Publications by authors named "Ran Liu"

682 Publications

Clinical significance of mucinous component in colorectal adenocarcinoma: a propensity score-matched study.

BMC Cancer 2021 Dec 1;21(1):1286. Epub 2021 Dec 1.

Department of Pathology, Jinan Central Hospital Affiliated to Shandong First Medical University, Jinan, 250000, Shandong, China.

Background: This study aims to investigate the clinical significance and prognostic value of mucinous component (MC) in colorectal adenocarcinoma (AC).

Methods: Patients with colorectal AC and AC with MC (ACMC) (1-100%) underwent surgical resection between January 2007 and February 2018 were retrospectively reviewed. Propensity score matching (PSM) was performed according to a 1:1 ratio. Receiver-operating characteristic (ROC) curve was used to identify the optimal cut-off value of MC ratio for prognostic prediction. The clinicopathological features and 3-year overall survival (OS) of AC patients, mucinous adenocarcinoma (MAC) (MC > 50%) patients, and ACMC (1-50%) patients were compared before and after matching. Multivariable analysis was used for analyzing independent risk factors related to prognosis.

Results: A total of 532 patients were enrolled in this study. Patients with AC, MAC, and ACMC (1-50%) exhibited different clinicopathological features. However, their 3-year OS rates were similar (82.00% vs. 74.11% vs. 81.48%, P = 0.38). After matching, ROC curve determined 70% as the optimal cut-off value. And patients with ACMC > 70% had a much poorer 3-year OS compared with ACMC (1-70%) patients and AC patients (47.37% vs. 86.15% vs. 79.76%, P < 0.001). In addition, ACMC > 70% was revealed as a risk factor for poor survival in univariate analysis (HR = 1.643, 95%CI = 1.025-2.635, P = 0.039), though not an independent risk factor in multivariable analysis (HR = 1.550, 95%CI = 0.958-2.507, P = 0.074).

Conclusions: MAC is usually diagnosed at an advanced stage. MAC has a similar survival with AC and ACMC (1-50%) patients before and after matching. Patients with ACMC > 70% exhibited a much poorer OS, and should be given more clinical attention.
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http://dx.doi.org/10.1186/s12885-021-09031-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8638428PMC
December 2021

Integrated DIA proteomics and lipidomics analysis on non-small cell lung cancer patients with TCM syndromes.

Chin Med 2021 Nov 27;16(1):126. Epub 2021 Nov 27.

School of Pharmacy, National and Local Joint Engineering Laboratory for Key Technology of Chinese Material Medica Quality Control, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenyang, 110016, China.

Background: Lung cancer remains the leading cause of mortality from malignant tumors, non-small cell lung cancer (NSCLC) accounts for the majority of lung cancer cases, and individualized diagnosis and treatment is an effective trend. The individual characteristics of different traditional Chinese medicine (TCM) syndromes of NSCLC patients may be revealed by highly specific molecular profiles.

Methods: In this study, 10 NSCLC patients with Qi deficiency and Yin deficiency (QDYD) syndrome and 10 patients with Qi deficiency of lung-spleen (QDLS) syndrome in TNM stage III-IV as well as 10 healthy volunteers were enrolled. Aiming at the varied syndromes of NSCLC patients with "Yin deficiency" as the main difference, a proteomics research based on data-independent acquisition (DIA) was developed. Of the dysregulated proteins in NSCLC patients, lipid metabolism was significantly enriched. Thereafter, nontargeted lipidomics research based on UPLC-Q-TOF/MS was performed in 16 patients, with 8 individuals randomly selected from each syndrome group. Furthermore, the considerably different characteristics between the syndromes and pathological mechanisms of NSCLC were screened by statistical and biological integrations of proteomics and lipidomics and the differential metabolic pathways of the two similar syndromes were further explored. Besides, lipids biomarkers were verified by a clinically used anticancer Chinese medicine, and the level of key differential proteins in the two syndromes was also validated using ELISA.

Results: The results showed that glycerophospholipid metabolism, sphingolipid metabolism, glycolipid metabolism, and primary bile acid biosynthesis were altered in NSCLC patients and that glycerophospholipid metabolism was significantly changed between the two syndromes in lipidomics analysis. Among the proteins and lipids, ALDOC and lysophosphatidylcholine (LPCs) were revealed to have a strong relationship by statistical and biological integration analysis, and could effectively distinguish QDLS and QDYD syndromes. Notably, the patients with different syndromes had the most typical metabolic patterns in glycerophospholipid metabolism and glycolysis, reflecting the differences in the syndromes dominated by "Yin deficiency".

Conclusions: ALDOC and LPCs could be employed for the differentiation of NSCLC patients with QDLS and QDYD syndromes, and "Yin deficiency" might be associated with glycerophospholipid metabolism and glycolysis pathway. The results provided a theoretical basis for "Syndrome differentiation" in TCM diagnosis. Moreover, the developed integrated strategy could also provide a reference for individualized diagnosis and treatment of other diseases.
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http://dx.doi.org/10.1186/s13020-021-00535-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8627049PMC
November 2021

Establishment and validation a SIL-IS LC-MS/MS method for determination of ibuprofen in human plasma and its pharmacokinetic study.

Biomed Chromatogr 2021 Nov 26:e5287. Epub 2021 Nov 26.

Pharmacy School of Wannan Medical College, Wuhu, Anhui, People's Republic of China.

In this work, we developed and validated a highly sensitive, rapid and stable LC-MS/MS method for determination of ibuprofen in human plasma with ibuprofen-d3 as stable isotopically labeled internal standard (SIL-IS). Human plasma samples were prepared by one-step protein precipitation. The chromatographic separation was achieved on a Poroshell 120 EC-C (2.1 x 50 mm, 2.7 μm). Water solution (containing 0.05% acetic acid and 5 mM NH Ac) and methanol were selected as the mobile phase with gradient elution. An electrospray ionization source was applied and operated in negative ion mode. Multiple reaction monitoring (MRM) mode was used for quantification using target fragment ions m/z 205.0→161.1 for ibuprofen and m/z 208.0→164.0 for SIL-IS, respectively. This method exhibited a linear range of 0.05-36 μg/mL for ibuprofen with correlation coefficient >0.99. Mean recoveries of ibuprofen in human plasma ranged from 78.4% to 80.9%. RSD of intra-day and inter-day precision were both < 5%. The accuracy was between 88.2% and 103.67%. The matrix effect was ignorable in human plasma, including lipidemia and haemolytic plasma. A simple, efficient and accurate LC-MS/MS method was successfully established and applied to a pharmacokinetics study in Chinese healthy volunteers after a single oral administration of ibuprofen granules.
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http://dx.doi.org/10.1002/bmc.5287DOI Listing
November 2021

Ginsenoside Rb1 alleviates diabetic kidney podocyte injury by inhibiting aldose reductase activity.

Acta Pharmacol Sin 2021 Nov 22. Epub 2021 Nov 22.

Department of Nephrology, First Medical Center of Chinese PLA General Hospital, Nephrology Institute of the Chinese People's Liberation Army, State Key Laboratory of Kidney Diseases, National Clinical Research Center for Kidney Diseases, Beijing Key Laboratory of Kidney Disease Research, Beijing, 100853, China.

Panax notoginseng, a traditional Chinese medicine, exerts beneficial effect on diabetic kidney disease (DKD), but its mechanism is not well clarified. In this study we investigated the effects of ginsenoside Rb1 (Rb1), the main active ingredients of Panax notoginseng, in alleviating podocyte injury in diabetic nephropathy and the underlying mechanisms. In cultured mouse podocyte cells, Rb1 (10 μM) significantly inhibited high glucose-induced cell apoptosis and mitochondrial injury. Furthermore, Rb1 treatment reversed high glucose-induced increases in Cyto c, Caspase 9 and mitochondrial regulatory protein NOX4, but did not affect the upregulated expression of aldose reductase (AR). Molecular docking analysis revealed that Rb1 could combine with AR and inhibited its activity. We compared the effects of Rb1 with eparestat, a known aldose reductase inhibitor, in high glucose-treated podocytes, and found that both alleviated high glucose-induced cell apoptosis and mitochondrial damage, and Rb1 was more effective in inhibiting apoptosis. In AR-overexpressing podocytes, Rb1 (10 μM) inhibited AR-mediated ROS overproduction and protected against high glucose-induced mitochondrial injury. In streptozotocin-induced DKD mice, administration of Rb1 (40 mg·kg·d, ig, for 7 weeks) significantly mitigated diabetic-induced glomerular injuries, such as glomerular hypertrophy and mesangial matrix expansion, and reduced the expression of apoptotic proteins. Collectively, Rb1 combines with AR to alleviate high glucose-induced podocyte apoptosis and mitochondrial damage, and effectively mitigates the progression of diabetic kidney disease.
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http://dx.doi.org/10.1038/s41401-021-00788-0DOI Listing
November 2021

Multifactor Prediction of Embryo Transfer Outcomes Based on a Machine Learning Algorithm.

Front Endocrinol (Lausanne) 2021 2;12:745039. Epub 2021 Nov 2.

Reproductive and Genetic Hospital, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, China.

fertilization-embryo transfer (IVF-ET) technology make it possible for infertile couples to conceive a baby successfully. Nevertheless, IVF-ET does not guarantee success. Frozen embryo transfer (FET) is an important supplement to IVF-ET. Many factors are correlated with the outcome of FET which is unpredictable. Machine learning is a field of study that predict various outcomes by defining data attributes and using relevant data and calculation algorithms. Machine learning algorithm has been widely used in clinical research. The present study focuses on making predictions of early pregnancy outcomes in FET through clinical characters, including age, body mass index (BMI), endometrial thickness (EMT) on the day of progesterone treatment, good-quality embryo rate (GQR), and type of infertility (primary or secondary), serum estradiol level (E2) on the day of embryo transfer, and serum progesterone level (P) on the day of embryo transfer. We applied four representative machine learning algorithms, including logistic regression (LR), conditional inference tree, random forest (RF) and support vector machine (SVM) to build prediction models and identify the predictive factors. We found no significant difference among the models in the sensitivity, specificity, positive predictive rate, negative predictive rate or accuracy in predicting the pregnancy outcome of FET. For example, the positive/negative predictive rate of the SVM (gamma = 1, cost = 100, 10-fold cross validation) is 0.56 and 0.55. This approach could provide a reference for couples considering FET. The prediction accuracy of the present study is limited, which suggests that there may be some other more effective predictors to be developed in future work.
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http://dx.doi.org/10.3389/fendo.2021.745039DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8593232PMC
November 2021

Electroacupuncture Ameliorates Depression-Like Behaviour in Rats by Enhancing Synaptic Plasticity via the GluN2B/CaMKII/CREB Signalling Pathway.

Evid Based Complement Alternat Med 2021 3;2021:2146001. Epub 2021 Nov 3.

Department of Acupuncture, Shuguang Hospital affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, China.

Background: Hippocampal synaptic plasticity during the pathological process of depression has received increasing attention. Hippocampal neuron atrophy and the reduction in synaptic density induced by chronic stress are important pathological mechanisms of depression. Electroacupuncture (EA) exerts beneficial effects on depression, but the mechanism is unclear. This study explored the effect of EA on synaptic plasticity and the potential mechanism.

Methods: Forty-eight SD rats were randomly divided into the control, chronic unpredictable mild stress (CUMS), EA, and fluoxetine (FLX) groups, and each group consisted of 12 rats. The sucrose preference test, open field test, and forced swimming test were used for the evaluation of depression-like behaviour, and Golgi and Nissl staining were used for the assessment of synaptic plasticity. Western blotting and immunofluorescence were conducted to detect proteins related to synaptic plasticity and to determine their effects on signalling pathways.

Results: We found that CUMS led to depression-like behaviours, including a reduced preference for sucrose, a prolonged immobility time, and reduced exploration activity. The dendritic spine densities and neuron numbers and the protein levels of MAP-2, PSD-95, and SYN were decreased in the hippocampi of rats with CUMS-induced depression, and these trends were reversed by EA. The molecular mechanism regulating this plasticity may involve the GluN2B/CaMKII/CREB signalling pathway.

Conclusion: These results suggest that EA can improve depression-like behaviour and hippocampal plasticity induced by CUMS, and the mechanism may be related to the GluN2B/CaMKII/CREB pathway.
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http://dx.doi.org/10.1155/2021/2146001DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8580672PMC
November 2021

Co-existence and interrelationship between intracranial artery stenosis and extracranial carotid atherosclerosis in an asymptomatic rural population of 13 villages in northern China.

Clin Neurol Neurosurg 2021 11 29;210:107013. Epub 2021 Oct 29.

Department of Neurology, Peking University First Hospital, No.8 Xishiku Street, Xicheng District, Beijing 100034, People's Republic of China. Electronic address:

Objective: We investigated the characteristics and relationship of co-existing intracranial artery stenosis (ICAS) and extracranial carotid atherosclerosis in an asymptomatic rural population in northern China.

Methods: Asymptomatic residents ≥ 30 years old in 13 villages underwent simultaneous cervical vascular and transcranial Doppler ultrasound. ICAS was defined as ≥ 50% stenosis. Extracranial carotid atherosclerosis severity was classified as increased intimal medial thickness (IMT), plaques, and a plaque with ≥ 50% extracranial artery stenosis (ECAS). Demographic details, medical history, and blood biochemistry results were collected. The relationship between ICAS and extracranial carotid atherosclerosis severity was determined using the chi-square trend test and binary logistic regression analysis.

Results: A total of 2598 asymptomatic participants were included; 122 (4.7%) had ICAS, 1071 (41.2%) had extracranial carotid atherosclerosis, and 84 (3.2%) had co-existing extracranial carotid atherosclerosis and ICAS. Those with co-existing ICAS and extracranial carotid atherosclerosis were older (P = 0.006) and had a higher hypertension (HTN) and diabetes mellitus (DM) prevalence (P < 0.001). HTN (95% confidence interval [CI]=1.31-3.55, odds ratio [OR]=2.15) and DM (95% CI=1.17-4.30, OR=2.24) were found to be independent risk factors for asymptomatic ICAS with extracranial carotid atherosclerosis. Among those with ICAS, 38/122 had no extracranial carotid atherosclerosis, 8/122 had increased IMT, 64/122 had a plaque, and 12/122 had ECAS. As extracranial carotid atherosclerosis severity increases, ICAS prevalence increases.

Conclusion: Co-existing ICAS and extracranial carotid atherosclerosis occurred in 3.2% of asymptomatic populations in rural areas of northern China. As extracranial carotid atherosclerosis severity increased, ICAS prevalence also increased. HTN and DM might be independent indicators of co-existing ICAS and extracranial carotid atherosclerosis.
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http://dx.doi.org/10.1016/j.clineuro.2021.107013DOI Listing
November 2021

Thermoregulation of Eremias argus alters temperature-dependent toxicity of beta-cyfluthrin: Ecotoxicological effects considering ectotherm behavior traits.

Environ Pollut 2021 Nov 5;293:118461. Epub 2021 Nov 5.

Department of Applied Chemistry, China Agricultural University, Yuanmingyuan West Road 2, Beijing, 100193, China. Electronic address:

Risk assessments of the ecotoxicological effects insecticides impose on ectotherms have increasingly considered temperature. However, the changes toxicants induce in thermoregulatory behavioral traits may lead to a divergence of thermal selection and temperature-dependent changes of contaminant toxicity. This study demonstrated the interaction of behavioral thermoregulation and temperature-dependent toxicity of beta-cyfluthrin (BC) in the lizard Eremias argus. Based on the negative relationship between temperature and BC toxicity, seeking a warming environment was assumed to represent a self-rescue behavior (and vice versa). The results showed that BC-treated lizards (0-20 μg/g body weight (bw)) showed such self-rescue behavior, while lizards exposed to an extremely high BC dose (200 μg/g bw) sought a cooler environment. Biochemical assays showed that BC affected neurotransmitter systems, caused oxidative stress, and interfered with ion-transport in the central nervous system. Biomarkers of the cholinergic and glutamatergic system, ion-transport function, and oxidative stress were identified as potential biochemical variables related to thermoregulatory behavior. Apparently, seeking a warmer environment is a survival strategy with the aim to neutralize BC toxicity, while seeking a cooler environment aims to attenuate the harmful effects of metabolic and oxidative stress, and to decelerate internal BC diffusion. This phenomenon could be also explained by the concept of the "cooling trap", i.e., a behavior where cooler temperatures are sought. This impairs survival after exposure to BC at it has a negative temperature coefficient, derived from a dysfunction of the central nervous system regarding thermoregulation caused by the high dosage of neurotoxicant and resulting temperature maladaptation. Implications of the interaction between thermoregulatory behavior and temperature-dependent toxicity are presented, which may aid further temperature-dependent risk assessments.
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http://dx.doi.org/10.1016/j.envpol.2021.118461DOI Listing
November 2021

Prevalence of joint-specific osteoarthritis and joint pain in British Columbia, Canada.

Rheumatol Int 2021 Oct 29. Epub 2021 Oct 29.

Arthritis Research Canada, Vancouver, Canada.

The objective is to determine the prevalence of self-reported physician-diagnosed osteoarthritis (OA) and musculoskeletal symptoms (pain, stiffness or discomfort) in specific joints among adults in British Columbia (BC), Canada. We carried out a cross-sectional mixed-mode survey in a random population sample of persons 18 years of age and older. Estimates were weighted to reflect the age and sex distribution of the population of BC. We obtained responses from 2,233 individuals. Overall, 18.4% (95% CI 16.8-20.1) of the adult population reported OA. Of those, more than 40% had OA in multiple sites. Prevalence ranged from 8.8% (95% CI 7.6-10.1) in the knee to 2.7% (2.1-3.5) in the foot. One-year prevalence of symptoms ranged from 49.1% (47.0-51.2) in the lower back to 23.3% (21.5-25.1) in the hip. Females reported more symptoms and OA than males in all joints. The most common site of self-reported physician-diagnosed OA in BC is the knee, but OA in the hands, hips, and feet is also common. Having OA in one joint is a strong predictor of OA in other joints.
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http://dx.doi.org/10.1007/s00296-021-05031-xDOI Listing
October 2021

[Erosion process of loess slope and influencing factors in the loess hilly-gully region, China].

Ying Yong Sheng Tai Xue Bao 2021 Aug;32(8):2886-2894

Cultivation Base of State Key Laboratory of Urban Environmental Processes and Numerical Simulation, Beijing Key Laboratory of Resources Environment and GIS, Capital Normal University, Beijing 100048, China.

Rainfall intensity, slope length, and slope gradient are the important factors affecting runoff and sediment yield. In order to quantitatively analyze the effects of rainfall intensity, slope length, and slope gradient on the erosion process of Ansai loess slope in loess hilly and gully region, we analyzed the variation of runoff and sediment yield on Ansai loess with two slope lengths (5, 10 m), three slopes (5°, 10°, 15°) and two rainfall intensities (60, 90 mm·h) in an indoor simulated rainfall experiment. The results showed that the initial runoff generation time decreased with the increases of slope length, though the overall change was not significant. The initial runoff generation time decreased with the increases of rainfall intensity. Compared with the intensity of 60 mm·h, the initial runoff generation time decreased by 5.7-18 min under the intensity of 90 mm·h. Among them, the runoff initiation time on the slope of 10° was the fastest. With the duration of rainfall, runoff yield rate increased rapidly at first, and then gradually fluctuated around a certain value. The sediment yield rate increased rapidly in a short period of time at the initial stage of runoff generation, and then decreased after reaching the maximum, and being gradua-lly stable. The rates of runoff and sediment yield increased with the increases of slope length and rainfall intensity, but the law of change with slope was not obvious. With the increases of rainfall intensity, slope length and gradient, the total sediment yield increased accordingly. Under the rainfall intensity of 90 mm·h, the slope surface with the length of 10 m and slope of 15° generated rill, leading to the highest total erosion amount (11885.66 g). Under the rainfall intensity of 60 mm·h, the erosion amount per unit area decreased with the increases of slope length, and there was a critical erosion slope length in 5-10 m slope section. Slope length, slope and rainfall intensity all played a promoting role in runoff process. Rainfall intensity, slope length, and their interaction contributed more to runoff yield rate and total erosion amount. Rainfall intensity contributed the most to runoff yield rate, with a contribution rate of 49.8%. The contribution rate of slope length to the total erosion was the largest, which reached 37.8%.
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http://dx.doi.org/10.13287/j.1001-9332.202108.016DOI Listing
August 2021

Predictors and Prognosis of Symptomatic Intracranial Hemorrhage in Acute Ischemic Stroke Patients Without Thrombolysis: Analysis of Data From the Chinese Acute Ischemic Stroke Treatment Outcome Registry.

Front Neurol 2021 28;12:727304. Epub 2021 Sep 28.

Department of Neurology, Peking University First Hospital, Beijing, China.

There is limited information on symptomatic intracranial hemorrhage (sICH) in stroke patients without thrombolysis. This study aimed to evaluate the risk factors of sICH and the association between sICH and the prognosis at 3 and 12 months in acute ischemic stroke patients without thrombolysis. Data originated from the Chinese Acute Ischemic Stroke Treatment Outcome Registry. Univariate analysis and multivariate logistic regression were used to screen the risk factors of sICH. Multivariable logistic regression models were used to assess the association of sICH with poor outcome and all-cause mortality. Totally, 9,484 patients were included, of which 69 (0.73%) had sICH. Atrial fibrillation (odds ratio [OR], 3.682; 95% confidence interval [CI], 1.945-6.971; < 0.001), history of tumors (OR, 2.956; 95% CI, 1.115-7.593; = 0.024), and the National Institutes of Health Stroke Scale (NIHSS) score on admission ([6-15: OR, 2.344; 95% CI, 1.365-4.024; = 0.002] [>15: OR, 4.731; 95% CI, 1.648-13.583; = 0.004]) were independently associated with sICH. After adjustment of the confounders, patients with sICH had a higher risk of poor outcome (OR, 1.983; 95% CI, 1.117-3.521; = 0.018) at 3 months and that of all-cause mortality at 3 (OR, 6.135; 95% CI, 2.328-16.169; < 0.001) and 12 months (OR, 3.720; 95% CI, 1.513-9.148; = 0.004). sICH occurred in 0.73% of acute ischemic stroke patients without thrombolysis and was associated with a worse prognosis at 3 and 12 months. Atrial fibrillation, history of tumors, and NIHSS score at admission were independent risk factors of sICH.
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http://dx.doi.org/10.3389/fneur.2021.727304DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8506002PMC
September 2021

Prognostic value of microvessel density in esophageal squamous cell carcinoma-a systematic review and meta-analysis.

Pathol Res Pract 2021 Nov 5;227:153644. Epub 2021 Oct 5.

Key Laboratory of Environmental Medicine Engineering, Ministry of Education, School of Public Health, Southeast University, Nanjing 210009, China. Electronic address:

Objective: Angiogenesis produced by tumor microenvironment is play an important role in development of esophageal squamous cell carcinoma (ESCC). As a quantitative index of angiogenesis, literature has emerged contradictory results about the prognostic role of microvessel density (MVD) in ESCC. The aim of the study was to explore the impact of the correlation between MVD and the prognosis of ESCC based the published evidence.

Methods: Pubmed and Web of science database were screened for the relationship of MVD with prognostic feature in ESCC up to March, 2021. 11 relevant articles were used for meta-analysis. The following data were extracted from the literature: author, year, country, the patients number of high/low MVD, tumor-node-metastasis (TNM) classification, clinical stage, lymphoid infiltrates, vessel invasion, invasive depth, differential degree and survival rate. The hazard ratio (HR) and odds ratios (OR) with 95% CI were used to assess the associations between MVD and overall survival (OS). Chi-squared test and I statistics were completed to evaluate the heterogeneity in our study. A random-effects model was used when significant heterogeneity existed (I>50% and p < 0.05). Egger test was used to calculate the publication bias. Subgroup analysis was stratified by antibody, region, sample capacity to explore the source of heterogeneity.

Results: 11 studies with 1055 patients were analyzed. Our results suggested that high MVD is an important factor to advanced TNM classification and clinical stage, and the high MVD is positive correlation with the lymph node invasion and vascular invasion(p < 0.05) in ESCC, but irrelevant to poor differential and invasive depth(p > 0.05). The result also indicated that low MVD is a benefit factor to prolong the survival rate (p < 0.05). And the source of the heterogeneity maybe is that the antibody used to detect the MVD was not consistent, patient number was not large enough and the count method on MVD.

Conclusion: Across multiple studies, high MVD is correlated with clinicopathological criteria of poor prognosis and survival in ESCC. MVD could be the quantitative index to reactive angiogenesis and may play a pivotal role in ESCC development and progression. MVD may represent a valuable addition to current pathologic analysis and help to guide prognosis and treatment.
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http://dx.doi.org/10.1016/j.prp.2021.153644DOI Listing
November 2021

New insights into genetic characteristics between multiple myeloma and COVID-19: An integrative bioinformatics analysis of gene expression omnibus microarray and the cancer genome atlas data.

Int J Lab Hematol 2021 Dec 8;43(6):1325-1333. Epub 2021 Oct 8.

Department of Hematology (Key Department of Jiangsu Medicine), Medical School, Zhongda Hospital, Southeast University, Institute of Hematology Southeast University, Nanjing, China.

Background: Multiple myeloma (MM) is a hematological malignancy. Coronavirus disease 2019 (COVID-19) infection correlates with MM features. This study aimed to identify MM prognostic biomarkers with potential association with COVID-19.

Methods: Differentially expressed genes (DEGs) in five MM data sets (GSE47552, GSE16558, GSE13591, GSE6477, and GSE39754) with the same expression trends were screened out. Functional enrichment analysis and the protein-protein interaction network were performed for all DEGs. Prognosis-associated DEGs were screened using the stepwise Cox regression analysis in the cancer genome atlas (TCGA) MMRF-CoMMpass cohort and the GSE24080 data set. Prognosis-associated DEGs associated with COVID-19 infection in the GSE164805 data set were also identified.

Results: A total of 98 DEGs with the same expression trends in five data sets were identified, and 83 DEGs were included in the protein-protein interaction network. Cox regression analysis identified 16 DEGs were associated with MM prognosis in the TCGA cohort, and only the cytochrome c oxidase subunit 6C (COX6C) gene (HR = 1.717, 95% CI 1.231-2.428, p = .002) and the nucleotide-binding oligomerization domain containing 2 (NOD2) gene (HR = 0.882, 95% CI 0.798-0.975, p = .014) were independent factors related to MM prognosis in the GSE24080 data set. Both of them were downregulated in patients with mild COVID-19 infection compared with controls but were upregulated in patients with severe COVID-19 compared with patients with mild illness.

Conclusions: The NOD2 and COX6C genes might be used as prognostic biomarkers in MM. The two genes might be associated with the development of COVID-19 infection.
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http://dx.doi.org/10.1111/ijlh.13717DOI Listing
December 2021

Modified reference based imputation and tipping point analysis in the presence of missing data due to COVID-19.

Contemp Clin Trials 2021 11 28;110:106575. Epub 2021 Sep 28.

Data and Statistical Sciences, AbbVie Inc., North Chicago, IL 60064, USA.

In longitudinal clinical trials, missing data are inevitable due to intercurrent events (ICEs) such as treatment interruption or premature discontinuation for different reasons. The COVID-19 pandemic has had substantial impact on clinical trials since early 2020 as it may result in missing data due to missed visits and premature discontinuations. The missing data due to COVID-19 can reasonably be assumed as missing at random (MAR). We propose a combined hypothetical strategy for sensitivity analyses to handle missing data due to both COVID-19 and non-COVID reasons. We modify the commonly used missing not at random (MNAR) methods, reference based imputation (RBI) and tipping point analysis, under this strategy. We propose the standard multiple imputation approach and derive an analytic likelihood based approach to implement the proposed methods to improve efficiency in applications. The proposed strategy and methods are applicable to a more general scenario when there are missing data due to both MAR and MNAR reasons.
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http://dx.doi.org/10.1016/j.cct.2021.106575DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8479366PMC
November 2021

An interplay of soil salinization and groundwater degradation threatening coexistence of oasis-desert ecosystems.

Sci Total Environ 2022 Feb 27;806(Pt 2):150599. Epub 2021 Sep 27.

Fukang Station of Desert Ecology, Chinese Academy of Sciences, Fukang 831505, Xinjiang, China; State Key Laboratory of Desert and Oasis Ecology, Xinjiang Institute of Ecology and Geography, Chinese Academy of Sciences, Urumqi 830011, China.

In salt-affected and groundwater-fed oasis-desert systems, water and salt balance is critically important for stable coexistence of oasis-desert ecosystems, especially in the context of anthropogenic-induced over-development and perturbations due to climate variability that affects the sustainability of human-natural systems. Here, an investigation of the spatio-temporal variability of soil salinity and groundwater dynamics across four different hydrological regions in oasis-desert system is performed. An evaluation of the effects of soil salinization and groundwater degradation interplays on the coexistence of oasis-desert ecosystems in northwestern China is undertaken over 1995-2020, utilizing comprehensive measurements and ecohydrological modelling framework. We note that the process of salt migration and accumulation across different landscapes in oasis-desert system is reshaping, with soil salinization accelerating especially in water-saving agricultural irrigated lands. The continuous decline in groundwater tables, dramatic shifts in groundwater flow patterns and significant degradation of groundwater quality are occurring throughout the watershed. Worse so, a clear temporal-spatial relationship between soil salinization and groundwater degradation appearing to exacerbate the regional water-salt imbalance. Also, the eco-environmental flows are reaching to their limit with watershed closures, although these progressions were largely hidden by regional precipitation and streamflow variability. The oasis-desert ecosystems tend to display bistable dynamics with two preferential configurations of bare and vegetated soils, and soil salinization and groundwater degradation interplays are causing catastrophic shift in the oasis-desert ecosystems. The results highlight the importance of regional adaptive water and salt management to maintain the coexistence of oasis-desert ecosystems in arid areas.
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http://dx.doi.org/10.1016/j.scitotenv.2021.150599DOI Listing
February 2022

Increasing the heterologous production of spinosad in J1074 by regulating biosynthesis of its polyketide skeleton.

Synth Syst Biotechnol 2021 Dec 20;6(4):292-301. Epub 2021 Sep 20.

Key Laboratory of Combinatorial Biosynthesis and Drug Discovery, Ministry of Education and Wuhan University School of Pharmaceutical Sciences, Wuhan, 430071, PR China.

Spinosyns are natural broad-spectrum biological insecticides with a double glycosylated polyketide structure that are produced by aerobic fermentation of the actinomycete, However, their large-scale overproduction is hindered by poorly understood bottlenecks in optimizing the original strain, and poor adaptability of the heterologous strain to the production of spinosyn. In this study, we genetically engineered heterologous spinosyn-producer J1074 and optimized the fermentation to improve the production of spinosad (spinosyn A and spinosyn D) based on our previous work. We systematically investigated the result of overexpressing polyketide synthase genes (, , , , ) using a constitutive promoter on the spinosad titer in J1074. The supply of polyketide synthase precursors was then increased to further improve spinosad production. Finally, increasing or replacing the carbon source of the culture medium resulted in a final spinosad titer of ∼70 mg/L, which is the highest titer of spinosad achieved in heterologous species This research provides useful strategies for efficient heterologous production of natural products.
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http://dx.doi.org/10.1016/j.synbio.2021.09.008DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8453208PMC
December 2021

Reduction of Heavy Menstrual Bleeding in Women Not Designated as Responders to Elagolix Plus Add Back Therapy for Uterine Fibroids.

J Womens Health (Larchmt) 2021 Sep 28. Epub 2021 Sep 28.

Department of Obstetrics and Gynecology, University of Chicago, Chicago, Illinois, USA.

To assess outcomes of women with uterine fibroids (UFs) and heavy menstrual bleeding (HMB) treated with 300 mg elagolix twice daily plus add-back therapy (E2 1 mg/NETA 0.5 mg once daily) or placebo who were not considered responders in pooled analysis of two phase 3, 6-month randomized clinical trials (Elaris UF-1 and UF-2). Responders were defined as women who met both primary end point bleeding criteria (<80 mL menstrual blood loss [MBL] during the final month and ≥50% reduction in MBL from baseline to the final month) and either completed the study or discontinued due to predefined reasons. Thus, women termed nonresponders who were analyzed in this study who met neither or one bleeding end point or met both criteria but prematurely discontinued treatment because of adverse events, perceived lack of efficacy, or required surgical or interventional treatment for UFs were analyzed in this study. This analysis assessed mean changes from baseline in MBL, as well as adverse events. Among 367 women receiving elagolix with add-back with observed data, 89 (24%) were not considered responders. Within this subset, 17 (19%) women met both bleeding criteria but prematurely discontinued treatment for the reasons mentioned above, while 23 (26%) met one bleeding criterion and 49 (55%) met neither bleeding criteria, regardless of discontinuation status. Among all nonresponders, a numerical trend toward greater mean reductions in MBL was observed in those receiving elagolix with add-back, compared with placebo group nonresponders. No differences in adverse events were observed between responders and nonresponders. Forty of 89 (45%) women with HMB and UFs who were classified as nonresponders in the UF-1 or UF-2 trials may have had a clinically meaningful response to elagolix with add-back therapy because they met at least one of the objective bleeding criteria. Clinicaltrials.gov, NCT02654054 and NCT02691494. (NEJM 2020; 382:328-340) DOI: 10.1056/NEJMoa1904351.
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http://dx.doi.org/10.1089/jwh.2021.0152DOI Listing
September 2021

Depletion of Demethylase KDM6 Enhances Early Neuroectoderm Commitment of Human PSCs.

Front Cell Dev Biol 2021 8;9:702462. Epub 2021 Sep 8.

Department of Biological Repositories, Frontier Science Center for Immunology and Metabolism, Medical Research Institute, Zhongnan Hospital of Wuhan University, Wuhan University, Wuhan, China.

Epigenetic modifications play a crucial role in neurogenesis, learning, and memory, but the study of their role in early neuroectoderm commitment from pluripotent inner cell mass is relatively lacking. Here we utilized the system of directed neuroectoderm differentiation from human embryonic stem cells and identified that KDM6B, an enzyme responsible to erase H3K27me3, was the most upregulated enzyme of histone methylation during neuroectoderm differentiation by transcriptome analysis. We then constructed KDM6B-null embryonic stem cells and found strikingly that the pluripotent stem cells with KDM6B knockout exhibited much higher neuroectoderm induction efficiency. Furthermore, we constructed a series of embryonic stem cell lines knocking out the other H3K27 demethylase KDM6A, and depleting both KDM6A and KDM6B, respectively. These cell lines together confirmed that KDM6 impeded early neuroectoderm commitment. By RNA-seq, we found that the expression levels of a panel of WNT genes were significantly affected upon depletion of KDM6. Importantly, the result that WNT agonist and antagonist could abolish the differential neuroectoderm induction due to manipulating KDM6 further demonstrated that WNT was the major downstream of KDM6 during early neural induction. Moreover, we found that the chemical GSK-J1, an inhibitor of KDM6, could enhance neuroectoderm induction from both embryonic stem cells and induced pluripotent stem cells. Taken together, our findings not only illustrated the important role of the histone methylation modifier KDM6 in early neurogenesis, providing insights into the precise epigenetic regulation in cell fate determination, but also showed that the inhibitor of KDM6 could facilitate neuroectoderm differentiation from human pluripotent stem cells.
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http://dx.doi.org/10.3389/fcell.2021.702462DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8455897PMC
September 2021

Associations of plasma multiple metals with risk of hyperuricemia: A cross-sectional study in a mid-aged and older population of China.

Chemosphere 2022 Jan 20;287(Pt 3):132305. Epub 2021 Sep 20.

Shenzhen Center for Disease Control and Prevention, Shenzhen, 518055, China. Electronic address:

Background: Metal exposures are suspected to associate with the risk of hyperuricemia (HUA), but the current results are still conflicting.

Objective: To investigate the associations between multiple plasma metal exposures and HUA risk.

Methods: A cross-sectional study was conducted in 1406 Chinese Han adults who underwent routine physical examination in the Eighth Affiliated Hospital of Sun Yat-Sen University in Shenzhen. The plasma levels of 13 metals were measured by the inductively coupled plasma mass spectrometry (ICP-MS). Multivariable logistic, linear regression models, least absolute shrinkage and selection operator (LASSO) penalized regression analysis, and restricted cubic spline (RCS) models were applied to assess the associations.

Results: The median plasma uric acid concentration in HUA group (434 μmol/L) was significantly higher than that in non-HUA group (305 μmol/L). The multivariate-adjusted odds ratios (95% confidence intervals) of HUA were 1.62(1.08-2.43) for magnesium, 1.61(1.05-2.47) for copper, 1.62(1.06-2.49) for zinc, 1.87(1.26-2.81) for arsenic, 1.50(1.01-2.23) for selenium, and 1.70(1.16-2.49) for thallium based on the single-metal logistic regression models, comparing the highest versus the lowest quartile of metal levels. Further multi-metal logistic, linear regression models and the LASSO analysis all indicated positive associations of zinc, arsenic with HUA risk or uric acid levels. RCS model indicated an inverted V-shaped positive association between zinc levels and HUA risk (p for non-linearity = 0.048, p for overall association = 0.022), while arsenic levels showed a positive and linear dose-response relationship with HUA risk (p for non-linearity = 0.892, p for overall association<0.001).

Conclusions: Higher plasma levels of zinc and arsenic might increase HUA risk and showed positive dose-response relationships. Further cohort studies in larger population are required to testify our findings.
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http://dx.doi.org/10.1016/j.chemosphere.2021.132305DOI Listing
January 2022

Effects of temperature and PM on the incidence of hand, foot, and mouth in a heavily polluted area, Shijiazhuang, China.

Environ Sci Pollut Res Int 2021 Sep 22. Epub 2021 Sep 22.

The Department of Epidemic Treating and Preventing, Center for Disease Prevention and Control of Shijiazhuang City, Likang Road 3#, Shijiazhuang, 050011, China.

The influence of weather and air pollution factors on hand, foot, and mouth disease (HFMD) has received widespread attention. However, most of the existing studies came from lightly polluted areas and the results were inconsistent. There was a lack of relevant evidence of heavily polluted areas. This study aims to quantify the relationship between weather factors and air pollution with HFMD in heavily polluted areas. We collected the daily number of hand, foot, and mouth disease in Shijiazhuang, China from 2014 to 2018, as well as meteorological and air pollutant data over the same period. The generalized linear model combined with the distributed lag model was used to study the effect of meteorological factors and air pollutants on the daily cases of HFMD and its hysteresis effect. We found that the dose-response relationship between temperature, PM, and the risk of hand-foot-mouth disease was non-linear. Both low temperature and high temperature increased the risk of hand-foot-mouth disease. The cumulative effect of high temperature reached the maximum at 0-10 lag days, and the cumulative effect of low temperature reached the maximum at 0-3 lag days. The concentration of PM between 76 and 200 μg/m has a certain risk of the onset of hand, foot, and mouth disease, but the extreme PM concentration has a certain protective effect. In addition, low humidity, low wind speed, and low-O can increase the risk of HFMD. Risks of humidity and low concentration of O increased as lag days extended. In conclusion, our study found that climate factors and air pollutants exert varying degrees of impact on HFMD. Our research provided the scientific basis for establishing an early warning system so that medical staff and parents can take corresponding measures to prevent HFMD.
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http://dx.doi.org/10.1007/s11356-021-16397-7DOI Listing
September 2021

Detection of soybean transgenic event GTS-40-3-2 using electric field-induced release and measurement (EFIRM).

Anal Bioanal Chem 2021 Nov 14;413(26):6671-6676. Epub 2021 Sep 14.

Key Laboratory of Biotechnology and Bioresources Utilization of Ministry of Education, College of Life Science, Dalian Minzu University, Dalian, 116600, China.

Polymerase chain reaction (PCR) technology has become a standard technique for the detection of genetically modified organisms (GMOs). However, this method requires a PCR amplification process which is both expensive and time-consuming. Herein, we propose electric field-induced release and measurement (EFIRM) technology as an alternative method for GMO screening. The specificity and sensitivity of the EFIRM assay were proven to be comparable to those of the real-time PCR method for detecting genetically modified soybeans. After all the parameters had been evaluated, the actual evaluation of soybean samples from soybean cargoes was performed. An actual EFIRM screening was performed on 157 soybean cargo samples, which had 102 transgenic soybean samples containing the GTS-40-3-2 gene, through a blind trial at the Dalian port of China. Our results showed that 101 transgenic soybean samples were correctly detected, with only one false-negative case, and 55 non-transgenic soybean samples were detected as negative; this demonstrates that the EFIRM assay is an effective, accurate, simple, and economical novel method for detecting transgenic products, which may have a positive impact on the development of rapid on-site GMO monitoring platforms.
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http://dx.doi.org/10.1007/s00216-021-03634-8DOI Listing
November 2021

Metabolomics-based molecular signatures reveal the toxic effect of co-exposure to nitrosamines in drinking water.

Environ Res 2021 Sep 7;204(Pt B):111997. Epub 2021 Sep 7.

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

Nitrosamines, a group of emerging nitrogenous pollutants, are ubiquitously found in the drinking water system. However, less is known about how systemic biological responses resist or tolerate nitrosamines, especially long-term co-exposure at low concentrations. In this study, untargeted metabolomics was used to investigate the metabolic perturbations in human esophageal epithelial Het-1A cells induced by a mixture of nine common nitrosamines in drinking water at environmentally relevant, human-internal-exposure, and genotoxic concentrations. Generally, the disrupted metabolic spectrum became complicated with nitrosamines dose increasing. Notably, two inflammation-associated pathways, namely, cysteine (Cys) and methionine (MET) metabolism, and nicotinate and nicotinamide metabolism, changed significantly under the action of nitrosamines, even at the environmentally relevant level. Furthermore, targeted metabolomics and molecular biology indicators in cells were identified in mice synchronously. For one thing, the up-regulated Cys and MET metabolism provided methyl donors for histone methylation in the context of pro-inflammatory response. For another, the down-regulated NAD/NADH ratio inhibited the deacetylation of NF-кB p65 and eventually activated the NF-кB signaling pathway. Taken collectively, the metabolomics molecular signatures were important indicative markers for nitrosamines-induced inflammation. The potential crosstalk between the inflammatory cascade and metabolic regulation also requires further studies. These findings suggest that more attention should be paid to long-term co-exposure at low concentrations in the control of nitrosamines pollution in drinking water. Additionally, this study also highlights a good prospect of the combined metabolomic-molecular biology approach in environmental toxicology.
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http://dx.doi.org/10.1016/j.envres.2021.111997DOI Listing
September 2021

Risk factors and treatment of rectal stenosis after transanal endoscopic microsurgery.

Colorectal Dis 2021 Sep 7. Epub 2021 Sep 7.

Department of General Surgery, First Affiliated Hospital of Shandong First Medical University and Shandong Provincial Qianfoshan Hospital, Key Laboratory of Metabolism and Gastrointestinal Tumor, the First Affiliated Hospital of Shandong First Medical University, Key Laboratory of Laparoscopic Technology, the First Affiliated Hospital of Shandong First Medical University, Shandong Medicine and Health Key Laboratory of General Surgery, Jinan, Shandong, China.

Aim: Rectal stenosis is a relatively rare complication after transanal endoscopic microsurgery (TEM). This study aims to identify the predictive parameters for stenosis and the application of TEM in the treatment.

Method: The clinical data of patients who underwent TEM for rectal adenoma and early cancer from 2008 to 2019 were retrospectively reviewed. We compared the clinicopathological characteristics of patients with stenosis and those without stenosis and analysed the risk factors for stenosis. Treatment outcomes of stenosis with TEM were evaluated.

Results: A total of 230 patients were enrolled in this study. Overall, the postoperative complication rate was 11.7% (27/230), including eight (3.5%) patients with stenosis. Patients with stenosis exhibited a higher rate of tumour showing a laterally spreading morphology (P = 0.048), a wider circumferential extent of mucosal defect (P < 0.001), a shorter distance of the tumour from the anal verge (P = 0.001) and a wider longitudinal extent of mucosal defect (P = 0.027). A circumferential extent of mucosal defect >3/4 (OR 94.945, 95% CI 3.611-2496.41, P = 0.006) was identified as the only independent risk factor for stenosis. The four patients with both stenosis and clinical symptoms were treated by incising the stenosis ring using the TEM platform; the stenosis was cured, and symptoms disappeared after one to four courses of treatment.

Conclusions: Circumferential extent of mucosal defect ≥3/4 was an independent risk factor for stenosis in treating rectal adenoma and early cancer with TEM. Incision of the stenosis ring using the TEM platform is an effective strategy for treating stenosis.
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http://dx.doi.org/10.1111/codi.15904DOI Listing
September 2021

Cobalt-Nitrogen Compounds at High Pressure.

Inorg Chem 2021 Sep 30;60(18):14022-14030. Epub 2021 Aug 30.

State Key Laboratory of Superhard Materials, College of Physics, Jilin University, Changchun 130012, P.R. China.

The high-pressure phase diagram of Co-N compounds is enriched by proposing five stable phases (-CoN, 2-CoN, -CoN, -CoN, and 1̅-CoN) and two metastable phases (3̅1-CoN and 1̅-CoN). A systematic study has been performed for revealing the novel polymeric nitrogen structure and the outstanding properties of predicted polynitrides, such as structural characterization, energy analysis, stability analysis, and electronic analysis. 3̅1-CoN with the novel layer-shaped N-structure and 1̅-CoN with the novel band-shaped N-structure are first reported in this work. Moreover, 3̅1-CoN (6.14 kJ/g) and 1̅-CoN (5.18 kJ/g) with high energy density can be quenched down to ambient conditions. The proposed seven high-pressure phases are all metallic phases. A weak ionic bond interaction is observed between the Co and N atoms, while a strong N-N covalent bond interaction is observed in the -CoN, 1̅-CoN, 3̅1-CoN, and 1̅-CoN phases. The N atoms in the polynitrides hybridize in the sp state, for which the hybrid orbitals are constructed by the σ bond or lone electronic pair. The charge transfer between the Co and N atoms plays an important role to the structural stability. Moreover, the vibrational analysis of 3̅1-CoN and 1̅-CoN phases is performed to guide the future experimental study.
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http://dx.doi.org/10.1021/acs.inorgchem.1c01304DOI Listing
September 2021

The Wear Behavior of the Laser Cladded Ti-Al-Si Composite Coatings on Ti-6Al-4V Alloy with Additional TiC.

Materials (Basel) 2021 Aug 14;14(16). Epub 2021 Aug 14.

Department of Materials Science and Engineering, School of Mechanical and Materials Engineering, North China University of Technology, 5 Jinyuanzhuang Road, Beijing 100144, China.

In this study, the Ti-Al-Si + TiC ( = 0, 2, 6, 10 wt.%) composite coatings, each with a different content of TiC were fabricated on a Ti-6Al-4V alloy by laser surface cladding. The microstructure of the prepared coatings was analyzed by the scanning electron microscopy (SEM), energy dispersive spectroscopy (EDS), and X-ray diffraction (XRD). The microhardness and the wear resistance of these coatings were also evaluated. The results show that α-Ti, TiAl, TiSi, TiAl, TiAl, TiAlC and TiC particles can be found in the composites. The microstructure can obviously be refined by increasing the content of TiC particles, while the microhardness increases and the coefficient of friction decreases. The Ti-Al-Si-6TiC composite shows the best wear resistance, owing to its relatively fine microstructure and high content of TiC particles. The microhardness of this coating is 5.3 times that of the substrate, while the wear rate is only 0.43 times. However, when the content of TiC was up to 10 wt.%, the original TiC could not be dissolved completely during the laser cladding process, leading to formation of cracks on the coatings.
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http://dx.doi.org/10.3390/ma14164567DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8400223PMC
August 2021

Esophageal Cancer-Derived Extracellular Vesicle miR-21-5p Contributes to EMT of ESCC Cells by Disorganizing Macrophage Polarization.

Cancers (Basel) 2021 Aug 16;13(16). Epub 2021 Aug 16.

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

The disorganized polarization of tumor-associated macrophages (TAMs) exerts a critical effect on tumor progression. MicroRNAs (miRNAs) in extracellular vesicles (EVs) secreted from cancer cells may contribute to this process. However, the relationship between TAMs and EVs-miRNAs-mediated regulation in esophageal squamous cell carcinoma (ESCC) remains unclear. In the present study, immunoaffinity magnetic beads combined with antiepithelial cell adhesion molecules (EpCAM) were used to isolate and identify EVs-miR-21-5p from the plasma of ESCC patients. An in vitro coculture system was designed to evaluate the effect of esophageal cancer cells with miR-21-5p overexpression on macrophage polarization. We found that phorbol myristate acetate-induced THP-1 macrophages took up EVs-miR-21-5p from EC109 or EC9706 cells and were transformed into M2 macrophages. This, in turn, contributed to the excessive migration and invasion of esophageal cancer cells. The mechanism underlying these changes may involve activation of M2 macrophages by upregulated ESCC-derived EVs-miR-21-5p through the PTEN/AKT/STAT6 pathway. This may result in esophageal cancer cell epithelial-mesenchymal transition (EMT) via TGF-β/Smad2 signaling. Our results indicate positive feedback between M2 macrophage polarization and EMT of esophageal cancer cells in the tumor microenvironment via shuttling of miR-21-5p in tumor-derived EVs.
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http://dx.doi.org/10.3390/cancers13164122DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8392810PMC
August 2021

Hesitancy in the time of coronavirus: Temporal, spatial, and sociodemographic variations in COVID-19 vaccine hesitancy.

SSM Popul Health 2021 Sep 13;15:100896. Epub 2021 Aug 13.

Department of Communication and Media, University of Michigan, USA.

Leveraging nationally representative survey data on 443,680 respondents from January to March 2021, this study examines the temporal, spatial, and sociodemographic variations in COVID-19 vaccine hesitancy in the U.S. Findings reveal multidimensional determinants of vaccination intentions involving confidence, complacency, and circumspection factors. Using descriptive analyses and multilevel mixed-effects regression models, we find persistent partisan divide across states and significant racial disparities, with Blacks more likely to develop vaccine hesitancy due to confidence and circumspection than Whites. Vaccine hesitancy among Blacks declines dramatically across time but varies little across states, indicating new directions to effectively address inequalities in vaccination. Results also show nuanced gender differences, with women more likely to develop hesitancy due to circumspection and men more likely to have hesitancy due to complacency. Moreover, we find important intersection between race, gender, and education that calls for efforts to adequately address the concerns of the most vulnerable and disadvantaged groups.
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http://dx.doi.org/10.1016/j.ssmph.2021.100896DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8363184PMC
September 2021

Molecular and Biomechanical Adaptations to Mechanical Stretch in Cultured Myotubes.

Front Physiol 2021 2;12:689492. Epub 2021 Aug 2.

Department of Stomatology Medical Center, The Affiliated Hospital of Qingdao University, Qingdao, China.

Myotubes are mature muscle cells that form the basic structural element of skeletal muscle. When stretching skeletal muscles, myotubes are subjected to passive tension as well. This lead to alterations in myotube cytophysiology, which could be related with muscular biomechanics. During the past decades, much progresses have been made in exploring biomechanical properties of myotubes . In this review, we integrated the studies focusing on cultured myotubes being mechanically stretched, and classified these studies into several categories: amino acid and glucose uptake, protein turnover, myotube hypertrophy and atrophy, maturation, alignment, secretion of cytokines, cytoskeleton adaption, myotube damage, ion channel activation, and oxidative stress in myotubes. These biomechanical adaptions do not occur independently, but interconnect with each other as part of the systematic mechanoresponse of myotubes. The purpose of this review is to broaden our comprehensions of stretch-induced muscular alterations in cellular and molecular scales, and to point out future challenges and directions in investigating myotube biomechanical manifestations.
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http://dx.doi.org/10.3389/fphys.2021.689492DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8365838PMC
August 2021

Influenza vaccination and mortality among adults with heart failure in an integrated healthcare delivery system, 2009-2018.

J Gen Intern Med 2021 Aug 11. Epub 2021 Aug 11.

Department of Research & Evaluation, Kaiser Permanente Southern California, Pasadena, CA, USA.

Background: Influenza infection can result in decompensation or exacerbation of heart failure (HF) symptoms, hospitalization, and death.

Objective: To examine the association of influenza vaccination with mortality and hospitalization during influenza and non-influenza seasons between 2009 and 2018.

Design, Setting, And Participants: In this prospective, observational cohort study, we included Kaiser Permanente Southern California members with a HF diagnosis prior to September 1 each year from 2009 to 2017.

Exposure: The first influenza vaccination in each season (September 1 to May 31) was recorded. Vaccinated/unvaccinated patients were matched 1:1 on age, sex, and ejection fraction at the vaccination date (n-total = 74,870).

Main Outcomes: Patients were followed through the end of each influenza season for all-cause mortality. Secondary outcomes included cardiovascular mortality and all-cause hospitalization. In a sensitivity analysis, we examined mortality in the non-influenza season.

Results: Influenza vaccinated vs unvaccinated patients had more comorbidities and higher healthcare utilization. After multivariable adjustment for utilization, sociodemographics, comorbidities, and medications, influenza vaccinated vs unvaccinated patients had a lower risk of all-cause mortality and cardiovascular mortality during the influenza season (hazard ratio [HR] 0.66, 95% confidence interval [CI] 0.63, 0.70 and HR 0.68, 95% CI 0.63, 0.74, respectively) but a higher risk of all-cause hospitalization (HR 1.27, 95% CI 1.21, 1.31). There was no association between influenza vaccination and all-cause or cardiovascular mortality during the non-influenza season (HR 0.99, 95% CI 0.89, 1.09 and HR 1.00, 95% CI 0.84, 1.21, respectively).

Conclusions: Influenza vaccination in HF patients was associated with a lower risk of mortality during the influenza season. Our findings provide support for recommendations of universal influenza vaccination in patients with HF.
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http://dx.doi.org/10.1007/s11606-021-07068-xDOI Listing
August 2021
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