Publications by authors named "Bing Li"

3,151 Publications

  • Page 1 of 1

Prevalence of Multidrug-Resistant CTX-M Extended Spectrum Beta-Lactamase-Producing From Different Bovine Faeces in China.

Front Vet Sci 2022 1;9:738904. Epub 2022 Aug 1.

Lanzhou Institute of Husbandry and Pharmaceutical Sciences of Chinese Academy of Agricultural Science (CAAS), Lanzhou, China.

CTX-M extended spectrum beta-lactamase-producing cause severe health hazards in livestock breeding. To date, little is known about antibiotic resistance differences among bacterial isolates from yaks, cows, and beef cattle; therefore, the aims of this study were to analyse the prevalence of CTX-M-producing in yak, beef cattle, and dairy cattle feces from different provinces in China. A total of 790 fecal samples from yaks, beef cattle, and dairy cows were used. Among all the samples, 523 non duplicate isolates were identified, and 29.6% of samples harbored CTX-M producers. The results showed that these strains harbored 15 clusters of CTX-M genes: CTX-M-79, CTX-M-55, CTX-M-15, CTX-M-14, CTX-M-28, CTX-M-179, CTX-M-65, CTX-M-24, CTX-M-27, CTX-M-102, CTX-M-105, CTX-M-173, CTX-M-238, CTX-M-196, and CTX-M-10. The dominant resistance genes were CTX-M-15, CTX-M-14, and CTX-M-55. Moreover, the distribution of CTX-M genes was related to geographical region. Based on the above findings, we reasoned that bovines are potential reservoirs of antibiotic resistance, and this problem should be given adequate attention.
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http://dx.doi.org/10.3389/fvets.2022.738904DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9376260PMC
August 2022

Lenvatinib with or without Concurrent Drug-Eluting Beads Transarterial Chemoembolization in Patients with Unresectable, Advanced Hepatocellular Carcinoma: A Real-World, Multicenter, Retrospective Study.

Liver Cancer 2022 Jul 9;11(4):368-382. Epub 2022 Mar 9.

Department of Liver Diseases and Interventional Radiology, Digestive Diseases Hospital, Xi'an International Medical Center Hospital, Northwest University, Xi'an, China.

Introduction: Lenvatinib is the first-line treatment for advanced hepatocellular carcinoma (HCC). We aimed to compare the clinical outcomes of lenvatinib plus drug-eluting beads transarterial chemoembolization (DEB-TACE) versus lenvatinib alone in real-world practice.

Methods: This retrospective analysis included 142 consecutive patients who received lenvatinib plus DEB-TACE and 69 patients who received lenvatinib alone as first-line treatment from 15 Chinese academic centers from November 2018 to November 2019. Overall survival (OS), progression-free survival (PFS), objective response rate (ORR) were evaluated by modified Response Evaluation Criteria in Solid Tumors criteria, and safety profiles were compared between the two groups.

Results: The median OS and PFS were significantly longer in the combined therapy group than in the monotherapy group in whole cohort (median OS, 15.9 vs. 8.6 months, = 0.0022; median PFS, 8.6 vs. 4.4 months, < 0.001) and after propensity score matching analysis (median OS, 13.8 vs. 7.8 months, = 0.03; median PFS, 7.8 vs. 4.5 months, = 0.009). Moreover, the treatment option was an independent prognostic factor for OS and PFS with adjustment based upon baseline characteristics (adjusted hazard ratio [HR]: 0.53, 95% confidence interval [CI]: 0.36-0.78, = 0.001, and adjusted HR: 0.42, 95% CI: 0.30-0.60, < 0.001, respectively) and propensity score (adjusted HR: 0.52, 95% CI: 0.36-0.76, = 0.001, and adjusted HR: 0.46, 95% CI: 0.33-0.64, < 0.001, respectively). Moreover, a greater ORR was observed in the combined group (ORR: 46.48% vs. 13.05%, < 0.001). Furthermore, the most common adverse events (AEs) were elevated aspartate aminotransferase (54.9%) and fatigue (46.4%) in the lenvatinib plus DEB-TACE group and lenvatinib group, respectively. Most AEs were mild-to-moderate and manageable.

Conclusions: With well-tolerated safety, lenvatinib plus DEB-TACE was more effective than lenvatinib monotherapy in improving OS, PFS, and ORR. Thus, it may be a promising treatment for advanced HCC. Future prospective studies confirming these findings are warranted.
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http://dx.doi.org/10.1159/000523849DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9294948PMC
July 2022

Stream water quality optimized prediction based on human activity intensity and landscape metrics with regional heterogeneity in Taihu Basin, China.

Environ Sci Pollut Res Int 2022 Aug 17. Epub 2022 Aug 17.

Key Laboratory of Watershed Geographic Sciences, Nanjing Institute of Geography and Limnology, Chinese Academy of Sciences, Nanjing, 210008, China.

The driving effects of landscape metrics on water quality have been acknowledged widely, however, the guiding significance of human activity intensity and landscape metrics based on reference conditions for water environment management remains to be explored. Thus, we used the self-organized map, long- and short-term memory (LSTM) algorithm, and geographic detectors to simulate the response of human activity intensity and landscape metrics to water quality in Taihu Lake Basin, China. Fitting results of LSTM displayed that the accuracy was acceptable, and scenario 2 (regional heterogeneity) was more efficient than scenario 1 (regional consistent) in the improvement of water quality. In the driving analysis for the reference conditions, clusters I and II (urban agglomeration areas) were mainly affected by the amount of production wastewater per unit of developed land and the amount of livelihood wastewater per unit of developed land, respectively. Their optimal values were 0.09 × 10 t/km (reduction of 35.71%) and 0.2 × 10 t/km (reduction of 4.76%). Cluster III (agricultural production areas) was mainly affected by interference intensity, and the optimal value was 2.17 (increased 38.22%), and cluster IV (ecological forest areas) was mainly affected by the fragmentation of cropland, and the optimal value was 1.14 (reduction of 1.72%). The research provides a reference for the prediction of water quality response and presents an ecological and economic sustainability way for watershed governance.
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http://dx.doi.org/10.1007/s11356-022-22536-5DOI Listing
August 2022

Serum metabolomics reveals an innovative diagnostic model for salivary gland tumors.

Anal Biochem 2022 Aug 12:114853. Epub 2022 Aug 12.

Department of Oral and Maxillofacial Surgery, Nanjing Stomatological Hospital, Medical School of Nanjing University, Nanjing, 210029, China. Electronic address:

An early diagnosis of salivary gland tumors (SGTs) and determination of their malignancy are conducive to developing individualized therapeutic strategies and thus improving prognosis. The aim of this study was to investigate the difference of serum metabolic profiles in patients with SGTs to better understand the mechanism of this disease and disease risk stratification. We used ultrahigh-performance liquid chromatography Q Exactive mass spectrometry and multivariate statistical analyses to conduct a comprehensive analysis of serum metabolites in a population with normal control and SGTs. 32 differentially expressed metabolites were identified, while the level of serine and lactic acid were investigated to gradually upregulate in benign SGTs and malignant SGTs. Then, the expression of serine and lactic acid were assessed in validation cohort using multiple reaction monitoring (MRM) based targeted metabolite analysis. A risk score formula based on the amount of serine and lactic acid was developed and explored to be significantly related to benign SGTs and malignant SGTs in discovery and validation cohort. Our work highlights the possible use of the risk score assessment based on the serum metabolites not only reveal in the early diagnosis of SGTs but also assist in enhancing current therapeutic strategies in the clinic.
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http://dx.doi.org/10.1016/j.ab.2022.114853DOI Listing
August 2022

A Novel Leucyl-tRNA Synthetase Inhibitor, MRX-6038, Expresses Anti-Mycobacterium abscessus Activity and .

Antimicrob Agents Chemother 2022 Aug 15:e0060122. Epub 2022 Aug 15.

Department of Respiratory and Critical Care Medicine, Shanghai Pulmonary Hospital, School of Medicine, Tongji University, Shanghai, China.

Therapeutic options for Mycobacterium abscessus infections are extremely limited, and new drugs are needed. The anti-M. abscessus activity of MRX-6038, a new leucyl-tRNA synthetase inhibitor, was evaluated and . Antimicrobial susceptibility testing was performed on 12 nontuberculosis mycobacteria (NTM) reference strains and 227 clinical NTM isolates. A minimum bactericidal concentration assay was conducted to distinguish the bactericidal versus bacteriostatic activity of MRX-6038. The synergy between MRX-6038 and 12 clinically important antibiotics was determined using a checkerboard assay. The activity of MRX-6038 against M. abscessus residing inside macrophages was also evaluated. Finally, the potency of MRX-6038 was determined in a neutropenic mouse model that mimicked a pulmonary M. abscessus infection. MRX-6038 exhibited high anti-M. abscessus activity against extracellular M. abscessus in culture, with a MIC of 0.063 mg/L and a MIC of 0.125 mg/L. Fifty percent of the activity was bactericidal, and fifty percent was bacteriostatic. A synergy between MRX-6038 and clarithromycin or azithromycin was found in 25% of strains. No antagonism was evident between MRX-6038 and 12 antibiotics commonly used to treat NTM infections. MRX-6038 also exhibited activity against intracellular NTM, which caused a significant reduction in the bacterial load in the lungs of M. abscessus-infected neutropenic mice. In conclusion, MRX-6038 was active against M. abscessus and , and it represents a potential candidate for incorporation into strategies by which M. abscessus infections are treated.
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http://dx.doi.org/10.1128/aac.00601-22DOI Listing
August 2022

Doxorubicin-Induced Cardiotoxicity May Be Alleviated by Bone Marrow Mesenchymal Stem Cell-Derived Exosomal lncRNA via Inhibiting Inflammation.

J Inflamm Res 2022 6;15:4467-4486. Epub 2022 Aug 6.

Department of Cardiology, The Affiliated Hospital of Qingdao University, Qingdao, People's Republic of China.

Purpose: To explore the therapeutic mechanism of bone marrow mesenchymal stem cells derived exosomes (BMSC-Exos) for doxorubicin (DOX)-induced cardiotoxicity (DIC) and identify the long noncoding RNAs' (lncRNAs') anti-inflammation function derived by BMSC-Exos.

Materials And Methods: High-throughput sequencing and transcriptome bioinformatics analysis of lncRNA were performed between DOX group and BEC (bone marrow mesenchymal stem cells derived exosomes coculture) group. Elevated lncRNA (ElncRNA) in the cardiomyocytes of BEC group compared with DOX group were confirmed. Based on the location and co-expression relationship between ElncRNA and its target genes, we predicted two target genes of ElncRNA, named cis_targets and trans_targets. The target genes were analyzed by enrichment analyses. Then, we identified the key cellular biological pathways regulating DIC. Experiments were performed to verify the therapeutic effects of exosomes and the origin of lncRNAs in vitro and in vivo.

Results: Three hundred and one lncRNAs were differentially expressed between DOX and BEC groups (fold change >1.5 and p < 0.05), of which 169 lncRNAs were elevated in the BEC group compared with the DOX group. GO enrichment analysis of target genes of ElncRNAs showed that they were predominantly involved in inflammation-associated processes. KEGG analysis indicated that their regulatory pathways were mainly involved in oxidative stress-induced inflammation and proliferation of cardiomyocyte. The verification experiments in vitro showed that the oxidative stress and cell deaths were decreased in BEC groups. Moreover, from the top 10 ElncRNAs identified in the sequencing results, MSTRG.98097.4 and MSTRG.58791.2 were both decreased in the DOX group and elevated in BEC group. While in verification experiments in vivo, only the expression of MSTRG.58791.2 is consistent with the result in vitro.

Conclusion: Our results show that ElncRNA, MSTRG.58791.2, is possibly secreted by the BMSC-Exos and able to alleviate DIC by suppressing inflammatory response and inflammation-related cell death.
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http://dx.doi.org/10.2147/JIR.S358471DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9365022PMC
August 2022

Five novel RB1 gene mutations and genotype-phenotype correlations in Chinese children with retinoblastoma.

Int Ophthalmol 2022 Aug 12. Epub 2022 Aug 12.

Department of Ophthalmology, The Fifth Affiliated Hospital, Sun Yat-Sen University, No. 52 Mei Hua Dong Road, Zhuhai, 519000, People's Republic of China.

Purpose: To identify the spectrum of RB1 gene mutations in 114 Chinese patients with retinoblastoma.

Methods: Genomic DNA was extracted from the peripheral blood of 114 Rb patients. Polymerase chain reactions (PCRs) followed by direct Sanger sequencing were used to screen for mutations in the RB1 gene, which contains 26 exons with flanking intronic sequences, except exon 15. Clinical data, including gender, age at diagnosis, laterality of ocular lesions, and associated symptoms, were recorded and compared.

Results: We identified five novel mutations in the RB1 gene. Twenty-five other mutations found in this study have been previously reported. A higher rate of RB1 mutations, with 47.3% of mutations among bilaterally affected patients vs. 6.8% within unilaterally affected patients, was also observed (p < 0.0001). Bilaterally affected patients were diagnosed earlier when compared to unilaterally affected patients (11 ± 7 months versus 20 ± 14 months, p = 0.0002). Furthermore, nonsense mutations were abundant (n = 14), followed by frameshift mutations (n = 8), splicing site mutations (n = 5), while missense mutations were few (n = 3).

Conclusions: We found five novel mutations in RB1 genes, which expands the mutational spectrum of the gene. Children with bilateral Rb exhibited higher mutation rates and were diagnosed earlier than those with unilateral Rb. These findings will inform clinical diagnosis and genetic therapeutic targeting in Rb patients.
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http://dx.doi.org/10.1007/s10792-022-02341-2DOI Listing
August 2022

Insight into Isomeric Effect on the Photoluminescence and Mechanoluminescence of Cyanostilbene Derivatives.

J Phys Chem Lett 2022 Aug 12:7681-7688. Epub 2022 Aug 12.

Key Laboratory of New Lithium-Ion Battery and Mesoporous Material, College of Chemistry and Environmental Engineering, Shenzhen University, 1066 Xueyuan Avenue, Nanshan, Shenzhen 518055, China.

Molecular structures, packings, and intermolecular interactions significantly affect the photophysical properties of organic luminogens. In this work, the photoluminescence (PL) and mechanoluminescence (ML) of two pairs of isomers, / and /, were systematically explored. The fluorescence of crystals and is much brighter than that of their isomers and , respectively. Only is ML-active among all four molecules. Single-crystal structural analysis revealed that isomerization of a substituent group affected their molecular packing and intermolecular interactions. Stronger intermolecular interaction and intact three-dimensional hydrogen-bonded networks were formed only in crystal , which were essential for preventing slippage of molecular layers and generating ML; the other molecules were either lacking π-π interactions or C-H···π interactions. Theoretical calculation suggested that the energy barrier between the Franck-Condon (FC) structure and minimum energy crossing point (MECP) structure of / was much lower than that of /. Nonradiative decay channels of molecules and were thus more easily activated, which led to their lower quantum yield.
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http://dx.doi.org/10.1021/acs.jpclett.2c01866DOI Listing
August 2022

Novel Antibiofilm Inhibitor Ginkgetin as an Antibacterial Synergist against .

Int J Mol Sci 2022 Aug 8;23(15). Epub 2022 Aug 8.

Key Laboratory of New Animal Drug Project of Gansu Province, Lanzhou 730050, China.

As an opportunistic pathogen, ( forms biofilm that increases the virulence of bacteria and antibiotic resistance, posing a serious threat to human and animal health. Recently, ginkgetin (Gin) has been discovered to have antiinflammatory, antioxidant, and antitumor properties. In the present study, we evaluated the antibiofilm and antibacterial synergist of Gin against . Additionally, Alamar Blue assay combined with confocal laser scanning microscope (CLSM) and crystal violet (CV) staining was used to evaluate the effect of antibiofilm and antibacterial synergist against . Results showed that Gin reduces biofilm formation, exopolysaccharide () production, and motility against without limiting its growth and metabolic activity. Furthermore, we identified the inhibitory effect of Gin on AI-2 signaling molecule production, which showed apparent anti-quorum sensing (QS) properties. The qRT-PCR also indicated that Gin reduced the transcription of curli-related genes (, ), flagella-formation genes (, , , ), and QS-related genes (, , , ). Moreover, Gin showed obvious antibacterial synergism to overcome antibiotic resistance in with marketed antibiotics, including gentamicin, colistin B, and colistin E. These results suggested the potent antibiofilm and novel antibacterial synergist effect of Gin for treating infections.
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http://dx.doi.org/10.3390/ijms23158809DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9369100PMC
August 2022

Corrigendum to "SIRT2 regulates proliferation and chemotherapy response of MLL-ENL-driven acute myeloid leukemia".

Biochem Biophys Res Commun 2022 Oct 9;623:202-204. Epub 2022 Aug 9.

Department of Biochemistry and Molecular Cell Biology, Shanghai Jiao Tong University School of Medicine, 280 S. Chongqing Road, Shanghai, 200025, China. Electronic address:

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http://dx.doi.org/10.1016/j.bbrc.2022.07.082DOI Listing
October 2022

Chinese patent medicine shouhui tongbian capsule attenuated loperamide-induced constipation through modulating the gut microbiota in rat.

J Ethnopharmacol 2022 Aug 4:115575. Epub 2022 Aug 4.

School of Life Science, Jiangsu Normal University, Xuzhou, 221116, Jiangsu Province, PR China. Electronic address:

Ethnopharmacological Relevance: Shouhui tongbian capsule (SHTC) is a commercial Chinese patent medicine used in the treatment of constipation. However, its mechanism of action remains unclear.

Aim Of The Study: The present study was undertaken to assess SHTC relieved effects on the clinical symptoms of loperamide (LOP) induced constipation in Sprague Dawley (SD) rat model and to clarify the relationship between the protective effect of SHTC on constipation and the gut microbiota.

Materials And Methods: Constipation male SD rats models were induced with solution of LOP (1.5 mg/kg bw), and rats were treated with an oral dose of SHTC (35, 70 mg/kg bw) three times a day after successful modeling. All rats were assessed weekly by change in body weight, gastric emptying rate, fecal moisture content and wet/dry weight. Hematoxylin and eosin (H&E) were used to observe parts of the rats small intestine. The gut microbiota in colonic contents was analyzed using 16SrRNA gene sequencing. Contents of short-chain fatty acids (SCFAs) were analyzed by gas chromatography-mass spectrometer (GCMS).

Results: The results confirmed the therapeutic effects of SHTC on constipation. Specifically, SHTC could alleviate the decrease in body weight, gastric emptying rate and fecal moisture content caused by LOP-induced constipation. The pathological damage of small intestine was significantly improved by H&E staining. Notably, SHTC increased the relative abundances of Lactobacillus and the ratio of Firmicutes to Bacteroides (F/B). In addition, the content of acetic acid and propionic acid was significantly increased in constipated rats fed with SHTC.

Conclusion: SHTC could ameliorate the development of LOP-induced constipation in rats by remodeling the structure of gut microbial community and regulating production of intestinal metabolites.
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http://dx.doi.org/10.1016/j.jep.2022.115575DOI Listing
August 2022

Influence of zinc levels and Nrf2 expression in the clinical and pathological changes in patients with diabetic nephropathy.

Nutr Diabetes 2022 Aug 6;12(1):37. Epub 2022 Aug 6.

Department of Nephropathy, The Second Hospital of Jilin University, Changchun, Jilin Province, China.

Objective: We investigated the correlation between zinc levels and Nrf2 expression and potential effects on the clinicopathology of patients with diabetic nephropathy (DN).

Methods: We selected 30 patients with DN, diagnosed via renal biopsy at our hospital from March 2018 to November 2019, and enrolled 30 healthy individuals from a medical examination center as the control group. Patients with DN were divided into normal-zinc and low-zinc groups. We detected the levels of zinc, copper, and Nrf2 mRNA in their serum, and collected the clinical and pathological data of DN patients.

Results: Serum zinc level and Nrf2 mRNA expression were significantly decreased in patients with DN compared to those of healthy people (P < 0.05). Of the 30 patients, 16 had low zinc (53.3%) and 14 had normal zinc levels (46.7%). There was no significant difference in the blood Nrf2 mRNA expression between the two groups (P > 0.05). However, the expression of Nrf2 in the kidney tissue of the low-zinc group was significantly lower compared to the normal-zinc group (P < 0.05). Diastolic blood pressure and copper levels were significantly higher in the low-zinc group (P < 0.05). In contrast, body mass index, red blood cell count, Hb level, and the ratio of zinc to copper were significantly lower in the low-zinc group (P < 0.05). The pathological classifications of the low-zinc group were more severe (P < 0.05).

Conclusion: Patients with DN were more likely to have zinc deficiency and lower expression of Nrf2. Additionally, DN patients with zinc deficiency were prone to have more severe clinical and pathological manifestations.
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http://dx.doi.org/10.1038/s41387-022-00212-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9357008PMC
August 2022

On-chip integrated graphene aptasensor with portable readout for fast and label-free COVID-19 detection in virus transport medium.

Sens Diagn 2022 Jul 13;1(4):719-730. Epub 2022 Jun 13.

Department of Materials, Imperial College London London SW7 2AZ UK

Graphene field-effect transistor (GFET) biosensors exhibit high sensitivity due to a large surface-to-volume ratio and the high sensitivity of the Fermi level to the presence of charged biomolecules near the surface. For most reported GFET biosensors, bulky external reference electrodes are used which prevent their full-scale chip integration and contribute to higher costs per test. In this study, GFET arrays with on-chip integrated liquid electrodes were employed for COVID-19 detection and functionalized with either antibody or aptamer to selectively bind the spike proteins of SARS-CoV-2. In the case of the aptamer-functionalized GFET (aptasensor, Apt-GFET), the limit-of-detection (LOD) achieved was about 10 particles per mL for virus-like particles (VLPs) in clinical transport medium, outperforming the Ab-GFET biosensor counterpart. In addition, the aptasensor achieved a LOD of 160 aM for COVID-19 neutralizing antibodies in serum. The sensors were found to be highly selective, fast (sample-to-result within minutes), and stable (low device-to-device signal variation; relative standard deviations below 0.5%). A home-built portable readout electronic unit was employed for simultaneous real-time measurements of 12 GFETs per chip. Our successful demonstration of a portable GFET biosensing platform has high potential for infectious disease detection and other health-care applications.
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http://dx.doi.org/10.1039/d2sd00076hDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9280445PMC
July 2022

A Machine Learning Model Based on Health Records for Predicting Recurrence After Microwave Ablation of Hepatocellular Carcinoma.

J Hepatocell Carcinoma 2022 28;9:671-684. Epub 2022 Jul 28.

Department of Ultrasound, PLA Medical College & 5th Medical Center of Chinese PLA General Hospital, Beijing, 100853, People's Republic of China.

Background And Aim: Early recurrence (ER) presents a challenge for the survival prognosis of patients with hepatocellular carcinoma (HCC). The aim of this study was to investigate machine learning (ML) models using clinical data for predicting ER after microwave ablation (MWA).

Methods: Between August 2005 and December 2019, 1574 patients with early-stage HCC underwent MWA at four hospitals were reviewed. Then, 36 clinical data points per patient were collected, and the patients were assigned to the training, internal, and external validation set. Apart from traditional logistic regression (LR), three ML models-random forest, support vector machine, and eXtreme Gradient Boosting (XGBoost)-were built and validated for their predictive ability with the area under ROC curve (AUC). Algorithms such as SHapley Additive exPlanations (SHAP) and local interpretable model-agnostic explanations (LIME) were used to realize their interpretability.

Results: The three ML models all outperformed LR ( < 0.001 for all) in predictive ability. When nine variables (tumor number, platelet, α-fetoprotein, comorbidity score, white blood cell, cholinesterase, prothrombin time, neutrophils, and etiology) were extracted simultaneously using recursive feature elimination with cross-validation, the XGBoost model achieved the best discrimination among all models, with an AUC value 0.75 (95% CI [confidence interval]: 0.72-0.78) in the training set, 0.74 (95% CI: 0.69-0.80) in the internal validation set, and 0.76 (95% CI: 0.70-0.82) in the external validation set, and it was interpreted depending on the visualization of risk factors by the SHAP and LIME algorithms. The predictive system of post-ablation recurrence risk stratification was provided on online (http://114.251.235.51:8001/) based on XGboost analysis.

Conclusion: The XGBoost model based on clinical data can effectively predict ER risk after MWA, which can contribute to surveillance, prevention, and treatment strategies for HCC.
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http://dx.doi.org/10.2147/JHC.S358197DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9342890PMC
July 2022

Development of a borosilicate bioactive glass scaffold incorporating calcitonin gene-related peptide for tissue engineering.

Biomater Adv 2022 Jul 25;138:212949. Epub 2022 May 25.

Department of Orthopaedics, Fourth Affiliated Hospital of Guangxi Medical University/Liuzhou Worker's Hospital, Liuzhou 545000, PR China. Electronic address:

Protein delivery and release from synthetic scaffold materials are major challenges within the field of bone tissue engineering. In this study, 13-93B1.5 borosilicate bioactive glass (BSG) base paste was 3D printed to produce BSG-based scaffolds with high porosity (59.85 ± 6.04%) and large pore sizes (350-400 μm) for functionalization with a sodium alginate (SA)/calcitonin gene-related peptide (CGRP) hydrogel mixture. SA/CGRP hydrogel was uniformly filled into the interconnected pores of 3D printed BSG constructs to produce BSG-SA/CGRP scaffolds which were subject to bioactivity and biocompatibility analysis. BSG scaffolds filled with SA hydrogel underwent dissolution in simulated body fluid (SBF), resulting in the precipitation of hydroxyapatite (HA) on the borosilicate glass evidenced by scanning electron microscope (SEM), energy dispersive spectroscopy (EDS), X-ray diffraction (XRD) and Fourier transform infrared spectroscopy (FTIR). Around 90% of CGRP was released from scaffolds after 7 days of immersion in SBF, reaching a final released concentration of 893.00 ± 63.30 ng/mL. Cellular adhesion, proliferation, and differentiation of human bone marrow mesenchymal stem cells (HBMSCs) cultured with BSG-SA/CGRP scaffolds revealed improved biocompatibility and osteogenic capabilities compared with BSG-SA scaffolds in the absence of CGRP. When subcutaneously implanted in rat models, BSG-SA/CGRP scaffolds induced low localized inflammation without causing bodily harm in vivo. Findings revealed that bioactive glass scaffolds incorporating CGRP met the scaffold requirements for bone regeneration and that the addition of CGRP promoted osteogenic differentiation where it may potentially be utilized for future regenerative applications.
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http://dx.doi.org/10.1016/j.bioadv.2022.212949DOI Listing
July 2022

Microstate feature fusion for distinguishing AD from MCI.

Health Inf Sci Syst 2022 Dec 26;10(1):16. Epub 2022 Jul 26.

Institute of Applied Mathematics, Hebei Academy of Sciences, Shijiazhuang, China.

Electroencephalogram (EEG) microstates provide powerful tools for identifying EEG features due to their rich temporal information. In this study, we tested whether microstates can measure the severity of Alzheimer's disease (AD) and mild cognitive impairment (MCI) in patients and effectively distinguish AD from MCI. We defined two features using transition probabilities (), and one was used to evaluate between-group differences in microstate parameters to assess the within-group consistency of and MMSE scores. Another feature was used to distinguish AD from MCI in machine learning models. Tests showed that there were between-group differences in the temporal characteristics of microstates, and some kinds of were significantly correlated with MMSE scores within groups. Based on our newly defined time-factor transition probabilities () feature and partial accumulation strategy, we obtained promising scores for accuracy, sensitivity, and specificity of 0.938, 0.923, and 0.947, respectively. These results provide evidence for microstates as a neurobiological marker of AD.
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http://dx.doi.org/10.1007/s13755-022-00186-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9325930PMC
December 2022

Metabolomics of clinical samples reveal the treatment mechanism of lanthanum hydroxide on vascular calcification in chronic kidney disease.

Proc Jpn Acad Ser B Phys Biol Sci 2022 ;98(7):361-377

Department of Pharmacology, College of Pharmacy, Inner Mongolian Medical University.

Previous studies showed that lanthanum hydroxide (LH) has a therapeutic effect on chronic kidney disease (CKD) and vascular calcification, which suggests that it might have clinical value. However, the target and mechanism of action of LH are unclear. Metabolomics of clinical samples can be used to predict the mechanism of drug action. In this study, metabolomic profiles in patients with end-stage renal disease (ESRD) were used to screen related signaling pathways, and we verified the influence of LH on the ROS-PI3K-AKT-mTOR-HIF-1α signaling pathway by western blotting and quantitative real-time RT-qPCR in vivo and in vitro. We found that ROS and SLC16A10 genes were activated in patients with ESRD. The SLC16A10 gene is associated with six significant metabolites (L-cysteine, L-cystine, L-isoleucine, L-arginine, L-aspartic acid, and L-phenylalanine) and the PI3K-AKT signaling pathway. The results showed that LH inhibits the ESRD process and its cardiovascular complications by inhibiting the ROS-PI3K-AKT-mTOR-HIF-1α signaling pathway. Collectively, LH may be a candidate phosphorus binder for the treatment of vascular calcification in ESRD.
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http://dx.doi.org/10.2183/pjab.98.019DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9363596PMC
August 2022

Chitosan-based matrix solid-phase dispersion extraction assisted cell membrane magnetic bead ligand-affinity assay for screening active compounds from Fructus Cnidii.

J Sep Sci 2022 Jul 29. Epub 2022 Jul 29.

Tianjin Key Laboratory on Technologies Enabling Development of Clinical Therapeutics and Diagnostics, Department of Natural Medicine, School of Pharmacy, Tianjin Medical University, Tianjin, China.

Cell membrane ligand-affinity assay is a useful tool for screening the active compounds from natural products. However, in traditional cell membrane ligand-affinity assays, natural products need to be refluxed, before being analyzed. This process consumes considerable time and energy and cannot be used for screening natural products that contain thermally unstable compounds. Therefore, an efficient analytical method is required. In this study, chitosan-based matrix solid-phase dispersion extraction was combined with cell membrane magnetic bead ligand-affinity assay to form a novel method for identifying the active compounds in Fructus Cnidii such as osthole and imperatorin. When compared with traditional cell membrane ligand-affinity assays, this assay requires less energy, extraction time (7 min), solvent volume (1.2 mL), and fewer natural products (40 mg). This indicates that the chitosan-based matrix solid-phase dispersion extraction assisted cell membrane magnetic beads ligand-affinity assay is an alternative analytical method for studying natural products.
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http://dx.doi.org/10.1002/jssc.202200286DOI Listing
July 2022

SPD: Semi-Supervised Learning and Progressive Distillation for 3-D Detection.

IEEE Trans Neural Netw Learn Syst 2022 Jul 29;PP. Epub 2022 Jul 29.

Current learning-based 3-D object detection accuracy is heavily impacted by the annotation quality. It is still a challenge to expect an overall high detection accuracy for all classes under different scenarios given the dataset sparsity. To mitigate this challenge, this article proposes a novel method called semi-supervised learning and progressive distillation (SPD), which uses semi-supervised learning (SSL) and knowledge distillation to improve label efficiency. The SPD uses two big backbones to hand the unlabeled/labeled input data augmented by the periodic IO augmentation (PA). Then the backbones are compressed using progressive distillation (PD). Precisely, PA periodically shifts the data augmentation operations between the input and output of the big backbone, aiming to improve the network's generalization of the unseen and unlabeled data. Using the big backbone can benefit from large-scale augmented data better than the small one. And two backbones are trained by the data scale and ratio-sensitive loss (data-loss). It solves the over-flat caused by the large-scale unlabeled data from PA and helps the big backbone prevent overfitting on the limited-scale labeled data. Hence, using the PA and data loss during SSL training dramatically improves the label efficiency. Next, the trained big backbone set as the teacher CNN is progressively distilled to obtain a small student model, referenced as PD. PD mitigates the problem that student CNN performance degrades when the gap between the student and the teacher is oversized. Extensive experiments are conducted on the indoor datasets SUN RGB-D and ScanNetV2 and outdoor dataset KITTI. Using only 50% labeled data and a 27% smaller model size, SPD performs 0.32 higher than the fully supervised VoteNetqi2019deep which is adopted as our backbone. Besides, using only 2% labeled data, compared to the other fully supervised backbone PV-RCNNshi2020pv, SPD accomplishes a similar accuracy (84.1 and 84.83) and 30% less inference time.
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http://dx.doi.org/10.1109/TNNLS.2022.3193614DOI Listing
July 2022

PDNet: Towards Better One-stage Object Detection with Prediction Decoupling.

IEEE Trans Image Process 2022 Jul 28;PP. Epub 2022 Jul 28.

Recent one-stage object detectors follow a per-pixel prediction approach that predicts both the object category scores and boundary positions from every single grid location. However, the most suitable positions for inferring different targets, i.e., the object category and boundaries, are generally different. Predicting all these targets from the same grid location thus may lead to sub-optimal results. In this paper, we analyze the suitable inference positions for object category and boundaries, and propose a prediction-target-decoupled detector named PDNet to establish a more flexible detection paradigm. Our PDNet with the prediction decoupling mechanism encodes different targets separately in different locations. A learnable prediction collection module is devised with two sets of dynamic points, i.e., dynamic boundary points and semantic points, to collect and aggregate the predictions from the favorable regions for localization and classification. We adopt a two-step strategy to learn these dynamic point positions, where the prior positions are estimated for different targets first, and the network further predicts residual offsets to the positions with better perceptions of the object properties. Extensive experiments on the MS COCO benchmark demonstrate the effectiveness and efficiency of our method. With a single ResNeXt-64x4d-101-DCN as the backbone, our detector achieves 50.1 AP with single-scale testing, which outperforms the state-of-the-art methods by an appreciable margin under the same experimental settings. Moreover, our detector is highly efficient as a one-stage framework. Our code will be public.
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http://dx.doi.org/10.1109/TIP.2022.3193223DOI Listing
July 2022

Natural Halloysite-Templated Synthesis of Highly Graphitic Boron-Doped Hollow Carbon Nanocapsule Webs.

Nanomaterials (Basel) 2022 Jul 9;12(14). Epub 2022 Jul 9.

School of Environmental Science and Engineering, Guangzhou University, Guangzhou 510006, China.

Hollow carbon nanocapsules have been attracting growing interest due to their fascinating characteristics and extensive potential applications. In this work, a novel natural halloysite-templated synthesis approach for highly graphitic boron-doped hollow carbon nanocapsule webs (B-HCNCWs) using glucose as the carbon source and boric acid as the heteroatom dopant was first reported. The formation process and physicochemical properties of B-HCNCWs were revealed by SEM, TEM, XRD, Raman, Brunauer-Emmett-Teller (BET), and XPS characterization techniques. The outcomes showed that the as-obtained B-HCNCWs with hollow nanocapsule network architecture had a specific surface area of 263 m g, a pore volume of 0.8 cm g, a high degree of graphitization (81.4%), graphite-like interplanar spacing (0.3370 nm), and B-containing functional groups (0.77 at%). The density function theory (DFT) calculation demonstrated that the adsorption energies of Li on B-HCNCWs were much higher than that of HCNCWs, which proved that B-doping in a carbon matrix could increase the lithium intercalation capacity.
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http://dx.doi.org/10.3390/nano12142352DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9316536PMC
July 2022

Effects of Stocking Density on the Growth Performance, Physiological Parameters, Redox Status and Lipid Metabolism of in Integrated Rice-Fish Farming Systems.

Antioxidants (Basel) 2022 Jun 21;11(7). Epub 2022 Jun 21.

Key Laboratory of Integrated Rice-Fish Farming Ecology, Ministry of Agriculture and Rural Affairs, Freshwater Fisheries Research Center, Chinese Academy of Fishery Sciences, Wuxi 214081, China.

Stocking density has been identified as one of the main factors affecting fish growth, welfare and behavior. However, few studies have focused on the effects of stocking density on fish health in integrated rice-fish farming systems. Thus, the aim of this study was to evaluate the effects of different stocking densities on the growth performance, physiological parameters, redox status and lipid metabolism of in an integrated rice-fish farming system. The fish were reared at three densities: low density (LD, 40 g/m), medium density (MD, 80 g/m) and high density (HD, 120 g/m) for 90 days. At the end of the experiment, fish reared in the MD and HD groups showed lower growth performance than those from the LD group. The HD treatment significantly altered the physiological parameters, including glucose and lactate. Meanwhile, the HD treatment induced oxidative stress and lipid peroxidation after 90 days of farming. Furthermore, transcriptomic analysis revealed that HD treatment led to abnormal lipid metabolism. Interestingly, we found the suppression of three key pathways related to lipid metabolism, including the PPAR, insulin and adipocytokine signaling pathways, in the HD group. Overall, our data indicated that the HD treatment inhibited growth and caused physiological responses, oxidative stress and abnormal hepatic lipid metabolism in in an integrated rice-fish farming system.
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http://dx.doi.org/10.3390/antiox11071215DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9312047PMC
June 2022

Transporting a prediction model for use in a new target population.

Am J Epidemiol 2022 Jul 22. Epub 2022 Jul 22.

Department of Biostatistics, School of Public Health, Brown University, Providence, RI, CAUSALab, Harvard T.H. Chan School of Public Health, Boston, MA, Departments of Epidemiology and Biostatistics, Harvard T.H. Chan School of Public Health, Boston, MA.

We consider methods for transporting a prediction model for use in a new target population, when outcome and covariate data for model development are available from a source population that has a different covariate distribution compared to the target population, and when covariate data (but not outcome data) are available from the target population. We discuss how to tailor the prediction model to account for differences in the data distribution between the source population and the target population. We also discuss how to assess the model's performance (e.g., by estimating the mean squared prediction error) in the target population. We provide identifiability results for measures of model performance in the target populationfor a potentially misspecified prediction model under a sampling design where the source and the target population samples are obtained separately. We introduce the concept of prediction error modifiers that can be used to reason about tailoring measuresof model performance to the target population. We illustrate the methods in simulated data and apply them to transport a prediction model for lung cancer diagnosis from the National Lung Screening Trial to the nationally representative target population of trial-eligible individuals in the National Health and Nutrition Examination Survey.
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http://dx.doi.org/10.1093/aje/kwac128DOI Listing
July 2022

Roxadustat regulates iron metabolism in dialysis-dependent and non-dialysis-dependent chronic kidney disease patients: A meta-analysis.

J Formos Med Assoc 2022 Jul 20. Epub 2022 Jul 20.

Department of Nephrology, Institute of Nephrology, 2nd Affiliated Hospital of Hainan Medical University, Haikou, China. Electronic address:

Background/purpose: The effect of roxadustat on iron homeostasis in patients with chronic kidney disease (CKD) is unclear. This study aimed to evaluate the efficacy of roxadustat for the treatment of iron metabolism disorders in dialysis-dependent (DD) and non-dialysis-dependent (NDD) CKD patients.

Methods: We searched the PubMed, Embase, China National Knowledge Internet and Web of Science databases for randomized controlled trials (RCTs). The primary outcomes were changes in serum iron, total iron binding capacity (TIBC), transferrin saturation (TSAT), ferritin, transferrin, and hepcidin. The secondary outcomes included the changes in hemoglobin (Hb) and the incidences of adverse events (AEs) and severe adverse events (SAEs).

Results: Twelve RCTs comprising 4976 participants were included. Compared to the control group, increases in the serum iron (SMD = 0.21, 95% CI: 0.15 to 0.27, P < 0.00001), TIBC (SMD = 1.02, 95% CI: 0.82 to 1.22, P < 0.00001) and transferrin levels (WMD = 0.55, 95% CI: 0.41 to 0.69, P < 0.00001) were found in the roxadustat group. Compared to the control group, decreases in the ferritin levels (WMD = -37.82, 95% CI: -59.89 to -15.74, P = 0.0008) and hepcidin levels (WMD = -24.04, 95% CI: -36.28 to -11.79, P = 0.0001) were observed in the roxadustat group. The meta-analysis showed that roxadustat significantly increases Hb levels (WMD = 0.77, 95% CI: 0.42 to 1.12, P < 0.0001). The incidences of AEs and SAEs in the roxadustat group was significantly higher than that in the control group (RR = 1.03, 95% CI: 1.00 to 1.07, P = 0.04; RR = 1.08, 95% CI: 1.00 to 1.15, P = 0.04).

Conclusion: Our findings suggest that roxadustat could effectively improve iron metabolism in patients with CKD.
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http://dx.doi.org/10.1016/j.jfma.2022.06.008DOI Listing
July 2022

DDX24 promotes metastasis by regulating RPL5 in non-small cell lung cancer.

Cancer Med 2022 Jul 21. Epub 2022 Jul 21.

Department of Interventional Medicine, The Fifth Affiliated Hospital, Sun Yat-sen University, Zhuhai, P.R. China.

Purpose: Non-small cell lung cancer (NSCLC) is a leading cause of cancer death, and metastasis is a crucial determinant of increased cancer mortality. DDX24 has garnered increased attention due to its correlation with tumorigenesis and malignant progression. However, the correlation between DDX24 and NSCLC remains unclear.

Methods: DDX24 expression in NSCLC tissues and survival rate of patients was analyzed using bioinformatic analysis. Transwell assays, wound-healing assays, and tail vein lung colonization models were employed to determine the role of DDX24 in migration and invasion in vitro and in vivo. We searched for DDX24-interacting proteins using co-immunoprecipitation followed by mass spectroscopy and verified the interaction. The influence of DDX24 on RPL5 expression and ubiquitination was examined using protein stability assays.

Results: DDX24 expression was upregulated in NSCLC cell lines and tumors of patients, particularly those with high tumor grades. A high DDX24 level was also correlated with a poor prognosis. DDX24 upregulation enhanced the migration and invasion ability of NSCLC cells, whereas its downregulation had the opposite effects. In vivo xenograft experiments confirmed that tumors with high DDX24 expression had higher metastatic abilities. The interaction between DDX24 and RPL5 promoted its ubiquitination and destabilized it.

Conclusions: DDX24 acted as a pro-tumorigenic factor and promoted metastasis in NSCLC. DDX24 interacted with RPL5 to promote its ubiquitination and degradation. As a result, targeting DDX24/RPL5 axis may provide a novel potential therapeutic strategy for NSCLC.
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http://dx.doi.org/10.1002/cam4.4835DOI Listing
July 2022

The Efficacy of Twin-Block Appliances for the Treatment of Obstructive Sleep Apnea in Children: A Systematic Review and Meta-Analysis.

Biomed Res Int 2022 11;2022:3594162. Epub 2022 Jul 11.

The First Affiliated Hospital of Chongqing Medical University, No. 1 Youyi Road, Yuzhong District, Chongqing 400016, China.

Objective: To evaluate the efficacy of twin-block appliance in the treatment of children with obstructive sleep apnea (OSA).

Methods: Two independent reviewers conducted a systematic review of seven databases from database establishment until October 16, 2021. There were no language restrictions. The outcomes were changes in apnea-hypopnea index (AHI), oxyhemoglobin desaturation index (ODI), and lowest arterial oxygen saturation (lowest SaO). National Institute for Health and Clinical Excellence (NICE) tool was used to assess the quality of the studies included.

Results: A total of 207 articles were screened for relevance, and 6 of them met the inclusion criteria for our meta-analysis. Four of the studies were case series, 1 was nonrandomized control trial, and 1 was a randomized crossover clinical trial. After twin-block therapy, there was a significant decrease in AHI (4.35 events/hour, 95% CI: 4.04, 4.66, ≤ 0.001). The lowest SaO significantly increased by 9.17% (95% CI: 12.05, 6.28, ≤ 0.001). Sensitivity analysis by excluding studies one by one showed stable and favorable results in lowest SaO and AHI.

Conclusions: Results from the meta-analysis showed that the use of twin-block appliance significantly decreased AHI and significantly increased lowest SaO. Hence, twin-block appliance therapy may be an effective method for the treatment of pediatric OSA. Further large sample size randomized controlled trials are needed to assess this treatment efficacy in children with obstructive sleep apnea.
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http://dx.doi.org/10.1155/2022/3594162DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9293515PMC
July 2022

The Potential of miR-370-3p and miR-495-3p Serving as Biomarkers for Sepsis-Associated Acute Kidney Injury.

Comput Math Methods Med 2022 11;2022:2439509. Epub 2022 Jul 11.

Department of Nephrology, SINOPHARM North Hospital, Baotou, 014030 Inner Mongolia, China.

Objective: This study is aimed at evaluating the miR-370-3p and miR-495-3p expression in the urine of patients with sepsis-associated acute kidney injury (SA-AKI) and exploring its diagnosis value in for SA-AKI.

Methods: 184 sepsis invalids were collected and divided two groups (non-AKI group or AKI group) according to whether they had acute kidney injury. RT-qPCR was utilized to measure miR-370-3p and miR-495-3p expressions. ROC curve was performed to evaluate the diagnostic value of miR-370-3p and miR-495-3p for SA-AKI. Patients diagnosed with SA-AKI were followed up for 28 days to record survival time. The prognostic performance of miR-370-3p and miR-495-3p for SA-AKI was evaluated by survival curves.

Results: Compared with non-AKI invalids, miR-370-3p and miR-495-3p expressions were obviously lower in the urine of AKI invalids. miR-370-3p and miR-495-3p expressions were markedly negatively correlated with biomarkers of renal injury. Furthermore, the area under the curve (AUC) of miR-370-3p and miR-495-3p for diagnosing sepsis SA-AKI was 0.896 and 0.814, respectively. The higher 28 days-survival rate was observed in patients with high miR-370-3p and miR-495-3p expressions.

Conclusions: A novel biomarker for the early diagnosis of SA-AKI may be miR-370-3p and miR-495-3p, which was clearly reduced in the urine of SA-AKI patients.
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http://dx.doi.org/10.1155/2022/2439509DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9293507PMC
July 2022

Endoscopic Stricturotomy in the Treatment of Refractory Esophageal Anastomotic Strictures.

Dysphagia 2022 Jul 20. Epub 2022 Jul 20.

Department of Gastroenterology and Hepatology, The Second Affiliated Hospital of Harbin Medical University, No 246, Xuefu Road, NanGang District, Harbin, 150000, Heilongjiang, China.

Refractory esophageal anastomotic strictures are a frequent challenge for endoscopists. The current therapeutic strategies have a significant restenosis rate, and patients usually require repeated sessions and suffer from dysphagia. Therefore, we propose a modified method named endoscopic stricturotomy (ES) to treat refractory esophageal anastomotic strictures. The patients diagnosed with refractory esophageal anastomotic strictures were enrolled in the cohort study. The method of ES is to incise longitudinally only a single strip of mucosa at the most prominent part of fibrotic scar and completely cut fibrotic tissues under the mucosa. The primary endpoint was the times of endoscopic therapies. The secondary endpoints include the effective rate, success rate, recurrence rate, endoscopic treatment intervals, complications, length of hospital stay, and surgical cost. The patients were followed up for at least 6 months after ES. The median anastomotic diameter of 12 patients was 2 mm (range 1 to 4 mm). Dysphagia were dramatically relieved in all patients (dysphagia grade from 3 to 1), the effective rate was 100%. During the follow-up, the 12 patients received a total number of 38 sessions, and the median number of ES sessions was 2.5 (1-9), and the success rate were 83%. Nine of the patients (75%) developed restenosis during follow-up, with a median interval of 38 days (15-315 days). No complications occurred during treatment and following up. The median hospital stay was 2 days (2-2.9 days), and the hospitalization costs was 3887.4 RMB (3632.8 RMB-4116.9 RMB). ES seems to be an effective treatment modality for refractory esophageal anastomotic strictures. Large prospective clinical trials are needed to confirm its utility and its place in the management of refractory esophageal anastomotic strictures (ChiCTR2000032997).
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http://dx.doi.org/10.1007/s00455-022-10495-5DOI Listing
July 2022

International Trade of Masks and COVID-19 Pandemic Containment.

J Environ Public Health 2022 9;2022:2156950. Epub 2022 Jul 9.

School of Business, Beijing Union University, Beijing 100101, China.

This study analyzes the impact of the exports of China's masks and other antivirus supplies on the people from the importing countries who are subject to the severe pandemic during the coronavirus disease 2019 (COVID-19) pandemic. Our main data include the COVID-19 cases data of countries around the world published by Johns Hopkins University and the data of China's exports of masks or other antivirus supplies to these countries from the Chinese Customs Database. Using cross-sectional data of about 180 countries and multiple regression analysis, we find that the antivirus supplies from China have played an important role in combating the COVID-19 pandemic. Specifically, China's masks are shipped to countries around the world, and these masks can improve the recovery rate and protect people against the COVID-19 pandemic. Our findings are relevant to global efforts in the COVID-19 pandemic containment.
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http://dx.doi.org/10.1155/2022/2156950DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9288293PMC
July 2022

USP7 Enables Immune Escape of Glioma Cells by Regulating PD-L1 Expression.

Authors:
Bing Li Bin Wang

Immunol Invest 2022 Jul 19:1-17. Epub 2022 Jul 19.

Department of Interventional Radiology, Tianjin Huanhu Hospital, Tianjin Key Laboratory of Cerebral Vascular and Neurodegenerative Diseases, Tianjin, P.R. China.

Background: Glioma is the most common primary intracranial tumor. This study investigated the mechanism of ubiquitin-specific processing protease 7 (USP7) on the immune escape of glioma cells via the regulation of programmed cell death ligand-1 (PD-L1).

Methods: USP7 and PD-L1 expressions in glioma and normal brain tissues were detected using quantitative reverse transcriptase polymerase chain reaction and Western blot. The glioma cells U-251 MG were transfected with si-USP7 and pcDNA3.1-PD-L1, or treated with anti-PD-L1, after which the cell viability, colony-forming ability, and apoptosis rate were evaluated using cell counting kit-8, colony formation, and TdT-mediated dUTP nick-end labeling assays. Then, CD8+ T cells were purified, extracted, then co-cultured with U-251 MG cells. CD8+ T cell proliferation and the concentrations of interferon (IFN-γ), tumor necrosis factor (TNF)-α, transforming growth factor (TGF)-β, interleukin (IL)-1β, and IL-10 were verified using carboxyfluorescein succinimidyl amino ester proliferation assay and enzyme-linked immunosorbent assay. Afterwards, the interaction between USP7 and PD-L1 and the ubiquitination level of PD-L1 were also assessed.

Results: USP7 was highly-expressed and PD-L1 mRNA levels did not change, while PD-L1 protein levels were up-regulated in the glioma cells. Silencing USP7 in U-251 MG cells limited the growth of the glioma cells, promoted glioma cell apoptosis, and facilitated the proliferation of CD8+ T cells, thus inhibiting immune escape. USP7 stabilized PD-L1 expression through deubiquitination. PD-L1 overexpression reversed the inhibitory effect of silencing USP7 on the immune escape of glioma cells.

Conclusion: USP7 stabilized PD-L1 through deubiquitination and accelerated the immune escape of glioma cells.
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http://dx.doi.org/10.1080/08820139.2022.2083972DOI Listing
July 2022
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