Publications by authors named "Qi Xue"

279 Publications

Genomic features and tumor immune microenvironment alteration in NSCLC treated with neoadjuvant PD-1 blockade.

NPJ Precis Oncol 2022 Jan 13;6(1). Epub 2022 Jan 13.

Thoracic Surgery Department, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.

Several clinical trials have shown the safety and effectiveness of PD-1/PD-L1 inhibitors in neoadjuvant therapy in resectable non-small cell lung cancer (NSCLC). However, 18-83% patients can benefit from it. In this study, we aimed to assess the association of PD-L1 expression, tumor mutation burden, copy number alteration (CNA, including copy number gain and loss) burden with the pathologic response to neoadjuvant PD-1 blockade and investigate the changes in the tumor immune microenvironment (TIME) during neoadjuvant immunotherapy in NSCLC. Pre-immunotherapy treatment tumor samples from twenty-nine NSCLC patients who received neoadjuvant immunotherapy with sintilimab, an anti-PD-1 drug, were subjected to targeted DNA sequencing and PD-L1 immunochemistry staining. The pathological response was positively correlated with tumor proportion score (TPS) of PD-L1 and negatively correlated with copy number gain (CNgain) burden. Of note, the combination of CNgain burden and TPS can better stratify major pathological response (MPR) patients than did CNgain or TPS alone. Whereas, TMB showed a limited correlation with pathological regression. Additionally, PD-1 blockade led to an increase in CD8PD-1T cells which was clinically relevant to MPR as evaluated by multiplex immunofluorescence. A significant reduction in CD19 cells was observed in the Non-MPR group but not in the MPR group, indicating the involvement of B cells in improving neoadjuvant immunotherapy response in NSCLC. Together, our study provides new data for the correlation of PD-L1 expression and genomic factors with drug response in neoadjuvant immunotherapy settings in NSCLC. The changes of TIME may provide novel insight into the immune responses to neoadjuvant anti-PD-1 therapy.
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http://dx.doi.org/10.1038/s41698-021-00244-6DOI Listing
January 2022

Nomograms for predicting difficult airway based on ultrasound assessment.

BMC Anesthesiol 2022 Jan 13;22(1):23. Epub 2022 Jan 13.

Department of Anesthesiology, The Second Affiliated Hospital of Anhui Medical University, 678# Furong Road, Hefei, Anhui Province, China.

Background: Accurate prediction of the difficult airway (DA) could help to prevent catastrophic consequences in emergency resuscitation, intensive care, and general anesthesia. Until now, there is no nomogram prediction model for DA based on ultrasound assessment. In this study, we aimed to develop a predictive model for difficult tracheal intubation (DTI) and difficult laryngoscopy (DL) using nomogram based on ultrasound measurement. We hypothesized that nomogram could utilize multivariate data to predict DTI and DL.

Methods: A prospective observational DA study was designed. This study included 2254 patients underwent tracheal intubation. Common and airway ultrasound indicators were used for the prediction, including thyromental distance (TMD), modified Mallampati test (MMT) score, upper lip bite test (ULBT) score temporomandibular joint (TMJ) mobility and tongue thickness (TT). Univariate and the Akaike information criterion (AIC) stepwise logistic regression were used to identify independent predictors of DTI and DL. Nomograms were constructed to predict DL and DTL based on the AIC stepwise analysis results. Receiver operating characteristic (ROC) curves were used to evaluate the accuracy of the nomograms.

Results: Among the 2254 patients enrolled in this study, 142 (6.30%) patients had DL and 51 (2.26%) patients had DTI. After AIC stepwise analysis, ULBT, MMT, sex, TMJ, age, BMI, TMD, IID, and TT were integrated for DL nomogram; ULBT, TMJ, age, IID, TT were integrated for DTI nomogram. The areas under the ROC curves were 0.933 [95% confidence interval (CI), 0.912-0.954] and 0.974 (95% CI, 0.954-0.995) for DL and DTI, respectively.

Conclusion: Nomograms based on airway ultrasonography could be a reliable tool in predicting DA.

Trial Registration: Chinese Clinical Trial Registry (No. ChiCTR-RCS-14004539 ), registered on 13th April 2014.
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http://dx.doi.org/10.1186/s12871-022-01567-yDOI Listing
January 2022

Correlation between nurses' attitudes towards death and their subjective well-being.

Ann Palliat Med 2021 Dec;10(12):12159-12170

Department of Nursing, Nanfang Hospital, Southern Medical University, Guangzhou, China.

Background: With China's ageing society, the number of deaths increased gradually. Clinical nursing staff are among the first to come into contact with dying patients and scientific attitudes towards death will affect not only the quality of hospice care but also the physical and mental health of the nursing staff. Subjective well-being (SWB) mainly points to the overall emotional and cognitive evaluation of life quality. However, few studies have examined the correlation between attitudes towards death and subjective well-being in nurses.

Methods: A total of 810 nurses recruited from a tertiary hospital in Zhuhai were surveyed using the Chinese version of the Death Attitude Profile-Revised and the Subjective Well-being Scale. Pearson correlation coefficient was computed to analyze the correlation between attitudes towards death and the subjective well-being of the nursing staff.

Results: Subjective well-being was correlated with attitudes towards death (P<0.05). Multivariate analysis found that serious illness/acute or chronic disease, night shifts, and initial education level among nurses were also factors significantly related to subjective well-being (P<0.05).

Conclusions: The findings indicate a close correlation between nurses' attitudes towards death and their subjective well-being. Nursing managers should guide nursing staff to develop a more appropriate and healthier view of death so as to enhance their subjective well-being.
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http://dx.doi.org/10.21037/apm-21-2943DOI Listing
December 2021

The effects of nursing of Roy adaptation model on the elderly hypertensive: a randomised control study.

Ann Palliat Med 2021 Dec;10(12):12149-12158

Nursing Department, the Fifth Affiliated Hospital of Sun Yat-sen University, Zhuhai, China.

Background: Hypertension is a chronic disease affecting middle-aged and elderly patients worldwide. Self-management behavior plays a critical role in maintaining blood pressure. Roy adaptation model (RAM), which was proposed by Roy in 1970, has been used to guide hypertension nursing to improve self-management behavior of elderly patients. In the study, to explore the effect of nursing based on the RAM on the self-management behavior of elderly hypertensive patients.

Methods: A total of 120 elderly hypertensive patients admitted from June 2020 to March 2021 were selected and randomly divided into a control group and observation group based on odd and even numbers of the admission order, with 60 cases in each group. The control group received routine nursing measures while the observation group was given nursing based on the RAM. The self-management behavior, medication compliance, quality of life, and blood pressure control effect were compared between the two groups.

Results: The scores of the self-efficacy and self-management behaviors of the observation group and the total score of the scale were higher than those of the control group (P<0.05); the observation group patients' medication compliance score was 6.57±1.47, which was higher than that of the control group (4.90±2.16) (P<0.01); physiological function, physical pain, energy, social function, emotional function, mental health scores, and total scores of the SF-36 scale in the observation group were all higher than those of the control group (P<0.05), while comparison of the general health status dimension scores showed no statistically significant difference; the systolic blood pressure and diastolic blood pressure of the observation group were respectively lower than those of the control group (P<0.05); The blood pressure control compliance rate of the observation group was 85.4%, which was higher than that of the control group 64.6% (P<0.05).

Conclusions: Nursing intervention based on Roy's adaptation model can better enhance the self-efficacy and self-management ability of elderly hypertensive patients, have a positive effect on promoting healthy behavior changes and improving the quality of life, improve medication compliance, and achieve better blood pressure control effects.

Trial Registration: Chinese Clinical Trial Registry ChiCTR2100052466.
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http://dx.doi.org/10.21037/apm-21-2803DOI Listing
December 2021

Recurrence risk stratification based on a competing-risks nomogram to identify patients with esophageal cancer who may benefit from postoperative radiotherapy.

Ther Adv Med Oncol 2021 20;13:17588359211061948. Epub 2021 Dec 20.

Department of Radiation Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, 17 South Panjiayuan Lane, Beijing 100021, 100021 China.

Background: A reliable model is needed to estimate the risk of postoperative recurrence and the benefits of postoperative radiotherapy (PORT) in patients with thoracic esophageal squamous cell cancer (TESCC).

Methods: The study retrospectively reviewed 3652 TESCC patients in stage IB-IVA after radical esophagectomy, with or without PORT. In one institution as the training cohort ( = 1620), independent risk factors associated with locoregional recurrence (LRR), identified by the competing-risks regression, were used to establish a predicting nomogram, which was validated in an external cohort ( = 1048). Area under curve (AUC) values of receiver operating characteristic curves were calculated to evaluate discrimination. Risk stratification was conducted using a decision tree analysis based on the cumulative point score of the LRR nomogram. After balancing the baseline of characteristics between treatment groups by inverse probability of treatment weighting, the effect of PORT was evaluated in each risk group.

Results: Sex, age, tumor location, tumor grade, and N category were identified as independent risk factors for LRR and added into the nomogram. The AUC values were 0.638 and 0.706 in the training and validation cohorts, respectively. Three risk groups were established. For patients in the intermediate- and high-risk groups, PORT significantly improved the 5-year overall survival by 10.2% and 9.4%, respectively ( < 0.05). Although PORT was significantly associated with reduced LRR in the low-risk group, overall survival was not improved.

Conclusion: The nomogram can effectively estimate the individual risk of LRR, and patients in the intermediate- and high-risk groups are highly recommended to undergo PORT.
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http://dx.doi.org/10.1177/17588359211061948DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8721393PMC
December 2021

An immune-related lncRNA signature predicts prognosis and adjuvant chemotherapeutic response in patients with small-cell lung cancer.

Cancer Cell Int 2021 Dec 20;21(1):691. Epub 2021 Dec 20.

Department of Thoracic Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100021, China.

Background: Patients with small-cell lung cancer (SCLC) are burdened by limited treatment options and the disease's dismal prognosis. Long non-coding RNAs (lncRNAs) are essential regulators of genetic alteration and are actively involved in tumor immunity. However, few studies have examined interactions between immune genes and lncRNAs in SCLC.

Methods: Immune-related lncRNA (irlncRNA) expression profiles and their clinical significance were explored. We enrolled 227 patients with SCLC, including 79 cases from GSE65002 and 148 cases from a validation cohort with corresponding qPCR data. The least absolute shrinkage and selection operator (LASSO) model was applied to identify prognostic irlncRNAs for an irlncRNA-based SCLC signature. We additionally investigated the potential mechanisms and immune landscape of the signature using bioinformatics methods.

Results: An irlncRNA signature including 8 irlncRNAs (ENOX1-AS1, AC005162, LINC00092, RPL34-AS1, AC104135, AC015971, AC126544, AP001189) was established for patients with SCLC in the training cohort. Low-risk patients were more likely to benefit from chemotherapy and achieve a favorable prognosis. The signature was also well-validated in the validation cohort and various clinical subgroups. Compared to other clinical parameters, the irlncRNA signature exhibited superior predictive performance for chemotherapy response and prognosis. The signature was as an independent prognostic factor in the training and validation cohorts. Interestingly, low-risk patients showed an activated immune phenotype.

Conclusion: We constructed the first irlncRNA-based signature for chemotherapy efficacy and outcome prediction. The irlncRNA signature is a reliable and robust prognostic classifier that could be useful for clinical management and determination of potential chemotherapy benefit for patients with SCLC.
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http://dx.doi.org/10.1186/s12935-021-02357-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8691030PMC
December 2021

5-Nitrotetrazol and 1,2,4-Oxadiazole Methylene-Bridged Energetic Compounds: Synthesis, Crystal Structures and Performances.

Molecules 2021 Nov 23;26(23). Epub 2021 Nov 23.

Xi'an Modern Chemistry Research Institute, Xi'an 710065, China.

A new structural type for melt cast materials was designed by linking nitrotetrazole ring with 1,2,4-oxadiazole through a N-CH-C bridge for the first time. Three N-CH-C linkage bridged energetic compounds, including 3-((5-nitro-2H-tetrazol-2-yl) methyl)-1,2,4-oxadiazole (NTOM), 3-((5-nitro-2H-tetrazol-2-yl)methyl)-5-(trifluoromethyl)-1,2,4 -oxadiazole (NTOF) and 3-((5-nitro-2H-tetrazol-2-yl)methyl)-5-amine-1,2,4-oxadiazole (NTOA), were designed and synthesized through a two-step reaction by using 2-(5-nitro-2H-tetrazole -2-yl)acetonitrile as the starting material. The synthesized compounds were fully characterized by NMR (H, C), IR spectroscopy and elemental analysis. The single crystals of NTOM, NTOF and NTOA were successfully obtained and investigated by single-crystal X-ray diffraction. The thermal stabilities of these compounds were evaluated by DSC-TG measurements, and their apparent activation energies were calculated by Kissinger and Ozawa methods. The crystal densities of the three compounds were between 1.66 g/cm (NTOA) and 1.87 g/cm (NTOF). The impact and friction sensitivities were measured by standard BAM fall-hammer techniques, and their detonation performances were computed using the EXPLO 5 (v. 6.04) program. The detonation velocities of the three compounds are between 7271 m/s (NTOF) and 7909 m/s (NTOM). The impact sensitivities are >40 J, and the friction sensitivities are >360 N. NTOM, NTOF and NTOA are thermally stable, with decomposition points > 240 °C. The melting points of NTOM and NTOF are 82.6 °C and 71.7 °C, respectively. Hence, they possess potential to be used as melt cast materials with good thermal stabilities and better detonation performances than TNT.
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http://dx.doi.org/10.3390/molecules26237072DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8658944PMC
November 2021

Avoiding Absolute Quantification Trap: A Novel Predictive Signature of Clinical Benefit to Anti-PD-1 Immunotherapy in Non-Small Cell Lung Cancer.

Front Immunol 2021 19;12:782106. Epub 2021 Nov 19.

Department of Thoracic Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.

Immunotherapy has been focused on by many oncologists and researchers. While, due to technical biases of absolute quantification, few traditional biomarkers for anti-PD-1 immunotherapy have been applied in regular clinical practice of non-small cell lung cancer (NSCLC). Therefore, there is an urgent and unmet need for a feasible tool-immune to data source bias-for identifying patients who might benefit from ICIs in clinical practice. Using the strategy based on the relative ranking of gene expression levels, we herein proposed the novel BRGP index (BRGPI): four BRGPs significantly related with progression-free survival of NSCLC patients treated with anti-PD-1 immunotherapy in the multicohort analysis. Moreover, stratification and multivariate Cox regression analyses demonstrated that BRGPI was an independent prognostic factor. Notably, compared to PD-L1, BRGPI exerted the best predictive ability. Further analysis showed that the patients in the BRGPI-low and PD-L1-high subgroup derived more clinical benefits from anti-PD-1 immunotherapy. In conclusion, the prospect of applying the BRGPI to real clinical practice is promising owing to its powerful and reliable predictive value.
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http://dx.doi.org/10.3389/fimmu.2021.782106DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8640493PMC
November 2021

Plasma extracellular vesicle microRNA profiling and the identification of a diagnostic signature for stage I lung adenocarcinoma.

Cancer Sci 2021 Nov 27. Epub 2021 Nov 27.

Department of Thoracic Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.

At present, there is no effective noninvasive method for the accurate diagnosis of early-stage lung adenocarcinoma (LUAD). This study examined the profile of plasma extracellular vesicle (EV)-delivered microRNAs (miRNAs) in patients with invasive stage I LUAD. In this study, a total of 460 participants were enrolled, including 254 patients with LUAD, 76 patients with benign pulmonary nodules (BPNs), and 130 healthy control patients (HCs). miRNA sequencing was used to analyze the EV miRNA profile of the patient plasma samples (n = 150). A diagnostic signature (d-signature) was identified by applying a stepwise logistic regression algorithm, and a single-center training cohort (n = 150) was tested, followed by a multicenter validation cohort (n = 100). A d-signature comprising four EV-derived miRNAs (hsa-miR-106b-3p, hsa-miR-125a-5p, hsa-miR-3615, and hsa-miR-450b-5p) was developed for the early detection of LUAD. The d-signature had high precision with area under the curve (AUC) values of 0.917 and 0.902 in the training and test cohorts, respectively. Moreover, the d-signature could recognize patients with adenocarcinoma in situ (AIS) and minimally invasive adenocarcinoma (MIA) with AUC values of 0.846 and 0.92, respectively. To sum up, our study detailed the plasma EV-derived miRNA profile in early LUAD patients and developed an EV-derived miRNA d-signature to detect early LUAD.
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http://dx.doi.org/10.1111/cas.15222DOI Listing
November 2021

mA regulator expression profile predicts the prognosis, benefit of adjuvant chemotherapy, and response to anti-PD-1 immunotherapy in patients with small-cell lung cancer.

BMC Med 2021 Nov 22;19(1):284. Epub 2021 Nov 22.

Department of Thoracic Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100021, China.

Background: Small cell lung cancer (SCLC) is lethal and possesses limited therapeutic options. Platinum-based chemotherapy-with or without immune checkpoint inhibitors (anti-PDs)-is the current first-line therapy for SCLCs; however, its associated outcomes are heterogeneous. N-methyladenosine (mA) is a novel and decisive factor in tumour progression, chemotherapy resistance, and immunotherapy response. However, mA modification in SCLC remains poorly understood.

Methods: We systematically explored the molecular features and clinical significance of mA regulators in SCLC. We then constructed an mA regulator-based prognostic signature (mA score) based on our examination of 256 cases with limited-stage SCLC (LS-SCLC) from three different cohorts-including an independent cohort that contained 150 cases with qPCR data. We additionally evaluated the relationships between the mA score and adjuvant chemotherapy (ACT) benefits and the patients' responses to anti-PD-1 treatment. Immunohistochemical (IHC) staining and the HALO digital pathological platform were used to calculate CD8+ T cell density.

Results: We observed abnormal somatic mutations and expressions of mA regulators. Using the LASSO Cox model, a five-regulator-based (G3BP1, METTL5, ALKBH5, IGF2BP3, and RBM15B) mA score was generated from the significant regulators to classify patients into high- and low-score groups. In the training cohort, patients with high scores had shorter overall survival (HR, 5.19; 2.75-9.77; P < 0.001). The prognostic accuracy of the mA score was well validated in two independent cohorts (HR 4.6, P = 0.006 and HR 3.07, P < 0.001). Time-dependent ROC and C-index analyses found the mA score to possess superior predictive power than other clinicopathological parameters. A multicentre multivariate analysis revealed the mA score to be an independent prognostic indicator. Additionally, patients with low scores received a greater survival benefit from ACT, exhibited more CD8+ T cell infiltration, and were more responsive to cancer immunotherapy.

Conclusions: Our results, for the first time, affirm the significance of mA regulators in LS-SCLC. Our multicentre analysis found that the mA score was a reliable prognostic tool for guiding chemotherapy and immunotherapy selections for patients with SCLC.
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http://dx.doi.org/10.1186/s12916-021-02148-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8607595PMC
November 2021

Dynamic recurrence risk and adjuvant chemotherapy benefit prediction by ctDNA in resected NSCLC.

Nat Commun 2021 11 19;12(1):6770. Epub 2021 Nov 19.

Department of Thoracic Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.

Accurately evaluating minimal residual disease (MRD) could facilitate early intervention and personalized adjuvant therapies. Here, using ultradeep targeted next-generation sequencing (NGS), we evaluate the clinical utility of circulating tumor DNA (ctDNA) for dynamic recurrence risk and adjuvant chemotherapy (ACT) benefit prediction in resected non-small cell lung cancer (NSCLC). Both postsurgical and post-ACT ctDNA positivity are significantly associated with worse recurrence-free survival. In stage II-III patients, the postsurgical ctDNA positive group benefit from ACT, while ctDNA negative patients have a low risk of relapse regardless of whether or not ACT is administered. During disease surveillance, ctDNA positivity precedes radiological recurrence by a median of 88 days. Using joint modeling of longitudinal ctDNA analysis and time-to-recurrence, we accurately predict patients' postsurgical 12-month and 15-month recurrence status. Our findings reveal longitudinal ctDNA analysis as a promising tool to detect MRD in NSCLC, and we show pioneering work of using postsurgical ctDNA status to guide ACT and applying joint modeling to dynamically predict recurrence risk, although the results need to be further confirmed in future studies.
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http://dx.doi.org/10.1038/s41467-021-27022-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8605017PMC
November 2021

Comparison of surgical difficulty in patients with resectable non-small cell lung cancer under different neoadjuvant treatment modes: a retrospective cohort study.

J Thorac Dis 2021 Oct;13(10):5604-5616

Department of Thoracic Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.

Background: Previous studies have reported on the efficacy and safety of neoadjuvant use of a programmed cell death 1 (PD-1) antibody, sintilimab, in patients with non-small cell lung cancer (NSCLC). This study aimed to further evaluate the difficulty of this surgery and the postoperative complication rates in patients with NSCLC receiving neoadjuvant sintilimab.

Methods: Patients who received neoadjuvant sintilimab (200 mg) in the Department of Thoracic Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital from March 2018 to March 2019 were enrolled in the neoadjuvant immunotherapy group (NI group). Another two cohorts who did not receive sintilimab were retrospectively selected by propensity score matching (PSM) at a ratio of 1:1 in the upfront surgery (M-US) and neoadjuvant chemotherapy (M-NC) groups. The postoperative complication rate, postoperative days (PODs), and other detailed objective indicators were compared by -test or χ test.

Results: Thirty-seven patients were enrolled in each group. Postoperative complications were greater in the NI group (37.8%) than in the M-US (10.8%; P=0.013) or in the M-NC group (16.2%; P=0.036). The number of PODs (7) was greater in the NI group than in the M-US group (P=0.005). The total number of dissected lymph nodes was lower in the NI group than in the M-US group (P<0.001) or in the M-NC group (P<0.001). Lymph node dissection (LND) in the NI group was more difficult than in the M-US group (P=0.015), but intrathoracic adhesion, tumor invasion, and whole procedure difficulty were similar.

Conclusions: The administration of neoadjuvant sintilimab increased complications but did not increase the difficulty of surgery. Fewer lymph nodes were dissected in the NI group.
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http://dx.doi.org/10.21037/jtd-21-1007DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8575808PMC
October 2021

The effects of YKL-40 on angiogenic potential of HUVECs are partly mediated by syndecan-4.

Int J Med Sci 2021 15;18(16):3759-3767. Epub 2021 Oct 15.

Department of Cardiology, Zhejiang Provincial People's Hospital, People's Hospital of Hangzhou Medical College, Hangzhou 310014, Zhejiang, China.

YKL-40, a secreted glycoprotein, has a role in promoting tumor angiogenesis through syndecan-1 receptor. Syndecan-4 is a member of syndecan family. However, the effects of YKL-40 on migration and tube formation of human umbilical vein cells (HUVECs) mediated by syndecan-4 receptor are unknown. HUVECs were transfected with lentivirus encoding syndecan-4 short hairpin (sh) RNAs (lenti-synd4 shRNAs) and the efficiency of transfection was measured using qRT-PCR and western blotting. The effects of recombinant protein of YKL-40 on migration and angiogenesis of HUVECs adjusted by syndecan-4 were determined by wound healing and tube formation assay. The expressions of protein kinase Cα (PKCα) and extracellular signal regulated kinases (ERKs) 1 and 2 (ERK1/2) in HUVECs were measured using western blotting. The mRNA and protein expression of syndecan-4 were significantly decreased in HUVECs successfully transfected with lenti-synd4 shRNAs. Lenti-synd4 shRNAs remarkably inhibited the migration and tube formation of HUVECs stimulated by recombinant protein of YKL-40. The levels of PKCα and ratio of p-ERK1/2 to ERK1/2 in HUVECs were also decreased by down-regulating syndecan-4. The effects of YKL-40 on migration and tube formation of HUVECs are partly inhibited by knock-downing syndecan-4 through suppressing PKCα and ERK1/2 signaling pathways.
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http://dx.doi.org/10.7150/ijms.55406DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8579293PMC
October 2021

Electrochemical oxygenation of sulfides with molecular oxygen or water: switchable preparation of sulfoxides and sulfones.

Org Biomol Chem 2021 Dec 8;19(47):10314-10318. Epub 2021 Dec 8.

Key Laboratory of Jiangxi Province for Persistent Pollutants Control and Resources Recycle, Nanchang Hangkong University, Nanchang 330063, China.

A practical and eco-friendly method for the controllable aerobic oxygenation of sulfides by electrochemical catalysis was developed. The switchable preparation of sulfoxides and sulfones was effectively controlled by reaction time, in which both molecular oxygen and water can be used as the oxygen source under catalyst and external oxidant-free conditions. The electrochemical protocol features a broad substrate scope and excellent site selectivity and is successfully applied to the modification of some sulfide-containing pharmaceuticals and their derivatives.
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http://dx.doi.org/10.1039/d1ob01756jDOI Listing
December 2021

mA regulators as predictive biomarkers for chemotherapy benefit and potential therapeutic targets for overcoming chemotherapy resistance in small-cell lung cancer.

J Hematol Oncol 2021 11 10;14(1):190. Epub 2021 Nov 10.

Department of Thoracic Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100021, China.

Small-cell lung cancer (SCLC) is a devastating subtype of lung cancer with few therapeutic options. Despite the advent of immunotherapy, platinum-based chemotherapy is still the irreplaceable first-line therapy for SCLCs. However, drug resistance will invariably occur in most patients and the outcomes are heterogeneous. Therefore, clinically feasible classification strategies and potential therapeutic targets for overcoming chemotherapy resistance are urgently needed. N-methyladenosine (mA) is a novel epigenetic decisive factor that is involved in tumor progression and drug resistance. However, almost nothing is known about mA modification in SCLC. Here, we assessed 200 SCLC samples from patients who underwent chemotherapy from three different cohorts, including a validation cohort containing 71 cases with qPCR data and an independent cohort containing 79 cases with immunohistochemistry data (quantified as H-score). We systematically characterized the predictive landscape of mA regulators in SCLC patients following with chemotherapy. Using the LASSO Cox model, we built a seven-regulator-based (ZCCHC4, IGF2BP3, ALKBH5, YTHDF3, METTL5, G3BP1, and RBMX) chemotherapy benefit predictive classifier (mA score) and subsequently validated the classifier in two other cohorts. Time-dependent ROC and C-index analyses showed that the mA score to possessed superior predictive power for chemotherapy benefit in comparison with other clinicopathological parameters. A multicohort multivariate analysis revealed that the mA score is an independent factor that affects survival benefit across multiple cohorts. Our in vitro experimental results revealed that three regulators-ZCCHC4, G3BP1, and RBMX-may serve as promising novel therapeutic targets for overcoming chemoresistance in SCLCs. Our results, for the first time, demonstrate the predictive significance of mA regulators for chemotherapy benefit, as well as their potential as therapeutic targets for overcoming chemotherapy resistance in SCLC patients. The mA score was found to be a reliable prognostic tool that may help guide chemotherapy decisions for patients with SCLC.
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http://dx.doi.org/10.1186/s13045-021-01173-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8579518PMC
November 2021

Ferroptosis Characterization in Lung Adenocarcinomas Reveals Prognostic Signature With Immunotherapeutic Implication.

Front Cell Dev Biol 2021 20;9:743724. Epub 2021 Oct 20.

Department of Thoracic Surgery, National Cancer Center, National Clinical Research Center for Cancer, Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.

The iron-dependent cell death named ferroptosis has been implicated in the progression and therapeutic response of several tumors. However, potential role of ferroptosis in lung adenocarcinomas (LUAD) remained less well understood. In TCGA-LUAD cohort, unsupervised clustering was first conducted based on ferroptosis regulators extracted from FerrDb database. Comprehensive correlation analysis and comparisons were performed among ferroptosis subtypes. The ferroptosis-related prognostic (FRP) signature was identified based on filtered features and repeated LASSO and was validated in five independent cohorts. The clinical relevance between the risk score and therapeutic response was further explored by multiple algorithms. qPCR was implemented to verify gene expression. A total of 1,168 LUAD patients and 161 ferroptosis regulators were included in this study. Three ferroptosis subtypes were identified and patients in subtype B had the best prognosis among the three subtypes. Significant differences in immune microenvironment and biological function enrichment were illustrated in distinct subtypes. The Boruta algorithm was conducted on 308 common differentially expressed genes for dimensionality reduction. A total of 56 genes served as input for model construction and a six-gene signature with the highest frequencies of 881 was chosen as FRP. The prognostic significance of FRP was validated in five independent cohorts. High FRP risk score was also linked to increased tumor mutation burden, PD-L1 protein expression and number of neoantigens. Of the FRP genes, 83.3% was abnormally expressed in LUAD cell lines. In conclusion, ferroptosis plays a non-negligible role in LUAD. Exploration of the ferroptosis pattern will enhance the prognostic stratification of individual patients and move toward the purpose of personalized treatment.
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http://dx.doi.org/10.3389/fcell.2021.743724DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8563998PMC
October 2021

Multi-region sequencing reveals genetic correlation between esophageal squamous cell carcinoma and matched cell-free DNA.

Cancer Genet 2021 11 30;258-259:93-100. Epub 2021 Aug 30.

Department of Thoracic Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, People's Republic of China. Electronic address:

Purpose: This study aimed to determine if both ubiquitous and heterogeneous somatic mutations could be detected in circulating cell-free DNA (cfDNA) in patients with esophageal squamous cell carcinoma (ESCC).

Methods: Paired multi-regional tumor tissues, cfDNA, and white blood cells (WBCs) were collected from five ESCC patients before treatment, as part of an ongoing prospective study (NCT02395705). Samples from Cohort 1 were sequenced by whole-exome sequencing and samples from Cohort 2 were sequenced by targeted capture sequencing. Somatic single-nucleotide variations (SNVs) were detected by comparing solid tumor or cfDNA with matched WBCs, with a minimum variant allele frequency (VAF) of 0.1% and P value <0.05.

Results: Genomic DNA (gDNA) and plasma-derived cfDNA from 26 samples were sequenced successfully. In Cohort 1, a significant linear relationship between the tumor and cfDNA VAFs (R= 0.78, P < 0.0001) was found. In Cohort 2, cfDNA could recover an average of 60.7% (31/51; range, 35.7-76.2%) of somatic mutations present in matched solid tumors. There was a significant positive correlation in VAFs between cfDNA and matched solid tumor tissues (R= 0.92, P < 0.0001).

Conclusions: Both sequencing approaches revealed high intratumoral heterogeneity in ESCC, and enabled the detection of both ubiquitous and heterogeneous mutations in cfDNA.
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http://dx.doi.org/10.1016/j.cancergen.2021.08.005DOI Listing
November 2021

The landscape of mA regulators in small cell lung cancer: molecular characteristics, immuno-oncology features, and clinical relevance.

Mol Cancer 2021 09 27;20(1):122. Epub 2021 Sep 27.

Department of Thoracic Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100021, China.

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http://dx.doi.org/10.1186/s12943-021-01408-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8474928PMC
September 2021

Efficient Nitrate-to-Ammonia Electroreduction at Cobalt Phosphide Nanoshuttles.

ACS Appl Mater Interfaces 2021 Sep 20;13(38):45521-45527. Epub 2021 Sep 20.

Shaanxi Key Laboratory for Advanced Energy Devices, School of Materials Science and Engineering, Shaanxi Normal University, Xi'an 710062, PR China.

The nitrate electroreduction reaction (NO-ERR) is an efficient and green approach for nitrate remediation, which requires a highly active and selective electrocatalyst. In this work, porous and amorphous cobalt phosphide nanoshuttles (CoP PANSs) are successfully synthesized by using Mg ion-doped calcium carbonate nanoshuttles (Mg-CaCO NSs) as the initial reaction precursor via precipitation transformation and a high-temperature phosphidation strategy. Various physical characterizations show that CoP PANSs have porous architecture, amorphous crystal structure, and big surface area. Electrochemical measurements reveal for the first time that CoP PANSs have outstanding electroactivity for NO-ERR in a neutral electrolyte. At an applied potential of -0.5 V vs reversible hydrogen electrode, CoP PANSs can achieve a high Faraday efficiency (94.24 ± 2.8%) and high yield rate (19.28 ± 0.53 mg h mg) for ammonia production, which exceeds most reported values at various electrocatalysts for NO-ERR. Thus, the present result indicates that cobalt phosphide nanomaterials have promising application for NO-ERR.
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http://dx.doi.org/10.1021/acsami.1c12512DOI Listing
September 2021

Derivation and validation of prognostic models for predicting survival outcomes in Acute-on-chronic liver failure patients.

J Viral Hepat 2021 Dec 15;28(12):1719-1728. Epub 2021 Oct 15.

Department of Infectious Diseases, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing, China.

Acute-on-chronic liver failure (ACLF) is a syndrome characterized by acute decompensation of chronic liver disease associated with high bacterial infection (BI) and short-term mortality. However, many ACLF prognostic predictive modelsare complicated. The aim of this study is to develop prognostic models for ACLF patients to predict BI and mortality. We retrospective recruited 263 patients with ACLF from Shandong Provincial Hospital and Taizhou Enze Medical Center (Group) Enze Hospital. ACLF was defined according to the Asian Pacific Association for the Study of the Liver (APASL) criteria. Multivariable logistic regression was used to derive prediction models for occurring BI and 28-day mortality in ACLF patients. Ninety seven of 263 patients (37%) occurred BI and 41 of 155 (26%) died within 28 days of admission. C-reactive protein (CRP), glucose, and albumin were the independent predictors for occurring BI during the hospital stay. We also found that hepatic encephalopathy (HE), prothrombin time, activated partial thromboplastin time (APRI), and glucose were the independent predictors of 28-day mortality of ACLF patients. Using logistic regression model, we generated a new modified MELD model (M-MELD) by incorporating HE, APRI, and glucose. AUC of M-MELD model was 0.871, which were significantly higher than MELD score (AUC:0.734), MELD-Na score (AUC:0.742), and integrated MELD score (iMELD) (AUC:0.761). HE, MELD score, APRI, and blood glucose were independent risk factors for 28-day mortality of ACLF patients. The modified MELD model (M-MELD) by incorporating HE, APRI, and glucose has better discriminative performances compared with MELD in predicting 28-day mortality.
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http://dx.doi.org/10.1111/jvh.13611DOI Listing
December 2021

Therapeutic effects of different polar fractions of hawthorn extract on blood stasis model rats revealed by liquid chromatography-mass spectrometry metabolomics.

J Sep Sci 2021 Nov 14;44(21):4005-4016. Epub 2021 Sep 14.

College of Traditional Chinese Medicine, Guangdong Pharmaceutical University, Guangzhou, P. R. China.

Hawthorn, a commonly used traditional Chinese medicine, has been suggested to have therapeutic effects on cardiovascular disease. However, effective fractions of hawthorn extract in the treatment of cardiovascular disease, together with possible therapeutic mechanisms, remain unclear. This study aimed to investigate the effects of four different polar fractions of hawthorn extract on blood stasis model rats, and explore the possible metabolic mechanisms by using a liquid chromatography-mass spectrometry metabolomics approach. Evaluation of hemorheology and fibrinogen showed that n-butanol and ethyl acetate fractions of hawthorn extract had significant therapeutic effects on blood stasis model rats. Furthermore, metabolomics analysis showed that n-butanol and ethyl acetate fractions of hawthorn extract could reverse imbalanced biomarkers in plasma and urine of blood stasis model rats. Additionally, metabolic pathway analysis revealed that plasma biomarkers were responsible for several important pathways, including d-glutamine and d-glutamate metabolism, phenylalanine, tyrosine and tryptophan biosynthesis, alanine, aspartate, and glutamate metabolism, sphingolipid metabolism, and arginine biosynthesis. Meanwhile, urine biomarkers were responsible for some important pathways, including phenylalanine metabolism, tyrosine metabolism, and lysine degradation. This study demonstrated that n-butanol and ethyl acetate fractions of hawthorn extract had significant therapeutic effects on blood stasis model rats, and the underlying mechanisms involved multiple metabolic pathways.
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http://dx.doi.org/10.1002/jssc.202100569DOI Listing
November 2021

Severe hypoglycemia and finger clubbing in a patient with a BRCA1 mutation in a solitary fibrous tumor: a case report.

Ann Transl Med 2021 Jul;9(13):1093

Department of Thoracic Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.

Solitary fibrous tumors (SFTs) are rare tumors that stem from mesenchymal cells of submesothelial tissues belonging to the pleura. They can occur in many places such as the spinal canal, intracranial, neck, kidney, liver, pelvis, limbs and other places, most commonly in the chest and abdomen. Pleural SFTs are one of the most common types, and are common in middle-aged people. Pleural SFTs can have an insidious expression, such that the illness can progress for years before diagnosis. SFTs can induce paraneoplastic syndromes, such as reactive hypoglycemia [Doege-Potter syndrome (DPS)] or hypertrophic osteoarthropathy [Pierre-Marie-Bamberger syndrome (PMBS)]. In this article, we report a case study of a 51-year-old man with pleural SFTs. Preoperative imaging examinations, including chest X-ray, computed tomography (CT), and magnetic resonance imaging (MRI), showed a huge mass in the right thoracic cavity, compressing surrounding tissues and organs and may invade other tissues. In addition, he suffers from severe hypoglycemia and finger clubbing, and has successfully undergone a complete resection, and now attends regular follow-up appointments. The paraneoplastic syndromes have resolved, and no recurrence has been found. Importantly, we used next-generation sequencing (NGS) to explore the molecular characteristics of the patient's pathological tissue at the DNA level and mRNA level, and found that breast cancer gene 1 (BRAC1) mutations may be an important pathogenic factor.
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http://dx.doi.org/10.21037/atm-21-914DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8339833PMC
July 2021

Treatment-related adverse events of PD-1 and PD-L1 inhibitor-based combination therapies in clinical trials: a systematic review and meta-analysis.

Lancet Oncol 2021 09 13;22(9):1265-1274. Epub 2021 Aug 13.

Department of Thoracic Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China; State Key Laboratory 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.

Background: Numerous ongoing trials are testing anti-PD-1-based or anti-PD-L1-based cancer treatment combinations. Understanding the toxicity profiles of treatment-related adverse events is essential. The aim of this study was to comprehensively investigate the incidences and profiles of treatment-related adverse events across different combination therapies.

Methods: We did a systematic review and meta-analysis comparing different chemotherapy, targeted therapy, immunotherapy, and radiotherapy combinations with PD-1 or PD-L1 inhibitors. We searched Pubmed, Embase, and Cochrane databases for articles published in English between Jan 1, 2000, and May 21, 2020, investigating globally approved PD-1 or PD-L1 inhibitor-based combination therapies. Only prospective trials reporting overall incidence or tabulated data of treatment-related adverse events were included. Trials investigating sequential therapies, comprising three or more classes of therapies, and enrolling less than ten patients were excluded. The primary outcomes were overall incidences and profiles for all-grade and grade 3 or higher treatment-related adverse events by random-effect models. Heterogeneity between studies was assessed with I statistics. The summary measures for main outcomes are incidences (95% CI). The 95% CI were calculated together with the incidence through a random-effects model with a logit transformation. The protocol is registered with PROSPERO (CRD42020189617).

Findings: We identified 2540 records, of which 161 studies (17 197 patients) met the inclusion criteria. The overall incidence of treatment-related adverse events in the chemotherapy combination was 97·7% (95% CI 96·4-98·5; I=75%) for all-grade adverse events and 68·3% (60·7-75·0; I=93%) for grade 3 or higher adverse events; in the targeted therapy combination was 94·5% (90·7-96·8; I=86%) for all-grade adverse events and 47·3% (37·3-57·5; I=93%) for grade 3 or higher adverse events; in the immunotherapy combination was 86·8% (80·9-91·1; I=94%) for all-grade adverse events and 35·9% (29·5-42·9; I=92%) for grade 3 or higher adverse events; and in the radiotherapy combination was 89·4% (69·0-96·9; I=74%) for all-grade adverse events and 12·4% (4·4-30·6; I=73%) for grade 3 or higher adverse events. For these four combination therapies, the most common all-grade adverse events were anaemia (45.4% [95% CI 32·4-59·1]), fatigue (34·3% [27·5-41·9]), fatigue (26·4% [19·2-35·2]), and dysphagia (30·0% [18·7-44·5]), respectively, and the most common grade 3 or higher adverse events were neutropenia (19·6% [13·5-27·7]), hypertension (9·3% [5·7-14·9]), lipase increased (7·2% [5·2-9·9]), and lymphopenia (10·3% [4·5-21·8]). All included randomised controlled trials had a low risk of bias.

Interpretation: Our study provides comprehensive data on treatment-related adverse events of different PD-1 or PD-L1 inhibitor-based combination therapies. Our results provide an essential reference of toxicity profiles of PD-1 or PD-L1 inhibitor-based combination therapies for clinicians in routine practice of cancer care.

Funding: National Key Research and Development Programme, National Natural Science Foundation of China key program, National Natural Science Foundation of China general program, Chinese Academy of Medical Sciences Initiative for Innovative Medicine, Beijing Municipal Science and Technology Commission, Non-profit Central Research Institute Fund.
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http://dx.doi.org/10.1016/S1470-2045(21)00333-8DOI Listing
September 2021

Tuberculosis infection screening in children with close contact: a hospital-based study.

BMC Infect Dis 2021 Aug 13;21(1):815. Epub 2021 Aug 13.

National Clinical Research Center for Respiratory Diseases, National Key Discipline of Pediatrics, Capital Medical University, Key Laboratory of Major Diseases in Children, Ministry of Education, Beijing Children's Hospital, Capital Medical University, National Center for Children's Health, Beijing, China.

Background: Identifying and prioritizing at-risk populations is critical for pediatric tuberculosis control. We aimed to identify a latent tuberculosis infection (LTBI) screening strategy that is appropriate for the Chinese context among children with different TB exposure levels and to explore its clinical importance.

Methods: During 2013-2015, we enrolled hospitalized children with suspected respiratory infectious disease (RID) for LTBI screening using the tuberculin skin test (TST) and interferon-γ release assay (IGRA) T-SPOT.TB as part of a work up for their RID. Participants with confirmed diagnosis were classified into three subgroups according to level of exposure to TB: no reported contact risk, with household contact risk, and with non-household contact risk.

Results: A total 6202 children (median age: 4.76 years; interquartile range: 1.0-8.0 years) were enrolled. Children with no reported contact risk had the lowest proportions of positive results for the IGRA (0.7%) and TST (3.3%). The proportion of positive results for each test was higher for household contacts than non-household contacts. The TST positive proportion was much higher than that for the IGRA in all three groups. Children with IGRA+/TST+ results had larger indurations than those with IGRA- /TST+  results (15 mm vs. 13 mm, P = 0.02). For IGRA, older age (> 5 years) and non-household or household contact risk were associated with a positive result.

Conclusions: Positive IGRA results in children with a contact risk can serve as a critical reference for LTBI management. IGRA can be used, in preference to TST, for Chinese children with a TB exposure risk.
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http://dx.doi.org/10.1186/s12879-021-06480-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8364055PMC
August 2021

Enhanced Artificial Enzyme Activities on the Reconstructed Sawtoothlike Nanofacets of Pure and Pr-Doped Ceria Nanocubes.

ACS Appl Mater Interfaces 2021 Aug 9;13(32):38061-38073. Epub 2021 Aug 9.

Departamento de Ciencia de los Materiales, Ingeniería Metalúrgica y Química Inorgánica, Facultad de Ciencias, Universidad de Cádiz, Campus Río San Pedro, Puerto Real, Cádiz E-11510, Spain.

In this work, a simple one-step thermal oxidation process was established to achieve a significant surface increase in {110} and {111} nanofacets on well-defined, pure and Pr-doped, ceria nanocubes. More importantly, without changing most of the bulk properties, this treatment leads to a remarkable boost of their enzymatic activities: from the oxidant (oxidase-like) to antioxidant (hydroxyl radical scavenging) as well as the paraoxon degradation (phosphatase-like) activities. Such performance improvement might be due to the thermally generated sawtoothlike {111} nanofacets and defects, which facilitate the oxygen mobility and the formation of oxygen vacancies on the surface. Finally, possible mechanisms of nanoceria as artificial enzymes have been proposed in this manuscript. Considering the potential application of ceria as artificial enzymes, this thermal treatment may enable the future design of highly efficient nanozymes without changing the bulk composition.
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http://dx.doi.org/10.1021/acsami.1c09992DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8674880PMC
August 2021

TRAF2/ASK1/JNK Signaling Pathway Is Involved in the Lung Apoptosis of Swine Induced by Cadmium Exposure.

Biol Trace Elem Res 2021 Aug 8. Epub 2021 Aug 8.

College of Veterinary Medicine, Northeast Agricultural University, Harbin, 150030, People's Republic of China.

Cadmium (Cd), a toxic heavy metal, exists widely in the environment, which can enter organisms through a variety of ways and cause damage to various organs and tissues. However, the mechanism of lung toxicity in swine after Cd exposure is still unclear. To explore the molecular mechanism of swine lung damage caused by Cd exposure, we established the model of Cd exposure, and Cd chloride (20 mg/kg CdCl) was added to the diet of swine for continuous exposure for 40 days. TUNEL staining showed that the apoptosis of swine lung increased significantly after Cd exposure. Meanwhile, the results of qRT-PCR showed that Cd induced oxidative stress and inhibited the expression of antioxidant enzymes including CAT, GCLM, GST, SOD, and GSH-px in lung tissue. Cd exposure activated mitochondrial apoptosis pathway via the TRAF2/ASK1/JNK signaling pathway. In brief, we considered that Cd exposure causes oxidative stress in lung and induces lung cell apoptosis through the TRAF2/ASK1/JNK pathway and increases the expression of HSPs to resist the toxicity of Cd. Our research enriches the theoretical basis of Cd toxicity and provides reference for comparative medicine.
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http://dx.doi.org/10.1007/s12011-021-02860-6DOI Listing
August 2021

Downregulation of Interleukin-13 Receptor α2 Inhibits Angiogenic Formation Mediated by Chitinase 3-Like 1 in Late Atherosclerotic Lesions of apoE Mice.

Front Physiol 2021 19;12:690109. Epub 2021 Jul 19.

Department of Cardiology, Zhejiang Provincial People's Hospital, People's Hospital of Hangzhou Medical College, Hangzhou, China.

Chitinase 3-like 1 (CHI3L1) has the potential to prompt proliferation and angiogenic formation. Interleukin-13 receptor α2 (IL-13Rα2) was regarded as a receptor of CHI3L1; however, it is unknown whether CHI3L1 adjusts the neovascularization in late atherosclerotic lesions of apoE mice IL-13Rα2. Silicone collars were placed around one of the common carotid arteries of apoE mice fed with a high-fat diet. The mice were further injected with Ad.CHI3L1 alone or Ad.CHI3L1 + Ad.IL-13Rα2 shRNA through the caudal vein. The plaque areas in the whole aorta and aortic root were evaluated by Oil Red O staining and H&E staining. The contents of CD31, CD42b, and collagen in carotid plaques were investigated by immunohistochemistry and Masson trichrome staining. The role of CHI3L1 in migration and tube formation of human umbilical vein endothelial cells (HUVECs) was determined by transwell and Matrigel tests. The effect of CHI3L1 on the expression of AKT and extracellular signal-regulated kinase (ERK) was evaluated with the Western blot. The plaque loads in the aorta were significantly more extensive in apoE mice injected with Ad.CHI3L1 than those with Ad.CHI3L1 + Ad.IL-13Rα2 shRNA. CHI3L1 significantly increased the contents of CD31 and CD42b and decreased the element of collagen in late-stage atherosclerotic lesions of the carotid arteries. The effects of CHI3L1 on migration, tube formation, and upregulation of phospho-AKT and phospho-ERK of HUVECs were prohibited by inhibitors of phosphatidylinositol 3-kinase (PI3K) and mitogen-activated protein kinase kinase (MEK) as well as IL-13Rα2 shRNA. To some extent, CHI3L1 promotes migration and tube formation of HUVECs and neovascularization in atherosclerotic plaques possibly mediated by IL-13Rα2 through AKT and ERK signal pathways.
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http://dx.doi.org/10.3389/fphys.2021.690109DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8327173PMC
July 2021

Improving the overall survival prognosis prediction accuracy: A 9-gene signature in CRC patients.

Cancer Med 2021 09 4;10(17):5998-6009. Epub 2021 Aug 4.

Department of General Surgery & Guangdong Province Key Laboratory of Precision Medicine for Gastrointestinal Tumor, The First School of Clinical Medicine, Nanfang Hospital, Southern Medical University, Guangzhou, China.

Colorectal cancer (CRC) is a malignant tumor and morbidity rates are among the highest in the world. The variation in CRC patients' prognosis prompts an urgent need for new molecular biomarkers to improve the accuracy for predicting the CRC patients' prognosis or as a complement to the traditional TNM staging for clinical practice. CRC patients' gene expression data of HTSeq-FPKM and matching clinical information were downloaded from The Cancer Genome Atlas (TCGA) datasets. Patients were randomly divided into a training dataset and a test dataset. By univariate and multivariate Cox regression survival analyses and Lasso regression analysis, a prediction model which divided each patient into high-or low-risk group was constructed. The differences in survival time between the two groups were compared by the Kaplan-Meier method and the log-rank test. The weighted gene co-expression network analysis (WGCNA) was used to explore the relationship between all the survival-related genes. The survival outcomes of patients whose overall survival (OS) time were significantly lower in the high-risk group than that in the low-risk group both in the training and test datasets. Areas under the ROC curves which termed AUC values of our 9-gene signature achieved 0.823 in the training dataset and 0.806 in the test dataset. A nomogram was constructed for clinical practice when we combined the 9-gene signature with TNM stage and age to evaluate the survival time of patients with CRC, and the C-index increased from 0.739 to 0.794. In conclusion, we identified nine novel biomarkers that not only are independent prognostic indexes for CRC patients but also can serve as a good supplement to traditional clinicopathological factors to more accurately evaluate the survival of CRC patients.
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http://dx.doi.org/10.1002/cam4.4104DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8419765PMC
September 2021

Compensating nonlinear temperature dependence of ultrasonic motor.

Ultrasonics 2021 Dec 14;117:106522. Epub 2021 Jul 14.

Center of Ultra-precision Optoelectronic Instrument Engineering, Harbin Institute of Technology, Harbin 150080, China; Key Lab of Ultra-precision Intelligent Instrumentation (Harbin Institute of Technology), Ministry of Industry and Information Technology, Harbin 150080, China.

This article aims at realizing the linear parameter-varying (LPV) controller synthesis to compensate temperature dependence for the ultrasonic motor (USM). Initially, based on the improved optimal frequency tracking scheme, the compact LPV model is investigated to approximate the nonlinear temperature dependence. With the aid of the simulation tool, the accuracy of the proposed LPV model is proven. The LPV controller can be an appropriate choice to ensure the stability of passive nonlinear system. In view of the very strictly passivity (VSP) theorem, the VSP LPV controller is constructed as negative feedback. A set of well-designed experimental setup employed the Shinsei USR60 type USM is built afterwards, and the controller implemented by the host is applied to verify the control effect. Compared with the non-model-based controller, the USM with the proposed controller displays better performance, such as more stable output rotational speed. The feasible model in this paper is of great significance to USM. Particularly, the proposed modeling and control methodology are beneficial to the existing optimum frequency tracking technology for the USM.
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http://dx.doi.org/10.1016/j.ultras.2021.106522DOI Listing
December 2021

Bifunctional [email protected] Core-Shell Nanodendrites for Methanol Electrolysis.

ACS Appl Mater Interfaces 2021 Aug 26;13(30):35767-35776. Epub 2021 Jul 26.

Key Laboratory of Macromolecular Science of Shaanxi Province, Key Laboratory of Applied Surface and Colloid Chemistry (Ministry of Education), Shaanxi Key Laboratory for Advanced Energy Devices, School of Materials Science and Engineering, Shaanxi Normal University, Xi'an 710062, People's Republic of China.

Methanol electrolysis is a promising strategy to achieve energy-saving and efficient electrochemical hydrogen (H) production. In this system, the advanced electrocatalysts with high catalytic performance for both the methanol oxidation reaction (MOR) and hydrogen evolution reaction (HER) are highly desirable. Inspired by the complementary catalytic properties of rhodium (Rh) and palladium (Pd) for MOR and HER, herein, several Pd core-RhPd alloy shell nanodendrites ([email protected] NDs) are synthesized through the galvanic replacement reaction between Pd nanodendrites (Pd NDs) and rhodium trichloride. For MOR, [email protected] NDs exhibit Rh content-determined catalytic activity, in which [email protected] NDs have an optimal combination of oxidation potential and oxidation current due to the synergistic catalytic process of Pd/Rh double active sites. For HER, the introduction of Rh greatly improves the catalytic activity of [email protected] NDs compared to that of Pd NDs, suggesting that Rh is the main activity site for HER. Unlike MOR, however, the HER activity of [email protected] NDs is not sensitive to the Rh content. Using [email protected] NDs as robust bifunctional electrocatalysts, the as-constructed two-electrode methanol electrolysis cell shows a much lower voltage (0.813 V) than that of water electrolysis (1.672 V) to achieve electrochemical H production at 10 mA cm, demonstrating the application prospect of methanol electrolysis for H production.
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http://dx.doi.org/10.1021/acsami.1c09029DOI Listing
August 2021
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