Publications by authors named "Jian Cui"

490 Publications

Integrating transcriptome and metabolome analyses of the response to cold stress in pumpkin (Cucurbita maxima).

PLoS One 2021 6;16(5):e0249108. Epub 2021 May 6.

Qingdao Institute of Agricultural Science Research, Qingdao, Shandong, China.

Cucurbita maxima belong to the genus Cucurbita and are of nutritional and economic importance. Physiological activity, transcriptome, and metabolome analyses of leaf samples from the C. maxima inbreding line IL7 treated at 5 °C and 25 °C were performed. Cold stress resulted in a significant increase in the malondialdehyde content, relative electrical conductivity, soluble protein, sugar content, and catalase activity. A total of 5,553 differentially expressed genes were identified, of which 2,871 were up-regulated and 2,682 down-regulated. In addition, the transcription of differentially expressed genes in the plant hormone signal transduction pathway and transcription factor families of AP2/ERF, bHLH, WRKY, MYB, and HSF was activated. Moreover, 114 differentially expressed metabolites were identified by gas chromatography time-of-flight mass spectrometry, particularly through the analysis of carboxylic acids and derivatives, and organooxygen compounds. The demonstration of a series of potential metabolites and corresponding genes highlighted a comprehensive regulatory mechanism. These findings will provide novel insights into the molecular mechanisms associated with the response to cold stress in C. maxima.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0249108PLOS
May 2021

A compact and interpretable convolutional neural network for cross-subject driver drowsiness detection from single-channel EEG.

Methods 2021 Apr 24. Epub 2021 Apr 24.

Fraunhofer Singapore, Nanyang Technological University, Singapore. Electronic address:

Driver drowsiness is one of the main factors leading to road fatalities and hazards in the transportation industry. Electroencephalography (EEG) has been considered as one of the best physiological signals to detect drivers' drowsy states, since it directly measures neurophysiological activities in the brain. However, designing a calibration-free system for driver drowsiness detection with EEG is still a challenging task, as EEG suffers from serious mental and physical drifts across different subjects. In this paper, we propose a compact and interpretable Convolutional Neural Network (CNN) to discover shared EEG features across different subjects for driver drowsiness detection. We incorporate the Global Average Pooling (GAP) layer in the model structure, allowing the Class Activation Map (CAM) method to be used for localizing regions of the input signal that contribute most for classification. Results show that the proposed model can achieve an average accuracy of 73.22% on 11 subjects for 2-class cross-subject EEG signal classification, which is higher than conventional machine learning methods and other state-of-art deep learning methods. It is revealed by the visualization technique that the model has learned biologically explainable features, e.g., Alpha spindles and Theta burst, as evidence for the drowsy state. It is also interesting to see that the model uses artifacts that usually dominate the wakeful EEG, e.g., muscle artifacts and sensor drifts, to recognize the alert state. The proposed model illustrates a potential direction to use CNN models as a powerful tool to discover shared features related to different mental states across different subjects from EEG signals.
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http://dx.doi.org/10.1016/j.ymeth.2021.04.017DOI Listing
April 2021

A study of the sequential treatment of acute heart failure with sacubitril/valsartan by recombinant human brain natriuretic peptide: A randomized controlled trial.

Medicine (Baltimore) 2021 Apr;100(16):e25621

Department of Cardiology, Tianjin Union Medical Center, Tianjin, China.

Abstract: This study aimed to investigate the effects of the basic treatment for heart failure and sequential treatment with rh-brain natriuretic peptide (rhBNP) alone or the combination of rhBNP and sacubitril/valsartan. Cardiac structure, pulmonary artery pressure, inflammation and oxidative stress in patients with acute heart failure were evaluated.Three hundred patients with acute heart failure were included. According to the random number table method, the patients were divided into 3 groups of 100 patients per group: the standard treatment group (treated with an angiotensin-converting enzyme inhibitor, β receptor blocker, and corticosteroid antagonist), rhBNP group (basic treatment combined with rhBNP) and sequential treatment group (basic treatment for heart failure combined with rhBNP followed by sacubitril/valsartan). The changes in NT-probrain natriuretic peptide (BNP) levels, cardiac troponin T (cTnT) levels, cardiac structure, pulmonary artery pressure, and the levels inflammatory factors and oxidative stress factors were compared among the 3 groups at 1, 4, 12, and 36 weeks after treatment.The sequential treatment group displayed superior outcomes than the standard treatment group and the rhBNP group in terms of left atrium diameter, left ventricular end diastolic volume, left ventricular ejection fraction, pulmonary artery pressure, NT-proBNP levels, and cTnT levels, which respond to damage to the heart structure and myocardium. This result may be related to the decreased levels of inflammatory factors and the correction of oxidative stress imbalance.Sacubitril/valsartan significantly reduce the serum levels of inflammatory factors in patients with acute heart failure while decreasing the levels of oxidizing factors and increasing the levels of antioxidant factors. These changes may be one of the explanations for the better cardiac structure and better pulmonary artery pressure observed in the sequential treatment group.
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http://dx.doi.org/10.1097/MD.0000000000025621DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8078236PMC
April 2021

The biphasic and age-dependent impact of Klotho on hallmarks of aging and skeletal muscle function.

Elife 2021 Apr 20;10. Epub 2021 Apr 20.

Department of Physical Medicine and Rehabilitation, University of Pittsburgh, Pittsburgh, United States.

Aging is accompanied by disrupted information flow, resulting from accumulation of molecular mistakes. These mistakes ultimately give rise to debilitating disorders including skeletal muscle wasting, or sarcopenia. To derive a global metric of growing 'disorderliness' of aging muscle, we employed a statistical physics approach to estimate the state parameter, entropy, as a function of genes associated with hallmarks of aging. Escalating network entropy reached an inflection point at old age, while structural and functional alterations progressed into oldest-old age. To probe the potential for restoration of molecular 'order' and reversal of the sarcopenic phenotype, we systemically overexpressed the longevity protein, Klotho, via AAV. Klotho overexpression modulated genes representing all hallmarks of aging in old and oldest-old mice, but pathway enrichment revealed directions of changes were, for many genes, age-dependent. Functional improvements were also age-dependent. Klotho improved strength in old mice, but failed to induce benefits beyond the entropic tipping point.
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http://dx.doi.org/10.7554/eLife.61138DOI Listing
April 2021

Gastric tumorigenesis after radical resection combined with adjuvant chemotherapy for colorectal cancer: two case reports and a literature review.

J Int Med Res 2021 Apr;49(4):3000605211007050

Department of Colorectal and Anal Surgery, The Second Hospital of Jilin University, Changchun, Jilin, China.

Radical resection with or without adjuvant chemotherapy is a common option for stage II and III colorectal cancer. Few reports exist regarding gastric tumorigenesis, including gastric cancer, gastric intraepithelial neoplasia, and gastric stromal tumor, in patients who received this protocol as the standard treatment for colorectal cancer. We present two cases of gastric tumorigenesis in patients with colorectal cancer following radical resection combined with adjuvant chemotherapy. Both patients underwent gastrectomy and D2 lymphadenectomy for their gastric tumors; neither patient developed recurrence up to 2 years after treatment. These cases indicate that patients should be monitored closely for gastric tumorigenesis after treatment for colorectal cancer. Early detection and active surgical treatment can provide satisfactory results for colorectal cancer followed by gastric tumorigenesis. Long-term follow-up and regular examinations, especially gastroscopy, are necessary to detect gastric tumorigenesis after colorectal cancer. The focus on monitoring colorectal cancer alone in colorectal cancer patients should be changed to include a broader range of cancers in addition to precancers and other tumors, such as gastric stromal tumor.
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http://dx.doi.org/10.1177/03000605211007050DOI Listing
April 2021

Real-world data combined with studies on Regulatory B Cells for newly diagnosed Multiple Myeloma from a tertiary referral Hospital in South-Western China.

J Cancer 2021 5;12(9):2633-2642. Epub 2021 Mar 5.

Department of Hematology, West China Hospital, Sichuan University, China.

Multiple myeloma (MM) is a heterogeneous disease that remains incurable with significant interpatient variability in outcomes. Regulatory B cells (Bregs) were observed to be involved into specific defects in MM. Here, we provide our risk-adapted approach to newly diagnosed MM (NDMM), combining with the fundamental dysfunction of Bregs. We reported one hundred consecutive patients with NDMM from South-Western China, primarily treated with bortezomib plus dexamethasone with or without a 3 agent, were enrolled from 2017. Bone marrow aspirates were obtained and flow cytometry (FCM) was used to quantify the percentage of Bregs from the bone marrow. The correlation between Bregs and clinical characters were further analyzed. This study found using bortezomib plus dexamethasone as backbone showed promising efficacy with acceptable tolerability in NDMM. The relatively compromised progression free survival (PFS) points to the essential synergy of bortezomib and lenalidomide here. This study also found that altered proportions of Bregs were closely correlated with treatment efficacy and prognosis in MM. Further understanding of Bregs biology might provide new opportunities to develop immunotherapy, which could prove beneficial in treating MM.
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http://dx.doi.org/10.7150/jca.53209DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8040702PMC
March 2021

Compensation for the absence of the catalytically active half of DNA polymerase ε in yeast by positively selected mutations in CDC28.

Genetics 2021 Apr 12. Epub 2021 Apr 12.

Department of Genetics and Biotechnology, Saint-Petersburg State University, Saint-Petersburg, Russia, 199034.

Current eukaryotic replication models postulate that leading and lagging DNA strands are replicated predominantly by dedicated DNA polymerases. The catalytic subunit of the leading strand DNA polymerase ε, Pol2, consists of two halves made of two different ancestral B-family DNA polymerases. Counterintuitively, the catalytically active N-terminal half is dispensable, while the inactive C-terminal part is required for viability. Despite extensive studies of yeast Saccharomyces cerevisiae strains lacking the active N-terminal half, it is still unclear how these strains survive and recover. We designed a robust method for constructing mutants with only the C-terminal part of Pol2. Strains without the active polymerase part show severe growth defects, sensitivity to replication inhibitors, chromosomal instability, and elevated spontaneous mutagenesis. Intriguingly, the slow-growing mutant strains rapidly accumulate fast-growing clones. Analysis of genomic DNA sequences of these clones revealed that the adaptation to the loss of the catalytic N-terminal part of Pol2 occurs by a positive selection of mutants with improved growth. Elevated mutation rates help generate sufficient numbers of these variants. Single nucleotide changes in the cell cycle-dependent kinase gene, CDC28, improve the growth of strains lacking the N-terminal part of Pol2, and rescue their sensitivity to replication inhibitors and, in parallel, lower mutation rates. Our study predicts that changes in mammalian homologs of cyclin-dependent kinases may contribute to cellular responses to the leading strand polymerase defects.
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http://dx.doi.org/10.1093/genetics/iyab060DOI Listing
April 2021

Moderate whole-body heating attenuates the exercise pressor reflex responses in older humans.

Am J Physiol Regul Integr Comp Physiol 2021 Mar 31. Epub 2021 Mar 31.

Penn State Heart and Vascular Institute, Pennsylvania State University College of Medicine, United States.

Prior reports show that whole-body heat stress attenuates the pressor response to exercise in young healthy subjects. The effects of moderate whole-body heating (WBH, e.g. increase in internal temperature Tcore ~0.4-0.5 °C) or limb heating on sympathetic and cardiovascular responses to exercise in older healthy humans remains unclear. We examined the muscle sympathetic nerve activity (MSNA), mean arterial blood pressure (MAP) and heart rate (HR) in 14 older (62 ± 2 yrs) healthy subjects during fatiguing isometric handgrip exercise and post exercise circulatory occlusion (PECO). The protocol was performed under normothermic, moderate WBH and local limb (i.e. forearm) heating conditions during 3 visits. During the mild WBH stage (increase in Tcore <0.3 °C), HR increased, whereas BP and MSNA decreased from baseline. Under the moderate WBH condition (increase in Tcore ~0.4 °C), BP decreased, HR increased, while MSNA was unchanged from baseline. Compared with the normothermic trial, the absolute MAP during fatiguing exercise and PECO were lower during the WBH trial. Moreover, MSNA and MAP responses (i.e. changes) to fatiguing exercise were also less than those seen during the normothermic trial. Limb heating induced a similar increase in forearm muscle temperature with that seen in the WBH trial (~0.7-1.5 °C). Limb heating did not alter resting MAP, HR or MSNA. The MSNA and hemodynamic responses to exercise in limb heating trial were not different from those in the normothermic trial. These data suggest that moderate WBH attenuates MSNA and BP responses to exercise in older healthy humans.
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http://dx.doi.org/10.1152/ajpregu.00232.2020DOI Listing
March 2021

NLRP3 protects mice from radiation-induced colon and skin damage via attenuating cGAS-STING signaling.

Toxicol Appl Pharmacol 2021 05 17;418:115495. Epub 2021 Mar 17.

Department of Gastroenterology and Hepatology, Jinling Hospital, The First School of Clinical Medicine, Southern Medical University, Nanjing 210002, China; Department of Gastroenterology and Hepatology, Jinling Hospital, Medical School of Nanjing University, 305 Zhongshan East Road, Nanjing 210002, Jiangsu Province, China. Electronic address:

In the present study, the effects of NLRP3 on radiation-induced tissue damage, including colon and skin damage in mice, and the possible mechanisms were explored in vivo and in vitro. The mice were subjected to whole abdomen radiation by timed exposure to X-ray at a cumulative dose of 14 Gy. The survival rate showed that NLRP3 deficiency increased the mortality rate in mice. Furthermore, colon damage, evaluated by H&E staining and barrier function analysis, were significantly aggravated by NLRP3 deficiency. Enhanced phosphorylation of p-TBK1 and p-IRF3 in colonic tissue as well as elevated IFN-β levels in the serum indicated hyperactivation of cGAS-STING signaling. Moreover, radiation-induced expression of p-TBK1, p-IRF3, and IFN-β in BMDMs increased in vitro after NLRP3 knockout. Thus, our study outcomes suggest that NLRP3 may protect mice from radiation-induced tissue damage via attenuating cGAS-STING signaling.
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http://dx.doi.org/10.1016/j.taap.2021.115495DOI Listing
May 2021

Impact of the COVID-19 Pandemic on Elective Surgery for Colorectal Cancer.

J Gastrointest Cancer 2021 Mar 17. Epub 2021 Mar 17.

Department of General Surgery, Institute of Geriatric Medicine, Beijing Hospital, National Center of Gerontology, Chinese Academy of Medical Sciences, Beijing, People's Republic of China.

Purpose: To investigate the impact of the COVID-19 pandemic on patients with colorectal cancer undergoing elective surgery.

Methods: The medical records of patients with colorectal cancer who underwent elective surgery in our department during the COVID-19 pandemic (February 1 to May 31, 2020) were collected and analyzed. We compared the clinical data with colorectal cancer during the same 4-month period in 2018 and 2019.

Results: Sixty-seven patients with colorectal cancer underwent elective surgery during the COVID-19 pandemic. This was 66% of the number of patients that underwent the procedure during the same period in 2018 and 2019. During the COVID-19 pandemic, the proportion of patients without any digestive system symptoms decreased to 3% and severe clinical symptoms decreased by 20.9%. The proportion of right colon cancer decreased by 17.9%, while the proportion of rectal cancer increased by 52.2%, as compared with 2018 and 2019. The fraction of protective stoma was significantly higher than in 2018 (23.9% vs. 8.7%, p = 0.011). Compared with 2019, the average post-operative stay was significantly shorter than in 2018 (9.6 ± 3.7 vs. 12.1 ± 9.1, p = 0.015). Compared with 2019, the number of patients with perineural invasion (a feature of adverse prognosis) significantly increased (p = 0.009).

Conclusion: During the COVID-19 pandemic, the number of patients undergoing elective surgery for colorectal cancer was reduced. However, the tumor stage of patients did not change substantially. We suggest that the clinical diagnosis and treatment of colorectal cancer should strictly comply with national and professional standards.
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http://dx.doi.org/10.1007/s12029-021-00621-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7966617PMC
March 2021

Development and Validation of Machine Learning-based Model for the Prediction of Malignancy in Multiple Pulmonary Nodules: Analysis from Multicentric Cohorts.

Clin Cancer Res 2021 Apr 24;27(8):2255-2265. Epub 2021 Feb 24.

Department of Thoracic Surgery, Peking University People's Hospital, Beijing, China.

Purpose: Nodule evaluation is challenging and critical to diagnose multiple pulmonary nodules (MPNs). We aimed to develop and validate a machine learning-based model to estimate the malignant probability of MPNs to guide decision-making.

Experimental Design: A boosted ensemble algorithm (XGBoost) was used to predict malignancy using the clinicoradiologic variables of 1,739 nodules from 520 patients with MPNs at a Chinese center. The model (PKU-M model) was trained using 10-fold cross-validation in which hyperparameters were selected and fine-tuned. The model was validated and compared with solitary pulmonary nodule (SPN) models, clinicians, and a computer-aided diagnosis (CADx) system in an independent transnational cohort and a prospective multicentric cohort.

Results: The PKU-M model showed excellent discrimination [area under the curve; AUC (95% confidence interval (95% CI)), 0.909 (0.854-0.946)] and calibration (Brier score, 0.122) in the development cohort. External validation (583 nodules) revealed that the AUC of the PKU-M model was 0.890 (0.859-0.916), higher than those of the Brock model [0.806 (0.771-0.838)], PKU model [0.780 (0.743-0.817)], Mayo model [0.739 (0.697-0.776)], and VA model [0.682 (0.640-0.722)]. Prospective comparison (200 nodules) showed that the AUC of the PKU-M model [0.871 (0.815-0.915)] was higher than that of surgeons [0.790 (0.711-0.852), 0.741 (0.662-0.804), and 0.727 (0.650-0.788)], radiologist [0.748 (0.671-0.814)], and the CADx system [0.757 (0.682-0.818)]. Furthermore, the model outperformed the clinicians with an increase of 14.3% in sensitivity and 7.8% in specificity.

Conclusions: After its development using machine learning algorithms, validation using transnational multicentric cohorts, and prospective comparison with clinicians and the CADx system, this novel prediction model for MPNs presented solid performance as a convenient reference to help decision-making.
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http://dx.doi.org/10.1158/1078-0432.CCR-20-4007DOI Listing
April 2021

Neuroprotective Effect of Fisetin Against the Cerebral Ischemia-Reperfusion Damage via Suppression of Oxidative Stress and Inflammatory Parameters.

Authors:
Peng Zhang Jian Cui

Inflammation 2021 Feb 22. Epub 2021 Feb 22.

Department of Neurosurgery, Xi'an No.1 Hospital, No.30 South Street Powder Lane, Beilin District, Xi'an, 710002, Shaanxi, China.

It is well established that inflammatory reactions and oxidative stress play an imperial role in cerebral ischemia-reperfusion pathogenesis. Fisetin is a flavonoid and has an antioxidant and anti-inflammatory effect on various diseases. In this study, we have been working to examine the neuroprotective effect of fisetin in brain injuries triggered by cerebral ischemic-reperfusion and explore the potential role of nuclear factor kappa B (NF-κB) signaling. In vitro, fisetin was examined against the cell viability, lactate dehydrogenase (LDH) leakage, cytokines, and apoptosis after ischemia/reperfusion (I/R) induced in the cells. In vivo, I/R injury was induced in the brain via transient middle cerebral artery occlusion (2 h) and reperfusion (20 h). The infarction area, brain water content, and neurofunctional parameters were also estimated. Inflammatory cytokines and brain injury markers were scrutinized at the end of the study. Fisetin treatment alleviated cell injury and suppressed the inflammatory cytokines (interleukin-1 (IL-1), tumor necrosis factor- α (TNF-α), inducible nitric oxide synthase (iNOS), interleukin-1β (IL-1β), cyclooxygenase-2 (COX-2), interleukin-16 (IL-6), and prostaglandin E (PGE)) and antioxidant parameters in a dose-dependent manner. Fisetin significantly (P < 0.001) reduced the infarct volume, brain water content. Fisetin significantly (P < 0.001) suppressed the neurological parameters and inflammatory cytokines such as IL-1, TNF-α, iNOS, IL-1β, COX-2, IL-6, PGE, and oxidative markers in a dose-dependent manner. Fisetin significantly (P < 0.001) reduced the inflammatory mediators including NF-κB and intercellular adhesion molecule 1 (ICAM-1). Further studies also showed that fisetin significantly inhibited the NF-κB activity via inflammatory and antioxidant pathways. In conclusion, by suppressing inflammatory cytokines, fisetin protected the brain tissue against I/R injury, and this effect could be due to reduced NF-κB activity.
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http://dx.doi.org/10.1007/s10753-021-01434-xDOI Listing
February 2021

Removal effects of Myriophyllum aquaticum on combined pollutants of nutrients and heavy metals in simulated swine wastewater in summer.

Ecotoxicol Environ Saf 2021 Apr 11;213:112032. Epub 2021 Feb 11.

Institute of Botany, Jiangsu Province and Chinese Academy Sciences, Nanjing 210014, China; Jiangsu Engineering Research Center of Aquatic Plant Resources and Water Environment Remediation, Nanjing 210014, China. Electronic address:

Swine wastewater (SW) treatment by Myriophyllum aquaticum is an important biotechnology for its resource utilization. However, some knowledge gaps remain in compound-pollutant removal in SW, especially in practical applications. To clarify the responses of M. aquaticum to the compound pollutants as well as the related operational parameters in SW treatment, three initial doses (0.5, 1.0, and 1.5 kg per pond in 150 L simulated SW) of M. aquaticum and a control (no plant; CK) were allocated to 12 ponds under a plastic roof in Nanjing city of Eastern China during 75 days in the summer of 2019. Results showed that M. aquaticum could be used as a pioneer plant to efficiently remove compounded pollutants of nitrogen (N), phosphorus (P), and especially for heavy metals in simulated SW. Compared with CK, M. aquaticum assisted in improving the total N, NH-N, NO-N, NO-N, and dissolved organic N by 30.1%, 100%, 100%, 97.6%, 20.2%, 39.8% whereas Cu, Zn, and Cd by 50.4%, 36.4% and 47.9% on average during the 75-day experiment in summer, respectively. Moreover, concentrations of Cu and Cd at day 75 were in the ranges of 1.92-2.82 and 0.64-1.47 g kg DW, respectively, exceeding the corresponding limits of the heavy-metal hyperaccumulator. For the operational parameters, the optimized initial dose was 1.0 kg per pond with M. aquaticum harvested after 45 summer days, respectively. Given that M. aquaticum has been widely used as animal feed in recent years and limit values for Cu and Zn in animal feed are not set in China, the toxicities of Cu and Zn should be assessed and the guideline of their limit values needs to be established for safe feed production. Interestingly, NH-N could dominate the removal of heavy metals especially Cd in the simulated SW, however, related mechanisms are needed for further study.
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http://dx.doi.org/10.1016/j.ecoenv.2021.112032DOI Listing
April 2021

MicroRNA: a novel implication for damage and protection against ionizing radiation.

Environ Sci Pollut Res Int 2021 Apr 3;28(13):15584-15596. Epub 2021 Feb 3.

Hengyang Medical College, Institute of Cytology and Genetics, The Hengyang Key Laboratory of Cellular Stress Biology, University of South China, Hengyang, 421001, Hunan Province, People's Republic of China.

Ionizing radiation (IR) is a form of high energy. It poses a serious threat to organisms, but radiotherapy is a key therapeutic strategy for various cancers. It is significant to reduce radiation injury but maximize the effect of radiotherapy. MicroRNAs (miRNAs) are posttranscriptionally regulatory factors involved in cellular radioresponse. In this review, we show how miRNAs regulate important genes on cellular response to IR-induced damage and how miRNAs participate in IR-induced carcinogenesis. Additionally, we summarize the experimental and clinical evidence for miRNA involvement in radiotherapy and discuss their potential for improvement of radiotherapy. Finally, we highlight the role that miRNAs play in accident exposure to IR or radiotherapy as predictive biomarker. miRNA therapeutics have shown great perspective in radiobiology; miRNA may become a novel strategy for damage and protection against IR.
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http://dx.doi.org/10.1007/s11356-021-12509-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7854028PMC
April 2021

High-precision frequency measurement for microresonant sensors based on improved modified multi-phase clock method.

Rev Sci Instrum 2021 Jan;92(1):015004

National Key Laboratory of Science and Technology on Micro/Nano Fabrication, Institute of Microelectronics, Peking University, Beijing 100871, People's Republic of China.

Microelectromechanical system resonant sensors are widely used in high precision applications. Frequency measurement plays an important role in such frequency readout sensors. This paper proposed an improved modified frequency measurement method based on the multi-phase clock (MPC), which can effectively improve the measurement accuracy but does not reduce the output rate. Innovative claims include (1) building a model of measurement error for MPC in which the probability of triggering error under different conditions is calculated, (2) improving the accuracy of the MPC measurement by phase reverse, and (3) proposing an algorithm to eliminate jitters of the measured signal. We compared the measurement results of this optimized MPC realized by the field programmable gate array (FPGA) device with those of the conventional MPC, spectral measurement, and equal precision measurement implemented with the National Instruments acquisition equipment PXI-4461 and USB-6366, respectively. The results show that the bias instability of the adopted method is ∼10 µHz obtained by Allan variance analysis, which is better than that of the other three methods. It can meet the accuracy requirements for the resonant frequency measurement of state-of-the-art resonant accelerometers. In addition, an algorithm running in FPGA is proposed to eliminate jitters caused by the noise of the measured signal for enhancing the robust of optimized MPC. The results demonstrate that the optimized MPC has features of high accuracy and anti-interference capability and can be easily transferred to the application specific integrated circuit in the future due to its full digital circuit version.
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http://dx.doi.org/10.1063/5.0026712DOI Listing
January 2021

Association of air pollution and greenness with carotid plaque: A prospective cohort study in China.

Environ Pollut 2021 Jan 15;273:116514. Epub 2021 Jan 15.

Department of Epidemiology and Preventive Medicine, School of Public Health and Preventive Medicine, Monash University, Melbourne, Australia.

Previous studies indicated that exposure to air pollution was associated with the progress of atherosclerosis, but evidence is very limited in China and even in the world. This study aims to assess the associations of long-term exposures to air pollution and greenness with the occurrence of carotid plaque. Participants of this cohort study were urban residents and office workers who visited Hebei General Hospital for routine physical examination annually from September 2016 through to December 2018. Eligible participants were people diagnosed the absence of carotid plaque clinically at their first hospital visit and were followed up at their second or third hospital visit. Exposure to particulate matter with aerodynamic diameter less than 2.5 μm (PM), nitrogen dioxide (NO) and ozone (O) were estimated using an inverse distance weighted (IDW) method. The level of greenness was assessed using the Normalized Difference Vegetation Index (NDVI) and Enhanced Vegetation Index (EVI). The associations were evaluated using Cox proportional hazards regression models. Among 4,137 participants, 575 showed the occurrence of carotid plaque during the follow-up period. After controlling for potential confounders, the hazard ratios (HRs) and 95% confidence intervals (95%CIs) of carotid plaque associated with per interquartile range (IQR) increase in PM, NO, and O were 1.78 (1.55, 2.03), 1.32 (1.14, 1.53) and 1.99 (1.71, 2.31), respectively. Increased EVI and NDVI were significantly associated with lower risk of carotid plaque [HR (and 95%CI): 0.84 (0.77, 0.93) and 0.87 (0.80, 0.94)]. PM significantly mediated 80.47% or 93.00% of the estimated association between EVI or NDVI and carotid plaque. In light of the significant associations between air pollution, greenness and carotid plaque in this study, continued efforts are needed to curb air pollution and plan more green space considering their effects on vascular disease.
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http://dx.doi.org/10.1016/j.envpol.2021.116514DOI Listing
January 2021

Microarray gene expression profiling provides insights into functions of TIPE2 in HBV-related apoptosis.

Mol Immunol 2021 03 6;131:137-143. Epub 2021 Jan 6.

Department of Immunology, Shandong University School of Basic Medical Science, Ji'nan, China; Key Laboratory of Infection and Immunity of Shandong Province, Shandong University School of Basic Medical Science, Jinan, China. Electronic address:

Tumor necrosis factor-α-induced protein-8 like-2 (TNFAIP8L2, TIPE2), a member of TNFAIP8 family, functions as a regulator in inflammation. Our previous studies showed that TIPE2 can negatively regulate HBV-specific CD8 T lymphocyte functions. But the effect of TIPE2 on the apoptosis of HBV-infected hepatocytes which is very important for eliminating viruses remains unclear. Using gene expression microarray analysis, we find that TIPE2 deficiency can regulate the expression of apoptotic genes in liver tissues from HBV hydrodynamic injection (HI) mouse model. TIPE2 protein was detected in TUNEL staining positive hepatocytes in HBV-infected C57 mice. Interestingly, the TIPE2 expressed hepatocytes were just the HBV infected cells. Furthermore, TIPE2 upregulates the mRNA levels of FasL, Bim and TNFRsF1b which promote cells death, when TIPE2 was transfected into HepG2 cells in vitro. As a result, TIPE2 overexpression cells showed a higher number of apoptotic cells and increased level of cleavage caspase3 compared to controls. Those results indicate that TIPE2 participates in HBV infection by regulating apoptosis of virus-infected hepatocytes.
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http://dx.doi.org/10.1016/j.molimm.2020.12.031DOI Listing
March 2021

Improvement of magnesium isoglycyrrhizinate on DSS-induced acute and chronic colitis.

Int Immunopharmacol 2021 Jan 4;90:107194. Epub 2020 Dec 4.

State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, 163 Xianlin Avenue, Nanjing 210023, China; Jiangsu Key Laboratory of New Drug Research and Clinical Pharmacy, Xuzhou Medical University, 209 Tongshan Road, Xuzhou 221004, Jiangsu, China. Electronic address:

Inflammatory bowel disease (IBD) is a worldwide prototypical complex disease, owing to its multifactorial causes, relapsing and remitting condition and high incidence. Thus, effective therapeutic approaches need to be developed for patients with IBD. Currently, we reported the improving effect of magnesium isoglycyrrhizinate on colitis induced by dextran sulfate sodium (DSS). We found that magnesium isoglycyrrhizinate treatment significantly alleviated DSS-induced acute and chronic colitis by inhibiting the inflammatory response characterized by reduce of the infiltrations of immune cell and the level of pro-inflammatory cytokines. Besides, magnesium isoglycyrrhizinate treatment significantly inhibited the level of ROS and decreased the gut barrier destruction after DSS treatment. Furthermore, the results also showed that administration of magnesium isoglycyrrhizinate significantly reduced the colonic fibrosis. Taken together, these results revealed the potency of magnesium isoglycyrrhizinate on the intestinal inflammation, by which points to the possible use of magnesium isoglycyrrhizinate for IBD therapy in clinical applications.
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http://dx.doi.org/10.1016/j.intimp.2020.107194DOI Listing
January 2021

Single-cell lineage analysis reveals extensive multimodal transcriptional control during directed beta-cell differentiation.

Nat Metab 2020 12 30;2(12):1443-1458. Epub 2020 Nov 30.

Department of Genetics and Genome Sciences, School of Medicine, Case Western Reserve University, Cleveland, OH, USA.

The in vitro differentiation of insulin-producing beta-like cells can model aspects of human pancreatic development. Here, we generate 95,308 single-cell transcriptomes and reconstruct a lineage tree of the entire differentiation process from human embryonic stem cells to beta-like cells to study temporally regulated genes during differentiation. We identify so-called 'switch genes' at the branch point of endocrine/non-endocrine cell fate choice, revealing insights into the mechanisms of differentiation-promoting reagents, such as NOTCH and ROCKII inhibitors, and providing improved differentiation protocols. Over 20% of all detectable genes are activated multiple times during differentiation, even though their enhancer activation is usually unimodal, indicating extensive gene reuse driven by different enhancers. We also identify a stage-specific enhancer at the TCF7L2 locus for diabetes, uncovered by genome-wide association studies, that drives a transient wave of gene expression in pancreatic progenitors. Finally, we develop a web app to visualize gene expression on the lineage tree, providing a comprehensive single-cell data resource for researchers studying islet biology and diabetes.
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http://dx.doi.org/10.1038/s42255-020-00314-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7744443PMC
December 2020

Retraction Note: Suppressor capacity of copper nanoparticles biosynthesized using Crocus sativus L. leaf aqueous extract on methadone-induced cell death in adrenal phaeochromocytoma (PC12) cell line.

Sci Rep 2020 Nov 30;10(1):21236. Epub 2020 Nov 30.

Sen Research Group, Department of Biochemistry, University of Dumlupınar, 43000, Kütahya, Turkey.

Editor's Note: this Article has been retracted; the Retraction Note is available at https://doi.org/10.1038/s41598-020-77741-4 .
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http://dx.doi.org/10.1038/s41598-020-77741-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7705752PMC
November 2020

Highly diversified core promoters in the human genome and their effects on gene expression and disease predisposition.

BMC Genomics 2020 Nov 30;21(1):842. Epub 2020 Nov 30.

Cancer Centre and Institute of Translational Medicine, Faculty of Health Sciences, University of Macau, Macau, SAR, China.

Background: Core promoter controls transcription initiation. However, little is known for core promoter diversity in the human genome and its relationship with diseases. We hypothesized that as a functional important component in the genome, the core promoter in the human genome could be under evolutionary selection, as reflected by its highly diversification in order to adjust gene expression for better adaptation to the different environment.

Results: Applying the "Exome-based Variant Detection in Core-promoters" method, we analyzed human core-promoter diversity by using the 2682 exome data sets of 25 worldwide human populations sequenced by the 1000 Genome Project. Collectively, we identified 31,996 variants in the core promoter region (- 100 to + 100) of 12,509 human genes ( https://dbhcpd.fhs.um.edu.mo ). Analyzing the rich variation data identified highly ethnic-specific patterns of core promoter variation between different ethnic populations, the genes with highly variable core promoters, the motifs affected by the variants, and their involved functional pathways. eQTL test revealed that 12% of core promoter variants can significantly alter gene expression level. Comparison with GWAS data we located 163 variants as the GWAS identified traits associated with multiple diseases, half of these variants can alter gene expression.

Conclusion: Data from our study reals the highly diversified nature of core promoter in the human genome, and highlights that core promoter variation could play important roles not only in gene expression regulation but also in disease predisposition.
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http://dx.doi.org/10.1186/s12864-020-07222-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7706239PMC
November 2020

Renal medullary oxygenation decreases with lower body negative pressure in healthy young adults.

J Appl Physiol (1985) 2021 Jan 19;130(1):48-56. Epub 2020 Nov 19.

Penn State Heart and Vascular Institute, Penn State College of Medicine, Hershey, Pennsylvania.

One in three Americans suffer from kidney diseases such as chronic kidney disease, and one of the etiologies is suggested to be long-term renal hypoxia. Interestingly, sympathetic nervous system activation evokes a renal vasoconstrictor effect that may limit oxygen delivery to the kidney. In this report, we sought to determine if sympathetic activation evoked by lower body negative pressure (LBNP) would decrease cortical and medullary oxygenation in humans. LBNP was activated in a graded fashion (LBNP; -10, -20, and -30 mmHg), as renal oxygenation was measured (T2*, blood oxygen level dependent, BOLD MRI; = 8). At a separate time, renal blood flow velocity (RBV) to the kidney was measured ( = 13) as LBNP was instituted. LBNP significantly reduced RBV ( = 0.041) at -30 mmHg of LBNP (Δ-8.17 ± 3.75 cm/s). Moreover, both renal medullary and cortical T2* were reduced with the graded LBNP application (main effect for the level of LBNP = 0.0008). During recovery, RBV rapidly returned to baseline, whereas medullary T2* remained depressed into the first minute of recovery. In conclusion, sympathetic activation reduces renal blood flow and leads to a significant decrease in oxygenation in the renal cortex and medulla. In healthy young adults, increased sympathetic activation induced by lower body negative pressure, led to a decrease in renal cortical and medullary oxygenation measured by T2*, a noninvasive magnetic resonance derived index of deoxyhemoglobin levels. In this study, we observed a significant decrease in renal cortical and medullary oxygenation with LBNP as well as an increase in renal vasoconstriction. We speculate that sympathetic renal vasoconstriction led to a significant reduction in tissue oxygenation by limiting oxygen delivery to the renal medulla.
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http://dx.doi.org/10.1152/japplphysiol.00739.2019DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7944934PMC
January 2021

iTRAQ-Based Proteomic Profiling of Potential Biomarkers in Rat Serum for Uranium Tailing Suspension Intratracheal Instillation.

J Proteome Res 2021 01 5;20(1):995-1004. Epub 2020 Nov 5.

The Hengyang Key Laboratory of Cellular Stress Biology, Key Discipline Laboratory for National Defense for Biotechnology in Uranium Mining and Hydrometallurgy, University of South China, Hengyang, Hunan 421001, P. R. China.

Protection against low-dose ionizing radiation is of great significance. Uranium tailings are formed as a byproduct of uranium mining and a potential risk to organisms. In this study, we identified potential biomarkers associated with exposure to low-dose radiation from uranium tailings. We established a Wistar rat model of low dose rate irradiation by intratracheal instillation of a uranium tailing suspension. We observed pathological changes in the liver, lung, and kidney tissues of the rats. Using isobaric tags for relative and absolute quantification, we screened 17 common differentially expressed proteins in three dose groups. We chose -1 antiproteinase (Serpina1), keratin 17 (Krt17), and aldehyde dehydrogenase (Aldh3a1) for further investigation. Our data showed that expression of Serpina1, Krt17, and Aldh3a1 had changed after the intratracheal instillation in rats, which may be potential biomarkers for uranium tailing low-dose irradiation. However, the underlying mechanisms require further investigation.
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http://dx.doi.org/10.1021/acs.jproteome.0c00766DOI Listing
January 2021

Overexpression of hsa_circ_0001715 is a Potential Diagnostic and Prognostic Biomarker in Lung Adenocarcinoma.

Onco Targets Ther 2020 23;13:10775-10783. Epub 2020 Oct 23.

Department of Respiratory Medicine, Nanjing Chest Hospital, Nanjing, Jiangsu 210029, People's Republic of China.

Background: Circular RNAs (circRNAs) play important roles in tumorigenesis, including lung cancer. However, the expression profile and clinical value of circRNAs in lung adenocarcinoma remain unclear. The purpose of this study was to establish the circRNAs expression profile of lung adenocarcinoma and determine its potential diagnostic and prognostic value.

Materials And Methods: The global expression profile of circRNAs in lung adenocarcinoma tissue was determined from five paired lung adenocarcinoma tissues and adjacent normal tissues. The expression levels of selected candidate circRNA were validated by qRT-PCR. Sequence analysis was used to confirm the specificity of amplified circRNA. The candidate circRNA level was further detected in plasma samples from lung adenocarcinoma patients and healthy controls. The relationships between their levels and clinicopathological factors were explored. Receiver operating characteristic (ROC) curve was constructed to differentiate lung adenocarcinoma from healthy controls. Kaplan-Meier was performed to show survival curves and survival characteristics. The significance of different prognostic factors for overall survival (OS) was analyzed using Cox proportional hazards model.

Results: CircRNA microarray showed 394 circRNAs were differentially expressed, including 215 up-regulated and 179 down-regulated circRNAs. Hsa_circ_0001715 was the most up-regulated circRNA in lung adenocarcinoma tissues. Plasma hsa_circ_0001715 levels were significantly higher in lung adenocarcinoma patients versus healthy controls ( < 0.001). We further found that high plasma hsa_circ_0001715 was significantly correlated with TNM stage ( = 0.039) and distant metastasis ( = 0.030). Furthermore, ROC curve analysis showed that hsa_circ_0001715 had high diagnostic value, and the area under the curve (AUC) was 0.871. Lung adenocarcinoma patients with plasma hsa_circ_0001715 levels over 0.417 had significantly shorter OS than those with lower levels ( = 0.004). Univariate and multivariate survival analysis showed that plasma hsa_circ_0001715 level was an independent prognostic factor for the OS.

Conclusion: Our study revealed an aberrant circRNA expression profile in lung adenocarcinoma, and hsa_circ_0001715 is up-regulated and could act as a novel diagnostic and prognostic biomarker for lung adenocarcinoma.
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http://dx.doi.org/10.2147/OTT.S274932DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7591015PMC
October 2020

The prognostic significance of the treatment response of regional lymph nodes and the refinement of the current TNM staging system in locally advanced rectal cancer after neoadjuvant chemoradiotherapy.

Cancer Med 2020 Dec 20;9(24):9373-9384. Epub 2020 Oct 20.

Department of Colorectal Surgery and State Key Lab of Molecular Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.

The current TNM staging system uses the same category definitions for both rectal cancer patients with and without neoadjuvant chemoradiotherapy (NCRT). However, ypTNM stage, especially ypN stage does not predict patient survival after NCRT well. Whether tumor regression in lymph nodes (LRG) may improve the prediction has not been well studied. In total, 358 patients with rectal cancer who received NCRT followed by radical resection were recruited from 2004 to 2015, and the median follow-up time was 57.5 months. The main outcome measure was disease-free survival (DFS). In univariate analysis, factors associated with DFS were ypT stage, ypN stage, number of negative lymph nodes (NLN), lymph node ratio (LNR), tumor regression grade (TRG), M-TTRG (modified ypT stage by combining ypT stage and TRG), maximum LRG (LRGmax), sum score of LRG (LRGsum), LRG ratio (average value of LRGsum), and M-NLRG (modified ypN stage by combining LRGmax and LNR). In the multivariate Cox regression analysis, M-TTRG and M-NLRG (p < 0.001 and p = 0.030, respectively) were significantly associated with DFS. The estimated 5-year DFS rates were 86.6%, 60.3%, and 36.4% for patients with M-NLRG-0, M-NLRG-1, and M-NLRG-2, respectively (p < 0.001). A significant difference in survival was observed among patients with NCRT after incorporating TRG and LRG simultaneously into the current ypTNM staging system (p < 0.001). LRG was an important prognostic factor in rectal cancer patients treated with NCRT and could refine the ypTNM staging system. The modified ypTNM staging system in combination with LRGmax, LNR, and TRG could improve the DFS prediction in each subset of patients.
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http://dx.doi.org/10.1002/cam4.3553DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7774730PMC
December 2020

Propofol downregulates the activity of glutamatergic neurons in the basal forebrain via affecting intrinsic membrane properties and postsynaptic GABAARs.

Neuroreport 2020 12;31(17):1242-1248

Departments of Pain Care.

Propofol anesthesia rapidly causes loss of consciousness, while the neural mechanism underlying this phenomenon is still unclear. Glutamatergic neurons in the basal forebrain play an important role in initiation and maintenance of wakefulness. Here, we selectively recorded the activity of glutamatergic neurons in vGlut-2-Cre mice. Propofol induced outward currents in a concentration-dependent manner. Bath application of propofol generated membrane hyperpolarization and suppressed the firing rates in these neurons. Propofol-induced stable outward currents persisted after blockade of the action potentials, implying a direct postsynaptic effect of propofol. Furthermore, propofol selectively increased the GABAergic inhibitory synaptic inputs via affecting the GABAARs, but did not affect the glutamatergic transmissions. Together, propofol inhibits the excitability of the glutamatergic neurons via direct influencing the membrane intrinsic properties and the inhibitory synaptic transmission. This inhibitory effect might provide a novel mechanism for the propofol-induced anesthesia.
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http://dx.doi.org/10.1097/WNR.0000000000001540DOI Listing
December 2020

Andrographolide sulfate inhibited NF-κB activation and alleviated pneumonia induced by poly I:C in mice.

J Pharmacol Sci 2020 Dec 26;144(4):189-196. Epub 2020 Aug 26.

State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, 163 Xianlin Avenue, Nanjing, 210023, China; Jiangsu Key Laboratory of New Drug Research and Clinical Pharmacy, Xuzhou Medical University, 209 Tongshan Road, Xuzhou, 221004, Jiangsu, China. Electronic address:

Pneumonia is a common illness that continues to be the major killer of remaining to be a significant source of morbidity and mortality in the patient population. Many microorganisms cause pneumonia, and now concern is turning to the importance of the cause the new therapies for viral pneumonia. In the current study, we report the effect of andrographolide sulfonate, a water-soluble form of andrographolide (trade name: Xi-Yan-Ping Injection), on poly I: C-induced pneumonia. Andrographolide sulfonate was administrated through intraperitoneal injection to mice with poly I: C-induced pneumonia. Recruitment of airway inflammatory cells, alteration of lung histological induced by Poly I: C were significantly ameliorated by andrographolide sulfonate. The protein levels of pro-inflammatory cytokines in bronchoalveolar fluid (BALF) and serum were reduced by andrographolide sulfonate treatment. The levels of MUC5AC and MUC5B in lung tissue were also suppressed. These results reveal that andrographolide sulfate remarkably alleviated pneumonia induced by poly I:C in mice. Moreover, andrographolide sulfonate markedly inhibited the activation of nuclear factor-κB (NF-κB). Taken together, we demonstrated that andrographolide sulfonate ameliorated poly I: C-induced pneumonia in mice, suggesting the possible use of andrographolide sulfonate for virus-induced pneumonia in clinical.
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http://dx.doi.org/10.1016/j.jphs.2020.08.005DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7448882PMC
December 2020

Evaluation of Contrast-enhanced Transcranial Color-coded Duplex Sonography (CE-TCCD) Applied in Stroke Patients with Intracranial Collateral Circulation.

Curr Med Imaging 2020 ;16(7):887-891

Department of Neurology, Capital Medical University, FuXing Hospital, Beijing, 100038, China.

Background and Introduction: Collateral circulation is very crucial for the prognosis of stroke patients. Transcranial color-coded duplexsonography (TCCD) is used widely to evaluate the intracranial arterial blood flow. However, approximately 20% - 30% of the patients with cerebral infarction cannot be detected via TCCD due to the interruption of thickened temporal bones. We assessed the diagnostic efficacy of contrast-enhanced transcranial color-coded duplexsonography (CE-TCCD) in stroke patients with limited bone windows.

Methods: CE-TCCD was applied to 70 patients (51 males and 19 females) who presented with ischemic symptoms, to detect the openness of the anterior communicating artery (ACoA) and posterior communicating artery (PCoA) of the Willis ring before Computed Tomography angiography (CTA) or Magnetic Resonance Angiography (MRA) examination. The results from CETCCD is used to compare with CTA/MRA result to verify the diagnostic efficacy.

Results: Forty-one communicating artery openings were detected by CE-TCCD, among which 37 were PCoA and 4 were ACoA. Among the 70 patients, 23 of 70 patients indicated severe stenosis within intracranial and/or extracranial arteries. Eighteen out of the 23 patients showed collateral circulation, accounting for 78.3% (18/23). Moderate stenosis were 23 cases in total, in which 7 cases showed collateral circulation, accounting for 30.4% (7/23). Slight stenosis were 24 cases in total, none of which showed collateral circulation.

Conclusion: In the stroke patients with limited bone windows, CE-TCCD can evaluate intracranial collateral circulation.
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http://dx.doi.org/10.2174/1573405615666191007152625DOI Listing
January 2020

Inhibition Mir-92a Alleviates Oxidative Stress and Apoptosis of Alveolar Epithelial Cells Induced by Lipopolysaccharide Exposure through TLR2/AP-1 Pathway.

Biomed Res Int 2020 16;2020:9673284. Epub 2020 Sep 16.

Department of Intensive Care Unit (ICU), People's Hospital of Rizhao, Shandong Province, China.

Objective: To probe into the role of miR-92a in alleviating oxidative stress and apoptosis of alveolar epithelial cell (AEC) injury induced by lipopolysaccharide (LPS) exposure through the Toll-like receptor (TLR) 2/activator protein-1 (AP-1) pathway.

Methods: Acute lung injury (ALI) rat model and ALI alveolar epithelial cell model were constructed to inhibit the expression of miR-92a/TLR2/AP-1 in rat and alveolar epithelial cells (AECs), to detect the changes of oxidative stress, inflammatory response, and cell apoptosis in rat lung tissues and AECs, and to measure the changes of wet-dry weight (W/D) ratio in rat lung tissues.

Results: Both inhibition of miR-92a expression and knockout of TLR2 and AP-1 gene could reduce LPS-induced rat ALI, alleviate pulmonary edema, inhibit oxidative stress and inflammatory response, and reduce apoptosis of lung tissue cells. In addition, the TLR2 and AP-1 levels in the lung tissues of ALI rats were noticed to be suppressed when inhibiting the expression of miR-92a, and the AP-1 level was also decreased after the knockout of TLR2 gene. Further, we verified this relationship in AECs and found that inhibition of miR-92a/TLR2/AP-1 also alleviated LPS-induced AEC injury, reduced cell apoptosis, and inhibited oxidative stress and inflammatory response. What is more, like that in rat lung tissue, the phenomenon also existed in AECs, that is, when the expression of miR-92a was inhibited, the expression of TLR2 and AP-1 was inhibited, and silencing TLR2 can reduce the expression level of AP-1.

Conclusion: MiR-92a/TLR2/AP-1 is highly expressed in ALI, and its inhibition can improve oxidative stress and inflammatory response and reduce apoptosis of AECs.
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http://dx.doi.org/10.1155/2020/9673284DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7516709PMC
April 2021

Fibrinogen/Albumin Ratio Index Is an Independent Prognosis Predictor of Recurrence-Free Survival in Patients After Surgical Resection of Gastrointestinal Stromal Tumors.

Front Oncol 2020 18;10:1459. Epub 2020 Aug 18.

Department of Gastrointestinal Surgery, National Center of Gerontology, Beijing Hospital, Beijing, China.

Nutritional status, systemic inflammation, and coagulation mechanism are closely related to tumor progression. Herein, we examined the role of fibrinogen-to-albumin ratio index (FARI) in the prognosis of gastrointestinal stromal tumors (GISTs) and developed a novel nomogram predicting recurrence-free survival (RFS). We retrospectively analyzed data from 357 GIST patients admitted at the gastrointestinal surgery of the Beijing Hospital from January 2008 to January 2018 and underwent curative resection. FARI was calculated as fibrinogen level (g/L) /albumin level (g/L). The cutoff point of FARI was set using the point with the largest Youden index on the receiver operating characteristic curve with the 5-years recurrence-free survival as an endpoint. We used the Kaplan-Meier approach and multivariable Cox regression model to study the impact of FARI on recurrence-free survival. Finally, we developed a nomogram based on tumor size, location, mitotic index, and FARI to predict RFS. The nomogram was assessed by calculating concordance probabilities and testing calibration of predicted RFS with observed RFS. Concordance probabilities were also compared with the National Institute of Health (NIH) risk classification system. The ROC curve revealed that the best cutoff point of the FARI was set as 0.08. The patients were classified into the FARI-high (≥0.08) and FARI-low (<0.08) groups. FARI was significantly associated with age, size of the tumor, NIH risk category, and Mitotic Index (all < 0.05). FARI was weakly associated with NLR and PLR. FARI and PNI had a weak negative association. Multivariate analysis showed that the NIH risk category and FARI were independent prognostic predictors for worse outcomes concerning RFS in GIST patients. In the high-risk subgroup, patients with low FARI also had a more prolonged RFS than patients with high FARI ( < 0.05). The nomogram had a concordance probability of 0.802 (SE 0.025). Nomogram predictions were well-calibrated. Concordance probabilities of the nomogram were better than NIH risk classification system [0.802 [0.025] vs. 0.737 [0.024], < 0.01]. We established that preoperative FARI is a novel serum biomarker to predict the prognosis after surgical resection of GISTs. The nomogram incorporating FARI could be used to help the decision-making of clinical treatment.
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http://dx.doi.org/10.3389/fonc.2020.01459DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7462001PMC
August 2020