Publications by authors named "Ying Cheng"

815 Publications

Differential mA RNA landscapes across hematopoiesis reveal a role for IGF2BP2 in preserving hematopoietic stem cell function.

Cell Stem Cell 2021 Oct 13. Epub 2021 Oct 13.

The State Key Laboratory Breeding Base of Basic Science of Stomatology & Key Laboratory of Oral Biomedicine Ministry of Education, School & Hospital of Stomatology, Wuhan University, Wuhan, China; Frontier Science Center for Immunology and Metabolism, Medical Research Institute, School of Medicine, Wuhan University, Wuhan, China; RNA Institute, Wuhan University, Wuhan, China. Electronic address:

N-methyladenosine (mA) on mRNA plays critical roles in various cellular processes. However, the landscape and dynamics of mA modification in hematopoietic system remain unknown. Here, we delineate a comprehensive mA landscape across hematopoietic hierarchy and uncover that IGF2BP2 is required for preserving the function of hematopoietic stem cells (HSCs). Our data reveal a cell-type-specific mA landscape in hematopoiesis. mA modifications arise mostly in the early stage of hematopoiesis and prefer to play distinct roles for determining mRNA fates in HSCs and committed progenitors. Mechanistically, increased mA-IGF2BP2 expression controls transcriptional state and maintenance of HSCs. IGF2BP2 deficiency induces quiescence loss and impairs HSC function. Moreover, IGF2BP2 loss increases mitochondrial activity of HSCs by accelerating Bmi1 mRNA decay, leading to de-repression of mitochondria-related genes. Collectively, our results present a fascinating portrait of mA modification of hematopoietic hierarchy and reveal a key role of IGF2BP2 in maintaining HSC function by restraining mitochondrial activity.
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http://dx.doi.org/10.1016/j.stem.2021.09.014DOI Listing
October 2021

Easily Fabricated Low-Energy Consumption Joule-Heated Superhydrophobic Foam for Fast Cleanup of Viscous Crude Oil Spills.

ACS Appl Mater Interfaces 2021 Oct 22. Epub 2021 Oct 22.

School of Chemistry and Chemical Engineering, Jiangsu University, Zhenjiang 212013, Jiangsu Province, China.

Effective cleanup of viscous crude oil spills remains a persistent and crippling challenge. Herein, this work presents a Joule-heated superhydrophobic flower-like Cu(POOH)(PO)·7HO-coated copper foam ([email protected]) for rapid cleanup of viscous crude oil spills via a facile strategy. The [email protected] shows outstanding water repellency and excellent stability of hydrophobicity in harsh environments. Due to the high electrical conductivity and thermal conductivity, it requires lower power energy consumption (less than 1 V of voltage input) to raise the temperature significantly, which dramatically reduces the viscosity of crude oil (from ∼2 × 10 to ∼60 mPa s) and then increases the oil absorption rate, effectively avoiding the poor mobility and ineffective absorption of viscous crude oil. Notably, the [email protected] can achieve continuous and quick cleanup of crude oil under in situ pumping force. The high-performance Joule-heated [email protected] sorbent with a strong porous skeleton, corrosion resistance, and low predicted operational costs holds a promise of promoting its practical applications in the cleanup of intractable and large-area viscous oil spills.
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http://dx.doi.org/10.1021/acsami.1c13574DOI Listing
October 2021

Camrelizumab in different PD-L1 expression cohorts of pre-treated advanced or metastatic non-small cell lung cancer: a phase II study.

Cancer Immunol Immunother 2021 Oct 20. Epub 2021 Oct 20.

Guangdong Lung Cancer Institute , Guangdong General Hospital & Guangdong Academy of Medical Sciences, No. 106, Zhongshan Second Road, Guangzhou, 510080, China.

Background: This phase II study evaluated camrelizumab in different PD-L1 expression cohorts of patients with previously treated advanced/metastatic non-small cell lung cancer (NSCLC; NCT03085069, registered March 21, 2017).

Methods: Patients who progressed during/after chemotherapy were enrolled and divided into four cohorts based on PD-L1 tumor proportion score (TPS). Patients with EGFR/ALK alterations and PD-L1 TPS ≥ 50% were also eligible. All enrolled patients received camrelizumab at 200 mg IV Q2W. The primary endpoint was objective response rate.

Results: A total of 146 patients were enrolled. As of data cutoff on Aug 20, 2020, the median follow-up was 29.5 months (95% CI 27.4-30.8). Objective response rate was 17.8% (95% CI 12.0-25.0) and improved with the increasing PD-L1 TPS (TPS < 1%, 12.2% [95% CI 5.7-21.8]; ≥ 1-< 25%, 19.4% [95% CI 7.5-37.5]; ≥ 25-< 50%, 36.4% [95% CI 10.9-69.2]; ≥ 50%, 23.3% [95% CI 9.9-42.3]). No response was observed in the five patients harboring EGFR mutations. Median progression-free survival was 3.2 months (95% CI 2.0-3.4), and patients with positive PD-L1 TPS had longer progression-free survival. Median overall survival was 14.8 months (95% CI 10.2-18.7). Treatment-related adverse events (TRAEs) of any grade occurred in 87.7% of patients, and 21.2% had grade ≥ 3 TRAEs.

Conclusion: Camrelizumab showed improved efficacy compared with historical data of the second-line chemotherapy in pre-treated advanced/metastatic NSCLC. Patients with positive PD-L1 expression derived greater benefit from camrelizumab. Camrelizumab has a manageable safety profile.
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http://dx.doi.org/10.1007/s00262-021-03091-3DOI Listing
October 2021

Pembrolizumab Plus Chemotherapy for Chinese Patients With Metastatic Squamous NSCLC in KEYNOTE-407.

JTO Clin Res Rep 2021 Oct 25;2(10):100225. Epub 2021 Sep 25.

Department of Medical Oncology, Hospital Universitario 12 de Octubre, Madrid, Spain.

Introduction: Pembrolizumab plus chemotherapy significantly improved survival outcomes versus placebo plus chemotherapy in patients with previously untreated metastatic squamous NSCLC in the randomized, double-blind, phase 3 KEYNOTE-407 study. We present the results of Chinese patients enrolled in the KEYNOTE-407 global and China extension studies.

Methods: Patients enrolled from mainland China in the KEYNOTE-407 global (NCT02775435) and China extension studies (NCT03875092) were randomized 1:1 to 35 cycles of pembrolizumab or placebo plus four cycles of carboplatin and paclitaxel or nab-paclitaxel. Dual primary end points were overall survival (OS) and progression-free survival (PFS) (based on the Response Evaluation Criteria in Solid Tumors version 1.1 by blinded independent central review).

Results: A total of 125 patients were randomized (pembrolizumab-chemotherapy, n = 65; placebo-chemotherapy, n = 60). As of September 30, 2020, median (range) study follow-up was 28.1 (25.1‒40.9) months. Pembrolizumab-chemotherapy improved OS (hazard ratio [HR] = 0.44, 95% confidence interval [CI]: 0.28-0.70) and PFS (HR = 0.35, 95% CI: 0.24-0.52) versus placebo-chemotherapy. Two-year OS and PFS rates for pembrolizumab-chemotherapy versus placebo-chemotherapy were 56.9% versus 31.7% and 24.2% versus 3.3%, respectively. Treatment-related grade 3 to 5 adverse events occurred in 81.5% and 81.7%, respectively. Relative to baseline, pembrolizumab-chemotherapy improved global health status/quality of life scores at week 18 versus placebo-chemotherapy (difference in least squares means = 7.6, 95% CI: 1.5-13.7) and prolonged time to deterioration in cough, chest pain, or dyspnea (HR = 0.50, 95% CI: 0.28-0.89).

Conclusions: Pembrolizumab-chemotherapy prolonged survival versus placebo-chemotherapy with manageable toxicity and preserved or improved health-related quality of life in Chinese patients with metastatic squamous NSCLC. These findings support pembrolizumab-chemotherapy as first-line therapy in this population.
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http://dx.doi.org/10.1016/j.jtocrr.2021.100225DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8503629PMC
October 2021

Arsenic-fluoride co-exposure induced endoplasmic reticulum stress resulting in apoptosis in rat heart and H9c2 cells.

Chemosphere 2021 Oct 9;288(Pt 2):132518. Epub 2021 Oct 9.

School of Public Health, Shanxi Medical University, Taiyuan, Shanxi, 030001, China. Electronic address:

Exposure to arsenic (As) or fluoride (F) has been shown to cause cardiovascular disease (CVDs). However, evidence about the effects of co-exposure to As and F on myocardium and their mechanisms remain scarce. Our aim was to fill the gap by establishing rat and H9c2 cell exposure models. We determined the effects of As and/or F exposure on the survival rate, apoptosis rate, morphology and ultrastructure of H9c2 cells; in addition, we tested the related genes and proteins of endoplasmic reticulum stress (ERS) and apoptosis in H9c2 cells and rat heart tissues. The results showed that As and/or F exposure induced early apoptosis of H9c2 cells and caused endoplasmic reticulum expansion. Additionally, the mRNA and protein expression levels of GRP78, PERK and CHOP in H9c2 cells were higher in the exposure groups than in the control group, and could be inhibited by 4-PBA. Furthermore, we found that As and/or F exposure increased the expression level of GRP78 in rat heart tissues, but interestingly, the expression level of CHOP protein was increased in the F and As groups, while significantly decreased in the co-exposure group. Overall, our results suggested that ERS-induced apoptosis was involved in the damage of myocardium by As and/or F exposure. In addition, factorial analysis results showed that As and F mainly play antagonistic roles in inducing myocardial injury, initiating ERS and apoptosis after exposure.
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http://dx.doi.org/10.1016/j.chemosphere.2021.132518DOI Listing
October 2021

High-accuracy twist measurement based on the spherical wave Talbot effect for a bi-grid modulation collimator.

Appl Opt 2021 Aug;60(22):6547-6553

The bi-grid modulation collimator is a significant way for imaging solar flares in hard x rays. It implements many subcollimators that consist of separated grid pairs (so-called front grid and rear grid) whose line orientations are parallel. However, when the twist of the front grid with respect to the other will be induced during testing of the bi-grid modulation collimator in the ground verification phase, the line orientation of the grid pairs are no longer parallel. Knowledge of the relative twist between the rear grid and the front grid is very helpful in improving the imaging quality of the bi-grid collimator. However, because of the wide spacing between grid pairs and the requirement of high measurement accuracy, it is a challenge to measure the relative twist. To meet this demand, a method based on the spherical wave Talbot effect is proposed. The Talbot images of the front grid and the rear grid are imaged on the same plane, respectively, through two proper spherical waves. The relative twist can be figured out through the angle between the stripes in the Talbot images of the front grid and the rear grid. In experiments, the measurement accuracy of the relative twist angle can reach 9 arcsec in the range of 370 arcsec. It demonstrates that this method can effectively measure the relative twist between the grid pairs with very high accuracy.
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http://dx.doi.org/10.1364/AO.429980DOI Listing
August 2021

Ginsenoside Rh2 Inhibits Glycolysis through the STAT3/c-MYC Axis in Non-Small-Cell Lung Cancer.

J Oncol 2021 25;2021:9715154. Epub 2021 Sep 25.

Department of Medical Thoracic Oncology, Jilin Cancer Hospital, Changchun 130012, China.

Ginsenoside Rh2 (Rh2) is one of the pharmacologically active components of ginseng with an antitumor effect. However, its effect on non-small-cell lung cancer (NSCLC), especially on aerobic glycolysis, which plays a crucial role in the proliferation and progression of tumor cells, has not been characterized. Here, we demonstrated that Rh2 inhibited the proliferation and metastasis of NSCLC cells by promoting apoptosis and suppressing epithelial-mesenchymal transition, respectively. Notably, Rh2 exerted a glycolysis inhibition effect through regulating GLUT1, PKM2, and LDHA, which are key enzymes of the glycolysis process. Furthermore, the metabolic shift function of Rh2 was dependent on the STAT3/c-Myc axis in NSCLC. This novel regulatory role of Rh2 provides a new perspective for NSCLC treatment and highlights the potentiality of Rh2 to be used as a tumor energy blocker. The combination of Rh2 with an STAT3 or c-Myc inhibitor revealed a promising therapeutic approach for patients with NSCLC.
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http://dx.doi.org/10.1155/2021/9715154DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8487371PMC
September 2021

Mechanism of subchronic vinyl chloride exposure combined with a high-fat diet on hepatic steatosis.

J Appl Toxicol 2021 Oct 3. Epub 2021 Oct 3.

Department of Toxicology, School of Public Health, Shanxi Medical University, Taiyuan, China.

Vinyl chloride (VC) is a common industrial organic chlorine and environmental pollutant. In recent years, the dietary structure of residents especially Chinese has gradually shifted to western dietary patterns. VC aggravates dietary fatty acid-induced hepatic steatosis, but its mechanism is still unclear. And if the risk factors for steatosis persist, more severe diseases such as fibrosis and cirrhosis will occur. Therefore, we studied the effects and mechanisms of VC (160 and 800 mg/m ) and its metabolite (chloroacetaldehyde, 2.25, 4.5, and 9 μM) on hepatic steatosis of high-fat diet (HFD)-fed mice and palmitic acid (PA, 100 μM) treated HepG2 cells. Liver and serum biochemical indicators and pathological staining of the liver showed that the hepatic steatosis of VC combined with HFD groups was more severe than that of single-exposure groups (HFD group, low-dose VC group, and high-dose VC group). Moreover, VC enhanced HFD-induced oxidative stress (OS) and endoplasmic reticulum stress (ERS) and further upregulated the expression of sterol regulatory element-binding protein 1 (SREBP-1) and FAS. Besides, antioxidants and ERS inhibitors reduced the steatosis of HepG2 cells induced by VC metabolites and PA. These results suggest that VC exposure can enhance the degree of hepatic steatosis in HFD-fed mice. VC combined with HFD led to OS and ERS and upregulated the expression of de novo lipogenesis-related proteins, which may be related to the occurrence of hepatic steatosis. And the increased expression of CYP2E1 induced by VC combined with HFD may be the cause of OS.
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http://dx.doi.org/10.1002/jat.4234DOI Listing
October 2021

Effectiveness of anlotinib in patients with small-cell lung cancer and pleural effusion: Subgroup analysis from a randomized, multicenter, phase II study.

Thorac Cancer 2021 Oct 1. Epub 2021 Oct 1.

Department of Medical Oncology, Liaoning Cancer Hospital, Shenyang, China.

Background: The presence of pleural effusion is an independent predictor for poor survival in patients with small-cell lung cancer (SCLC). The aim of this study was to assess the efficacy and safety of anlotinib in patients with SCLC and pleural effusion.

Methods: This was a randomized, double-blind, multicenter, phase II trial. Patients histologically diagnosed with SCLC and pleural effusion and had received at least two lines of chemotherapy were enrolled into the study. The patients received anlotinib 12 mg/day or a placebo.

Results: The overall response rate (ORR) was 3.7% for anlotinib (n = 27) and 0% in the placebo group (n = 15) (p = 1.000). The disease control rate (DCR) of the anlotinib group (63.0%) was higher than that of the placebo group (0%, p < 0.0001). The median progression-free survival (PFS) increased in the anlotinib group (2.8 months) compared to the placebo group (0.7 months, HR = 0.10, 95% CI: 0.03-0.28, p < 0.001). The median overall survival of the anlotinib group (6.5 months) was higher than that of the placebo group (2.8 months, HR = 0.52, 95% CI: 0.22-1.23, p = 0.1285). The incidence of any grade adverse events was 100% in both groups. The percentage of grade 3-4 adverse events in the anlotinib group was 44.4% (12/27) compared to 40.0% (6/15) in the placebo group. Hypertension (37.0%), fatigue (29.6%), and loss of appetite (29.6%) typically appeared in the anlotinib group.

Conclusions: In this post hoc analysis, anlotinib was associated with improved PFS in patients with SCLC and baseline pleural effusion. However, additional studies with a large sample size are necessary to substantiate the current findings.
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http://dx.doi.org/10.1111/1759-7714.14176DOI Listing
October 2021

Non-Hermitian topological whispering gallery.

Nature 2021 Sep 29;597(7878):655-659. Epub 2021 Sep 29.

Department of Physics, Universidad Carlos III de Madrid, Madrid, Spain.

In 1878, Lord Rayleigh observed the highly celebrated phenomenon of sound waves that creep around the curved gallery of St Paul's Cathedral in London. These whispering-gallery waves scatter efficiently with little diffraction around an enclosure and have since found applications in ultrasonic fatigue and crack testing, and in the optical sensing of nanoparticles or molecules using silica microscale toroids. Recently, intense research efforts have focused on exploring non-Hermitian systems with cleverly matched gain and loss, facilitating unidirectional invisibility and exotic characteristics of exceptional points. Likewise, the surge in physics using topological insulators comprising non-trivial symmetry-protected phases has laid the groundwork in reshaping highly unconventional avenues for robust and reflection-free guiding and steering of both sound and light. Here we construct a topological gallery insulator using sonic crystals made of thermoplastic rods that are decorated with carbon nanotube films, which act as a sonic gain medium by virtue of electro-thermoacoustic coupling. By engineering specific non-Hermiticity textures to the activated rods, we are able to break the chiral symmetry of the whispering-gallery modes, which enables the out-coupling of topological 'audio lasing' modes with the desired handedness. We foresee that these findings will stimulate progress in non-destructive testing and acoustic sensing.
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http://dx.doi.org/10.1038/s41586-021-03833-4DOI Listing
September 2021

A homozygous R148W mutation in Semaphorin 7A causes progressive familial intrahepatic cholestasis.

EMBO Mol Med 2021 Sep 29:e14563. Epub 2021 Sep 29.

Cholestatic Liver Diseases Center, Department of Gastroenterology, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing, China.

Semaphorin 7A (SEMA7A) is a membrane-bound protein that involves axon growth and other biological processes. SEMA7A mutations are associated with vertebral fracture and Kallmann syndrome. Here, we report a case with a mutation in SEMA7A that displays familial cholestasis. WGS reveals a SEMA7A homozygous mutation in a female child with elevated levels of serum ALT, AST, and total bile acid (TBA) of unknown etiology. This patient also carried a SLC10A1 allele, but Slc10a1 homozygous mice exhibited normal liver function. Similar to the child, Sema7a homozygous mice displayed elevated levels of serum ALT, AST, and TBA. Remarkably, liver histology and LC-MS/MS analyses exhibited hepatocyte hydropic degeneration and increased liver bile acid (BA) levels in Sema7a homozygous mice. Further mechanistic studies demonstrated that Sema7a mutation reduced the expression of canalicular membrane BA transporters, bile salt export pump (Bsep), and multidrug resistance-associated protein-2 (Mrp2), causing intrahepatic cholestasis in mice. Administration with ursodeoxycholic acid and a dietary supplement glutathione improved liver function in the child. Therefore, Sema7a homozygous mutation causes intrahepatic cholestasis by reducing hepatic Bsep and Mrp2 expression.
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http://dx.doi.org/10.15252/emmm.202114563DOI Listing
September 2021

The Chinese Thoracic Oncology Group (CTONG) therapeutic option scoring system: a multiple-parameter framework to assess the value of lung cancer treatment options.

Transl Lung Cancer Res 2021 Aug;10(8):3594-3607

Guangdong Lung Cancer Institute, Guangdong Provincial People's Hospital & Guangdong Academy of Medical Sciences, Guangzhou, China.

Background: Currently, there is no standard context that conforms to the Chinese national framework for evaluating medical decisions regarding the treatment of lung cancer.

Methods: This draft was formulated after a systematic review and a focus group discussion among 20 experts, who were senior physicians with extensive clinical experience from the Chinese Thoracic Oncology Group (CTONG) task force. Subsequently, a draft and a five-point Likert scale were sent to 300 CTONG working group members. These were modified according to feedback from a four-round modified Delphi approach. Hence, the first version of the 'Therapeutic option of lung cancer: CTONG scoring system' was formulated. Afterward, a corresponding questionnaire was designed to collect opinions on the weight allocation of various indicators. This was issued through the WeChat platform, "Oncology News" application and e-mails from October 23, 2020, to November 25, 2020. Participants from numerous occupations in cancer-related fields from various regions of China were included in the study. Overall and subgroup analyses regarding weight allocations were performed. The differences between participant-allocated and reference weights were considered to adjust the framework.

Results: The framework contained four aspects and six indicators, including efficacy [progression-free survival (PFS)/overall survival (OS) and subsequent treatment], safety [treatment-related severe adverse event (SAE), dose adjustment], quality of life (Qol), and compensation. The reference weights were 50%, 5%, 10%, 5%, 10%, and 20% for each indicator. By November 25, 2020, 1,043 valid questionnaires had been obtained. The majority of the questionnaires were completed by physicians (86.5%). Subgroup analysis among the various groups showed an overall consistent trend. Besides, significant differences between the participant-allocated and reference weights were found among PFS/OS (difference: -11.5%), compensation (difference: -10.1%), and subsequent treatment (difference: 9.7%) indicators. After discussion, the final weight allocations were set at 45%, 10%, 15%, 5%, 10%, and 15% for PFS/OS, subsequent treatment, treatment-related SAE, dose adjustment, Qol, and compensation, respectively.

Conclusions: The CTONG scoring system, as an objective evaluation model that involves multiple parameters, is a breakthrough method for evaluating the therapeutic value of lung cancer treatment options in China, which is worthy of further verification in future clinical practice.
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http://dx.doi.org/10.21037/tlcr-21-388DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8435396PMC
August 2021

Impact of diabetic hyperglycemia on clinical outcomes in patients with diabetes mellitus following traumatic brain injury.

Turk Neurosurg 2021 Mar 29. Epub 2021 Mar 29.

Chang Gung Medical College and University, Chang Gung Memorial Hospital at Linkou, Department of Neurosurgery, Taiwan.

Aim: Diabetes mellitus (DM) is known to induce negative systemic effects in patients with trauma. However, data on the association between DM and isolated traumatic brain injury (TBI) is limited, especially in the Asian population. This study aimed to identify the effect of patients with DM with TBI in Taiwan.

Material And Methods: Data from the trauma registry in Chang Gung Memorial Hospital, Linkou, Taiwan were collected and reviewed. Several clinical characteristics and outcomes were extracted and analyzed. The trauma databank includes 3090 patient medical records, of which 475 patients were identified as having DM. Because several baseline characteristics of patients with TBI in the DM group differed from those in the non-DM group, we performed propensity score matching to eliminate confounding factors.

Results: After propensity score matching, 895 patients with TBI comprised the non-DM group, and no significant differences were noted in the baseline characteristics between groups. Patients in the DM group had more craniotomies, longer hospital stays, and longer ICU stays. We also segmented the DM group into two subgroups based on survival status. Compared with the survivor group, the nonsurvivor group had a significantly higher serum glucose level. Furthermore, patients with DM were divided into four subgroups according to their serum glucose level. The in-hospital mortality rate was higher in the subgroup with glucose levels greater than 200mg/dL than in the other subgroups. A receiver-operating-characteristic analysis revealed that the ability of serum glucose level to predict in-hospital mortality was modest, with an area under the curve of 0.641 and an associated optimal cutoff of 206 mg/dl.

Conclusion: DM should be considered a risk factor for patients with TBI receiving neurosurgical intervention and a predictor of longer hospitalization and stay in an intensive care unit. Moreover, in patients with TBI with DM, higher admission serum glucose levels are associated with a higher in-hospital mortality rate.
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http://dx.doi.org/10.5137/1019-5149.JTN.33659-21.3DOI Listing
March 2021

Recent advances in the contribution of circRNAs to cisplatin chemotherapy resistance in cancers.

Neoplasma 2021 Sep 17. Epub 2021 Sep 17.

Department of Pathology, Guangdong Medical University, Dongguan, Guangdong, China.

Worldwide, cancer is a serious threat to the health of citizens of every country, with the incidence and mortality increasing year by year. Cisplatin is the first-line anticancer drug commonly used in clinics and is widely used for the treatment of solid tumors including lung, gastric, liver, bladder, and ovarian cancer. Although cisplatin-based chemotherapy has a high clinical response efficacy, patients will inevitably develop drug resistance after repeated using, leading to severe restrictions of its application. Circular RNAs (circRNAs) are a promising class of non-coding RNAs capable of promoting or suppressing cancer via functioning as miRNAs sponges. Recently, an increasing amount of evidence shows that circRNAs are closely related to the cisplatin resistance of cancers. Therefore, standing at the perspective of the cisplatin chemotherapy resistance, this paper reviews the research progress of circRNAs related to cisplatin resistance of various cancers.
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http://dx.doi.org/10.4149/neo_2021_210624N846DOI Listing
September 2021

Application of neurally adjusted ventilatory assist in ventilator weaning of infants ventilator weaning.

Brain Behav 2021 Sep 14:e2350. Epub 2021 Sep 14.

Department of Pediatric Critical Medicine, Maternal and Child Health Care Hospital of Hubei Province, Wuhan, China.

Background: To analyze the application of neurally adjusted ventilatory assist in ventilator weaning of infants.

Methods: A total of 25 infants (15 boys and 10 girls) who were mechanically ventilated by PICU in Hubei Maternal and Child Health Hospital were selected as the study subjects. After the improvement of the basic disease, regular spontaneous breathing, and the withdrawal of the ventilator, all the children obtained the electrical activity of the diaphragm (EAdi) signal. Then, each child was given CPAP and NAVA mode mechanical ventilation 1 h before the withdrawal of the ventilator. Each detection index was recorded 30 min after each mode of ventilation.

Results: Two of the 25 children were tracheotomized because of respiratory muscle weakness and could not be converted to NAVA mode without the EAdi signal. Hemodynamic indexes were not statistically different between the two groups of CPAP and NAVA. PaCO is not significantly different in the two modes, and both were at normal levels. The PIP in NAVA mode is lower than that in CPAP mode (p < .05), and its EAdi signal was correspondingly low. There were significant differences in the peak pressure (Ppeak), mean pressure (Pmean), and compliance and mean arterial pressure (p < .01) between the CPAP and NAVA model ventilation in 23 patients.

Conclusion: NAVA can significantly improve the coordination of patients. The therapeutic effect of NAVA was better, which was beneficial to the prognosis of patients and had positive application value in the withdrawal of ventilators in patients.
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http://dx.doi.org/10.1002/brb3.2350DOI Listing
September 2021

Effect of Camrelizumab vs Placebo Added to Chemotherapy on Survival and Progression-Free Survival in Patients With Advanced or Metastatic Esophageal Squamous Cell Carcinoma: The ESCORT-1st Randomized Clinical Trial.

JAMA 2021 09;326(10):916-925

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

Importance: Standard first-line therapy for advanced or metastatic esophageal carcinoma is chemotherapy, but the prognosis remains poor. Camrelizumab (an anti-programmed death receptor 1 [PD-1] antibody) showed antitumor activity in previously treated advanced or metastatic esophageal squamous cell carcinoma.

Objective: To evaluate the efficacy and adverse events of camrelizumab plus chemotherapy vs placebo plus chemotherapy as a first-line treatment in advanced or metastatic esophageal squamous cell carcinoma.

Design, Setting, And Participants: This randomized, double-blind, placebo-controlled, multicenter, phase 3 trial (ESCORT-1st study) enrolled patients from 60 hospitals in China between December 3, 2018, and May 12, 2020 (final follow-up, October 30, 2020). A total of 751 patients were screened and 596 eligible patients with untreated advanced or metastatic esophageal squamous cell carcinoma were randomized.

Interventions: Patients were randomized 1:1 to receive either camrelizumab 200 mg (n = 298) or placebo (n = 298), combined with up to 6 cycles of paclitaxel (175 mg/m2) and cisplatin (75 mg/m2). All treatments were given intravenously every 3 weeks.

Main Outcomes And Measures: Coprimary end points were overall survival (significance threshold, 1-sided P < .02) and progression-free survival (significance threshold, 1-sided P < .005).

Results: Of the 596 patients randomized (median age, 62 years [interquartile range, 56-67 years]; 523 men [87.8%]), 1 patient in the placebo-chemotherapy group did not receive planned treatment. A total of 490 patients (82.2%) had discontinued the study treatment. The median follow-up was 10.8 months. The overall survival for the camrelizumab-chemotherapy group was a median of 15.3 months (95% CI, 12.8-17.3; 135 deaths) vs a median of 12.0 months (95% CI, 11.0-13.3; 174 deaths) for the placebo-chemotherapy group (hazard ratio [HR] for death, 0.70 [95% CI, 0.56-0.88]; 1-sided P = .001). Progression-free survival for camrelizumab plus chemotherapy was a median of 6.9 months (95% CI, 5.8-7.4; 199 progression or deaths) vs 5.6 months (95% CI, 5.5-5.7; 229 progression or deaths) for the placebo-chemotherapy group (HR for progression or death, 0.56 [95% CI, 0.46-0.68]; 1-sided P < .001). Treatment-related adverse events of grade 3 or higher occurred in 189 patients (63.4%) in the camrelizumab-chemotherapy group and 201 (67.7%) in the placebo-chemotherapy group, including treatment-related deaths among 9 patients (3.0%) and 11 patients (3.7%), respectively.

Conclusions And Relevance: Among patients with advanced or metastatic esophageal squamous cell carcinoma, the addition of camrelizumab to chemotherapy, compared with placebo and chemotherapy, significantly improved overall survival and progression-free survival.

Trial Registration: ClinicalTrials.gov Identifier: NCT03691090.
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http://dx.doi.org/10.1001/jama.2021.12836DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8441593PMC
September 2021

Baicalin attenuates angiotensin II-induced blood pressure elevation and modulates MLCK/p-MLC signaling pathway.

Biomed Pharmacother 2021 Nov 4;143:112124. Epub 2021 Sep 4.

Academy of Integrative Medicine, Fujian University of Traditional Chinese Medicine, Fuzhou, Fujian 350122, China; Fujian Key Laboratory of Integrative Medicine on Geriatrics, Fujian University of Traditional Chinese Medicine, Fuzhou, Fujian 350122, China; Chen Keji Academic Thought Inheritance Studio, Fujian University of Traditional Chinese Medicine, Fuzhou, Fujian 350122, China. Electronic address:

Scutellaria baicalensis Georgi is an extensively used medicinal herb for the treatment of hypertension in traditional Chinese medicine. Baicalin, is an important flavonoid in Scutellaria baicalensis Georgi extracts, which exhibits therapeutic effects on anti-hypertension, but its underlying mechanisms remain to be further explored. Therefore, we investigated the effects and molecular mechanisms of Baicalin on anti-hypertension. In vivo studies revealed that Baicalin treatment significantly attenuated the elevation in blood pressure, the pulse propagation and thickening of the abdominal aortic wall in C57BL/6 mice infused with Angiotensin II (Ang II). Moreover, RNA-sequencing and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses identified 537 differentially expressed transcripts and multiple enriched signaling pathways (including vascular smooth muscle contraction and calcium signaling pathway). Consistently, we found that Baicalin pretreatment significantly alleviated the Ang II induced constriction of abdominal aortic ring, while promoted NE pre-contracted vasodilation of abdominal aortic ring at least partly dependent on L-type calcium channel. In addition, Ang II stimulation significantly increased cell viability and PCNA expression, while were attenuated after Baicalin treatment. Moreover, Baicalin pretreatment attenuated Ang II-induced intracellular Ca release, Angiotensin II type 1 receptor (AT1R) expression and activation of MLCK/p-MLC pathway in vascular smooth muscle cells (VSMCs). The present work further addressed the pharmacological and mechanistic insights on anti-hypertension of Baicalin, which may help better understand the therapeutic effect of Scutellaria baicalensis Georgi on anti-hypertension.
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http://dx.doi.org/10.1016/j.biopha.2021.112124DOI Listing
November 2021

Ensartinib vs Crizotinib for Patients With Anaplastic Lymphoma Kinase-Positive Non-Small Cell Lung Cancer: A Randomized Clinical Trial.

JAMA Oncol 2021 Sep 2. Epub 2021 Sep 2.

Guangdong Lung Cancer Institute, Guangdong Provincial People's Hospital and Guangdong Academy of Medical Sciences, Guangzhou, China.

Importance: Ensartinib, an oral tyrosine kinase inhibitor of anaplastic lymphoma kinase (ALK), has shown systemic and central nervous system efficacy for patients with ALK-positive non-small cell lung cancer (NSCLC).

Objective: To compare ensartinib with crizotinib among patients with advanced ALK-positive NSCLC who had not received prior treatment with an ALK inhibitor.

Design, Setting, And Participants: This open-label, multicenter, randomized, phase 3 trial conducted in 120 centers in 21 countries enrolled 290 patients between July 25, 2016, and November 12, 2018. Eligible patients were 18 years of age or older and had advanced, recurrent, or metastatic ALK-positive NSCLC.

Interventions: Patients were randomized (1:1) to ensartinib, 225 mg once daily, or crizotinib, 250 mg twice daily.

Main Outcomes And Measures: The primary end point was blinded independent review committee-assessed progression-free survival (PFS). Secondary end points included systemic and intracranial response, time to central nervous system progression, and overall survival. Efficacy was evaluated in the intent-to-treat (ITT) population as well as a prespecified modified ITT (mITT) population consisting of patients with central laboratory-confirmed ALK-positive NSCLC.

Results: A total of 290 patients (149 men [51.4%]; median age, 54 years [range, 25-90 years]) were randomized. In the ITT population, the median PFS was significantly longer with ensartinib than with crizotinib (25.8 [range, 0.03-44.0 months] vs 12.7 months [range, 0.03-38.6 months]; hazard ratio, 0.51 [95% CI, 0.35-0.72]; log-rank P < .001), with a median follow-up of 23.8 months (range, 0-44 months) for the ensartinib group and 20.2 months (range, 0-38 months) for the crizotinib group. In the mITT population, the median PFS in the ensartinib group was not reached, and the median PFS in the crizotinib group was 12.7 months (95% CI, 8.9-16.6 months; hazard ratio, 0.45; 95% CI, 0.30-0.66; log-rank P < .001). The intracranial response rate confirmed by a blinded independent review committee was 63.6% (7 of 11) with ensartinib vs 21.1% (4 of 19) with crizotinib for patients with target brain metastases at baseline. Progression-free survival for patients without brain metastases was not reached with ensartinib vs 16.6 months with crizotinib as a result of a lower central nervous system progression rate (at 12 months: 4.2% with ensartinib vs 23.9% with crizotinib; cause-specific hazard ratio, 0.32; 95% CI, 0.16-0.63; P = .001). Frequencies of treatment-related serious adverse events (ensartinib: 11 [7.7%] vs crizotinib: 9 [6.1%]), dose reductions (ensartinib: 34 of 143 [23.8%] vs crizotinib: 29 of 146 [19.9%]), or drug discontinuations (ensartinib: 13 of 143 [9.1%] vs crizotinib: 10 of 146 [6.8%]) were similar, without any new safety signals.

Conclusions And Relevance: In this randomized clinical trial, ensartinib showed superior efficacy to crizotinib in both systemic and intracranial disease. Ensartinib represents a new first-line option for patients with ALK-positive NSCLC.

Trial Registration: ClinicalTrials.gov Identifier: NCT02767804.
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http://dx.doi.org/10.1001/jamaoncol.2021.3523DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8414368PMC
September 2021

Ultra-sparse metamaterials absorber for broadband low-frequency sound with free ventilation.

J Acoust Soc Am 2021 Aug;150(2):1044

Key Laboratory of Modern Acoustics, Department of Physics and Collaborative Innovation Center of Advanced Microstructures, Nanjing University, Nanjing 210093, China.

An absorptive device for broadband low-frequency sound with ventilation is essential but challenging in acoustic engineering, which is subjected to the narrow-band limitation and difficulty of balancing high-efficiency absorption and excellent ventilation. Here, we have theoretically and experimentally demonstrated an ultra-sparse (with filling ratio of 53.7%) broadband metamaterial absorber which can efficiently absorb (absorptance  >90%) sound energy ranging from 307 to 341 Hz, while enabling air to flow freely. The broadband absorber is constructed by parallel coupling four ventilated metamaterials absorbers (VMAs) showing different operating frequencies. Each VMA is composed of three folded Fabry-Pérot resonators as paste components, which are patched subsequently to the walls of a waveguide and correspondingly act as dark, middle, and bright modes following the coupled mode theory. In the VMA, the dark mode is highly over-damped to absorb sound energy, while the bright mode is highly under-damped to be an effective acoustic soft boundary, and the middle mode in-between should be slightly over-damped to strengthen the absorptions. Further investigation demonstrates that broadband high-efficiency absorption is robust against oblique incident angles. The proposed VMA provides a clear scheme for efficiently absorbing low-frequency sound while allowing free air flow simultaneously, which may prompt versatile applications in noise control.
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http://dx.doi.org/10.1121/10.0005850DOI Listing
August 2021

Non-canonical phosphorylation of Bmf by p38 MAPK promotes its apoptotic activity in anoikis.

Cell Death Differ 2021 Aug 30. Epub 2021 Aug 30.

Frontier Institute of Science and Technology, Xi'an Jiaotong University, Xi'an, China.

Bmf contributes to the onset of anoikis by translocating from cytoskeleton to mitochondria when cells lose attachment to the extracellular matrix. However, the structural details of Bmf cytoskeleton tethering and the control of Bmf release upon loss of anchorage remained unknown. Here we showed that cell detachment induced rapid and sustained activation of p38 MAPK in mammary epithelial cell lines. Inhibition of p38 signaling or Bmf knockdown rescued anoikis. Activated p38 MAPK could directly phosphorylate Bmf at multiple sites including a non-proline-directed site threonine 72 (T72). Crystallographic studies revealed that Bmf T72 directly participated in DLC2 binding and its phosphorylation would block Bmf/DLC2 interaction through steric hindrance. Finally, we showed that phosphomimetic mutation of T72 enhanced Bmf apoptotic activity in vitro and in a knock-in mouse model. This work unraveled a novel regulatory mechanism of Bmf activity during anoikis and provided structural basis for Bmf cytoskeleton tethering and dissociation.
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http://dx.doi.org/10.1038/s41418-021-00855-3DOI Listing
August 2021

Visible-Light-Driven Photoredox-Catalyzed Three-Component Radical Cyanoalkylfluorination of Alkenes with Oxime Esters and a Fluoride Ion.

Org Lett 2021 Sep 25;23(17):6987-6992. Epub 2021 Aug 25.

CCNU-uOttawa Joint Research Centre, Key Laboratory of Pesticides & Chemical Biology Ministry of Education, College of Chemistry, Central China Normal University, 152 Luoyu Road, Wuhan, Hubei 430079, China.

A metal-free, photoredox-catalyzed three-component cyanoalkylfluorination of alkenes under mild and redox-neutral conditions is reported. This protocol features use of readily available alkenes, oxime esters, and cost-effective nucleophilic fluoride reagents, giving diverse cyanoalkylfluorinated products with generally good yields. Excellent functional group tolerance and mild reaction conditions also render this protocol suitable for cyanoalkylfluorination of pharmaceutically relevant molecule-derived alkene.
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http://dx.doi.org/10.1021/acs.orglett.1c02686DOI Listing
September 2021

Transmission of Severe Acute Respiratory Syndrome Coronavirus 2 to Close Contacts, China, January-February 2020.

Emerg Infect Dis 2021 09;27(9):2288-2293

We estimated the symptomatic, PCR-confirmed secondary attack rate (SAR) for 2,382 close contacts of 476 symptomatic persons with coronavirus disease in Yichang, Hubei Province, China, identified during January 23-February 25, 2020. The SAR among all close contacts was 6.5%; among close contacts who lived with an index case-patient, the SAR was 10.8%; among close-contact spouses of index case-patients, the SAR was 15.9%. The SAR varied by close contact age, from 3.0% for those <18 years of age to 12.5% for those >60 years of age. Multilevel logistic regression showed that factors significantly associated with increased SAR were living together, being a spouse, and being >60 years of age. Multilevel regression did not support SAR differing significantly by whether the most recent contact occurred before or after the index case-patient's onset of illness (p = 0.66). The relatively high SAR for coronavirus disease suggests relatively high virus transmissibility.
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http://dx.doi.org/10.3201/eid2709.202035DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8386800PMC
September 2021

A transcriptome-wide association study identifies novel susceptibility genes for psoriasis.

Hum Mol Genet 2021 Aug 18. Epub 2021 Aug 18.

Key Laboratory of Biomedical Information Engineering of Ministry of Education, School of Life Science and Technology, Xi'an Jiaotong University, Xi'an, Shaanxi, 710049, P. R. China.

Although more than 80 psoriasis genetic risk loci have been reported through genome-wide association studies (GWASs), the genetic mechanism of psoriasis remains unclear. To identify novel candidate genes associated with psoriasis and reveal the potential effects of genetic factors in the development of psoriasis, we conducted a transcriptome-wide association study (TWAS) based on summary statistics from GWAS of psoriasis (5175 cases and 447 089 controls) and gene expression levels from six tissues datasets (blood and skin). We identified 11 conditionally independent genes for psoriasis after Bonferroni corrections, such as the most significant genes UBLCP1 (PYFS = 2.98 × 10-16), and LCE3C (PSNSE = 9.72 × 10-12, PSSE = 6.24 × 10-12). The omnibus test identified additional 5 genes associated with psoriasis via the joint association model from multiple reference tissues. Among the 16 identified genes, 5 genes (CTSW, E1F1AD, KLRC3, FIBP, and EFEMP2) were regarded as novel genes for psoriasis. We evaluated the 16 candidate genes by querying public databases and identified 11 differentially expressed genes and 8 genes proved by the knockout mice models. Through GO enrichment analyses, we found that TWAS genes were enriched in the known GO terms associated with skin development, such as cornified envelope (P = 4.80 × 10-8) and peptide cross-linking (P = 1.50 × 10-7). Taken together, our results detected multiple novel candidate genes for psoriasis, providing clues for understanding the genetic mechanism of psoriasis.
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http://dx.doi.org/10.1093/hmg/ddab237DOI Listing
August 2021

Subgroup Analysis by Liver Metastasis in the FRESCO Trial Comparing Fruquintinib versus Placebo Plus Best Supportive Care in Chinese Patients with Metastatic Colorectal Cancer.

Onco Targets Ther 2021 11;14:4439-4450. Epub 2021 Aug 11.

Eli Lilly and Company, Shanghai, People's Republic of China.

Objective: The aim of the present subgroup analysis of the FRESCO trial is to determine the efficacy and hepatotoxicity of fruquintinib in Chinese patients with metastatic CRC with liver metastasis (CRLM) who were receiving third-line or posterior-line therapy.

Methods: Overall survival (OS) and progression-free survival (PFS) were evaluated by Kaplan-Meier method. Hazard ratio (HR) was estimated through Cox proportional hazards model. Hepatotoxicity was coded using the standardized MedDRA queries of hepatic failure, fibrosis, cirrhosis, and other liver injury-related conditions and graded using the Common Terminology Criteria Adverse Events grades. The efficacy of fruquintinib in patients with CRLM was evaluated in various subgroups.

Results: A total of 287 (69.0%) patients with metastatic CRC had liver metastasis (LM, fruquintinib: 185 and placebo: 102). Median OS in patients with CRLM was significantly prolonged with fruquintinib compared with placebo (8.61 months vs 5.98 months; HR=0.59, 95% CI, 0.45-0.77, P<0.001). In patients with CRLM, the incremental median PFS for patients in the fruquintinib-treated group was significantly higher than in the placebo group (median PFS: 3.71 vs.1.84 months; HR=0.22, 95% CI: 0.17-0.30; P<0.001). Compared with placebo, significant improvements in OS were observed with fruquintinib in LM patients regardless of lung metastasis, prior target therapy, and K-RAS status. In patients with CRLM, treatment-emergent hepatotoxicities of any grade occurred in 7 (3.8%) patients in the fruquintinib group vs 2 (2.0%) in the placebo group.

Conclusion: Fruquintinib demonstrated a statistically significant increase in OS and PFS as compared with placebo in Chinese patients with CRLM. The hepatotoxicity of fruquintinib was less reported, and comparable with placebo in patients with CRLM.

Clinicaltrialsgov Identifier: NCT02314819.
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http://dx.doi.org/10.2147/OTT.S307273DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8364970PMC
August 2021

Photoinduced Copper-Catalyzed Asymmetric Three-Component Coupling of 1,3-Dienes: An Alternative to Kharasch-Sosnovsky Reaction.

Angew Chem Int Ed Engl 2021 10 9;60(42):22956-22962. Epub 2021 Sep 9.

CCNU-uOttawa Joint Research Centre, Key Laboratory of Pesticides & Chemical Biology Ministry of Education, College of Chemistry, Central China Normal University, 152 Luoyu Road, Wuhan, Hubei, 430079, China.

Kharasch-Sosnovsky reaction is one of the most powerful methods for allylic oxidation of alkenes. However, the inherent radical mechanism and use of peroxides as both oxidants and oxygen nucleophiles render dearth of universal catalytic systems for highly enantioselective variants and limited scope. Herein, an alternative to the asymmetric Kharasch-Sosnovsky reaction that utilized a chiral copper catalyst and purple-LED irradiation to enable the three-component coupling of 1,3-dienes, oxime esters, and carboxylic acids is reported. This protocol features mild conditions, remarkable scope and functional group tolerance as evidenced by >80 examples and utility in the late-stage modification of pharmaceuticals and natural products. Detailed mechanistic studies provide evidences for the radical-based reaction pathway.
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http://dx.doi.org/10.1002/anie.202110084DOI Listing
October 2021

Retro-labyrinthine Lesion Site Detected by Galvanic Vestibular Stimulation Elicited Vestibular-evoked Myogenic Potentials in Patients with Auditory Neuropathy.

Curr Med Sci 2021 Aug 17;41(4):695-704. Epub 2021 Aug 17.

Department of Otorhinolaryngology, Head, and Neck Surgery, Second Affiliated Hospital of Xi'an Jiaotong University School of Medicine, Xi'an, 710000, China.

Objective: Auditory neuropathy (AN) is a unique pattern of hearing loss with preservation of hair cell function. The condition is characterized by the presence of otoacoustic emissions (OAE) or cochlear microphonic (CM) responses with severe abnormalities of the auditory brainstem response (ABR). The vestibular branches of the VIII cranial nerve and the structures innervated by it can also be affected. However, the precise lesion sites in the vestibular system are not well characterized in patients with AN.

Methods: The air-conducted sound (ACS) vestibular-evoked myogenic potentials (VEMPs) and galvanic vestibular stimuli (GVS)-VEMPs were examined in 14 patients with AN.

Results: On examination of VEMPs (n=14, 28 ears), the absent rates of ACS-cervical VEMP (cVEMP), ACS-ocular VEMP (oVEMP), GVS-cVEMP, GVS-oVEMP and caloric test were 92.9% (26/28), 85.7% (24/28), 67.9% (19/28), 53.6% (15/28), and 61.5% (8/13), respectively. Impaired functions of the saccule, inferior vestibular nerve, utricle, superior vestibular nerve, and horizontal semicircular canal were found in 25.0% (7/28), 67.9% (19/28), 32.1% (9/28), 53.6% (15/28) and 61.5% (8/13) patients, respectively. On comparing the elicited VEMPs parameters of AN patients with those of normal controls, both ACS-VEMPs and GVS-VEMPs showed abnormal results in AN patients (such as, lower presence rates, elevated thresholds, prolonged latencies, and decreased amplitudes).

Conclusion: The study suggested that patients with AN often have concomitant vestibular disorders. Retro-labyrinthine lesions were more frequently observed in this study. GVS-VEMPs combined with ACS-VEMPs may help identify the lesion sites and facilitate detection of areas of vestibular dysfunction in these patients.
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http://dx.doi.org/10.1007/s11596-021-2411-5DOI Listing
August 2021

Qingda Granule Attenuates Angiotensin II-Induced Blood Pressure and Inhibits Ca/ERK Signaling Pathway.

Front Pharmacol 2021 29;12:688877. Epub 2021 Jul 29.

Academy of Integrative Medicine, Fuzhou, China.

As a well-known traditional Chinese medicine formula prescribed by academician Ke-ji Chen, Qingda granule (QDG) lowered the blood pressure of spontaneously hypertensive rats and attenuated hypertensive cardiac remodeling and inflammation. However, its functional role and underlying mechanisms on hypertensive vascular function remain largely unclear. This study aims to assess the effects of QDG treatment on Angiotensin II- (AngII-) induced hypertension and vascular function and explore its underlying mechanisms both and . In an study, 25 male C57BL/6 mice were randomly divided into five groups, including Control, AngII, AngII + QDG-L, AngII + QDG-M, and AngII + QDG-H groups ( = 5 for each group). Mice in AngII and AngII + QDG-L/-M/-H groups were infused with AngII (500 ng/kg/min), while in the Control group, they were infused with saline. Mice in AngII + QDG were intragastrically given different concentrations of QDG (0.5725, 1.145, or 2.29 g/kg/day), while in Control and AngII groups, they were intragastrically given equal volumes of double distilled water for 2 weeks. Blood pressure was determined at 0, 1, and 2 weeks of treatment. Ultrasound was used to detect the pulse wave velocity (PWV) and HE staining to detect the pathological change of the abdominal aorta. RNA sequencing (RNA-seq) was performed to identify the differentially expressed transcripts (DETs) and related signaling pathways. IHC was used to detect the expression of p-ERK in the abdominal aorta. Primary isolated rat vascular smooth muscle cells (VSMCs) were used to assess the cellular Ca release and activation of the ERK pathway by confocal microscope and western blotting analysis, respectively. QDG treatment significantly alleviated the elevated blood pressure, the PWV, and the thickness of the abdominal aorta in AngII-induced hypertensive mice. RNA-seq and KEGG analyses identified 1,505 DETs and multiple enriched pathways (including vascular contraction and calcium signaling pathway) after QDG treatment. Furthermore, confocal microscope showed that QDG treatment partially attenuated the increase of Ca release with the stimulation of AngII in cultured VSMCs. In addition, IHC and western blotting indicated that QDG treatment also partially alleviated the increase of phospho-ERK levels in abdominal aorta tissues of mice and cultured VSMCs after the infusion or stimulation of AngII. QDG treatment attenuated the elevation of blood pressure, abdominal aorta dysfunction, pathological changes, Ca release, and activation of the ERK signaling pathway.
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http://dx.doi.org/10.3389/fphar.2021.688877DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8358933PMC
July 2021

Bevacizumab plus erlotinib in Chinese patients with untreated, EGFR-mutated, advanced NSCLC (ARTEMIS-CTONG1509): A multicenter phase 3 study.

Cancer Cell 2021 Sep 12;39(9):1279-1291.e3. Epub 2021 Aug 12.

Guangdong Provincial Key Laboratory of Translational Medicine in Lung Cancer, Guangdong Lung Cancer Institute, Guangdong Provincial People's Hospital and Guangdong Academy of Medical Sciences, Guangzhou, China. Electronic address:

Dual inhibition of epidermal growth factor receptor (EGFR) and vascular endothelial growth factor (VEGF) pathways may delay therapeutic resistance in advanced non-small cell lung cancer (NSCLC). This phase 3 study investigated the efficacy and safety of an erlotinib plus bevacizumab regimen in untreated patients with advanced NSCLC. In total, 311 patients received bevacizumab plus erlotinib (n = 157) or erlotinib only (n = 154). Progression-free survival (PFS) was 17.9 months (95% confidence interval [CI], 15.2-19.9) for bevacizumab plus erlotinib and 11.2 months (95% CI, 9.7-13.8) for erlotinib only (hazard ratio [HR] = 0.55; 95% CI, 0.41-0.73; p < 0.001). A brain metastases subgroup treated with bevacizumab plus erlotinib also showed improved PFS (HR = 0.48; 95% CI, 0.27-0.84; p = 0.008). Grade ≥3 treatment-related adverse events occurred in 86 (54.8%) and 40 (26.1%) patients, respectively. Bevacizumab plus erlotinib significantly improved PFS in patients with untreated metastatic EGFR-mutated NSCLC, including those with brain metastases at baseline.
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http://dx.doi.org/10.1016/j.ccell.2021.07.005DOI Listing
September 2021

Activation of peroxymonosulfate by iron oxychloride with hydroxylamine for ciprofloxacin degradation and bacterial disinfection.

Sci Total Environ 2021 Dec 5;799:149506. Epub 2021 Aug 5.

Key Laboratory of Microbial Technology for Industrial Pollution Control of Zhejiang Province, College of Environment, Zhejiang University of Technology, Hangzhou 310014, China. Electronic address:

Iron oxychloride (FeOCl) is a known effective iron-based catalyst and has been used in advanced oxidation processes (AOPs). This study intends to achieve more facile free radicals generation from peroxymonosulfate (PMS) activation by exploring the Fe(III)/Fe(II) cycle of FeOCl in the presence of hydroxylamine (HA). With 0.2 g/L FeOCl, 1.5 mM PMS, and 1 mM HA, the PMS/FeOCl/HA system could effectively achieve 98.88% of the oxidative degradation of 5 mg/L ciprofloxacin (CIP) in 15 min and quickly inactivate 99.99% of E. coli (10 CFU/mL) in 5 min at near-neutral pH. HA played an important role in promoting the Fe(III)/Fe(II) cycle, thereby greatly improving the oxidation activity of the system. The reactive oxygen species (ROS) such as HO, SO and O were identified as the dominated free radicals produced in the system. The intermediate products of CIP detected by liquid chromatograph-mass spectrometer (LC-MS) and three possible degradation pathways of CIP were proposed. The presence of common anions in the PMS/FeOCl/HA system, including HCO, Cl, SO, and NO, enhanced the degradation efficiency of CIP to varying degrees at the concentrations of 10 mM. Moreover, FeOCl maintained a high degradation capability for CIP after several recycles. This work offers a new promising means of catalyzing the PMS-based AOPs in the degradation of refractory organics.
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http://dx.doi.org/10.1016/j.scitotenv.2021.149506DOI Listing
December 2021

Targeting NUFIP1 Suppresses Growth and Induces Senescence of Colorectal Cancer Cells.

Front Oncol 2021 23;11:681425. Epub 2021 Jul 23.

Department of Gastroenterology, Fujian Medical University Union Hospital, Fuzhou, China.

NUFIP1 is an RNA-binding protein that interacts with fragile X mental retardation protein (FMRP) in the messenger ribonucleoprotein particle (mRNP). We previously showed that NUFIP1 was upregulated in colorectal cancer (CRC), but how the protein may contribute to the disease and patient prognosis is unknown. Here we combine database analysis, microarray, quantitative PCR, and immunohistochemistry of patients' samples to confirm our previous findings on NUFIP1 overexpression in CRC, and to reveal that increased expression of NUFIP1 in CRC tissues correlated with worse overall, recurrence-free, event-free and disease-free survival in patients, as well as with more advanced CRC clinicopathological stage. Loss of function analysis demonstrated that NUFIP1 knockdown suppressed cell growth and , inhibited cell viability and survival, and induced cell cycle arrest and apoptosis , as well as up-regulated Bax and down-regulated Bcl-2 protein expression. In addition, as a natural anticancer triterpene from various fruits and vegetables, ursolic acid (UA) treatment suppressed cell proliferation, down-regulated NUFIP1 protein expression, and further enhanced the effects of NUFIP1 knockdown in CRC cells . NUFIP1 knockdown up-regulated the expression of 136 proteins, down-regulated the expression of 41 proteins, and enriched multiple signaling pathways including the senescence-associated heterochromatin foci (SAHF) pathway. Furthermore, NUFIP1 knockdown enhanced the expression of senescence-associated-β-galactosidase (SA-β-gal), the SAHF markers HP1γ and trimethylation (H3k9me3), and the senescence-related protein HMGA2, as well as both p53 and its downstream p21 protein expression. Our findings suggest that NUFIP1 is overexpressed in CRC and correlates with disease progression and poor patient survival. NUFIP1 may exert oncogenic effects partly by altering senescence. UA may show potential to treat CRC by down-regulating NUFIP1.
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http://dx.doi.org/10.3389/fonc.2021.681425DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8343530PMC
July 2021
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