Publications by authors named "Tao Wang"

7,213 Publications

  • Page 1 of 1

Fermentation process optimization, chemical analysis, and storage stability evaluation of a probiotic barley malt kvass.

Bioprocess Biosyst Eng 2022 May 26. Epub 2022 May 26.

College of Food Science and Engineering, Northwest A&F University, Yangling, No. 22 Xinong Road, Yangling District, Xianyang, 712100, Shaanxi, China.

Kvass is a popular low-alcohol beverage produced by the natural fermentation of dark rye bread or malt with complex microbial flora. However, few pieces of research focus on the microflora of traditional bread kvass, and the industrial kvass based on malt concentrate has some disadvantages, including the lack of viable probiotics and containing multiple artificial additives. Therefore, in the present study, based on the different homemade traditional bread kvass, the predominant species including Lacticaseibacillus paracasei, Acetobacter pasteurianus, and Saccharomyces cerevisiae were screened and identified. In addition, barley malt was used instead of bread for kvass production, and the co-fermentation conditions with three different strains were optimized as wort concentration of 7.4°Brix, cell ratio of 2/2/1 (S. cerevisiae/L. paracasei/A. pasteurianus), inoculum amount of 8%, fermentation temperature of 29.5 °C and fermentation time of 24.6 h. Moreover, the physicochemical (pH, total soluble solids, color, and alcohol content) and probiotic (microorganisms counting and antioxidant activity) properties of the barley malt kvass prepared at optimal conditions were symmetrically evaluated. Besides, compared with the commercial kvass products, the produced barley malt kvass exhibited better taste and more desirable antioxidant activity, and also maintained around 6-7 log CFU/mL of viable probiotic microorganisms during a week of storage. The present study not only enriched the biological resource of the traditional kvass, but also promoted the development of the kvass as a live-bacteria beverage.
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http://dx.doi.org/10.1007/s00449-022-02734-8DOI Listing
May 2022

Traffic costs of air pollution: the effect of PM on traffic violation.

Environ Sci Pollut Res Int 2022 May 25. Epub 2022 May 25.

School of Economics and Management, Wuhan University, Wuhan, People's Republic of China.

Although emerging studies have investigated the effect of air pollution on traffic crashes, it is unclear to scholars whether air pollution affects another road safety problem-traffic violations. To address this gap, the current paper constructs a data set from 1,390,221 traffic violation records of 640,971 drivers from the Wuhan Traffic Management Bureau between January 2018 and December 2018. An ordered logistic regression was conducted to verify our hypotheses. The result shows that PM has no overall impact on the severity of traffic violations, but each 1% increase in the daily concentration of PM leads to a 1.02-fold increase in the odds of serious inexperience-related violations and a 0.99-fold decrease in the odds of serious overconfidence-related violations. This effect is the strongest in PM, followed by NO, and has not been observed in CO and O. In addition, robustness tests indicate that the relationship between air pollution and traffic violations is consistent among the different subsets (e.g., clear weather, no rain and snow, and good visibility). We also provide valuable practical advice for drivers and traffic authorities.
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http://dx.doi.org/10.1007/s11356-022-20790-1DOI Listing
May 2022

Enhancing or inhibiting apoptosis? The effects of ucMSC-Ex in the treatment of different degrees of traumatic pancreatitis.

Apoptosis 2022 May 25. Epub 2022 May 25.

General Surgery Center, General Hospital of Western Theater Command, No. 270, Rongdu Rd, Jinniu District, Chengdu, 610083, Sichuan, China.

The animal models of traumatic pancreatitis (TP) were established to evaluate the specific mechanisms by which umbilical cord mesenchymal stem cell-derived exosomes (ucMSC-Ex) exert therapeutic effects. Sixty four rats were randomly divided into eight groups, including TP groups with three different degrees and relevant groups with ucMSC-Ex treated. The degrees of pancreatic tissue injury were evaluated by Histological Examination. Furthermore, enzyme-linked immunosorbent assay were applied to evaluate the activity of pancreatic enzymes and levels of inflammatory factors in serum. Finally, the apoptotic effects of each group were evaluated by TUNEL, western blot (WB), and real time fluorescence quantitative polymerase chain reaction (RT-qPCR). The pancreatic histopathological score and serum amylase and lipase levels gradually increased in various degrees of TP and the levels in the treatment group were all significantly decreased. The apoptosis index gradually increased in each TP group and significantly decreased in the treatment group in TUNEL results. WB and RT-qPCR showed the same trend, that bax and caspase-3 gradually increased and bcl-2 gradually decreased in TP groups. Compared with TP groups, the expression of bax and caspase-3 were lower while bcl-2 expression was higher in the treatment group. ucMSC-Ex suppressed the inflammatory response and inhibited pancreatic acinar cell apoptosis to promote repair of injured pancreatic tissue.
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http://dx.doi.org/10.1007/s10495-022-01732-1DOI Listing
May 2022

Synthesis,  Antitumor of Sinomenine Derivatives and Apoptotic Induction via IL-6/PI3K/Akt/NF-κB Signaling Pathway in MCF-7 Cells.

ChemMedChem 2022 May 25. Epub 2022 May 25.

Guangzhou University of Chinese Medicine, School of Pharmaceutical Sciences, 510006, Guangzhou, CHINA.

Natural products have been widely considered as an important resource for new drugs or lead compounds. Sinomenine (SIN) and its derivatives exert antitumor activity via regulation of inflammatory mediators. For these reasons we synthesized three series of SIN derivatives (compounds 4a-i, 7a-c and 11a-c) as antitumor agents from this natural product. All compounds were prepared by the modification at the C1 and C4 positions of A ring, the C4 position of A ring and the C6 and C7 positions of C ring, respectively. All the derivatives were subjected to in vitro antitumor activity against HeLa, A549, HepG-2, MCF-7 and HT-29 cell lines. To observe the apoptotic induction of SIN derivatives and its mechanism, fluorescent staining and western bolt were carried out for active compound against MCF-7. Based on the screening results, most of SIN derivatives showed better antitumor activity than SIN. Some of them were found to possess broad spectrum antitumor activity. Most notably, 11c exhibited obvious antitumor activity in both cell lines with IC50 value less than 11 μM. Besides, 11c induced apoptosis of MCF-7 in a dose-dependent manner. Western blot assay demonstrated that 11c inhibited IL-6-mediated activation of PI3K/Akt pathway. A docking study revealed that 11c had stronger binding interaction with the residues of IL-6 than SIN. All these results indicate that 11c may be a potential anti-breast cancer agent by directly targeting IL-6.
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http://dx.doi.org/10.1002/cmdc.202200234DOI Listing
May 2022

Histone Methyltransferase SUVR2 Promotes the DSB Repair via Chromatin Remodeling and Liquid-Liquid Phase Separation.

Mol Plant 2022 May 23. Epub 2022 May 23.

State Key Laboratory of Agrobiotechnology, College of Biological Sciences, China Agricultural University, Beijing 100193, China. Electronic address:

Maintaining genomic integrity and stability is particularly important for stem cells, which are at the top of the cell lineage origin. Here, we discovered that the plant-specific histone methyltransferase SUVR2 maintains the integrity of the root tip stem cell genome through chromatin remodeling and liquid-liquid phase separation (LLPS) when facing DNA double-strand breaks (DSBs). MtSUVR2 has histone methyltransferase activity and catalyzes the conversion of H3K9me1 to H3K9me2/3 in vitro and in Medicago truncatula. Under DNA damage, the proportion of heterochromatin decreased, and the DSB damage marker γ-H2AX level increased in the suvr2 mutants, indicating that MtSUVR2 compacted the chromatin structure through H3K9 methylation modification to protect DNA from damage. More importantly, MtSUVR2 was induced by DSBs to phase separate and form droplets to localize at the damage sites, which was confirmed by immunofluorescence and fluorescence recovery after photobleaching (FRAP) experiments. The IDR1 and LCD regions of MtSUVR2 determined the phase separation in nuclei, while the IDR2 region determined the interaction with homologous recombinase MtRAD51. MtSUVR2 drove the phase separation of MtRAD51 to form "DNA repair bodies", which enhanced the stability of MtRAD51 proteins to facilitate the error-free homologous recombination (HR) repair of stem cells. This study reveals that chromatin remodeling-associated proteins participate in DNA repair through LLPS.
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http://dx.doi.org/10.1016/j.molp.2022.05.007DOI Listing
May 2022

Fudosteine attenuates acute lung injury in septic mice by inhibiting pyroptosis via the TXNIP/NLRP3/GSDMD pathway.

Eur J Pharmacol 2022 May 21:175047. Epub 2022 May 21.

Division of Pulmonary Diseases, State Key Laboratory of Biotherapy, and Department of Respiratory and Critical Care Medicine, West China Hospital of Sichuan University, Chengdu, China. Electronic address:

There is a dearth of effective pharmacotherapies for sepsis-induced acute lung injury/acute respiratory distress syndrome (ALI/ARDS) to which oxidative stress and excessive inflammation are major contributors. We hypothesized that fudosteine, a cysteine derivative, may protect against sepsis-induced ALI/ARDS given its anti-oxidant capacities. This study aimed to investigate the effects and mechanisms of fudosteine in a mouse model of sepsis-induced ALI. Sepsis was induced by cecal ligation and puncture (CLP). The intragastrical administration of fudosteine (25 mg/kg, 50 mg/kg, and 100 mg/kg) dose-dependently decreased proinflammatory cytokine levels in bronchoalveolar lavage fluid (BALF) and serum and reduced BALF/serum albumin and lung wet/dry weight ratios in septic mice. The lung injury score was significantly lowered by fudosteine [e.g., 0.18 ± 0.03 (100 mg/kg) vs. 0.42 ± 0.03 (CLP), P < 0.0001]. Fudosteine also reduced the biomarkers of lung epithelial injury in BALF and markedly improved oxidative stress indicators in lung tissues [e.g., malondialdehyde: 337.70 ± 23.78 (100 mg/kg) vs. 686.40 ± 28.36 (CLP) nmol/mg protein, P < 0.0001]. Lung tissue transcriptomics analyses revealed suppressed inflammatory responses and oxidative stress with fudosteine and the involvement of the inflammasome and pyroptosis pathways. Western blot analyses indicated that fudosteine inhibited the sepsis-induced activation of gasdermin D (GSDMD) and caspase-1 and the upregulation of thioredoxin-interacting protein (TXNIP), nucleotide-binding domain, leucine-rich repeat-containing receptor, pyrin domain-containing-3 (NLRP3), and apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC). Fudosteine therefore protects against sepsis-induced ALI in mice, and the inhibition of pyroptosis via the TXNIP/NLRP3/GSDMD pathway may be an underlying mechanism.
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http://dx.doi.org/10.1016/j.ejphar.2022.175047DOI Listing
May 2022

A core group of structurally similar HLA-DPB1 alleles drives permissiveness after hematopoietic cell transplantation.

Blood 2022 May 24. Epub 2022 May 24.

German Cancer Consortium (DKTK), partner site Essen/Düsseldorf, Germany.

Clinically tolerable, permissive HLA-DPB1 mismatches defined by the T-cell epitope (TCE) model improve the selection of unrelated donors in allogeneic hematopoietic cell transplantation (HCT). Mechanistically, overlapping immunopeptidomes in structurally close HLA-DP allotypes with similar peptide-binding motifs are fundamental for permissiveness in vitro, but their relevance in vivo is still unknown. Here, we hypothesized that a similarity measure reflecting the peptide-binding region of HLA-DPB1 alleles could constitute a proxy for immunopeptidome overlap and hence predict permissive mismatches in the clinical setting. To test this, we used multidimensional scaling techniques based on 28 polymorphic amino acid positions, resulting in the stratification of HLA-DPB1 alleles from the heterogeneous TCE group 3 (TCE3) into a subgroup of four frequent, structurally related, and less immunogenic "core" TCE3 alleles compared to the remaining "non-core" alleles. In a CIBMTR cohort of 5140 10/10-matched patients transplanted for AML, ALL, or MDS from 2008-2017, the risks of aGVHD II-IV increased progressively from "core" TCE3 permissive (N=930; HR 1.12 [0.98-1.28]; p=0.1012) to "non-core" TCE3-permissive (N=1286; HR 1.24 [1.06-1.46]; p= 0.0082), and non-permissive mismatches (N=2023; HR 1.32 [1.16-1.50]; p<.0001) compared to allele-matched patients (N=785). "Core" TCE3-permissive pairs (HR 0.78 [0.68-0.88]; p=0.0002), but not "non-core" TCE3-permissive pairs (HR 0.95 [0.83-1.09]; p=0.4578) showed significantly lower risks of TRM when compared to non-permissive pairs. Our results suggest that frequent mismatches between structurally similar "core" HLA-DPB1 alleles are the main drivers of permissiveness after HCT, and provide evidence for a role of immunopeptidome differences between mismatched HLA-DPB1 alleles in the clinical outcome of HCT.
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http://dx.doi.org/10.1182/blood.2022015708DOI Listing
May 2022

The role of selenium in severe fever with thrombocytopenia syndrome: an integrative analysis of surveillance data and clinical data.

Int J Infect Dis 2022 May 20. Epub 2022 May 20.

State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Beijing, P. R. China; Beijing Key Laboratory of Vector Borne and Natural Focus Infectious Diseases, Beijing 100071, P. R. China; Graduate School of Anhui Medical University, Hefei 230601, P.R. China. Electronic address:

Objectives: Selenium deficiency can be associated with increased susceptibility to some viral infections, and even severer disease. Here we aim to examine whether this associate applies to severe fever with thrombocytopenia syndrome (SFTS).

Method: An observational study was conducted based on the data of 13,305 human SFTS cases reported in the mainland of China from 2010 to 2020. The association between incidence, case fatality rate of SFTS and crop selenium concentration at the county level were explored. The selenium level in a cohort of SFTS patients was tested and its relationship with clinical outcomes was evaluated.

Results: The association between selenium-deficient in crops and incidence rate of SFTS was confirmed by multivariate Poisson analysis, with an estimated incidence rate ratio (IRR, 95% CI) of 4.549 (4.215-4.916) for moderate-selenium-deficient counties and 16.002 (14.706-17.431) for severe-selenium-deficient counties. In addition, a higher mortality rate was also observed from severe-selenium-deficient counties with IRR of 1.409 (95% CI: 1.061-1.909). Clinical study on 120 SFTS patients showed an association between serum selenium deficiency and severe SFTS (OR: 2.94; 95% CI: 1.00-8.67) or fatal SFTS (OR: 7.55; 95% CI: 1.14-50.16).

Conclusions: Selenium deficiency is associated with increased susceptibility to SFTS and poor clinical outcomes.
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http://dx.doi.org/10.1016/j.ijid.2022.05.042DOI Listing
May 2022

The pyrethroids metabolite 3-phenoxybenzoic acid induces dopaminergic degeneration.

Sci Total Environ 2022 May 20:156027. Epub 2022 May 20.

Department of Neurology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China. Electronic address:

Exposure to pyrethroids, a significant class of the most widely used agricultural chemicals, has been associated with an increased risk of Parkinson's disease (PD). However, although many different pyrethroids induce roughly the same symptoms of Parkinsonism, the underlying mechanisms remain unknown. To find the shared key features among these mechanisms, we focused on 3-phenoxybenzoic acid (3-PBA), a common and prominent metabolite of most pyrethroids produced via hydrolysis by CEs in mammals. To determine the contribution of 3-PBA to the initiation and progression of PD, we performed in vivo and in vitro experiments, respectively, and found that 3-PBA not only accumulates in murine brain tissues over time but also further induces PD-like pathologies (increased α-syn and phospho-S129, decreased TH) to the same or even greater extent than the precursor pyrethroid. A before-after study of PET-DAT in the same mice revealed that low concentrations of 3-PBA (0.5 mg/kg) could paradoxically cause DAT to increase (22.46% higher than pre-drug test). The intervention of DAT inhibitors and activators respectively alleviated and enhanced the dopaminergic toxicity of 3-PBA, indicating that 3-PBA interacts with DAT. In particular, low concentrations of 3-PBA increase the DAT, which in turn induces 3-PBA to enter the dopaminergic neurons to exert toxic effects. Finally, we described a mechanism underlying this potential role of 3-PBA in the pathological aggregation of α-syn. Specifically, 3-PBA was found to dysregulate C/EBP β levels and further anomalously activate AEP in vivo and in vitro, accompanied by increased accumulation of pathologically cleaved α-syn (N103 fragments) and accelerated α-syn aggregation. All these results suggest that 3-PBA exposure could mimic the pathological and pathogenetic features of PD, showing that this metabolite is a key pathogenic compound in pyrethroid-related pathological effects and a possible dopamine neurotoxin. Additionally, our findings provide a crucial reference for the primary prevention of PD.
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http://dx.doi.org/10.1016/j.scitotenv.2022.156027DOI Listing
May 2022

Metal-Organic Framework-Derived Graphene Mesh: a Robust Scaffold for Highly Exposed Fe-N Active Sites toward an Excellent Oxygen Reduction Catalyst in Acid Media.

J Am Chem Soc 2022 May 23. Epub 2022 May 23.

Kagami Memorial Institute for Materials Science and Engineering, Waseda University, Nishi-Waseda 2-8-26, Shinjuku-ku, Tokyo 169-0051, Japan.

This study demonstrates a special ultrathin N-doped graphene nanomesh (NGM) as a robust scaffold for highly exposed Fe-N active sites. Significantly, the pore sizes of the NGM can be elaborately regulated by adjusting the thermal exfoliation conditions to simultaneously disperse and anchor Fe-N moieties, ultimately leading to highly loaded Fe single-atom catalysts (SA-Fe-NGM) and a highly exposed morphology. The SA-Fe-NGM is found to deliver a superior oxygen reduction reaction (ORR) activity in acidic media (half-wave potential = 0.83 V RHE) and a high power density of 634 mW cm in the H/O fuel cell test. First-principles calculations further elucidate the possible catalytic mechanism for ORR based on the identified Fe-N active sites and the pore size distribution analysis. This work provides a novel strategy for constructing highly exposed transition metals and nitrogen co-doped carbon materials (M-N-C) catalysts for extended electrocatalytic and energy storage applications.
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http://dx.doi.org/10.1021/jacs.2c00719DOI Listing
May 2022

Financial Budgets of Technology-Based SMEs From the Perspective of Sustainability and Big Data.

Front Public Health 2022 4;10:861074. Epub 2022 May 4.

School of Business, Zhejiang University City College, Hangzhou, China.

In this contemporary world, the words data and sustainability play a crucial role in determining the financial budgets of small and medium-sized enterprises (SMEs). Usually, it is stated that the survival of small and medium-sized enterprises (SMEs) is directly proportional to the growth and sustainability factor of the nation. The economic sustainability of a nation is dependent on appropriate functioning of SMEs. Any kind of direct impact on the working of SMEs will have its impact on the whole economy of a nation. There are different factors such as lack of financial capacity, low market demands, restrictions with regard to the capital, and barriers in the supply chain that affect the sustainability of SMEs worldwide. Nevertheless, small, and medium sized enterprises around the world are greatly investing on skills, innovation, and other capital related resources to mark up the demands of the external market. The main objective of this study is to examine the financial budgets of technology-based SMEs from the perspective of sustainability and big data. For this, the study collects data through a questionnaire from 1,800 Small and Medium Sized Enterprises. Based on a detailed and careful examination of the data, only 1,400 of the responses received were considered valid (79.75%). To test the hypothesis stated, the study employs structural equation modeling. This will help the researcher to examine the direct effect of financial budget and technology adaption of SMEs from the perspective of sustainability and big data. Results of the study stated that SMEs sustainability and big data are directly and positively related to the financial budget planning of technology-based SMEs. The study also found that big data plays an important role in the businesses, specifically for their own growth.
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http://dx.doi.org/10.3389/fpubh.2022.861074DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9116573PMC
May 2022

ZKSCAN5 Activates Expression by Recruiting SETD7 to Promote the Lymphangiogenesis, Tumour Growth, and Metastasis of Breast Cancer.

Front Oncol 2022 5;12:875033. Epub 2022 May 5.

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

The growth of lymphatic vessels (lymphangiogenesis) plays a pivotal role in breast cancer progression and metastasis and the immune response. Vascular endothelial growth factor C (VEGFC) has been demonstrated to accelerate cancer metastasis and modulate the immune system by enhancing lymphangiogenesis. However, it remains largely unclear how transcription factors physically regulate VEGFC expression by interacting with histone-modifying enzymes. Like many histone-modifying enzymes, SETD7 plays a key role in cell proliferation and inhibits tumour cell differentiation. In this study, we identified the role of the transcription factor zinc finger with KRAB and SCAN domains 5 (ZKSCAN5) in interacting with histone methyltransferase SETD7 and mediating VEGFC transcription and tumour lymphangiogenesis. ZKSCAN5 interacts with and recruits SETD7 to the VEGFC promoter. By regulating breast cancer-secreted VEGFC, ZKSCAN5 could induce the tube formation of lymph endothelial cells, which promotes tumour proliferation, migration, and metastasis. Clinically, the expression of ZKSCAN5 was frequently upregulated in patients with breast cancer and positively correlated with the expression of VEGFC and the number of lymphatic microvessels. ZKSCAN5 is a poor prognostic factor for patients with breast cancer. Our results characterise the role of ZKSCAN5 in regulating VEGFC transcription and predict ZKSCAN5 as a breast cancer therapeutic target.
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http://dx.doi.org/10.3389/fonc.2022.875033DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9117617PMC
May 2022

Hydrophilic Realgar Nanocrystals Prolong the Survival of Refractory Acute Myeloid Leukemia Mice Through Inducing Multi-Lineage Differentiation and Apoptosis.

Int J Nanomedicine 2022 16;17:2191-2202. Epub 2022 May 16.

Department of Biomedical Engineering, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, 100005, People's Republic of China.

Introduction: Acute myeloid leukemia (AML) is a heterogeneous clonal disorder of hematopoietic progenitor cells, and the AML cells are differentiation retarded which results in the hyperproliferation of those malignant tumor cells. To stop the uncontrollable proliferation, inducing the AML cell differentiation is one highly expected therapy because it can bring relatively low systematic side effects compared to conventional chemotherapies; however, there are few options of inductive therapeutics in the clinical applications so far. This study aims to investigate the differentiation-induction effects of lab-developed hydrophilic nanocrystals of AsS (ee-AsS).

Methods: In this work, ee-AsS was applied upon a refractory mouse model co-expressing AML1-ETO and HyC-KIT as well as a related human AML cell line, Kasumi-1, to investigate whether the nanocrystals can break the retardation of differentiation and drive the cells undergo apoptosis.

Results: It was shown that ee-AsS induced the upregulation of surface markers CD11b, CD235a, and CD41a, which indicate granulocytic, erythroid, and megakaryocytic differentiation respectively, leading to the multiple-lineage differentiation and post-differentiation apoptosis, and the inhibition of histone deacetylase activity was largely involved with the differentiation-induction effects. In the AML mice, orally administered ee-AsS increased the level of Ter119, CD11b, and CD41 in bone marrow-derived leukemia cells while reducing the percentage of leukemic cells in the bone marrow. Also, ee-AsS improved the hemogram and relieved the hepatomegaly and splenomegaly of the AML mice. As a result, the survival of the AML mice was significantly prolonged. Importantly, ee-AsS did not cause acute or chronic toxicity in healthy mice.

Conclusion: In conclusion, ee-AsS induced effective and multiple-lineage differentiation and apoptosis of AML cells in the refractory AML mouse model and cell line, suggesting that it holds promising potential as a novel inductive agent in differentiation therapy of AML.
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http://dx.doi.org/10.2147/IJN.S358469DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9122054PMC
May 2022

Mendelian randomization highlights causal association between genetically increased C-reactive protein levels and reduced Alzheimer's disease risk.

Alzheimers Dement 2022 May 22. Epub 2022 May 22.

Beijing Institute of Brain Disorders, Laboratory of Brain Disorders, Ministry of Science and Technology, Collaborative Innovation Center for Brain Disorders, Capital Medical University, Beijing, China.

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http://dx.doi.org/10.1002/alz.12687DOI Listing
May 2022

A Small Molecule Selected from a DNA-Encoded Library of Natural Products That Binds to TNF-α and Attenuates Inflammation In Vivo.

Adv Sci (Weinh) 2022 May 21:e2201258. Epub 2022 May 21.

Shanghai Institute for Advanced Immunochemical Studies, ShanghaiTech University, Shanghai, 201210, P. R. China.

Tumor necrosis factor α (TNF-α) inhibitors have shown great success in the treatment of autoimmune diseases. However, to date, approved drugs targeting TNF-α are restricted to biological macromolecules, largely due to the difficulties in using small molecules for pharmaceutical intervention of protein-protein interactions. Herein the power of a natural product-enriched DNA-encoded library (nDEL) is exploited to identify small molecules that interfere with the protein-protein interaction between TNF-α and the cognate receptor. Initially, to select molecules capable of binding to TNF-α , "late-stage" DNA modification method is applied to construct an nDEL library consisted of 400 sterically diverse natural products and pharmaceutically active chemicals. Several natural products, including kaempferol, identified not only show direct interaction with TNF-α, but also lead to the blockage of TNF-α/TNFR1 interaction. Significantly, kaempferol attenuates the TNF-α signaling in cells and reduces the 12-O-tetradecanoylphorbol-13-acetateinduced ear inflammation in mice. Structure-activity-relationship analyses demonstrate the importance of substitution groups at C-3, C-7, and C-4' of kaempferol. The nDEL hit, kaempferol, represents a novel chemical scaffold capable of specifically recognizing TNF-α and blocking its signal transduction, a promising starting point for the development of a small molecule TNF-α inhibitor for use in the clinical setting.
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http://dx.doi.org/10.1002/advs.202201258DOI Listing
May 2022

Increased versus standard gonadotrophin dosing in predicted poor responders of IVF: an open-label randomized controlled trial.

Hum Reprod 2022 May 20. Epub 2022 May 20.

The Assisted Reproduction Center, Northwest Women's and Children's Hospital, Xi'an, Shaanxi Province, China.

Study Question: Does an increased dosing of FSH improve the live birth rate as compared to standard FSH dosing in expected poor responders who undergo IVF?

Summary Answer: In this trial, women with an expected poor response allocated to increased FSH dosing did not have a statistically significant increase in cumulative live births as compared to a standard FSH dose.

What Is Known Already: Poor ovarian reserve leads to worse IVF outcomes owing to the low number and quality of oocytes. Clinicians often individualize the FSH dose using ovarian reserve tests, including antral follicle count (AFC), and basal plasma FSH or anti-Müllerian hormone level. However, the evidence that increased FSH dosing improves fertility outcomes in women with an expected poor response is lacking.

Study Design, Size, Duration: We performed a parallel, open-label randomized controlled trial between March 2019 and October 2021 in an assisted reproduction centre.

Participants/materials, Setting, Methods: Women <43 years of age with AFC <10 referred for their first IVF cycle were randomized for increased or standard FSH dosing. In participants allocated to increased FSH dosing, women with AFC 1-6 started with 300 IU/day, while women with AFC 7-9 started with 225 IU/day. In participants allocated to the standard care, women started with 150 IU/day. The primary outcome was cumulative live birth attributable to the first IVF cycle including fresh and subsequent frozen-thawed cycles within 18 months of randomization. Live birth was defined as the delivery of one or more living infants ≥24 weeks' gestation. This trial was powered to detect an 11% difference in live birth attributable to the first IVF cycle. Outcomes were evaluated from an intention-to-treat perspective.

Main Results And The Role Of Chance: We randomized 661 women to start FSH at increased dosing (n = 328) or standard dosing (n = 333). The primary outcome cumulative live birth occurred in 162/328 (49.4%) women in the increased group versus 141/333 (42.3%) women in the standard group [risk ratio (RR) 1.17 (95% CI, 0.99-1.38), risk difference 0.07 (95% CI, -0.005, 0.15), P = 0.070]. The live birth rate after the first embryo transfer in the increased versus standard group was 125/328 (38.1%) versus 117/333 (35.1%), respectively [RR 1.08 (95% CI, 0.83-1.33), P = 0.428]. Cumulative clinical pregnancy rates were 59.1% versus 57.1% [RR 1.04 (95% CI, 0.91-1.18), P = 0.586] with miscarriage rates of 9.8% versus 14.4% [RR 0.68 (95% CI, 0.44-1.03), P = 0.069] in the increased versus standard group, respectively. Other secondary outcomes, including biochemical pregnancy, ongoing pregnancy, multiple pregnancy and ectopic pregnancy, were not significantly different between the two groups both from the first and cumulative embryo transfer.

Limitations, Reasons For Caution: As this study is open-label, potential selective cancelling and small dose adjustments could have influenced the results.

Wider Implications Of The Findings: In women with predicted poor response, we did not find evidence that increased FSH dosing improves live birth rates. A standard dose of 150 IU/day is recommended at the start of IVF in these women to reduce potential adverse effects and costs.

Study Funding/competing Interest(s): This study was funded by the General Projects of Social Development in Shaanxi Province (No. 2022SF-565). B.W.M. is supported by NHMRC (GNT1176437). B.W.M. reports personal fees from ObsEva, and funding from Merck and Ferring outside the submitted work.

Trial Registration Number: Registered at Chinese clinical trial registry (www.chictr.org.cn). Registration number ChiCTR1900021944.

Trial Registration Date: 17 March 2019.

Date Of First Patient’s Enrolment: 20 March 2019.
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http://dx.doi.org/10.1093/humrep/deac113DOI Listing
May 2022

Tislelizumab combined with chemotherapy as neoadjuvant therapy for surgically resectable esophageal cancer: A prospective, single-arm, phase II study (TD-NICE).

Int J Surg 2022 May 17:106680. Epub 2022 May 17.

Department of Thoracic Surgery, Tangdu Hospital, Air Force Military Medical University, No.1. Xinsi Road, Xi'an, Shaanxi, China. Electronic address:

Background: Clinical benefit of neoadjuvant immunotherapy in resectable esophageal squamous cell carcinoma (ESCC). remains unclear. This study evaluated the efficacy and safety of the programmed death 1 (PD-1) inhibitor tislelizumab combined with chemotherapy as neoadjuvant therapy in patients with resectable ESCC.

Methods: Treatment-naïve patients were enrolled and eligible patients received 3 cycles of neoadjuvant therapy with tislelizumab, carboplatin, and nab-paclitaxel. The primary endpoint was surgery patients major pathological response (MPR). Subgroup analysis was stratified by tumor downstaging, circumferential resection margin (CRM), PD-ligand 1 (PD-L1) expression, and tumor mutation burden (TMB). Safety was assessed by adverse events (AEs) and postoperative complications.

Results: Between September 2020 and March 2021, 45 patients were enrolled. Thirty-six (80.0%) of 45 patients underwent surgery, and 29 (80.5%) underwent successful R0 resection. MPR and pathological complete response (pCR) for surgery patients were 72.0% and 50.0%, respectively. Intention to treatment (ITT) patients MPR and PCR were 57.5% and 40%. Downgrading occurred in 75% of 36 patients. MPR and pCR were identified to be associated with tumor downstaging and CRM but not PD-L1 expression or TMB. TPS levels in MPR and pCR group were significantly higher than that in Non-MPR and Non-pCR group, respectively. Treatment-related AEs of grade 3-4 and immune-related AEs occurred in 42.2% and 22.2% of 45 patients, respectively, and postoperative complications occurred in 77.8% of 36 patients. No treatment-related surgical delay or death occurred. No associations between gene mutation and pathological efficacy were observed.

Conclusions: Tislelizumab plus chemotherapy as neoadjuvant therapy demonstrates promising antitumor activity for resectable ESCC with high rates of MPR, pCR, and R0 resection, as well as acceptable tolerability.
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http://dx.doi.org/10.1016/j.ijsu.2022.106680DOI Listing
May 2022

High CO-Tolerant Ru-Based Catalysts by Constructing an Oxide Blocking Layer.

J Am Chem Soc 2022 May 20. Epub 2022 May 20.

Collaborative Innovation Center of Chemistry for Energy Materials, State Key Laboratory of Physical Chemistry of Solid Surfaces, Tan Kah Kee Innovation Laboratory, College of Chemistry and Chemical Engineering, Xiamen University, Xiamen 361005, PR China.

CO poisoning of Pt-group metal catalysts is a long-standing problem, particularly for hydrogen oxidation reaction in proton exchange membrane fuel cells. Here, we report a catalyst of Ru oxide-coated Ru supported on TiO ([email protected]/TiO), which can tolerate 1-3% CO, enhanced by about 2 orders of magnitude over the classic PtRu/C catalyst, for hydrogen electrooxidation in a rotating disk electrode test. This catalyst can work stably in 1% CO/H for 50 h. About 20% of active sites can survive even in a pure CO environment. The high CO tolerance is not via a traditional bifunctional mechanism, i.e., oxide promoting CO oxidation, but rather via hydrous metal oxide shell blocking CO adsorption. An ab initio molecular dynamics (AIMD) simulation indicates that water confined in grain boundaries of the Ru oxide layer and Ru surface can suppress the diffusion and adsorption of CO. This oxide blocking layer approach opens a promising avenue for the design of high CO-tolerant electrocatalysts for fuel cells.
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http://dx.doi.org/10.1021/jacs.2c00602DOI Listing
May 2022

Maternal serum CFHR4 protein as a potential non-invasive marker of ventricular septal defects in offspring: evidence from a comparative proteomics study.

Clin Proteomics 2022 May 19;19(1):17. Epub 2022 May 19.

The Joint Laboratory for Lung Development and Related Diseases of West China Second University Hospital, Sichuan University and School of Life Sciences of Fudan University, West China Institute of Women and Children's Health, West China Second University Hospital, Sichuan University, Chengdu, China.

Background: Despite advances in diagnosis of congenital heart defects, there is no non-invasive biomarker clinically available for the early detection of fetal ventricular septal defects (VSD).

Methods: This study was to profile differentially expressed proteins (DEP) in the first trimester maternal plasma samples that were collected in the 12th-14th week of gestation and identify potential biomarkers for VSD. Maternal plasma samples of ten case-control pairs of women (who had given birth to an isolated VSD infant or not) were selected from a birth cohort biospecimen bank for identifying DEPs by using high-performance liquid chromatography-tandem mass spectrometry-based comparative proteomics.

Results: There were 35 proteins with significantly different levels between cases and controls, including 9 upregulated and 26 downregulated proteins. With Gene Ontology, Kyoto Encyclopedia of Genes and Genomes pathway enrichment, and protein-protein interaction analyses, most of the DEPs were clustered in pathways related to B cell-mediated immune responses, complement activation, and phagocytosis. Three DEPs were validated using enzyme-linked immunosorbent assay in another set of samples consisting of 31 cases and 33 controls. And CFHR4, a key regulator in complement cascades, was found to be significantly upregulated in cases as compared to controls.

Conclusions: Subsequent logistic regression and receiver operating characteristic analysis suggested maternal serum CFHR4 as a promising biomarker of fetal VSD. Further studies are warranted to verify the findings.
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http://dx.doi.org/10.1186/s12014-022-09356-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9117979PMC
May 2022

Defect-Regulated Frustrated-Lewis-Pair Behavior of Boron Nitride in Ambient Pressure Hydrogen Activation.

J Am Chem Soc 2022 May 19. Epub 2022 May 19.

Department of Chemistry, Institute for Advanced Materials and Manufacturing, University of Tennessee, Knoxville, Tennessee 37996, United States.

The construction of heterogeneous frustrated Lewis pairs (FLPs) with performance comparable to or surpassing the homogeneous counterparts in H activation is a long-standing challenge. Herein, sterically hindered Lewis acid ("B" center) and Lewis base ("N" center) sites were anchored within the rigid lattice of highly crystalline hexagonal boron nitride (h-BN) scaffolds. The active sites were created via precision defect regulation during the molten-salt-involved (NaNH and NaBH) h-BN construction procedure. The as-afforded h-BN scaffolds achieved highly efficient H/D activation and dissociation under ambient pressure via FLP-like behavior, and attractive catalytic efficiency in hydrogenation reactions surpassing the current heterogeneous analogues.
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http://dx.doi.org/10.1021/jacs.2c00343DOI Listing
May 2022

Controversial molecular functions of CBS versus non-CBS domain variants of PRKAG2 in arrhythmia and cardiomyopathy: A case report and literature review.

Mol Genet Genomic Med 2022 May 19:e1962. Epub 2022 May 19.

Key Laboratory of Birth Defects and Related Diseases of Women and Children of MOE, Department of Pediatrics, West China Second University Hospital, Sichuan University, Chengdu, China.

Background: PRKAG2 cardiac syndrome is a rare autosomal dominant genetic disorder caused by a PRKAG2 gene variant. There are several major adverse cardiac presentations, including hypertrophic cardiomyopathy (HCM) and life-threatening arrhythmia. Two cases with pathogenic variants in the PRKAG2 gene are reported here who presents different cardiac phenotypes.

Methods: Exome sequencing and variant analysis of PRKAG2 were performed to obtain genetic data, and clinical characteristics were determined.

Results: The first proband was a 9-month-old female infant (Case 1), and was identified with severe DCM and resistant heart failure. The second proband was a 10-year-old female infant (Case 2), and presented with HCM and ventricular preexcitation. Exome sequencing identified a de novo c.425C > T (p.T142I) heterozygous variant in the PRKAG2 gene for Case 1, and a c.869A > T (p.K290I) for Case 2. The mutated sites in the protein were labeled and identified as p.K290 in the CBS domain and p.T142 in the non-CBS domain. Differences in the molecular functions of CBS and non-CBS domains have not been resolved, and variants might lead to the different cardiomyopathy phenotypes. Single-cell RNA analysis demonstrated similar expression levels of PRKAG2 in cardiomyocytes and conductive tissues. These results suggest that the arrhythmia induced by the PRKAG2 variant was the primary change, and not secondary to cardiomyopathy.

Conclusion: In summary, this is the first case report to describe a DCM phenotype with early onset in patients possessing a PRKAG2 c.425C > T (p.T142I) pathogenic variant. Our results aid in understanding the molecular function of non-CBS variants in terms of the disordered sequence of transcripts. Moreover, we used scRNA-seq to show that electrically conductive cells express a higher level of PRKAG2 than do cardiomyocytes. Therefore, variants in PRKAG2 are expected to also alter the biological function of the conduction system.
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http://dx.doi.org/10.1002/mgg3.1962DOI Listing
May 2022

Improving HfO-Based Resistive Switching Devices by Inserting a TaO Thin Film via Engineered In Situ Oxidation.

ACS Appl Mater Interfaces 2022 May 18. Epub 2022 May 18.

King Abdullah University of Science and Technology (KAUST), Thuwal 23955-6900, Saudi Arabia.

Resistive switching (RS) devices with binary and analogue operation are expected to play a key role in the hardware implementation of artificial neural networks. However, state of the art RS devices based on binary oxides (e.g., HfO) still do not exhibit enough competitive performance. In particular, variability and yield still need to be improved to fit industrial requirements. In this study, we fabricate RS devices based on a TaO/HfO bilayer stack, using a novel methodology that consists of the in situ oxidation of a Ta film inside the atomic layer deposition (ALD) chamber in which the HfO film is deposited. By means of X-ray reflectivity (XRR) and time-of-flight secondary ion mass spectrometry (ToF-SIMS), we realized that the TaO film shows a substoichiometric structure, and that the TaO/HfO bilayer stack holds a well-layered structure. An exhaustive electrical characterization of the TaO/HfO-based RS devices shows improved switching performance compared to the single-layer HfO counterparts. The main advantages are higher forming yield, self-compliant switching, lower switching variability, enhanced reliability, and better synaptic plasticity.
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http://dx.doi.org/10.1021/acsami.2c03364DOI Listing
May 2022

Role of microbial metabolites of histidine in the development of colitis.

Mol Nutr Food Res 2022 May 18:e2101175. Epub 2022 May 18.

State Key Laboratory of Component-based Chinese Medicine, Tianjin University of Traditional Chinese Medicine. 10 Poyanghu Road, Jinghai District, Tianjin, 301617, China.

Scope: Colitis is a chronic relapsing inflammatory disease of colon. Clinical studies show that meat-rich diet plays a critical role in the relapse of colitis. However, it is unclear whether the microbial metabolites of histidine, which is an amino acid widely found in meat, have an impact on the health of the intestine.

Methods And Results: Six metabolites of histidine were given to IEC-6 cells. The cell activity measurement shows that imidazole propionate (IMP) is the most detrimental metabolite to the viability of IEC-6 cells. To further investigate the effects of IMP on intestinal physiology in vivo, we injected IMP to mice by rectal administration, with blood and colon tissues collected for the measurement of intestinal barrier related parameters, inflammatory cytokines, and expression of miRNAs. The results show that treatment with IMP significantly increased NF-κB, iNOS, and IL-6 levels, decreased number of goblet cell, and inhibited expressions of miR-146b. However, overexpression of miR-146b in mice rescued the decline of the physical condition and destruction of intestinal mucosa. Additionally, Notch1 was identified as a target gene of miR-146b. Further analysis shows that miR-146b restored the abundance of goblet cells by regulating Notch1 signaling pathway.

Conclusion: IMP was able to induce intestinal inflammation, impair the intestinal barrier and affect the proliferation of goblet cells. The underlined mechanism may partially contribute to the dysregulation of miR-146b/Notch1 axis. This article is protected by copyright. All rights reserved.
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http://dx.doi.org/10.1002/mnfr.202101175DOI Listing
May 2022

Percutaneous transluminal angioplasty and stenting for vertebral artery stenosis.

Cochrane Database Syst Rev 2022 05 17;5:CD013692. Epub 2022 May 17.

Department of Neurosurgery, Xuanwu Hospital, Capital Medical University, Beijing, China.

Background: Vertebral artery stenosis (narrowing of the vertebral artery) is an important cause of posterior circulation ischaemic stroke. Medical treatment (MT) e.g. controlling risk-factors and drug treatment, surgery, and endovascular treatment (ET) are the prevailing treatment strategies for symptomatic vertebral artery stenosis. ET consist s of percutaneous transluminal angioplasty (balloon catheter through the skin), with or without stenting. However, optimal management of people with symptomatic vertebral artery stenosis has not yet been established.

Objectives: To assess the safety and efficacy of percutaneous transluminal angioplasty, with or without stenting, combined with MT, compared to MT alone, in people with episodes of cerebral ischaemia due to vertebral artery stenosis.

Search Methods: We searched the Cochrane Stroke Group, MEDLINE, Embase, BIOSIS, and two other indexes in Web of Science, China Biological Medicine Database, Chinese Science and Technique Journals Database, China National Knowledge Infrastructure and Wanfang Data, as well as ClinicalTrials.gov trials register and the World Health Organization (WHO) International Clinical Trials Registry Platform to 23 July 2021.

Selection Criteria: We included all randomised controlled trials (RCTs) that compared ET plus MT with MT alone in treating people aged 18 years or over with symptomatic vertebral artery stenosis. We included all types of ET modalities (e.g. angioplasty alone, balloon-mounted stenting, and angioplasty followed by placement of a self-expanding stent). MT included risk factor control, antiplatelet therapy, lipid-lowering therapy, and individualised management for people with hypertension or diabetes.

Data Collection And Analysis: Two review authors independently screened potentially eligible studies, extracted data, and assessed trial quality and risk of bias.  We applied the GRADE approach to assess the certainty of evidence. The primary outcomes were 30-day post-randomisation death/stroke (short-term outcome) and fatal/non-fatal stroke after 30 days post-randomisation to completion of follow-up (long-term outcome).  MAIN RESULTS: We included three RCTs with 349 participants with symptomatic vertebral artery stenosis with a mean age of 64.4 years. The included RCTs were at low risk of bias overall. However, all included studies had a high risk of performance bias because blinding of the ET was not feasible. There was no significant difference in 30-day post-randomisation deaths/strokes between ET plus MT and MT alone (risk ratio (RR) 2.33, 95% confidence interval (CI) 0.77 to 7.07; 3 studies, 349 participants; low-certainty evidence). There were no significant differences between ET plus MT and MT alone in fatal/non-fatal strokes in the territory of the treated vertebral artery stenosis after 30 days post-randomisation to completion of follow-up (RR 0.51, 95% CI 0.26 to 1.01; 3 studies, 349 participants; moderate-certainty evidence), ischaemic or haemorrhagic stroke during the entire follow-up period (RR 0.77, 95% CI 0.44 to 1.32; 3 studies, 349 participants; moderate-certainty evidence), death during the entire follow-up period (RR 0.78, 95% CI 0.37 to 1.62; 3 studies, 349 participants; low-certainty evidence), and stroke or transient ischaemic attack (TIA) during the entire follow-up period (RR 0.65, 95% CI 0.39 to 1.06; 2 studies, 234 participants; moderate-certainty evidence).

Authors' Conclusions: This Cochrane Review provides low- to moderate-certainty evidence indicating that there are no significant differences in either short- or long-term risks of stroke, death, or TIA between people with symptomatic vertebral artery stenosis treated with ET plus MT and those treated with MT alone.
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http://dx.doi.org/10.1002/14651858.CD013692.pub2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9112859PMC
May 2022

Role of endoscopic ultrasound and endoscopic resection in the diagnosis and treatment of esophageal granular cell tumors.

Scand J Gastroenterol 2022 May 16:1-8. Epub 2022 May 16.

Department of Gastroenterology and Hepatology, General Hospital, Tianjin Medical University, Tianjin, China.

Background And Aim: Diagnosis and complete resection of esophageal granular cell tumors (GCTs) is an area of concern. However, articles on endoscopic ultrasound (EUS) and endoscopic resection of esophageal granular cell tumors are few. To evaluate the role of endoscopic ultrasound and endoscopic resection in the diagnosis and treatment of esophageal granular cell tumors.

Methods: A retrospective analysis of 15 patients with esophageal granular cell tumors who underwent endoscopic ultrasound examination and endoscopic resection in our hospital was conducted. The clinical data, endoscopic ultrasound images, endoscopic treatment, pathological characteristics, postoperative complications and follow-up status of all patients were evaluated. Ten board-certified endoscopists independently evaluated the white light endoscopic images of the 15 patients (Test 1) and the endoscopic ultrasound images together with white light endoscopic images of the same patient set (Test 2).

Result: Female patients accounted for 53.4% of the participants. The average age at the time of diagnosis was 49.13 ± 9.31 years old. Ten lesions (66.67%) showed hypoechoic signal, four lesions (26.67%) showed hyperechoic signal and one lesion showed medium signal. The diagnostic accuracy was significantly higher with Test 2(65.3% vs. 92.0%, < .001). Complete endoscopic resection was performed in all the patients. No complications occurred in any of the patients. No esophageal stenosis, recurrence, or metastases was found in all patients during the follow-up period.

Conclusion: The endoscopic ultrasound images of esophageal granular cell tumors have certain characteristics that help diagnose esophageal granular cell tumors. Endoscopic resection of esophageal granular cell tumors is an effective, safe and feasible treatment method.
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http://dx.doi.org/10.1080/00365521.2022.2067784DOI Listing
May 2022

Analysis of clinical efficacy of intraperitoneal chemotherapy with lobaplatin for colorectal cancer.

Minerva Surg 2022 May 16. Epub 2022 May 16.

Department of Gastrointestinal Surgery, Tianjin Hospital of Integrated Traditional Chinese and Western Medicine, Tianjin, China -

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http://dx.doi.org/10.23736/S2724-5691.22.09583-1DOI Listing
May 2022

Prognostic Relevance of Estrogen Receptor Status in Circulating Tumor Cells in Breast Cancer Patients Treated With Endocrine Therapy.

Front Oncol 2022 28;12:866293. Epub 2022 Apr 28.

Breast Cancer Department, The Fifth Medical Center of PLA General Hospital, Beijing, China.

Recently, female breast cancer (BC) has surpassed lung cancer to occupy the first place of the most commonly diagnosed cancer. The unsatisfactory prognosis of endocrine therapy for breast cancer might be attributed to the discordance in estrogen receptor (ER) status between primary tumors and corresponding metastases, as well as temporal and spatial receptor status heterogeneity at point-in-time between biopsy and treatment. The purpose of this study was to evaluate the prognostic and predictive value of ER status in circulating tumor cells (CTCs) in BC patients. We analyzed ER expression on CTCs isolated using the [email protected] method in 2.0 ml of blood samples from 70 patients with BC and 67 female controls. The predictive and prognostic value of ER expression in CTCs and immunohistochemistry results of biopsies for progression-free survival (PFS) and overall survival (OS) of patients in response to therapies were assessed. The detection rate for CTCs was 95.71% (67/70 patients), with a median of 8 CTCs within 2 ml of peripheral venous blood (PVB). A concordance of 76.56% in ER status between CTCs and corresponding primary tumor and 69.23% between CTCs and corresponding metastases was observed. We also found that patients with ER-positive CTCs (CTC ) had longer PFS and OS than those without ER-positive CTCs (CTC ). Our findings suggested that ER status in CTCs of BC patients may provide valuable predictive and prognostic insights into endocrine therapies, although further evaluation in larger prospective trials is required.
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http://dx.doi.org/10.3389/fonc.2022.866293DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9097586PMC
April 2022

Efficacy and Safety of Recombinant Human Adenovirus Type 5 (H101) in Persistent, Recurrent, or Metastatic Gynecologic Malignancies: A Retrospective Study.

Front Oncol 2022 28;12:877155. Epub 2022 Apr 28.

Department of Radiation Oncology, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China.

Background: To assess the efficacy and safety of recombinant human adenovirus type 5 (H101) in patients with persistent, recurrent, or metastatic gynecologic malignancies.

Methods: The study retrospectively enrolled patients with persistent/recurrent/metastatic gynecologic malignancies who received H101-containing treatment at The First Affiliated Hospital of Xi'an Jiaotong University from September 1, 2019 to September 30, 2021. H101 was injected intratumorally into target lesions and dosage was calculated based on tumor diameter once a day for five consecutive days. The primary endpoint was local control (LC) rate. Secondary endpoints included objective response rate (ORR), duration of response (DOR) and progression-free survival (PFS). Safety was the exploratory endpoint. Depending on prior treatment, patients received H101 either as monotherapy or as a combination therapy.

Results: Totally, 29 patients were enrolled in the study. Median follow-up was 6.3 months (range: 3.2-27.9) from data analysis cut-off on December 31, 2021. The LC rate at 3 months was 44.8%, while ORR was 72.4%. Median DOR and PFS rates were not determined. The DOR rate, PFS rate at 6 and 12 months were 88.1%, 74.6% and 70.5%, 62.2%, respectively. Responses were observed in all four cancer types. Most treatment-related adverse events (90.5%) were grade 1 or 2, with the most common being fever (70%). Clinically significant adverse events were uncommon (7.9% in grade 3 and 1.6% in grade 4). No treatment-related deaths occurred.

Conclusion: Our study showed that H101 (either monotherapy or combination therapy) has promising efficacy and favorable safety in patients with persistent, recurrent, metastatic gynecologic malignancies.
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http://dx.doi.org/10.3389/fonc.2022.877155DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9095970PMC
April 2022

Diagnostic test of bioimpedance-based neural network algorithm in early cervical cancer.

Ann Transl Med 2022 Apr;10(8):471

Division of Gynecology, West China Second Hospital, Sichuan University, Chengdu, China.

Background: Colposcopy is a critical component of cervical cancer screening services, but the accuracy of colposcopy varies greatly due to the lack of standardized training for colposcopists and pathologists. Thus, to improve the accuracy of colposcopy in the detection of cervical lesions intelligently is urgent. Here, we explored the sensitivity and specificity of a bioimpedance-based neural network algorithm in distinguishing normal and precancerous cervical tissues.

Methods: Bioimpedance data were collected using a bioimpedance analyzer (Mscan1.0B, Sealand Technology, Chengdu, China) from the cervices of 102 female patients with abnormal cervical cytology (≥atypical squamous cells of undetermined significance) who required further colposcopy. Finally, the data of 106 samples from 37 patients were included, among which 85were used as the training set and 21 as the validation set. Using the biopsy pathology at each locus as the gold standard, the sensitivity, specificity, predictive value, likelihood ratio, and false positive and false negative rates of the bioimpedance-based neural network in identifying the normal and precancerous cervical tissues were calculated.

Results: The bioimpedance method had a sensitivity of 0.90 [95% confidence interval (CI): 0.54 to 0.99], specificity of 0.82 (95% CI: 0.48 to 0.97), positive predictive value of 0.82 (95% CI: 0.48 to 0.97), and a negative predictive value of 0.90 (95% CI: 0.54 to 0.99) in distinguishing normal and precancerous cervical tissues. The Kappa value was 0.72.

Conclusions: The bioimpedance method was an intelligent method with relative good sensitivity and specificity in distinguishing benign cervical tissue and precancerous lesions and can therefore be used as an adjunctive test to colposcopy to improve the detection of cervical lesions.
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http://dx.doi.org/10.21037/atm-22-1366DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9096428PMC
April 2022

Increased expression of β2-adrenoceptors is involved in the pathogenesis of vitiligo associated gray hair.

J Cosmet Dermatol 2022 May 15. Epub 2022 May 15.

Department of Dermatology, Hangzhou Third People's Hospital, Hangzhou, Zhejiang Province, China.

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http://dx.doi.org/10.1111/jocd.15083DOI Listing
May 2022
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