Publications by authors named "Lin Fan"

562 Publications

A nomogram combining plasma fibrinogen and systemic immune‑inflammation index predicts survival in patients with resectable gastric cancer.

Sci Rep 2021 May 13;11(1):10301. Epub 2021 May 13.

Department of General Surgery, The First Affiliated Hospital of Xi'an Jiaotong University, 277 Yanta West Road, Xi'an, 710061, Shanxi Province, China.

Hyperfibrinogenemia and cancer-associated systemic inflammatory response are strongly associated with cancer progression and prognosis. We aimed to develop a novel prognostic score (F-SII score) on the basis of preoperative fibrinogen (F) and systemic immunoinflammatory index (SII), and evaluate its predictive value in patients with resectable gastric cancer (GC). Patients diagnosed with GC between January 2012 and December 2016 were reviewed. The F-SII score was 2 for patients with a high fibrinogen level (≥ 3.37 g/L) and a high SII (≥ 372.8), whereas that for patients with one or neither was 1 or 0, respectively. A high F-SII score was significantly associated with older patient age, a high ASA score, large tumor size, large proportion of perineural invasion, and late TNM stage. Multivariate analysis indicated that the F-SII score, histological grade, and TNM stage were independent factors for overall survival (OS). The Harrell's concordance index (C-index) of a nomogram based on the F-SII score and several clinicopathological manifestations was 0.72, which showed a better predictive ability for OS than the TNM stage alone (0.68). In conclusion, preoperative F-SII may serve as a useful predictive factor for OS and refine outcome prediction for patients with resectable GC combined with traditional clinicopathological analysis.
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http://dx.doi.org/10.1038/s41598-021-89648-9DOI Listing
May 2021

Image reconstruction with the chaotic fiber laser in scattering media.

Appl Opt 2021 May;60(13):4004-4012

The reconstruction of the size, position, optical properties, and structure of the object in scattering media was realized with a chaotic fiber laser. The light from the chaotic fiber laser was split into two parts. One part was used as the detection signal to detect the object, and the other was used as the reference signal; then, the two signals were cross correlated. The attenuation of light in scattering media was attributed to scattering and absorption. The theoretical model of the peak value of cross correlation of the chaotic signals as projection data were established by the attenuation law, and the filtered back-projection algorithms were used to realize the image reconstruction. The mean squared error, the normalized mean squared error, the peak signal-to-noise ratio, and the structural similarity index of the reconstructed image were analyzed. The results show that the high resolution of the reconstructed image benefits from the high signal-to-noise ratio with the chaotic fiber laser based on a delta-like cross-correlation function.
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http://dx.doi.org/10.1364/AO.420441DOI Listing
May 2021

Mycobacterium tuberculosis effector PPE36 attenuates host cytokine storm damage via inhibiting macrophage M1 polarization.

J Cell Physiol 2021 May 7. Epub 2021 May 7.

State Key Laboratory Breeding Base of Eco-Environment and Bio-Resource of the Three Gorges Area, Key Laboratory of Eco-environments in Three Gorges Reservoir Region, Ministry of Education, School of Life Sciences, Institute of Modern Biopharmaceuticals, Southwest University, Chongqing, China.

Tuberculosis caused by Mycobacterium tuberculosis remains a serious global public health threat. Macrophage polarization is crucial for the innate immunity against M. tuberculosis. However, how M. tuberculosis interferes with macrophage polarization is elusive. We demonstrated here that M. tuberculosis PPE36 (Rv2108) blocked macrophage M1 polarization, preventing the cytokine storm, and alleviating inflammatory damage to mouse immune organs. PPE36 inhibited the polarization of THP-1 cell differentiation to M1 macrophages, reduced mitochondrial dehydrogenase activity, inhibited the expression of CD16, and repressed the expression of pro-inflammatory cytokines IL-6 and TNF-α, as well as chemokines CXCL9, CXCL10, CCL3, and CCL5. Intriguingly, in the mouse infection model, PPE36 significantly alleviated the inflammatory damage of immune organs caused by a cytokine storm. Furthermore, we found that PPE36 inhibited the polarization of macrophages into mature M1 macrophages by suppressing the ERK signaling. The study provided novel insights into the function and mechanism of action of M. tuberculosis effector PPE36 both at the cellular and animal level.
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http://dx.doi.org/10.1002/jcp.30411DOI Listing
May 2021

Association Between ApoA1 Gene Polymorphisms and Antipsychotic Drug-Induced Dyslipidemia in Schizophrenia.

Neuropsychiatr Dis Treat 2021 30;17:1289-1297. Epub 2021 Apr 30.

Department of Medical Laboratory, Huai'an Third People's Hospital, Huai'an, People's Republic of China.

Purpose: Dyslipidemia frequently occurs in schizophrenia patients treated with antipsychotic drugs (APDs), especially atypical APDs. Apolipoprotein A1 (ApoA1) plays a key role in lipid metabolism. The aim of this study was to investigate whether ApoA1 gene polymorphisms are associated with APD-induced dyslipidemia in schizophrenia patients.

Patients And Methods: A total of 1987 patients with schizophrenia were enrolled in this study. Serum lipid profiles were determined with a biochemistry analyzer. Genotyping for the rs5072 polymorphism of ApoA1 was performed with TaqMan assay. Logistic regression analysis was carried out to evaluate the relationship between ApoA1 gene polymorphisms and APD-induced dyslipidemia. The effects of drug classification (typical vs atypical APD) and drug regimen (monotherapy vs combination therapy) on serum lipid levels were also analyzed.

Results: A significant association was found between rs5072 and triglyceride (TG) levels in the recessive model of the logistic regression analysis (adjusted odds ratio [OR]=1.50, 95% confidence interval [CI]: 1.03, 2.17; P<0.05). TG level was significantly higher in patients treated with combination therapy (1.03 (0.71, 1.51) mmol/l) compared to monotherapy (0.93 (0.67, 1.43) mmol/l) and was also associated with sex. There were significant differences in TG levels among the three genotypes of ApoA1 rs5072 (GG, GA, and AA) in the whole study population and in patients treated with atypical APDs.

Conclusion: The ApoA1 rs5072 variant is associated with dysregulated TG metabolism in schizophrenia patients treated with APDs, which may increase susceptibility to dyslipidemia.
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http://dx.doi.org/10.2147/NDT.S305200DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8096449PMC
April 2021

Rapamycin protects against aristolochic acid nephropathy in mice by potentiating mammalian target of rapamycin‑mediated autophagy.

Mol Med Rep 2021 Jul 6;24(1). Epub 2021 May 6.

Department of Nephrology, Qilu Hospital, Shandong University, Jinan, Shandong 250015, P.R. China.

Autophagy serves a crucial role in the etiology of kidney diseases, including drug‑induced renal impairment, inherited kidney disease, diabetic nephropathy and aristolochic acid nephropathy (AAN) and is, therefore, a potential target for treatment. We previously demonstrated that rapamycin could attenuate AAN in mice; however, the underlying mechanism remains to be elucidated. Therefore, whether the renal protective effect of rapamycin (an autophagy activator) is related to autophagy in aristolochic acid (AA)‑treated mice was of particular interest. The pathophysiological roles of rapamycin were investigated in AA‑induced nephrotoxicity in mice and the mechanisms of rapamycin action were explored by evaluating the modulation of autophagy in rapamycin‑treated mice and cultured renal tubular epithelial cells. Supplementation with rapamycin reversed AA‑induced kidney injury in mice and improved AA‑induced autophagy damage and . Mechanistically, rapamycin inhibited the renal expression of phosphorylated (p‑)mammalian target of rapamycin (mTOR) and p‑ribosomal S6 protein kinase 1, which in turn activated renal autophagy and decreased apoptosis, probably by removing AA‑elicited damaged mitochondria and misfolded proteins. The findings of the present study demonstrated that rapamycin protects against AA‑induced nephropathy by activating the mTOR‑autophagy axis and suggested that rapamycin may be a promising pharmacological target for the treatment of AAN.
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http://dx.doi.org/10.3892/mmr.2021.12134DOI Listing
July 2021

Use of the prostate-specific antigen test in the U.S. for men age 30 to 64 in 2011 to 2017 using a large commercial claims database: Implications for practice interventions.

Cancer Rep (Hoboken) 2021 May 2:e1365. Epub 2021 May 2.

Division of Cancer Prevention and Control, CDC, Atlanta, Georgia, USA.

Background: Given the public health relevance of PSA-based screening, various professional organizations have issued recommendations on the use of the PSA test to screen for prostate cancer in different age groups.

Aim: Using a large commercial claims database, we aimed to determine the most recent rates of PSA testing for privately insured men age 30 to 64 in the context of screening recommendations.

Methods And Results: Data from employer plans were from MarketScan commercial claims database. Annual PSA testing rate was the proportion of men with ≥1 paid test(s) per 12 months of continuous enrollment. Men with diagnosis of any prostate-related condition were excluded. Annual percent change (APC) in PSA test use was estimated using joinpoint regression analysis. In 2011 to 2017, annual testing rate encompassing 5.02 to 5.53 million men was approximately 1.4%, age 30 to 34; 3.4% to 4.1%, age 35 to 39; 11% to 13%, age 40 to 44; 18% to 21%, age 45 to 49; 31% to 33%, age 50 to 54; 35% to 37%, age 55 to 59; and 38% to 41%, age 60 to 64. APC for 2011 to 2017 was -0.5% (P = .11), age 30 to 34; -3.0% (P = .001), age 35-39; -3.1% (P < .001), age 40 to 44; -2.4% (P = .001), age 45 to 49; -0.2% (P = .66), age 50 to 54; 0.0% (P = .997), age 55 to 59; and -3.3% (P = .054) from 2011 to 2013 and 1.2% (P = .045) from 2013 to 2017, age 60 to 64. PSA testing rate decreased from 2011 to 2017 for age groups between 35 and 49 by 13.4% to 16.9%.

Conclusions: Based on these data, PSA testing rate has modestly decreased from 2011 to 2017. These results, however, should be considered in view of the limitation that MarketScan claims data may not be equated to actual PSA testing practices in the entire U.S. population age 30 to 64. Future research should be directed to understand why clinicians continue ordering PSA test for men younger than 50.
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http://dx.doi.org/10.1002/cnr2.1365DOI Listing
May 2021

Effects of phonological loop on inferential processing during Chinese text reading: Evidence from a dual-task paradigm.

Psych J 2021 May 2. Epub 2021 May 2.

School of International Studies, Hebei Normal University, Hebei, China.

The role of working memory (WM) components, such as phonological loop, in online inferential processing has thus far not been empirically examined with a dual-task paradigm. The current study used an online method to examine the effects of the two components of phonological loop-the articulatory rehearsal device and the phonological store device-on online causal inference generation during Chinese text reading. Eighty-five Chinese university students read three-sentence inference and control texts and responded to comprehension questions related to targeted inferences in different reading conditions. The results showed that in the articulatory suppression condition, response times (RTs) for comprehension questions of inference texts were considerably longer, and response errors were significantly higher than those in the normal reading condition, which indicated the effects of the articulatory rehearsal device on readers' online causal inference processes during Chinese text reading. Moreover, RTs for comprehension questions of inference texts in the irrelevant speech condition were significantly shorter than those in the normal reading condition, suggesting effects of the phonological store device on readers' causal inference processes during reading. Taken together, these findings indicate that the articulatory rehearsal device plays an important role in inference processes, but readers allocate more cognitive resources to facilitate the construction of causal relations during text-based inferential comprehension when function of the phonological store device is impaired.
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http://dx.doi.org/10.1002/pchj.451DOI Listing
May 2021

Use of the prostate-specific antigen (PSA) test in the United States for men age ≥65, 1999-2015: Implications for practice interventions.

Cancer Rep (Hoboken) 2021 May 1:e1352. Epub 2021 May 1.

Division of Cancer Prevention and Control, CDC, Atlanta, Georgia, USA.

Background: Various professional organizations have issued recommendations on use of the PSA test to screen for prostate cancer in different age groups.

Aims: Using Medicare claims databases, we aimed to determine rates of PSA testing in the context of screening recommendations during 1999-2015 for US men age ≥65, stratified by age group and census regions, after excluding claims relating to all prostate-related conditions.

Methods And Results: Medicare claims databases encompassed 9.71-11.12 million men for the years under study. PSA testing rate was the proportion of men with ≥1 test(s) per 12 months of continuous enrollment. Men diagnosed with any prostate-related condition were excluded. Annual percent change (APC) in PSA test use was estimated using joinpoint regression analysis. In 1999-2015, annual testing rate was 10.1%-23.1%, age ≥85; 16.6%-31.0%, age 80-84; 23.8%-35.8%, age 75-79; 28.3%-36.9%, age 70-74; and 26.4%-33.6%, age 65-69. From 1999 to 2015, PSA testing rate decreased 40.7%, 29.9%, 13.9%, and 2.9%, respectively, for men age ≥85, 80-84, 75-79, and 70-74. For men age 65-69, test use increased by 0.3%. Significant APC trends were: APC = +8.1%, P = .029 and APC = -9.0%, P < .001 for men age ≥85; APC = -7.1%, P = .001 for men age 80-84; APC = -2.5%, P < .001 for men age 75-79; APC = -3.3%, P = .007 for men age 70-74; and APC = -5.2%, P = .014 for men age 65-69.

Coclusion: Although decreased from 1999 to 2015, PSA testing rates remained high for men age ≥70. Further research could help understand why PSA testing continues inconsistent with recommendations.
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http://dx.doi.org/10.1002/cnr2.1352DOI Listing
May 2021

Hypothermic oxygenated perfusion (HOPE) with defatting cocktail further improves steatotic liver grafts in a transplantation rat model.

Artif Organs 2021 Apr 28. Epub 2021 Apr 28.

Zhongnan Hospital of Wuhan University, Institute of Hepatobiliary Diseases, Wuhan University, Transplant Center of Wuhan University, Hubei Key Laboratory of Medical Technology on Transplantation, Wuhan Hubei, 430071, PR China.

Background: In this study, we evaluated the restoring and defatting effect of hypothermic oxygenated perfusion (HOPE) on severe steatotic liver grafts with a defatting cocktail (DF) in a rat model.

Methods: Severe (≥60%) hepatic macrosteatosis was induced by a high-fat diet (HFD) for six weeks, after which the rats were randomly divided into four following groups: Control group, with lean livers being preserved in static cold storage (SCS) at 0-4℃ for 45 min; SCS group, with a steatotic liver graft (SLG) being preserved in SCS at 0-4℃ for 4 hours; HOPE group, where SLG was perfused with 3-h HOPE followed by 1-h SCS; HOPE+DF group, HOPE with the addition of DF. Graft function after orthotopic liver transplantation was assessed in terms of mitochondrial function (ATP, Glycogen), endoplasmic reticulum stress (PPY, GRP78, CHOP, and ATF-6), cell apoptosis (Tunel assay, Caspase-3), inflammatory level (HMGB1, TLR4, IL-1β, IL-6. TNF-α, Factor V), and post-transplantation survival.

Results: HOPE protected steatotic liver grafts from microcirculation disturbance and endoplasmic reticulum stress and then promoted ATP and glycogen synthesis that improved mitochondrial function. Meanwhile, under conditions of ischemia-reperfusion injury, it prevented nuclear injury and endothelial damage by suppressing the release of an inflammatory mediator. The high efficacy of HOPE was enhanced after the addition of the defatting cocktail.

Conclusion: Defatting cocktail agents cannot promote the lipid decomposition of the steatotic liver graft at 0-4℃, but they can further improve steatotic liver and postoperative survival compared to the HOPE. The defatted steatotic liver grafts can be safely used in rat orthotopic liver transplantation.
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http://dx.doi.org/10.1111/aor.13976DOI Listing
April 2021

Facilities for Centralized Isolation and Quarantine for the Observation and Treatment of Patients with COVID-19: Experience from Wuhan, China.

Engineering (Beijing) 2021 Apr 22. Epub 2021 Apr 22.

China CDC Key Laboratory of Environment and Population Health, National Institute of Environmental Health, Chinese Center for Disease Control and Prevention, Beijing 100021, China.

The coronavirus disease 2019 (COVID-19) pandemic increased the burden on many healthcare systems and in the process, exposed the need for medical resources and physical space. While few studies discussed the efficient utilization of medical resources and physical space so far. Therefore, this study aimed to summarize experiences related to facilities used for centralized isolation for medical observation and treatment during the COVID-19 pandemic in China and to provide suggestions to further improve the management of confirmed cases, suspected cases, and close contacts. In China, three types of facilities for centralized isolation (Fangcang shelter hospitals, refitted non-designated hospitals, and quarantine hotels) underwent retrofitting for the treatment and isolation of confirmed and suspected cases. These facilities mitigated the immediate high demand for space. Moreover, in order to minimize infection risks in these facilities, regulators and governmental agencies implemented new designs, management measures, and precautionary measures to minimize infection risk. Other countries and regions could refer to China's experience in optimally allocating social resources in response to the COVID-19 pandemic. As a conclusion, government should allocate social resources and construct centralized isolation and quarantine facilities for an emergency response, health authorities should issue regulations for centralized isolation facilities and pay strict attention to the daily management of these facilities, a multidisciplinary administration team is required to support the daily operation of a centralized isolation facility, in-depth studies and international collaboration on the centralized isolation policy are encouraged.
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http://dx.doi.org/10.1016/j.eng.2021.03.010DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8061092PMC
April 2021

Quantitative visual pathway abnormalities predict visual field defects in patients with pituitary adenomas: a diffusion spectrum imaging study.

Eur Radiol 2021 Apr 24. Epub 2021 Apr 24.

Department of Radiology, Shenzhen Second People's Hospital, the First Affiliated Hospital of Shenzhen University, Shenzhen, 518035, Guangdong, China.

Objectives: This study was to investigate clinical applicability of diffusion spectrum imaging (DSI) for quantitative detection of visual pathway abnormalities to predict the degree of visual field defects (VFD) in patients with pituitary adenomas.

Methods: Sixty-five patients with pituitary adenomas and 33 healthy controls underwent conventional MRI and DSI scanning that allowed high-angular-resolution fiber tracking. Optic chiasmal compression and VFD were confirmed in all patients via radiological and neuro-ophthalmological examinations. Quantitative assessments of chiasmal lift, VFD, and DSI parameters from the optic nerve, optic tract, and optic radiation were performed. Group comparisons and correlation analyses were conducted in patients and controls. Using the 5-fold cross-validation method, the support vector machine classifiers were constructed to predict the degree of visual defects.

Results: The mean values of quantitative anisotropy and generalized fractional anisotropy in optic nerve and optic tract showed significant differences between patients and controls (p < 0.05). These parameters were also significantly correlated with the chiasmal lift distance and degree of visual defects (p < 0.05). All patients were divided into mild (n = 42) and severe (n = 23) VFD groups, using the mean deviation value of -8 dB as the threshold. The classifiers achieved an accuracy of 0.83, sensitivity of 0.78, and specificity of 0.86 to discriminate patients with mild and severe visual defects.

Conclusions: Using high-angular-resolution fiber tracking, DSI may provide quantitative information to detect visual pathway abnormalities and be a potential diagnostic tool for determining the degree of visual field defects in pituitary adenomas.

Key Points: • Abnormal QA and GFA values of optic nerve and optic tract in adenoma patients • Close relationship between DSI parameters and VFD degree in adenoma patients • The classifiers achieved an accuracy of 0.83, sensitivity of 0.78, and specificity of 0.86 to discriminate patients with mild and severe VFD.
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http://dx.doi.org/10.1007/s00330-021-07878-xDOI Listing
April 2021

Source, Characterization of Indoor Dust PAHs and the Health Risk on Chinese Children.

Curr Med Sci 2021 Apr 20;41(2):199-210. Epub 2021 Apr 20.

China CDC Key Laboratory of Environment and Population Health, National Institute of Environmental Health, Chinese Center for Disease Control and Prevention, Beijing, 100021, China.

Polycyclic aromatic hydrocarbons (PAHs) in indoor dust are one of the common exposure sources for children worldwide. The aim of this study is to explore PAHs pollution status in indoor dust and estimate health risk on Chinese children with big data. Weighted average concentration was used to analyze source and characterization of PAHs in indoor dust based on peer-reviewed literature. According to specific inclusion criteria, 17 studies were included finally to analyze weighted average concentration. The national average concentration of ΣPAHs was approximately 25.696 µg/g. The highest concentration of ΣPAHs was in Shanxi (2111.667 µg/g), and the lowest was in Hong Kong (1.505 µg/g). The concentrations in Shanxi and Guangdong were higher than national level and the over standard rate was 18.18%. The concentrations of individual PAHs varied greatly across the country, and Flu in Shanxi was the highest (189.400 µg/g). The sources of PAHs varied in different regions and combustion processes played a leading role. PAHs exposure through ingestion and dermal contact was more carcinogenic than inhalation. The incremental lifetime cancer risk model indicated that children lived in Shanxi were found in the highest health risk coupled with the highest BaPE concentration (54.074 µg/g). Although PAHs concentrations of indoor dust showed a downward trend from 2005 to 2018, indoor environmental sanitation should be improved with multidisciplinary efforts. Health standard should be possibly established to minimize children exposure to PAHs in indoor dust in China.
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http://dx.doi.org/10.1007/s11596-021-2337-yDOI Listing
April 2021

Double-endpoint Genotoxicity Quantification and PAHs Characterization of Drinking Water Source alongside Polluted Yinghe River with High Tumor Mortality.

Curr Med Sci 2021 Apr 20;41(2):189-198. Epub 2021 Apr 20.

National Institute of Environmental Health, Chinese Center for Disease Control and Prevention, China CDC Key Laboratory of Environment and Population Health, Beijing, 100021, China.

The etiology for the high tumor mortality in heavy polluted Yinghe river basin is still unclear and polycyclic aromatic hydrocarbons (PAHs) belong to the priority pollutants in water based on the former surveillance data. In order to explore the potential genotoxicants contributing to the double-endpoint genotoxicity of polluted drinking water source, 12 groundwater and 3 surface water samples were collected from 3 villages and the nearby rivers alongside Yinghe river basin, respectively and their comprehensive genotoxicity was estimated with a bioassay group of SOS/umu test and micronucleus (MN) test (MNT). Some groundwater samples showed positive genotoxicity and all surface water samples were highly genotoxic. Eight groundwater samples showed DNA genotoxic effect with the average 4-NQO equivalent concentration (TEQ) of 0.067 µg/L and 0.089 µg/L in wet and dry season, respectively. The average MN ratios of groundwater samples were 14.19‰ and 17.52‰ in wet and dry season, respectively. Groundwater samples showed different genotoxic effect among 3 villages. The total PAHs concentrations in all water samples ranged from 8.98 to 25.17 ng/L with an average of 14.97±4.85 ng/L. BaA, CHR, BkF, BaP and DBA were the main carcinogenic PAHs contributing to the genotoxicity of water samples. In conclusion, carcinogenic PAHs are possibly related to the high tumor mortality in the target area. Characterization of carcinogenic PAHs to genotoxicity of drinking water source may shed light on the etiology study for high tumor mortality in Yinghe river basin.
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http://dx.doi.org/10.1007/s11596-021-2336-zDOI Listing
April 2021

Characterization and exposure assessment of household fine particulate matter pollution in China.

Indoor Air 2021 Apr 20. Epub 2021 Apr 20.

China CDC Key Laboratory of Environment and Population Health, National Institute of Environmental Health, Chinese Center for Disease Control and Prevention, Beijing, China.

Household fine particulate matter (PM ) pollution greatly impacts residents' health. To explore the current national situation of household PM pollution in China, a study was conducted based on literature published from 1998 to 2018. After extracting data from the literature in conformity with the requirements, the nationwide household-weighted mean concentration of household PM (HPL) was calculated. Subgroup analyses of spatial, geographic, and temporal differences were also done. The estimated overall HPL in China was 132.2 ± 117.7 μg/m . HPL in the rural area (164.3 ± 104.5 μg/m ) was higher than that in the urban area (123.9 ± 122.3 μg/m ). For HPLs of indoor sampling sites, the kitchen was the highest, followed by the bedroom and living room. There were significant differences of geographic distributions. The HPLs in the South were higher than the North in four seasons. The inhaled dose of household PM among school-age children differed from provinces with the highest dose up to 5.9 μg/(kg·d). Countermeasures should be carried out to reduce indoor pollution and safeguard health urgently.
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http://dx.doi.org/10.1111/ina.12843DOI Listing
April 2021

A Rapid Screening Workflow to Identify Potential Combination Therapy for GBM using Patient-Derived Glioma Stem Cells.

J Vis Exp 2021 03 28(169). Epub 2021 Mar 28.

Department of Cell Biology, School of Basic Medical Sciences, Nanjing Medical University; Institute for Brain Tumors & Key Laboratory of Rare Metabolic Diseases, Nanjing Medical University; Nanjing Medical University Affiliated Cancer Hospital; Key Laboratory of Human Functional Genomics of Jiangsu Province;

The glioma stem cells (GSCs) are a small fraction of cancer cells which play essential roles in tumor initiation, angiogenesis, and drug resistance in glioblastoma (GBM), the most prevalent and devastating primary brain tumor. The presence of GSCs makes the GBM very refractory to most of individual targeted agents, so high-throughput screening methods are required to identify potential effective combination therapeutics. The protocol describes a simple workflow to enable rapid screening for potential combination therapy with synergistic interaction. The general steps of this workflow consist of establishing luciferase-tagged GSCs, preparing matrigel coated plates, combination drug screening, analyzing, and validating the results.
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http://dx.doi.org/10.3791/62312DOI Listing
March 2021

Associations between sleep duration patterns and cognitive decline trajectories in older Chinese adults.

Aging Clin Exp Res 2021 Apr 10. Epub 2021 Apr 10.

Department of Preventive Medicine, North Sichuan Medical College, Fujiang Road, Shunqing, Nanchong, 234, Sichuan, China.

Background: Abnormal sleep duration has been identified as a risk factor for cognitive decline. However, most studies have measured sleep duration and cognitive function at a single time point, while both tend to decrease with age.

Aims: This study aimed to investigate the association between changes in sleep duration patterns and cognitive trajectories in older adults.

Methods: Using longitudinal data (2005-2014) from the Chinese Longitudinal Healthy Longevity Survey, a total of 4347 subjects were included in this study. Cognitive function was measured with the Chinese version of the Mini-Mental State Examination. Group-based trajectory models were used to identify the trajectories of sleep duration and cognitive decline within the study sample as the participants aged. Furthermore, the association between sleep duration patterns and cognitive trajectories was examined by multinomial logistic regression analysis.

Results: Using the medium-stable sleep duration pattern as a reference, the trajectory with a long and increased sleep duration pattern was more likely to be associated with the slight cognitive decline trajectory (OR = 1.80; 95% CI 1.31-2.44). Persistent short sleep was associated with a decreased likelihood of having a rapid cognitive decline trajectory (OR = 0.32; 95% CI 0.12-0.75).

Discussion: Changes in sleep duration over time were independently associated with cognitive decline and may be a marker of cognitive decline.

Conclusions: Tracking of sleep duration over time in older adults may provide a useful insight for prevention of cognitive decline, and the increased sleep duration should be noticed with greater vigilance.
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http://dx.doi.org/10.1007/s40520-021-01851-wDOI Listing
April 2021

Diluted-CdS Quantum Dot-Assisted SnO Electron Transport Layer with Excellent Conductivity and Suitable Band Alignment for High-Performance Planar Perovskite Solar Cells.

ACS Appl Mater Interfaces 2021 Apr 31;13(14):16326-16335. Epub 2021 Mar 31.

College of Mechanical Engineering, JiLin Engineering Normal University, Changchun 130052, PR China.

An electron transport layer (ETL) with excellent conductivity and suitable band alignment plays a key role in accelerating charge extraction and transfer for achieving highly efficient planar perovskite solar cells (PSCs). Herein, a novel diluted-cadmium sulfide quantum dot (CdS QD)-assisted SnO ETL has been developed with a low-temperature fabrication process. The slight addition of CdS QDs first enhances the crystallinity and flatness of SnO ETLs so that it provides a promising workstation to obtain high-quality perovskite absorption layers. It also amazingly increases the conductivity of the SnO ETL by an order of magnitude and regulates the energy level matching between the SnO ETL and perovskite. These outstanding properties greatly accelerate the charge extraction and transfer. Thus, the MAPbI-based PSCs with such a diluted-CdSQD-assisted SnO ETL achieve a maximum power conversion efficiency of 20.78% and obtain a better stability of devices in air. These findings testify the importance and potential of semiconductor QD modification on ETLs, which may pave the way for developing such composite ETLs for further enhancing photovoltaic performance of planar PSCs.
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http://dx.doi.org/10.1021/acsami.1c00896DOI Listing
April 2021

Transesophageal electrophysiology study in the diagnosis of dual atrioventricular nodal nonreentrant tachycardia.

Ann Noninvasive Electrocardiol 2021 Mar 30:e12845. Epub 2021 Mar 30.

Division of Cardiology and Department of Internal Medicine, TongJi Hospital, TongJi Medical College, Huazhong University of Science and Technology, Wuhan, China.

"Double fire" is generally characterized by 1:2 atrioventricular conduction of sinus beats traveling down fast and slow pathways that result in double ventricular response. When this phenomenon repeats rapidly, dual atrioventricular nodal nonreentrant tachycardia (DAVNNT) occurs. We report a case of an irregular tachycardia with a comprehensive record that includes an electrocardiogram, a transesophageal electrophysiology study, and an intracardiac electrophysiology study. This is the first report of transesophageal electrophysiology study in the diagnosis of DAVNNT. A diagnosis of DAVNNT was deduced, and the patient was successfully treated with radiofrequency ablation of the slow pathway.
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http://dx.doi.org/10.1111/anec.12845DOI Listing
March 2021

Aquaporin 3 promotes human extravillous trophoblast migration and invasion.

Reprod Biol Endocrinol 2021 Mar 29;19(1):49. Epub 2021 Mar 29.

Department of Reproductive Health and Infertility, Guangdong Women and Children Hospital, Guangzhou, Guangdong, China.

Problem: Does aquaporin 3 (AQP3) affect the migration and invasion of human extravillous trophoblast (HTR8/Svneo) cells?

Method Of Study: A lentivirus infection system was used to construct stable cell lines with either AQP3 knockdown or overexpression. RT-PCR and western blotting were used to verify the efficiencies of AQP3 knockdown or overexpression in HTR8/Svneo cells at mRNA and protein levels, respectively. Cell Counting Kit-8 and flow cytometry assays were used to detect the influence of AQP3 knockdown or overexpression on proliferation and apoptosis of HTR8/Svneo cells. In addition, wound healing and Transwell invasion assays were used to detect the effects of AQP3 knockdown or overexpression on migration and invasion capabilities of HTR8/Svneo cells. An Agilent gene chip was used to screen for significant differentially expressed genes after AQP3 knockdown. Finally, mechanisms by which AQP3 influences the migration and invasion of HTR8/Svneo cells were explored using bioinformatic analysis.

Results: Compared with controls, migration and invasion capabilities of HTR8/Svneo cells were significantly reduced after AQP3 knockdown, and significantly increased after AQP3 overexpression. Subsequent bioinformatic analysis of gene chip expression profiles indicated downregulation of genes related to adhesion such as PDGF-B, as well as signaling pathways (such as PIK3/AKT, NF-κB, and TNF) after AQP3 knockdown.

Conclusions: AQP3 could significantly promote migration and invasion capabilities of human extravillous trophoblasts, it may mediate embryo invasion and adhesion to endometrium by regulating PDGF-B, PIK3/AKT signaling pathways, although this requires further verification.
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http://dx.doi.org/10.1186/s12958-021-00726-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8006384PMC
March 2021

LncRNA SNHG12 promotes proliferation and epithelial mesenchymal transition in hepatocellular carcinoma through targeting HEG1 via miR-516a-5p.

Cell Signal 2021 Mar 24;84:109992. Epub 2021 Mar 24.

Department of Hepatobiliary Surgery, The First Affiliated Hospital of Jinan University, Guangzhou 510630, Guangdong Province, PR China; Department of Hepatobiliary Surgery, The First Clinical Medical College of Jinan University, Guangzhou 510630, Guangdong Province, PR China. Electronic address:

Hepatocellular carcinoma (HCC) is the most common cancer and its prognosis is poor due to metastasis and recurrence. EMT is associated with metastasis. A deep understanding of regulatory mechanism of EMT is critical. LncRNA is involved in regulation of various biological processes including EMT. This study aimed to investigate the regulatory signal axis among lncRNA SNHG12, miR-516a-5p and the target gene HEG1 during EMT. Cell cycle and apoptosis were analyzed by flow cytometry. Tumorigenesis was analyzed by clone formation assay. Wound healing assay and transwell assay was performed to detect migration and invasion, respectively. Interaction among SNHG12, miR-516a-5p and HEG1 were analyzed by dual luciferase assay and RIP assay. We also detected expression of RNA and protein by QPCR and western blotting. Finally, tumor growth was analyzed by tumorigenesis assay in vivo. Ki-67 and HEG1 level in tumor tissues was analyzed by IHC. SNHG12 and HEG1 were upregulated, miR-516a-5p was downregulated in HCC cell lines. SNHG12 could interact with and inhibit miR-516a-5p. MiR-516a-5p could interact with HEG1 and inhibit HEG1 expression. Knock down SNHG12 inhibited proliferation, migration, invasion, EMT and promoted apoptosis of HCC cells. Such effects were antagonized by inhibiting miR-516a-5p. SNHG12 overexpression lead to opposite results. Similar results were observed in mice. SNHG12 could promote EMT in HCC through targeting and inhibiting miR-516a-5p, which eventually upregulated HEG1 expression, in both cell and mice.
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http://dx.doi.org/10.1016/j.cellsig.2021.109992DOI Listing
March 2021

Predicting the stages of liver fibrosis with multiphase CT radiomics based on volumetric features.

Abdom Radiol (NY) 2021 Mar 22. Epub 2021 Mar 22.

Department of Radiology, The First Affiliated Hospital of Shenzhen University, Health Science Center, Shenzhen Second People's Hospital, 3002 SunGangXi Road, Shenzhen, 518035, People's Republic of China.

Purposes: To develop and externally validate a multiphase computed tomography (CT)-based machine learning (ML) model for staging liver fibrosis (LF) by using whole liver slices.

Materials And Methods: The development dataset comprised 232 patients with pathological analysis for LF, and the test dataset comprised 100 patients from an independent outside institution. Feature extraction was performed based on the precontrast (PCP), arterial (AP), portal vein (PVP) phase, and three-phase CT images. CatBoost was utilized for ML model investigation by using the features with good reproducibility. The diagnostic performance of ML models based on each single- and three-phase CT image was compared with that of radiologists' interpretations, the aminotransferase-to-platelet ratio index, and the fibrosis index based on four factors (FIB-4) by using the receiver operating characteristic curve with the area under the curve (AUC) value.

Results: Although the ML model based on three-phase CT image (AUC = 0.65-0.80) achieved higher AUC value than that based on PCP (AUC = 0.56-0.69) and PVP (AUC = 0.51-0.74) in predicting various stage of LF, significant difference was not found. The best CT-based ML model (AUC = 0.65-0.80) outperformed the FIB-4 in differentiating advanced LF and cirrhosis and radiologists' interpretation (AUC = 0.50-0.76) in the diagnosis of significant and advanced LF.

Conclusion: All PCP, PVP, and three-phase CT-based ML models can be an acceptable in assessing LF, and the performance of the PCP-based ML model is comparable to that of the enhanced CT image-based ML model.
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http://dx.doi.org/10.1007/s00261-021-03051-6DOI Listing
March 2021

Bedaquiline-containing regimens in patients with pulmonary multidrug-resistant tuberculosis in China: focus on the safety.

Infect Dis Poverty 2021 Mar 19;10(1):32. Epub 2021 Mar 19.

Department of Tuberculosis, The Second Affiliated Hospital of Hainan Medical University, Haikou, People's Republic of China.

Background: World Health Organization recommends countries introducing new drug and short treatment regimen for drug resistant tuberculosis (DR-TB) should develop and implement a system for active pharmacovigilance that allows for detection, reporting and management of adverse events. The aim of the study is to evaluate the frequency and severity of adverse events (AEs) of bedaquiline-containing regimen in a cohort of Chinese patients with multidrug-resistant (MDR)/extensively drug-resistant (XDR)-TB based on active drug safety monitoring (aDSM) system of New Drug Introduction and Protection Program (NDIP).

Methods: AEs were prospectively collected with demographic, bacteriological, radiological and clinical data from 54 sites throughout China at patient enrollment and during treatment between February, 2018 and December, 2019. This is an interim analysis including patients who are still on treatment and those that have completed treatment. A descriptive analysis was performed on the patients evaluated in the cohort.

Results: By December 31, 2019, a total of 1162 patients received bedaquiline-containing anti-TB treatment. Overall, 1563 AEs were reported, 66.9% were classified as minor (Grade 1-2) and 33.1% as serious (Grade 3-5). The median duration of bedaquiline treatment was 167.0 [interquartile range (IQR): 75-169] days. 86 (7.4%) patients received 36-week prolonged treatment with bedaquiline. The incidence of AEs and serious AEs was 47.1% and 7.8%, respectively. The most frequently reported AEs were QT prolongation (24.7%) and hepatotoxicity (16.4%). There were 14 (1.2%) AEs leading to death. Out of patients with available corrected QT interval by Fridericia's formula (QTcF) data, 3.1% (32/1044) experienced a post-baseline QTcF ≥ 500 ms, and 15.7% (132/839) had at least one change of QTcF ≥ 60 ms from baseline. 49 (4.2%) patients had QT prolonged AEs leading to bedaquiline withdrawal. One hundred and ninety patients reported 361 AEs with hepatotoxicity ranking the second with high occurrence. Thirty-four patients reported 43 AEs of hepatic injury referred to bedaquiline, much lower than that referred to protionamide, pyrazinamide and para-aminosalicylic acid individually.

Conclusions: Bedaquiline was generally well-tolerated with few safety concerns in this clinical patient population without any new safety signal identified. The mortality rate was generally low. These data inform significant positive effect to support the WHO recent recommendations for the wide use of bedaquiline.
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http://dx.doi.org/10.1186/s40249-021-00819-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7977294PMC
March 2021

Sublobectomy is a safe alternative for localized cavitary pulmonary tuberculosis.

J Cardiothorac Surg 2021 Mar 17;16(1):22. Epub 2021 Mar 17.

Department of Thoracic Surgery, Shanghai Pulmonary Hospital, Tongji University School of Medicine, No. 507 Zhengmin Road, Shanghai, 200433, China.

Objective: Surgical resection plays an essential role in the treatment of Pulmonary Tuberculosis (PTB). There are few reports comparing lobectomy and sublobectomy for pulmonary TB with cavity. To compare the advantages between lobectomy and sublobectomy for localized cavitory PTB, we performed a single-institution cross sectional cohort study of the surgical patients.

Methods: We consecutively included 203 patients undergoing lobectomy or sublobectomy surgery for localized cavitary PTB. All patients were followed up, recorded and compared their surgical complication, outcome and associated characteristics.

Results: Both groups had similar outcomes after follow up for 13.1 ± 12.1 months, however, sublobectomy group suffered fewer intraoperative blood losses, shorter length of stay, and fewer operative complications than lobectomy group (P <  0.05). Both groups obtained satisfactory outcome with postoperatively medicated for similar period of time and few relapse (P > 0.05).

Conclusion: Both sublobectomy and lobectomy resection were effective ways for cavitary PTB with surgical indications. If adequate anti-TB chemotherapy had been guaranteed, sublobectomy is able to be recommended due to more lung parenchyma retain, faster recover, and fewer postoperative complications.
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http://dx.doi.org/10.1186/s13019-021-01401-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7968317PMC
March 2021

MicroRNA-9 rescues hyperglycemia-induced endothelial cell dysfunction and promotes arteriogenesis through downregulating Notch1 signaling.

Mol Cell Biochem 2021 Mar 15. Epub 2021 Mar 15.

Department of Cardiology, Fujian Medical University Union Hospital, Xinquan Road 29#, Fuzhou, 350001, China.

Hyperglycemia-induced endothelial dysfunction plays a major role in the pathogenesis of diabetic vascular complications. MicroRNAs are potential therapeutic agents to improve hyperglycemia-induced endothelial dysfunction. This study examined the relationship of miR-9 with Notch1 signaling in hyperglycemia-induced endothelial dysfunction. Human umbilical vein endothelial cells (HUVECs) were exposed to 30 mM glucose concentration. Cell viability including proliferation, adhesion, migration and tube formation was significantly impaired. Quantitative real time polymerase chain reaction (qRT-PCR) or Western blot demonstrated that miR-9 expression remarkably decreased and expression of Notch1 and its effectors (Hes1, Hey1, Hey2) were upregulated. Transfection with miR-9 improved cell function, inhibited mRNA and protein expression of Notch1 and its effectors. Although basal expression of the arterial endothelium biomarker Ephrin B2 was almost undetectable in HUVECs, double-label immunofluorescence revealed that transfection with miR-9 upregulated Ephrin B2 expression. By contrast, such protective effects of miR-9 overexpression were eliminated due to use of miR-9 inhibitor. Dual luciferase assay further confirmed a significant inverse correlation between miR-9 and Notch1. In addition, Notch1 overactiviation was mimicked in HUVECs by transfecting with Notch1 intracellular domain (NICD1). MiR-9 significantly inhibited NICD1 mRNA expression and alleviated hyperglycemia-induced injury of the NICD1-overexpressing cells. Taken together, our data support upregulating miR-9 expression as a potential therapeutic strategy to antagonize hyperglycemia-induced injury by inhibiting Notch1 signaling.
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http://dx.doi.org/10.1007/s11010-021-04075-8DOI Listing
March 2021

Diffusion Spectrum Imaging of Corticospinal Tracts in Idiopathic Normal Pressure Hydrocephalus.

Front Neurol 2021 25;12:636518. Epub 2021 Feb 25.

Department of Radiology, Health Science Center, Shenzhen Second People's Hospital, The First Affiliated Hospital of Shenzhen University, Shenzhen, China.

The purpose of this study was to measure the diffusion spectrum imaging (DSI) parameters of corticospinal tracts (CSTs) and evaluate diffusional changes in CSTs in patients with idiopathic normal pressure hydrocephalus (iNPH) by DSI. Twenty-three iNPH patients and twenty-one healthy controls (HCs) were involved in this study. Brain DSI data for all participants were collected through the same MR scanning procedure. The diffusion parameters measured and analyzed included quantitative anisotropy (QA), the isotropic diffusion component (ISO), general fractional anisotropy (GFA), fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD), and radial diffusivity (RD) of corticospinal tracts. The QA and ISO values of corticospinal tracts in iNPH patients were significantly lower than those in HCs (P = 0.008, P = 0.016, P = 0.024, P = 0.016). The mean MD, AD, and RD values in iNPH patients were significantly higher than those in HCs (P = 0.032, P = 0.032, P = 0.048,). No significant differences in GFA and FA values were noted between iNPH patients and HCs. Decreased QA and ISO values of corticospinal tracts were found in iNPH patients. Quantitative CST evaluation using DSI may lead to information that can improve the present understanding of the disease mechanism.
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http://dx.doi.org/10.3389/fneur.2021.636518DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7947286PMC
February 2021

Assessment of prostate imaging reporting and data system version 2.1 false-positive category 4 and 5 lesions in clinically significant prostate cancer.

Abdom Radiol (NY) 2021 Mar 12. Epub 2021 Mar 12.

Department of Radiology, The First Affiliated Hospital of Shenzhen University, Health Science Center, Shenzhen Second People's Hospital, 3002 SunGangXi Road, Shenzhen, 518035, China.

Purpose: To determine the incidence and false-positive rates of clinically significant prostate cancer (CSPC) in prostate imaging reporting and data system (PI-RADS) category 4 and 5 lesions using PI-RADS v2.1.

Methods: One hundred and eighty-two lesions in 169 subjects with a PI-RADS score of 4 or 5 were included in our study. Lesions with clinically insignificant prostate cancer (CIPC) or benign pathologic findings were reviewed and categorized by a radiologist. The initial comparison of demographic and clinical data was performed by t-test and χ test, and then the logistic regression model was used to determine factors associated with CIPC or benign pathological findings.

Results: Of the 182 PI-RADS category 4 and 5 lesions, 84.6% (154/182) were prostate cancer (PCa), 73.1% (133/182) were CSPC, and 26.9% (49/182) were CIPC or benign pathologic findings. The false-positive cases included 44.9% (22/49) with inflammation, 42.9% (21/49) with CIPC, 8.2% (4/49) with BPH nodules and 4.1% (2/49) with normal anatomy cases. In multivariate analysis, factors associated with CIPC or benign features included those in both the peripheral zone (PZ) and central gland (CG) (odds ratio [OR] 0.062; p = 0.003) and a low prostate-specific antigen density (PSAD) (OR 0.34; p = 0.012).

Conclusion: The integration of clinical information (PSAD and lesion location) into mpMRI to identify lesions helps with obtaining a clinically significant diagnosis and decision-making.
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http://dx.doi.org/10.1007/s00261-021-03023-wDOI Listing
March 2021

Safety and feasibility of single-incision radical vulvectomy: a novel approach for the treatment of vulvar cancer.

Ann Transl Med 2021 Feb;9(4):320

Department of Gynecology, Obstetrics and Gynecology Center, Zhujiang Hospital, Southern Medical University, Guangzhou, China.

Background: In the process of decreasing the morbidity of wound-related complications after vulvectomy and IL for treating vulvar malignancy, we performed a novel surgical procedure-single-incision radical vulvectomy (SIRV). Here, we share our initial experience and report its safety and feasibility.

Methods: Patients with advanced local vulvar tumors were sequentially enrolled in this prospective cohort study to undergo SIRV. While performing SIRV, routine radical vulvectomies were performed first. Subsequently, the flaps of the bridge area between the vulvectomy incisions and femoral triangles were separated and the lymph nodes underneath were removed. Anterior working spaces (AWS) before the femoral triangle were then made. The saphenous vein was carefully identified and retained, while the superficial and deep inguinal lymph nodes were removed from the medial to the lateral sides. After careful hemostasis, the wounds were sutured. Patient demographics, clinical data, pathologic data, operation time, node count, and complications were recorded.

Results: Ten patients underwent SIRV for vulvar cancer. Average hospital stay was 11.70±3.16 (range, 9-13) days. The average number of harvested lymph nodes was 7.59±3.62 (range, 3-15) and 15.14±3.63 (range, 11-20) for per side or both sides of the groin. Blood loss was ≤35 mL. Three patients developed inguinal lymphoceles and underwent needle aspirations. Two patients had impaired wound healing and achieved healing after dressing change. No other postoperative complications were noted during follow-up.

Conclusions: Compared with conventional open inguinal lymphadenectomy (COIL) and video endoscopic inguinal lymphadenectomy (VEIL), SIRV is a more minimally invasive procedure. Our short-term observations showed that SIRV is safe and feasible and has good future application prospects for vulvar cancer. However, definitive conclusions cannot be made. Therefore, long-term oncologic outcomes and large-scale clinical trials are warranted.
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http://dx.doi.org/10.21037/atm-20-6077DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7944291PMC
February 2021

Contrast-Enhanced Spectral Mammography-Based Radiomics Nomogram for the Prediction of Neoadjuvant Chemotherapy-Insensitive Breast Cancers.

Front Oncol 2021 22;11:605230. Epub 2021 Feb 22.

Department of Radiology, Yantai Yuhuangding Hospital, Affiliated Hospital of Qingdao University, Yantai, China.

Purpose: We developed and validated a contrast-enhanced spectral mammography (CESM)-based radiomics nomogram to predict neoadjuvant chemotherapy (NAC)-insensitive breast cancers prior to treatment.

Methods: We enrolled 117 patients with breast cancer who underwent CESM examination and NAC treatment from July 2017 to April 2019. The patients were grouped randomly into a training set (n = 97) and a validation set (n = 20) in a ratio of 8:2. 792 radiomics features were extracted from CESM images including low-energy and recombined images for each patient. Optimal radiomics features were selected by using analysis of variance (ANOVA) and least absolute shrinkage and selection operator (LASSO) regression with 10-fold cross-validation, to develop a radiomics score in the training set. A radiomics nomogram incorporating the radiomics score and independent clinical risk factors was then developed using multivariate logistic regression analysis. With regard to discrimination and clinical usefulness, radiomics nomogram was evaluated using the area under the receiver operator characteristic (ROC) curve (AUC) and decision curve analysis (DCA).

Results: The radiomics nomogram that incorporates 11 radiomics features and 3 independent clinical risk factors, including Ki-67 index, background parenchymal enhancement (BPE) and human epidermal growth factor receptor-2 (HER-2) status, showed an encouraging discrimination power with AUCs of 0.877 [95% confidence interval (CI) 0.816 to 0.924] and 0.81 (95% CI 0.575 to 0.948) in the training and validation sets, respectively. DCA revealed the increased clinical usefulness of this nomogram.

Conclusion: The proposed radiomics nomogram that integrates CESM-derived radiomics features and clinical parameters showed potential feasibility for predicting NAC-insensitive breast cancers.
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http://dx.doi.org/10.3389/fonc.2021.605230DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7937952PMC
February 2021

Performance of Interferon-Gamma Release Assays in the Diagnosis of Nontuberculous Mycobacterial Diseases-A Retrospective Survey From 2011 to 2019.

Front Cell Infect Microbiol 2020 18;10:571230. Epub 2021 Feb 18.

Shanghai Clinical Research Center for Tuberculosis, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, China.

There is an urgent need for precise diagnosis to distinguish nontuberculous mycobacterial (NTM) diseases from pulmonary tuberculosis (PTB) and other respiratory diseases. The aim of this study is to evaluate the diagnostic performance of Interferon-gamma (IFN-γ) release assays (IGRAs), including antigen-specific peripheral blood-based quantitative T cell assay (T-SPOT.TB) and QuantiFERON-TB-Gold-Test (QFT-G), in differentiating NTM infections ( = 1,407) from culture-confirmed PTB ( = 1,828) and other respiratory diseases ( = 2,652). At specie level, 2.56%, 10.73%, and 16.49% of NTM-infected patients were infected by , , and with - complex (MAC), respectively. Valid analyses of T-SPOT.TB (ESAT-6, CFP-10) and QFT-G were available for 37.03% and 85.79% in NTM-infected patients, including zero and 100% (36/36) of infection, 21.85% (33/151) and 92.05% (139/151) of infection, and 17.67% (41/232) and 91.24% (211/232) of MAC infection. Based on means comparisons and further ROC analysis, T-SPOT.TB and QFT-G performed moderate accuracy when discriminating NTM from PTB at modified cut-off values (ESAT-6 < 4 SFCs, CFP-10 < 3 SFCs, and QFT-G < 0.667 IU/ml), with corresponding AUC values of 0.7560, 0.7699, and 0.856. At species level of NTM, QFT-G effectively distinguished between MAC (AUC=0.8778), (AUC=0.8834) or (AUC=0.8783) than T-SPOT.TB. No significant differences in discriminatory power of these three IGRA tools were observed when differentiating NTM and Controls. Our results demonstrated that T-SPOT.TB and QFT-G were both efficient methods for differentiating NTM disease from PTB, and QFT-G possessed sufficient discriminatory power to distinguish infections by different NTM species.
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http://dx.doi.org/10.3389/fcimb.2020.571230DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7930076PMC
February 2021

The Role of -Catenin in Th1 Immune Response against Tuberculosis and Profiles of Expression in Patients with Pulmonary Tuberculosis.

J Immunol Res 2021 11;2021:6625855. Epub 2021 Feb 11.

Shanghai Clinical Research Center for Tuberculosis, Shanghai Key Lab of Tuberculosis, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, China.

-Catenin is a key molecule of canonical Wnt/-catenin pathway. Its roles and expression profiles in T cells of tuberculosis (TB) remain unclear. The aim of this study was to explore the role of -catenin in CD4 T cells and its expression characteristics in patients with pulmonary tuberculosis (PTB). In this study, CD4 T cell-specific -catenin conditional knockout mice (-CAT-cKO mice) were aerosol infected with () H37R with wild-type mice as controls. Four weeks after infection, the mRNA expression of IFN-, TNF-, and TCF-7 in the lungs of mice was measured. CD4, CD8, -catenin, IFN-, and TNF- in mononuclear cells from the lungs and spleens were measured by flow cytometry, and the pathological changes of lungs were also observed. Patients with PTB were enrolled, with blood samples collected and PBMCs isolated. The expressions of -catenin, IFN-, TNF-, and PD-1 in CD4 and CD8 T cells were measured by flow cytometry. Results showed a decreased frequency of and reduced IFN-/TNF- mRNA expression and secretion by CD4 T cells in the lungs of infected -CAT-cKO mice compared with infected wild-type controls, and only slightly more inflammatory changes were observed in the lungs. -catenin expressions in CD4 and CD8 T cells were significantly decreased in blood cells of patients with severe PTB compared with those in mild PTB. The stimulation of peripheral blood mononuclear cells (PBMCs) with lithium chloride (LiCl), a stimulant of -catenin, resulted in the increase in CD4 T cell frequency, as well as their secretion of IFN- and TNF-. -Catenin demonstrated a moderately positive correlation with PD-1 in CD4 T cells. -Catenin along with PD-1 and IFN- in CD4 T cells had a high correlation with those in CD8 T cells. In conclusion, -catenin may be involved in the regulation of Th1 response and CD4 T cell frequency in TB.
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http://dx.doi.org/10.1155/2021/6625855DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7892223PMC
February 2021