Publications by authors named "Yi Hu"

1,038 Publications

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Increasing prevalence and influencing factors of childhood asthma: a cross-sectional study in Shanghai, China.

World J Pediatr 2021 Jun 10. Epub 2021 Jun 10.

Department of Clinical Epidemiology and Biostatistics, Shanghai Children's Medical Center, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.

Background: Asthma has been a global problem, especially in children. We aim to evaluate the contemporary prevalence and influencing factors of asthma among children aged 3-7 years in Shanghai, China.

Methods: A random sample of preschool children was included in this study. The International Study of Asthma and Allergies in Childhood questionnaire was adopted to assess the childhood asthma. Multivariable logistic regression models were used to evaluate the associations between independent variables and childhood asthma.

Results: Of 6389 preschool children who were invited to take part in this study, 6163 (response rate: 96.5%) completed the questionnaire and were included in the analysis. The overall prevalence of asthma was 14.6% which increased more than six folds from 2.1% in 1990. Being male, younger age, preterm delivery, being born in spring or autumn, being delivered by elective cesarean section without indication, miscarriage, high socioeconomic status, having allergy history, and exposure to passive smoking, latex paint, and dust were potential risk factors for childhood asthma. Spending more time outdoors (> 30 min/day), having indoor plants, and cleaning rooms more frequently were potential protective factors.

Conclusions: The prevalence of childhood asthma in Shanghai has increased dramatically during the past three decades. The findings about risk and protective factors of childhood asthma could be used to develop appropriate strategies to prevent and control childhood asthma in Shanghai and in other similar metropolitan cities.
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http://dx.doi.org/10.1007/s12519-021-00436-xDOI Listing
June 2021

Codonopsis pilosula Polysaccharides Alleviate Aβ1-40-Induced PC12 Cells Energy Dysmetabolism via CD38/NAD+ Signaling Pathway.

Curr Alzheimer Res 2021 Jun 7. Epub 2021 Jun 7.

Shanghai Geriatric Institute of Chinese Medicine, Shang-hai200031, China.

Background: Alzheimer's disease (AD) is the most common type of dementia and has a complex pathogenesis with no effective treatment. Energy metabolism disorders, as an early patho- logical event of AD,have attracted attention as a promising area of AD research. Codonopsis pilo- sula Polysaccharides are the main effective components of Codonopsis pilosula, which have been demonstrated to regulate energy metabolism.

Methods: In order to further study the roles and mechanisms of Codonopsis pilosula polysaccharides in AD, this study used an Aβ1-40-induced PC12 cells model to study the protective effects of Codonopsis pilosula polysaccharides and their potential mechanisms in improving energy metabolism dysfunction.

Results: The results showed that Aβ1-40 induced a decrease in PC12 cells viability, energy metabolism molecules (ATP, NAD+, and NAD+/NADH) and Mitochondrial Membrane Potential (MMP) and an increase in ROS. Additionally, it was found that Aβ1-40 increased CD38 expres- sion related to NAD+ homeostasis, whereas Silent Information Regulation 2 homolog1 (SIRT1), SIRT3, Peroxisome proliferator-activated receptor γ coactivator-1 α (PGC-1α) and SIRT3 activity were decreased. Codonopsis pilosula polysaccharides increased NAD+, NAD+/NADH, SIRT3, SIRT1, and PGC-1α related to NAD+, thus partially recovering ATP.

Conclusions: Our findings reveal that Codonopsis pilosula polysaccharides protected PC12 cells from Aβ1-40-induced damage, suggesting that these components of the Codonopsis pilosula herb may represent an early treatment option for AD patients.Recent Advances in Anti-Infective Drug Discovery.
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http://dx.doi.org/10.2174/1567205018666210608103831DOI Listing
June 2021

Flexible, Mechanically Robust, Solid-State Electrolyte Membrane with Conducting Oxide-Enhanced 3D Nanofiber Networks for Lithium Batteries.

Nano Lett 2021 Jun 8. Epub 2021 Jun 8.

Department of Mechanical Engineering, University of Delaware, Newark, Delaware 19716, United States.

Using a three-dimensional (3D) Li-ion conducting ceramic network, such as LiLaZrO (LLZO) garnet-type oxide conductor, has proved to be a promising strategy to form continuous Li ion transfer paths in a polymer-based composite. However, the 3D network produced by brittle ceramic conductor nanofibers fails to provide sufficient mechanical adaptability. In this manuscript, we reported a new 3D ion-conducting network, which is synthesized from highly loaded LLZO nanoparticles reinforced conducting polymer nanofibers, by creating a lightweight continuous and interconnected LLZO-enhanced 3D network to outperform conducting heavy and brittle ceramic nanofibers to offer a new design principle of composite electrolyte membrane featuring all-round properties in mechanical robustness, structural flexibility, high ionic conductivity, lightweight, and high surface area. This composite-nanofiber design overcomes the issues of using ceramic-only nanoparticles, nanowires, or nanofibers in polymer composite electrolyte, and our work can be considered as a new generation of composite electrolyte membrane in composite electrolyte development.
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http://dx.doi.org/10.1021/acs.nanolett.1c01704DOI Listing
June 2021

Mean-Field Caging in a Random Lorentz Gas.

J Phys Chem B 2021 Jun 7. Epub 2021 Jun 7.

Laboratoire de Physique de l'Ecole Normale Supérieure, ENS, Université PSL, CNRS, Sorbonne Université, Université de Paris, F-75005 Paris, France.

The random Lorentz gas (RLG) is a minimal model of both percolation and glassiness, which leads to a paradox in the infinite-dimensional, → ∞ limit: the localization transition is then expected to be for the former and for the latter. As a putative resolution, we have recently suggested that, as increases, the behavior of the RLG converges to the glassy description and that percolation physics is recovered thanks to finite- perturbative and nonperturbative (instantonic) corrections [Biroli et al. 2021, 103, L030104]. Here, we expand on the → ∞ physics by considering a simpler static solution as well as the dynamical solution of the RLG. Comparing the 1/ correction of this solution with numerical results reveals that even perturbative corrections fall out of reach of existing theoretical descriptions. Comparing the dynamical solution with the mode-coupling theory (MCT) results further reveals that, although key quantitative features of MCT are far off the mark, it does properly capture the discontinuous nature of the → ∞ RLG. These insights help chart a path toward a complete description of finite-dimensional glasses.
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http://dx.doi.org/10.1021/acs.jpcb.1c02067DOI Listing
June 2021

Comparison of Immediate and Sequential Withdrawal of a Systemic Glucocorticoid in the Treatment of Acute Exacerbations of Chronic Obstructive Pulmonary Disease: A Multicenter, Randomized, Double-Blind, Parallel-Controlled, Open-Label Study.

Front Mol Biosci 2021 20;8:639079. Epub 2021 May 20.

Department of Respiratory and Critical Care Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

Patients with acute exacerbations of chronic obstructive pulmonary disease (AECOPD) were treated with immediate or sequential withdrawal after 5 days of systemic glucocorticoids. The effects of the two withdrawal methods on the prognosis of patients were compared at 30, 90, 180, and 360 days after discharge. A multicenter, randomized, double-blind, parallel-controlled, open-label study was conducted in the respiratory department of tertiary hospitals in Central China. Patients met inclusion criteria for AECOPD and needed to use systemic glucocorticoids. They were randomly assigned to immediate and sequential withdrawal groups at a 1:1 ratio. The study was completed in August 2020 and is registered at the China Clinical Trials Registry (Chictr.org) (ChiCTR1800018894). According to general data and clinical characteristics, there were no statistically significant differences between the 329 patients in the immediate withdrawal group and the 310 patients in the sequential withdrawal group ( > 0.05). At the 30, 90, 180, and 360-days follow-up, the acute exacerbation frequency, rehospitalization rate, mortality, and intensive care unit (ICU) treatment rate were not significantly different between the immediate withdrawal group and sequential withdrawal group ( > 0.05). The modified Medical Research Council (mMRC) and COPD assessment test (CAT) scores were also not significantly different between the two groups. At the 180- and 360-day follow-up, forced expiratory volume in 1 s (FEV1%) and peak expiratory flow (PEF) were not significantly different between the two groups ( > 0.05). The time from discharge to first acute exacerbation was significantly lower in the immediate withdrawal group (46.12 days) than in sequential withdrawal group (49.02 days) ( < 0.05). The time of stay in the hospital for the first time after discharge was not significantly different between the two groups ( > 0.05). Adverse events were not significantly different between the immediate withdrawal group and sequential withdrawal group ( < 0.05). Subgroup analysis was performed according to age, degree of disease, and relevant indicators. At the 30-day follow-up, the acute exacerbation frequency of patients with advanced age, high global strategy for chronic obstructive lung disease (GOLD), and high fractional exhaled nitric oxide was significantly higher in the immediate withdrawal group than in the sequential withdrawal group ( < 0.05). In addition, according to receiver operating characteristic (ROC) curve analysis, the frequency of acute exacerbations at the 30-day follow-up was significantly higher in patients with age > 63.5 years or GOLD > 3 in the immediate withdrawal group than in the sequential withdrawal group, suggesting that the short-term efficacy was poor.
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http://dx.doi.org/10.3389/fmolb.2021.639079DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8173198PMC
May 2021

Inhibiting autophagy enhances sulforaphane-induced apoptosis targeting NRF2 in esophageal squamous cell carcinoma.

Acta Pharm Sin B 2021 May 15;11(5):1246-1260. Epub 2020 Dec 15.

State Key Laboratory of Esophageal Cancer Prevention & Treatment, School of Pharmaceutical Sciences, Zhengzhou University, Zhengzhou 450001, China.

Sulforaphane (SFN), a natural anti-tumor compound from cruciferous vegetables, has been reported to induce protective autophagy to cancer cells, which might impair the anti-tumor efficiency of SFN. However, the accurate function and mechanism of SFN inducing autophagy in cancers are still obscure, especially in esophageal squamous cell carcinoma (ESCC), one of malignancies with high incidence in North China. Here, we mainly explored the potential function of autophagy upon SFN treatment in ESCC and molecular mechanism. We demonstrated that SFN could inhibit cell proliferation and induce apoptosis by activating caspase pathway. Moreover, we found activation of NRF2 pathway by SFN was responsible for the induction of autophagy and also a disadvantage element to the anti-tumor effects of SFN on ESCC, indicating that SFN might induce protective autophagy in ESCC. We, therefore, investigated effects of autophagy inhibition on sensitivity of ESCC cells to SFN and found that chloroquine (CQ) could neutralize the activation of SFN on NRF2 and enhance the activation of SFN on caspase pathway, thus improved the anti-tumor efficiency of SFN on ESCC and . Our study provides a preclinical rationale for development of SFN and its analogs to the future treatment of ESCC.
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http://dx.doi.org/10.1016/j.apsb.2020.12.009DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8148075PMC
May 2021

Environmental Exposure and Childhood Atopic Dermatitis in Shanghai: A Season-Stratified Time-Series Analysis.

Dermatology 2021 Jun 3:1-8. Epub 2021 Jun 3.

Department of Clinical Epidemiology and Biostatistics, Shanghai Children's Medical Center, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.

Background: Childhood atopic dermatitis (AD) is an inflammatory skin disease which sometimes predisposes to allergies. Environmental factors (low humidity, irritants, etc.) are prominent causative triggers of AD.

Objectives: This study aims to explore the effects of both meteorological factors and air pollutants on childhood AD, and the modification effects by season in Shanghai, China.

Methods: Quasi-Poisson generalized linear regression model, combined with a distributed lag nonlinear model was used to examine the nonlinear and lagged effects of environmental factors on childhood AD from 2009 to 2017 in Shanghai. We also performed a season-stratified analysis to determine the modification effects of environmental exposure by season on childhood AD.

Results: There were 1,043,240 outpatient visits for childhood AD in total, at 3 major pediatric hospitals. Low temperature and relative humidity (RH), and high daily temperature difference (DTD) and air pollutants (i.e., NO2) increased the relative risks (RRs) of outpatient visits for childhood AD in the whole year. In the cold season, an increased risk of outpatient visits for childhood AD was associated with low RH (RR 2.26, 95% CI 1.69-3.02) and high NO2 (1.11, 95% CI 1.06-1.17). In the warm season, outpatient visits for childhood AD were associated with low temperature (3.49, 95% CI 3.22-3.77), low RH (1.89, 95% CI 1.74-2.06), high DTD (1.41, 95% CI 1.31-1.53), and high NO2 (1.05, 95% CI 1.03-1.06).

Conclusions: This study suggests that environmental exposure may be a key trigger for outpatient visits for childhood AD with apparent seasonal effects. Tailored preventive strategies to avoid environmental triggers of childhood AD should be developed.
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http://dx.doi.org/10.1159/000514685DOI Listing
June 2021

An Iron Oxide Nanoparticle-Based Transdermal Nanoplatform for Dual-Modal Imaging-Guided Chemo-Photothermal Therapy of Superficial Tumors.

Acta Biomater 2021 May 31. Epub 2021 May 31.

Hefei National Lab for Physical Sciences at the Microscale and Centers for Biomedical Engineering, University of Science and Technology of China, Hefei, Anhui, 230027, China. Electronic address:

Transdermal delivery is an attractive strategy for treating superficial tumors. However, the applications of existing transdermal systems have been limited by low transdermal efficiency and poor therapeutic outcomes. Here, we develop a transdermal nanoplatform (+)T-SiDs, based on superparamagnetic iron oxide core, surface-modified with cationic lipids, transdermal enhanced peptide TD, and 1,1'-dioctadecyl-3,3,3',3'-tetramethylindotricarbocyanine iodide (DiR), and loaded with doxorubicin. The (+)T-SiDs compositions enable MR/NIR dual-modal imaging guided synergistic chemo-photothermal therapy to superficial tumors treatment via transdermal delivery. The (+)T-SiDs exhibit good stability, efficient cellular uptake, pH/photothermal responsive drug release, and high photothermal conversion efficiency (47.45%). Importantly, the transdermal delivery of (+)T-SiDs is significantly enhanced by TD functionalization. In vivo MR/NIR imaging shows that the (+)T-SiDs exhibit high transdermal efficiency and specificity in localization to the tumor site. Moreover, in comparison with individual chemo- or photothermal therapies, the combination of chemo-photothermal therapy exhibits more efficient tumor inhibition effects. This work presents a new transdermal treatment nanoplatform for dual-modal imaging-guided chemo-photothermal therapy of superficial tumors, with efficient tumor eradication and low systemic toxicity thus offering strong potential for clinical adoption.
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http://dx.doi.org/10.1016/j.actbio.2021.05.033DOI Listing
May 2021

[Retracted] Knockdown of PREX2a inhibits the malignant phenotype of glioma cells.

Mol Med Rep 2021 Aug 3;24(2). Epub 2021 Jun 3.

Department of Neurosurgery, People's Hospital of Ningxiang County, Changsha, Hunan 410600, P.R. China.

Following the publication of this paper, it was drawn to the Editors' attention by a concerned reader that cell invasion assay data in the article (featured in Fig. 4A) were strikingly similar to data appearing in different form in another article by different authors at different research institutions, which had already been published elsewhere at the time of the present article's submission. Furthermore, flow cytometric data featured in Fig. 2D were strikingly similar to those in another previously published paper, and cell cyle data included in Fig. 3 had apparently previously published elsewhere. Owing to the fact that the contentious data in the above article had already appeared in different form in other articles prior to its submission to , the Editor has decided that this paper should be retracted from the Journal. The authors also expressed their intention to retract the paper on the grounds that the corresponding author and several of the authors failed to confirm the approval of the final version of the manuscript. The Editor apologizes to the readership for any inconvenience caused. [the original article was published on 13: 2301‑2307, 2016; DOI: 10.3892/mmr.2016.4799].
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http://dx.doi.org/10.3892/mmr.2021.12184DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8185513PMC
August 2021

An Approach to Accelerate Healing and Shorten the Hospital Stay of Patients With Anastomotic Leakage After Esophagectomy: An Explorative Study of Systematic Endoscopic Intervention.

Front Oncol 2021 17;11:657955. Epub 2021 May 17.

Sun Yat-Sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, China.

Objective: To explore the comprehensive role of systemic endoscopic intervention in healing esophageal anastomotic leak.

Methods: In total, 3919 consecutive patients with esophageal cancer who underwent esophagectomy and immediate esophageal reconstruction were screened. In total, 203 patients (5.10%) diagnosed with anastomotic leakage were included. The participants were divided into three groups according to differences in diagnosis and treatment procedures. Ninety-four patients received conventional management, 87 patients received endoscopic diagnosis only, and the remaining 22 patients received systematic endoscopic intervention. The primary endpoint was overall healing of the leak after oncologic esophageal surgery. The secondary endpoints were the time from surgery to recovery and the occurrence of adverse events.

Results: 173 (85.2%; 95% CI, 80.3-90.1%) of the 203 patients were successfully healed, with a mean healing time of 66.04 ± 3.59 days (median: 51 days; range: 13-368 days), and the overall healing rates differed significantly among the three groups according to the stratified log-rank test (P<0.001). The median healing time of leakage was 37 days (95% CI: 33.32-40.68 days) in the endoscopic intervention group, 51 days (95% CI: 44.86-57.14 days) in the endoscopic diagnostic group, and 67 days (95% CI: 56.27-77.73 days) in the conventional group. The overall survival rate was 78.7% (95% CI: 70.3 to 87.2%) in the conventional management group, 89.7% (95% CI: 83.1 to 96.2%) in the endoscopic diagnostic group and 95.5% (95% CI: 86.0 to 100%) in the systematic endoscopic intervention group. Landmark analysis indicated that the speed of wound healing in the endoscopic intervention group was 2-4 times faster at any period than that in the conservative group. There were 20 (21.28%) deaths among the 94 patients in the conventional group, 9 (10.34%) deaths among the 87 patients in the endoscopic diagnostic group and 1 (4.55%) death among the 22 patients in the endoscopic intervention group; this difference was statistically significant (Fisher exact test, P < 0.05).

Conclusion: Tailored endoscopic treatment for postoperative esophageal anastomotic leakage based on endoscopic diagnosis is feasible and effective. Systematic endoscopic intervention shortened the treatment period and reduced mortality and should therefore be considered in the management of this disease.
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http://dx.doi.org/10.3389/fonc.2021.657955DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8166318PMC
May 2021

Two Different Inoculation Methods Unveiled the Relative Independence of DON Accumulation in Wheat Kernels from Disease Severity on Spike after Infection by Fusarium Head Blight.

Toxins (Basel) 2021 05 14;13(5). Epub 2021 May 14.

Jiangsu Key Laboratory of Crop Genomics and Molecular Breeding/Key Laboratory of Plant Functional Genomics of the Ministry of Education/Collaborative-Innovation of Modern Crops and Food Crops in Jiangsu/Jiangsu Key Laboratory of Crop Genetics and Physiology, College of Agriculture, Yangzhou University, Yangzhou 225009, China.

Fusarium head blight (FHB) causes wheat yield loss and mycotoxin (deoxynivalenol, DON) accumulation in wheat kernel. Developing wheat cultivars with overall resistance to both FHB spread within a spike and DON accumulation in kernels is crucial for ensuring food security and food safety. Here, two relatively novel inoculation methods, bilateral floret inoculation (BFI) and basal rachis internode injection (BRII), were simultaneously employed to evaluate disease severity and DON content in kernels in a segregating population of recombinant inbred lines (RILs) developed from Ning 7840 (carrying ) and Clark (without ). Under both inoculation methods, four contrasting combinations of disease severity and DON content were identified: high severity/high DON (HSHD), high severity/low DON (HSLD), low severity/high DON (LSHD) and low severity/low DON (LSLD). Unexpectedly, the BRII method clearly indicated that disease severity was not necessarily relevant to DON concentration. The effects of on disease severity, and on DON concentrations, agreed very well across the two methods. Several lines carrying showed extremely higher severity and (or) DON content under both inoculation methods. The "Mahalanobis distance" (MD) method was used to rate overall resistance of a line by inclusion of both disease severity and DON content over both methods to select LSLD lines.
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http://dx.doi.org/10.3390/toxins13050353DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8156083PMC
May 2021

Treatment of iodine-containing water by the UV/NHCl process: Dissolved organic matters transformation, iodinated trihalomethane formation and toxicity variation.

Water Res 2021 May 17;200:117256. Epub 2021 May 17.

CAS Key Laboratory of Urban Pollutant Conversion, Department of Environmental Science and Engineering, University of Science and Technology of China, Hefei, China. Electronic address:

UV/NHCl process is becoming increasingly important for water treatment, while its impact on iodine-containing water remains unknown. In this study, the structure transformation of dissolved organic matters (DOMs), generation of iodinated trihalomethanes (I-THMs), and variation of acute toxicity were evaulated during the UV/NHCl treatment of iodine-containing water. The combination of exciation emission matrix-parallel factor analysis and two-dimensional correlation spectroscopy integrated with synchronous fluorescence and infrared absorption spectroscopy showed that fulvic-like fraction of DOM was more susceptible to UV/NHCl process and particularly iodo and polysaccharide groups gave the fastest resopnses. Consequently, UV fluence lower than 60 mJ/cm promoted the production of I-THMs, while excessive UV exhausted NHCl and reactive iodine species and subsequently reduced I-THM generation. Moreover, DOM concentration and source, NHCl dosage, and I concentration had significant impacts on I-THM formation in the UV/NHCl process. Additionally, a positive correlation was found between acute toxicity variation and I-THM formation when treating iodine-containing waters with UV/NHCl. These results together provide a comprehensive understanding on UV/NHCl treatment of iodine-containing water.
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http://dx.doi.org/10.1016/j.watres.2021.117256DOI Listing
May 2021

The LINC01119-SOCS5 axis as a critical theranostic in triple-negative breast cancer.

NPJ Breast Cancer 2021 May 31;7(1):69. Epub 2021 May 31.

Department of Pathology and Cancer Center, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA.

The development of triple-negative breast cancer (TNBC) is critically regulated by certain tumor-microenvironment-associated cells called mesenchymal stem/stromal cells (MSCs), which we and others have shown promote TNBC progression by activating pro-malignant signaling in neighboring cancer cells. Characterization of these cascades would better our understanding of TNBC biology and bring about therapeutics that eliminate the morbidity and mortality associated with advanced disease. Here, we focused on the emerging class of RNAs called long non-coding RNAs or lncRNAs and utilized a MSC-supported TNBC progression model to identify specific family members of functional relevance to TNBC pathogenesis. Indeed, although some have been described to play functional roles in TNBC, activities of lncRNAs as mediators of tumor-microenvironment-driven TNBC development remain to be fully explored. We report that MSCs stimulate robust expression of LINC01119 in TNBC cells, which in turn induces suppressor of cytokine signaling 5 (SOCS5), leading to accelerated cancer cell growth and tumorigenesis. We show that LINC01119 and SOCS5 exhibit tight correlation across multiple breast cancer gene sets and that they are highly enriched in TNBC patient cohorts. Importantly, we present evidence that the LINC01119-SOCS5 axis represents a powerful prognostic indicator of adverse outcomes in TNBC patients, and demonstrate that its repression severely impairs cancer cell growth. Altogether, our findings identify LINC01119 as a major driver of TNBC development and delineate critical non-coding RNA theranostics of potential translational utility in the management of advanced TNBC, a class of tumors in most need of effective and targeted therapy.
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http://dx.doi.org/10.1038/s41523-021-00259-zDOI Listing
May 2021

'Skywalker' surgical robot for total knee arthroplasty: An experimental sawbone study.

Int J Med Robot 2021 May 31:e2292. Epub 2021 May 31.

Department of Orthopaedic Surgery, Shanghai Key Laboratory of Orthopaedic Implants, Shanghai Ninth People's Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China.

Background: Currently, robot-assisted surgical systems are used to reduce the error range of total knee arthroplasty (TKA) osteotomy and component positioning.

Methods: We used 20 sawbone models of the femur and 20 sawbone models of the tibia and fibula to evaluate the osteotomy effect of 'Skywalker' robot-assisted TKA.

Results: The maximal movement of the cutting jig was less than 0.25 mm at each osteotomy plane. The mean and standard deviation values of the angle deviation between the planned osteotomy plane and the actual osteotomy plane at each osteotomy plane were not more than 1.03° and 0.55°, respectively. The mean and standard deviation values of absolute error of resection thickness at each osteotomy position were less than 0.78 and 0.71 mm, respectively.

Conclusions: The 'Skywalker' system has good osteotomy accuracy, can achieve the planned osteotomy well and is expected to assist surgeons in performing accurate TKA in clinical applications in future.
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http://dx.doi.org/10.1002/rcs.2292DOI Listing
May 2021

A next generation sequencing combined genome-wide association study identifies novel tuberculosis susceptibility loci in Chinese population.

Genomics 2021 May 28;113(4):2377-2384. Epub 2021 May 28.

Bio-X Institutes, Key Laboratory for the Genetics of Developmental and Neuropsychiatric Disorders (Ministry of Education), Shanghai Jiao Tong University, Shanghai 200030, China; Collaborative Innovation Center, Jining Medical University, Jining, Shandong 272067, China. Electronic address:

The genetic factors of tuberculosis (TB) susceptibility have been widely recognized. Here we performed a two-stage study in 616 TB patients and 709 healthy controls to systematically identify the genetic markers of TB susceptibility. In the discovery stage, we identified 93 single nucleotide polymorphisms (SNPs) and 3 human leucocyte antigen (HLA) class II alleles that had potential associations with TB susceptibility. In the validation stage, we confirmed that 6 nominally significant SNPs, including 2 novel missense variants at RAB17 and DCTN4 (odds ratio (OR) = 1.40, P = 4.98 × 10 and OR = 2.30, P = 3.17 × 10 respectively), were associated with the predisposition to TB. Moreover, our study found that HLA-II allele DQA1*05:05 (P = 0.0011, OR = 1.44, 95%CI = 1.15-1.77) was a TB susceptibility locus for the first time. This study comprehensively investigated the genetic variants that were associated with TB susceptibility and provided insight into the tuberculosis pathogenesis.
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http://dx.doi.org/10.1016/j.ygeno.2021.05.035DOI Listing
May 2021

GM-CSF mediates immune evasion via upregulation of PD-L1 expression in extranodal natural killer/T cell lymphoma.

Mol Cancer 2021 May 29;20(1):80. Epub 2021 May 29.

State Key Laboratory of Oncology in South China, Collaborative Innovation Center of Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, 510060, Guangdong, China.

Background: Granulocyte-macrophage colony stimulating factor (GM-CSF) is a cytokine that is used as an immunopotentiator for anti-tumor therapies in recent years. We found that some of the extranodal natural killer/T cell lymphoma (ENKTL) patients with the treatment of hGM-CSF rapidly experienced disease progression, but the underlying mechanisms remain to be elucidated. Here, we aimed to explore the mechanisms of disease progression triggered by GM-CSF in ENKTL.

Methods: The mouse models bearing EL4 cell tumors were established to investigate the effects of GM-CSF on tumor growth and T cell infiltration and function. Human ENKTL cell lines including NK-YS, SNK-6, and SNT-8 were used to explore the expression of programmed death-ligand 1 (PD-L1) induced by GM-CSF. To further study the mechanisms of disease progression of ENKTL in detail, the mutations and gene expression profile were examined by next-generation sequence (NGS) in the ENKTL patient's tumor tissue samples.

Results: The mouse-bearing EL4 cell tumor exhibited a faster tumor growth rate and poorer survival in the treatment with GM-CSF alone than in treatment with IgG or the combination of GM-CSF and PD-1 antibody. The PD-L1 expression at mRNA and protein levels was significantly increased in ENKTL cells treated with GM-CSF. STAT5A high-frequency mutation including p.R131G, p.D475N, p.F706fs, p.V707E, and p.S710F was found in 12 ENKTL cases with baseline tissue samples. Importantly, STAT5A-V706fs mutation tumor cells exhibited increased activation of STAT5A pathway and PD-L1 overexpression in the presence of GM-CSF.

Conclusions: These findings demonstrate that GM-CSF potentially triggers the loss of tumor immune surveillance in ENKTL patients and promotes disease progression, which is associated with STAT5 mutations and JAK2 hyperphosphorylation and then upregulates the expression of PD-L1. These may provide new concepts for GM-CSF application and new strategies for the treatment of ENKTL.
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http://dx.doi.org/10.1186/s12943-021-01374-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8164269PMC
May 2021

Could COVID-19 pandemic be stopped with joint efforts of travel restrictions and public health countermeasures? A modelling study.

BMJ Open 2021 05 24;11(5):e046157. Epub 2021 May 24.

Key Laboratory of Environmental Medicine Engineering, School of Public Health, Southeast University, Nanjing, China

Objective: We aim to explore and compare the effect of global travel restrictions and public health countermeasures in response to COVID-19 outbreak.

Design: A data-driven spatio-temporal modelling to simulate the spread of COVID-19 worldwide for 150 days since 1 January 2020 under different scenarios.

Setting: Worldwide.

Interventions: Travel restrictions and public health countermeasures.

Main Outcome: The cumulative number of COVID-19 cases.

Results: The cumulative number of COVID-19 cases could reach more than 420 million around the world without any countermeasures taken. Under timely and intensive global interventions, 99.97% of infections could be avoided comparing with non-interventions. The scenario of carrying out domestic travel restriction and public health countermeasures in China only could contribute to a significant decrease of the cumulative number of infected cases worldwide. Without global travel restriction in the study setting, 98.62% of COVID-19 cases could be avoided by public health countermeasures in China only compared with non-interventions at all.

Conclusions: Public health countermeasures were generally more effective than travel restrictions in many countries, suggesting multinational collaborations in the public health communities in response to this novel global health challenge.
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http://dx.doi.org/10.1136/bmjopen-2020-046157DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8149266PMC
May 2021

Activating Titanium Metal with H Plasma for the Hydrogen Evolution Reaction.

ACS Appl Mater Interfaces 2021 Jun 19;13(21):24682-24691. Epub 2021 May 19.

Science and Technology on Surface Physics and Chemistry Laboratory, Jiangyou 621908, China.

Developing a high-performance nonprecious metal electrocatalyst for water splitting is a strong demand for the large-scale application of electrochemical H production. In this work, we design a facile and scalable strategy to activate titanium metal for the hydrogen evolution reaction (HER) in alkaline media through incorporating hydrogen into the α-Ti crystal lattice by H plasma bombardment. Benefiting from the accelerated charge transfer and enlarged electrochemical surface area after H plasma treatment, the H-incorporated Ti shows remarkably enhanced HER activity with a much lower overpotential at -10 mA cm by 276 mV when compared to the pristine Ti. It is revealed that the retention of the incorporated H(D) atoms in the Ti crystal lattice during HER accounts for the durable feature of the catalyst. Density functional theory calculations demonstrate the effectiveness of hydrogen incorporation in tuning the adsorption energy of reaction species via charge redistribution. Our work offers a novel route to activate titanium or other metals by H incorporation through a controllable H plasma treatment to tune the electronic structure for water splitting reactions.
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http://dx.doi.org/10.1021/acsami.1c02646DOI Listing
June 2021

Decomposable black phosphorus nano-assembly for controlled delivery of cisplatin and inhibition of breast cancer metastasis.

J Control Release 2021 May 14;335:59-74. Epub 2021 May 14.

School of Pharmaceutical Sciences, Nanjing Tech University, Nanjing 211816, PR China; State Key Laboratory of Materials-Oriented Chemical Engineering, Nanjing Tech University, Nanjing 211816, PR China. Electronic address:

Novel platforms for cisplatin delivery with a controllable manner and combinable with other treatment modality to achieve synergistic antitumor effect and inhibition metastasis for treatment of triple negative breast cancer (TNBC) are highly desirable. Herein, we report a black phosphorus (BP) nanosheets-based nano-assembly which consists of cisplatin, BP, polydopamine (PDA) and hyaluronic acid (HA), cisplatin/BP/PDA-HA (CBPH), for controlled delivery of cisplatin and inhibition tumor growth as well as lung metastasis of TNBC. For constructing CBPH, the surface of BP was dual modified by PDA and HA, resulting in enhanced stability, tumor target ability and photothermal efficiency of BP. Cisplatin was released in response both to internal and external stimuli existed in tumor microenvironment, including low pH, hydrogen peroxide and NIR light, as accompanied by decomposition of BP. In vitro experiments demonstrated CBPH-treated 4 T1 cells showed elevated intracellular content of Pt and Pt-DNA adduct, which was further improved when exposure to NIR light, leading to potent antitumor effect in a synergistic pattern. Anti-metastasis studies in 2D monolayers and 3D organoids revealed that CBPH plus NIR light treatment exhibited significantly decreased migration, invasion and regrowth ability of 4 T1 cells. Furthermore, TNBC-bearing mice with systemic administrate of CBPH showed enhanced tumor accumulation of cisplatin and light-triggered inhibition of tumor growth at primary site and lung metastasis, with alleviated toxicity. But CBPH is yet to be optimized for realizing smart cisplatin delivery in response to acidic and redox stimuli in vivo. Collectively, our study demonstrates that this novel BP-based nano-assembly with controllable tumor delivery of cisplatin and metastasis inhibition of breast cancer expand the use of BP in biomedicine field and hold great promise for further development.
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http://dx.doi.org/10.1016/j.jconrel.2021.05.013DOI Listing
May 2021

3-month, 6-month, 9-month, and 12-month respiratory outcomes in patients following COVID-19-related hospitalisation: a prospective study.

Lancet Respir Med 2021 May 5. Epub 2021 May 5.

Biological Sciences, Faculty of Environmental and Life Sciences, University of Southampton, Southampton, UK; Institute for Life Sciences, University of Southampton, Southampton, UK; NIHR Southampton Biomedical Research Centre, University Hospital Southampton, Southampton, UK. Electronic address:

Background: The consequences of COVID-19 in those who recover from acute infection requiring hospitalisation have yet to be clearly defined. We aimed to describe the temporal trends in respiratory outcomes over 12 months in patients hospitalised for severe COVID-19 and to investigate the associated risk factors.

Methods: In this prospective, longitudinal, cohort study, patients admitted to hospital for severe COVID-19 who did not require mechanical ventilation were prospectively followed up at 3 months, 6 months, 9 months, and 12 months after discharge from Renmin Hospital of Wuhan University, Wuhan, China. Patients with a history of hypertension; diabetes; cardiovascular disease; cancer; and chronic lung disease, including asthma or chronic obstructive pulmonary disease; or a history of smoking documented at time of hospital admission were excluded at time of electronic case-note review. Patients who required intubation and mechanical ventilation were excluded given the potential for the consequences of mechanical ventilation itself to influence the factors under investigation. During the follow-up visits, patients were interviewed and underwent physical examination, routine blood test, pulmonary function tests (ie, diffusing capacity of the lungs for carbon monoxide [DLCO]; forced expiratory flow between 25% and 75% of forced vital capacity [FVC]; functional residual capacity; FVC; FEV; residual volume; total lung capacity; and vital capacity), chest high-resolution CT (HRCT), and 6-min walk distance test, as well as assessment using a modified Medical Research Council dyspnoea scale (mMRC).

Findings: Between Feb 1, and March 31, 2020, of 135 eligible patients, 83 (61%) patients participated in this study. The median age of participants was 60 years (IQR 52-66). Temporal improvement in pulmonary physiology and exercise capacity was observed in most patients; however, persistent physiological and radiographic abnormalities remained in some patients with COVID-19 at 12 months after discharge. We found a significant reduction in DLCO over the study period, with a median of 77% of predicted (IQR 67-87) at 3 months, 76% of predicted (68-90) at 6 months, and 88% of predicted (78-101) at 12 months after discharge. At 12 months after discharge, radiological changes persisted in 20 (24%) patients. Multivariate logistic regression showed increasing odds of impaired DLCO associated with female sex (odds ratio 8·61 [95% CI 2·83-26·2; p=0·0002) and radiological abnormalities were associated with peak HRCT pneumonia scores during hospitalisation (1·36 [1·13-1·62]; p=0·0009).

Interpretation: In most patients who recovered from severe COVID-19, dyspnoea scores and exercise capacity improved over time; however, in a subgroup of patients at 12 months we found evidence of persistent physiological and radiographic change. A unified pathway for the respiratory follow-up of patients with COVID-19 is required.

Funding: National Natural Science Foundation of China, UK Medical Research Council, and National Institute for Health Research Southampton Biomedical Research Centre.

Translation: For the Chinese translation of the abstract see Supplementary Materials section.
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http://dx.doi.org/10.1016/S2213-2600(21)00174-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8099316PMC
May 2021

Response to first-line treatment predicts progression-free survival benefit of small-cell lung cancer patients treated with anlotinib.

Cancer Med 2021 May 6. Epub 2021 May 6.

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

Background: Anlotinib significantly extended progression-free survival (PFS) and overall survival (OS) in small-cell lung cancer (SCLC) as third or later line treatment.

Methods: In this study, we retrospectively analyzed the efficacy and safety of anlotinib in the clinical practice and aimed to identify risk factors for predicting the clinical benefit of anlotinib in SCLC patients. 29 SCLC patients treated with anlotinib monotherapy or combination therapy as second or later line treatment were included. PFS, OS, objective response rate (ORR), disease control rate (DCR), and adverse events (AEs) were analyzed.

Results: In whole patients, the median PFS was 2.1 months (95% confidence interval (CI): 1.1-3.2 months); The ORR and DCR were 10.3% and 48.3%, respectively; The median OS was 7.2 months (95%CI: 3.2-11.2 months). Cox regression analysis demonstrated that response to first-line treatment was the independent risk factor for PFS. The ORR (20.0% vs. 0%) and DCR (53.3% vs. 42.9%) were promoted in patients treated with anlotinib combination therapy comparing to anlotinib monotherapy. The most common AEs were hoarseness, fatigue, decreased appetite, oral mucositis, and anemia. No treatment-related AEs graded 3 or more.

Conclusion: Anlotinib is an effective option for SCLC patients with tolerable toxicity as second or later line treatment. Patients sensitive to first-line treatment had longer PFS when treated with anlotinib. Anloitnib combined with other therapy increased the efficacy without adding toxicity.
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http://dx.doi.org/10.1002/cam4.3941DOI Listing
May 2021

A new method for facilitating ultrasound-guided in-plane cannulation of the subclavian vein: a randomized clinical trial.

Sci Rep 2021 May 5;11(1):9605. Epub 2021 May 5.

Department of Anesthesiology, Daping Hospital, Army Medical University, 10 ChangjiangZhilu, Yuzhong District, Chongqing, 400042, China.

The objective of this study was to propose a new method for facilitating needle-beam alignment ultrasound-guided in-plane catheterization of the subclavian vein (SCV). Three hundred patients were recruited, and ultrasound examination of the SCV was performed. Then, the patients were divided into two groups and SCV catheterization was performed: ultrasound-guided catheterization with the aiming method (group A) and ultrasound-guided catheterization with needle guide (group NG). The success rate, insertion time, number of skin breaks, number of needle redirections, needle visibility and rate of mechanical complications were documented and compared for each procedure. To depict the optimum long-axis view of the SCV, there was a 30° ± 7.3° angle (rotation) between the long axis of the ultrasound probe and the clavicle, while there was a 39° ± 7.4° angle (tilt) between the ultrasound beam plane and the right chest wall. The aiming method was associated with fewer skin breaks [(mean (IQR): 1 (1-1) times vs 1 (1-2) times, P = 0.009], a shorter time to cannulation [(mean (IQR): 39 (32-48.5) s vs 48 (44-54.8) s, P = 0.000] and more needle redirections [(mean (IQR): 0 (0-1) vs 0 (0-0), P = 0.000]. There were no differences between group A and group NG in the overall success rate, first puncture success rate, needle visibility or mechanical complication rate. In conclusion, during ultrasound-guided in-plane catheterization of the SCV, the aiming method provides comparable needle-beam alignment with a lower cannulation time than the needle guide technique.
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http://dx.doi.org/10.1038/s41598-021-88798-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8099870PMC
May 2021

Response Efficacy of PD-1 and PD-L1 Inhibitors in Clinical Trials: A Systematic Review and Meta-Analysis.

Front Oncol 2021 16;11:562315. Epub 2021 Apr 16.

Department of Medical Oncology, Chinese People's Liberation Army (PLA) General Hospital, Beijing, China.

Background: Immune checkpoint inhibitors targeting the PD-1/PD-L1 pathway have demonstrated promise in treating a variety of advanced cancers; however, little is known regarding their efficacy under various clinical situations, including different cancer types, treatment lines, drug combinations, and therapeutic regimens.

Methods: Published articles and conference abstracts (in English) in PubMed, Embase, the Cochrane Central Register, and Web of Science were searched up to February 10, 2020. The data were analyzed by the meta-analysis program in Stata.

Results: A total of 16,400 patients from 91 clinical trials were included in this meta-analysis. PD-1/PD-L1 inhibitors had a mean ORR of 19.56% (95% CI: 15.09-24.03), a median TTR of 2.05 months (m) (95%CI: 1.85-2.26), and a median DOR of 10.65 m (95%CI: 7.78-13.52). First-line treatment had a higher ORR (36.57% vs. 13.18%) but a shorter DOR (9.00 m vs. 13.42 m) compared to the second-line or subsequent treatment. Immunotherapy combined with chemotherapy (I+C) (46.81% [95%CI: 36.02-57.60]) had a statistically significant higher ORR compared to immunotherapy (I) (17.75% [95%CI: 14.47-21.03]) or immunotherapy combined with immunotherapy (I+O) (12.25% [95%CI: 1.56-22.94]), while I+C (8.09 m [95%CI: 6.86-9.32]) appeared to reduce the DOR compared to I (12.39 m [95%CI: 7.60-17.18]). PD-1 inhibitors were associated with better ORR (21.65% vs. 17.60%) and DOR (11.26 m vs. 10.03 m) compared to PD-L1 inhibitors. There were no significant differences in TTR under different situations.

Conclusions: PD-1/PD-L1 inhibitors were promising immunotherapeutic agents to achieve satisfactory response efficacies with different cancer types, treatment lines, drug combinations, and therapeutic regimens. This comprehensive summary of the response efficacy of PD-1/PD-L1 inhibitors serves as a reference for clinicians to make evidence-based decisions.
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http://dx.doi.org/10.3389/fonc.2021.562315DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8085334PMC
April 2021

Metabolites in the Tumor Microenvironment Reprogram Functions of Immune Effector Cells Through Epigenetic Modifications.

Front Immunol 2021 13;12:641883. Epub 2021 Apr 13.

Microbiology and Immunology Department, School of Medicine, Jinan University, Guangzhou, China.

Cellular metabolism of both cancer and immune cells in the acidic, hypoxic, and nutrient-depleted tumor microenvironment (TME) has attracted increasing attention in recent years. Accumulating evidence has shown that cancer cells in TME could outcompete immune cells for nutrients and at the same time, producing inhibitory products that suppress immune effector cell functions. Recent progress revealed that metabolites in the TME could dysregulate gene expression patterns in the differentiation, proliferation, and activation of immune effector cells by interfering with the epigenetic programs and signal transduction networks. Nevertheless, encouraging studies indicated that metabolic plasticity and heterogeneity between cancer and immune effector cells could provide us the opportunity to discover and target the metabolic vulnerabilities of cancer cells while potentiating the anti-tumor functions of immune effector cells. In this review, we will discuss the metabolic impacts on the immune effector cells in TME and explore the therapeutic opportunities for metabolically enhanced immunotherapy.
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http://dx.doi.org/10.3389/fimmu.2021.641883DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8078775PMC
April 2021

Does lock-down of Wuhan effectively restrict early geographic spread of novel coronavirus epidemic during chunyun in China? A spatial model study.

BMC Public Health 2021 04 29;21(1):825. Epub 2021 Apr 29.

Key Laboratory of Environmental Medicine Engineering, Ministry of Education; School of Public Health, Southeast University, Nanjing, 210009, Jiangsu, China.

Background: Prior to Wuhan lock-down in 2020, chunyun, the largest population mobility on this planet, had begun. We quantified impact of Wuhan lock-down on COVID-19 spread during chunyun across the nation.

Methods: During the period of January 1 to February 9, 2020, a total of 40,278 confirmed COVID-19 cases from 319 municipalities in mainland China were considered in this study. The cross-coupled meta-population methods were employed using between-city Baidu migration index. We modelled four scenarios of geographic spread of COVID-19 including the presence of both chunyun and lock-down (baseline); lock-down without chunyun (scenario 1); chunyun without lock-down (scenario 2); and the absence of both chunyun and lock-down (scenario 3).

Results: Compared with the baseline, scenario 1 resulted in 3.84% less cases by February 9 while scenario 2 and 3 resulted in 20.22 and 32.46% more cases by February 9. The geographic distribution of cases revealed that chunyun facilitated the COVID-19 spread in the majority but not all cities, and the effectiveness of Wuhan lock-down was offset by chunyun. Impacts of Wuhan lock-down during chunyun on the COVID-19 spread demonstrated heterogenetic geographic patterns.

Conclusion: Our results strongly supported the travel restriction as one of the effective responses and highlighted the importance of developing area-specific rather than universal countermeasures.
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http://dx.doi.org/10.1186/s12889-021-10837-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8082222PMC
April 2021

Differential effects of traditional and social media use on COVID-19 preventive behaviors: The mediating role of risk and efficacy perceptions.

J Health Psychol 2021 Apr 28:13591053211003125. Epub 2021 Apr 28.

Huazhong University of Science and Technology, China.

The study explored how traditional and social media use produced various cognitive responses toward COVID-19, including perceived severity, susceptibility, and efficacy, and direct and indirect facilitation of COVID-19 preventive behaviors. We tested the hypotheses on data collected from 433 university students in Wuhan, China, using structural equation modeling. We found that traditional media enhanced engagement for preventive behaviors both directly and indirectly by enhancing perceived severity and efficacy, whereas social media showed no impact on preventive behaviors, either directly or indirectly. Furthermore, the direct effect of traditional media on preventive behaviors was markedly stronger than the indirect effect through perceptions.
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http://dx.doi.org/10.1177/13591053211003125DOI Listing
April 2021

Rs2686344 and serum squamous cell carcinoma antigen could predict clinical efficacy of neoadjuvant chemotherapy for cervical cancer.

Curr Probl Cancer 2021 Apr 18:100755. Epub 2021 Apr 18.

Department of Gynecology & Obstetrics, the Central Hospital of Wuhan, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, P.R. China. Electronic address:

Objective: To evaluate the predictive value of a single nucleotide polymorphism (SNP) rs2686344 and squamous cell carcinoma antigen (SCCAg) levels in the clinical efficacy of neoadjuvant chemotherapy (NACT) for cervical cancer.

Methods: A total of 92 patients with stage IB2-IIIB carcinoma of the uterine cervix who received NACT treatment were enrolled. The relationship between the genotypes of SNP rs2686344 which is located on CAMKK2 on chromosome 12, SCCAg levels and the response to NACT was analyzed. The relationship between the SNP rs2686344 genotypes, SCCAg levels, the response to NACT and the five-year survival rate was evaluated.

Results: The effective group accounted for 84.85% in patients with low level (≤3.5 ng/mL) of post-treatment SCCAg (post-SCCAg), while the ineffective group accounted for 15.15%. The post-SCCAg levels and the genotypes of rs2686344 were significantly correlated with NACT response (P = 0.003, and P = 0.006). In patients with CC or CT genotype of SNP rs2686344, effective group accounted for 81.18%, while ineffective group accounted for 18.82%; For patients with TT genotype, effective response group accounted for 28.57%, ineffective group accounted for 71.43%. Post-SCCAg level >3.5 ng/mL and TT genotype of SNP rs2686344 showed as independent risk factors for NACT response in the multivariate analysis (P = 0.002, and P = 0.048). There was no significant difference in 5-year overall survival and 5-year disease-free survival between patients with different levels of post-SCCAg, or among different rs2686344 genotypes.

Conclusion: The high level of post-SCCAg (>3.5 ng/mL) and TT genotype of rs2686344 may suggest a higher risk of poor response to NACT.
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http://dx.doi.org/10.1016/j.currproblcancer.2021.100755DOI Listing
April 2021

Identification of Metastasis-Associated MicroRNAs in Metastatic Melanoma by miRNA Expression Profile and Experimental Validation.

Front Genet 2021 9;12:663110. Epub 2021 Apr 9.

Department of Oncology, Longhua Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, China.

It is reported that microRNAs (miRNA) have paramount functions in many cellular biological processes, development, metabolism, differentiation, survival, proliferation, and apoptosis included, some of which are involved in metastasis of tumors, such as melanoma. Here, three metastasis-associated miRNAs, miR-18a-5p (upregulated), miR-155-5p (downregulated), and miR-93-5p (upregulated), were identified from a total of 63 different expression miRNAs (DEMs) in metastatic melanoma compared with primary melanoma. We predicted 262 target genes of miR-18a-5p, 904 miR-155-5p target genes, and 1220 miR-93-5p target genes. They participated in pathways concerning melanoma, such as TNF signaling pathway, pathways in cancer, FoxO signaling pathway, cell cycle, Hippo signaling pathway, and TGF-beta signaling pathway. We identified the top 10 hub nodes whose degrees were higher for each survival-associated miRNA as hub genes through constructing the PPI network. Using the selected miRNA and the hub genes, we constructed the miRNA-hub gene network, and PTEN and CCND1 were found to be regulated by all three miRNAs. Of note, miR-155-5p was obviously downregulated in metastatic melanoma tissues, and miR-18a-5p and miR-93-5p were obviously regulated positively in metastatic melanoma tissues. In validating experiments, miR-155-5p's overexpression inhibited miR-18a-5p's and miR-93-5p's expression, which could all significantly reduce SK-MEL-28 cells' invasive ability. Finally, miR-93-5p and its potential target gene UBC were selected for further validation. We found that miR-93-5p's inhibition could reduce SK-MEL-28 cell's invasive ability through upregulated the expression of UBC, and the anti-invasive effect was reserved by downregulation of UBC. The results show that the selected three metastasis-associated miRNAs participate in the process of melanoma metastasis via regulating their target genes, providing a potential molecular mechanism for this disease.
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http://dx.doi.org/10.3389/fgene.2021.663110DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8063111PMC
April 2021

[Chinese Experts Consensus on Immune Checkpoint Inhibitors 
for Non-small Cell Lung Cancer (2020 Version)].

Zhongguo Fei Ai Za Zhi 2021 Apr 26;24(4):217-235. Epub 2021 Apr 26.

Cancer Center, Eastern Theater General Hospital of the Chinese PLA, Nanjing 210002, China.

Non-small cell lung cancer (NSCLC) is the most common pathological type of lung cancer. The systemic antitumor therapy of advanced NSCLC has undergone renovations of chemotherapy, targeted therapy and immunotherapy, which results in greatly improved survival for patients with advanced NSCLC. Immune checkpoint inhibitors (ICIs), especially targeting programmed cell death protein 1 (PD-1)/programmed death-ligand 1 (PD-L1), has changed the treatment paradigm of NSCLC. ICIs have become the standard treatment for advanced NSCLC without epidermal growth factor receptor(EGFR) mutation or anaplastic lymphomakinase(ALK) translocation in the first- or second-line setting, and for locally advanced NSCLC following concurrent radiotherapy and chemotherapy. ICIs are also promising in adjuvant/neoadjuvant therapy. More and more ICIs have been approved domestically for the treatment of NSCLC. Led by the NSCLC expert committee of Chinese Society of Clinical Oncology (CSCO), this consensus was developed and updated based on thoroughly reviewing domestic and foreign literatures, clinical trial data, systematic reviews, experts' discussion and the consensus(2019 version). This consensus will aid domestic clinicians in the treatment of NSCLC with ICIs.
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http://dx.doi.org/10.3779/j.issn.1009-3419.2021.101.13DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8105610PMC
April 2021

Emergence of additional drug resistance during treatment of multidrug-resistant tuberculosis in China: a prospective cohort study.

Clin Microbiol Infect 2021 Apr 23. Epub 2021 Apr 23.

Department of Epidemiology, School of Public Health and Key Laboratory of Public Health Safety, Fudan University, Shanghai, China. Electronic address:

Objectives: Little is known about how additional second-line drug resistance emerges during multidrug-resistant tuberculosis (MDR-TB) treatment. The present study aimed to investigate the influence of microevolution, exogenous reinfection and mixed infection on second-line drug resistance during the recommended 2-year MDR-TB treatment.

Methods: Individuals with MDR-TB were enrolled between 2013 and 2016 in a multicentre prospective observational cohort study and were followed up for 2 years until treatment completion. Whole-genome sequencing (WGS) was applied for serial Mycobacterium tuberculosis isolates from study participants throughout the treatment, to study the role of microevolution, exogenous reinfection and mixed infection in the development of second-line drug resistance.

Results: Of the 286 enrolled patients with MDR-TB, 63 (22.0%) M. tuberculosis isolates developed additional drug resistance during the MDR-TB treatment, including 5 that fulfilled the criteria of extensively drug-resistant TB. By comparing WGS data of serial isolates retrieved from the patients throughout treatment, 41 (65.1%) of the cases of additional second-line drug resistance were the result of exogenous reinfection, 18 (28.6%) were caused by acquired drug resistance, i.e. microevolution, while the remaining 4 (6.3%) were caused by mixed infections with drug-resistant and drug-susceptible strains. In multivariate analysis, previous TB treatment (adjusted hazard ratio (aHR) 2.51, 95% CI 1.51-4.18), extensive disease on chest X-ray (aHR 3.39, 95% CI 2.03-5.66) and type 2 diabetes mellitus (aHR 4.00, 95% CI 2.22-7.21) were independent risk factors associated with the development of additional second-line drug resistance.

Conclusions: A large proportion of additional second-line drug resistance emerging during MDR-TB treatment was attributed to exogenous reinfection, indicating the urgency of infection control in health facilities as well as the need for repeated drug susceptibility testing throughout MDR-TB treatment.
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http://dx.doi.org/10.1016/j.cmi.2021.04.001DOI Listing
April 2021