pyraclostrobin in fish, which can promote the ecotoxicological research of agrochemicals on aquatic organisms.
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http://dx.doi.org/10.1016/j.envpol.2021.117188DOI Listing
April 2021

Tumor Microenvironmental Competitive Endogenous RNA Network and Immune Cells Act as Robust Prognostic Predictor of Acute Myeloid Leukemia.

Front Oncol 2021 9;11:584884. Epub 2021 Apr 9.

State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou, China.

Acute myeloid leukemia (AML) is malignant hematologic tumors with frequent recurrence and cause high mortality. Its fate is determined by abnormal intracellular competitive endogenous RNA (ceRNA) network and extracellular tumor microenvironment (TME). This study aims to build a ceRNA network related to AML TME to explore new prognostic and therapeutic targets. The RNA expression data of AML were obtained from The Cancer Genome Atlas (TCGA) database. First, we used the ESTIMATE algorithm to calculate the immune cells and stromal cells infiltration scores in the TME and found that all scores were highly correlated with AML's prognostic characteristics. Subsequently, differentially expressed mRNAs and lncRNAs between high and low score groups were identified to construct a TME-related ceRNA network. Further, the Cox-lasso survival model was employed to screen out the hub prognostic ceRNA network composed of two mRNAs (EPB41L3, COL2A1), three miRNAs (hsa-mir-26a-5p, hsa-mir-148b-3p, hsa-mir-148a-3p), and two lncRNAs (CYP1B1-AS1, C9orf106), and construct nomograms. Finally, we used CIBERSORT algorithm and Kaplan-Meier survival analysis to identify the prognostic TME immune cells and found that naive B cells, M2-type macrophages, and helper follicular T cells were related to prognosis, and the hub ceRNAs were highly correlated with immune cell infiltration. This study provided a new perspective to elucidate how TME regulates AML process and put forward the new therapy strategies combining targeting tumor cells with disintegrating TME.
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http://dx.doi.org/10.3389/fonc.2021.584884DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8063692PMC
April 2021

The study of hydrothermal liquefaction of corn straw with Nano ferrite + inorganic base catalyst system at low temperature.

Bioresour Technol 2021 Aug 16;333:125185. Epub 2021 Apr 16.

Henan Key Laboratory of Rare Earth Functional Materials, Zhoukou, Henan, China.

Hydrothermal liquefaction of corn straw with different catalytic systems and temperatures were investigated in this study. Results showed dual catalytic system can effectively promote the degradation of corn straw at low temperature. With increase of temperature, aqueous phase increased and straw residue decreased for all catalytic systems. The heavy bio-oil yield increased with the increasing of temperature for single catalytic system, while the trend was opposite for dual catalytic system. In single catalytic system, ZnFeO was more suitable for preparation of heavy bio-oil, and the maximum yield reached 34.02 wt% at 180 °C. The proportion of monophenyl compounds in heavy bio-oil for dual catalytic system reached the maximum of 84% at 220 °C with ZnFeO. At 180 °C, the contents of Benzofuran,2,3-dihydro and 2-Methoxy-4-vinylphenol reached the maximum of 31.42% and 17.64% in CoFeO catalyst system, and the maximum yield of Vanillin was 10.82% with ZnFeO.
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http://dx.doi.org/10.1016/j.biortech.2021.125185DOI Listing
August 2021

Risk factors for 28-day mortality in patients with sepsis-related myocardial injury in intensive care units.

J Int Med Res 2021 Apr;49(4):3000605211004759

Department of Critical Care Medicine, Beijing Friendship Hospital, Capital Medical University, Beijing, China.

Objective: This study aimed to identify the risk factors for death in patients with sepsis-related myocardial injury.

Methods: A retrospective study was conducted in 158 patients with sepsis-related myocardial injury in a mixed medical intensive care unit from January 2009 to March 2020. The patients were divided into those who survived and those who died on the basis of whether they survived after 28 days. Demographic and clinical parameters were collected. Multivariate logistic regression was performed.

Results: Sixty-nine (43.7%) patients died within 28 days after admission to the intensive care unit. Multivariate logistic regression analysis showed that the oxygenation index (odds ratio [OR]: 0.979, 95% confidence interval [CI]: 0.970-0.989), acute kidney injury (OR: 4.787, 95% CI: 1.674-13.693), norepinephrine dose (OR: 1.706, 95% CI: 1.375-2.117), and abdominopelvic cavity infection (OR: 0.257, 95% CI: 0.076-0.866) were significantly associated with mortality within 28 days after admission in patients with sepsis-related myocardial injury.

Conclusions: Patients with sepsis-related myocardial injury have a high mortality rate. A high oxygenation index, occurrence of acute kidney injury, high norepinephrine dose, and occurrence of abdominopelvic cavity infection are independent risk factors for 28-day mortality in patients with sepsis-related myocardial injury.
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http://dx.doi.org/10.1177/03000605211004759DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8072103PMC
April 2021

Preparation of Core-Shell Silica Microspheres with Controllable Shell Thickness for Fast High Performance Liquid Chromatography Separation of Alkyl Benzenes and Intact Proteins.

J Biomed Nanotechnol 2021 Mar;17(3):439-446

As it is difficult to prevent secondary nucleation and agglomeration during the preparation of core-shell silica microspheres, these issues have been successfully resolved in this study using template-dissolution-induced redeposition. The non-porous particles are transformed into core-shell silica microspheres (CSSMs) in the presence of cetyltrimethylammonium bromide and octyltrimethylammonium bromide under basic conditions. The shell thickness and pore sizes of the CSSMs are controlled by adjusting the etching time and molar ratio of the template, respectively. The CSSMs are modified using octadecyltrimethylammonium chloride to separate the mixture of alkyl benzenes, and a high column separation efficiency is achieved within two minutes. The CSSMs are used for the separation and analysis of proteins and the digests of bovine serum albumin. The chromatographic column packed with core-shell particles affords a significantly higher separation efficiency than the commercial column. Therefore, as a chromatographic stationary phase, these core-shell particles can potentially be used for the fast separation of proteins, small solutes, and complex samples.
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http://dx.doi.org/10.1166/jbn.2021.3042DOI Listing
March 2021

Core-Shell Poly(l-lactic acid)-Hyaluronic Acid Nanofibers for Cell Culture and Pelvic Ligament Tissue Engineering.

J Biomed Nanotechnol 2021 Mar;17(3):399-406

Pelvic organ prolapse (POP) has become one of the most common serious diseases affecting parous women. Weakening of pelvic ligaments plays an essential role in the pathophysiology of POP. Currently, synthetic materials are widely applied for pelvic reconstructive surgery. However, synthetic nondegradable meshes for POP therapy cannot meet the clinical requirements due to its poor biocompatibility. Herein, we fabricated electrospun core-shell nanofibers of poly(l-lactic acid)-hyaluronic acid (PLLA/HA). After that, we combined them with mouse bone marrow-derived mesenchymal stem cells (mBMSCs) to assess the cellular response and pelvic ligament tissue engineering . The cellular responses on the composite nanofibers showed that the core-shell structure nanofibers displayed with excellent biocompatibility and enhanced cellular activity without cytotoxicity. Moreover, compared with PLLA nanofibers seeded with mBMSCs, PLLA/HA nanofibers exhibited more cellular function, as revealed by the quantitative real-time polymerase chain reaction (RT-qPCR) for pelvic ligament-related gene markers including Col1a1, Col1a3 and Tnc. These features suggested that this novel core-shell nanofiber is promising in stem cell-based tissue engineering for pelvic reconstruction.
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http://dx.doi.org/10.1166/jbn.2021.3057DOI Listing
March 2021

A new robotically assisted system for total knee arthroplasty: A sheep model study.

Int J Med Robot 2021 Apr 14:e2264. Epub 2021 Apr 14.

Department of Orthopaedic Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.

Background: We investigated the accuracy and safety of a new HURWA robotic-assisted total knee arthroplasty (TKA) system in a sheep model.

Methods: Ten male small-tailed Han sheep were used in this study. Sheep were imaged by computed tomography scan before and after bone resection and the cutting errors between actual bone preparation and preoperative planning of the femur and tibia in three dimensions were measured.

Results: The overall accuracies after surgery compared with that from preoperative surgical planning of the left and right femurs were 1.93 ± 1.02° and 1.93 ± 1.23°, respectively. Additionally, similarly high overall accuracies for the left and right tibia of 1.26 ± 1.04 and 1.68 ± 0.92°, respectively, were obtained. The gap distances of the distal cut, anterior chamfer, anterior cut, posterior chamfer and posterior cut on the medial side were 0.47 ± 0.35 mm, 0.41 ± 0.37 mm, 0.12 ± 0.26 mm, 0.41 ± 0.44 mm and 0.12 ± 0.23 mm, respectively. No intraoperative complications, such as intraoperative fracture, massive bleeding or death, occurred.

Conclusion: This new HURWA robotic-assisted TKA system is an accurate and safe tool for TKA surgery based on the sheep model.
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http://dx.doi.org/10.1002/rcs.2264DOI Listing
April 2021

Better precision of a new robotically assisted system for total knee arthroplasty compared to conventional techniques: A sawbone model study.

Int J Med Robot 2021 Apr 10:e2263. Epub 2021 Apr 10.

Department of Orthopaedic Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.

Background: The purpose of this study was to compare the accuracy of this new HURWA robotic-assisted total knee arthroplasty (TKA) technique to the accuracy of the conventional technique in a sawbone model.

Methods: The HURWA robotic-assisted TKA system was applied in the robotic group. After bone resection, all of these sawbones were scanned by the use of a structured light scanning system. Measurements of bone resections, femoral coronal and sagittal measurements, and tibial coronal and sagittal measurements were recorded.

Results: Compared to the conventional technique, the HURWA robotic-assisted system significantly improved the accuracy of the bone resection levels and angles. In the robotic group, the accuracy of all of the bone resection levels was below 0.6 mm (with standard deviation [SD] below 0.6 mm), and all of the bone resection angles were below 0.6° (with SD below 0.4°).

Conclusion: Our data suggest that this novel HURWA robotic-assisted system can significantly improve the accuracy of bone resection levels and angles.
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http://dx.doi.org/10.1002/rcs.2263DOI Listing
April 2021

Co-Delivery of Paclitaxel and siRNA with pH-Responsive Polymeric Micelles for Synergistic Cancer Therapy.

J Biomed Nanotechnol 2021 Feb;17(2):322-329

Henan Eye Hospital, Henan Provincial People's Hospital, People's Hospital of Zhengzhou University, Zhengzhou 450003, P. R. China.

Due to the complex physiological characteristics of tumors, chemotherapy or gene therapy alone cannot completely kill tumor cells. Therefore, combining chemotherapy with gene therapy for combination therapy is the key to solving this problem. However, there are still significant challenges in how to simultaneously deliver and rapidly release the drugs and siRNA into cancer cells. In this work, a triblock copolymer was synthesized to co-deliver siRNA and paclitaxel to tumor cells. This system has an acid-sensitive subsurface layer, which can not only load siRNA to prevent premature drug release but also has good controlled release performance. experiments showed that polymeric vectors can efficiently deliver siRNA and paclitaxel simultaneously into tumor cells for rapid release within the tumor cells. This study reveals that this novel polymeric micelle is a suitable vector for the codelivery of chemotherapeutic drugs and siRNA to cancer cells, representing an important advance in nanotechnology, nanomedicine, drug delivery, and cancer therapy.
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http://dx.doi.org/10.1166/jbn.2021.3039DOI Listing
February 2021

Encapsulation state of messenger RNA inside lipid nanoparticles.

Biophys J 2021 Mar 25. Epub 2021 Mar 25.

Moderna, Inc., Cambridge, Massachusetts.

Understanding the structure of messenger RNA (mRNA) lipid nanoparticles, and specifically the microenvironment of the mRNA molecules within these entities, is fundamental to advancing their biomedical potential. Here, we show that a permeating cationic dye, thionine, can serve as a cryogenic electron microscopy contrasting agent by binding selectively to encapsulated mRNA without disturbing lipid nanoparticle morphology. Cryo-electron microscopy images identify the mRNA location, revealing that mRNA may exist within solvent-filled cavities or may be substantially lipid associated.
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http://dx.doi.org/10.1016/j.bpj.2021.03.012DOI Listing
March 2021

Study on Relationships of Tumor Status and Gene Polymorphism With Blood Concentration of MTX and Toxicities in 63 Pediatric Mature B Cell Lymphoma in Chinese Population.

Technol Cancer Res Treat 2021 Jan-Dec;20:1533033821995288

Pathology Department, 117984Beijing Children's Hospital, Capital Medical University, National Center for Children's Health, Beijing, China.

Objective: This study investigated the relationships of tumor status (stage, renal involvement, bone marrow status, bulky disease, liver function), tumor gene polymorphism, and methotrexate (MTX) dosage (stratified by treatment group) with blood MTX levels and adverse reactions (ADR).

Methods: We retrospectively reviewed 63 mature B cell lymphoma patients who were treated in our center. Genotyping of the MTHFR 677 and SLCO1B1 genes was carried out, and the relationships between tumor status, polymorphism of the genes, MTX level, and ADR were analyzed.

Results: Altogether, 63 children were included. The mean blood MTX concentration was 0.25 ± 0.2 umol/L at 45 h. Liver dysfunction and bulky disease were both correlated with MTX level (both P < 0.05). ADRs were higher among patients with blood MTX > 0.5 mmol/l at 45 h than for the groups with lower blood MTX. The MTHFR 677 CT genotype was correlated with liver function damage (P = 0.04); the rs11045879 locus CC genotype of SLCO1B1, stage IV, and bulky disease at the time of diagnosis were correlated with 4° neutropenia (P < 0.05). Stage IV, bulky disease, leukemia stage at the time of diagnosis, and C2 treatment group were correlated with severe anemia (P < 0.05). Stage IV, bulky disease, leukemia stage, renal invasion at the time of diagnosis, and C2 treatment group were associated with severe thrombocytopenia (P < 0.05). Bulky disease and renal invasion at the time of diagnosis were associated with severe mucositis and severe infection (P < 0.05).

Conclusion: Taken together, our data demonstrate that gene polymorphism, MTX levels, tumor status, and treatment group might be useful to optimize MTX therapy and estimate toxicity.
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http://dx.doi.org/10.1177/1533033821995288DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8010844PMC
March 2021

Emulating Quantum Teleportation of a Majorana Zero Mode Qubit.

Phys Rev Lett 2021 Mar;126(9):090502

Hefei National Laboratory for Physical Sciences at the Microscale and Department of Modern Physics, University of Science and Technology of China, Hefei 230026, China.

Topological quantum computation based on anyons is a promising approach to achieve fault-tolerant quantum computing. The Majorana zero modes in the Kitaev chain are an example of non-Abelian anyons where braiding operations can be used to perform quantum gates. Here we perform a quantum simulation of topological quantum computing, by teleporting a qubit encoded in the Majorana zero modes of a Kitaev chain. The quantum simulation is performed by mapping the Kitaev chain to its equivalent spin version and realizing the ground states in a superconducting quantum processor. The teleportation transfers the quantum state encoded in the spin-mapped version of the Majorana zero mode states between two Kitaev chains. The teleportation circuit is realized using only braiding operations and can be achieved despite being restricted to Clifford gates for the Ising anyons. The Majorana encoding is a quantum error detecting code for phase-flip errors, which is used to improve the average fidelity of the teleportation for six distinct states from 70.76±0.35% to 84.60±0.11%, well beyond the classical bound in either case.
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http://dx.doi.org/10.1103/PhysRevLett.126.090502DOI Listing
March 2021

Treatment outcome in children with central nervous system-positive Burkitt lymphoma using only intrathecal and systemic chemotherapy combined with rituximab.

Chin Med J (Engl) 2021 Mar 17;134(11):1329-1334. Epub 2021 Mar 17.

Beijing Key Laboratory of Pediatric Haematology Oncology, National Discipline of Pediatrics, Ministry of Education, MOE Key Laboratory of Major Diseases in Children, Haematology Oncology Center, Beijing Children's Hospital, Beijing 100045, China.

Background: With current chemotherapy treatment, >90% of survival has been obtained for Burkitt lymphoma (BL). In this study, the demographic characteristics and treatment outcomes are presented for 78 children in China with central nervous system-positive (CNS+) BL.

Methods: This retrospective study consecutively enrolled 78 CNS+ BL patients in Beijing Children's Hospital (BCH) from 2007 to 2019 who received the BCH B-cell non-Hodgkin's lymphoma regimen (modified by French-American-British mature lymphoma B-cell 96 [FAB/LMB96] C1 arm ± rituximab). Clinical characteristics, methods of disease detection in the CNS, and outcomes were evaluated. Univariate and multivariate analyses were used to assess prognostic factors.

Results: The median age of 65 boys and 13 girls at the time of diagnosis was 5.7 years (ranging from 1 to 14 years). Patients were followed up for a median time of 34 months (ranging from 1 to 72 months). Bone marrow invasion was found in 38 (48.7%) patients. There were 48 (61.5%), 44 (56.4%), and 25 (32%) patients with cranial nerve palsy, intracerebral mass (ICM), and para-meningeal extension, respectively. Abnormal cerebrospinal fluid (CSF) morphology and CSF immunophenotype appeared in 15 (19.2%) and 15 (19.2%) patients, respectively. There were 69 (88.5%) patients treated with chemotherapy combined with rituximab, and nine patients were treated solely with chemotherapy. Finally, five patients died of treatment-related infection, recurrence occurred for 13, and one developed a second tumor. The 3-year overall survival and event-free survival rates were 78.9% ± 4.7% and 71.4% ± 6.0%, respectively. Treatment with chemotherapy only, ICM positivity, and >4 organs involved at diagnosis were independent risk factors.

Conclusions: Rituximab combined with a modified LMB96 regimen has greatly increased the efficacy of treatment for Chinese children with CNS+ BL, and with the continuous collection of outcome data, treatment-related complications are decreasing. For further verification, a large sample multicentre randomized controlled study should be performed to explore a treatment scheme for Chinese children with even greater efficacy.
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http://dx.doi.org/10.1097/CM9.0000000000001386DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8183724PMC
March 2021