Publications by authors named "Yan Xu"

3,696 Publications

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Glucose oxidase loaded Cu based metal-organic framework for glutathione depletion/reactive oxygen species elevation enhanced chemotherapy.

Biomed Pharmacother 2021 Jun 18;141:111606. Epub 2021 Jun 18.

Department of Radiology, The Fourth Affiliated Hospital of Harbin Medical University, Harbin, China. Electronic address:

Introduction: The development of multidrug resistance (MDR) is a major cause for the failure of chemotherapy, which requires the aid of nanomedicine.

Methods: Here in our study, a Cu based metal-organic framework (COF) was firstly developed and employed as a carrier for the delivery of glucose oxidase (GOx) and doxorubicin (Dox) (COF/GOx/Dox) for the therapy of MDR lung cancers.

Results: Our results showed that the GOx can catalyze glucose and produce HO. In the mean time, the Cu can react with GSH and then transform into Cu, which resulted in GSH depletion. Afterwards, the produced Cu and HO trigger Fenton reaction to generate ROS to damage the redox equilibrium of cancer cells. Both effects contributed to the reverse of MDR in A549/Dox cells and finally resulted in significantly enhanced in vitro/in vivo anticancer performance.

Discussion: The combination of glutathione depletion/reactive oxygen species elevation might be a promising strategy to enhance the efficacy of chemotherapy and reverse MDR in cancers.
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http://dx.doi.org/10.1016/j.biopha.2021.111606DOI Listing
June 2021

Metabolite profiling of Shuganzhi tablets in rats and pharmacokinetics study of four bioactive compounds with liquid chromatography combined with electrospray ionization tandem mass spectrometry.

J Chromatogr B Analyt Technol Biomed Life Sci 2021 Jun 12;1179:122827. Epub 2021 Jun 12.

Experiment Center for Teaching and Learning, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China; School of Pharmacy, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China.

Shuganzhi Tablets (SGZT) is developed on the basis of a clinical empirical formula as a hospital preparation for the treatment of fatty liver. In this study, a rapid and highly sensitive LC-MS/MS method was established and validated for simultaneous determination of ginsenoside Re, ginsenoside Rg1, notoginsenoside R1, naringin, specnuezhenide, emodin, polydatin, hesperidin and saikosaponin A in rat plasma. Multiple reaction monitoring mode played an important role in simultaneous quantitative analysis of multiple components. The analytes were separated by the action of an ACQUITY UPLC® BEH C18 column (2.1 × 50 mm, 1.7 μm) in five minutes. The validated LC-MS/MS method was successfully applied to the pharmacokinetic analysis of hesperidin, emodin, polydatin and naringin of SGZT in rat plasma after administration. A UHPLC system couple with a quadrupole combined with time of flight mass spectrometer was used for qualitatively analyzing of the composition of SGZT and its metabolites in serum, urine, bile and feces of rats. The results showed that a total of 65 components were detected in rat biological samples, including 10 prototype components and 55 metabolites. It was speculated that the ingredients of SGZT experienced mainly the following reactions in rats: phase I reaction such as hydrolysis, oxidation, hydroxylation, carboxylation and dehydroxylation and phase Ⅱ reaction such as glucuronidation and sulfation. These results provide useful information for the further study of its active ingredients.
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http://dx.doi.org/10.1016/j.jchromb.2021.122827DOI Listing
June 2021

Inhibition of dynamin-related protein 1 ameliorates the mitochondrial ultrastructure via PINK1 and Parkin in the mice model of Parkinson's disease.

Eur J Pharmacol 2021 Jun 16:174262. Epub 2021 Jun 16.

Department of Anatomy, School of Chinese Medicine, Beijing University of Chinese Medicine, Beijing, 102488, China. Electronic address:

Parkinson's disease (PD) is the prevalent neurodegenerative disorder characterized by the degeneration of the nigrostriatal neurons. Dynamin-related protein 1 (Drp1) is a key regulator mediating mitochondrial fission and affecting mitophagy in neurons. It has been reported that the inhibition of Drp1 may be beneficial to PD. However, the role of Drp1 and mitophagy in PD remains elusive. Therefore, in this research, we investigated the role of Drp1 and the underlying mechanisms in the mice model of PD. We used the dynasore, a GTPase inhibitor, to inhibit the expression of Drp1. We found that inhibition of Drp1 could ameliorate the motor deficits and the expression of tyrosine hydroxylase in the mice of the PD model. But Drp1 inhibition did not affect mitochondria number and morphological parameters. Moreover, suppression of Drp1 up-regulated the mitochondrial expressions of PINK1 and Parkin while not affected the expressions of NIX and BNIP3. Conclusively, our findings suggest that the inhibition of Drp1 ameliorated the mitochondrial ultrastructure at least via regulating PINK1 and Parkin in the mice of the PD model. This study also implicates that inhibition of Drp1 might impact mitophagy and recover mitochondrial homeostasis in PD.
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http://dx.doi.org/10.1016/j.ejphar.2021.174262DOI Listing
June 2021

Treatment of steroid-resistant checkpoint inhibitor pneumonitis with pirfenidone: A case report.

Thorac Cancer 2021 Jun 18. Epub 2021 Jun 18.

Department of Pulmonary and Critical Care Medicine, Peking Union Medical Hospital, Chinese Academy of Medical Science & Peking Union Medical College, Beijing, China.

With the increased use of immune checkpoint inhibitors (ICIs) in lung cancer, which are of great benefit to patients, more and more immune-related adverse events (irAEs) are being reported. Checkpoint inhibitor pneumonitis (CIP) is one of the most challenging adverse events, which pose a huge challenge to clinical diagnosis and treatment, and its incidence in the real world is greatly underestimated. Currently, the treatment of CIP mainly depends on the use of glucocorticoids. As for steroid-resistant CIP, there is no unified standardized treatment strategy. Herein, we report a case of steroid-resistant CIP induced by pembrolizumab in a patient with advanced non-small cell lung cancer (NSCLC), in which their symptoms were successfully controlled with pirfenidone.
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http://dx.doi.org/10.1111/1759-7714.13921DOI Listing
June 2021

Red Phosphorus Decorated TiO Nanorod Mediated Photodynamic and Photothermal Therapy for Renal Cell Carcinoma.

Small 2021 Jun 19:e2101837. Epub 2021 Jun 19.

Department of Nephrology, The Affiliated Hospital of Qingdao University, Qingdao, 266003, China.

Clear cell renal cell carcinoma (ccRCC) is a serious and tenacious disease. Photodynamic therapy (PDT) and photothermal therapy (PTT) are effective means of cancer treatment. However, PDT combined with PTT has been rarely reported in ccRCC treatment. In the present study, by developing the core-shell structured TiO @red phosphorus nanorods (TiO @RP NRs) as a photosensitizer, the feasibility and effectiveness of synchronous PDT and PTT treatments for ccRCC are demonstrated. The core-shell structured TiO @RP NRs are synthesized to drive the PDT and PTT for ccRCC, in which the RP shell is the sensitizer even in the near-infrared (NIR) region. The optimized TiO @RP NRs can respond to NIR and produce local heat under irradiation. The NRs are estimated in ccRCC treatments via cell counting kit-8 assay, propidium iodide staining, qRT-PCR, and reactive oxygen species (ROS) probes in vitro, while terminal deoxynucleotidyl transferase dUTP nick-end labeling is conducted in vivo. After NIR irradiation, TiO @RP NRs can efficiently kill ccRCC cells by producing local heat and ROS and cause low injury to normal kidney cells. Furthermore, treatment with TiO @RP NRs and NIR can kill significant numbers of deep-tissue ccRCC cells in vivo. This work highlights a promising photo-driven therapy for kidney cancer.
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http://dx.doi.org/10.1002/smll.202101837DOI Listing
June 2021

Noninvasive assessment of endometrial fibrosis in patients with intravoxel incoherent motion MR imaging.

Sci Rep 2021 Jun 18;11(1):12887. Epub 2021 Jun 18.

Department of Radiology, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing, 210008, China.

Recently, few noninvasive methods have been reported to evaluate endometrial fibrosis. Our study was to investigate the feasibility of intravoxel incoherent motion (IVIM) MR imaging in the detection of endometrial fibrosis in patients with intrauterine injury. 30 patients with hysteroscopy-confirmed endometrial fibrosis and 28 healthy women were enrolled to undergo MR examination including the IVIM sequence. Endometrial thickness (ET); apparent diffusion coefficient (ADC); and IVIM parameters, including pure diffusion coefficient (D), pseudodiffusion coefficient (D*) and vascular fraction (f) were evaluated. A multivariable model combing ADC, D, and f values using binary logistic regression analysis was built to diagnose endometrial fibrosis. Endometrial fibrosis patients demonstrated lower endometrial ADC, D, f values and ET (all p < 0.05). The multivariable model, ADC, D, f values and ET performed well in diagnosing endometrial fibrosis with AUC of 0.979, 0.965, 0.920, 0.901 and 0.833, respectively. The multivariable model revealed a better diagnostic accuracy than D, f and ET (all p < 0.05). Although ADC achieved a better diagnostic value than ET (z = 2.082, p < 0.05), no difference in AUC was shown among ADC, D, and f (all p > 0.05); between ET and D (p > 0.05); and between ET and f (p > 0.05). The reproducibility of ADC, D, f and D* values in patients with endometrial fibrosis and healthy women were good to excellent (ICC: 0.614-0.951). IVIM parameters exhibit promising potential to serve as imaging biomarkers in the noninvasive assessment of endometrial fibrosis.
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http://dx.doi.org/10.1038/s41598-021-92383-wDOI Listing
June 2021

Light Absorption and Hydrophobicity of a Polystyrene / Multiwall Carbon Nanotube Composite with Surface Nanostructures.

Nanotechnology 2021 Jun 18. Epub 2021 Jun 18.

Industrial Systems Engineering, The Hong Kong Polytechnic University, 11 Yuk Choi Rd, Hung Hom, Kowloon, HONG KONG.

This paper describes an investigation into how combined carbon nanotube doping and surface nanostructuring affects the surface properties of polystyrene. Multiwall carbon nanotubes have unique anisotropic electrical properties that can be utilized for light absorption, electromagnetic shielding and nanoscale electostatic forces. Polystyrene was doped with 5 wt% multiwall carbon nanotubes and the resulting composite was wetted onto a porous anodic alumina template to form a nanostructure surface of nanotubes. Scanning electron microscopy revealed a hierarchical surface structure with the composite nanotubes bundled together as the multiwall carbon nanotubes increased the attractive forces between the composite nanotubes. Water droplet testing revealed that this hierarchical surface structure was superhydrophobic. Though the presence of the multiwall carbon nanotubes caused a direct increase in absorption, the hierarchical surface structure increased reflection . The addition of 5 wt% of the anionic surfactant Sodium Dodecyl Benzene Sulfonate to ensure multiwall carbon nanotube dispersal did not significantly change hydrophobicity or light absorption despite the hierarchical surface structure becoming finer. The created composite has potential use as a surface layer on an organic surface cell as it provides reduced cleaning needs and electrical disturbance but further work is required to reduce the reflection.
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http://dx.doi.org/10.1088/1361-6528/ac0cb2DOI Listing
June 2021

Aroma of Icewine: A Review on How Environmental, Viticultural, and Oenological Factors Affect the Aroma of Icewine.

Authors:
Yue Ma Yan Xu Ke Tang

J Agric Food Chem 2021 Jun 18. Epub 2021 Jun 18.

Key Laboratory of Industrial Biotechnology of Ministry of Education, Jiangnan University, 1800 Lihu Avenue, Wuxi, Jiangsu 214122, People's Republic of China.

The aroma of a wine is mostly driven by not only the factors in the vineyard, such as the grape variety and harvest time, but also the fermentation process. Icewine is a unique, intensely sweet wine made from late harvested grapes that have frozen naturally on the vine. Different from normal table wines, the grapes used in icewine naturally undergo a dehydration process and freeze-thaw cycles, and the must for icewine making has to be pressed from frozen grapes. This pressing process leaves water behind as ice crystals and allows the grape juice to be concentrated with more sugars, acids, and other dissolved solids, resulting in a slower than normal fermentation. These special procedures can lead to a unique aroma characteristic of icewine. This review delves into recent advances in chemical compounds related to icewine aroma characteristics and addresses how changes in these aroma characteristics and composition are influenced by environmental, viticultural, and oenological factors in the vineyard and winery. Deficiencies in previous studies and future trends related to the flavor science of icewine were also briefly addressed.
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http://dx.doi.org/10.1021/acs.jafc.1c01958DOI Listing
June 2021

Inhibitors Targeting YAP in Gastric Cancer: Current Status and Future Perspectives.

Drug Des Devel Ther 2021 9;15:2445-2456. Epub 2021 Jun 9.

Department of Surgical Oncology and General Surgery, Key Laboratory of Precision Diagnosis and Treatment of Gastrointestinal Tumors, Ministry of Education, The First Affiliated Hospital of China Medical University, Shenyang, Liaoning Province, 110001, People's Republic of China.

Gastric cancer (GC) is one of the most common cancers globally, threatening global health. The deregulation of the Hippo signaling pathway has been discovered in GC and may be related to cancer development, proliferation, metastasis, and drug resistance. Yes-associated protein (YAP), as a downstream effector of the Hippo signaling pathway and a crucial co-transcription factor in the nucleus, is a promising and vital potential drug target for the treatment of GC. A series of drugs or compounds that inhibit YAP has been developed or confirmed. Therefore, this review will focus on summarizing the drugs and small-molecule inhibitors that have been reported to inhibit YAP and discuss the clinical prospects of YAP inhibitors in GC.
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http://dx.doi.org/10.2147/DDDT.S308377DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8203099PMC
June 2021

Surfactant protein C mutation links postnatal type 2 cell dysfunction to adult disease.

JCI Insight 2021 Jun 17. Epub 2021 Jun 17.

Divisions of Neonatology and Pulmonary Biology, Cincinnati Children's Hospital Medical Center, Cincinnati, United States of America.

Mutations in the gene (SFTPC) encoding surfactant protein C (SP-C) are associated with interstitial lung disease in children and adults. To assess the natural history of disease, we knocked-in a familial, disease-associated SFTPC mutation, L188Q [L184Q (LQ) in mice], into the mouse Sftpc locus. Translation of the mutant proprotein, proSP-CLQ, exceeded that of proSP-CWT in neonatal alveolar type 2 epithelial (AT2) cells and was associated with transient activation of oxidative stress and apoptosis leading to impaired expansion of AT2 cells during postnatal alveolarization. Differentiation of AT2 to AT1 cells was also inhibited in ex vivo organoid culture of AT2 cells isolated from LQ mice; importantly, treatment with antioxidant promoted alveolar differentiation. Upon completion of alveolarization, SftpcLQ expression was downregulated leading to resolution of chronic stress responses; however, the failure to restore AT2 cell numbers resulted in a permanent loss of AT2 cells that was linked to decreased regenerative capacity in the adult lung. Collectively, these data support the hypothesis that susceptibility to disease in adult LQ mice is established during postnatal lung development and provide a potential explanation for the delayed onset of disease in patients with familial pulmonary fibrosis.
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http://dx.doi.org/10.1172/jci.insight.142501DOI Listing
June 2021

Impact of Amine Additives on Perovskite Precursor Aging: A Case Study of Light-Emitting Diodes.

J Phys Chem Lett 2021 Jun 17:5836-5843. Epub 2021 Jun 17.

Department of Physics Chemistry and Biology (IFM), Linköping University, Linköping SE-58183, Sweden.

Amines are widely employed as additives for improving the performance of metal halide perovskite optoelectronic devices. However, amines are well-known for their high chemical reactivity, the impact of which has yet to receive enough attention from the perovskite light-emitting diode community. Here, by investigating an unusual positive aging effect of CHNHI/CsI/PbI precursor solutions as an example, we reveal that amines gradually undergo N-formylation in perovskite precursors over time. This reaction is initialized by hydrolysis of dimethylformamide in the acidic chemical environment. Further investigations suggest that the reaction products collectively impact perovskite crystallization and eventually lead to significantly enhanced external quantum efficiency values, increasing from ∼2% for fresh solutions to ≳12% for aged ones. While this case study provides a positive aging effect, a negative aging effect is possible in other perovksite systems. Our findings pave the way for more reliable and reproducible device fabrication and call for further attention to underlying chemical reactions within the perovskite inks once amine additives are included.
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http://dx.doi.org/10.1021/acs.jpclett.1c01349DOI Listing
June 2021

Ultrasensitive detection of SARS-CoV-2 spike protein in untreated saliva using SERS-based biosensor.

Biosens Bioelectron 2021 Jun 9;190:113421. Epub 2021 Jun 9.

State Key Laboratory on Integrated Optoelectronics, Jilin Key Laboratory on Advanced Gas Sensor, College of Electronic Science and Engineering, Jilin University, Changchun, 130012, China. Electronic address:

Early diagnosis and monitoring of SARS-CoV-2 virus is essential to control COVID-19 outbreak. In this study, we propose a promising surface enhanced Raman scattering (SERS)-based COVID-19 biosensor for ultrasensitive detection of SARS-CoV-2 virus in untreated saliva. The SERS-immune substrate was fabricated by a novel oil/water/oil (O/W/O) three-phase liquid-liquid interfaces self-assembly method, forming two layers of dense and uniform gold nanoparticle films to ensure the reproducibility and sensitivity of SERS immunoassay. The detection was performed by an immunoreaction between the SARS-CoV-2 spike antibody modified SERS-immune substrate, spike antigen protein and Raman reporter-labeled immuno-Ag nanoparticles. This SERS-based biosensor was able to detect the SARS-CoV-2 spike protein at concentrations of 0.77 fg mL in phosphate-buffered saline and 6.07 fg mL in untreated saliva. The designed SERS-based biosensor exhibited excellent specificity and sensitivity for SARS-CoV-2 virus without any sample pretreatment, providing a potential choice for the early diagnosis of COVID-19.
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http://dx.doi.org/10.1016/j.bios.2021.113421DOI Listing
June 2021

[Clinical features of preterm infants with a birth weight less than 1 500 g undergoing different intensities of resuscitation: a multicenter retrospective analysis].

Zhongguo Dang Dai Er Ke Za Zhi 2021 Jun;23(6):593-598

Department of Neonatology, Women's Hospital of Nanjing Medical University/Nanjing Maternity and Child Health Care Hospital, Nanjing 210004, China.

Objective: To evaluate the clinical features of preterm infants with a birth weight less than 1 500 g undergoing different intensities of resuscitation.

Methods: A retrospective analysis was performed for the preterm infants with a birth weight less than 1 500 g and a gestational age less than 32 weeks who were treated in the neonatal intensive care unit of 20 hospitals in Jiangsu, China from January 2018 to December 2019. According to the intensity of resuscitation in the delivery room, the infants were divided into three groups:non-tracheal intubation (=1 184), tracheal intubation (=166), and extensive cardiopulmonary resuscitation (ECPR; =116). The three groups were compared in terms of general information and clinical outcomes.

Results: Compared with the non-tracheal intubation group, the tracheal intubation and ECPR groups had significantly lower rates of cesarean section and use of antenatal corticosteroid ( < 0.05). As the intensity of resuscitation increased, the Apgar scores at 1 minute and 5 minutes gradually decreased ( < 0.05), and the proportion of infants with Apgar scores of 0 to 3 at 1 minute and 5 minutes gradually increased ( < 0.05). Compared with the non-tracheal intubation group, the tracheal intubation and ECPR groups had significantly higher mortality rate and incidence rates of moderate-severe bronchopulmonary dysplasia and serious complications ( < 0.05). The incidence rates of grade Ⅲ-Ⅳ intracranial hemorrhage and retinopathy of prematurity (stage Ⅲ or above) in the tracheal intubation group were significantly higher than those in the non-tracheal intubation group ( < 0.05).

Conclusions: For preterm infants with a birth weight less than 1 500 g, the higher intensity of resuscitation in the delivery room is related to lower rate of antenatal corticosteroid therapy, lower gestational age, and lower birth weight. The infants undergoing tracheal intubation or ECRP in the delivery room have an increased incidence rate of adverse clinical outcomes. This suggests that it is important to improve the quality of perinatal management and delivery room resuscitation to improve the prognosis of the infants.
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June 2021

Pilose Antler Peptide-3.2KD Ameliorates Adriamycin-Induced Myocardial Injury Through TGF-β/SMAD Signaling Pathway.

Front Cardiovasc Med 2021 28;8:659643. Epub 2021 May 28.

School of Pharmaceutical, Changchun University of Chinese Medicine, Changchun, China.

Adriamycin (ADR)-based combination chemotherapy is the standard treatment for some patients with tumors in clinical, however, long-term application can cause dose-dependent cardiotoxicity. Pilose Antler, as a traditional Chinese medicine, first appeared in the Han Dynasty and has been used to treat heart disease for nearly a thousand years. Previous data revealed pilose antler polypeptide (PAP, 3.2KD) was one of its main active components with multiple biological activities for cardiomyopathy. PAP-3.2KD exerts protective effects againt myocardial fibrosis. The present study demonstrated the protective mechanism of PAP-3.2KD against Adriamycin (ADR)-induced myocardial injury through using animal model with ADR-induced myocardial injury. PAP-3.2KD markedly improved the weight increase and decreased the HW/BW index, heart rate, and ST height in ADR-induced groups. Additionally, PAP-3.2KD reversed histopathological changes (such as disordered muscle bundles, myocardial fibrosis and diffuse myocardial cellular edema) and scores of the heart tissue, ameliorated the myocardial fibrosis and collagen volume fraction through pathological examination, significantly increased the protein level of Bcl-2, and decreased the expression levels of Bax and caspase-3 in myocardial tissue by ELISA, compared to those in ADR-induced group. Furthermore, ADR stimulation induced the increased protein levels of TGF-β1 and SMAD2/3/4, the increased phosphorylation levels of SMAD2/3 and the reduced protein levels of SMAD7. The expression levels of protein above in ADR-induced group were remarkably reversed in PAP-3.2KD-treated groups. PAP-3.2KD ameliorated ADR-induced myocardial injury by regulating the TGF-β/SMAD signaling pathway. Thus, these results provide a strong rationale for the protective effects of PAP against ADR-induced myocardial injury, when ADR is used to treat cancer.
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http://dx.doi.org/10.3389/fcvm.2021.659643DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8194399PMC
May 2021

The Epidemiology of COVID-19 and MS-Related Characteristics in a National Sample of People With MS in China.

Front Neurol 2021 28;12:682729. Epub 2021 May 28.

Department of Cardiology, Peking Union Medical College, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing, China.

Few studies have focused on immune status and disease activity in MS patients during the coronavirus disease 2019 (COVID-19) pandemic. The aim of this study is to investigate immune status, COVID-19 infection, and attacks in MS patients during the pandemic. An online questionnaire about COVID-19 infection, MS attack, and MS treatment during the pandemic was administered to all 525 MS patients registered in our hospital database from January 1, 2011, to June 1, 2020. Only 384 responded, of which 361 patients could be included in the final analysis. During the pandemic, 42.1% of the 361 patients and 65.0% of the 234 patients on immunotherapies were exposed to teriflunomide. Compared to patients who didn't receive treatment, patients exposed to DMTs had significantly lower levels of neutrophils ( < 0.01) and immunoglobulin G ( < 0.01), and patients exposed to immunosuppressants had significantly lower levels of immunoglobulin G ( < 0.05). Over 80% of our patients followed effective protective measures and none of the 361 MS patients in our cohort contracted COVID-19. Patients whose treatment was disrupted had a significantly higher annualized relapse rate (ARR) during than before the pandemic ( < 0.01), while the ARR of patients with continuous treatment or without treatment remained unchanged. During the pandemic, the risk of MS attack due to treatment disruption possibly outweighs the risk of COVID-19 infection under preventive measures, and MS treatment maintenance might be necessary.
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http://dx.doi.org/10.3389/fneur.2021.682729DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8193356PMC
May 2021

Association between telomere length in the DNA of peripheral blood leukocytes and the propofol dose in anesthesia induction: an observational study.

Braz J Anesthesiol 2021 Jun 10. Epub 2021 Jun 10.

The Affiliated Lianyungang No. 2 People's Hospital of Jiangsu University, Department of Anesthesiology, Lianyungang, China. Electronic address:

Introduction: Propofol is a widely used anesthetic and its dose is closely related to aging. Telomere length (TL) is a unique heritable trait, and emerging as a biomarker of aging, health and disease. Telomerase RNA component (TERC) plays an important role in maintaining TL. We proposed a hypothesis that propofol dose in general anesthesia can be predicted by measuring TL before operation, which greatly reduced the risk of anesthesia, especially the elderly.

Methods: The association between the propofol dose in anesthesia induction and: TL in the DNA of peripheral blood leukocytes; body weight; sex; difference of the Bispectral Index (BIS) before and after anesthesia induction in patients was evaluated by multivariable linear regression analyses. The mutation at the 5'end or 3'end of TERC was detected. We recruited 100 patients of elective surgery.

Results: We found that propofol dose in anesthesia induction was clearly correlated significantly with TL (r = 0.78, p < 0.001), body weight (r = 0.84, p = 0.004), sex (r = 0.83, p= 0.84, p = 0.004), sex (r = 0.83, p = 0.004), and difference of BIS before and after anesthesia induction (r = 0.85, p = 0.029). By comparing the absolute values of standardized regression coefficients (0.58, 0.21, 0.19, and 0.12) of the four variables, it can be seen that TL contributes the most to the propofol dose in anesthesia induction. However, the mutation at the 5' end or 3' end of TERC was not found.

Conclusions: These findings provide preliminary evidence that the propofol dose in anesthesia induction was clearly correlated with genetically determined TL. TL may be a promising predictor of the propofol dose, which is beneficial to improve the safety of anesthesia and reduce perioperative complications.
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http://dx.doi.org/10.1016/j.bjane.2021.05.014DOI Listing
June 2021

Two three-dimensional polyanionic clusters [M(PMo)] (M = Co, Zn) exhibiting excellent photocatalytic CO reduction performance.

Dalton Trans 2021 Jun 11. Epub 2021 Jun 11.

College of Chemical Engineering, State Key Laboratory of Materials-Oriented Chemical Engineering, Nanjing Tech University, Nanjing 211800, P. R. China. and State Key Laboratory of Coordination Chemistry, Nanjing University, Nanjing 210023, P. R. China.

Two captivating {P4Mo6}-based compounds, formulated as (H2bbi)2{[Co2(bbi)][Co2.33(H2O)4][H9.33CoP8Mo12O62]}·4H2O (1) and (H2bbi){[Zn(Hbbi)]2[Zn0.75(bbi)][K2Zn(H2O)4][H8.5ZnP8Mo12O62]} (2) [bbi = 1,1'-(1,4-butanediyl)bis(imidazole)], were successfully synthesized under hydrothermal conditions. Structural analysis demonstrates that compounds 1 and 2 are constructed from hourglass-shaped structures [M(P4Mo6O31)2]n- (M = Co, Zn), which are all made up of molybdophosphates and one transition metal ion as the central connecting node. Compounds 1 and 2 feature three-dimensional (3D) frameworks, which are all connected to form a 3D structure by metal ions and bbi ligands. More interestingly, compound 1 exhibits higher catalytic activity than 2 in CO2 photoreduction due to the suitable energy band structure of Co species in {P4Mo6} clusters. The CO yield was 3261 μmol g-1 with high selectivity in 8 h for compound 1 in photocatalytic CO2 reduction, which is highly promising in the photocatalytic field. Additionally, the photoluminescence properties of 2 were investigated.
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http://dx.doi.org/10.1039/d1dt00809aDOI Listing
June 2021

[Study of the root position of palatally malposed maxillary lateral incisor based on cone-beam CT images].

Shanghai Kou Qiang Yi Xue 2021 Apr;30(2):129-134

Department of Orthodontics, Shanghai Stomatological Hospital; Oral Biomedical Engineering Laboratory, Fudan University. Shanghai 200001, China.

Purpose: The goal of this investigation was to measure and analyze the root position of palatally malposed maxillary lateral incisor based on cone-beam CT(CBCT)images, in order to provide references for orthodontists to move this kind of teeth scientifically.

Methods: CBCT data from 200 patients meeting the selection criteria with palatally malposed maxillary lateral incisor were investigated in this study. The root was divided into eight equal parts by length, then T1 to T8 were orderly pointed from root apex to alveolar ridge crest. The labial and palatal bone thickness at each point was measured; meanwhile, the angle between the long axis of the tooth and that of the alveolar bone was measured.The data was analyzed using SPSS 19.0 software package.

Results: The mean labial bone thicknesses at all researched points were less than 1.00 mm, except for point T1,T7 and T8. The mean labial bone thicknesses at point T3, T4 and T5 were the thinnest, which were all less than 0.5 mm(P<0.05). The mean thicknesses of labial bone gradually increased from T4 to T8(P<0.05). The mean palatal bone thicknesses were all more than 1.00 mm at the eight points,the mean thicknesses of palatal bone gradually increased from T8 to T1(P<0.05). All the angulations between the long axes of teeth and those of the alveolar bone were negative, indicating the root was close to the labial alveolar wall. The average angulation was minus 31.06 degrees.

Conclusions: Results suggest that the root of palatally malposed maxillary lateral incisor is close to the labial wall of the alveolar bone, its labial alveolar bone is frequently quite thin or even deficient, especially in the zone between 1/4 root length to the root apex and the mid-root. If we move the palatally malposed maxillary lateral incisor labially, it is better to choose tipping movement, instead of bodily movement, in order to avoid serious bone fenestration and dehiscence or root absorption.
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April 2021

Selective adsorption of malachite green (MG) and fuchsin acid (FA) by ZIF-67 hybridized polyvinylidene fluoride (PVDF) membranes.

Dalton Trans 2021 Jun 10. Epub 2021 Jun 10.

Department of Chemistry, College of Sciences, Northeastern University, Shenyang, 110819, China.

MOF/polymer hybrid membranes integrate the surface activity of MOFs and the advantages of PVDF membranes, and can be used as adsorption membranes in the efficient removal of target organics. In this work, a new hybrid membrane of ZIF-67/PVDF with varying ZIF-67 dosages has been fabricated through a facile mechanical blending followed by a lyotropic phase transition. Methods including field-emission scanning electron microscopy (FESEM), X-ray diffraction (XRD), FT-IR analyses and surface hydrophobicity/hydrophilicity measurements are applied to characterize the structure, physicochemical properties and membrane performances. Two synthetic triarylmethane dyes, cationic malachite green (MG) and anionic fuchsin acid (FA), are chosen as the main adsorption targets to evaluate the adsorption capacities of the resulting ZIF-67/PVDF hybrid membranes. Interestingly, all of the ZIF-67/PVDF hybrid membranes exhibit distinctly favorable efficiencies and selectivities toward MG and FA compared to pristine PVDF, which proves the positive roles of ZIF-67 in the adsorption ability of the hybrid membranes. The adsorption conditions are optimized and the adsorption kinetics and thermodynamics are analysed to study the adsorption mechanism. The reusability and the structural stability of the hybrid membranes undergoing cyclic adsorption processes are also discussed. To the best of our knowledge, this is the first time that good adsorption capacities for MG and FA for these MOF/PVDF membranes have been reported. This work highlights the prospective applications of MOF/PVDF hybrid membranes in the rapid and effective removal of target organics in the treatment of waste water.
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http://dx.doi.org/10.1039/d1dt01000jDOI Listing
June 2021

The Mediating Role of Perceived Social Support Between Resilience and Anxiety 1 Year After the COVID-19 Pandemic: Disparity Between High-Risk and Low-Risk Nurses in China.

Front Psychiatry 2021 24;12:666789. Epub 2021 May 24.

The Affiliated Suzhou Science and Technology Town Hospital of Nanjing Medical University, Suzhou, China.

One year after the Coronavirus disease 2019 (COVID-19) outbreak, China has made substantial progress in the prevention and control of the pandemic, while the epidemic situation remains grim in China since virus may easily survive with the falling temperature in winter. The present study aimed to compare the prevalence and associated factors of anxiety between high-risk and low-risk nurses 1 year after the COVID-19 outbreak, and examine the association between resilience and anxiety and its underlying mechanisms. Connor-Davidson Resilience scale, Perceived Social Support Scale and Generalized Anxiety Disorder Scale were administrated to 701 nurses from Jiangsu Province, China, 1 year after the COVID-19 outbreak. The mediating effect was examined by Mackinnon's four-step procedure, while the moderated mediation model was tested by Hayes PROCESS macro. The findings presented the prevalence of anxiety among nurses was 21.4% 1 year after the COVID-19 pandemic. High-risk nurses presented a higher prevalence of anxiety (24.5 vs. 19.3%) than low-risk nurses. Age and professional title were significantly associated with anxiety only in high-risk nurses (all < 0.05). Perceived social support mediated the association between resilience and anxiety and the indirect effect was stronger for high-risk nurses than low-risk nurses. Anxiety remains prevalent among nurses 1 year after the COVID-19 outbreak, and resilience plays a protective role against anxiety. Programs that enhance resilience and social support should be designed and special attention should be paid to nurses from high-risk units.
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http://dx.doi.org/10.3389/fpsyt.2021.666789DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8180566PMC
May 2021

Prevalence and Risk Factors Associated with Insomnia Symptoms Among the Chinese General Public After the Coronavirus Disease 2019 Epidemic Was Initially Controlled.

Nat Sci Sleep 2021 1;13:703-712. Epub 2021 Jun 1.

Department of Psychiatry, Nanfang Hospital, Southern Medical University, Guangzhou, People's Republic of China.

Introduction: The prevalence rate and related factors of insomnia remained unknown after the COVID-19 epidemic had been under control. Therefore, we conducted this survey to investigate the prevalence rate and related factors of insomnia symptoms in the Chinese general public after the COVID-19 had been initially control.

Methods: An online survey was conducted among Chinese citizens through the JD Health APP. The questionnaire was used for collecting demographic data and self-designed questions related to the COVID-19 outbreak. Insomnia Severity Index, Patient Health Questionnaire-9, Somatic Symptom Scale-8 and Impact of Events Scale-Revised were used for measuring psychological symptoms. To examine the associations of sociodemographic and psychological factors with insomnia symptoms, a binary logistic regression was used.

Results: In total, there were 14,894 eligible participants, and 4601 (30.9%) participants were found to have insomnia symptoms. The regression model revealed that a higher risk of insomnia symptoms was associated with being over the age of 40 years, having history of psychiatric disorders, smoking, having infected friends or colleagues, having depressive or somatic symptoms, experiencing psychological distress and feeling estranged from family members. Meanwhile a lower risk of insomnia symptoms was associated with being female, having closer family relationships, not feeling alienated from others and being satisfied with the available information.

Conclusion: In our study, 30.9% of the participants in the general public reported insomnia symptoms after the COVID-19 epidemic had been initially controlled. When providing precise interventions for insomnia, extra attention should be paid to the individuals who are male, elderly and smokers, and those with psychiatric disorder history, with infected friends or colleagues, with psychological symptoms and with poor social support.
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http://dx.doi.org/10.2147/NSS.S307996DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8180302PMC
June 2021

Rg1 exerts protective effect in CPZ-induced demyelination mouse model via inhibiting CXCL10-mediated glial response.

Acta Pharmacol Sin 2021 Jun 8. Epub 2021 Jun 8.

State Key Laboratory of Bioactive Substances and Functions of Natural Medicines, Institute of Materia Medica & Neuroscience Center, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing 100050, China.

Myelin damage and abnormal remyelination processes lead to central nervous system dysfunction. Glial activation-induced microenvironment changes are characteristic features of the diseases with myelin abnormalities. We previously showed that ginsenoside Rg1, a main component of ginseng, ameliorated MPTP-mediated myelin damage in mice, but the underlying mechanisms are unclear. In this study we investigated the effects of Rg1 and mechanisms in cuprizone (CPZ)-induced demyelination mouse model. Mice were treated with CPZ solution (300 mg· kg· d, ig) for 5 weeks; from week 2, the mice received Rg1 (5, 10, and 20 mg· kg· d, ig) for 4 weeks. We showed that Rg1 administration dose-dependently alleviated bradykinesia and improved CPZ-disrupted motor coordination ability in CPZ-treated mice. Furthermore, Rg1 administration significantly decreased demyelination and axonal injury in pathological assays. We further revealed that the neuroprotective effects of Rg1 were associated with inhibiting CXCL10-mediated modulation of glial response, which was mediated by NF-κB nuclear translocation and CXCL10 promoter activation. In microglial cell line BV-2, we demonstrated that the effects of Rg1 on pro-inflammatory and migratory phenotypes of microglia were related to CXCL10, while Rg1-induced phagocytosis of microglia was not directly related to CXCL10. In CPZ-induced demyelination mouse model, injection of AAV-CXCL10 shRNA into mouse lateral ventricles 3 weeks prior CPZ treatment occluded the beneficial effects of Rg1 administration in behavioral and pathological assays. In conclusion, CXCL10 mediates the protective role of Rg1 in CPZ-induced demyelination mouse model. This study provides new insight into potential disease-modifying therapies for myelin abnormalities.
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http://dx.doi.org/10.1038/s41401-021-00696-3DOI Listing
June 2021

Residential airborne culturable fungi under general living scenario: On-site investigation in 12 typical cities, China.

Environ Int 2021 Jun 5;155:106669. Epub 2021 Jun 5.

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

Background: Residential airborne fungi may present obvious risk to human health. However, many countries do not recognize the necessarily need to control residential airborne culturable fungi (RAF). In China, few systemic investigations have been conducted to illustrate the distribution of residential airborne fungi and identify the association between indoor influencing variables and RAF under general living scenario in China.

Objective: This study aimed to investigate RAF with the on-site research of 12 typical cities in China, and provided the latest characteristics and potential influencing factors of RAF under general living scenario.

Methods: We measured RAF and investigated residential characteristics in 12 typical cities in China, 2018. At least 50 resident families were randomly selected both from downwind and upwind districts in each city with pre-proposed requirements. The RAF were sampled by the six-stage Anderson impactor. PM and PM were monitored by calibrated light-scattering dust meters. CO and CO were monitored by non-dispersive infrared analyzer method. NO was determined by Saltzman method. General linear model was used to evaluate the association between RAF exposure and residential characteristics with adjustment for potential confounders.

Results: The RAF concentrations ranged from 0 to 9371 CFU/m with a median concentration of 396 CFU/m. The median concentrations of RAF in the warm season were statistically higher than the cold season in Panjin, Qingdao, Lanzhou and Luoyang, but lower than the cold season in Shijiazhuang, Ningbo and Nanning. RAF in the bedrooms were more than the living rooms in all cities except Xi'an. Temperature and humidity had an interactive effect on the RAF (OR = 1.0006, 95% CI: 1.0005, 1.0006). Some residential environmental pollutants, including PM (OR = 0.9989, 95% CI: 0.9988, 0.9989), PM (OR = 0.9993, 95% CI: 0.9993, 0.9993), and CO (OR = 0.0236, 95% CI: 0.0230, 0.0243), were negatively correlated with RAF. CO (OR = 1.1450, 95% CI: 1.1433, 1.1467) and NO (OR = 1.0026, 95% CI: 1.0024, 1.0028) were positively correlated with RAF. Architectural characteristics (sunlight exposure, building history, longitude, latitude, total living area, living floor, distance from the road, house type, the layers of window glass and decoration), family-related information (income) and lifestyle behaviors (keeping pets, growing plants, cooking, using insecticide, burning incense, heating, using air conditioner and cleaning frequencies) were also significantly related with RAF.

Conclusions: This study reported nation-wide baseline condition of RAF and related influencing factors under general living scenario with quantitative details, which are exceedingly promising for evidence-driven standard and reasonable control strategy of residential airborne culturable in China.
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http://dx.doi.org/10.1016/j.envint.2021.106669DOI Listing
June 2021

Tacrolimus Protects Podocytes from Apoptosis via Downregulation of TRPC6 in Diabetic Nephropathy.

J Diabetes Res 2021 20;2021:8832114. Epub 2021 May 20.

Department of Nephrology, Affiliated Hospital of Qingdao University, Qingdao, Shandong, China.

Podocyte injury plays an important role in diabetic nephropathy (DN), and apoptosis is one of its mechanisms. The transient receptor potential channel 6 (TRPC6) is expressed in podocytes and mediates podocyte injury induced by high glucose levels. Tacrolimus is a novel immunosuppressive agent that is reported to play an important role in podocyte protection. The purpose of this study was to investigate the potential mechanism of podocyte protection by tacrolimus in a type 2 diabetic mellitus (T2DM) rat model and in immortalized mouse podocytes (MPC5). Transmission electron microcopy was used to evaluate renal injury morphology. After treatment with FK506, we measured 24-hour urinary albumin-to-creatinine ratios and creatinine clearance rates as well as major biochemical parameters such as glucose, insulin, serum creatinine, urea nitrogen, total cholesterol, triglycerides, alanine transaminase, and aspartate aminotransferase. Nephrin and TRPC6 protein expression and podocyte apoptotic rates and were measured using immunohistochemical staining, TUNEL assays, and flow cytometry, respectively. Western blot was used to measure expression of cleaved-caspase-3 and bax/bcl-2. Exposed to high glucose (HG), DM rats exhibited disrupted biochemical conditions and impaired podocyte structure. Decreased expression of nephrin and increased expression of TRPC6, cleaved-caspase-3, and bax/bcl-2 ratios were found in podocytes, along with higher apoptotic percentage, while tacrolimus intervention counteracted the effect of HG on podocytes. Our results suggest that tacrolimus protects podocytes during the progression of type 2 diabetic nephropathy, possibly ameliorating podocyte apoptosis by downregulating the expression of TRPC6.
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http://dx.doi.org/10.1155/2021/8832114DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8163546PMC
May 2021

Lung Segmentation and Automatic Detection of COVID-19 Using Radiomic Features from Chest CT Images.

Pattern Recognit 2021 Jun 2:108071. Epub 2021 Jun 2.

Department of Applied Computing, Michigan Technological University, Houghton, MI, 49931, USA.

This paper aims to develop an automatic method to segment pulmonary parenchyma in chest CT images and analyze texture features from the segmented pulmonary parenchyma regions to assist radiologists in COVID-19 diagnosis. A new segmentation method, which integrates a three-dimensional (3D) V-Net with a shape deformation module implemented using a spatial transform network (STN), was proposed to segment pulmonary parenchyma in chest CT images. The 3D V-Net was adopted to perform an end-to-end lung extraction while the deformation module was utilized to restrict the V-Net output according to the prior shape knowledge. The proposed segmentation method was validated against the manual annotation generated by experienced operators. The radiomic features measured from our segmentation results were further analyzed by sophisticated statistical models with high interpretability to discover significant independent features and detect COVID-19 infection. Experimental results demonstrated that compared with the manual annotation, the proposed segmentation method achieved a Dice similarity coefficient of 0.9796, a sensitivity of 0.9840, a specificity of 0.9954, and a mean surface distance error of 0.0318 mm. Furthermore, our COVID-19 classification model achieved an area under curve (AUC) of 0.9470, a sensitivity of 0.9500, and a specificity of 0.9270 when discriminating lung infection with COVID-19 from community-acquired pneumonia and healthy controls using statistically significant radiomic features. The significant features measured from our segmentation results agreed well with those from the manual annotation. Our approach has great promise for clinical use in facilitating automatic diagnosis of COVID-19 infection on chest CT images.
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http://dx.doi.org/10.1016/j.patcog.2021.108071DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8169223PMC
June 2021

Effect of carbon source on nitrous oxide emission characteristics and sludge properties during anoxic/aerobic wastewater treatment process.

Environ Sci Pollut Res Int 2021 Jun 5. Epub 2021 Jun 5.

School of Environment, Key Laboratory for Yellow River and Huai River Water Environment and Pollution Control, Ministry of Education, Henan Key Laboratory for Environmental Pollution Control, Henan Normal University, Xinxiang, 453007, Henan, China.

Carbon sources are an important parameter in wastewater treatment processes and are closely related to treatment efficiency and nitrous oxide (NO) emissions. In this study, three parallel sequencing batch reactors (SBRs) were processed with acetic acid, propionic acid, and a 1:1 mixture of both acids (calculated in COD) to study the effect of carbon sources on NO generation and sludge properties (including intracellular polymer content, extracellular polymeric substance (EPS) composition, particle size distribution, settleability, and microbial community structure). The results showed that the highest COD, NH-N, and TP removal efficiencies (92.2%, 100%, and 82.3%, respectively) were achieved by the reactor with mixed acid as the carbon source, whereas the reactor using acetic acid had the highest TN removal rate (82.6%) and the lowest NO-N conversion rate (1.4%, based on TN removal). The reactor with the carbon source of mixed acid produced the highest polyhydroxyalkanoate (PHA) content, which led to an increase in NO generation from the aerobic denitrification pathway. The SBR with mixed acid carbon source also had the highest concentration of EPS, which resulted in the largest particle size and the lowest settleability of sludge flocs among the SBRs. Microbial analysis results revealed that the difference in carbon sources resulted in a variation in the microbial community as well as in the relative abundances of functional microbes involved in biological nitrogen removal processes. The mixed acid promoted the development of ammonia-oxidizing bacteria (AOB), which conducted the primary NO generation pathway of aerobic denitrification bioreactions. The carbon source of acetic acid promoted the growth of denitrifying bacteria (DNB), which led to the highest TN removal rate. This study provides a comprehensive understanding of the effects of carbon sources on NO generation and sludge properties for WWTPs.
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http://dx.doi.org/10.1007/s11356-021-14713-9DOI Listing
June 2021

LINC00943 is correlated with gastric cancer and regulates cancer cell proliferation and chemosensitivity via hsa-miR-101-3p.

Int J Clin Oncol 2021 Jun 4. Epub 2021 Jun 4.

Department of Endocrinology, Rizhao People's Hospital, Rizhao, 276800, Shandong Province, China.

Background: Non-coding RNAs have emerged as important regulators in human cancers. In this work, we investigated the role of long intergenic non-protein-coding RNA 943 (LINC00943) in gastric cancer (GC).

Methods: LINC00943 expression was evaluated in GC patient tissues and cell lines. In SNU-5 and MKN-45 cells, LINC00943 was knocked down to investigate its roles in regulating GC cell proliferation, 5-FU chemosensitivity and in vivo explant growth. Possible downstream target of LINC00943, human mature microRNA-101-3p (hsa-miR-101-3p) was also evaluated.

Results: LINC00943 was aberrantly overexpressed in in situ GC tumors and immortal GC cell lines. LINC00943 overexpression was associated with GC patients' poor prognosis. LINC00943 knockdown reduced GC cell proliferation, 5-FU resistance and in vivo explant growth. Hsa-miR-101-3p was found to be regulated by LINC00943 in GC. Hsa-miR-101-3p downregulation reversed the tumor-suppressing functions of LINC00943 knockdown in GC cells.

Conclusion: In summary, our results indicated that LINC00943 was correlated with gastric cancer and regulates cancer cell proliferation and chemosensitivity via hsa-miR-101-3p.
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http://dx.doi.org/10.1007/s10147-021-01945-5DOI Listing
June 2021

Immune-related genes and gene sets for predicting the response to anti-programmed death 1 therapy in patients with primary or metastatic non-small cell lung cancer.

Oncol Lett 2021 Jul 19;22(1):540. Epub 2021 May 19.

Thoracic Medicine Department 2, Cancer Hospital Affiliated to Xiangya Medical College, Central South University, Changsha, Hunan 410013, P.R. China.

Although antibodies targeting the immune checkpoint protein programmed death-1 (PD-1) exert therapeutic effects in patients with primary or metastatic non-small cell lung cancer (NSCLC), the majority of patients exhibit partial or complete resistance to anti-PD1 treatment. Thus, the aim of the present study was to identify reliable biomarkers for predicting the response to anti-PD-1 therapy. The present study analyzed tumor specimens isolated from 24 patients (13 with primary and 11 with metastatic NSCLC) prior to treatment with approved PD1-targeting antibodies. The expression profile of 395 immune-related genes was examined using RNA immune-oncology panel sequencing. The results demonstrated that six immune-related differently expressed genes (DEGs), including HLA-F-AS1, NCF1, RORC, DMBT1, KLRF1 and IL-18, and five DEGs, including HLA-A, HLA-DPA1, TNFSF18, IFI6 and PTK7, may be used as single biomarkers for predicting the efficacy of anti-PD-1 treatment in patients with primary and with metastatic NSCLC, respectively. In addition, two DEG sets comprising either six (HLA-F-AS1, NCF1, RORC, DMBT1, KLRF and IL-18) or two (HLA-A and TNFSF18) DEGs as potential combination biomarkers for predicting the efficacy of anti-PD-1 therapy in patients with NSCLC. Patients with a calculated expression level of the DEG sets >6.501 (primary NSCLC) or >6.741 (metastatic NSCLC) may benefit from the anti-PD-1 therapy. Overall, these findings provided a basis for the identification of additional biomarkers for predicting the response to anti-PD-1 treatment.
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http://dx.doi.org/10.3892/ol.2021.12801DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8161458PMC
July 2021

Mechanistic physiology-based pharmacokinetic modeling to elucidate vincristine-induced peripheral neuropathy following treatment with novel kinase inhibitors.

Cancer Chemother Pharmacol 2021 Jun 2. Epub 2021 Jun 2.

Quantitative Clinical Pharmacology, AstraZeneca , South San Francisco, CA, USA.

Purpose: Limited information is available regarding the drug-drug interaction (DDI) potential of molecular targeted agents and rituximab plus cyclophosphamide, doxorubicin (hydroxydaunorubicin), vincristine (Oncovin), and prednisone (R-CHOP) therapy. The addition of the Bruton tyrosine kinase (BTK) inhibitor ibrutinib to R-CHOP therapy results in increased toxicity versus R-CHOP alone, including higher incidence of peripheral neuropathy. Vincristine is a substrate of P-glycoprotein (P-gp, ABCB1); drugs that inhibit P-gp could potentially cause increased toxicity when co-administered with vincristine through DDI. While the combination of the BTK inhibitor acalabrutinib and R-CHOP is being explored clinically, the DDI potential between these therapies is unknown.

Methods: A human mechanistic physiology-based pharmacokinetic (PBPK) model of vincristine following intravenous dosing was developed to predict potential DDI interactions with combination therapy. In vitro absorption, distribution, metabolism, and excretion and in vivo clinical PK parameters informed PBPK model development, which was verified by comparing simulated vincristine concentrations with observed clinical data.

Results: While simulations suggested no DDI between vincristine and ibrutinib or acalabrutinib in plasma, simulated vincristine exposure in muscle tissue was increased in the presence of ibrutinib but not acalabrutinib. Extrapolation of the vincristine mechanistic PBPK model to other P-gp substrates further suggested DDI risk when ibrutinib (area under the concentration-time curve [AUC] ratio: 1.8), but not acalabrutinib (AUC ratio: 0.92), was given orally with venetoclax or digoxin.

Conclusion: Overall, these data suggest low DDI risk between acalabrutinib and P-gp substrates with negligible increase in the potential risk of vincristine-induced peripheral neuropathy when acalabrutinib is added to R-CHOP therapy.
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http://dx.doi.org/10.1007/s00280-021-04302-5DOI Listing
June 2021

Extracellular Vesicles: An Emerging Regenerative Treatment for Oral Disease.

Front Cell Dev Biol 2021 17;9:669011. Epub 2021 May 17.

Department of Periodontics, The Affiliated Stomatological Hospital of Nanjing Medical University, Nanjing Medical University, Nanjing, China.

Extracellular Vesicles (EVs) are small lipid-enclosed particles containing biological molecules such as RNA and proteins that have emerged as vital modulators of intercellular communication. Increasingly, studies have shown that EVs play an essential role in the occurrence and prognosis of oral diseases. EVs are increasingly considered a research hotspot of oral diseases. In addition, the characteristics of carrying active molecules have also been studied in oral tissue regeneration. Evidence has shown that EVs regulate the homeostasis of the inflammatory microenvironment, promote angiogenesis, and repair damaged tissues. In this review, we summarized the characteristics of EVs and highlighted the role of EVs in oral tissue regeneration, including dental pulp, periodontal tissue, cartilage, and bone. We also discussed their deficiencies and prospects as a potential therapeutic role in the regeneration treatment of oral disease.
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http://dx.doi.org/10.3389/fcell.2021.669011DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8165191PMC
May 2021