Publications by authors named "Ze Li"

157 Publications

Phlorizin from sweet tea inhibits the progress of esophageal cancer by antagonizing the JAK2/STAT3 signaling pathway.

Oncol Rep 2021 Jul 26;46(1). Epub 2021 May 26.

School of Public Health, North China University of Science and Technology, Tangshan, Hebei 063210, P.R. China.

Phlorizin, an important member of the dihydrochalcone family, has been widely used as a Chinese Traditional Medicine for treatment of numerous diseases. The present study aimed to investigate the potential therapeutic effects of phlorizin on esophageal cancer. Phlorizin, extracted from sweet tea, was used to treat esophageal cancer cells. Cell proliferation, migration and invasion were determined using Cell Counting Kit‑8 and colony formation assays, and wound healing and Transwell assays, respectively. RNA sequencing and bioinformatics analysis was used to investigate the potential mechanism of phlorizin in the development of esophageal cancer. Fluorescent staining and flow cytometry was used to measure the level of apoptosis. The expression level of the proteins, P62/SQSTM1 and LC3 І/II, and the effect of phlorizin on the JAK2/STAT3 signaling pathway was detected using western blot analysis. The results demonstrated that phlorizin could inhibit cell proliferation, migration and invasion. Bioinformatics analysis showed that phlorizin might be involved in pleiotropic effects, such as the 'JAK/STAT signaling pathway' (hsa04630), 'MAPK signaling pathway'(hsa04010) and 'apoptosis' (hsa04210). It was also confirmed that phlorizin promoted apoptosis and inhibited autophagy in the esophageal cancer cells. Notably, phlorizin might inhibit the proteins in the JAK/STAT signaling pathway, which would affect cancer cells. Taken together, the present data showed that phlorizin inhibited the progression of esophageal cancer by antagonizing the JAK2/STAT3 signaling pathway.
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http://dx.doi.org/10.3892/or.2021.8088DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8165578PMC
July 2021

Serum Exosomal EphA2 is a Prognostic Biomarker in Patients with Pancreatic Cancer.

Cancer Manag Res 2021 7;13:3675-3683. Epub 2021 May 7.

Department of Laboratory, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin's Clinical Research Center for Cancer, Tianjin, 300060, People's Republic of China.

Background: Pancreatic cancer (PC) is one of the worst prognoses amongst all malignant diseases. It is therefore of great significance to identify biomarkers with predictive clinical value for the prognosis and recurrence of PC.

Methods: In our study, enzyme-linked immunosorbent assays (ELISA) were used to detect the expression of Exo-EphA2 in the serum of PC patients and controls. Kaplan-Meier curve and Cox regression analyses were used to evaluate the prognostic value of Exo-EphA2 expression in patients with primary and recurrent PC.

Results: The level of serum Exo-EphA2 was significantly higher in the PC group when compared to that of the control group. High expression of Exo-EphA2 in PC was associated with shorter overall survival (OS) and proved to be a significant negative prognostic factor in the multivariate analysis (HR = 1.04, 95% CI: 1.00-1.09, P <0.001). Additionally, we found that the level of serum Exo-EphA2 in recurrent PC patients (first recurrence < 12 months) was positively correlated with the level of Exo-EphA2 at primary diagnosis. Multivariate analysis showed that a high expression of Exo-EphA2 in recurrent PC was associated with shorter recurrence-free survival (RFS) (HR = 1.41, 95% CI: 1.10-1.70, P < 0.001).

Conclusion: High expression of serum Exo-EphA2 represents a novel biomarker for a poor prognosis in PC patients.
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http://dx.doi.org/10.2147/CMAR.S304719DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8112875PMC
May 2021

Transferrin receptor 1 ablation in satellite cells impedes skeletal muscle regeneration through activation of ferroptosis.

J Cachexia Sarcopenia Muscle 2021 Jun 6;12(3):746-768. Epub 2021 May 6.

Guangdong Provincial Key Laboratory of Microbial Culture Collection and Application, State Key Laboratory of Applied Microbiology Southern China, Institute of Microbiology, Guangdong Academy of Sciences, Guangzhou, China.

Background: Satellite cells (SCs) are critical to skeletal muscle regeneration. Inactivation of SCs is linked to skeletal muscle loss. Transferrin receptor 1 (Tfr1) is associated with muscular dysfunction as muscle-specific deletion of Tfr1 results in growth retardation, metabolic disorder, and lethality, shedding light on the importance of Tfr1 in muscle physiology. However, its physiological function regarding skeletal muscle ageing and regeneration remains unexplored.

Methods: RNA sequencing is applied to skeletal muscles of different ages to identify Tfr1 associated to skeletal muscle ageing. Mice with conditional SC ablation of Tfr1 were generated. Between Tfr1 and Tfr1 (n = 6-8 mice per group), cardiotoxin was intramuscularly injected, and transverse abdominal muscle was dissected, weighted, and cryosectioned, followed by immunostaining, haematoxylin and eosin staining, and Masson staining. These phenotypical analyses were followed with functional analysis such as flow cytometry, tread mill, Prussian blue staining, and transmission electron microscopy to identify pathological pathways that contribute to regeneration defects.

Results: By comparing gene expression between young (2 weeks old, n = 3) and aged (80 weeks old, n = 3) mice among four types of muscles, we identified that Tfr1 expression is declined in muscles of aged mice (~80% reduction, P < 0.005), so as to its protein level in SCs of aged mice. From in vivo and ex vivo experiments, Tfr1 deletion in SCs results in an irreversible depletion of SCs (~60% reduction, P < 0.005) and cell-autonomous defect in SC proliferation and differentiation, leading to skeletal muscle regeneration impairment, followed by labile iron accumulation, lipogenesis, and decreased Gpx4 and Nrf2 protein levels leading to reactive oxygen species scavenger defects. These abnormal phenomena including iron accumulation, activation of unsaturated fatty acid biosynthesis, and lipid peroxidation are orchestrated with the occurrence of ferroptosis in skeletal muscle. Ferroptosis further exacerbates SC proliferation and skeletal muscle regeneration. Ferrostatin-1, a ferroptosis inhibitor, could not rescue ferroptosis. However, intramuscular administration of lentivirus-expressing Tfr1 could partially reduce labile iron accumulation, decrease lipogenesis, and promote skeletal muscle regeneration. Most importantly, declined Tfr1 but increased Slc39a14 protein level on cellular membrane contributes to labile iron accumulation in skeletal muscle of aged rodents (~80 weeks old), leading to activation of ferroptosis in aged skeletal muscle. This is inhibited by ferrostatin-1 to improve running time (P = 0.0257) and distance (P = 0.0248).

Conclusions: Satellite cell-specific deletion of Tfr1 impairs skeletal muscle regeneration with activation of ferroptosis. This phenomenon is recapitulated in skeletal muscle of aged rodents and human sarcopenia. Our study provides mechanistic information for developing novel therapeutic strategies against muscular ageing and diseases.
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http://dx.doi.org/10.1002/jcsm.12700DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8200440PMC
June 2021

Negative pressure wound therapy for surgical site infections: A systematic review and meta-analysis.

J Adv Nurs 2021 Apr 27. Epub 2021 Apr 27.

Department of Emergency Surgery, The Affiliated Hospital of Qingdao University, Qingdao, China.

Objective: Negative pressure wound therapy is one of the most common treatments for infected wounds. The aim of this meta-analysis was to compare the efficacy of negative pressure wound therapy with conventional treatment methods in the treatment of surgical site infection.

Design: This study is registered with International Prospective Register of Systematic Reviews.

Data Sources: The Pubmed, Embase and the Cochrane Central Register of Controlled Trials databases were searched.

Methods: The systematic review was searched by the Preferred Reporting Items for Systematic Reviews and Meta-Analyses method. All trials reporting the use of negative pressure wound therapy for surgical site infection treatment were included regardless of surgery type. The primary outcome measure was wound healing. Secondary outcomes were length of hospital stay, medical costs, adverse events, and reoperation rates. Results are presented with 95% confidence intervals and report estimates as odds ratios. Heterogeneity was determined through the I test, with I  > 50% indicating substantial heterogeneity and p < .10 significance. The search was performed on 10 March 2020.

Results: We identified 13 eligible trial comparisons, of which 2 were randomized controlled trials and 11 cohort study. Negative pressure wound therapy in surgical site infection (SSI) patients significantly increased wound healing rate, accelerated wound healing time, increased daily wound healing area, reduced hospital stay, and reduced adverse events. However, negative pressure wound therapy was associated with increased medical costs.

Conclusion: Negative pressure wound therapy may be more effective for the treatment of surgical site infection relative to conventional debridement, dressings and other treatments. However, further high-quality randomized controlled trials are needed to determine the most optimal application of negative pressure wound therapy.

Impact: Negative pressure wound therapy is the best treatment strategy for surgical site infection. This study can improve medical practitioners' awareness of negative pressure wound therapy for surgical site infection, promoting the development of relevant randomized controlled trials.
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http://dx.doi.org/10.1111/jan.14876DOI Listing
April 2021

PIVKA-II serves as a potential biomarker that complements AFP for the diagnosis of hepatocellular carcinoma.

BMC Cancer 2021 Apr 13;21(1):401. Epub 2021 Apr 13.

Department of Laboratory, Tianjin Medical University Cancer Institute and Hospital, Tianjin's Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, National Clinical Research Center for Cancer, Huanhuxi Road, Hexi District, Tianjin, 300060, China.

Background: Hepatocellular carcinoma (HCC) is one of the most common malignant tumors of the digestive system and has high morbidity and mortality rates. It is essential to search new biomarkers to improve the accuracy of early HCC diagnosis. Therefore, we evaluated the diagnostic value of prothrombin induced by vitamin K deficiency or antagonist- II (PIVKA-II) as a potential biomarker that complements α-fetoprotein (AFP) in HCC by detecting the serum PIVKA-II levels.

Methods: Serum PIVKA-II levels were compared in 168 HCC patients, 150 benign liver disease patients and 153 healthy controls to investigate the PIVKA-II potential to be a HCC biomarker. Receiver operating characteristic curve (ROC) analysis was used to evaluate the value of PIVKA-II in the diagnosis of HCC and its complementary role of AFP. The correlation between serum PIVKA-II levels and clinicopathological characteristics was analyzed to study the value of PIVKA-II in assessing HCC progression and prognosis. Finally, the ability of PIVKA-II in assessing the surgical treatment effects of HCC was studied by comparing the pre- and post-operative serum PIVKA-II levels in 89 HCC patients.

Results: Serum PIVKA-II levels in HCC patients were significantly higher than that in patients with benign liver disease and healthy controls. The PIVKA-II performance in the diagnosing HCC as an individual biomarker was remarkable. The combined detection of PIVKA-II and AFP improved the diagnostic efficiency of HCC. PIVKA-II retained significant diagnosis capabilities for AFP-negative HCC patients. Significant correlations were found between PIVKA-II expression levels and some clinicopathological characteristics, including tumor size, tumor stage, tumor metastasis, differentiation degree and complications. PIVKA-II expression obviously decreased after surgical resection.

Conclusions: PIVKA-II is a promising serum biomarker for the HCC diagnosis that can be used as a supplement for AFP. The combined diagnosis of the two markers greatly improved the diagnostic efficiency of HCC. The PIVKA-II levels in HCC patients were widely associated with clinicopathological characteristics representing tumor cell dissemination and/or poor prognosis. PIVKA-II can be used to evaluate the curative effects of HCC resection.
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http://dx.doi.org/10.1186/s12885-021-08138-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8045263PMC
April 2021

Characterization of mandarin fish (Siniperca chuatsi) IL-6 and IL-6 signal transducer and the association between their SNPs and resistance to ISKNV disease.

Fish Shellfish Immunol 2021 Jun 14;113:139-147. Epub 2021 Apr 14.

Pearl River Fisheries Research Institute, Chinese Academy of Fishery Sciences, Key Laboratory of Fishery Drug Development, Ministry of Agriculture and Rural Affairs, Key Laboratory of Aquatic Animal Immune Technology, Guangdong Provinces, Guangzhou, 510380, China.

In fish, interleukin-6 (IL-6) is a very important immune-regulatory cytokine that plays a polyfunctional role in inflammation, metabolism, regeneration, and neural processes. IL-6 signal transducer (IL-6ST) is a specific receptor for IL-6 and expressed mainly in immune cells and hepatocytes. In this study, the complete cDNA and genomic DNA sequences of mandarin fish (Siniperca chuatsi) IL-6 and IL-6ST genes were identified and analyzed. Quantitative real-time PCR showed that IL-6 and IL-6ST were chiefly expressed in the immune organs. After challenge with infectious spleen and kidney necrosis virus (ISKNV), the expression levels of IL-6 were significantly up-regulated after 6 h and 24 h in the head kidney and spleen, respectively (p < 0.01), the peak value for both reached at 72 h, IL-6ST increased significantly after 120 h with a peak at 168 h in the head kidney (p < 0.01) and improved markedly at 168 h in the spleen (p < 0.01). Besides, IL-6 and IL-6ST have been identified 3 and 8 single nucleotide polymorphisms (SNPs), respectively. Statistical analysis showed that one SNP locus (1625C/T) in the coding region of IL-6 was significantly related to the resistance of mandarin fish against ISKNV. The 1625C→T locus in the coding region of IL-6 is a synonymous mutation; compared with the susceptible group, the frequency of allele T in the disease resistance group was significantly higher, which may be due to the rare codon produced by the mutation affecting translation. The involvement of IL-6 and IL-6ST in response to ISKNV infection in mandarin fish clearly indicate that the role of SNP markers in IL-6 was associated with the ISKNV resistance, which was demonstrated for the first time in our results. Thus, the current study may provide fundamental information for further breeding of mandarin fish with resistance to ISKNV infection.
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http://dx.doi.org/10.1016/j.fsi.2021.04.003DOI Listing
June 2021

Prospective multicenter study on the incidence of surgical site infection after emergency abdominal surgery in China.

Sci Rep 2021 Apr 8;11(1):7794. Epub 2021 Apr 8.

Department of Emergency Medicine, The Affiliated Hospital of Qingdao University, 16 Jiangsu Road, Qingdao, 266000, People's Republic of China.

There is still a lack of relevant studies on surgical site infection (SSI) after emergency abdominal surgery (EAS) in China. This study aims to understand the incidence of SSI after EAS in China and discuss its risk factors. All adult patients who underwent EAS in 47 hospitals in China from May 1 to 31, 2018, and from May 1 to June 7, 2019, were enrolled in this study. The basic information, perioperative data, and microbial culture results of infected incision were prospectively collected. The primary outcome measure was the incidence of SSI after EAS, and the secondary outcome variables were postoperative length of stay, ICU admission rate, ICU length of stay, 30-day postoperative mortality, and hospitalization cost. Univariate and multivariate logistic regression were used to analyze the risk factors. The results were expressed as the odds ratio and 95% confidence interval. A total of 953 patients [age 48.8 (SD: 17.9), male 51.9%] with EAS were included in this study: 71 patients (7.5%) developed SSI after surgery. The main pathogen of SSI was Escherichia coli (culture positive rate 29.6%). Patients with SSI had significantly longer overall hospital (p < 0.001) and ICU stays (p < 0.001), significantly higher ICU admissions (p < 0.001), and medical costs (p < 0.001) than patients without SSI. Multivariate logistic regression analysis showed that male (P = 0.010), high blood glucose level (P < 0.001), colorectal surgery (P < 0.001), intestinal obstruction (P = 0.045) and surgical duration (P = 0.007) were risk factors for SSI, whereas laparoscopic surgery (P < 0.001) was a protective factor. This study found a high incidence of SSI after EAS in China. The occurrence of SSI prolongs the patient's hospital stay and increases the medical burden. The study also revealed predictors of SSI after EAS and provides a basis for the development of norms for the prevention of surgical site infection after emergency abdominal surgery.
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http://dx.doi.org/10.1038/s41598-021-87392-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8032698PMC
April 2021

Incorporation of Urinary Neutrophil Gelatinase-Associated Lipocalin and Computed Tomography Quantification to Predict Acute Kidney Injury and In-Hospital Death in COVID-19 Patients.

Kidney Dis (Basel) 2021 Mar 15;7(2):120-130. Epub 2020 Sep 15.

Department of Nephrology, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, China.

Background: The prevalence of acute kidney injury (AKI) in COVID-19 patients is high, with poor prognosis. Early identification of COVID-19 patients who are at risk for AKI and may develop critical illness and death is of great importance.

Objective: The aim of this study was to develop and validate a prognostic model of AKI and in-hospital death in patients with COVID-19, incorporating the new tubular injury biomarker urinary neutrophil gelatinase-associated lipocalin (u-NGAL) and artificial intelligence (AI)-based chest computed tomography (CT) analysis.

Methods: A single-center cohort of patients with COVID-19 from Wuhan Leishenshan Hospital were included in this study. Demographic characteristics, laboratory findings, and AI-assisted chest CT imaging variables identified on hospital admission were screened using least absolute shrinkage and selection operator (LASSO) and logistic regression to develop a model for predicting the AKI risk. The accuracy of the AKI prediction model was measured using the concordance index (C-index), and the internal validity of the model was assessed by bootstrap resampling. A multivariate Cox regression model and Kaplan-Meier curves were analyzed for survival analysis in COVID-19 patients.

Results: One hundred seventy-four patients were included. The median (±SD) age of the patients was 63.59 ± 13.79 years, and 83 (47.7%) were men.u-NGAL, serum creatinine, serum uric acid, and CT ground-glass opacity (GGO) volume were independent predictors of AKI, and all were selected in the nomogram. The prediction model was validated by internal bootstrapping resampling, showing results similar to those obtained from the original samples (i.e., 0.958; 95% CI 0.9097-0.9864). The C-index for predicting AKI was 0.955 (95% CI 0.916-0.995). Multivariate Cox proportional hazards regression confirmed that a high u-NGAL level, an increased GGO volume, and lymphopenia are strong predictors of a poor prognosis and a high risk of in-hospital death.

Conclusions: This model provides a useful individualized risk estimate of AKI in patients with COVID-19. Measurement of u-NGAL and AI-based chest CT quantification are worthy of application and may help clinicians to identify patients with a poor prognosis in COVID-19 at an early stage.
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http://dx.doi.org/10.1159/000511403DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7573910PMC
March 2021

Structural insights into preinitiation complex assembly on core promoters.

Science 2021 04 1;372(6541). Epub 2021 Apr 1.

Fudan University Shanghai Cancer Center, Institutes of Biomedical Sciences, State Key Laboratory of Genetic Engineering and Shanghai Key Laboratory of Medical Epigenetics, Shanghai Medical College of Fudan University, Shanghai 200032, China.

Transcription factor IID (TFIID) recognizes core promoters and supports preinitiation complex (PIC) assembly for RNA polymerase II (Pol II)-mediated eukaryotic transcription. We determined the structures of human TFIID-based PIC in three stepwise assembly states and revealed two-track PIC assembly: stepwise promoter deposition to Pol II and extensive modular reorganization on track I (on TATA-TFIID-binding element promoters) versus direct promoter deposition on track II (on TATA-only and TATA-less promoters). The two tracks converge at an ~50-subunit holo PIC in identical conformation, whereby TFIID stabilizes PIC organization and supports loading of cyclin-dependent kinase (CDK)-activating kinase (CAK) onto Pol II and CAK-mediated phosphorylation of the Pol II carboxyl-terminal domain. Unexpectedly, TBP of TFIID similarly bends TATA box and TATA-less promoters in PIC. Our study provides structural visualization of stepwise PIC assembly on highly diversified promoters.
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http://dx.doi.org/10.1126/science.aba8490DOI Listing
April 2021

An Alternative Splicing Variant of PtRD26 Delays Leaf Senescence by Regulating Multiple NAC Transcription Factors in Populus.

Plant Cell 2021 Feb 6. Epub 2021 Feb 6.

Beijing Advanced Innovation Center for Tree Breeding by Molecular Design, Beijing Forestry University, Beijing, 100083, China.

During leaf senescence, the final stage of leaf development, nutrients are recycled from leaves to other organs, and therefore proper control of senescence is thus critical for plant fitness. Although substantial progress has been achieved in understanding leaf senescence in annual plants, the molecular factors that control leaf senescence in perennial woody plants are largely unknown. Using RNA sequencing, we obtained a high-resolution temporal profile of gene expression during autumn leaf senescence in poplar (Populus tomentosa). Identification of hub transcription factors (TFs) by co-expression network analysis of genes revealed that senescence-associated NAC-family TFs (Sen-NAC TFs) regulate autumn leaf senescence. Age-dependent alternative splicing (AS) caused an intron-retention (IR) event in the pre-mRNA encoding PtRD26, a NAC-TF. This produced a truncated protein PtRD26IR, which functions as a dominant-negative regulator of senescence by interacting with multiple hub Sen-NAC TFs, thereby repressing their DNA-binding activities. Functional analysis of senescence-associated splicing factors identified two U2 auxiliary factors that are involved in AS of PtRD26IR. Correspondingly, silencing of these factors decreased PtRD26IR transcript abundance and induced early senescence. We propose that an age-dependent increase of IR splice variants derived from Sen-NAC TFs is a regulatory program to fine tune the molecular mechanisms that regulate leaf senescence in trees.
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http://dx.doi.org/10.1093/plcell/koab046DOI Listing
February 2021

Analgesic Effect of Noninvasive Brain Stimulation for Neuropathic Pain Patients: A Systematic Review.

Pain Ther 2021 Jun 22;10(1):315-332. Epub 2021 Mar 22.

Specific Lab for Mitochondrial Plasticity Underlying Nervous System Diseases, National Demonstration Center for Experimental Preclinical Medicine Education, Air Force Medical University, Xi'an, 710032, China.

Introduction: The objective of this review is to systematically summarize the consensus on best practices for different NP conditions of the two most commonly utilized noninvasive brain stimulation (NIBS) technologies, repetitive transcranial magnetic stimulation (rTMS), and transcranial direct current stimulation (tDCS).

Methods: PubMed was searched according to the predetermined keywords and criteria. Only English language studies and studies published up to January 31, 2020 were taken into consideration. Meta-analyses, reviews, and systematic reviews were excluded first, and those related to animal studies or involving healthy volunteers were also excluded. Finally, 29 studies covering 826 NP patients were reviewed.

Results: The results from the 24 enrolled studies and 736 NP patients indicate that rTMS successfully relieved the pain symptoms of 715 (97.1%) NP patients. Also, five studies involving 95 NP patients (81.4%) also showed that tDCS successfully relieved NP. In the included studied, the M1 region plays a key role in the analgesic treatment of NIBS. The motor evoked potentials (MEPs), the 10-20 electroencephalography system (EEG 10/20 system), and neuro-navigation methods are used in clinical practice to locate therapeutic targets. Based on the results of the review, the stimulation parameters of rTMS that best induce an analgesic effect are a stimulation frequency of 10-20 Hz, a stimulation intensity of 80-120% of RMT, 1000-2000 pulses, and 5-10 sessions, and the most effective parameters of tDCS are a current intensity of 2 mA, a session duration of 20-30 min, and 5-10 sessions.

Conclusions: Our systematically reviewed the evidence for positive and negative responses to rTMS and tDCS for NP patient care and underscores the analgesic efficacy of NIBS in patients with NP. The treatment of NP should allow the design of optimal treatments for individual patients.
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http://dx.doi.org/10.1007/s40122-021-00252-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8119533PMC
June 2021

[Study on mechanism of enhancing antioxidant activity in fermented Ziziphi Spinosae Semen with Poria cocos].

Zhongguo Zhong Yao Za Zhi 2021 Feb;46(3):620-629

Institute of Pharmaceutical & Food engineering, Shanxi University of Chinese Medicine Taiyuan 030619, China.

In this study, the antioxidant property changes in fermented Ziziphi Spinosae Semen(FZSS) with Poria cocos were analyzed by DPPH, ABTS and FRAP methods. Then the content determination of active ingredients and ~1H nuclear magnetic resonance(~1H-NMR) spectroscopy were also used to investigate the mechanism of FZSS with P. cocos in enhancing the antioxidant activity. The results showed that the content of active ingredients such as total phenols, total saponins and total polysaccharides were significantly increased during the fermentation time. The results of ~1H-NMR metabonomics showed that the contents of amino acids such as leucine, lysine, valine and alanine, nitrogen compounds such as creatine, creatinine, and betaine, and secondary metabolites, for instance, jujuboside A and spinosin were higher after fermentation, and above components showed positive correlation with antioxidant capacity in Pearson correlation analysis. Therefore, it was inferred that the enhancement of antioxidant activity of FZSS may be the result of the joint action of various chemical components. This study preliminarily clarified the mechanism of FZSS in enhancing the antioxidant activity, and provided new research ideas for the product development and utilization of FZSS.
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http://dx.doi.org/10.19540/j.cnki.cjcmm.20201012.202DOI Listing
February 2021

miR-18b regulates the function of rabbit ovary granulosa cells.

Reprod Fertil Dev 2021 Mar;33(5):363-371

College of Grassland Agriculture, Northwest A&F University, Yangling, Shaanxi, PR China; and Corresponding author. Email:

MicroRNAs (miRNAs) have been determined to participate in the process of oestradiol production. Generally, there are two pathways by which oestradiol levels change, one being the state of cells (i.e. the status of enzymes involved in the synthesis of hormones such as oestradiol) and the other being the number of cells that secrete oestradiol. It is known that oestrogens are the main steroids produced by granulosa cells (GCs) of mature ovarian follicles. In this study we explored the function of miR-18b in rabbit GCs by overexpressing or inhibiting its activity. We found that miR-18b silencing promoted the secretion of oestradiol by significantly affecting the expression of steroidogenesis-related genes. Thus, miR-18b may act as a negative regulator of the production of enzymes related to oestradiol synthesis and affect oestradiol production. Furthermore, the effects of miR-18b on the proliferation, cell cycle and apoptosis of GCs were investigated using a cell counting kit (CCK-8) proliferation assay, detection of annexin V-fluorescein isothiocyanate apoptosis, flow cytometry and quantitative polymerase chain reaction. The results showed that miR-18b upregulated GC apoptosis (miR-18b overexpression decreases cell growth and stimulates apoptosis). These findings suggest that miR-18b and the oestrogen receptor 1 (ESR1) gene may be attractive targets to further explore the molecular regulation of GCs. The miR-18b may also explain, in part, the abnormal folliculogenesis in mammals caused by conditions such as polycystic ovary syndrome, primary ovarian insufficiency, and others.
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http://dx.doi.org/10.1071/RD20237DOI Listing
March 2021

Abnormal Expression of Dysferlin in Blood Monocytes Supports Primary Dysferlinopathy in Patients Confirmed by Genetic Analyses.

Front Neurol 2020 4;11:540098. Epub 2021 Feb 4.

Department of Neurology, Guangzhou First People's Hospital, School of Medicine, South China University of Technology, Guangzhou, China.

Dysferlin deficiency causes dysferlinopathy. This study aimed to expand the mutational spectrum of dysferlinopathies, to further study one case with diagnostic ambiguity, and to identify the diagnostic value of dysferlin expression in total peripheral blood mononuclear cells (PBMC). The clinical and molecular profiles of dysferlinopathies in eight Chinese patients were evaluated. We also conducted magnetic resonance imaging (6/8) and determined dysferlin protein expression in muscle (7/8) and PBMC (3/8). Nine of the 13 mutations identified were novel. One patient was homozygous for the Gln111Ter mutation by genomic DNA sequencing but was found to be heterozygous by sequencing of cDNA from total PBMC. A daughter of this patient did not carry any Gln111Ter mutation. Abnormal muscle MRI with predominant involvement of the medial gastrocnemius and soleus muscle was observed in 5/6 patients. Dysferlin levels were significantly reduced (immunohistochemistry/immunoblot) or absent (immunohistochemistry) in muscle and total PBMC (26-39%) for most patients. Sarcoplasmic accumulation of dysferlin was detected in one patient. Genomic DNA sequencing detects frequent homozygous mutations, while fewer heterozygous mutations in cDNA are detected after posttranscription. Total PBMC may serve as an alternative to confirm diagnosis and to guide further testing in dysferlinopathies. Our results contribute to the mutational spectrum of dysferlinopathies.
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http://dx.doi.org/10.3389/fneur.2020.540098DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7890250PMC
February 2021

Wnt5a promotes renal tubular inflammation in diabetic nephropathy by binding to CD146 through noncanonical Wnt signaling.

Cell Death Dis 2021 01 18;12(1):92. Epub 2021 Jan 18.

Department of Nephrology, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, China.

Immune and inflammatory factors have emerged as key pathophysiological mechanisms in the progression of diabetic renal injury. Noncanonical Wnt5a signaling plays an essential role in obesity- or diabetes-induced metabolic dysfunction and inflammation, but its explicit molecular mechanisms and biological function in diabetic nephropathy (DN) remain unknown. In this study, we found that the expression of Wnt5a and CD146 in the kidney and the level of soluble form of CD146 (sCD146) in serum and urine samples were upregulated in DN patients compared to controls, and this alteration was correlated with the inflammatory process and progression of renal impairment. Blocking the activation of Wnt5a signaling with the Wnt5a antagonist Box5 prevented JNK phosphorylation and high glucose-induced inflammatory responses in db/db mice and high glucose-treated HK-2 cells. Similar effects were observed by silencing Wnt5a with small-interfering RNA (siRNA) in cultured HK-2 cells. Knockdown of CD146 blocked Wnt5a-induced expression of proinflammatory cytokines and activation of JNK, which suggests that CD146 is essential for the activation of the Wnt5a pathway. Finally, we confirmed that Wnt5a directly interacted with CD146 to activate noncanonical Wnt signaling in HK-2 cells. Taken together, our findings suggest that by directly binding to CD146, Wnt5a-induced noncanonical signaling is a contributing mechanism for renal tubular inflammation in diabetic nephropathy. The concentration of sCD146 in serum and urine could be a potential biomarker to predict renal outcomes in DN patients.
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http://dx.doi.org/10.1038/s41419-020-03377-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7814016PMC
January 2021

FOSL1 promotes tumorigenesis in colorectal carcinoma by mediating the FBXL2/Wnt/β-catenin axis via Smurf1.

Authors:
Yi Liu Meng Yue Ze Li

Pharmacol Res 2021 Mar 12;165:105405. Epub 2021 Jan 12.

Department of Colorectal and Stomach Cancer Surgery-1, Jilin Cancer Hospital, Changchun, Jilin, 130000, PR China. Electronic address:

Colorectal carcinoma (CC), one of the most prevalent digestive cancers with high mortality and morbidity globally, still lacks powerful therapies to improve the prognosis. Here, we established that the expression of fos-like antigen-1 (Fosl1) was elevated in CC tissues versus adjacent tissues. Importantly, high Fosl1 expression was related to dismal prognosis among CC patients. Functional assays displayed that Fosl1 increased the viability, epithelial-to-mesenchymal transition (EMT), migration and invasion of CC cells. Additionally, a xenograft assay showed that silencing of Fosl1 in CC cells retarded lung, liver and kidney metastases in vivo. Further investigation demonstrated that Fosl1 was involved in malignant aggressiveness of CC cells by binding to smad ubiquitination regulatory factor 1 (Smurf1). Mechanistically, Smurf1-induced F-Box and leucine rich repeat protein 2 (FBXL2) ubiquitination resulted in its degradation, while FBXL2 disrupted the activation of the Wnt/β-catenin signaling. In summary, Fosl1 plays a pro-metastatic and carcinogenetic role in CC, and we provided forceful evidence that Fosl1 inhibition might act as a prognostic and therapeutic option in CC.
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http://dx.doi.org/10.1016/j.phrs.2020.105405DOI Listing
March 2021

Clinical and morphologic spectrum of renal involvement in idiopathic hypereosinophilic syndrome.

Clin Exp Nephrol 2021 Mar 4;25(3):270-278. Epub 2021 Jan 4.

National Clinical Research Center of Kidney Diseases, Jinling Hospital, Nanjing University School of Medicine, Nanjing, China.

Background: To explore the clinical and pathological features of renal lesions in patients with kidney involvement in idiopathic hypereosinophilic syndrome (IHES).

Methods: The demographic, clinical, and pathological characteristics and the treatment and follow-up data were analyzed.

Results: We identified 18 patients with IHES and renal involvement. Eleven patients presented with nephrotic syndrome, and 6 patients had impaired renal function. 15 patients underwent renal biopsy, and the pathological findings included the following: membranoproliferative glomerulonephritis in 3 patients; minimal-change disease in 3; mesangial proliferative nephritis in two; IgA nephropathy in 2; membranous nephropathy in two; chronic interstitial nephritis in two; focal segmental sclerosis in one; and eosinophil infiltration into the renal interstitium in 11 and into the glomerulus in 3. After treatment with glucocorticoids, the eosinophil count decreased. 15 patients were followed up, and 14 showed a decrease in urinary protein or renal function recovery. When glucocorticoids were discontinued, eosinophil increased (8 cases), urine protein increased (1 case), and 1 patient progressed to end-stage renal disease.

Conclusions: Nephrotic syndrome with or without renal insufficiency is the main clinical manifestation. A wide spectrum of renal lesions can be observed in patients with IHES. Eosinophil infiltration into the renal interstitium was common in these patients. Most patients have a good prognosis after glucocorticoid therapy.
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http://dx.doi.org/10.1007/s10157-020-02012-5DOI Listing
March 2021

Long Non-Coding RNA C1QTNF1 Antisense RNA 1 Upregulates Hexokinase 2 by Sponging microRNA-484 to Promote the Malignancy of Colorectal Cancer.

Cancer Manag Res 2020 24;12:12053-12066. Epub 2020 Nov 24.

Department of Colorectal and Stomach Cancer Surgery-1, Jilin Cancer Hospital, Changchun, Jilin 130000, People's Republic of China.

Purpose: The long noncoding RNA 1 () contributes to hepatocellular carcinoma development. However, its expression and roles in colorectal cancer (CRC) have not been fully explored. Therefore, this study determined the expression and roles of in CRC and elucidated its detailed mechanism of action.

Methods: expression in CRC tissues and cell lines was assessed by reverse transcription-quantitative polymerase chain reaction (RT-qPCR). We used Cell Counting Kit-8, flow cytometry, cell migration and invasion assays, and a xenograft tumor model to test the effects of on CRC malignancy. The associations among , microRNA-484 (miR-484), and () were explored using luciferase reporter assay, RNA immunoprecipitation, RT-qPCR, and Western blotting.

Results: was overexpressed in CRC and related to poor prognosis. interference inhibited CRC cell proliferation, migration, and invasion but induced apoptosis. Furthermore, deficiency impaired tumor growth in vivo. Mechanistically, adsorbed miR-484, thereby increasing the expression of its target . Rescue experiments revealed that the effects of deficiency in CRC cells were reversed by inhibiting miR-484 or upregulating .

Conclusion: drives CRC progression by sponging miR-484 and consequently upregulating . The /miR-484/ pathway may serve as a diagnostic and therapeutic target for CRC.
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http://dx.doi.org/10.2147/CMAR.S262096DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7700093PMC
November 2020

NtMYB12a acts downstream of sucrose to inhibit fatty acid accumulation by targeting lipoxygenase and SFAR genes in tobacco.

Plant Cell Environ 2021 03 10;44(3):775-791. Epub 2020 Dec 10.

China Tobacco Gene Research Center, Zhengzhou Tobacco Research Institute of CNTC, Zhengzhou, China.

MYB12 promotes flavonol biosynthesis in plants by targeting several early biosynthesis genes (EBGs) of this pathway. The transcriptions of these EBGs are also induced by sucrose signal. However, whether MYB12 is activated by sucrose signal and what the other roles MYB12 has in regulating plant metabolism are poorly understood. In this study, two NtMYB12 genes were cloned from Nicotiana tabacum. Both NtMYB12a and NtMYB12b are involved in regulating flavonoids biosynthesis in tobacco. NtMYB12a is further shown to inhibit the accumulation of fatty acid (FA) in tobacco leaves and seeds. Post-translational activation and chromatin immunoprecipitation assays demonstrate that NtMYB12a directly promotes the transcriptions of NtLOX6, NtLOX5, NtSFAR4 and NtGDSL2, which encode lipoxygenase (LOX) or SFAR enzymes catalyzing the degradation of FA. NtLOX6 and NtLOX5 are shown to prevent the accumulation of FA in the mature seeds and significantly reduced the percentage of polyunsaturated fatty acids (PUFAs) in tobacco. Sucrose stimulates the transcription of NtMYB12a, and loss function of NtMYB12a partially suppresses the decrease of FA content in tobacco seedlings caused by sucrose treatment. The regulation of sucrose on the expression of NtLOX6 and NtGDSL2 genes is mediated by NtMYB12a, whereas those of NtLOX5 and NtSFAR4 genes are independent of sucrose.
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http://dx.doi.org/10.1111/pce.13957DOI Listing
March 2021

In-depth transcriptomic analyses of LncRNA and mRNA expression in the hippocampus of APP/PS1 mice by Danggui-Shaoyao-San.

Aging (Albany NY) 2020 11 18;12(23):23945-23959. Epub 2020 Nov 18.

Key Laboratory of Hunan Province for Integrated Traditional Chinese and Western Medicine on Prevention and Treatment of Cardio-Cerebral Diseases, Hunan University of Chinese Medicine, Changsha 410208, Hunan, China.

Alzheimer's disease (AD) is an age-related neurodegenerative disease with a high incidence worldwide, and with no medications currently able to prevent the progression of AD. Danggui-Shaoyao-San (DSS) is widely used in traditional Chinese medicine (TCM) and has been proven to be effective for memory and cognitive dysfunction, yet its precise mechanism remains to be delineated. The present study was designed to investigate the genome-wide expression profile of long non-coding RNAs (LncRNAs) and messenger RNAs (mRNAs) in the hippocampus of APP/PS1 mice after DSS treatment by RNA sequencing. A total of 285 differentially expressed LncRNAs and 137 differentially expressed mRNAs were identified (fold-change ≥2.0 and < 0.05). Partial differentially expressed LncRNAs and mRNAs were selected to verify the RNA sequencing results by quantitative polymerase chain reaction (qPCR). A co-expression network was established to analyze co-expressed LncRNAs and genes. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were used to evaluate the biological functions related to the differentially co-expressed LncRNAs, and the results showed that the co-expressed LncRNAs were mainly involved in AD development from distinct origins, such as APP processing, neuron migration, and synaptic transmission. Our research describes the lncRNA and mRNA expression profiles and functional networks involved in the therapeutic effect of DSS in APP/PS1 mice model. The results suggest that the therapeutic effect of DSS on AD involves the expression of LncRNAs. Our findings provide a new perspective for research on the treatment of complex diseases using traditional Chinese medicine prescriptions.
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http://dx.doi.org/10.18632/aging.104068DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7762474PMC
November 2020

Nbnrp1 mediates Verticillium dahliae effector PevD1-triggered defense responses by regulating sesquiterpenoid phytoalexins biosynthesis pathway in Nicotiana benthamiana.

Gene 2021 Feb 10;768:145280. Epub 2020 Nov 10.

The State Key Laboratory for Biology of Plant Disease and Insect Pests, Institute of Plant Protection, Chinese Academy of Agricultural Science, No. 2 Yuanmingyuan West Rode, Beijing 100093, China. Electronic address:

PevD1, a fungal effector secreted by Verticillium dahliae, could induce hypersensitive responses-like necrosis and systemic acquired resistance (SAR) in cotton and tobacco plants. PevD1 could drastically induce the expression of Nbnrp1, which is an asparagine-rich protein (NRP) of Nicotiana benthamiana. Our previous research indicated that Nbnrp1 positively regulated PevD1-induced cell necrosis and disease resistance. In this study, we further investigated PevD1-induced immune responses in both wild-type (WT) and Nbnrp1-RNAi lines through RNA-seq, in order to reveal the underlying mechanism of Nbnrp1-modulated PevD1-induced disease resistance in N. benthamiana. Results showed that Nbnrp1-RNAi lines exhibited reduced PevD1-induced immune responses, like inhibiting HO accumulation and MAPK phosphorylation. To silence Nbnrp1 inhibited the expression of PevD1-induced differential expression genes (DEGs) involved in pathways associated with sesquiterpenoid and triterpenoid biosynthesis, flavone and flavonol biosynthesis, plant-pathogen interaction and phenylpropanoid biosynthesis, etc. It is worth noting that sesquiterpene phytoalexin capsidiol accumulation were obviously decreased in Nbnrp1-RNAi plants after PevD1 treatment, accompanied with the down-expression of EAS and EAH, which were two key genes related to capsidiol biosynthesis. These results suggested that Nbnrp1 mediates PevD1-induced defense responses by regulating sesquiterpenoid phytoalexins biosynthesis pathway.
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http://dx.doi.org/10.1016/j.gene.2020.145280DOI Listing
February 2021

Temporal changes in Egr-1 and c-fos expression in rat models of myocardial ischemia.

Ann Palliat Med 2021 Feb 20;10(2):1411-1420. Epub 2020 Oct 20.

Department of Pathology, School of Forensic Medicine, Shanxi Medical University, Taiyuan, China.

Background: The pathological diagnosis of sudden cardiac death caused by myocardial ischemia is a difficult problem. Relevant evidence shows that the expression of Egr-1 and c-fos undergo changes in the early stage of myocardial ischemia, but the detailed temporal variation of them is not clear. Therefore, the aim of this study was to observe the temporal changes in mRNA and protein expression of Egr-1 and c-fos in ischemic myocardium in rats.

Methods: Sixty-six Sprague-Dawley rats were divided into the control group, the early myocardial ischemia (EMI) group, the sham operated group and the allergy group. The EMI rats were further divided into eight subgroups according to the different time points (30 min and 1, 2, 4, 8, 12, 24, and 48 h) after modeling. The mRNA and protein of Egr-1 and c-fos of each group were detected by real-time quantitative polymerase chain reaction and immunohistochemistry, respectively.

Results: In the EMI group, Egr-1 mRNA in ischemic myocardium rose 30 min after ischemia and peaked at 2 h; the plateau was maintained up to 8 h after ischemia, and then returned to the baseline level at 12 h. The c-fos mRNA in ischemic myocardium demonstrated a consistent changing curve with that of Egr-1. The mRNA of Egr-1 and c-fos showed no significant changes in the control group, the sham operated group and the allergy group. Immunohistochemistry showed that Egr-1 protein in the myocardial ischemic area was slightly positive 30 min after ischemia, and then strongly positive at 4 and 8 h, decreased at 12 h, and was negative at 24 h. The changing trends of c-fos protein were almost the same as that of Egr-1. Immunohistochemistry of Egr-1 and c-fos protein were all negative in the control group, the sham operated group and the allergy group.

Conclusions: The mRNA and protein expression of Egr-1 and c-fos presented rapid and temporal changes after myocardial ischemia, and this may be helpful in distinguishing sudden death induced by myocardial ischemia from that of allergy.
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http://dx.doi.org/10.21037/apm-20-89DOI Listing
February 2021

Effect of Lignin Content on Properties of Flexible Transparent Poplar Veneer Fabricated by Impregnation with Epoxy Resin.

Polymers (Basel) 2020 Nov 5;12(11). Epub 2020 Nov 5.

College of Materials Science and Engineering, Nanjing Forestry University, Nanjing 210037, China.

In this work, poplar veneer (PV) rotary-cut from fast-growing polar was delignified to prepare flexible transparent poplar veneer (TPV). Lignin was gradually removed from the PV and then epoxy resin filled into the delignified PV. The study mainly concerns the effect of lignin content on microstructure, light transmittance, haze, tensile strength, and thermal stability of the PVs impregnated with epoxy resin. The results indicate that the lignin could be removed completely from the PV when the delignification time was around 8 h, which was proved by FTIR spectra and chemical component detection. Moreover, according to SEM observation and XRD testing, the porosity and crystallinity of the PVs were gradually increased with the removal of lignin. Also, the optical properties measurement indicated that the light transmittance and haze of the TPVs gradually increased, and the thermal stability also became more stable as shown by thermogravimetric analysis (TG). However, the tensile strength of the TPVs declined due to the removal of lignin. Among them, TPV exhibited excellent optical properties, thermal stability, and tensile strength. Consequently, it has great potential to be used as a substrate in photovoltaics, solar cells, smart windows, etc.
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http://dx.doi.org/10.3390/polym12112602DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7694516PMC
November 2020

Involvement of BbTpc1, an important Zn(II)Cys transcriptional regulator, in chitin biosynthesis, fungal development and virulence of an insect mycopathogen.

Int J Biol Macromol 2021 Jan 4;166:1162-1172. Epub 2020 Nov 4.

Maize Research Institute, Shandong Academy of Agricultural Sciences, Jinan, China.

Chitin is one of the major components of the fungal cell wall and contributes to the mechanical strength and shape of the fungal cell. Zn(II)Cys transcription factors are unique to the fungal kingdom and have a variety of functions in some fungi. However, the mechanisms by which Zn(II)Cys proteins affect entomopathogenic fungi are largely unknown. Here, we characterized the Zn(II)Cys transcription factor BbTpc1 in the insect pathogenic fungus Beauveria bassiana. Disruption of BbTpc1 resulted in a distinct changes in vegetative growth and septation patterns, and a significant decrease in conidia and blastospore yield. The ΔBbTpc1 mutant displayed impaired resistance to chemical stresses and heat shock and attenuated virulence in topical and intrahemocoel injection assays. Importantly, the ΔBbTpc1 mutant had an abnormal cell wall with altered wall thickness and chitin synthesis, which were accompanied by transcriptional repression of the chitin synthetase family genes. In addition, comparative transcriptomics revealed that deletion of BbTpc1 altered fungal asexual reproduction via different genetic pathways. These data revealed that BbTpc1 regulates fungal development, chitin synthesis and biological control potential in B. bassiana.
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http://dx.doi.org/10.1016/j.ijbiomac.2020.10.271DOI Listing
January 2021

Diagnosis and Treatment of Retroperitoneal Infection.

Surg Infect (Larchmt) 2021 Jun 3;22(5):477-484. Epub 2020 Nov 3.

Department of Emergency Surgery, The Affiliated Hospital of Qingdao University, Qingdao, P.R. China.

Retroperitoneal infection is a persistent and widespread infectious disease that is difficult to treat. It is usually caused by secondary complications such as inflammation, damage, or perforation of adjacent organs in the retroperitoneal space. Pathogenic bacteria invade the retroperitoneal space through retroperitoneal and interstitial organs, peripheral tissue, and the blood. As a result, infections mostly arise from severe acute pancreatitis, acute colonic diverticulitis, inflammatory bowel disease, kidney abscess, and biliary tract injury. Initially manifested by the presence of lumbago, this disease spreads easily, is persistent, and is often misdiagnosed. Review and synthesis of pertinent literature and guidelines pertaining to abdominal infection and retroperitoneal infection. Recent data indicate that mortality rates associated with retroperitoneal infection have been increasing annually. Early diagnosis and treatment have been shown to improve the prognosis. In the early stage, infection is insidious and lacks typical symptoms, and is primarily diagnosed with computed tomography (CT). Strategies that control the source of infection, rational use of antibiotic agents, and nutritional interventions are the primary approaches to treat the infections. Emergence of minimally invasive drainage technologies, including the ultrasound/CT-guided puncture and drainage, percutaneous nephroscope puncture and drainage, and drainage using a catheter through an abdominal puncture device (trocar) have shortened the treatment cycle and disease burden. However, current diagnosis and treatment for retroperitoneal infection are not sufficiently effective because some patients do not show typical clinical manifestations. Moreover, sensitivity and specificity of available auxiliary examination methods are not supported by sufficient evidence-based medical research. Additionally, there are no uniform standards on the timing of surgical intervention and treatment options. Therefore, we summarized the progresses on current diagnosis and treatment approaches for retroperitoneal infection.
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http://dx.doi.org/10.1089/sur.2020.126DOI Listing
June 2021

Genetic variants in the regulation region of TLR4 reduce the gastric cancer susceptibility.

Gene 2021 Jan 30;767:145181. Epub 2020 Sep 30.

School of Public Health, North China University of Science and Technology, Tangshan 063210, China; College of Life Science, North China University of Science and Technology, Tangshan 063210, China. Electronic address:

Gastric cancer (GC) is one of the most common cancers diagnosed in China. It has been suggested that the genetic polymorphisms of Toll-like receptors (TLRs) might be in close relation to tumorigenesis and development of gastric cancer. In this study, we performed a case-control study to investigate the genetic polymorphisms of TLR3, 4, 5, 7 with the genetic susceptibility of gastric cancer. TLRs gene polymorphisms in 471 gastric cancer (GC) patients and 471 healthy controls were analyzed by polymerase chain reaction-restrictive fragment length polymorphism (PCR-RFLP) analysis or TaqMan assays. Odds ratio (OR) and its 95% confidence interval (95%CI) were used to evaluate the association of TLR4 variants with the GC risk via unconditional logistic regression. Our results suggested that variant genotypes of TLR4 rs7869402 (OR = 0.61, 95%CI = 0.40-0.92, P = 0.02) and TLR4 rs7873784 (OR = 0.17, 95%CI = 0.09-0.33, P < 0.01) gene polymorphisms reduced the risk of GC. Stratified analysis showed that rs7869402 T-containing genotype significantly decreased the susceptibility of GC among females (OR = 0.38, 95%CI = 0.16-0.91, P = 0.03), older subjects (OR = 0.48, 95%CI = 0.26-0.87, P = 0.02), non-smokers (OR = 0.41, 95%CI = 0.23-0.71, P < 0.01) and non-drinkers (OR = 0.58, 95%CI = 0.30-0.78, P < 0.01). In case of rs7873784 polymorphism, C-containing genotype reduced the risk of GC among males (OR = 0.08, 95%CI = 0.03-0.21, P < 0.01), but not among females (OR = 0.53, 95%CI = 0.22-1.27, P = 0.15). As to the other four SNPs (TLR3 rs5743303, TLR4 rs1927914, TLR5 rs1640816 and TLR7 rs3853839), no significant correlations were found to be related to the risk of gastric carcinoma. Our research demonstrated the significance of TLRs polymorphisms in decreasing the risk of GC.
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http://dx.doi.org/10.1016/j.gene.2020.145181DOI Listing
January 2021

EphA2‑enriched exosomes promote cell migration and are a potential diagnostic serum marker in pancreatic cancer.

Mol Med Rep 2020 Oct 28;22(4):2941-2947. Epub 2020 Jul 28.

Department of Laboratory, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin's Clinical Research Center for Cancer, Tianjin 300060, P.R. China.

Pancreatic cancer (PC) is the fourth most common cause of cancer‑related mortality worldwide and is characterized by high invasiveness and early metastasis. To identify novel diagnostic markers, the present study aimed to understand the mechanism underlying PC progression. The present study demonstrated that exosomes derived from the highly metastatic Panc‑1 PC cell line were internalized by a low metastatic cell line, resulting in increased migration of the latter. Proteomics analysis further revealed that the receptor tyrosine kinase Eph receptor A2 (EphA2) was overexpressed in the Panc‑1 exosomes, and these Exo_EphA2 had the ability to transfer metastatic potential to recipient cells. Consistent with this, circulating Exo_EphA2 levels were higher in patients with PC compared with healthy controls. Taken together, these results indicated that Exo_EphA2 acts an oncogene in PC and is a potential tumor maker for PC diagnosis.
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http://dx.doi.org/10.3892/mmr.2020.11384DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7466360PMC
October 2020

Molecular transformation of dissolved organic matter in refinery wastewater.

Water Sci Technol 2020 Jul;82(1):107-119

State Key Laboratory of Heavy Oil Processing, China University of Petroleum, Beijing 102249, China E-mail:

Dissolved organic matter (DOM) has an important impact on the water treatment and reuse of petroleum refinery wastewater. In order to improve the treatment efficiency, it is necessary to understand the chemical composition of the DOM in the treatment processes. In this paper, the molecular composition of DOM in wastewater samples from a representative refinery were characterized. The transformation of various compounds along the wastewater treatment processes was investigated. A total of 61 heteroatomic class species were detected from the DOM extracts, in which CHO (molecules composed of carbon, hydrogen, and oxygen atoms) and CHOS (CHO molecules that also contained sulfur) class species were the most abundant and account for 78.43% in relative mass peak abundance. The solid phase extraction DOM from the dichloromethane unextractable fraction exhibited a more complex molecular composition and contained more oxygen atoms than in the dichloromethane extract. During wastewater treatment processes, the chemical oxygen demand (COD) and ammonia-nitrogen were reduced by more than 90%. Volatile organic compounds (VOCs) accounted for about 30% of the total COD, in which benzene and toluene were dominant. After biochemical treatment, the VOCs were effectively removed but the molecular diversity of the DOM was increased and new compounds were generated. Sulfur-containing class species were more recalcitrant to biodegradation, so the origin and transformation of these compounds should be the subject of further research.
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http://dx.doi.org/10.2166/wst.2020.334DOI Listing
July 2020

Serum Exo-EphA2 as a Potential Diagnostic Biomarker for Pancreatic Cancer.

Pancreas 2020 10;49(9):1213-1219

From the Departments of Laboratory.

Objectives: Pancreatic cancer (PC) is a highly malignant tumor with poor detection sensitivity and specificity in biomarkers and diagnosis. Previous research indicated that serum Ephrin type-A receptor 2 in exosomes (Exo-EphA2) was highly expressed and might have facilitated cell migration in PC cells. However, the dynamics of clinical performance of serum Exo-EphA2 in PC patients are unknown. Thus, this study evaluated serum Exo-EphA2 as a potential diagnostic biomarker in PC.

Methods: The expressions of serum Exo-EphA2 were assessed by enzyme-linked immunosorbent assay for N = 353 serum samples, including from 204 PC patients, 75 patients with benign pancreatic disease, and 74 healthy control patients. Carbohydrate antigen 19-9 (CA 19-9) and carbohydrate antigen 242 (CA 242) were measured by automated immunoassay.

Results: Serum Exo-EphA2 levels were significantly higher in PC patients than in benign pancreatic disease and healthy control patients. Receiver operating characteristic curve analysis suggested that using combined diagnoses of Exo-EphA2 with CA 19-9 and CA 242 was more effective to discriminate early stage (stage I and II) in PC than in healthy controls and benign disease patients.

Conclusions: Novel findings suggest that serum Exo-EphA2 is a potential early diagnostic biomarker complementing CA 19-9 and CA 242 in PC.
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http://dx.doi.org/10.1097/MPA.0000000000001660DOI Listing
October 2020

Computational fluid dynamics model and flow resistance characteristics of Jatropha curcas L xylem vessel.

Sci Rep 2020 09 7;10(1):14728. Epub 2020 Sep 7.

Faculty of Civil Engineering and Mechanics, Kunming University of Science and Technology, Kunming, 650500, Yunnan, China.

Xylem vessels are the channels used for water transport in Jatropha curcas L. Vessel complexity has a great influence on water transport. Therefore, using anatomical experiments and numerical simulations, the water transport characteristics of J. curcas L xylem vessels with perforation plate and secondary wall thickening (pit structures) were analyzed. The results showed that the xylem vessel in J. curcas provided a low resistance path. The xylem vessel resistance was composed of three elements: smooth vessels, secondary wall thickening and perforation plate. The proportion of smooth vessel resistance was the largest, accounting for 66.20% of the total resistance. Then the secondary wall thickening resistance accounted for 30.20% of the total resistance, and finally the perforation plate resistance accounted for 3.60% of the total resistance. The total resistance of the vessel model was positively correlated with the pit depth, perforation plate height and perforation plate width and negatively correlated with the vessel inner diameter and pit membrane permeability. The vessel inner diameter and the pit depth had a great influence on the total resistance. The total resistance of the vessel inner diameter of 52 µm was 89.15% higher than that of 61 µm, the total resistance of the pit depth of 5.6 µm was 21.98% higher than that of 2.6 µm. The pit structure in the secondary wall thickening caused the vessel to be transported radially, and the radial transmission efficiency of the vessel was positively correlated with the pit depth and pit membrane permeability and negatively correlated with the vessel inner diameter. The pit membrane permeability had the greatest influence on the radial transmission efficiency, and its radial transmission efficiency was 0-5.09%.
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http://dx.doi.org/10.1038/s41598-020-71576-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7477118PMC
September 2020