Publications by authors named "Shuangshuang Li"

131 Publications

The germline/somatic DNA damage repair gene mutations modulate the therapeutic response in Chinese patients with advanced pancreatic ductal adenocarcinoma.

J Transl Med 2021 Jul 12;19(1):301. Epub 2021 Jul 12.

Department of Abdominal Oncology, Cancer Center, West China Hospital, Sichuan University, Chengdu, China.

Background: Pancreatic ductal adenocarcinoma (PDAC) is a fatal disease with molecular heterogeneity, inducing differences in biological behavior, and therapeutic strategy. NGS profiles of pathogenic alterations in the Chinese PDAC population are limited. We conducted a retrospective study to investigate the predictive role of DNA damage repair (DDR) mutations in precision medicine.

Methods: The NGS profiles were performed on resected tissues from 195 Chinese PDAC patients. Baseline clinical or genetic characteristics and survival status were collected. The Kaplan-Meier survival analyses were performed by the R version 3.6.1.

Results: The main driver genes were KRAS, TP53, CDKN2A, and SMAD4. Advanced patients with KRAS mutation showed a worse OS than KRAS wild-type (p = 0.048). DDR pathogenic deficiency was identified in 30 (15.38%) of overall patients, mainly involving BRCA2 (n = 9, 4.62%), ATM (n = 8, 4.10%) and RAD50 genes (n = 3, 1.54%). No significance of OS between patients with or without DDR mutations (p = 0.88). But DDR mutation was an independent prognostic factor for survival analysis of advanced PDAC patients (p = 0.032). For DDR mutant patients, treatment with platinum-based chemotherapy (p = 0.0096) or olaparib (p = 0.018) respectively improved the overall survival. No statistical difference between tumor mutation burden (TMB) and DDR mutations was identified. Treatment of PD-1 blockades did not bring significantly improved OS to DDR-mutated patients than the naive DDR group (p = 0.14).

Conclusions: In this retrospective study, we showed the role of germline and somatic DDR mutation in predicting the efficacy of olaparib and platinum-based chemotherapy in Chinese patients. However, the value of DDR mutation in the prediction of hypermutation status and the sensitivity to the PD-1 blockade needed further investigation.
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http://dx.doi.org/10.1186/s12967-021-02972-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8273977PMC
July 2021

Effects of water and fertilizer coupling on the physiological characteristics and growth of rabbiteye blueberry.

PLoS One 2021 6;16(7):e0254013. Epub 2021 Jul 6.

Faculty of Agricultural Sciences and Technology, Department of Agronomy, Bahauddin Zakariya University Multan, Multan, Pakistan.

Understanding the impact of irrigation and fertilizer on rabbiteye blueberry (Vaccinium virgatum) physiology is necessary for its precision planting. Here, we applied varied irrigation and fertilizer under completely randomized experimental design to see its impact on the physiological characteristics and bush growth of rabbiteye blueberries. A comprehensive evaluation of the membership function was used to establish the best water-fertilizer coupling regimes. Rabbiteye blueberry enhanced the net photosynthetic rate, stomatal conductance and transpiration rate of leaf and improved its photosynthetic capacity at maximum level of irrigation water and fertilizer application (F3W4). The high fertilizer-medium water treatment (F3W3) increased leaf-soluble protein contents. The medium fertilizer-medium water treatment (F2W3, F2W2) increased leaf- soluble sugar, superoxide dismutase, and chlorophyll contents; decreased the malondialdehyde content; and enhanced leaf resistance and metabolism. It also promoted the growth of flower buds and new shoots. Combined membership function and cluster analyses revealed that the optimal water and fertilizer conditions for promoting rabbiteye blueberry plant growth were the medium fertilizer-medium water [(NH4)2SO4:Ca(H2PO4)2:K2SO4 at 59:10:20 g plant-1; 2.5 L water plant-1], medium fertilizer-medium-high water [(NH4)2SO4:Ca(H2PO4)2:K2SO4 at 59:10:20 g plant-1; 3.75 L water plant-1], and high fertilizer-medium-high water [(NH4)2SO4:Ca(H2PO4)2:K2SO4 at 118:20:40 g plant-1; 3.75 L water plant-1] treatments. The findings of this study could be used in improving the precision and efficacy of rabbiteye blueberry planting in Guizhou, China. Such an approach can increase the productivity and profitability for local fruit farmers.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0254013PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8259967PMC
July 2021

The Efficacy and Safety of Hypofractionated Radiation Therapy With Tomotherapy for Advanced or Recurrent Hepatocellular Carcinoma.

Front Oncol 2021 31;11:559112. Epub 2021 May 31.

Comprehensive Cancer Centre of Nanjing Drum Tower Hospital, Clinical College of Nanjing Medical University, Nanjing, China.

The effects of radiotherapy on hepatocellular carcinoma (HCC) still remain to be further proved. The dose of radiotherapy is generally 2Gy*25f. In the current study, we prospectively investigated the clinical outcomes of advanced or recurrent HCC patients who received hypofractionated radiotherapy at a dose of 5Gy*10f with tomotherapy. A study involving hypofractionated radiotherapy (5Gy*10f) based on TOMO was conducted in HCC patients with Child-Pugh grade A or B who were unsuitable candidates for resection or radiofrequency ablation or with residual disease after transarterial chemoembolization (TACE). The prescription dose was 50 grays in 10 fractions. From Sep. 2016 and Dec. 2017, 65 patents were evaluated with a median follow-up of 24 months (range: 7-41 months). 10 patients were treatment-naïve (failure to undergo surgery or intervention due to the presence of a portal or portal branch tumor thrombus), 15 patients were treated for residual HCC after TACE as salvage therapy, and 40 cases were treated for recurrent HCC. The median overalls survival (OS) of these patients was 18 months. Among them, 27 patients classified as BCLC stage B had a median OS of 22 months. Moreover, 28 patients classified as BCLC stage C had a median OS of 14 months. None of the patients experienced recurrence in the area of radiotherapy. The local control rate of primary tumor at 3 months, 6 months, 1 year and 2 years was 100%. The 3-month survival rate was 100%, the 6-month survival rate was 100%, the 1-year survival rate was 75.4%, and the 2-year survival rate was 43%. In addition, 14 patients had the opportunity to continue the treatment of PD-1 antibody after the disease progression, and their prognosis was not surprisingly better compared with the patients who did not receive PD-1 antibody treatment (NR . 15 months, P=0.04). No serious side effect was found in all patients during and after radiotherapy. Hypofractionated radiotherapy (5Gy*10f) based on TOMO achieved high local control rate and OS with tolerable toxicities for HCC patients. TOMO therapy could be used to effectively against HCC in treatment-naive, intrahepatic failure, residual disease, and recurrent settings.
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http://dx.doi.org/10.3389/fonc.2021.559112DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8201615PMC
May 2021

In Vitro and In Vivo Comparative Evaluation of a Shellac-Ammonium Paclitaxel-Coated Balloon versus a Benchmark Device.

J Interv Cardiol 2021 25;2021:9962313. Epub 2021 May 25.

Department of Medical Affair, Cardionovum Co, Ltd, Wuhan, China.

Objectives: The present study was designed to compare the characteristics and performance regarding drug delivery of a novel drug-coated balloon (DCB) to a benchmark device (Restore® versus SeQuent® Please) in an in vitro and in vivo model.

Background: Although Restore® and SeQuent® are both paclitaxel-coated, they use different coating excipient, shellac-ammonium salt and iopromide, respectively. Preclinical study comparing these two different commercial DCBs regarding their characteristics and effects on early vascular response is sparse.

Methods: Restore® and SeQuent® DCBs were scanned with electron microscopy for surface characteristic assessment. Both DCBs were transported in an in vitro vessel model for the evaluation of drug wash-off rate and particulate formation. Eighteen coronary angioplasties with either Restore® or SeQuent® DCBs were conducted in 6 swine (three coronary vessels each). Histopathological images of each vessel were evaluated for vessel injury.

Results: The surface of Restore® DCB was smooth and evenly distributed with hardly visible crystal, while SeQuent® DCB showed a rougher surface with relatively larger apparent crystals. Restore® DCB had a lower drug wash-off rate and fewer large visible particles, compared to the SeQuent® DCB. No significant difference in mean injure score was found between Restore® and SeQuent® group.

Conclusion: Our results suggest that Restore® is better in preclinical performance regarding less release of particles and lower drug wash-off rate as compared to SeQuent® Please. The Restore® DCB, using stable amorphous coating and shellac-ammonium salt as an excipient, appears to provide an advantage in drug delivery efficacy; however, further clinical studies are warranted.
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http://dx.doi.org/10.1155/2021/9962313DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8172300PMC
July 2021

The RNA demethylase ALKBH5 promotes osteoblast differentiation by modulating Runx2 mRNA stability.

FEBS Lett 2021 Jun 9. Epub 2021 Jun 9.

Department of Paediatrics, Affiliated Maternity and Child Health Care Hospital of Nantong University, China.

AlkB homolog 5 (ALKBH5) has been reported as a key m6A demethylase that is involved in development and diseases; however, the function of ALKBH5 in osteogenesis remains unknown. In this study, we report that ALKBH5 mRNA and protein expression were upregulated during osteoblast differentiation and that ALKBH5 knockdown suppressed osteoblast differentiation, mineralization, and the expression of osteogenic biomarkers. Conversely, ALKBH5 overexpression promoted osteogenesis. Moreover, the expression of wild-type ALKBH5, but not the m6A-modified active site mutant ALKBH5, could rescue ALKBH5 knockdown-induced osteogenesis inhibition. Furthermore, knockdown of ALKBH5 significantly impaired the mRNA stability of the transcription factor Runx2, which plays a key role in osteoblast differentiation. Taken together, our results suggest that ALKBH5 promotes osteogenesis through modulating Runx2 mRNA stability.
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http://dx.doi.org/10.1002/1873-3468.14145DOI Listing
June 2021

Peptidome Analysis of Pancreatic Tissue Derived from T1DM Mice: Insights into the Pathogenesis and Clinical Treatments of T1DM.

Biomed Res Int 2021 21;2021:9987042. Epub 2021 May 21.

Department of Pediatrics, Affiliated Maternity and Child Health Care Hospital of Nantong University, Nantong, Jiangsu, China.

Bioactive peptides attract growing concerns for their participation in multiple biological processes. Their roles in the pathogenesis of type 1 diabetes mellitus remain poorly understood. In this study, we used LC-MS/MS technology to compare the peptide profiling between pancreatic tissue of T1DM mice and pancreatic tissue of matched control groups. A total of 106 peptides were differentially expressed in T1DM pancreatic tissue, including 43 upregulated and 63 downregulated peptides. Most of the precursor proteins are insulin. Further bioinformatics analysis (GO and pathway analysis) indicated that the potential functions of these differential peptides were tightly related to regulation of endoplasmic reticulum stress. In conclusion, this study highlights new candidate peptides and provides a new perspective for exploring T1DM pathogenesis and clinical treatments.
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http://dx.doi.org/10.1155/2021/9987042DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8164536PMC
May 2021

The Physical Adsorption of Gelatinized Starch with Tannic Acid Decreases the Inhibitory Activity of the Polyphenol against α-Amylase.

Foods 2021 May 28;10(6). Epub 2021 May 28.

College of Food Science and Engineering, Northwest A & F University, Xianyang 712100, China.

The effects of mixing orders of tannic acid (TA), starch, and α-amylase on the enzyme inhibition of TA were studied, including mixing TA with α-amylase before starch addition (order 1), mixing TA with pre-gelatinized starch before α-amylase addition (order 2) and co-gelatinizing TA with starch before α-amylase addition (order 3). It was found that the enzyme inhibition was always highest for order 1 because TA could bind with the enzyme active site thoroughly before digestion occurred. Both order 2 and 3 reduced α-amylase inhibition through decreasing binding of TA with the enzyme, which resulted from the non-covalent physical adsorption of TA with gelatinized starch. Interestingly, at low TA concentration, α-amylase inhibition for order 2 was higher than order 3, while at high TA concentration, the inhibition was shown with the opposite trend, which arose from the difference in the adsorption property between the pre-gelatinized and co-gelatinized starch at the corresponding TA concentrations. Moreover, both the crystalline structures and apparent morphology of starch were not significantly altered by TA addition for order 2 and 3. Conclusively, although a polyphenol has an acceptable inhibitory activity in vitro, the actual effect may not reach the expected one when taking processing procedures into account.
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http://dx.doi.org/10.3390/foods10061233DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8226663PMC
May 2021

Partial Deficiency of Zfp217 Resists High-Fat Diet-Induced Obesity by Increasing Energy Metabolism in Mice.

Int J Mol Sci 2021 May 20;22(10). Epub 2021 May 20.

Key Laboratory of Animal Genetics, Breeding and Reproduction Ministry of Education, College of Animal Science and Technology, Huazhong Agricultural University, Wuhan 430070, China.

Obesity-induced adipose tissue dysfunction and disorders of glycolipid metabolism have become a worldwide research priority. Zfp217 plays a crucial role in adipogenesis of 3T3-L1 preadipocytes, but about its functions in animal models are not yet clear. To explore the role of Zfp217 in high-fat diet (HFD)-induced obese mice, global Zfp217 heterozygous knockout (Zfp217) mice were constructed. Zfp217 mice and Zfp217 mice fed a normal chow diet (NC) did not differ significantly in weight gain, percent body fat mass, glucose tolerance, or insulin sensitivity. When challenged with HFD, Zfp217 mice had less weight gain than Zfp217 mice. Histological observations revealed that Zfp217 mice fed a high-fat diet had much smaller white adipocytes in inguinal white adipose tissue (iWAT). Zfp217 mice had improved metabolic profiles, including improved glucose tolerance, enhanced insulin sensitivity, and increased energy expenditure compared to the Zfp217 mice under HFD. We found that adipogenesis-related genes were increased and metabolic thermogenesis-related genes were decreased in the iWAT of HFD-fed Zfp217 mice compared to Zfp217 mice. In addition, adipogenesis was markedly reduced in mouse embryonic fibroblasts (MEFs) from Zfp217-deleted mice. Together, these data indicate that Zfp217 is a regulator of energy metabolism and it is likely to provide novel insight into treatment for obesity.
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http://dx.doi.org/10.3390/ijms22105390DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8161011PMC
May 2021

Neutrophil to lymphocyte ratio and fibrinogen values in predicting patients with type B aortic dissection.

Sci Rep 2021 May 31;11(1):11366. Epub 2021 May 31.

Department of Vascular Surgery, Changhai Hospital, Navy Medical University, Shanghai, 200433, China.

The aim of this study is to detect the diagnosis value of neutrophil lymphocyte ratio (NLR) and fibrinogen (FIB) in type B aortic dissection (TBAD) patients. This retrospective observation study consisted patients with TBAD, aortic aneurysm and physical examination between January 1, 2016 and December 31, 2019. Demographic and clinical information after the first admission were collected. Multivariate logistic regression analysis was performed to explore the correlational relationship between NLR, FIB and TBAD. Receiver Operating Characteristic Curve (ROC) was performed to evaluate the diagnostic implication of NLR and FIB in TBAD patients. Six hundred and six patients who were first diagnosed with TBAD were included. Control groups were 202 aortic aneurysm and 140 physical examination subjects. The level of NLR and FIB in aortic dissection patients was significantly higher than aortic aneurysm patients and healthy group (P < 0.001). According to the results of multivariate logistic regression analysis, NLR and FIB were independent risk factors of aortic dissection, and the odds ratio (OR) and 95% confidence interval (CI) value of NLR and FIB were 1.499 (1.126-1.738) and 1.914 (1.475-2.485), respectively. The area under the curve (AUC) was 0.836 of NLR and 0.756 of FIB. NLR and FIB showed high specificity, 89% and 83% respectively. This is the first study provided information on the diagnosis performance of NLR and FIB in TBAD patients. NLR and FIB showed high specificity, which may be a valuable tool for the diagnosis of TBAD.
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http://dx.doi.org/10.1038/s41598-021-90811-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8166888PMC
May 2021

Risk Factors for Recurrent Tracheoesophageal Fistula After Gross Type C Esophageal Atresia Repair.

Front Pediatr 2021 13;9:645511. Epub 2021 May 13.

National Center for Children's Health, Department of Neonatal Surgery, Beijing Children's Hospital, Capital Medical University, Beijing, China.

To determine the possible risk factors of recurrent tracheoesophageal fistula (rTEF) after Gross type C esophageal atresia (EA) and tracheoesophageal fistula (TEF) repair. The medical records of 343 pediatric patients with Gross type C EA/TEF who underwent surgical repair were retrospectively analyzed. The patients were retrospectively divided into two groups according to whether they had rTEF. Univariate and multivariable logistic regression analysis were performed to identify risk factors for rTEF. After the diagnosis of EA/TEF, 343 patients (221 boys) underwent primary repairs after birth. According to the follow-up results (257 patients survived, 42 died, and 43 were lost to follow-up), 259 patients (257 survived and two died after rTEF repair) were included in the analysis. rTEF occurred in 33 patients (33/259, 12.74%), with a median onset time to recurrence of 3.8 (2.2, 8.2) months. Multivariate analysis showed that closing the original TEF with ligation and hospital stay ≥ 28.5 days were significant risk factors of rTEF with OR of 4.083 (1.481, 11.261) and 3.228 (1.431, 7.282). Surgical closure technique of original TEF and the length of initial stay could influence the occurrence of rTEF after Gross type C EA/TEF repair.
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http://dx.doi.org/10.3389/fped.2021.645511DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8155366PMC
May 2021

Thoracoscopy for Esophageal Diverticula After Esophageal Atresia With Tracheo-Esophageal Fistula.

Front Pediatr 2021 4;9:663705. Epub 2021 May 4.

Department of Neonatal Surgery, Beijing Children's Hospital, National Center for Children's Health, Capital Medical University, Beijing, China.

Esophageal diverticulum (ED) is an extremely rare complication of congenital esophageal atresia (EA) with or without tracheoesophageal fistula (TEF) surgery. We aimed to investigate feasible methods for the treatment of this rare complication. We retrospectively reviewed all patients with EA/TEF at Beijing Children's Hospital from January 2015 to September 2019. The clinicopathological features of patients with ED after EA/TEF surgery were recorded. Follow-up was routinely performed after surgery until December 2020. Among 198 patients with EA/TEF, ED only occurred in four patients (2.02%; one male, three female). The four patients had varying complications after the initial operation, including anastomotic leakage (3/4), esophageal stenosis (3/4), and recurrence of TEF (1/4). The main clinical symptoms of ED included recurrent pneumonia (4/4), coughing (4/4), and dysphagia (3/4). All ED cases occurred near the esophageal anastomosis. Patients' age at the time of diverticulum repair was 6.6-16.8 months. All patients underwent thoracoscopic esophageal diverticulectomy (operation time: 1.5-3.5 h). Anastomotic leakage occurred in one patient and spontaneously healed after 2 weeks. The other three patients had no peri-operative complications. All patients were routinely followed up after surgery for 14-36 months. During the follow-up period, all patients could eat orally, had good growth and weight gain, and showed no ED recurrence or anastomotic leakage on esophagogram. ED is a rare complication after EA/TEF surgery and is a clear indication for diverticulectomy. During the midterm follow-up, thoracoscopic esophageal diverticulectomy was safe and effective for ED after EA/TEF surgery.
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http://dx.doi.org/10.3389/fped.2021.663705DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8129005PMC
May 2021

Risk Factors and Reasons for Treatment Abandonment for Patients With Esophageal Atresia: A Study From a Tertiary Care Hospital in Beijing, China.

Front Pediatr 2021 27;9:634573. Epub 2021 Apr 27.

Department of Neonatal Surgery, National Center for Children's Health, Beijing Children's Hospital, Capital Medical University, Beijing, China.

This study aims to identify the risk factors and reasons for treatment abandonment for patients with esophageal atresia (EA) in a tertiary care hospital in China. A retrospective study was conducted on 360 patients with EA admitted to Beijing Children's Hospital between January 1, 2007 and June 1, 2020. Medical records for treatment abandonment and non-treatment abandonment patients were compared. Univariate and multivariate logistic regression analyses were conducted to identify potential risk factors for treatment abandonment. After the diagnosis of EA, parents of 107 patients refused surgical repair and discharged against medical advice, and 253 patients underwent surgical repair. Among these 253 patients, parents of 59 patients abandoned treatment after surgery; 52 patients were discharged in an unstable condition, and parents of seven patients abandoned resuscitation leading to death in the hospital. By comparing clinical characteristics between treatment abandonment before surgery ( = 107) and non-treatment abandonment ( = 253) groups, we found that mother's parity >1, unplanned admission to intensive care unit before surgery, associated anomalies, and Gross type A/B were significant independent risk factors for treatment abandonment before surgery. Furthermore, birth weight <2,545 g, being discharged from neonatal center/intensive care unit and other departments, unplanned admission to intensive care unit after surgery, operative time >133 min, admission before 2016, pneumothorax, and anastomotic leakage were significant independent risk factors for treatment abandonment after surgery. The reasons for treatment abandonment included financial difficulties, multiple malformations with poor prognosis, belief of incurability and concerns about the prognosis of the diseases, postoperative complications, and extensive length of intensive care unit stay. Treatment abandonment of children with EA/TEF is still a common and serious problem in China. This study showed that EA/TEF patients in critical conditions, with associated anomalies, Gross type A/B, and who had occurrence of complications had high-risk for treatment abandonment.
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http://dx.doi.org/10.3389/fped.2021.634573DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8112547PMC
April 2021

The Regulatory Role of Oxygen Metabolism in Exercise-Induced Cardiomyocyte Regeneration.

Front Cell Dev Biol 2021 15;9:664527. Epub 2021 Apr 15.

Institute for Brain Sciences Research, School of Life Sciences, Henan University, Kaifeng, China.

During heart failure, the heart is unable to regenerate lost or damaged cardiomyocytes and is therefore unable to generate adequate cardiac output. Previous research has demonstrated that cardiac regeneration can be promoted by a hypoxia-related oxygen metabolic mechanism. Numerous studies have indicated that exercise plays a regulatory role in the activation of regeneration capacity in both healthy and injured adult cardiomyocytes. However, the role of oxygen metabolism in regulating exercise-induced cardiomyocyte regeneration is unclear. This review focuses on the alteration of the oxygen environment and metabolism in the myocardium induced by exercise, including the effects of mild hypoxia, changes in energy metabolism, enhanced elimination of reactive oxygen species, augmentation of antioxidative capacity, and regulation of the oxygen-related metabolic and molecular pathway in the heart. Deciphering the regulatory role of oxygen metabolism and related factors during and after exercise in cardiomyocyte regeneration will provide biological insight into endogenous cardiac repair mechanisms. Furthermore, this work provides strong evidence for exercise as a cost-effective intervention to improve cardiomyocyte regeneration and restore cardiac function in this patient population.
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http://dx.doi.org/10.3389/fcell.2021.664527DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8083961PMC
April 2021

SEMPANet: A Modified Path Aggregation Network with Squeeze-Excitation for Scene Text Detection.

Sensors (Basel) 2021 Apr 9;21(8). Epub 2021 Apr 9.

Guangdong Key Laboratory of Intelligent Information Processing and Shenzhen Key Laboratory of Media Security, Shenzhen 518060, China.

Recently, various object detection frameworks have been applied to text detection tasks and have achieved good performance in the final detection. With the further expansion of text detection application scenarios, the research value of text detection topics has gradually increased. Text detection in natural scenes is more challenging for horizontal text based on a quadrilateral detection box and for curved text of any shape. Most networks have a good effect on the balancing of target samples in text detection, but it is challenging to deal with small targets and solve extremely unbalanced data. We continued to use PSENet to deal with such problems in this work. On the other hand, we studied the problem that most of the existing scene text detection methods use ResNet and FPN as the backbone of feature extraction, and improved the ResNet and FPN network parts of PSENet to make it more conducive to the combination of feature extraction in the early stage. A SEMPANet framework without an anchor and in one stage is proposed to implement a lightweight model, which is embodied in the training time of about 24 h. Finally, we selected the two most representative datasets for oriented text and curved text to conduct experiments. On ICDAR2015, the improved network's latest results further verify its effectiveness; it reached 1.01% in F-measure compared with PSENet-1s. On CTW1500, the improved network performed better than the original network on average.
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http://dx.doi.org/10.3390/s21082657DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8069456PMC
April 2021

Dapagliflozin reverses the imbalance of T helper 17 and T regulatory cells by inhibiting SGK1 in a mouse model of diabetic kidney disease.

FEBS Open Bio 2021 May 1;11(5):1395-1405. Epub 2021 May 1.

Department of Endocrinology and Metabolism, Nanfang Hospital, Southern Medical University, Guangzhou, China.

An imbalance between T helper 17 (Th17) and T regulatory (Treg) cell subsets contributes to the pathogenesis of diabetic kidney disease (DKD). However, the underlying regulatory mechanisms that cause this imbalance are unknown. Serum/glucocorticoid-regulated kinase 1 (SGK1) has been suggested to affect Th17 polarization in a salt-dependent manner, and sodium/glucose cotransporter 2 inhibitors (SGLT2i) have been demonstrated to regulate sodium-mediated transportation in the renal tubules. This study aimed to evaluate the potential benefits of dapagliflozin (Dap) on DKD, as well as its influence on shifting renal T-cell polarization and related cytokine secretion. We treated male db/db mice with Dap or voglibose (Vog) and measured blood and kidney levels of Th17 and Treg cells using flow cytometry. We found that Th17 cells were significantly increased, while Treg cells were significantly decreased in diabetic mice. Moreover, Dap suppressed the polarization of Th17/Treg cells by inhibiting SGK1 in diabetic kidneys, and this was accompanied by attenuation of albuminuria and tubulointerstitial fibrosis independent of glycemic control. Taken together, these results demonstrate that the imbalance of Th17/Treg cells plays an important role in the progression of DKD. Moreover, Dap protects against DKD by inhibiting SGK1 and reversing the T-cell imbalance.
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http://dx.doi.org/10.1002/2211-5463.13147DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8091586PMC
May 2021

Designing nanofibrous membrane with biomimetic caterpillar-like structured for highly-efficient and simultaneous removal of insoluble emulsified oils and soluble dyes towards sewage remediation.

J Hazard Mater 2021 07 17;414:125442. Epub 2021 Feb 17.

State Key Lab of Oil and Gas Reservoir Geology and Exploitation, Southwest Petroleum University, Chengdu 610500, PR China.

Purification of insoluble emulsified oils and soluble organic pollutants from sewage has attracted tremendous attention in today's society. Herein, a stable and environmentally friendly nanofibrous membrane with hierarchical caterpillar-like structure was fabricated via in-situ hydrothermal growing the nickel-cobalt layered double hydroxides (NiCo-LDHs) on tche polyacrylonitrile (PAN) electrospun nanofibers. The wrapped hydrophilic NiCo-LDHs constructed the hierarchical structure and endowed the membrane attractive superhydrophilicity (≈ 0°)/underwater superoleophobicity (≈ 161°) and enhanced oil-repellency performance. Meanwhile, the [email protected]/oPAN NFMs can display the ultra-fast flux of SSEs (xylene/water emulsion, 4175 L m h) and satisfactory separation efficiency (99.07%). Moreover, the introduction of positively charged NiCo-LDHs increased plentiful adsorption active sites for membranes, which is beneficial to demulsify ionic SSEs and adsorb organic pollutants. Finally, for simultaneous purification of complex sewage by the dead-end and cross-flow filtration experiment, the composite membrane both displayed splendid removal rate of oil (> 99.0%) and dyes (> 99.0%), robust regeneration recycle-ability and no secondary pollution. Hence, it is expected that such strategy of combining electrospun and chelating-assisted in-situ hydrothermal can provide a low energy consumption and high decontamination technology for severe environmental crisis.
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http://dx.doi.org/10.1016/j.jhazmat.2021.125442DOI Listing
July 2021

One-step in-situ fabrication of carbon nanotube/stainless steel mesh membrane with excellent anti-fouling properties for effective gravity-driven filtration of oil-in-water emulsions.

J Colloid Interface Sci 2021 Jun 16;592:87-94. Epub 2021 Feb 16.

State Key Laboratory of Oil & Gas Reservoir Geology and Exploitation, Southwest Petroleum University, Chengdu, Sichuan 610500, China; College of Chemistry and Chemical Engineering, Southwest Petroleum University, Chengdu, Sichuan 610500, China.

The occurrence of membrane fouling has resulted in limited wastewater treatment applications. The development of superhydrophilic-underwater superoleophobic materials has received significant attention owing to their good anti-fouling properties. However, to fabricate such materials need costly regents and tedious steps. Thus, developing a one-step process to prepare a low-cost material for oil/water separation is still desired. In this study, bio-inspired from an arachnid, inorganic carbon nanotube stainless steel meshes ([email protected]) having superhydrophilic-underwater superoleophobic and excellent anti-fouling properties and a unique fiber structure were fabricated via a one-step thermal chemical vapor deposition method. The [email protected] had a small pore size enabling a high water flux of 10,639 L mh and the separation of oily wastewater, including various emulsions, at a high rejection ratio of >98.89%. As a result of its excellent chemical stability under high temperatures, a broad pH range, and saline environments, the [email protected] has the potential to be used in extreme conditions. In summary, these [email protected] are easy to fabricate and are low-cost as a result of inexpensive reagents involved. Moreover, these novel superwetting membranes are promising candidates for treatment of hazardous oily wastewater.
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http://dx.doi.org/10.1016/j.jcis.2021.02.043DOI Listing
June 2021

Diabetes Mellitus Lowers the Risk of Aortic Dissection: a Systematic Review and Meta-Analysis.

Ann Vasc Surg 2021 Jan 30. Epub 2021 Jan 30.

Department of Vascular Surgery, Changhai Hospital, the Naval Military Medical University, Shanghai, China. Electronic address:

Background: This systematic review and meta-analysis aimed to investigate the association between diabetes mellitus and aortic dissection.

Methods: The PubMed and Embase databases were searched until December 2019 to identify all articles reporting diabetes mellitus and aortic dissection. The pooled odds ratio and 95% confidence interval were calculated using random-effects model.

Results: A total of 14 articles with 15,794 participants, of which 2133 diabetes mellitus patients, were eligible and included in this meta-analysis. The data suggested that diabetes mellitus decreased the risk of aortic dissection. In the subgroup analysis, this association was significant in worldwide studies except for the Chinese cohort and in studies adjusted for confounding factors. The results were stable after sensitivity analysis and no evidence of publication bias was found among studies.

Conclusions: The result of this meta-analysis indicated that diabetes mellitus was associated with a lower risk of aortic dissection.
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http://dx.doi.org/10.1016/j.avsg.2020.12.016DOI Listing
January 2021

MiR-144-3p-mediated dysregulation of EIF4G2 contributes to the development of hepatocellular carcinoma through the ERK pathway.

J Exp Clin Cancer Res 2021 Feb 1;40(1):53. Epub 2021 Feb 1.

State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, Zhejiang University School of Medicine, 79# Qingchun Road, Hangzhou, 310003, China.

Background: Hepatocellular carcinoma (HCC) is one of the most common cancers with high incidence and mortality. However, the underlying mechanisms of HCC still remain unclear. Eukaryotic translation initiation factors (eIFs) have a substantial effect on tumor development. In this study, we were aimed to investigate the role of eukaryotic translation initiation factor 4 gamma 2 (EIF4G2) in HCC.

Methods: Western blot (WB) of 30 paired HCC tissues and tissue microarrays (TMAs) conducted by immunohistochemistry (IHC) in 89 paired HCC samples were performed to assess EIF4G2 expression. Clone formation, real-time cell analysis (RTCA), wound healing and transwell assays were adopted to evaluate the role of EIF4G2 on HCC cell proliferation, migration and invasion abilities. The function of EIF4G2 in HCC tumor growth was assessed in a xenograft nude mouse model in vivo. The regulation of EIF4G2 by miR-144-3p was performed by luciferase reporter assay and WB.

Results: The EIF4G2 protein was clearly upregulated in HCC tissues, and high EIF4G2 expression was closely related to HCC prognosis. EIF4G2 silencing could inhibit HCC cell growth and metastasis in vitro, and suppress tumorigenesis in vivo by repressing the ERK signaling pathway. The results of luciferase reporter assays, WB and IHC staining verified that EIF4G2 was negatively regulated by miR-144. And re-expression of EIF4G2 could partially reverse the inhibiting effect of miR-144 in HCC.

Conclusion: In summary, our study revealed the role of EIF4G2 in HCC development via the activation of the ERK pathway. We also found that EIF4G2 could be negatively regulated by the tumor suppressor miR-144. Our investigations indicated that EIF4G2 might be a promising therapeutic target in HCC.
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http://dx.doi.org/10.1186/s13046-021-01853-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7852102PMC
February 2021

ZMYND8 promotes the growth and metastasis of hepatocellular carcinoma by promoting HK2-mediated glycolysis.

Pathol Res Pract 2021 Mar 19;219:153345. Epub 2021 Jan 19.

Department of Hepatopancreatobiliary Surgery & Minimally Invasive Surgery, Zhejiang Provincial People's Hospital (People's Hospital of Hangzhou Medical College), Hangzhou, 310014, China. Electronic address:

The bromodomain protein zinc finger MYND-type containing 8 (ZMYND8) plays a critical role in human breast cancer. However, the expression and biological function of ZMYND8 in hepatocellular carcinoma (HCC) are poorly understood. In this study, ZMYND8 expression was found to be elevated in HCC based on the cancer genome atlas (TCGA) and gene expression omnibus (GEO) databases. Next, we confirmed that ZMYND8 was frequently overexpressed in HCC tissues compared with adjacent non-tumor tissues. The up-regulated level of ZMYND8 was also observed in HCC cell lines. Elevated ZMYND8 expression was correlated with unfavorable clinicopathological features and poor prognosis of HCC patients. Functionally, ectopic expression of ZMYND8 potentiated the proliferation, migration, and invasion of Hep3B cells. Conversely, ZMYND8 knockdown led to the reduced proliferation and invasiveness of HCCLM3 cells. ZMYND8 silencing restrained the growth of HCCLM3 cells in vivo. Mechanistically, ZMYND8 enhanced glucose consumption, lactate production, and ATP level in HCC cells. Pharmacological inhibition of glycolysis using 2-DG blocked the promoting effects of ZMYND8 on HCC cell proliferation and mobility. Furthermore, hexokinase 2 (HK2), a key enzyme of glycolysis, was identified as the downstream target of ZMYND8 in HCC cells. ZMYND8 promoted HK2 transcription by recruiting bromodomain containing 4 (BRD4) to its promoter. Knockdown of HK2 abrogated the oncogenic functions of ZMYND8 in HCC. Altogether, these data indicated that ZMYND8 promoted the growth and metastasis of HCC by promoting HK2-mediated glycolysis and might serve as a promising biomarker and therapeutic target for HCC.
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http://dx.doi.org/10.1016/j.prp.2021.153345DOI Listing
March 2021

Analysis of cytokines and trace elements in children with febrile seizures.

Transl Pediatr 2020 Dec;9(6):809-817

Department of Pediatrics, Nantong Maternal and Child Health Care Hospital, Nantong, China.

Background: Febrile seizure (FS) is a common neurological condition in children and affects 2-5% of cases of fever. FS occurs with temperature >38 °C without symptoms of central nervous system infection, severe electrolyte imbalance, or clear cause.

Methods: From June 2018 to December 2019, 65 children with FS, and 60 children with acute upper respiratory tract infections without seizures who were admitted to the pediatric department, and 60 healthy children as the control group were selected for the study. The serum iron (SI), serum calcium (SC), interleukin (IL)-6, IL-10 and procalcitonin (PCT) levels in the two groups of children were detected. The FS group was further divided into simple FS (SFS) and complex FS (CFS).

Results: The duration of fever in the FS group was significantly longer than in the control group (P<0.05). The SC and SI levels of the FS group were significantly lower than those in the control group (P<0.05). The SC and SI levels of the CFS group were also lower than those of the SFS group (P<0.05), and the IL-6 levels of the CFS group were significantly higher than in the SFS group (P<0.05).

Conclusions: A decrease in the levels of SI, and SC and an increase of IL-6 were closely related to the occurrence of FS, suggesting that clinical attention should be paid to monitoring changes of SI, SC and IL-6 levels in children with FS. As the levels of SI and SC decrease, the frequency of possible seizures may increase. Care should be taken to correct electrolyte disorders in time.
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http://dx.doi.org/10.21037/tp-20-398DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7804487PMC
December 2020

Effects of different types of microbial inoculants on available nitrogen and phosphorus, soil microbial community, and wheat growth in high-P soil.

Environ Sci Pollut Res Int 2021 May 12;28(18):23036-23047. Epub 2021 Jan 12.

Environment Research Institute, Shandong University, Binhai Road 72, Qingdao, 266237, Shandong, China.

Irrational application of chemical fertilizers causes soil nutrient imbalance, reduced microbial diversity, soil diseases, and other soil quality problems and is one of the main sources of non-point pollution. The application of microbial inoculant (MI) can improve the soil environment and crop growth to reduce problems caused by irrational application of chemical fertilizers. Field experiments were carried out in high-phosphorus soils to study the effects of the addition of various MIs combined with chemical fertilizers on soil properties, wheat growth, and soil microbial composition and structure. The MIs consisted of one fungal agent: Trichoderma compound agent (TC) and five bacterial agents, namely soil remediation agent (SR), anti-repeat microbial agent (AM), microbial agent (MA), plant growth-promoting rhizobacteria (PG), and biological fertilizer agent (BF). The wheat yield increased by 15.2-33.4% with the addition of MIs, and PG with Bacillus subtilis as the core microorganism had the most obvious effect on increasing the production (p < 0.05). For the entire growth period of wheat, all MIs applied significantly increased the available nitrogen (AN) (p < 0.05) but did not significantly affect the available phosphorus (AP). BF has the best effect on increasing AN in the soil. The 16S rRNA sequencing results indicated that the dominant phyla of soil bacteria were Proteobacteria, Acidobacteria, Bacteroidetes, Actinobacteria, and Verrucomicrobia. The addition of MIs increased the relative abundance of Acidobacteria, Actinobacteria, Chloroflexi and decreased Proteobacteria and Bacteroidetes. The diversity of soil bacterial community (Chao1) was significantly higher in the soil added with TC than that added with BF (p < 0.05). All bacterial agents significantly enriched various genera (p < 0.05), while the fungal agent (TC) did not enrich the genera significantly. pH and AN, but not TP, were closely related to the dominant bacteria phylum in high-P soil. The application of MIs improved AN in soil, increased the wheat yield, and changed the relative abundance of the soil dominant phylum, and these changes were closely related to the type of MIs. The results provide a scientific basis for rational use of different types of MIs in high-P soil.
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http://dx.doi.org/10.1007/s11356-020-12203-yDOI Listing
May 2021

Infectivity and pathogenicity of different hepatitis E virus genotypes/subtypes in rabbit model.

Emerg Microbes Infect 2020 Dec;9(1):2697-2705

Department of Microbiology and Infectious Disease Centre, School of Basic Medical Sciences, Peking University Health Science Centre, Beijing, People's Republic of China.

The pathogenicity of each hepatitis E virus (HEV) genotypes/subtypes may be different. This study aimed to investigate the infectivity and pathogenicity of different HEV genotypes/subtypes from different mammalian sources especially human in rabbits, and to assess whether rabbits are an appropriate animal model to study different HEV genotypes/subtypes. Thirty-seven rabbits were randomly divided into nine groups and inoculated with eight different HEV strains, including human-derived HEV3b (hHEV-3b), hHEV-4a, hHEV-4d and hHEV-4h, swine-derived HEV4d (sHEV-4d) and sHEV-4h, rabbit-derived HEV3 (HEV-3ra) and camel-derived HEV8. HEV RNA, antigen, anti-HEV and alanine aminotransferase (ALT) in serum or/and feces were monitored weekly. One rabbit from each group was euthanized at seven weeks post inoculation and the liver specimens were taken for histopathological analysis and immunofluorescence staining of HEV ORF2 proteins. hHEV-4d, sHEV-4d and HEV-3ra infections were successfully established in rabbits and typical acute hepatitis symptoms were observed, including viraemia/antigenemia, fecal virus/antigen shedding, elevated ALT level and liver histopathological changes. One rabbit infected with HEV-3ra showed chronic infection. hHEV-4d and sHEV-4d are less infectious and pathogenic than HEV-3ra in rabbits. hHEV-3b and HEV8 only caused inapparent infection in rabbits as 60% (3/5) and 20% (1/5) of the rabbits seroconverted to anti-HEV, respectively. No obvious signs of HEV infection in rabbits inoculated with hHEV-4a, hHEV-4h and sHEV-4h. The infectivity and pathogenicity of different HEV genotypes/subtypes in rabbits is different, which may be related to the species specificity of HEV. Rabbit can be used as an animal model for the study of HEV-3ra and more importantly human HEV-4d.
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http://dx.doi.org/10.1080/22221751.2020.1858178DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7781933PMC
December 2020

Dose-dependent effect of human milk on Bronchopulmonary dysplasia in very low birth weight infants.

BMC Pediatr 2020 11 16;20(1):522. Epub 2020 Nov 16.

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

Background And Aim: Human milk has potential protective effects against bronchopulmonary dysplasia (BPD). However, studies on the association between the dose of human milk and BPD in China are limited. This study aimed to evaluate the dose-dependent effects of human milk on BPD and other neonatal morbidities in very low birth weight (VLBW) infants.

Methods: This retrospective cohort study of preterm infants was conducted on preterm infants of gestational age ≤ 34 weeks and birth weight < 1500 g admitted to the multicenter clinical research database for breastfeeding quality improvement in Jiangsu province. The multivariate analysis was performed to compare the effect outcomes of daily graded doses [1-24 mL/(kg · day), 25-49 mL/(kg · day), and ≥ 50 mL/(kg · day) of body weight] of human milk on neonatal outcomes throughout the first 4 weeks of life versus a reference group receiving no human milk. The models were adjusted for potential confounding variables.

Results: Of 964 included infants, 279 (28.9%) received exclusive preterm formula, 128 (13.3%) received 1-24 ml/(kg · day), 139 (14.4%) received 25-49 ml/(kg · day), and 418 (43.4%) received ≥50 ml/(kg · day) human milk for the first 4 weeks of life. Compared with infants receiving exclusive formula, those receiving the highest volume of human milk daily [≥50 mL/(kg · day)] had lower incidences of BPD [27.5% in ≥50 mL/(kg · day) vs 40.1% in 0 mL/(kg · day) human milk, P = 0.001)], moderate and severe BPD [8.9% in ≥50 mL/(kg · day) vs 16.1% in 0 mL/(kg · day), P = 0.004], necrotizing enterocolitis [NEC; 3.8% in ≥50 mL/(kg · day) vs 10.8% in 0 mL/(kg · day), P = 0.001], late-onset sepsis [LOS; 9.3% in ≥50 mL/(kg · day) vs 19.7% in 0 mL/(kg · day), P <0.01], and extrauterine growth retardation [EUGR; 38.5% in ≥50 mL/(kg · day) vs 57.6% in 0 mL/(kg · day), P <0.01)]. The logistic regression indicated that those receiving ≥50 ml/kg · day human milk had lower odds of BPD [adjusted odds ratio (AOR) 0.453; 95% confidence interval (CI): 0.309, 0.666], moderate and severe BPD (AOR 0.430; 95% CI: 0.249, 0.742), NEC (AOR 0.314; 95% CI: 0.162, 0. 607), LOS (AOR 0.420; 95% CI: 0.263, 0.673), and EUGR (AOR 0.685; 95% CI: 0.479, 0.979).

Conclusions: A daily threshold amount of ≥50 ml/(kg · day) human milk in the first 4 weeks of life was associated with lower incidence of BPD as well as NEC, LOS, and EUGR in VLBW infants.

Trial Registration: ClinicalTrials.gov Identifier: NCT03453502 . Registration date: March 5, 2018. This study was retrospectively registered.
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http://dx.doi.org/10.1186/s12887-020-02394-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7666971PMC
November 2020

circRNA Hsa_circ_0020850 Silence Represses the Development of Lung Adenocarcinoma via Regulating miR-195-5p/IRS2 Axis.

Cancer Manag Res 2020 28;12:10679-10692. Epub 2020 Oct 28.

Department of Gastrointestinal Cancer Surgery, The First Affiliated Hospital of Xinjiang Medical University, Urumqi, Xinjiang, 830054, People's Republic of China.

Background: The dysregulated circular RNAs (circRNAs) are relevant to lung adenocarcinoma development. Nevertheless, the function and mechanism of hsa_circ_0020850 (circ_0020850) in lung adenocarcinoma development are uncertain.

Methods: A total of 35 lung adenocarcinoma patients were recruited, and the tumor and normal tissue samples were harvested. A549 and PC-9 cells were exhibited for the experiments in vitro. circ_0020850, microRNA-195-5p (miR-195-5p) and insulin receptor substrate 2 (IRS2) abundances were detected via quantitative reverse transcription-polymerase chain reaction or Western blot. Cell proliferation, apoptosis, migration and invasion were measured via cell counting kit-8 (CCK8) assay, colony formation, flow cytometry, transwell and Western blot. The relationship between miR-195-5p and circ_0020850 or IRS2 was tested via dual-luciferase reporter analysis. The function of circ_0020850 on cell growth in vivo was measured via xenograft model.

Results: circ_0020850 expression was enhanced in lung adenocarcinoma tissues and cells. circ_0020850 silence suppressed cell proliferation, migration and invasion and facilitated apoptosis. miR-195-5p was targeted via circ_0020850, and its knockdown reversed the inhibitive effect of circ_0020850 silence on lung adenocarcinoma development. IRS2 was targeted via miR-195-5p, and miR-195-5p inhibited cell proliferation, migration and invasion and induced apoptosis via decreasing IRS2. circ_0020850 knockdown decreased IRS2 expression via regulating miR-195-5p. circ_0020850 down-regulation decreased lung adenocarcinoma xenograft tumor growth.

Conclusion: circ_0020850 knockdown repressed lung adenocarcinoma cell proliferation, migration and invasion and promoted apoptosis via regulating miR-195-5p and IRS2.
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http://dx.doi.org/10.2147/CMAR.S257764DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7604289PMC
October 2020

Rosthorin A inhibits non-small cell lung cancer cell growth and metastasis through repressing epithelial-mesenchymal transition via downregulating Slug.

Anticancer Drugs 2020 11;31(10):997-1003

Department of Basic Medicine, Wuxi School of Medicine, Jiangnan University.

Lung cancer always ranks first in the number of cancer deaths every year, accounting for 18.4% of total cancer deaths in 2018. Metastasis is the main cause of death in lung cancer patients. The identification of bioactive components of traditional Chinese medicine is very important for the development of novel reagents against non-small cell lung cancer (NSCLC). Rosthorin A has originated from Rabdosia rosthornii (Diels) Hara which excerpts from 'Chinese materia medica', and is known to have 'clear heat phlegm' properties in the folk. Little is known about the biological functions and mechanisms of Rosthorin A in cancer cells at present. The role of EMT in metastasis of a tumor cell is self-evident. Slug is an important EMT inducer, which is related to the development of lung cancer. Cell growth, clone assay, cell migration, cell invasion, and protein expression, and NSCLC transplanted tumor growth were performed in A549, H1299, and H1975 cells. Rosthorin A significantly inhibited the growth of NSCLC cells, it could prolong the survival of nude mice. Rosthorin A inhibited the migration and invasion of A549, H1299, and H1975 cells. Rosthorin A up-regulated E-cadherin expression level and down-regulated the expression of β-catenin, N-cadherin, vimentin, Slug, and Twist. Rosthorin A could promote the expression of E-cadherin and inhibit the development of EMT by downregulating Slug, to inhibit the development and metastasis of NSCLC cells. In summary, Rosthorin A could be used as a promising candidate for the treatment of NSCLC patients with recurrence and metastasis.
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http://dx.doi.org/10.1097/CAD.0000000000000973DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7566306PMC
November 2020

Exosomes from different cells: Characteristics, modifications, and therapeutic applications.

Eur J Med Chem 2020 Dec 11;207:112784. Epub 2020 Sep 11.

College of Biotechnology, China International Science and Technology, Cooperation Base of Food Nutrition/Safety and Medicinal Chemistry, Tianjin International Cooperation Research Centre of Food Nutrition/Safety and Medicinal Chemistry, Tianjin University of Science & Technology/Tianjin Enterprise Key Laboratory for Application Research of Hyaluronic Acid, Tianjin, 300457, China. Electronic address:

Exosomes are cystic vesicles secreted by living cells with a phospholipid bilayer membrane. Importantly, these vesicles could serve to carry lipids, proteins, genetic materials, and transmit biological information in vivo. The cell-specific proteins and genetic materials in exosomes are capable of reflecting their cell origin and physiological status. Based on the different tissues and cells (macrophage, dendritic cells, tumor cells, mesenchymal stem cells, various body fluids, and so on), exosomes exhibit different characteristics and functions. Furthermore, owing to their high delivery efficiency, biocompatibility, and multifunctional properties, exosomes are expected to become a new means of drug delivery, disease diagnosis, immunotherapy, and precise treatment. At the same time, in order to supplement or enhance the therapeutic applicability of exosomes, chemical or biological modifications can be used to broaden, change or improve their therapeutic capabilities. This review focuses on three aspects: the characteristics and original functions of exosomes secreted by different cells, the modification and transformation of exosomes, and the application of exosomes in different diseases.
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http://dx.doi.org/10.1016/j.ejmech.2020.112784DOI Listing
December 2020

Anastomotic stricture indexes for endoscopic balloon dilation after esophageal atresia repair: a single-center study.

Dis Esophagus 2021 Jun;34(6)

Center for Clinical Epidemiology & Evidence-based Medicine, Beijing Children's Hospital, Capital Medical University, National Center for Children's Health, Beijing, China.

We investigated changes in anastomotic stricture indexes (SIs) and stricture diameter (SD) between before and 6 months after the first dilatation in children with anastomotic stricture after esophageal atresia (EA) repair and identified predictors of medium-term dilatation success (success for at least 3 months). We retrospectively reviewed the records and measurement indexes of patients who underwent post-EA repair endoscopic balloon dilatation between November 2017 and August 2019 in our hospital. We identified diagnostic and performance indicators that predicted medium-term dilatation success by univariate and multivariate analyses and receiver operator characteristic (ROC) curve analysis. Sixty patients (34 boys and 26 girls) showed post-EA repair anastomotic stricture. Paired sample t-tests showed that SD (P < 0.001), upper pouch SI (U-SI, P < 0.001), lower pouch SI (L-SI, P < 0.001), upper pouch esophageal anastomotic SI (U-EASI, P < 0.001) and lower pouch EASI (L-EASI, P < 0.001) were significantly better at 6 months after than before the first dilatation. Logistic regression analysis showed that dilatation number (P = 0.002) and U-SI at 6 months after the first dilatation (P = 0.019) significantly predicted medium-term dilatation success. ROC curve analysis revealed that combining U-SI (cut-off value = 55.6%) and dilatation number (cut-off value = 10) had good accuracy in predicting medium-term dilatation success 6 months after the first dilatation (area under the curve-ROC: 0.95). In conclusion, endoscopic balloon dilatation significantly improved SD and SIs in children with post-EA repair anastomotic stricture. Dilatation number and U-SI at 6 months after the first dilatation were useful in predicting medium-term dilatation success and could represent a supplementary method to improve judgment regarding whether further dilatation is needed 6 months after the first dilatation.
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http://dx.doi.org/10.1093/dote/doaa103DOI Listing
June 2021

Inhibiting Rab27a in renal tubular epithelial cells attenuates the inflammation of diabetic kidney disease through the miR-26a-5p/CHAC1/NF-kB pathway.

Life Sci 2020 Nov 25;261:118347. Epub 2020 Aug 25.

Department of Endocrinology and Metabolism, Nanfang Hospital, Southern Medical University, Guangzhou, China. Electronic address:

The effect of exosomes on receptor cells participating in intercellular communication has been extensively studied, but the effect of exosomes on donor cells remains unclear. It has been reported that exosomes secreted by renal proximal tubular epithelial cells (PTECs) under different stimuli accelerate acute and chronic kidney diseases. This study aimed to explore whether inhibiting exosomal secretion in PTECs by knocking out Rab27a, a key exosome regulatory gene, inhibits the excessive inflammatory response in PTECs and delays diabetic kidney disease (DKD). First, we proved that the bovine serum albumin (BSA)-induced inflammatory response in HK-2 cells was inhibited by knocking out Rab27a and that Rab27a, IL-6, TNF-α and COL-1 expression was markedly increased in an HFD/STZ-induced diabetic mouse model. Furthermore, miR-26a-5p expression in exosomes secreted by BSA-treated HK-2 cells was significantly increased but correspondingly decreased in the cells; after knocking out Rab27a, miR-26a-5p levels in the cells rebounded. Next, we confirmed that a miR-26a-5p mimic suppressed the inflammatory response, while a miR-26a-5p inhibitor accelerated the inflammatory response. Then, we found that miR-26a-5p targets the 3'-untranslated region (UTR) of CHAC1. Furthermore, the inflammatory response and NF-κB signalling pathway activation induction by the miR-26a-5p inhibitor were abolished by CHAC1 knockout. Therefore, we conclude that inhibiting exosome secretion by BSA-induced PTECs promotes miR-26a-5p expression in cells, thereby inhibiting the CHAC1/NF-κB pathways to prevent the inflammatory response in PTECs and delaying the development of DKD. This study provides new insight into the pathogenic mechanism of exosomes and a new therapeutic target for DKD.
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http://dx.doi.org/10.1016/j.lfs.2020.118347DOI Listing
November 2020

Characterization of hepatitis E virus natural infection in farmed rabbits.

J Viral Hepat 2021 01 14;28(1):186-195. Epub 2020 Sep 14.

Department of Microbiology and Center of Infectious Disease, School of Basic Medical Sciences, Peking University Health Science Center, Beijing, China.

Rabbit hepatitis E virus (HEV3-ra) is widely distributed in rabbits worldwide and several recent reports found that HEV3-ra can infect humans. Therefore, people exposed to rabbits are at high risk of HEV infection. This study was conducted to investigate the characteristics and outcomes of HEV3-ra natural infection in rabbits. Seventy farmed rabbits (3-month-old) were surveyed in a farm in Beijing, China. Rabbits tested positive for HEV RNA were followed weekly for testing of HEV RNA, antigen, antibody and alanine aminotransferase (ALT) level. Liver and kidney tissue was collected for histopathology. Complete genome sequencing of the isolated HEV3-ra strain was performed (CHN-BJ-r4, GenBank: MT364355). The infectivity of CHN-BJ-r4 was tested in ten naïve rabbits by intravenous injection or gavage. Anti-HEV antibody and HEV RNA were tested positive in 7.14% (5/70) and 11.4% (8/70) of rabbits, respectively. Eight naturally infected rabbits were followed, and 37.5% (3/8) of the observed rabbits were found to have fecal shedding of HEV ranging from 3-22 weeks with high viral load (10 -10 copies/g). Two out of eight rabbits showed temporary viremia. Naturally infected rabbits presented elevated ALT level, seroconversion, and liver histopathology. Complete genome of HEV3-ra isolated in this study shared 84.61%-94.36% nucleotide identity with known HEV3-ra complete genomes. The isolated HEV3-ra strain was infectious and could infect other rabbits through intravenous and fecal-oral route. Naturally infected rabbits showed up to 22-week fecal virus shedding with high viral load. These features increased the risk of rabbit-to-rabbit and rabbit-to-human transmission.
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http://dx.doi.org/10.1111/jvh.13387DOI Listing
January 2021