Publications by authors named "Di Huang"

338 Publications

Enhenced cell adhesion on collagen I treated parylene-C microplates.

J Biomater Sci Polym Ed 2021 Jul 21:1-12. Epub 2021 Jul 21.

Department of Biomedical Engineering, Research Center for Nano-biomaterials & Regenerative Medicine, College of Biomedical Engineering, Taiyuan University of Technology, Taiyuan, PR China.

On account of unique mechanical property and inertia, parylene-C has become a promising material for microdevices especially in three-dimensional microstructures loaded with cells. However, parylene-C is not favorable for cell adhesion, and a routine procedure is to modify it with a new adhesive layer. Herein, the parylene-C substrates with or without collagen I (Col-I) coating were adopted to estimate the influence of micro-environment change on cell attachment and spreading. After modification with Col-I, cauliflower-like particles presented on the substrate surface. Contact angle was significantly decreased after Col-I modification, which suggested the surface hydrophilicity was enhanced. Furthermore, cells cultured on parylene-C surface with Col-I treatment showed increased proliferation rate and spreading areas. In order to test the adhesion strength, a series of fixed size parylene-C microplates was fabricated, and cell suspension concentration was adjusted to culture a single cell on one microplate. The microplate was folded by the autogenous shrinkage force of cell. The folding angles of parylene-C microplates with Col-I treatment exhibited higher folding angle (112.6 ± 15.6°) than untreated samples (46.7 ± 5.9°). The work proved the existence of Col-I layer was particularly important, especially in analysis of cells mechanics using parylene-C microplate as a substrate.
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http://dx.doi.org/10.1080/09205063.2021.1958465DOI Listing
July 2021

Remdesivir Inhibits Tubulointerstitial Fibrosis in Obstructed Kidneys.

Front Pharmacol 2021 2;12:626510. Epub 2021 Jul 2.

Department of Nephrology, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, China.

Kidney impairment is observed in patients with COVID-19. The effect of anti-COVID-19 agent remdesivir on kidneys is currently unknown. We aimed to determine the effect of remdesivir on renal fibrosis and its downstream mechanisms. Remdesivir and its active nucleoside metabolite GS-441524 were used to treat TGF-β stimulated renal fibroblasts (NRK-49F) and human renal epithelial (HK2) cells. Vehicle or remdesivir were given by intraperitoneal injection or renal injection through the left ureter in unilateral ureteral obstruction (UUO) mice. Serum and kidneys were harvested. The concentrations of remdesivir and GS-441524 were measured using LC-MS/MS. Renal and liver function were assessed. Renal fibrosis was evaluated by Masson's trichrome staining and Western blotting. Remdesivir and GS-441524 inhibited the expression of fibrotic markers (fibronectin and aSMA) in NRK-49F and HK2 cells. Intraperitoneal injection or renal injection of remdesivir attenuated renal fibrosis in UUO kidneys. Renal and liver function were unchanged in remdesivir treated UUO mice. Two remdesivir metabolites were detected after injection. Phosphorylation of Smad3 that was enhanced in cell and animal models for renal fibrosis was attenuated by remdesivir. In addition, the expression of Smad7, an anti-fibrotic factor, was increased after remdesivir treatment and . Moreover, knockdown of Smad7 blocked the antifibrotic effect of GS and RDV on renal cells. Remdesivir inhibits renal fibrosis in obstructed kidneys.
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http://dx.doi.org/10.3389/fphar.2021.626510DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8284048PMC
July 2021

Inertial microfluidics in contraction-expansion microchannels: A review.

Biomicrofluidics 2021 Jul 2;15(4):041501. Epub 2021 Jul 2.

School of Mechanical Engineering, and Jiangsu Key Laboratory for Design and Manufacture of Micro-Nano Biomedical Instruments, Southeast University, Nanjing 211189, China.

Inertial microfluidics has brought enormous changes in the conventional cell/particle detection process and now become the main trend of sample pretreatment with outstanding throughput, low cost, and simple control method. However, inertial microfluidics in a straight microchannel is not enough to provide high efficiency and satisfying performance for cell/particle separation. A contraction-expansion microchannel is a widely used and multifunctional channel pattern involving inertial microfluidics, secondary flow, and the vortex in the chamber. The strengthened inertial microfluidics can help us to focus particles with a shorter channel length and less processing time. Both the vortex in the chamber and the secondary flow in the main channel can trap the target particles or separate particles based on their sizes more precisely. The contraction-expansion microchannels are also capable of combining with a curved, spiral, or serpentine channel to further improve the separation performance. Some recent studies have focused on the viscoelastic fluid that utilizes both elastic forces and inertial forces to separate different size particles precisely with a relatively low flow rate for the vulnerable cells. This article comprehensively reviews various contraction-expansion microchannels with Newtonian and viscoelastic fluids for particle focusing, separation, and microfluid mixing and provides particle manipulation performance data analysis for the contraction-expansion microchannel design.
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http://dx.doi.org/10.1063/5.0058732DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8254650PMC
July 2021

Generation of an induced pluripotent stem cell line from a patient with Stargardt disease caused by biallelic c.[5461-10T>C;5603A>T];[6077T>C] mutations in the ABCA4 gene.

Stem Cell Res 2021 Jul 24;54:102439. Epub 2021 Jun 24.

Ocular Tissue Engineering Laboratory, Lions Eye Institute, Nedlands, Western Australia, Australia; Centre for Ophthalmology and Visual Sciences, The University of Western Australia, Nedlands, Western Australia, Australia; Australian Inherited Retinal Disease Registry and DNA Bank, Department of Medical Technology and Physics, Sir Charles Gairdner Hospital, Nedlands, Western Australia, Australia; Department of Ophthalmology, Royal Perth Hospital, Perth, Western Australia, Australia; Department of Ophthalmology, Perth Children's Hospital, Nedlands, Western Australia, Australia.

Mutations in ABCA4 gene are causative for autosomal recessive Stargardt disease (STGD1), the most common inherited retinal dystrophy. Here, we report the generation of an induced pluripotent stem cell (iPSC) line from a STGD1 patient carrying biallelic c.[5461-10T>C;5603A>T];[6077T>C] mutations in the ABCA4 gene. Episomes carrying OCT4, SOX2, KLF4, L-MYC, LIN28 and mp53DD were employed for the reprogramming of patient-derived fibroblasts. This iPSC line expressed comparable pluripotency markers as in a commercially available human iPSC line, displayed normal karyotype and potential for trilineage differentiation, and were negative for both reprogramming episomes and mycoplasma test.
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http://dx.doi.org/10.1016/j.scr.2021.102439DOI Listing
July 2021

High Temporal Resolution Land Use Regression Models with POI Characteristics of the PM Distribution in Beijing, China.

Int J Environ Res Public Health 2021 06 7;18(11). Epub 2021 Jun 7.

School of Environment, Beijing Normal University, Beijing 100875, China.

PM is one of the primary components of air pollutants, and it has wide impacts on human health. Land use regression models have the typical disadvantage of low temporal resolution. In this study, various point of interests (POIs) variables are added to the usual predictive variables of the general land use regression (LUR) model to improve the temporal resolution. Hourly PM concentration data from 35 monitoring stations in Beijing, China, were used. Twelve LUR models were developed for working days and non-working days of the heating season and non-heating season, respectively. The results showed that these models achieved good fitness in winter and summer, and the highest R of the winter and summer models were 0.951 and 0.628, respectively. Meteorological factors, POIs, and roads factors were the most critical predictive variables in the models. This study also showed that POIs had time characteristics, and different types of POIs showed different explanations ranging from 5.5% to 41.2% of the models on working days or non-working days, respectively. Therefore, this study confirmed that POIs can greatly improve the temporal resolution of LUR models, which is significant for high precision exposure studies.
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http://dx.doi.org/10.3390/ijerph18116143DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8201188PMC
June 2021

Generation of two induced pluripotent stem cell lines from a patient with Stargardt disease caused by compound heterozygous mutations in the ABCA4 gene.

Stem Cell Res 2021 Jul 24;54:102448. Epub 2021 Jun 24.

Ocular Tissue Engineering Laboratory, Lions Eye Institute, Nedlands, Western Australia, Australia; Centre for Ophthalmology and Visual Sciences, The University of Western Australia, Nedlands, Western Australia, Australia. Electronic address:

Stargardt disease (STGD1) is the most common inherited retinal dystrophy and ABCA4 c.546--10 T>C is the most commonly reported splice mutation. Here, we generated and characterized two induced pluripotent stem cell (iPSC) lines from a STGD1 patient with compound heterozygous mutations in ABCA4 (c.[5461-10 T > C;5603A > T];[4163 T > C;455G > A]). Episomal vectors containing OCT4, SOX2, KLF4, L-MYC, LIN28 and mp53DD were employed to conduct the reprogramming of patient-derived fibroblasts. Both lines had a normal karyotype, displayed iPSC morphology, expressed pluripotency markers and showed trilineage differentiation potential. These lines can provide a powerful platform for further investigating the pathophysiological consequences of mutations in ABCA4.
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http://dx.doi.org/10.1016/j.scr.2021.102448DOI Listing
July 2021

Human Cancer Cell Membrane-Cloaked FeO Nanocubes for Homologous Targeting Improvement.

J Phys Chem B 2021 Jul 29;125(27):7417-7426. Epub 2021 Jun 29.

Department of Biomedical Engineering, Research Center for Nano-biomaterials & Regenerative Medicine, College of Biomedical Engineering, Taiyuan University of Technology, Taiyuan, Shanxi 030024, China.

Surface modification of nanoparticles with cellular protein components is a new biomimetic modification strategy, which utilizes the inherent affinity between homologous cells to introduce the same surface molecules into nanoparticles to improve the targeting performance. In this study, oleic acid (OA)-coated FeO nanocubes were prepared by a high-temperature thermal decomposition method and modified by 3, 4-dihydroxyphenylpropionic acid (DHCA); then, HeLa cell membranes were introduced onto the surface of the nanocubes through mixed coextrusion to try to endow them with the targeting function of natural cells. The results show that the prepared FeO nanocubes have high monodispersity, excellent water solubility, and biocompatibility. Moreover, the FeO nanocubes encapsulated by cellular protein show an obvious core-shell structure and the specific targeting property to HeLa cells is improved significantly, which is expected to be used in clinical targeted diagnosis and treatment of cancer.
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http://dx.doi.org/10.1021/acs.jpcb.1c04383DOI Listing
July 2021

Targeting regulator of G protein signaling 1 in tumor-specific T cells enhances their trafficking to breast cancer.

Nat Immunol 2021 Jul 17;22(7):865-879. Epub 2021 Jun 17.

Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Medical Research Center, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, China.

Reduced infiltration of anti-tumor lymphocytes remains a major cause of tumor immune evasion and is correlated with poor cancer survival. Here, we found that upregulation of regulator of G protein signaling (RGS)1 in helper T1 cells and cytotoxic T lymphocytes (CTLs) reduced their trafficking to and survival in tumors and was associated with shorter survival of patients with breast and lung cancer. RGS1 was upregulated by type II interferon (IFN)-signal transducer and activator of transcription (STAT)1 signaling and impaired trafficking of circulating T cells to tumors by inhibiting calcium influx and suppressing activation of the kinases ERK and AKT. RGS1 knockdown in adoptively transferred tumor-specific CTLs significantly increased their infiltration and survival in breast and lung tumor grafts and effectively inhibited tumor growth in vivo, which was further improved when combined with programmed death ligand (PD-L)1 checkpoint inhibition. Our findings reveal RGS1 is important for tumor immune evasion and suggest that targeting RGS1 may provide a new strategy for tumor immunotherapy.
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http://dx.doi.org/10.1038/s41590-021-00939-9DOI Listing
July 2021

Search for Light Dark Matter-Electron Scattering in the PandaX-II Experiment.

Phys Rev Lett 2021 May;126(21):211803

Research Center for Particle Science and Technology, Institute of Frontier and Interdisciplinary Science, Shandong University, Qingdao 266237, Shandong, China.

We report constraints on light dark matter through its interactions with shell electrons in the PandaX-II liquid xenon detector with a total 46.9  tonnes/day exposure. To effectively search for these very low energy electron recoils, ionization-only signals are selected from the data. 1821 candidates are identified within an ionization signal range between 50 and 75 photoelectrons, corresponding to a mean electronic recoil energy from 0.08 to 0.15 keV. The 90% C.L. exclusion limit on the scattering cross section between the dark matter and electron is calculated with systematic uncertainties properly taken into account. Under the assumption of point interaction, we provide the world's most stringent limit within the dark matter mass range from 15 to 30  MeV/c^{2}, with the corresponding cross section from 2.5×10^{-37} to 3.1×10^{-38}  cm^{2}.
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http://dx.doi.org/10.1103/PhysRevLett.126.211803DOI Listing
May 2021

Prolonged exposure to the herbicide atrazine suppresses immune cell functions by inducing spleen cell apoptosis in rats.

Ecotoxicol Environ Saf 2021 Sep 2;220:112386. Epub 2021 Jun 2.

School of Nursing, Jilin University, Changchun 130021, Jilin, China. Electronic address:

Atrazine (ATR) is a herbicide used widely worldwide. Because of its prolonged persistence in the environment and accumulation in the body, ATR exposure is a potential threat to human health. Our previous study showed that subacute exposure to ATR suppresses cellular immune function in mice. In this study, the effects of long-term exposure to ATR on rat immunological system function were measured. Four-week-old female Sprague-Dawley (SD) rats were treated with 0.4 μmol/L, 2 μmol/L and 10 μmol/L ATR for 24 weeks. The results showed that the spleen index increased, white blood cells decreased, and monocytes and eosinophils increased. No obvious changes were detected in the numbers of neutrophils and lymphocytes. Th1, Th2, and Th17 cells decreased significantly, while Treg cells increased after long-term ATR exposure. Moreover, serum levels of cytokines, including TNF-α, INF-γ, IL-6, and IL-12, decreased, while IL-1, IL-4, and IL-5 increased. Degenerative changes and cell apoptosis were found in the spleen; Caspase-3 and Caspase-9 were upregulated, and Bcl-2 was downregulated. These results suggested that long-term ATR exposure may inhibit immune system function.
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http://dx.doi.org/10.1016/j.ecoenv.2021.112386DOI Listing
September 2021

In situ Raman enhancement strategy for highly sensitive and quantitative lateral flow assay.

Anal Bioanal Chem 2021 Jun 5. Epub 2021 Jun 5.

Key Laboratory for Chemical Biology of Fujian Province, MOE Key Laboratory of Spectrochemical Analysis & Instrumentation, Collaborative Innovation Center of Chemistry for Energy Materials, State Key Laboratory of Physical Chemistry of Solid Surfaces, College of Chemistry and Chemical Engineering, Xiamen University, Xiamen, 361005, Fujian, China.

As a paper-based analytical platform, lateral flow assay (LFA) gets benefit from the rapid analysis, low cost, high selectivity, good stability, and user-friendliness, and thus has been widely used in rapid screening or assisted diagnosis. Nevertheless, LFA still suffers from low detection sensitivity via the naked eye, limiting its applications to qualitative and semi-quantitative tests. To enhance the signal readout, various nanoparticle signal tags have been employed to replace traditional colloidal gold nanoparticles (AuNPs), such as fluorescent nanoparticles (FNPs), magnetic nanoparticles (MNPs), and Raman reporter-labeled nanoparticles. In particular, Raman reporter-labeled nanoparticles are extremely sensitive due to remarkable signal enhancement effect on metal surface. However, the application of LFA is still hampered by the poor stability of Raman reporter-labeled nanoparticles. Herein, we developed an in situ Raman enhancement strategy to create a surface-enhanced Raman scattering (SERS) signal on the AuNPs, shortened as "i-SERS," which not only preserves the original advantages of the colloidal gold strip (AuNPs-LFA), but also realizes highly sensitive and quantitative detection. We applied the i-SERS for procalcitonin (PCT) detection. The experimental process takes only 16 min, and the limit of detection (LOD) is 0.03 ng mL, far below the value using AuNPs-LFA. These results indicate that i-SERS assay was highly sensitive and suitable for the rapid detection of PCT.
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http://dx.doi.org/10.1007/s00216-021-03419-zDOI Listing
June 2021

The influence of hyperbilirubinemia on indexes of kidney function in neonates.

Pediatr Nephrol 2021 Jun 1. Epub 2021 Jun 1.

Department of Neonatology, Xuzhou Central Hospital (Xuzhou School of Clinical Medicine of Nanjing Medical University), Xuzhou, 221009, China.

Background: To study the influence of hyperbilirubinemia on indexes of neonatal kidney function.

Methods: A prospective cohort study was conducted September 2019 to March 2020 in Neonatology Department of Xuzhou Central Hospital. Neonates with gestational age ≥ 35 weeks and aged ≤ 7 days were included and divided into mild, moderate, and severe groups according to total serum bilirubin level. Epidemiologic and demographic data and daily urine output were recorded. Total serum bilirubin, serum creatinine, serum cystatin C, serum neutrophil gelatinase-associated lipocalin (NGAL), urine NGAL, and kidney injury molecule-1 were tested before and 12~18 h after phototherapy. Parameters of kidney function were compared between groups.

Results: Fifty-three, 52, and 49 neonates were included in the mild, moderate, and severe groups, respectively. Urine NGAL was higher in severe (1.36 ± 0.24 μg/L) compared to moderate (1.22 ± 0.19 μg/L) and mild groups (1.16 ± 0.19 μg/L), and differences were statistically significant (P = 0.004 and < 0.001, respectively). Urine NGAL was not significantly different between moderate and mild groups (P > 0.05). No significant differences in other kidney function indexes were observed between the three groups (all P > 0.05). Significant reduction in urine NGAL levels 12~18 h after stopping phototherapy was found in severe group ((1.17 ± 0.28) μg/L vs. (1.35 ± 0.23) μg/L, P < 0.001). Urine NGAL positively correlated with total serum bilirubin (r = 0.575, P < 0.001). Among all cases, neither serum creatinine nor daily urine output met neonatal acute kidney injury diagnostic criteria.

Conclusion: Severe hyperbilirubinemia may temporarily impair renal tubular reabsorption functions in full-term and near-term neonates, which is likely reversible. However, it has little effect on glomerular filtration function. A higher resolution version of the Graphical abstract is available as Supplementary information.
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http://dx.doi.org/10.1007/s00467-021-05151-3DOI Listing
June 2021

Alginate microgels as delivery vehicles for cell-based therapies in tissue engineering and regenerative medicine.

Carbohydr Polym 2021 Aug 28;266:118128. Epub 2021 Apr 28.

School of Bioengineering, State Key Laboratory of Fine Chemistry, Dalian University of Technology, Dalian 116023, PR China. Electronic address:

Conventional stem cell delivery typically utilize administration of directly injection of allogenic cells or domesticated autogenic cells. It may lead to immune clearance of these cells by the host immune systems. Alginate microgels have been demonstrated to improve the survival of encapsulated cells and overcome rapid immune clearance after transplantation. Moreover, alginate microgels can serve as three-dimensional extracellular matrix to support cell growth and protect allogenic cells from rapid immune clearance, with functions as delivery vehicles to achieve sustained release of therapeutic proteins and growth factors from the encapsulated cells. Besides, cell-loaded alginate microgels can potentially be applied in regenerative medicine by serving as injectable engineered scaffolds to support tissue regrowth. In this review, the properties of alginate and different methods to produce alginate microgels are introduced firstly. Then, we focus on diverse applications of alginate microgels for cell delivery in tissue engineering and regenerative medicine.
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http://dx.doi.org/10.1016/j.carbpol.2021.118128DOI Listing
August 2021

Neutrophil extracellular traps promote gastric cancer metastasis by inducing epithelial‑mesenchymal transition.

Int J Mol Med 2021 Jul 20;48(1). Epub 2021 May 20.

The Second Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang 150086, P.R. China.

The risks of tumor recurrence following the successful resection of the primary tumor have been known for decades; however, the precise mechanisms underlying treatment failures remain unknown. The formation of neutrophil extracellular traps (NETs) has increasingly been demonstrated to be associated with thrombi formation in cancer patients, as well as with the development and metastasis of cancer. The present study demonstrated that the level of peripheral blood NETs in patients with gastric cancer (GC) was associated with tumor progression, and patients with stage III/IV disease exhibited significant differences compared with the healthy controls and patients with stage I/II disease, which may be associated with an increased risk of metastasis. In addition, plasma from patients with stage III/IV GC was more prone to stimulate neutrophils to form NETs; thus, it was hypothesized that the formation of NETs may be affected by the tumor microenvironment. A higher deposition of NETs in GC tissues compared with normal resection margins was also identified. , following treatment with phorbol myristate acetate, which promotes the formation of NETs, or with DNAse‑1/GSK‑484, which inhibits the formation of NETs, it was found that the tumor migratory ability was altered; however, no significant changes were observed in cell proliferation and cell cycle progression. Epithelial‑mesenchymal transition (EMT) is a key event associated with dissemination and metastasis in GC pathogenesis. Finally, the present study demonstrated that NETs promote a more aggressive mesenchymal phenotype and promote the progression of GC and . On the whole, to the best of our knowledge, the present study reports a previously unknown role of NETs in the regulation of GC, which is associated with EMT and migration. Therefore, targeting NETs may prove to be therapeutically beneficial.
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http://dx.doi.org/10.3892/ijmm.2021.4960DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8128417PMC
July 2021

Positive reverse transcription-polymerase chain reaction assay results in patients recovered from COVID-19: Report of two cases.

World J Clin Cases 2021 Apr;9(12):2816-2822

Department of Radiology, The Affiliated Hospital of Zunyi Medical University, Zunyi 563000, Guizhou Province, China.

Background: Coronavirus disease 2019 (COVID-19) has spread around the globe. On February 28, 2020, the World Health Organization adjusted the risk of spread and impact of COVID-19 to "very high" at the global level. Studies have mainly focused on the etiology, epidemiology, and treatment of COVID-19 to limit further spread and the negative impact of the disease, while less attention has been devoted to the follow-up and reexamination of patients who recovered from COVID-19 or were released from quarantine.

Case Summary: This study reports two cases where patients who had negative reverse transcription-polymerase chain reaction (RT-PCR) test results and met the criteria for discharge subsequently had positive RT-PCR test results. The clinical manifestations and computed tomography (CT) findings of these patients were examined. The conversion of RT-PCR test results in these two patients may be related to false-negative and false-positive outcomes of the test. CT images helped track improvement of pulmonary lesions.

Conclusion: The timing of discharge of COVID-19 patients should be determined by comprehensive analysis of CT images and RT-PCR test results.
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http://dx.doi.org/10.12998/wjcc.v9.i12.2816DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8058663PMC
April 2021

Reversed-engineered human alveolar lung-on-a-chip model.

Proc Natl Acad Sci U S A 2021 05;118(19)

Division of Engineering in Medicine, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Cambridge, MA 02139;

Here, we present a physiologically relevant model of the human pulmonary alveoli. This alveolar lung-on-a-chip platform is composed of a three-dimensional porous hydrogel made of gelatin methacryloyl with an inverse opal structure, bonded to a compartmentalized polydimethylsiloxane chip. The inverse opal hydrogel structure features well-defined, interconnected pores with high similarity to human alveolar sacs. By populating the sacs with primary human alveolar epithelial cells, functional epithelial monolayers are readily formed. Cyclic strain is integrated into the device to allow biomimetic breathing events of the alveolar lung, which, in addition, makes it possible to investigate pathological effects such as those incurred by cigarette smoking and severe acute respiratory syndrome coronavirus 2 pseudoviral infection. Our study demonstrates a unique method for reconstitution of the functional human pulmonary alveoli in vitro, which is anticipated to pave the way for investigating relevant physiological and pathological events in the human distal lung.
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http://dx.doi.org/10.1073/pnas.2016146118DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8126776PMC
May 2021

Response Efficacy of PD-1 and PD-L1 Inhibitors in Clinical Trials: A Systematic Review and Meta-Analysis.

Front Oncol 2021 16;11:562315. Epub 2021 Apr 16.

Department of Medical Oncology, Chinese People's Liberation Army (PLA) General Hospital, Beijing, China.

Background: Immune checkpoint inhibitors targeting the PD-1/PD-L1 pathway have demonstrated promise in treating a variety of advanced cancers; however, little is known regarding their efficacy under various clinical situations, including different cancer types, treatment lines, drug combinations, and therapeutic regimens.

Methods: Published articles and conference abstracts (in English) in PubMed, Embase, the Cochrane Central Register, and Web of Science were searched up to February 10, 2020. The data were analyzed by the meta-analysis program in Stata.

Results: A total of 16,400 patients from 91 clinical trials were included in this meta-analysis. PD-1/PD-L1 inhibitors had a mean ORR of 19.56% (95% CI: 15.09-24.03), a median TTR of 2.05 months (m) (95%CI: 1.85-2.26), and a median DOR of 10.65 m (95%CI: 7.78-13.52). First-line treatment had a higher ORR (36.57% vs. 13.18%) but a shorter DOR (9.00 m vs. 13.42 m) compared to the second-line or subsequent treatment. Immunotherapy combined with chemotherapy (I+C) (46.81% [95%CI: 36.02-57.60]) had a statistically significant higher ORR compared to immunotherapy (I) (17.75% [95%CI: 14.47-21.03]) or immunotherapy combined with immunotherapy (I+O) (12.25% [95%CI: 1.56-22.94]), while I+C (8.09 m [95%CI: 6.86-9.32]) appeared to reduce the DOR compared to I (12.39 m [95%CI: 7.60-17.18]). PD-1 inhibitors were associated with better ORR (21.65% vs. 17.60%) and DOR (11.26 m vs. 10.03 m) compared to PD-L1 inhibitors. There were no significant differences in TTR under different situations.

Conclusions: PD-1/PD-L1 inhibitors were promising immunotherapeutic agents to achieve satisfactory response efficacies with different cancer types, treatment lines, drug combinations, and therapeutic regimens. This comprehensive summary of the response efficacy of PD-1/PD-L1 inhibitors serves as a reference for clinicians to make evidence-based decisions.
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http://dx.doi.org/10.3389/fonc.2021.562315DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8085334PMC
April 2021

A missense variant in NDUFA6 confers schizophrenia risk by affecting YY1 binding and NAGA expression.

Mol Psychiatry 2021 Apr 30. Epub 2021 Apr 30.

Key Laboratory of Animal Models and Human Disease Mechanisms of the Chinese Academy of Sciences & Yunnan Province, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, Yunnan, China.

Genome-wide association studies (GWASs) have revealed that genetic variants at the 22q13.2 risk locus were robustly associated with schizophrenia. However, the causal variants at this risk locus and their roles in schizophrenia remain elusive. Here we identify the risk missense variant rs1801311 (located in the 1st exon of NDUFA6 gene) as likely causal for schizophrenia at 22q13.2 by disrupting binding of YY1, TAF1, and POLR2A. We systematically elucidated the regulatory mechanisms of rs1801311 and validated the regulatory effect of this missense variant. Intriguingly, rs1801311 physically interacted with NAGA (encodes the alpha-N-acetylgalactosaminidase, which is mainly involved in regulating metabolisms of glycoproteins and glycolipids in lysosome) and showed the most significant association with NAGA expression in the human brain, with the risk allele (G) associated with higher NAGA expression. Consistent with eQTL analysis, expression analysis showed that NAGA was significantly upregulated in brains of schizophrenia cases compared with controls, further supporting that rs1801311 may confer schizophrenia risk by regulating NAGA expression. Of note, we found that NAGA regulates important neurodevelopmental processes, including proliferation and differentiation of neural stem cells. Transcriptome analysis corroborated that NAGA regulates pathways associated with neuronal differentiation. Finally, we independently confirmed the association between rs1801311 and schizophrenia in a large Chinese cohort. Our study elucidates the regulatory mechanisms of the missense schizophrenia risk variant rs1801311 and provides mechanistic links between risk variant and schizophrenia etiology. In addition, this study also revealed the novel role of coding variants in gene regulation and schizophrenia risk, i.e., genetic variant in coding region of a specific gene may confer disease risk through regulating distal genes (act as regulatory variant for distal genes).
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http://dx.doi.org/10.1038/s41380-021-01125-xDOI Listing
April 2021

Occurrences, congener group profiles, and risk assessment of short- and medium-chain chlorinated paraffins in cup instant noodles from China.

Chemosphere 2021 Sep 16;279:130503. Epub 2021 Apr 16.

State Key Laboratory of Environmental Chemistry and Ecotoxicology, Research Center for Eco-Environmental Sciences, Chinese Academy of Sciences, Beijing, 100085, China; University of Chinese Academy of Sciences, Beijing, 100049, China.

Dietary intake is an important route of human exposure to chlorinated paraffins (CPs). Cup instant noodles are widely popular food and millions packet of instant noodles are consumed every year. To investigate the levels, congener groups, and health risk of SCCPs and MCCPs in each component of cup instant noodles, samples of nine common brands were collected and analyzed by comprehensive two dimensional gas chromatography coupled with mass spectrometry. The mean concentrations in the noodles were 1.2 × 10 ng/g wet weight (ww) (SCCPs) and 1.2 × 10 ng/g ww (MCCPs), the mean concentrations in the seasoning were 1.4 × 10 ng/g ww (SCCPs) and 1.3 × 10 ng/g ww (MCCPs), and the mean concentrations in the soup were 5.6 × 10 ng/L (SCCPs) and 5.4 × 10 ng/L (MCCPs). The SCCP to MCCP ratio were similar in the soup and soup container, which means CPs in the soup might be migrated from the soup container. Seasoning and noodles from the same brands have similar congener profiles of SCCPs and MCCPs, which may be raised from the manufacturing process or food packaging materials. The dominant SCCP congener groups were CCl in noodles and seasoning, and CCl in soup. The dominant MCCP congener groups were CCl in noodles and seasoning, and CCl in soup. A preliminary health risk assessment indicated that the current intakes of SCCPs and MCCPs through cup instant noodles in China did not pose a significant risk to human health.
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http://dx.doi.org/10.1016/j.chemosphere.2021.130503DOI Listing
September 2021

Berberine carried gelatin/sodium alginate hydrogels with antibacterial and EDTA-induced detachment performances.

Int J Biol Macromol 2021 Jun 20;181:1039-1046. Epub 2021 Apr 20.

Department of Biomedical Engineering, Research Center for Nano-Biomaterials & Regenerative Medicine, College of Biomedical Engineering, Taiyuan University of Technology, Taiyuan 030024, PR China; Shanxi Key Laboratory of Material Strength & Structural Impact, Institute of Biomedical Engineering, Taiyuan University of Technology, Taiyuan 030024, PR China. Electronic address:

Most existing hydrogel wound dressings lack gentle detachment property. In this work, novel hydrogels with anti-bacterial and induced detachment properties were prepared. Both gelatin (G) and sodium alginate (SA) are natural polymer materials. The G/SA hydrogels were prepared by dual cross-linking. The addition of SA significantly improves the mechanical properties of composite hydrogels. The tensile modulus and elongation at break of the G/SA hydrogels with 2.0% SA could reach 99.23 ± 2.18 kPa and 85.47 ± 5.01%, respectively. In addition, the interconnected porous network and high swelling ratio (over 9.99 ± 0.33) are beneficial to the transmission of oxygen and absorption of exudates to accelerate the healing of wound. Subsequently, berberine (BBR) was loaded into the G/SA hydrogels. The BBR/G/SA hydrogels show sustained drug release for 168 h and exhibit anti-bacterial effect against Staphylococcus aureus. The results of L929 cells cultured with the hydrogel extracts indicate good biocompatibility. Finally, results of EDTA-induced detachment performances demonstrate that the hydrogels could be removed from the wound as the internal structure destroyed. All illustrated results above demonstrated the BBR carried G/SA hydrogels have potential used as wound dressing materials in future.
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http://dx.doi.org/10.1016/j.ijbiomac.2021.04.114DOI Listing
June 2021

Prognostic value of baseline and change in neutrophil-to-lymphocyte ratio for survival in advanced non-small cell lung cancer patients with poor performance status receiving PD-1 inhibitors.

Transl Lung Cancer Res 2021 Mar;10(3):1397-1407

Department of Medical Oncology, Chinese PLA General Hospital, Beijing, China.

Background: Advanced non-small cell lung cancer (NSCLC) patients with poor performance status (PS) are likely to receive programmed cell death 1 (PD-1) inhibitors, despite limited evidence. The aim of the present study was to report the clinical outcomes and potential prognostic biomarkers in advanced NSCLC patients with poor PS receiving PD-1 inhibitors.

Methods: We conducted a retrospective study enrolling 101 advanced NSCLC patients from our hospital. Data of patients with poor PS 2-4 receiving PD-1 inhibitors were retrieved from medical records. Patients were stratified based on dichotomized baseline neutrophil-to-lymphocyte ratio (NLR), change in NLR (ΔNLR; 6 weeks post-treatment NLR minus baseline NLR), and their combination. The receiver-operating characteristic curve was used to assess the best cutoff for NLR. Multivariate Cox analysis was used to evaluate the prognostic value of NLR and ΔNLR for patients' survival.

Results: The optimal cutoff for NLR was 4.5. The median follow-up was 25.7 months, baseline NLR ≥4.5, and ΔNLR ≥0, which were independently and significantly associated with shorter overall survival (both P=0.002) and progression-free survival (P=0.004 for NLR and P<0.001 for ΔNLR). Furthermore, simultaneous elevation of the 2 factors was associated with worsened prognosis; patients with both NLR ≥4.5 and ΔNLR ≥0 had significantly increased risk of death [hazards ratio (HR): 10.79, 95% confidence interval (CI): 4.30-27.10] and disease progression (HR: 10.49, 95% CI: 4.39-25.09), compared with both low NLR and ΔNLR patients. Patients with either NLR ≥4.5 or ΔNLR ≥0 showed an intermediate risk for death (HR: 3.12, 95% CI: 1.35-7.21) and progression (HR: 3.45, 95% CI: 1.62-7.36).

Conclusions: High baseline NLR and increased post-treatment NLR might aid in the stratification of high progression and death risk groups in advanced NSCLC patients with poor PS receiving PD-1 inhibitors.
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http://dx.doi.org/10.21037/tlcr-21-43DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8044483PMC
March 2021

Efficacy and safety of crizotinib plus bevacizumab in positive non-small cell lung cancer: an open-label, single-arm, prospective observational study.

Am J Transl Res 2021 15;13(3):1526-1534. Epub 2021 Mar 15.

School of Medicine, Nankai University Weijin Road 94#, Nankai District, Tianjin 300071, China.

Background: Crizotinib is a tyrosine kinase inhibitor (TKI) effective in positive non-small cell lung cancer (NSCLC) patients. Bevacizumab is an antiangiogenic monoclonal antibody, and improves clinical benefit of NSCLC in combination with EGFR-TKIs or chemotherapy. However, the efficacy and safety of crizotinib plus bevacizumab in treating naive positive NSCLC patients have not been studied.

Methods: In this open-label, single-arm, prospective observational study, locally advanced or metastatic rearrangement/ fusion/ amplification NSCLC patients were treated with crizotinib (250 mg orally twice daily) and bevacizumab (7.5 mg/kg intravenous every three weeks) until disease progression or intolerant toxicity or death. Primary end point was progressive free survival (PFS), secondary end points were duration of response (DOR), overall response rate (ORR), disease control rate (DCR) and safety. Patients receiving ≥1 cycle of treatment were evaluated.

Findings: Fourteen patients were eligible for analyzing between June 2016 and October 2017. There were 12 patients with rearrangement, 1 patient with fusion, and 1 patient with amplification. The median follow-up time was 42.8 months. The median PFS and DOR of the patients with rearrangement were 13.9 and 14.8 months respectively. Of the 12 patients, 7 gained partial response, 5 gained stable disease. The ORR and DCR were 58.3% and 100%. The PFS were 12.9 months and 1.9 months for patient with fusion or amplification. The most two common treatment-related adverse events were fatigue (28.6%) and rash (21.4%). 3 patients discontinued therapy because of liver damage or hemoptysis.

Interpretation: This study demonstrated that crizotinib plus bevacizumab showed benefit in treating naive rearrangement NSCLC patients, and the toxicity was relatively tolerant. Our results suggested that crizotinib plus bevacizumab might be a promising treatment strategy in positive NSCLC patients.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8014364PMC
March 2021

[Risk factors for neutropenia of late newborns].

Zhongguo Dang Dai Er Ke Za Zhi 2021 Apr;23(4):375-380

Department of Neonatology, Xuzhou Central Hospital/Xuzhou School of Clinical Medicine of Nanjing Medical University, Xuzhou, Jiangsu 221009, China.

Objective: To study the risk factors and treatment for neutropenia of late newborns (NLN).

Methods: Related clinical data were collected from the preterm infants and critically ill neonates who were admitted to the neonatal intensive care unit from July 2019 to January 2020. A total of 46 newborns with a blood absolute neutrophil count (ANC) of < 1.5×10/L for two consecutive times at weeks 2-4 after birth were enrolled as the NLN group. A total of 92 late newborns with a blood ANC of ≥ 1.5×10/L, matched at a ratio of 1:2, were enrolled as the control group. Possible risk factors associated with NLN and the treatment process were recorded. A logistic regression analysis was performed to identify the risk factors for NLN.

Results: Among the 46 neonates in the NLN group, 29 had a gestational age of < 32 weeks, 14 had a gestational age of 32-37 weeks, and 3 had a gestational age of > 37 weeks. There was no significant difference between the two groups in the incidence rates of gestational hypertension, premature rupture of membranes > 18 hours and intrauterine distress, 5-minute Apgar score, the duration of positive pressure ventilation, the incidence rate of early-onset sepsis, and the type of initially used antibiotics ( > 0.05). Compared with the control group, the NLN group had a higher incidence rate of late-onset sepsis and a longer duration of antibiotic use ( < 0.05). Late-onset sepsis and prolonged duration of antibiotic use were independent risk factors for NLN ( < 0.05). With the presence of late-onset sepsis, the risk of NLN was increased by 1.537 times in neonates, and the risk of NLN was increased by 76.9% for every 3-day increase in the duration of antibiotic use. The mean age at the diagnosis of NLN was (21±6) days for the 46 neonates in the NLN group. Thirteen neonates with NLN were administered with recombinant human granulocyte colony-stimulating factor (G-CSF, 10 μg/kg) once or twice. O the 13 neonates, 6 had an ANC of < 0.5×10/L and 7 had a gestational age of < 32 weeks or severe disease conditions. After treatment the ANC returned to > 1.0×10/L in the 13 neonates. No drug-related adverse reactions were found. After the diagnosis of NLN, 2 neonates developed sepsis, and the remaining 44 neonates did not develop any common purulent infections.

Conclusions: The risk of NLN increases with the presence of late-onset sepsis and the increase in the duration of antibiotic use. NLN is generally a benign process. G-CSF appears to be safe and effective for NLN with severe disease conditions or severe reduction in ANC.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8050555PMC
April 2021

Nurses reports of actual work hours and preferred work hours per shift among frontline nurses during coronavirus disease 2019 (COVID-19) epidemic: A cross-sectional survey.

Int J Nurs Stud Adv 2021 Nov 28;3:100026. Epub 2021 Mar 28.

Affiliated Hospital of Zunyi Medical University, 149 Dalian Road, Huichuan District, Zunyi, Guizhou 563003, China.

Background: The Coronavirus disease (COVID-19) pandemic is an ongoing pandemic all over the world, leading to 126, 372, 442 people diagnosed and 2, 769, 696 deaths globally as of March 28, 2021. Nurses are providing care to patients with COVID-19 who require hospitalization. To ensure adequate response capacity and to maintain the health of nurses, it is important to analyse the actual work hours and the nurses reported preferred work hours per shift among frontline nurses.

Objective: To analyse the actual work hours and preferred work hours per shift of nurses reports among frontline nurses fighting the COVID-19 epidemic and to explore the influencing factors on the nurses reported preferred work hours.

Design: Cross-sectional survey.

Settings: This study was conducted in 10 designated hospitals providing treatments to patients with COVID-19 in China.

Participants: Nurses providing care to patients with COVID-19 in designated hospitals in China.

Methods: A questionnaire with open-ended questions was used to assess frontline nurses caring for COVID-19 cases in 10 designated hospitals. Quantitative and qualitative methods were used to analyse the actual work hours, the nurses reported preferred work hours and factors influencing nurses reported preferred work hours among the frontline nurses.

Results: A total of 109 nurses responded to the survey. The shift length exceeded the nurses' preferred work hours [Median (interquartile range): 5.00 (2.00) h vs 4.00 (2.00) h; Minimum-Maximum: 4-12 h vs 4-8 h], and 60.55% (66/109) of the nurses regarded 4 h as the preferred number of work hours per shift. Five key themes associated with the influencing factors emerged, including circumstances; personal preventable equipment; the nurses' physical and emotional needs of nurse; and the nurses' safety needs and work intensity.

Conclusions: These findings suggest that there is a gap between the actual work hours and the nurses preferred work hours among frontline nurses in different units and different posts. The main influencing factors were circumstances, personal protective equipment, the nurses' physical and emotional needs, and the nurses' safety needs and work intensity.
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http://dx.doi.org/10.1016/j.ijnsa.2021.100026DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8005253PMC
November 2021

Reversine and herbal Xiang-Sha-Liu-Jun-Zi decoction ameliorate thioacetamide-induced hepatic injury by regulating the RelA/NF-κB/caspase signaling pathway.

Open Life Sci 2020 15;15(1):696-710. Epub 2020 Sep 15.

Department of Surgery, Guangzhou First People's Hospital, School of Medicine, South China University of Technology, No.1 Panfu Road, Yuexiu District, Guangzhou, Guangdong 518180, People's Republic of China.

This study investigated the anti-fibrotic effects of reversine and Chinese medicine Xiang-Sha-Liu-Jun-Zi decoction (XSLJZD) on thioacetamide (TAA)-induced hepatic injury. Sprague-Dawley rats were intraperitoneally administered with TAA, then injected with reversine intraperitoneally, and/or orally provided with XSLJZD. TAA resulted in liver injury with increases in the liver index and levels of serum aspartate aminotransferase (AST) and alanine aminotransferase. Reversine alleviated the liver index and AST level and improved TAA-induced pathological changes but decreased TAA-induced collagen deposition, and α-smooth muscle actin and transforming growth factor-β1 expression. Reversine also modulated the mRNA levels of inflammatory cytokines, such as RelA, interleukin (IL)-17A, IL-22, IL-1β, IL-6, NLR family pyrin domain containing 3, platelet-derived growth factor, and monocyte chemoattractant protein, and suppressed nuclear factor (NF)-κB (p65) phosphorylation and caspase 1 activation. Meanwhile, XSLJZD protected TAA-injured liver without increasing fibrosis and enhanced the regulating effect of reversine on RelA, IL-17A, IL-1β, and MCP-1 cytokines. In conclusion, reversine ameliorates liver injury and inhibits inflammation reaction by regulating NF-κB, and XSLJZD protects the liver through its synergistic effect with reversine on regulating inflammatory cytokines.
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http://dx.doi.org/10.1515/biol-2020-0059DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7747499PMC
September 2020

High Expression of PRSS3 Indicates Unfavorable Clinical Outcomes in Colon Adenocarcinoma.

Appl Immunohistochem Mol Morphol 2021 Mar 22. Epub 2021 Mar 22.

Department of General Surgery, Tianjin Medical University General Hospital, Tianjin The Second Department of General Surgery, Affiliated Hospital of Shan Dong Medical College Shandong Medical College, Linyi Department of Gastrointestinal Oncological Surgery, The First Affiliated Hospital of Hebei North University, Zhangjiakou, China.

Introduction: Serine proteases have been implicated as key drivers and facilitators of cancer malignancy. Protease, serine, 3 (PRSS3), which belongs to the serine proteases family, is reported to be abundantly expressed in a variety of types of tumor and contributes to the initiation and development of cancers. However, the clinical role of PRSS3 in colon adenocarcinoma (CAC) was not clarified yet. In the present study, we explored the potential effect of PRSS3 in CAC and whether it is related to the poor survival of CAC patients.

Materials And Methods: The mRNA and protein levels of PRSS3 were examined in CAC samples and connective noncancerous colon samples through quantitative real-time polymerase chain reaction assay and immunohistochemistry staining. Univariate and multivariate analyses were performed to estimate the prognostic role of PRSS3 in enrolled CAC patients.

Results: PRSS3 expression in CAC samples was significantly increased compared with connective noncancerous samples. Moreover, a higher level of PRSS3 was found to be correlated with the larger tumor size, advanced T stage, and positive lymph node metastasis. In addition, PRSS3 was also defined as an unfavorable prognosis factor for CAC patients.

Conclusions: High expression of PRSS3 was significantly related to the unfavorable clinical features and poor prognosis in CAC patients. It suggested that PRSS3 might serve as a novel prognostic indicator and potential drug target for CAC treatment.
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http://dx.doi.org/10.1097/PAI.0000000000000921DOI Listing
March 2021

Highly elevated levels, infant dietary exposure and health risks of medium-chain chlorinated paraffins in breast milk from China: Comparison with short-chain chlorinated paraffins.

Environ Pollut 2021 Jun 10;279:116922. Epub 2021 Mar 10.

State Key Laboratory of Environmental Chemistry and Ecotoxicology, Research Center for Eco-Environmental Sciences, Chinese Academy of Sciences, Beijing, 100085, China.

Short-chain chlorinated paraffins (SCCPs) are persistent organic pollutants which are toxic to human. Median-chain chlorinated paraffins (MCCPs) have similar toxicity to SCCPs. The productions of chlorinated paraffins (CPs) in China were 1 million tons in 2013 and remained high after that, which may lead to high risks for human exposure to CPs. To investigate temporal trends and health risks of SCCPs and MCCPs in breast milk in China, samples (n = 2020) were collected from urban and rural areas of 11 Chinese provinces in 2017 and mixed into 42 pooled samples. SCCPs and MCCPs were analyzed by two-dimensional gas chromatography with electron-capture negative-ionization mass spectrometry (GC × GC-ECNI-MS). The MCCP concentrations (median (range)) were 472 (94-1714) and 567 (211-1089) ng g lipid in urban and rural areas, respectively, which showed continuously rapidly increasing during 2007-2017. The SCCP concentrations (median (range)) were 393 (131-808) and 525 (139-1543) ng g lipid in urban and rural areas, respectively. The results showed SCCP levels decreased in urban areas between 2007 and 2017. Significant increases in MCCP/SCCP ratios might arise from extensive manufacturing and use of MCCPs. The median estimated dietary intake via breast milk in urban and rural samples were 1230 and 2510 ng kg d, respectively, for SCCPs and 2150 and 1890 ng kg d, respectively, for MCCPs. Preliminarily risk assessment showed that SCCPs posed a significant health risk to infants via breastfeeding. The high MCCP levels should also be of concern because of continuous growth and negative effect on infants. Correspondence analysis indicated congeners with higher carbon and chlorine numbers in dietary tend to accumulate in breast milk.
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http://dx.doi.org/10.1016/j.envpol.2021.116922DOI Listing
June 2021

[Levels and Risk Assessment of Short and Medium-Chain Chlorinated Paraffins in Soil from Paper Mill Area].

Huan Jing Ke Xue 2021 Mar;42(3):1131-1140

State Key Laboratory of Environmental Chemistry and Ecotoxicology, Research Center for Eco-Environmental Sciences, Chinese Academy of Sciences, Beijing 100085, China.

Short-chain chlorinated paraffins are persistent organic pollutants, and chlorinated paraffins were widely used as sizing agent in the paper industry. In order to investigate the levels and risk assessment of short-chain and medium-chain chlorinated paraffins in the paper mill plant, the surface soil and soil of different depths were collected.The concentrations, congener group profiles of short-chain chlorinated paraffins (SCCPs) and medium-chain chlorinated paraffins (MCCPs) in soil were determined by two-dimensional gas chromatography coupled with electron capture-negative ion mass spectrometry. The SCCPs and MCCPs concentrations were 42-3853 ng·g and 34-2091 ng·g. The chlorine contents were 59.9%-61.9% and 48.7%-52.8%. The concentrations of SCCPs and MCCPs were different in the soil collected in different sampling site. The concentration of SCCPs and MCCPs were relatively higher in soil of sewage treatment area and coating area. The CP levels in soil from the paper mill plant were at a high level compared with those in other regions. CCl and CCl were the main congener groups in most soil samples. The results of principal component analysis showed that the CP52 commercial products may be sources of SCCPs and MCCPs in the soil. The risk quotient (RQ) for SCCPs and MCCPs were assessed in soil of paper mill plant. The results showed that the RQ values for SCCPs in soil ranged from 0.01 to 0.73 which are the medium risk, and the RQ values for MCCPs in soil ranged from 0 to 0.07, which are the low risk. The human exposure values of children and adults are lower than TDI[10 μg·(kg·d)] in both cases. The health risks caused by non-dietary exposure under paper mill area are low.
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http://dx.doi.org/10.13227/j.hjkx.202011004DOI Listing
March 2021

Efficacy and safety of anti-PD-1-based therapy in combination with PARP inhibitors for patients with advanced solid tumors in a real-world setting.

Cancer Immunol Immunother 2021 Mar 19. Epub 2021 Mar 19.

Department of Medical Oncology, Chinese PLA General Hospital, Beijing, 100853, China.

Background: Rationale exists for combining immune checkpoint inhibitors and PARP inhibitors (PARPi), and results of clinical trials in ovarian cancer are promising, but data in other cancers are limited.

Method: Efficacy and safety of PARPi/anti-PD-1 in advanced solid tumors were retrospectively analyzed. The efficacy measures included objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS) and overall survival (OS).

Results: This retrospective study included data from 40 patients. The ORR was 27.5% (95% CI, 13.0-42.0%), with a DCR of 85.0% (95% CI, 73.4-96.6%). Except four patients in first-line treatment (three with PR and one with SD), the ORR of ≥second-line treatment, non-small cell lung cancer (NSCLC) and small cell lung cancer (SCLC) was 22.2%, 23.1% and 28.6%, and the DCR was 83.3%, 84.6% and 71.4%, separately. The median PFS of all patients, ≥second-line treatment, NSCLC and SCLC was 4.6 m, 4.2 m, 4.5 m and 3.7 m. The median OS was 9.4 m, 11.4 m, 12.7 m and 5.4 m, respectively. Multivariable analysis revealed that BRCA1/2 mutation was positively correlated with ORR (P = 0.008), and LDH≥250U/L was negatively correlated with lowered DCR (P = 0.018), while lymphocyte number, ECOG and LDH significantly influenced both PFS and OS. We found that the possible resistant mechanisms were sarcomatous degeneration and secondary mutation, including BRCA2 truncation mutation, A2M, JAK1,T790M, KEAP1 and mTOR mutation. 37.5% patients had ≥grade 3 adverse events.

Conclusion: PARPi/anti-PD-1 is an effective and tolerable method for patients with advanced solid tumors, and BRCA1/2 is a potential biomarker.
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http://dx.doi.org/10.1007/s00262-021-02852-4DOI Listing
March 2021

The Synergistic Effect of PARP Inhibitors and Immune Checkpoint Inhibitors.

Clin Med Insights Oncol 2021 25;15:1179554921996288. Epub 2021 Feb 25.

Department of Medical Oncology, Chinese PLA General Hospital, Beijing, China.

Poly (ADP-ribose) polymerase (PARP) inhibitors have demonstrated great promise for treating cancers with homologous recombination (HR) defects, such as germline BRCA1/2 mutation. Further studies suggest that PARP inhibitors (PARPi) can also exhibit efficacy in HR-competent cancers, by amplifying the DNA damage and inducing immunogenic cell death, and PARPi lead to increasing tumor neoantigen, upregulation of interferons and PD-L1, and modulation of the tumor microenvironment, which may facilitate a more profound antitumor immune response. Immune checkpoint inhibitors (ICIs) targeting PD-1/PD-L1 or CTLA-4 have achieved impressive success in the treatment of different malignancies. However, only a subset of populations derive clinical benefit, and the biomarkers and resistance mechanisms are not fully understood. Therefore, given that PARPi could potentiate the therapeutic effect of ICIs, PARPi combined with ICIs are becoming an alternative for patients who cannot benefit from ICI monotherapy. In this review, we focus on the mechanisms and immune role of PARPi and discuss the rationale and clinical studies of this combined regimen.
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http://dx.doi.org/10.1177/1179554921996288DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7934064PMC
February 2021