Publications by authors named "Fei Zhou"

770 Publications

Acute toxicity, 28-day repeated-dose toxicity and toxicokinetic study of timosaponin BII in beagle dogs.

J Asian Nat Prod Res 2021 Oct 26:1-17. Epub 2021 Oct 26.

School of Pharmaceutical Sciences, Zhejiang Chinese Medical University, Hangzhou 310053, China.

The safety evaluation of timosaponin BII (TBII) in beagle dogs with toxicokinetic study was performed. For the acute oral toxicity study, the minimum lethal dose (MLD) of TBII was more than 2000 mg/kg and suggested the characteristics of absorption saturation. For the 28-day repeated dose oral toxicity and toxicokinetic studies, there was no significant effect on all test parameters except for prolonged APTT in the 60 and 180 mg/kg groups, which recovered after withdrawal. The increase of drug exposure of 180 mg/kg group was not proportional to the increase of administration dose, showing the characteristics of absorption saturation.
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http://dx.doi.org/10.1080/10286020.2021.1993834DOI Listing
October 2021

Bio-inspired low-tortuosity carbon host for high-performance lithium-metal anode.

Natl Sci Rev 2019 Mar 26;6(2):247-256. Epub 2018 Nov 26.

Department of Chemistry, CAS Center for Excellence in Nanoscience, Hefei Science Center of CAS, University of Science and Technology of China, Hefei 230026, China.

Lithium metal is one of the most promising anode materials for high-energy-density Li batteries. However, low stability caused by dendrite growth and volume change during cycling hinders its practical application. Herein, we report an ingenious design of bio-inspired low-tortuosity carbon with tunable vertical micro-channels to be used as a host to incorporate nanosized Sn/Ni alloy nucleation sites, which can guide Li metal's plating/stripping and meanwhile accommodate the volume change. The pore sizes of the vertical channels of the carbon host can be regulated to investigate the structure-performance correlation. After compositing Li, the bio-inspired carbon host with the smallest pore size (∼14 μm) of vertical channels exhibits the lowest overpotential (∼18 mV at 1 mA cm), most stable tripping/plating voltage profiles, and best cycling stability (up to 500 cycles) in symmetrical cells. Notably, the carbon/Li composite anode is more rewarding than Li foil when coupled with LiFePO in full cells, exhibiting a much lower polarization effect, better rate capability and higher capacity retention (90.6% after 120 cycles). This novel bio-inspired design of a low-tortuosity carbon host with nanoalloy coatings may open a new avenue for fabricating advanced Li-metal batteries with high performance.
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http://dx.doi.org/10.1093/nsr/nwy148DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8291544PMC
March 2019

A Vimentin-Targeting Oral Compound with Host-Directed Antiviral and Anti-Inflammatory Actions Addresses Multiple Features of COVID-19 and Related Diseases.

mBio 2021 Oct 12:e0254221. Epub 2021 Oct 12.

Jiangsu Key Laboratory of Neuropsychiatric Diseases and Cambridge-Su Genomic Resource Center, Medical School of Soochow University, Suzhou, Jiangsu, China.

Damage in COVID-19 results from both the SARS-CoV-2 virus and its triggered overactive host immune responses. Therapeutic agents that focus solely on reducing viral load or hyperinflammation fail to provide satisfying outcomes in all cases. Although viral and cellular factors have been extensively profiled to identify potential anti-COVID-19 targets, new drugs with significant efficacy remain to be developed. Here, we report the potent preclinical efficacy of ALD-R491, a vimentin-targeting small molecule compound, in treating COVID-19 through its host-directed antiviral and anti-inflammatory actions. We found that by altering the physical properties of vimentin filaments, ALD-491 affected general cellular processes as well as specific cellular functions relevant to SARS-CoV-2 infection. Specifically, ALD-R491 reduced endocytosis, endosomal trafficking, and exosomal release, thus impeding the entry and egress of the virus; increased the microcidal capacity of macrophages, thus facilitating the pathogen clearance; and enhanced the activity of regulatory T cells, therefore suppressing the overactive immune responses. In cultured cells, ALD-R491 potently inhibited the SARS-CoV-2 spike protein and human ACE2-mediated pseudoviral infection. In aged mice with ongoing, productive SARS-CoV-2 infection, ALD-R491 reduced disease symptoms as well as lung damage. In rats, ALD-R491 also reduced bleomycin-induced lung injury and fibrosis. Our results indicate a unique mechanism and significant therapeutic potential for ALD-R491 against COVID-19. We anticipate that ALD-R491, an oral, fast-acting, and non-cytotoxic agent targeting the cellular protein with multipart actions, will be convenient, safe, and broadly effective, regardless of viral mutations, for patients with early- or late-stage disease, post-COVID-19 complications, and other related diseases. With the Delta variant currently fueling a resurgence of new infections in the fully vaccinated population, developing an effective therapeutic drug is especially critical and urgent in fighting COVID-19. In contrast to the many efforts to repurpose existing drugs or address only one aspect of COVID-19, we are developing a novel agent with first-in-class mechanisms of action that address both the viral infection and the overactive immune system in the pathogenesis of the disease. Unlike virus-directed therapeutics that may lose efficacy due to viral mutations, and immunosuppressants that require ideal timing to be effective, this agent, with its unique host-directed antiviral and anti-inflammatory actions, can work against all variants of the virus, be effective during all stages of the disease, and even resolve post-disease damage and complications. Further development of the compound will provide an important tool in the fight against COVID-19 and its complications, as well as future outbreaks of new viruses.
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http://dx.doi.org/10.1128/mBio.02542-21DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8510534PMC
October 2021

FLT4/VEGFR3 activates AMPK to coordinate glycometabolic reprogramming with autophagy and inflammasome activation for bacterial elimination.

Autophagy 2021 Oct 10:1-16. Epub 2021 Oct 10.

State Key Laboratory of Cell Biology, Cas Center for Excellence in Molecular Cell Science, Shanghai Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences, University of Chinese Academy of Sciences, Shanghai, China.

Macrophages rapidly undergo glycolytic reprogramming in response to macroautophagy/autophagy, inflammasome activation and pyroptosis for the clearance of bacteria. Identification the key molecules involved in these three events will provide critical potential therapeutic applications. Upon infection, FLT4/VEGFR3 and its ligand VEGFC were inducibly expressed in macrophages, and FLT4 signaling inhibited CASP1 (caspase 1)-dependent inflammasome activation and pyroptosis but enhanced MAP1LC3/LC3 activation for elimination of the bacteria. Consistently, FLT4 mutants lacking the extracellular ligand-binding domain increased production of the proinflammatory metabolites such as succinate and lactate, and reduced antimicrobial metabolites including citrate and NAD(P)H in macrophages and liver upon infection. Mechanistically, FLT4 recruited AMP-activated protein kinase (AMPK) and phosphorylated Y247 and Y441/442 in the PRKAA/alpha subunit for AMPK activation. The AMPK agonist AICAR could rescue glycolytic reprogramming and inflammasome activation in macrophages expressing the mutant FLT4, which has potential translational application in patients carrying mutations to prevent recurrent infections. Collectively, we have elucidated that the FLT4-AMPK module in macrophages coordinates glycolytic reprogramming, autophagy, inflammasome activation and pyroptosis to eliminate invading bacteria.
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http://dx.doi.org/10.1080/15548627.2021.1985338DOI Listing
October 2021

Design and synthesis of novel tacrine-dipicolylamine dimers that are multiple-target-directed ligands with potential to treat Alzheimer's disease.

Bioorg Chem 2021 Nov 4;116:105387. Epub 2021 Oct 4.

Translational Medicine Center of Pain, Emotion and Cognition, Ningbo Key Laboratory of Behavioral Neuroscience, Zhejiang Provincial Key Laboratory of Pathophysiology, School of Medicine, Ningbo University, Ningbo 315211, China. Electronic address:

Alzheimer's disease (AD) is a prevalent neurodegenerative disorder that has multiple causes. Therefore, multiple-target-directed ligands (MTDLs), which act on multiple targets, have been developed as a novel strategy for AD therapy. In this study, novel drug candidates were designed and synthesized by the covalent linkings of tacrine, a previously used anti-AD acetylcholinesterase (AChE) inhibitor, and dipicolylamine, an β-amyloid (Aβ) aggregation inhibitor. Most tacrine-dipicolylamine dimers potently inhibited AChE and Aβ aggregation in vitro, and 13a exhibited nanomolar level inhibition. Molecular docking analysis suggested that 13a could interact with the catalytic active sites and the peripheral anion site of AChE, and bind to Aβ pentamers. Moreover, 13a effectively attenuated Aβ oligomers-induced cognitive dysfunction in mice by activating the cAMP-response element binding protein/brain-derived neurotrophic factor signaling pathway, decreasing tau phosphorylation, preventing synaptic toxicity, and inhibiting neuroinflammation. The safety profile of 13a in mice was demonstrated by acute toxicity experiments. All these results suggested that novel tacrine-dipicolylamine dimers, especially 13a, have multi-target neuroprotective and cognitive-enhancing potentials, and therefore might be developed as MTDLs to combat AD.
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http://dx.doi.org/10.1016/j.bioorg.2021.105387DOI Listing
November 2021

All optical metropolitan quantum key distribution network with post-quantum cryptography authentication.

Opt Express 2021 Aug;29(16):25859-25867

Quantum key distribution (QKD) provides information theoretically secure key exchange requiring authentication of the classic data processing channel via pre-sharing of symmetric private keys to kick-start the process. In previous studies, the lattice-based post-quantum digital signature algorithm Aigis-Sig, combined with public-key infrastructure (PKI), was used to achieve high-efficiency quantum security authentication of QKD, and we have demonstrated its advantages in simplifying the MAN network structure and new user entry. This experiment further integrates the PQC algorithm into the commercial QKD system, the Jinan field metropolitan QKD network comprised of 14 user nodes and 5 optical switching nodes, and verifies the feasibility, effectiveness and stability of the post-quantum cryptography (PQC) algorithm and advantages of replacing trusted relays with optical switching brought by PQC authentication large-scale metropolitan area QKD network. QKD with PQC authentication has potential in quantum-secure communications, specifically in metropolitan QKD networks.
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http://dx.doi.org/10.1364/OE.432944DOI Listing
August 2021

Clinical significance of circulating tumour cells and tumour marker detection in the chemotherapeutic evaluation of advanced colorectal cancer.

Colorectal Dis 2021 Oct 6. Epub 2021 Oct 6.

Department of Oncology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.

Aim: Systemic chemotherapy combining biological targeted therapies is the standard therapy for patients with metastatic colorectal cancer (mCRC), but effective markers are needed to identify clinical responders. Circulating tumour cells (CTCs) have been associated with prognosis in patients with mCRC. This study aimed to explore the relationship between CTC number and the clinical response of patients with advanced CRC.

Method: Epithelial cell adhesion molecule-independent enrichment and CD45 fluorescence in situ hybridization immunofluorescence were used to detect peripheral blood CTCs in 79 patients with advanced CRC. Fisher's exact test and Spearman's rank correlation coefficient were used to analyse the correlation between CTC number and efficacy of chemotherapy. Kaplan-Meier and Cox regression analyses were used to evaluate progression-free survival (PFS).

Results: Among the evaluable patients, CTCs were significantly correlated with clinical response (r =4.891, p = 0.031). High CTC numbers were associated with a poor treatment response (r = -0.250, p = 0.027). Dynamic decrease in CTC number was associated with clinical response (p = 0.046). High baseline CTC number and carcinoembryonic antigen levels were prognostic factors for unfavourable PFS in multivariable analysis [hazard ratio (HR) = 3.30, p = 0.011 and HR = 2.04, p = 0.044, respectively]. Compared with the CTC-positive group, the CTC-negative group showed superior PFS (median PFS 15.53 vs. 9.43 months, p = 0.041) among CRC patients receiving first-line treatment.

Conclusion: CTC number is a feasible biomarker for predicting outcomes in mCRC patients receiving systemic chemotherapy.
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http://dx.doi.org/10.1111/codi.15939DOI Listing
October 2021

Parkin Prevents Glutamate Excitotoxicity Through Inhibiting NLRP3 Inflammasome in Retinal Ganglion Cells.

Neuroscience 2021 Sep 30. Epub 2021 Sep 30.

Department of Ophthalmology, Xijing Hospital, the Fourth Military Medical University, 15 Changle West Road, Xi'an 71032, People's Republic of China. Electronic address:

Glutamate excitotoxicity is one of the important pathophysiological culprits in retinal ganglion cells (RGCs) damage after acute optic nerve injury such as traumatic optic neuropathies and glaucoma. It is necessary to elucidate the mechanism of glutamate injury to RGCs in order to find the relevant neuroprotector. In this study, it was observed that the expression of Parkin increased and peaked at 24 h after glutamate injury to RGCs. Moreover, upregulating Parkin attenuated glutamate induced apoptosis, mitochondrial dysfunction and oxidative stress. And, it was found that Parkin could exert neuroprotective effects on RGCs by inhibiting nucleotide-binding domain leucine-rich repeat containing family pyrin domain containing 3 (NLRP3) inflammasome. Moreover, the genetic and pharmacological downregulation of NLRP3 improved survival of RGCs against glutamate excitotoxicity. In the end, knockdown of Parkin exacerbated glutamate induced RGCs damage via triggering NLRP3 inflammasome activation. Taken together, these results shed light on the promising molecular targets for the prevention and treatment of acute optic nerve injury.
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http://dx.doi.org/10.1016/j.neuroscience.2021.09.018DOI Listing
September 2021

C-reactive protein or procalcitonin combined with rhinorrhea for discrimination of viral from bacterial infections in hospitalized adults in non-intensive care units with lower respiratory tract infections.

BMC Pulm Med 2021 Sep 28;21(1):308. Epub 2021 Sep 28.

Institute of Respiratory Medicine, Chinese Academy of Medical Science, Beijing, China.

Background: Whether procalcitonin (PCT) or C-reactive protein (CRP) combined with certain clinical characteristics can better distinguish viral from bacterial infections remains unclear. The aim of the study was to assess the ability of PCT or CRP combined with clinical characteristics to distinguish between viral and bacterial infections in hospitalized non-intensive care unit (ICU) adults with lower respiratory tract infection (LRTI).

Methods: This was a post-hoc analysis of a randomized clinical trial previously conducted among LRTI patients. The ability of PCT, CRP and PCT or CRP combined with clinical symptoms to discriminate between viral and bacterial infection were assessed by portraying receiver operating characteristic (ROC) curves among patients with only a viral or a typical bacterial infection.

Results: In total, 209 infected patients (viral 69%, bacterial 31%) were included in the study. When using CRP or PCT to discriminate between viral and bacterial LRTI, the optimal cut-off points were 22 mg/L and 0.18 ng/mL, respectively. When the optimal cut-off for CRP (≤ 22 mg/L) or PCT (≤ 0.18 ng/mL) combined with rhinorrhea was used to discriminate viral from bacterial LRTI, the AUCs were 0.81 (95% CI: 0.75-0.87) and 0.80 (95% CI: 0.74-0.86), which was statistically significantly better than when CRP or PCT used alone (p < 0.001). When CRP ≤ 22 mg/L, PCT ≤ 0.18 ng/mL and rhinorrhea were combined, the AUC was 0.86 (95% CI: 0.80-0.91), which was statistically significantly higher than when CRP (≤ 22 mg/L) or PCT (≤ 0.18 ng/mL) was combined with rhinorrhea (p = 0.011 and p = 0.021).

Conclusions: Either CRP ≤ 22 mg/L or PCT ≤ 0.18 ng/mL combined with rhinorrhea could help distinguish viral from bacterial infections in hospitalized non-ICU adults with LRTI. When rhinorrhea was combined together, discrimination ability was further improved.
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http://dx.doi.org/10.1186/s12890-021-01672-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8478003PMC
September 2021

Ferulic Acid Ameliorates Hepatic Inflammation and Fibrotic Liver Injury by Inhibiting PTP1B Activity and Subsequent Promoting AMPK Phosphorylation.

Front Pharmacol 2021 8;12:754976. Epub 2021 Sep 8.

School of Life Sciences, Beijing University of Chinese Medicine, Beijing, China.

Chronic inflammation in response to persistent exogenous stimuli or damage results in liver fibrosis, which subsequently progresses into malignant liver diseases with high morbidity and mortality. Ferulic acid (FA) is a phenolic acid widely isolated from abundant plants and exhibits multiple biological activities including anti-oxidant, anti-inflammation and enhancement of immune responses. Adenosine monophosphate-activated protein kinase (AMPK) functions as a critical energy sensor and is regulated through the phosphorylation of liver kinases like LKB1 or dephosphorylation by protein tyrosine phosphatases (PTPs). However, the role of FA in carbon tetrachloride (CCl)-induced chronic inflammation and liver fibrosis and AMPK activation has not been elucidated. Here we reported that FA ameliorated CCl-induced inflammation and fibrotic liver damage in mice as indicated by reduced levels of serum liver function enzyme activities and decreased expression of genes and proteins associated with fibrogenesis. Additionally, FA inhibited hepatic oxidative stress, macrophage activation and HSC activation via AMPK phosphorylation in different liver cells. Mechanically, without the participation of LKB1, FA-induced anti-inflammatory and anti-fibrotic effects were abrogated by a specific AMPK inhibitor, compound C. Combining with the results of molecular docking, surface plasmon resonance and co-immunoprecipitation assays, we further demonstrated that FA directly bound to and inhibited PTP1B, an enzyme responsible for dephosphorylating key protein kinases, and eventually leading to the phosphorylation of AMPK. In summary, our results indicated that FA alleviated oxidative stress, hepatic inflammation and fibrotic response in livers through PTP1B-AMPK signaling pathways. Taken together, we provide novel insights into the potential of FA as a natural product-derived therapeutic agent for the treatment of fibrotic liver injury.
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http://dx.doi.org/10.3389/fphar.2021.754976DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8455917PMC
September 2021

An intermittent detachment faulting system with a large sulfide deposit revealed by multi-scale magnetic surveys.

Nat Commun 2021 Sep 24;12(1):5642. Epub 2021 Sep 24.

Key Laboratory of Submarine Geosciences, MNR, Second Institute of Oceanography, MNR, Hangzhou, 310012, China.

Magmatic and tectonic processes can contribute to discontinuous crustal accretion and play an important role in hydrothermal circulation at ultraslow-spreading ridges, however, it is difficult to accurately describe the processes without an age framework to constrain crustal evolution. Here we report on a multi-scale magnetic survey that provides constraints on the fine-scale evolution of a detachment faulting system that hosts hydrothermal activity at 49.7°E on the Southwest Indian Ridge. Reconstruction of the multi-stage detachment faulting history shows a previous episode of detachment faulting took place 0.76~1.48 My BP, while the present fault has been active for the past ~0.33 My and is just in the prime of life. This fault sustains hydrothermal circulation that has the potential for developing a large sulfide deposit. High resolution multiscale magnetics allows us to constrain the relative balance between periods of detachment faulting and magmatism to better describe accretionary processes on an ultraslow spreading ridge.
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http://dx.doi.org/10.1038/s41467-021-25880-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8463574PMC
September 2021

Chemotherapy Should Be Combined With Checkpoint Inhibitors in the Treatment of Patients With Stage IV EGFR-Mutant NSCLC Whose Disease Has Progressed on All Available Tyrosine Kinase Inhibitors.

J Thorac Oncol 2021 10;16(10):1622-1626

Department of Medical Oncology, Shanghai Pulmonary Hospital, Thoracic Cancer Institute, School of Medicine, Tongji University, Shanghai, People's Republic of China. Electronic address:

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http://dx.doi.org/10.1016/j.jtho.2021.07.011DOI Listing
October 2021

Vision loss as the initial presentation during primary pulmonary hypertension treatment.

Int J Ophthalmol 2021 18;14(9):1460-1462. Epub 2021 Sep 18.

The First College of Clinical Medical Science, China Three Gorges University, Yichang 443002, Hubei Province, China.

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http://dx.doi.org/10.18240/ijo.2021.09.26DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8403845PMC
September 2021

miR-139/PDE2A-Notch1 feedback circuit represses stemness of gliomas by inhibiting Wnt/β-catenin signaling.

Int J Biol Sci 2021 12;17(13):3508-3521. Epub 2021 Aug 12.

State Key Laboratory of Cancer Biology, Department of Medical Genetics and Developmental Biology, Fourth Military Medical University, Xi'an 710032, China.

The malignant phenotypes of glioblastomas (GBMs) are primarily attributed to glioma stem cells (GSCs). Our previous study and other reports have suggested that both miR-139 and its host gene PDE2A are putative antitumor genes in various cancers. The aim of this study was to investigate the roles and mechanisms of miR-139/PDE2A in GSC modulation. Clinical samples were used to determine miR-139/PDE2A expression. Patient-derived glioma stem-like cells (PD-GSCs) were stimulated for immunofluorescent staining, sphere formation assays and orthotopic GBM xenograft models. Bioinformatic analysis and further experiments demonstrated the downstream molecular mechanisms of miR-139 and PDE2A. OX26/CTX-conjugated PEGylated liposome (OCP) was constructed to deliver miR-139 or PDE2A into glioma tissue specifically. We demonstrated that miR-139 was concomitantly transcribed with its host gene PDE2A. Both PDE2A and miR-139 indicated better prognosis of gliomas and were inversely correlated with GSC stemness. PDE2A or miR-139 overexpression suppressed the stemness of PD-GSCs. FZD3 and β-catenin, which induced Wnt/β-catenin signaling activation, were identified as targets of miR-139 and mediated the effects of miR-139 on GSCs. Meanwhile, PDE2A suppressed Wnt/β-catenin signaling by inhibiting cAMP accumulation and GSK-3β phosphorylation, thereby modulating the self-renewal of PD-GSCs. Notably, Notch1, which is also a target of miR-139, suppressed PDE2A/miR-139 expression directly via downstream Hes1, indicating that miR-139 promoted its own expression by the miR-139-Notch1/Hes1 feedback circuit. Expectedly, targeted overexpression miR-139 or PDE2A in glioma with OCP system significantly repressed the stemness and decelerated glioma progression. Our findings elaborate on the inhibitory functions of PDE2A and miR-139 on GSC stemness and tumorigenesis, which may provide new prognostic markers and therapeutic targets for GBMs.
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http://dx.doi.org/10.7150/ijbs.62858DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8416740PMC
August 2021

Clinical effect of TESSYS technique under spinal endoscopy combined with drug therapy in patients with lumbar disc herniation and its effect on quality of life and serum inflammatory factors: results of a randomized trial.

Ann Palliat Med 2021 Aug;10(8):8728-8736

Department of Spinal Orthopedics, The Second People's Hospital of Dongying, Dongying, China.

Background: This study was carried out based on the background that lumbar disc herniation seriously affects patients' quality of life but its clinical treatment effect remains unsatisfactory.

Methods: In total, 140 patients with lumbar disc herniation are randomly divided into a single operation group (SO) and a combined treatment group (CT). Among them, patients in the SO group received single treatment of TESSYS technique under spinal endoscopy, while patients in the CT group received combined drug therapy including coenzyme A, adenosine triphosphate, 10% glucose injection, 10% potassium chloride, vitamin B6, vitamin B12, dexamethasone, 20% mannitol and traditional Chinese medicine on the basis of the SO group. The clinical effect, Japanese Orthopaedic Association (JOA) score, visual analogue scale (VAS), recurrence rate, levels of interleukin-1β (IL-1β), interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α), and quality of life score were compared between the two groups.

Results: The treatment effectiveness rate of the CT group was markedly better than that in the SO group (P<0.01). At 3- and 6-month postoperatively, the JOA scores, VAS scores, World Health Organization Quality of Life Brief Questionnaire (WHOQOL-BREF) and the levels of IL-1β, IL-6, and TNF-α in the CT group were significantly better than those in the SO group (P<0.05). During the 6-12-month follow-up, the recurrence rate and WHOQOL-BREF scores in the SO group and CT group was no statistical difference (P>0.05).

Conclusions: TESSYS technique under spinal endoscopy combined with drug therapy in the treatment of lumbar disc herniation has a significant clinical effect. Therefore, it is worthy of clinical popularization.

Trial Registration: Chinese Clinical Trial Registry ChiCTR2100049153.
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http://dx.doi.org/10.21037/apm-21-1282DOI Listing
August 2021

Lithium Fluoride in Electrolyte for Stable and Safe Lithium-Metal Batteries.

Adv Mater 2021 Oct 3;33(42):e2102134. Epub 2021 Sep 3.

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

Electrolyte engineering via fluorinated additives is promising to improve cycling stability and safety of high-energy Li-metal batteries. Here, an electrolyte is reported in a porous lithium fluoride (LiF) strategy to enable efficient carbonate electrolyte engineering for stable and safe Li-metal batteries. Unlike traditionally engineered electrolytes, the prepared electrolyte in the porous LiF nanobox exhibits nonflammability and high electrochemical performance owing to strong interactions between the electrolyte solvent molecules and numerous exposed active LiF (111) crystal planes. Via cryogenic transmission electron microscopy and X-ray photoelectron spectroscopy depth analysis, it is revealed that the electrolyte in active porous LiF nanobox involves the formation of a high-fluorine-content (>30%) solid electrolyte interphase layer, which enables very stable Li-metal anode cycling over one thousand cycles under high current density (4 mA cm ). More importantly, employing the porous LiF nanobox engineered electrolyte, a Li || LiNi Co Mn O pouch cell is achieved with a specific energy of 380 Wh kg for stable cycling over 80 cycles, representing the excellent performance of the Li-metal pouch cell using practical carbonate electrolyte. This study provides a new electrolyte engineering strategy for stable and safe Li-metal batteries.
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http://dx.doi.org/10.1002/adma.202102134DOI Listing
October 2021

RecQ-like helicase 4 (RECQL4) exacerbates resistance to oxaliplatin in colon adenocarcinoma via activation of the PI3K/AKT signaling pathway.

Bioengineered 2021 12;12(1):5859-5869

Department of Colorectal Surgery, Jiangsu Provincial People's Hospital, China.

Oxaliplatin (OXA) resistance is a great challenge for colon adenocarcinoma (COAD) chemotherapy. The promoting role of RecQ-Like Helicase 4 (RECQL4) in chemoresistance to platinum-based drugs has been identified, whereas the effect and specific mechanism of RECQL4 in regulating OXA resistance within COAD have not been explicated yet. In this work, RECQL4 mRNA expression was detected by RT-qPCR. RECQL4, phosphorylated PI3K (p-PI3K), PI3K, phosphorylated AKT (p-AKT), and AKT protein expression were measured by western blotting. CCK-8, flow cytometry, wound healing, and transwell assays were utilized to analyze OXA resistance, cell proliferation, apoptosis, cell cycle, migration and invasion. Herein, we found RECQL4 was upregulated in COAD, especially in OXA-resistant COAD tissues and cells. RECQL4 overexpression facilitated proliferation and metastasis of OXA-resistant COAD cells; on the contrary, RECQL4 knockdown attenuated proliferative and metastatic capabilities in OXA-resistant COAD cells. Moreover, RECQL4 promoted OXA resistance in OXA-resistant COAD cells via activating the P13 K/AKT signaling. To sum up, the results suggest that RECQL4 depletion may be a crucial mechanism to reverse OXA resistance in COAD via inhibition of the P13 K/AKT pathway in vitro, thereby providing a novel target for overcoming OXA resistance in COAD.
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http://dx.doi.org/10.1080/21655979.2021.1964156DOI Listing
December 2021

Structural Basis and Mode of Action for Two Broadly Neutralizing Antibodies Against SARS-CoV-2 Emerging Variants of Concern.

bioRxiv 2021 Aug 3. Epub 2021 Aug 3.

Emerging variants of concern for the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can transmit more efficiently and partially evade protective immune responses, thus necessitating continued refinement of antibody therapies and immunogen design. Here we elucidate the structural basis and mode of action for two potent SARS-CoV-2 Spike (S) neutralizing monoclonal antibodies CV3-1 and CV3-25 that remained effective against emerging variants of concern in vitro and in vivo. CV3-1 bound to the (485-GFN-487) loop within the receptor-binding domain (RBD) in the "RBD-up" position and triggered potent shedding of the S1 subunit. In contrast, CV3-25 inhibited membrane fusion by binding to an epitope in the stem helix region of the S2 subunit that is highly conserved among β-coronaviruses. Thus, vaccine immunogen designs that incorporate the conserved regions in RBD and stem helix region are candidates to elicit pan-coronavirus protective immune responses.
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http://dx.doi.org/10.1101/2021.08.02.454546DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8351775PMC
August 2021

The Role of Circulating Tumor DNA in Advanced Non-Small Cell Lung Cancer Patients Treated With Immune Checkpoint Inhibitors: A Systematic Review and Meta-Analysis.

Front Oncol 2021 21;11:671874. Epub 2021 Jul 21.

Department of Medical Oncology, Shanghai Pulmonary Hospital, School of Medicine, Tongji University, Shanghai, China.

Background: The use of circulating tumor DNA (ctDNA) to reflect clinical benefits of advanced non-small cell lung cancer (NSCLC) patients during immune checkpoint inhibitor (ICI) therapy remains controversial. This study aimed to determine the association of pre-treatment and early dynamic changes of ctDNA with clinical outcomes in advanced NSCLC patients treated with ICIs.

Methods: Electronic databases (PubMed, Embase, Web of Science, and Cochrane) were systematically searched to include relevant studies published in English up to November 2020. The primary outcomes were overall survival (OS) and progression-free survival (PFS) and the secondary outcome was objective response rate (ORR) with RECIST criteria.

Results: A total of 1017 patients from 10 studies were identified. The baseline ctDNA levels (detected not detected) showed no significant association with clinical outcomes regarding OS (hazard ratio [HR], 1.18; 95% confidence interval [CI], 0.93-1.51), PFS (HR, 0.98; 95% CI, 0.80-1.21), and ORR (odds ratio [OR], 0.89; 95% CI, 0.54-1.46). Interestingly, when taken early longitudinal assessment of ctDNA into consideration, the early reduction of the concentration of ctDNA was associated with significant improvements of OS (HR, 0.19; 95% CI, 0.10-0.35), PFS (HR, 0.30; 95% CI, 0.22-0.41) and ORR (OR, 0.07; 95% CI, 0.03-0.18). Further subgroup analyses revealed that the reduction magnitude did not significantly impact the association between ctDNA and clinical outcomes, suggesting that both patients with decreased ctDNA or a ≥50% reduction of ctDNA was associated with improved OS, PFS and ORR.

Conclusion: Early reduction of ctDNA was associated with improved OS, PFS and ORR in advanced NSCLC patients treated with ICIs.

Systematic Review Registration: https://www.crd.york.ac.uk/PROSPERO, CRD42021226255.
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http://dx.doi.org/10.3389/fonc.2021.671874DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8335591PMC
July 2021

α-Mangostin Induces Apoptosis in Human Osteosarcoma Cells Through ROS-Mediated Endoplasmic Reticulum Stress via the WNT Pathway.

Cell Transplant 2021 Jan-Dec;30:9636897211035080

Orthopedics Department, YuLin NO.2 Hospital, Yulin, China.

α-mangostin has been confirmed to promote the apoptosis of MG-63 cells, but its specific pro-apoptosis mechanism in osteosarcoma (OS) remains further investigation. Here, we demonstrated that α-mangostin restrained the viability of OS cells (143B and Saos-2), but had little effect on the growth of normal human osteoblast. α-mangostin increased OS cell apoptosis by activating the caspase-3/8 cascade. Besides, α-mangostin induced endoplasmic reticulum (ER) stress and restrained the Wnt/β-catenin pathway activity. 4PBA (an ER stress inhibitor) or LiCl (an effective Wnt activator) treatment effectively hindered α-mangostin-induced apoptosis and the caspase-3/8 cascade. Furthermore, we also found that α-mangostin induced ER stress by promoting ROS production. And ER stress-mediated apoptosis caused by ROS accumulation depended on the inactivation of Wnt/β-catenin pathway. In addition, α-mangostin significantly hindered the growth of xenograft tumors, induced the expression of ER stress marker proteins and activation of the caspase-3/8 cascade, and restrained the Wnt/β-catenin signaling in vivo. In short, ROS-mediated ER stress was involved in α-mangostin triggered apoptosis, which might depended on Wnt/β-catenin signaling inactivation.
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http://dx.doi.org/10.1177/09636897211035080DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8323427PMC
July 2021

Detoxification difference of cadmium between the application of selenate and selenite in native cadmium-contaminated soil.

Environ Sci Pollut Res Int 2021 Jul 26. Epub 2021 Jul 26.

College of Natural Resources and Environment, Northwest A&F University, Yangling, Shaanxi, 712100, China.

Cadmium (Cd) has strong mobility and could cause toxicity to plants, and selenium (Se) can effectively detoxify Cd stress. However, differences in the detoxification effects of different species and dosages of exogenous Se on Cd and its mechanism are still unclear. In this study, a pot experiment was conducted to determine the effects of different rates of selenite and selenate application on radish growth, the uptake and translocation of Cd, and the fractions of Cd transformation in native Cd-contaminated soil. Results indicated that the decrease in radish biomass in selenate treatment was significantly greater than that in selenite treatment at a high Se application rate (2.5 mg·kg) (p < 0.05). In contrast to selenite treatments, the application of selenate significantly increased the translocation of Cd from radish roots to shoots (p < 0.05). Cadmium concentration and its bioaccumulation factor in radish decreased gradually with increasing selenite application rates, while these values decreased at low Se rate (1 mg·kg) and increased at high Se rate for selenate treatment. Different Se application rates resulted in Cd fractions distributions to change in soil. Therefore, the application of selenite treatment had a greater detoxification effect on Cd in soil than that in selenate treatment, and the double toxic effect was observed between Se and Cd in high selenate treatment (2.5 mg·kg). Combined with human health risk asseeement, the application of 2.5 mg·kg selenite could be a good approach for detoxification in native Cd-contaminated soil used in this study.
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http://dx.doi.org/10.1007/s11356-021-15564-0DOI Listing
July 2021

Improved Point-Line Feature Based Visual SLAM Method for Complex Environments.

Sensors (Basel) 2021 Jul 5;21(13). Epub 2021 Jul 5.

College of Communication and Information Engineering, Chongqing University of Posts and Telecommunications, Chongqing 400065, China.

Traditional visual simultaneous localization and mapping (SLAM) systems rely on point features to estimate camera trajectories. However, feature-based systems are usually not robust in complex environments such as weak textures or obvious brightness changes. To solve this problem, we used more environmental structure information by introducing line segments features and designed a monocular visual SLAM system. This system combines points and line segments to effectively make up for the shortcomings of traditional positioning based only on point features. First, ORB algorithm based on local adaptive threshold was proposed. Subsequently, we not only optimized the extracted line features, but also added a screening step before the traditional descriptor matching to combine the point features matching results with the line features matching. Finally, the weighting idea was introduced. When constructing the optimized cost function, we allocated weights reasonably according to the richness and dispersion of features. Our evaluation on publicly available datasets demonstrated that the improved point-line feature method is competitive with the state-of-the-art methods. In addition, the trajectory graph significantly reduced drift and loss, which proves that our system increases the robustness of SLAM.
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http://dx.doi.org/10.3390/s21134604DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8272192PMC
July 2021

Mechanisms underlying mercury detoxification in soil-plant systems after selenium application: a review.

Environ Sci Pollut Res Int 2021 Sep 12;28(34):46852-46876. Epub 2021 Jul 12.

College of Natural Resources and Environment, Northwest A&F University, Yangling, 712100, Shaanxi, China.

Feasible countermeasures to mitigate mercury (Hg) accumulation and its deleterious effects on crops are urgently needed worldwide. Selenium (Se) fertilizer application is a cost-effective strategy to reduce Hg concentrations, promote agro-environmental sustainability and food safety, and decrease the public health risk posed by Hg-contaminated soils and its accumulation in food crops. This holistic review focuses on the processes and detoxification mechanisms of Hg in whole soil-plant systems after Se application. The reduction of Hg bioavailability in soil, the formation of inert HgSe or/and HgSe-containing proteinaceous complexes in the rhizosphere and/or roots, and the reduction of plant root uptake and translocation of Hg in plant after Se application are systemically discussed. In addition, the positive responses in plant physiological and biochemical processes to Se application under Hg stress are presented to show the possible mechanisms for protecting the plant. However, application of high levels Se showed synergistic toxic effect with Hg and inhibited plant growth. The effectiveness of Se application methods, rates, and species on Hg detoxification is compared. This review provides a good approach for plant production in Hg-contaminated areas to meet food security demands and reduce the public health risk.
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http://dx.doi.org/10.1007/s11356-021-15048-1DOI Listing
September 2021

Field Test of Twin-Field Quantum Key Distribution through Sending-or-Not-Sending over 428 km.

Phys Rev Lett 2021 Jun;126(25):250502

Hefei National Laboratory for Physical Sciences at Microscale and Department of Modern Physics, University of Science and Technology ofChina, Hefei, Anhui 230026, People's Republic of China.

Quantum key distribution endows people with information-theoretical security in communications. Twin-field quantum key distribution (TF-QKD) has attracted considerable attention because of its outstanding key rates over long distances. Recently, several demonstrations of TF-QKD have been realized. Nevertheless, those experiments are implemented in the laboratory, and therefore a critical question remains about whether the TF-QKD is feasible in real-world circumstances. Here, by adopting the sending-or-not-sending twin-field QKD (SNS-TF-QKD) with the method of actively odd parity pairing (AOPP), we demonstrate a field-test QKD over 428 km of deployed commercial fiber and two users are physically separated by about 300 km in a straight line. To this end, we explicitly measure the relevant properties of the deployed fiber and develop a carefully designed system with high stability. The secure key rate we achieved breaks the absolute key rate limit of repeaterless QKD. The result provides a new distance record for the field test of both TF-QKD and all types of fiber-based QKD systems. Our work bridges the gap of QKD between laboratory demonstrations and practical applications and paves the way for an intercity QKD network with measurement-device-independent security.
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http://dx.doi.org/10.1103/PhysRevLett.126.250502DOI Listing
June 2021

A facile, versatile hydrogel bioink for 3D bioprinting benefits long-term subaqueous fidelity, cell viability and proliferation.

Regen Biomater 2021 Jun 14;8(3):rbab026. Epub 2021 Jun 14.

Biomanufacturing and Rapid Forming Technology Key Laboratory of Beijing, Department of Mechanical Engineering, Tsinghua University, Beijing 100084, China.

Both of the long-term fidelity and cell viability of three-dimensional (3D)-bioprinted constructs are essential to precise soft tissue repair. However, the shrinking/swelling behavior of hydrogels brings about inadequate long-term fidelity of constructs, and bioinks containing excessive polymer are detrimental to cell viability. Here, we obtained a facile hydrogel by introducing 1% aldehyde hyaluronic acid (AHA) and 0.375% -carboxymethyl chitosan (CMC), two polysaccharides with strong water absorption and water retention capacity, into classic gelatin (GEL, 5%)-alginate (ALG, 1%) ink. This GEL-ALG/CMC/AHA bioink possesses weak temperature dependence due to the Schiff base linkage of CMC/AHA and electrostatic interaction of CMC/ALG. We fabricated integrated constructs through traditional printing at room temperature and simulation printing at 37°C. The printed cell-laden constructs can maintain subaqueous fidelity for 30 days after being reinforced by 3% calcium chloride for only 20 s. Flow cytometry results showed that the cell viability was 91.38 ± 1.55% on day 29, and the cells in the proliferation plateau at this time still maintained their dynamic renewal with a DNA replication rate of 6.06 ± 1.24%. This work provides a convenient and practical bioink option for 3D bioprinting in precise soft tissue repair.
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http://dx.doi.org/10.1093/rb/rbab026DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8240632PMC
June 2021

Steroids Enable Mesenchymal Stromal Cells to Promote CD8 T Cell Proliferation Via VEGF-C.

Adv Sci (Weinh) 2021 06 2;8(12):2003712. Epub 2021 May 2.

CAS Key Laboratory of Tissue Microenvironment and Tumor Shanghai Institute of Nutrition and Health University of Chinese Academy of Sciences Chinese Academy of Sciences Shanghai 200031 China.

Mesenchymal stromal cells (MSCs) function as a formidable regulator of inflammation and tissue homeostasis and expanded MSCs are shown to be effective in treating various inflammatory diseases. Their therapeutic effects require the existence of certain inflammatory cytokines. However, in the absence of sufficient proinflammatory stimuli or in the presence of anti-inflammatory medications, MSCs are animated to promote immune responses and unable to alleviate inflammatory disorders. In this study, it is demonstrated that steroid co-administration interferes the efficacy of MSCs in treating acute graft-versus-host disease (aGvHD). Molecular analysis reveals that vascular endothelial growth factor C (VEGF-C) is highly induced in MSCs by steroids and TNF and VEGF-C in turn promotes CD8 T cell response. This immune promoting effect is abolished by blockade or specific genetic ablation of VEGFR3 in CD8 T cells. Additionally, administration of VEGF-C alone exacerbates aGvHD progression through eliciting more vigorous CD8 T cell activation and proliferation. Further studies demonstrate that VEGF-C augments the PI3K/AKT signaling process and the expression of downstream genes, such as Cyclin D1. Thus, the data demonstrate that steroids can reverse the immunosuppressive effect of MSCs via promoting VEGF-C-augmented CD8 T cell response and provide novel information for designing efficacious MSC-based therapies.
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http://dx.doi.org/10.1002/advs.202003712DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8224440PMC
June 2021

CircLRP6 contributes to prostate cancer growth and metastasis by binding to miR-330-5p to up-regulate NRBP1.

World J Surg Oncol 2021 Jun 22;19(1):184. Epub 2021 Jun 22.

Department of Urology, Xiangyang Central Hospital, Affiliated Hospital of Hubei University of Arts and Science, No. 136, Jingzhou Street, Xiangyang, 441021, Hubei, China.

Background: Circular RNA low-density lipoprotein receptor-related protein 6 (circLRP6) is considered as an oncogene in many types of cancers. However, the function and mechanisms of circLRP6 in prostate cancer (PCa) tumorigenesis remain largely undefined.

Methods: Quantitative real-time polymerase chain reaction (qRT-PCR) and western blot assays were conducted to assess the expression of circLRP6, microRNA (miR)-330-5p, and nuclear receptor binding protein 1 (NRBP1). Cell counting kit-8 (CCK-8), colony formation, 5-ethynyl-2'-deoxyuridine (EDU) incorporation, flow cytometry, transwell, wound healing, and western blot assays were performed to detect cell proliferation, apoptosis, and metastasis in vitro. Subcutaneous tumor growth was observed in nude mice to investigate the role of circLRP6 in vivo. The targeting relationship between miR-330-5p and NRBP1 or circLRP6 was verified using dual-luciferase reporter, pull-down, and RNA immunoprecipitation (RIP) assays. Immunohistochemistry was employed to test relative protein expression.

Results: CircLRP6 was highly expressed in PCa tissues and cells, knockdown of circLRP6 impaired PCa cell growth and metastasis in vitro by affecting cell proliferation, apoptosis, invasion, migration, and epithelial-mesenchymal transition (EMT). Mechanistic studies showed that circLRP6 could competitively bind with miR-330-5p to prevent the degradation of its target gene NRBP1. Rescue assay suggested that miR-330-5p inhibition reversed the inhibitory effects of circLRP6 knockdown on PCa cell growth and metastasis. Moreover, overexpression of miR-330-5p suppressed PCa progression via NRBP1. Notably, tumor formation assay indicated that circLRP6 silencing impeded tumor growth and EMT in vivo.

Conclusion: Our findings demonstrated that circLRP6 promoted PCa tumorigenesis and metastasis through miR-330-5p/NRBP1 axis, suggesting a potential therapeutic target for PCa.
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http://dx.doi.org/10.1186/s12957-021-02287-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8220703PMC
June 2021

A clinicopathological study of lung adenocarcinomas with pure ground-glass opacity > 3 cm on high-resolution computed tomography.

Eur Radiol 2021 Jun 16. Epub 2021 Jun 16.

Department of Radiology, Shanghai Pulmonary Hospital, Tongji University School of Medicine, 507 Zheng Min Road, Shanghai, 200433, China.

Objectives: This study aimed to discuss whether a diameter of 3 cm is a threshold for diagnosing lung adenocarcinomas presenting with radiological pure ground-glass mass (PGGM, pure ground-glass opacity > 3 cm) as adenocarcinomas in situ or minimally invasive adenocarcinomas (AIS-MIAs). Another aim was to identify CT features and patient prognosis that differentiate AIS-MIAs from invasive adenocarcinomas (IACs) in patients with PGGMs.

Methods: From June 2007 to October 2015, 69 resected PGGMs with HRCT and followed up for ≥ 5 years were included in this study and divided into AIS-MIA (n = 13) and IAC (n = 56) groups. Firth's logistic regression model was performed to determine CT characteristics that helped distinguish IACs from AIS-MIAs. The discriminatory power of the significant predictors was tested with the area under the receiver operating characteristics curve (AUC). Disease recurrence was also evaluated.

Results: Univariable and multivariable analyses identified that the mean CT attenuation (odds ratio: 1.054, p = 0.0087) was the sole significant predictor for preoperatively discriminating IACs from AIS-MIAs in patients with PGGMs. The CT attenuation had an excellent differentiating accuracy (AUC: 0.981), with the optimal cut-off value at -600 HU (sensitivity: 87.5%; specificity: 100%). Additionally, no recurrence was observed in patients manifesting with PGGMs > 3 cm, and the 5-year recurrence-free survival and overall survival rates were both 100%, even in cases of IAC.

Conclusions: This study demonstrated that PGGMs > 3 cm could still be AIS-MIAs. When PGGMs are encountered in clinical practice, the CT value may be the only valuable parameter to preoperatively distinguish IACs from AIS-MIAs.

Key Points: • Patients with pure ground-glass opacity > 3 cm in diameter are rare but can be diagnosed as adenocarcinomas in situ or minimally invasive adenocarcinomas. • The mean CT attenuation is the sole significant CT parameter that differentiates invasive adenocarcinoma from adenocarcinoma in situ or minimally invasive adenocarcinoma in patients with pure ground-glass opacity > 3 cm. • Lung adenocarcinoma with pure ground-glass opacity > 3 cm has an excellent prognosis, even in cases of invasive adenocarcinoma.
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http://dx.doi.org/10.1007/s00330-021-08115-1DOI Listing
June 2021

ICI plus chemotherapy prolonged survival over ICI alone in patients with previously treated advanced NSCLC.

Cancer Immunol Immunother 2021 Jun 7. Epub 2021 Jun 7.

Department of Medical Oncology, Shanghai Pulmonary Hospital, Thoracic Cancer Institute, Tongji University School of Medicine, No. 507, Zheng Min Road, Shanghai, 200433, People's Republic of China.

Objectives: Immune checkpoint inhibitors (ICI) monotherapy was standard of care in second-line treatment of patients with advance non-small cell lung cancer (NSCLC). This study aims to investigate the efficacy of ICI plus chemotherapy in patients with previously treated advanced NSCLC.

Patients And Methods: An investigator-initiated trial (IIT) aiming to evaluate the efficacy and safety of ICI in combination with chemotherapy as second line and beyond for patients with advanced NSCLC was undergone at Shanghai Pulmonary Hospital (ChiCTR1900026203). Patients who received ICI monotherapy as second or later line setting during the same period were also collected as a comparator.

Results: From April 2018 to June 2019, 31 patients were included into this IIT study, simultaneously 51 patients treated with ICI monotherapy were selected as a comparator. ICI plus chemotherapy showed a significantly higher ORR (35.5% vs. 15.7%, p=0.039), prolonged PFS (median: 5.6 vs. 2.5 months, p = 0.013) and OS (median: NE vs. 12.6 months, p = 0.038) compared with ICI alone. In the subgroup of negative PD-L1 expression (9 patients in combination group and 12 patients in monotherapy group), ICI plus chemotherapy also had a favorable ORR (44.4% vs. 8.3%, p = 0.119), longer PFS (median: 6.5 vs 3.0 months, p < 0.05) and OS (median: NE vs. 8.2 months, p = 0.117). Meanwhile, the addition of chemotherapy did not increase immune-related adverse events.

Conclusions: ICI plus chemotherapy showed superior ORR, PFS and OS than ICI alone patients with previous treated advanced NSCLC. These findings warrant further investigation.
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http://dx.doi.org/10.1007/s00262-021-02974-9DOI Listing
June 2021

Rosiglitazone alleviates lipopolysaccharide-induced inflammation in RAW264.7 cells via inhibition of NF-κB and in a PPARγ-dependent manner.

Exp Ther Med 2021 Jul 11;22(1):743. Epub 2021 May 11.

Department of Gastroenterology, Zhongshan Hospital Affiliated to Xiamen University, Xiamen, Fujian 361000, P.R. China.

Rosiglitazone is a synthetic peroxisome proliferator-activated receptor (PPAR)γ agonist widely used for the treatment of type 2 diabetes. Recent studies have demonstrated that rosiglitazone displays anti-inflammatory effects. The present study aimed to investigate whether rosiglitazone alleviates decreases in RAW264.7 cell viability resulting from lipopolysaccharide (LPS)-induced inflammation, as well as exploring the underlying mechanism. A macrophage inflammatory injury model was established by treating RAW264.7 cells with 100 ng/ml LPS. Cells were divided into LPS and rosiglitazone groups with different concentrations. Cell viability was assessed by performing an MTT assay. The expression of inflammatory cytokines was detected by conducting enzyme-linked immunosorbent assays and reverse transcription-quantitative PCR. Nitric oxidesecretion was assessed using the Griess reagent system. The expression levels of key nuclear factor-κB pathway-associated proteins were detected via western blotting. Rosiglitazone alleviated LPS-induced decrease in RAW264.7 cell viability and inhibited inflammatory cytokine expression in a concentration-dependent manner. Rosiglitazone significantly inhibited LPS-induced upregulation of p65 phosphorylation levels and downregulated IκBα expression levels. However, rosiglitazone-mediated inhibitory effects were reversed by PPARγ knockdown. The results of the present study demonstrated that rosiglitazone significantly inhibited LPS-induced inflammatory responses in RAW264.7 macrophage cells, which was dependent on PPARγ activation and NF-κB suppression.
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http://dx.doi.org/10.3892/etm.2021.10175DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8138265PMC
July 2021
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