Publications by authors named "Hongxia Xu"

126 Publications

Fat mass assessment using the triceps skinfold thickness enhances the prognostic value of the Global Leadership Initiative on Malnutrition criteria in patients with lung cancer.

Br J Nutr 2021 Jul 5:1-11. Epub 2021 Jul 5.

Department of Clinical Nutrition, Daping Hospital, Army Medical University (Third Military Medical University), Chongqing400042, People's Republic of China.

The present study evaluated whether fat mass assessment using the triceps skinfold (TSF) thickness provides additional prognostic value to the Global Leadership Initiative on Malnutrition (GLIM) framework in patients with lung cancer (LC). We performed an observational cohort study including 2672 LC patients in China. Comprehensive demographic, disease and nutritional characteristics were collected. Malnutrition was retrospectively defined using the GLIM criteria, and optimal stratification was used to determine the best thresholds for the TSF. The associations of malnutrition and TSF categories with survival were estimated independently and jointly by calculating multivariable-adjusted hazard ratios (HR). Malnutrition was identified in 808 (30·2 %) patients, and the best TSF thresholds were 9·5 mm in men and 12 mm in women. Accordingly, 496 (18·6 %) patients were identified as having a low TSF. Patients with concurrent malnutrition and a low TSF had a 54 % (HR = 1·54, 95 % CI = 1·25, 1·88) greater death hazard compared with well-nourished individuals, which was also greater compared with malnourished patients with a normal TSF (HR = 1·23, 95 % CI = 1·06, 1·43) or malnourished patients without TSF assessment (HR = 1·31, 95 % CI = 1·14, 1·50). These associations were concentrated among those patients with adequate muscle mass (as indicated by the calf circumference). Additional fat mass assessment using the TSF enhances the prognostic value of the GLIM criteria. Using the population-derived thresholds for the TSF may provide significant prognostic value when used in combination with the GLIM criteria to guide strategies to optimise the long-term outcomes in patients with LC.
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http://dx.doi.org/10.1017/S0007114521002531DOI Listing
July 2021

Metabolic profiling of liver and faeces in mice infected with echinococcosis.

Parasit Vectors 2021 Jun 14;14(1):324. Epub 2021 Jun 14.

Center of Scientific Technology of Ningxia Medical University, Yinchuan, 750004, Ningxia Hui Autonomous Region, People's Republic of China.

Background: Echinococcosis is a severe zoonotic parasitic disease which severely affects the health of the hosts. The diagnosis of echinococcosis depends mainly on imaging examination. However, the patient is often in the late stage of the disease when the symptoms appear, thus limiting the early diagnosis of echinococcosis. The treatment and prognosis of the patients are hampered because of long-term asymptomatic latency. Metabolomics is a new discipline developed in the late 1990s. It reflects a series of biological responses in pathophysiological processes by demonstrating the changes in metabolism under the influence of internal and external factors. When the organism is invaded by pathogens, the alteration in the characteristics of metabolites in cells becomes extremely sensitive. Here, we used a metabolomics approach involving liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS) to determine the molecular mechanism of cystic echinococcosis (CE) and to develop an effective method for CE diagnosis.

Methods: Twenty 8-week-old female BALB/c mice were divided into normal and Echinococcus granulosus infection groups. To develop the E. granulosus infection model, mice were infected with protoscoleces. Six weeks later, the abdomens of the mice showed significant bulging. An LC-MS/MS system-based metabolomics approach was used to analyse the liver and faeces to reveal the metabolic profiles of mice with echinococcosis.

Results: We found that the metabolism of nucleotides, alkaloids, amino acids, amides, and organic acids in mice is closely interrelated with E. granulosus infection. In the liver, the metabolic pathways of tyrosine and tryptophan biosynthesis; phenylalanine, valine, leucine and isoleucine biosynthesis; and phenylalanine metabolism were notably associated with the occurrence and development of hydatid disease, and in the faeces, pantothenate and CoA biosynthesis are thought to be closely associated with the development of CE.

Conclusion: The metabolomics approach used in this study provides a reference for a highly sensitive and specific diagnostic and screening method for echinococcosis.
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http://dx.doi.org/10.1186/s13071-021-04807-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8201681PMC
June 2021

A FRET-based fluorescent Zn sensor: 3D ratiometric imaging, flow cytometric tracking and cisplatin-induced Zn fluctuation monitoring.

Chem Sci 2020 Sep 15;11(40):11037-11041. Epub 2020 Sep 15.

State Key Laboratory of Coordination Chemistry, Coordination Chemistry Institute, School of Chemistry and Chemical Engineering, Nanjing University Nanjing 210023 P. R. China

Monitoring labile Zn homeostasis is of great importance for the study of physiological functions of Zn in biological systems. Here we report a novel ratiometric fluorescent Zn sensor, CPBT, which was constructed based on chelation-induced alteration of FRET efficiency. CPBT was readily cell membrane permeable and showed a slight preferential localization in the endoplasmic reticulum. With this sensor, 3D ratiometric Zn imaging was first realized in the head of zebra fish larvae Z-stack mode. CPBT could track labile Zn in a large number of cells through ratiometric flow cytometric assay. More interestingly, both ratiometric fluorescence imaging and flow cytometric assay demonstrated that the labile Zn level in MCF-7 cells (cisplatin-sensitive) decreased while that in SKOV3 cells (cisplatin-insensitive) increased after cisplatin treatment, indicating that Zn may play an important role in cisplatin induced signaling pathways in these cancer cells.
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http://dx.doi.org/10.1039/d0sc03037fDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8162301PMC
September 2020

Development and application of quality checklist for the prevention and control of COVID-19 in fever clinic and isolation ward of the general hospital.

Zhejiang Da Xue Xue Bao Yi Xue Ban 2021 02;50(1):74-80

Department of Nosocomial Infections,Sir Run Run Shaw Hospital,Zhejiang University School of Medicine,Hangzhou 310016,China.

To develop a quality control checklist for the prevention and control of coronavirus disease 2019 (COVID-19) in fever clinic and isolation ward of the general hospital and to assess its application. Based on the relevant prevention and control plans and technical guidelines for COVID-19,Delphi method was used to identity items for evaluation,and a quality control checklist for the prevention and control of COVID-19 in the fever clinic and isolation ward was developed in Sir Run Run Shaw Hospital. The checklists included 8 dimensions and 32 items for fever clinic,7 dimensions and 27 items for the isolation ward. The appointed inspectors conducted daily quality control for each shift with this checklist. The expert authority coefficient was 0.88,the mean of the importance of each index in the quality control table was not less than 4.8,and the coefficient of variation was not more than 0.07. During the entire February 2020,8 problems were found and rectified on-the-spot with the application of the checklist. Quality inspection rate was 100% in both isolation wards and fever clinic. The compliance rate and accuracy rate of hand hygiene were 100%; the correct rate of wearing and removing protective equipment increased from 96% to 100%. During the same period,a total of 1915 patients were admitted to the fever clinic,including 191 suspected patients (all were isolated in the hospital,3 were confirmed). There were no medical staff infected with COVID-19,no cross infection of patients and their families in the hospital. A quality control checklist for the prevention and control of COVID-19 has been developed and applied in the isolation wards and fever clinic,which plays an important role in preventing nosocomial infection.
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http://dx.doi.org/10.3724/zdxbyxb-2021-0003DOI Listing
February 2021

P53 inhibitor pifithrin-α inhibits ropivacaine-induced neuronal apoptosis via the mitochondrial apoptosis pathway.

J Biochem Mol Toxicol 2021 Jun 6:e22822. Epub 2021 Jun 6.

Department of Anesthesiology, Xiangyang No. 1 People's Hospital, Hubei University of Medicine, Xiangyang, Hubei, China.

The neurotoxicity of local anesthetics (LAs) has attracted more and more attention, However, they lack preventive and therapeutic measures. Many studies have shown that apoptosis plays an important role in the process of LA-induced neurotoxicity. As an important signaling molecule to activate apoptosis, p53 has been proved to be involved in the neurotoxicity induced by LAs, but the mechanism is unclear. In this study, we explored the effect of pifithrin-α (PFT-α), a p53 inhibitor, on apoptosis by ropivacaine (Rop) in vivo and in vitro. Cell viability and apoptosis detected by CCK-8 and a JC-1 apoptosis detection kit, the changes of spinal cord structure observed after hematoxylin and eosin staining, apoptosis of the spinal cord measured by terminal deoxynucleotidyl transferase dUTP nick end labeling staining, behavioral assessment of the nerve Injury evaluated by the detection of sciatic nerve conduction velocity (SNCV) andmechanical withdrawal threshold (MWT), the expression of p53 and many apoptosis-related genes included Bax, Bcl-2, and caspase-3 detected by quantitative real-time polymerase chain reaction, Western blot analysis, immunofluorescence, and immunohistochemistry. Results showed that PC12 cell viability decreased because of Rop, but the pretreatment of PFT-α could protect it. And PFT-α reduced the injuries in the spinal cord by Rop included vacuoles or edema. The results of immunofluorescence and immunohistochemistry testing showed that PFT-α inhibited the p53 protein upregulated by Rop. Apoptosis rate and many proapoptotic genes include p53, Bax, caspase-3 messenger RNA, and proteins were increased by Rop, but PFT-α could decrease it. In conclusion, PFT-α inhibited cell apoptosis and spinal cord injuries induced by Rop.
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http://dx.doi.org/10.1002/jbt.22822DOI Listing
June 2021

Different muscle mass indices of the Global Leadership Initiative on Malnutrition in diagnosing malnutrition and predicting survival of patients with gastric cancer.

Nutrition 2021 Apr 24;89:111286. Epub 2021 Apr 24.

Department of Gastrointestinal Surgery/Department of Clinical Nutrition, Beijing Shijitan Hospital, Capital Medical University, Beijing, China; Department of Oncology, Capital Medical University, Beijing, China; Beijing International Science and Technology Cooperation Base for Cancer Metabolism and Nutrition, Beijing, China. Electronic address:

Objective: Malnutrition is common and related to negative prognosis in patients with gastric cancer (GC). The Global Leadership Initiative on Malnutrition (GLIM), a novel consensus for the diagnosis of malnutrition, was proposed recently. However, the roles of GLIM in diagnosing malnutrition and predicting overall survival (OS) in patients with GC have been unclear.

Method: We conducted a multicenter, observational cohort study including 877 hospitalized patients with GC 2013 through 2018. Different anthropometric measurements were compared to assess reduced muscle mass. Kaplan-Meier curves and multivariate Cox regression were used to analyze the relationship between GLIM-defined malnutrition and the OS of patients with GC. Independent prognostic variables were incorporated to develop a nomogram for individualized survival prediction. The calibration curve was used to determine the predictive accuracy and discriminatory capacity of the nomogram. In addition, 219 patients with GC were enrolled for external validation.

Results: A total of 464 (53%) patients with GC were diagnosed with malnutrition. Patients diagnosed with severe malnutrition based on either midarm circumference or body weight-standardized hand grip strength had a shorter median survival time (16.7 mo; interquartile range, 8.4-32.7 mo) and a higher hazard ratio (HR, 1.49; 95% CI, 1.15-1.92; P = 0.002). Severe malnutrition was an independent risk factor for OS (HR, 1.32; 95% CI, 1.02-1.71; P = 0.038). The GLIM nomogram showed good performance in predicting 3-y survival in patients with GC.

Conclusions: Our findings support the effectiveness of GLIM in diagnosing malnutrition and predicting OS in patients with GC.
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http://dx.doi.org/10.1016/j.nut.2021.111286DOI Listing
April 2021

An MRI-trackable therapeutic nanovaccine preventing cancer liver metastasis.

Biomaterials 2021 07 19;274:120893. Epub 2021 May 19.

Key Laboratory of Biomass Chemical Engineering of Ministry of Education, Center for Bionanoengineering, And College of Chemical and Biological Engineering, Zhejiang University, Hangzhou, Zhejiang, 310027, China. Electronic address:

Cancer vaccines consisting of tumor-associated antigens (TAAs) can initiate a powerful antitumor immune response through antigen-presenting cells, such as dendritic cells (DCs) and macrophages, and have shown great potential in cancer prevention and therapy. However, poor anticancer efficacy and an uncertain immunization process have hitherto limited the application of cancer vaccines. Herein, a multifunctional nanovaccine comprising ovalbumin (OVA), MnO, and polydopamine (OMPN) was prepared by a facile one-pot method. OMPN displayed excellent anticancer efficacy against an orthotopic melanoma and could also prevent liver metastasis in a tumor re-challenge mice model. Additionally, the migration behavior of DCs in the inguinal lymph node after vaccination was tracked by MRI contrasted with OMPN, indicating successful DC activation and immune response. The superior anticancer efficacy, especially the high efficiency against tumor metastasis, and the capability of tracking the immunization process make OMPN a very promising multifunctional nanovaccine for cancer therapy.
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http://dx.doi.org/10.1016/j.biomaterials.2021.120893DOI Listing
July 2021

Effect of auto flash margin on superficial dose in breast conserving radiotherapy for breast cancer.

J Appl Clin Med Phys 2021 Jun 24;22(6):60-70. Epub 2021 May 24.

Department of Radiotherapy, Xinghua People's Hospital, Taizhou, Jiangsu, China.

Purpose: To investigate the dose-effect of Auto Flash Margin (AFM) on breast cancer's superficial tissues based on the Treatment Planning System (TPS) in the breast-conserving radiotherapy plan.

Methods: A total of 16 breast-conserving patients with early stage breast cancer were selected, using the X-ray Voxel Monte Carlo (XVMC) algorithm. Then, every included case plan was designed using a 2 cm-AFM (the value of AFM is 2 cm) and N-AFM (without AFM). Under the condition of ensuring the same configuration of #MU and collimator, the absorbed dose after a simulated inspiratory motion was calculated again using the new plan center, which moved backward to the linac source. The dose difference between the measurement points between AFM and N-AFM groups was compared.

Results: In the dose results, PTV of the AFM group was superior to that of the N-AFM group, PTV , PTV , Lung_Ipsi , Lung_Ipsi , and Body . Also, the dose results of the N-AFM group were significantly higher than those of the AFM group. However, there was no significant difference between Lung_Contra , Heart , and Breast_Contra in the two groups. In the collimator alignments at the same angle between groups, the AFM group formed an apparent air region outside the collimator compared with the N-AFM group. In the XVMC algorithm feature parameter, the AFM group had less #MU, higher QE, and slightly longer optimization time. The #segments of both groups were close to the 240 control points preset by the plan. The validation results of EBT3 film in both groups were more significant than 95%, meeting the clinical plan's application requirements. The difference in film results between groups was mainly reflected in the dose distribution at the near-source. 4DCT was used to summarize the maximum and minimum inspiratory motion distances of 7.31 ± 0.45 and 3.42 ± 0.91 mm respectively.

Conclusions: These results suggest that the AFM function application could significantly reduce the possibility of insufficient tumor target caused by inspiratory motion and ensure sufficient tumor target exposure.
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http://dx.doi.org/10.1002/acm2.13287DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8200433PMC
June 2021

Combined Anti-Cancer Effects of Platycodin D and Sorafenib on Androgen-Independent and PTEN-Deficient Prostate Cancer.

Front Oncol 2021 7;11:648985. Epub 2021 May 7.

Department of Clinical Nutrition, Daping Hospital, Army Medical University, Chongqing, China.

Castration-resistant (androgen-independent) and PTEN-deficient prostate cancer is a challenge in clinical practice. Sorafenib has been recommended for the treatment of this type of cancer, but is associated with several adverse effects. Platycodin D (PD) is a triterpene saponin with demonstrated anti-cancer effects and a good safety profile. Previous studies have indicated that PC3 cells (PTEN -/-, AR -/-) are sensitive to PD, suggesting that it may also be a useful treatment for castration-resistance prostate cancer. We herein investigated the effects of combining PD with sorafenib to treat PTEN-deficient prostate cancer cells. Our data show that PD promotes sorafenib-induced apoptosis and cell cycle arrest in PC3 cells. Of interest, PD only promoted the anti-cancer effects of sorafenib in Akt-positive and PTEN-negative prostate cancer cells. Mechanistic studies revealed that PD promoted p-Akt ubiquitination by increasing the p-Akt level. PD also increased the protein and mRNA expression of FOXO3a, the downstream target of Akt. Meanwhile, PD promoted the activity of FOXO3a and increased the protein expression of Fasl, Bim and TRAIL. Interestingly, when FOXO3a expression was inhibited, the antitumor effects of both PD and sorafenib were individually inhibited, and the more potent effects of the combination treatment were inhibited. Thus, the combination of PD and sorafenib may exert potent anti-cancer effects specifically FOXO3a. The use of Akt inhibitors or FOXO3a agonists, such as PD, may represent a promising approach for the treatment of androgen-independent and PTEN-deficient prostate cancer.
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http://dx.doi.org/10.3389/fonc.2021.648985DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8138035PMC
May 2021

Comparison of the AWGS and optimal stratification-defined handgrip strength thresholds for predicting survival in patients with lung cancer.

Nutrition 2021 Apr 3;90:111258. Epub 2021 Apr 3.

Department of Gastrointestinal Surgery, Department of Clinical Nutrition, Beijing Shijitan Hospital, Capital Medical University, Beijing, China. Electronic address:

Objectives: Handgrip strength (HGS) is related to cancer mortality. The aim of this study was to compare the performance of the Asian Working Group for Sarcopenia 2019 (AWGS)- and optimal stratification (OS)-defined HGS thresholds for predicting the survival of patients with lung cancer (LC).

Methods: We performed an observational cohort study including 3230 patients with LC admitted to five institutions in China from November 2011 to January 2019. Comprehensive baseline and follow-up information was documented. Sex-specific thresholds for identifying patients with a low HGS were defined based on the AWGS (<28 kg in men and <18 kg in women) and the OS. The associations of a low HGS with survival were estimated by calculating multivariable-adjusted hazard ratios (HRs), and the relationships were flexibly modeled using restricted cubic splines.

Results: The study included 1041 women and 2189 men with a mean age of 60 y and a median follow-up time of 761 d. The OS-calculated HGS thresholds were <31.2 kg in men and <22.4 kg in women. There were significant associations between a low HGS defined by the AWGS (n = 1392; 43.1%) or the OS (n = 2034; 63%) and various nutritional characteristics. An AWGS-defined low HGS was associated with prolonged hospitalization. The OS-defined low HGS group was associated with a 23% greater death hazard than the normal HGS group (HR, 1.23; 95% confidence interval, 1.08-1.40). An n-shaped non-linear association was observed between the HGS and survival in women (P = 0.003).

Conclusions: The OS-defined HGS thresholds show better performance than the AWGS for predicting the survival of patients with LC. Additionally, the HGS had n-shaped associations with the overall mortality among female patients with LC.
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http://dx.doi.org/10.1016/j.nut.2021.111258DOI Listing
April 2021

Rational construction of a reversible arylazo-based NIR probe for cycling hypoxia imaging in vivo.

Nat Commun 2021 05 13;12(1):2772. Epub 2021 May 13.

State Key Laboratory of Coordination Chemistry, School of Chemistry and Chemical Engineering, Chemistry and Biomedicine Innovation Center (ChemBIC), Nanjing University, Nanjing, China.

Reversible NIR luminescent probes with negligible photocytotoxicity are required for long-term tracking of cycling hypoxia in vivo. However, almost all of the reported organic fluorescent hypoxia probes reported until now were irreversible. Here we report a reversible arylazo-conjugated fluorescent probe (HDSF) for cycling hypoxia imaging. HDSF displays an off-on fluorescence switch at 705 nm in normoxia-hypoxia cycles. Mass spectroscopic and theoretical studies confirm that the reversible sensing behavior is attributed to the two electron-withdrawing trifluoromethyl groups, which stabilizes the reduction intermediate phenylhydrazine and blocks the further reductive decomposition. Cycling hypoxia monitoring in cells and zebrafish embryos is realized by HDSF using confocal imaging. Moreover, hypoxic solid tumors are visualized and the ischemia-reperfusion process in mice is monitored in real-time. This work provides an effective strategy to construct organic fluorescent probes for cycling hypoxia imaging and paves the way for the study of cycling hypoxia biology.
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http://dx.doi.org/10.1038/s41467-021-22855-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8119430PMC
May 2021

Association of Malnutrition, as Defined by the PG-SGA, ESPEN 2015, and GLIM Criteria, With Complications in Esophageal Cancer Patients After Esophagectomy.

Front Nutr 2021 26;8:632546. Epub 2021 Apr 26.

Department of Clinical Nutrition, Daping Hospital, Army Medical University (Third Military Medical University), Chongqing, China.

There are several approaches that can be used for the pre-treatment identification of malnutrition in oncology populations including the Patient-Generated Subjective Global Assessment (PG-SGA), the 2015 consensus statement by the European Society for Clinical Nutrition and Metabolism (ESPEN 2015) and the Global Leadership Initiative on Malnutrition (GLIM). This study aimed to evaluate whether malnutrition, as defined by these three methods, can be used to predict complications in esophageal cancer (EC) patients after esophagectomy. We performed a single center, observational cohort study that included 360 EC patients undergoing esophagectomy from December 2014 to November 2019 at Daping Hospital in China. The prevalence of malnutrition in the study population was prospectively defined using the PG-SGA (≥9 defined malnutrition), and retrospectively defined using the ESPEN 2015 and the GLIM. The prevalence of malnutrition and association with postoperative complications were compared in parallel for the three methods. The prevalence of malnutrition before surgery was 23.1% (83/360), 12.2% (44/360), and 33.3% (120/360) in the study population, as determined by the PG-SGA, the ESPEN 2015 and the GLIM, respectively. The PG-SGA and GLIM had higher diagnostic concordance (Kappa = 0.519, < 0.001) compared to the ESPEN 2015 vs. GLIM (Kappa = 0.361, < 0.001) and PG-SGA vs. ESPEN 2015 (Kappa = 0.297, < 0.001). The overall incidence of postoperative complications for the study population was 58.1% (209/360). GLIM- and ESPEN 2015-defined malnutrition were both associated with the total number of postoperative complications in multivariable analyses. Moreover, GLIM-defined malnutrition exhibited the highest power to identify the incidence of complications among all independent predictors in a pooled analysis. Among the PG-SGA, the ESPEN 2015 and the GLIM, the GLIM framework defines the highest prevalence rate of malnutrition and appears to be the optimal method for predicting postoperative complications in EC patients undergoing esophagectomy. These results support the importance of preoperatively identifying malnutrition using appropriate assessment tools, because it can facilitate the selection of management strategies that will optimize the clinical outcomes of EC patients.
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http://dx.doi.org/10.3389/fnut.2021.632546DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8107390PMC
April 2021

A novel model with nutrition-related parameters for predicting overall survival of cancer patients.

Support Care Cancer 2021 May 10. Epub 2021 May 10.

Department of Gastrointestinal Surgery/Department of Clinical Nutrition, Beijing Shijitan Hospital, Capital Medical University, Beijing, 100038, China.

Background: Increasing evidence indicates that nutritional status could influence the survival of cancer patients. This study aims to develop and validate a nomogram with nutrition-related parameters for predicting the overall survival of cancer patients.

Patients And Methods: A total of 8749 patients from the multicentre cohort study in China were included as the primary cohort to develop the nomogram, and 696 of these patients were recruited as a validation cohort. Patients' nutritional status were assessed using the PG-SGA. LASSO regression models and Cox regression analysis were used for factor selection and nomogram development. The nomogram was then evaluated for its effectiveness in discrimination, calibration, and clinical usefulness by the C-index, calibration curves, and decision curve analysis. Kaplan-Meier survival curves were used to compare the survival rate.

Results: Seven independent prognostic factors were identified and integrated into the nomogram. The C-index was 0.73 (95% CI, 0.72 to 0.74) and 0.77 (95% CI, 0.74 to 0.81) for the primary cohort and validation cohort, which were both higher than 0.59 (95% CI, 0.58 to 0.61) of the TNM staging system. DCA demonstrated that the nomogram was higher than the TNM staging system and the TNM staging system combined with PG-SGA. Significantly median overall survival differences were found by stratifying patients into different risk groups (score < 18.5 and ≥ 18.5) for each TNM category (all Ps < 0.001).

Conclusion: Our study screened out seven independent prognostic factors and successfully generated an easy-to-use nomogram, and validated and shown a better predictive validity for the overall survival of cancer patients.
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http://dx.doi.org/10.1007/s00520-021-06272-zDOI Listing
May 2021

Effect of root exudates on the stability and transport of graphene oxide in saturated porous media.

J Hazard Mater 2021 07 17;413:125362. Epub 2021 Feb 17.

Key Laboratory of Surficial Geochemistry of Ministry of Education, School of Earth Sciences and Engineering, Hydrosciences Department, Nanjing University, Nanjing 210023, China.

Root exudates are a major source of dissolved organic matters that strongly affect the stability and transport behaviors of nanomaterials in porous media. This study investigated the effect of citric acid (CA) and oxalic acid (OA), two common low molecular weight root exudates, on the stability and transport of graphene oxide (GO) in saturated sand columns under different combinations of pH (4.5, 7.0), ionic strength (IS: 10, 50 mM), and organic acid concentrations (10, 25 mM). Both OA and CA accelerated GO aggregation, especially under high IS and acid concentration conditions. With the presence of OA/CA (≥ 10 mM), the transport of GO was higher at pH of 7.0 than 4.5, and the GO mobility decreased with increasing IS and OA/CA concentrations, whereas, enhanced GO transport was observed at a low concentration of OA/CA (0.1 mM), indicating that the influence of organic acid was concentration-dependent. All the results suggest that perturbations of surface potential of GO and sand, as well as the chemical structure of organic acids under different solution chemistry conditions are crucial in controlling GO stability and transport behaviors. Mathematical models based on the advection-dispersion equation with one-site kinetics simulated the experimental breakthrough curves of GO very well.
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http://dx.doi.org/10.1016/j.jhazmat.2021.125362DOI Listing
July 2021

Alantolactone inhibits cervical cancer progression by downregulating BMI1.

Sci Rep 2021 Apr 29;11(1):9251. Epub 2021 Apr 29.

Hubei Clinical Research Center for Parkinson's Disease at Xiangyang No. 1 People's Hospital, Hubei Key Laboratory of Wudang Local Chinese Medicine Research, Hubei University of Medicine, Shiyan, 442000, People's Republic of China.

Cervical cancer is the second most common cancer in women. Despite advances in cervical cancer therapy, tumor recurrence and metastasis remain the leading causes of mortality. High expression of BMI1 is significantly associated with poor tumor differentiation, high clinical grade, and poor prognosis of cervical cancer, and is an independent prognostic factor in cervical carcinoma. Alantolactone (AL), a sesquiterpene lactone, exhibits potent anti-inflammatory and anticancer activities. In this paper, we investigated the mechanism of AL in reducing the proliferation, migration, and invasion of HeLa and SiHa cervical cancer cells as well as its promotion of mitochondrial damage and autophagy. BMI1 silencing decreased epithelial-mesenchymal transformation-associated proteins and increased autophagy-associated proteins in HeLa cells. These effects were reversed by overexpression of BMI1 in HeLa cells. Thus, BMI1 expression is positively correlated with invasion and negatively correlated with autophagy in HeLa cells. Importantly, AL decreased the weight, volume, and BMI1 expression in HeLa xenograft tumors. Furthermore, the structure of BMI1 and target interaction of AL were virtually screened using the molecular docking program Autodock Vina; AL decreased the expression of N-cadherin, vimentin, and P62 and increased the expression of LC3B and Beclin-1 in xenograft tumors. Finally, expression of BMI1 increased the phosphorylation of STAT3, which is important for cell proliferation, survival, migration, and invasion. Therefore, we suggest that AL plays a pivotal role in inhibiting BMI1 in the tumorigenesis of cervical cancer and is a potential therapeutic agent for cervical cancer.
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http://dx.doi.org/10.1038/s41598-021-87781-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8085045PMC
April 2021

Association between MMP-2 gene polymorphism and cataract susceptibility: A protocol for systematic review and meta-analysis.

Medicine (Baltimore) 2021 Apr;100(14):e25392

Department of Ophthalmology, The Affiliated Kunhua Hospital of Kunming University of Science and Technology, The First People's Hospital of Yunnan Province, Kunming 650032, Yunnan Province, China.

Background: Matrix metalloproteinase-2 (MMP-2) polymorphisms have been considered as risk factors of cataracts, but the results still remain controversial. In this study, we have performed a systematic meta-analysis to evaluate the association between MMP-2 polymorphisms and cataract risks.

Methods: Published literature was retrieved from Wanfang, Chinese Biomedical Literature Database, Chinese National Knowledge Infrastructure, Chongqing VIP Chinese Science and Technology Periodical Database, PubMed, Embase, and Web of Science databases. The case-control studies that explored the association between MMP-2 polymorphisms and cataract risks were included. Pooled odds ratio (OR) and 95% confidence interval (CI) were calculated using random- or fixed-effects model.

Results: This study could provide high-quality and evidence-based medical evidence for the correlation between MMP-2 polymorphisms and cataract risks.

Conclusion: The study could provide updated evidence for the evaluation of the relationship between MMP-2 polymorphism and cataract risk.

Ethics And Dissemination: The private information from individuals will not be published. This systematic review also will not involve endangering participant rights. Ethical approval is not available. The results may be published in a peer-reviewed journal or disseminated in relevant conferences.

Osf Registration Number: DOI 10.17605/OSF.IO/KU9NE.
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http://dx.doi.org/10.1097/MD.0000000000025392DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8036040PMC
April 2021

Glutathione-Responsive Magnetic Nanoparticles for Highly Sensitive Diagnosis of Liver Metastases.

Nano Lett 2021 03 18;21(5):2199-2206. Epub 2021 Feb 18.

Key Laboratory of Biomass Chemical Engineering of Ministry of Education, Center for Bionanoengineering, and College of Chemical and Biological Engineering, Zhejiang University, Hangzhou, Zhejiang, 310027, China.

Liver metastasis (LM) occurs in various cancers, and its early and accurate diagnosis is of great importance. However, the detection of small LMs is still a great challenge because of the subtle differences between normal liver tissue and small metastases. Herein, we prepare glutathione (GSH)-responsive hyaluronic acid-coated iron oxide nanoparticles (HIONPs) for highly sensitive diagnosis of LMs through a facile one-pot method. HIONPs greatly enhance the signal of MRI in tumor metastases as contrast agent (CA), whereas they substantially decrease the signal of liver as CA as they aggregate into clusters upon the high GSH in liver. Consequently, MRI contrasted by HIONPs clearly distinguishes metastatic tumors (bright) from surrounding liver tissues (dark). HIONPs with superior LM contrasting capability and facile synthesis are very promising for clinical translation and indicate a new strategy to develop an ultrasensitive MRI CA for LM diagnosis that exploits high GSH level in the liver.
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http://dx.doi.org/10.1021/acs.nanolett.0c04967DOI Listing
March 2021

Self-assembly of hyaluronic acid-mediated tumor-targeting theranostic nanoparticles.

Biomater Sci 2021 Mar 28;9(6):2221-2229. Epub 2021 Jan 28.

Department of Radiology, Sir Run Run Shaw Hospital (SRRSH) of School of Medicine, Zhejiang University, Hangzhou, Zhejiang 310016, China.

Theranostic nanoparticles (NPs) have emerged as promising candidates for cancer diagnosis and treatment. Manganese dioxide (MnO)-based NPs are potential contrast agents with excellent paramagnetic property and biocompatibility, exhibiting satisfactory magnetic resonance imaging (MRI) effects and biological safety. Recently, hyaluronic acid (HA) has gained increasing interest due to its tumor-targeting ability, which can improve the tumor affinity of manganese dioxide (MnO)-based NPs. In this study, HA-coated and albumin (BSA)-templated MnO and polydopamine hybrid nanoparticles (HMDNs) with tumor-targeting and superior imaging capability were fabricated via modifying the nanoparticles prepared by integrating dopamine polymerization and MnO biomineralization. The modification was found to enhance the cellular uptake of HMDNs by cancer cells. The prepared HMDN had high MRI contrasting capability with a longitudinal relaxivity of 22.2 mM s and strong photothermal therapy (PTT) effects with nearly complete tumor ablation under laser irradiation in vivo. HMDNs also showed effective clearance through kidneys, with no toxicity to important tissues. Therefore, HMDNs with superior imaging and PTT capability presented a new method to prepare tumor-targeting multifunctional nanotheranostics.
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http://dx.doi.org/10.1039/d0bm01855dDOI Listing
March 2021

Chronic isolated lightheadedness is a sign of abnormal plasma levels of phospholipids.

Exp Gerontol 2021 04 21;146:111249. Epub 2021 Jan 21.

Fu Xing Lu Clinics of the First Affiliated Hospital of Chinese Army General Hospital, China.

Objective: To evaluate whether Chronic Isolated Light-headedness (CIL) commonly manifested in elderly patients is related with cerebral oxygen insufficiency.

Methods: In this case-control study, 462 patients (aged 40-83 years) with CIL and 238 clinical data matched controls were enrolled consecutively from January 2011 to September 2014. The plasma levels of "phospholipids with solubility similar to that of lysophosphatidic acid" (PSS-LPA), a surrogate marker for cerebral oxygen insufficiency, were assayed for all subjects to compare the occurrence and severity of CIL with the values of PSS-LPA.

Results: Patients with CIL had significantly higher plasma levels of PSS-LPA than controls, regardless of having or having not psychogenic abnormalities, χ2 = 448, odds ratio (95% CI) = 140 (72-260), P < 0.001; the mean plasma levels, 0.573 vs. 0.290 mmol/L respectively (P < 0.001). Receiver operator characteristic (ROC) analyses showed plasma PSS-LPA was both sensitive and specific for CIL. The area under ROC curve (AUC) was as high as 0.953 (0.938-0.968). The changes in severity of CIL between two separate assays of one month apart were correlated closely with the changes in plasma levels of PSS-LPA for the same patients, correlation coefficient (Spearman) = 0.90, p < 0.001.

Conclusions: CIL is a manifestation of abnormal plasma levels of phospholipids which suggests cerebral oxygen insufficiency. This new finding shows that cerebral oxygen insufficiency is not rare especially in elderly persons.
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http://dx.doi.org/10.1016/j.exger.2021.111249DOI Listing
April 2021

Nutritional features-based clustering analysis as a feasible approach for early identification of malnutrition in patients with cancer.

Eur J Clin Nutr 2021 Jan 18. Epub 2021 Jan 18.

Department of Clinical Nutrition, Daping Hospital, Army Medical University (Third Military Medical University), Chongqing, 400042, China.

Background: Malnutrition is prevalent that can impair multiple clinical outcomes in oncology populations. This study aimed to develop and utilize a tool to optimize the early identification of malnutrition in patients with cancer.

Methods: We performed an observational cohort study including 3998 patients with cancer at two teaching hospitals in China. Hierarchical clustering was performed to classify the patients into well-nourished or malnourished clusters based on 17 features reflecting the phenotypic and etiologic dimensions of malnutrition. Associations between the identified clusters and patient characteristics were analyzed. A nomogram for predicting the malnutrition probability was constructed and independent validation was performed to explore its clinical significance.

Results: The cluster analysis identified a well-nourished cluster (n = 2736, 68.4%) and a malnourished cluster (n = 1262, 31.6%) in the study population, which showed significant agreement with the Patient-Generated Subjective Global Assessment and the Global Leadership Initiative on Malnutrition criteria (both P < 0.001). The malnourished cluster was negatively associated with the nutritional status, physical status, quality of life, short-term outcomes and was an independent risk factor for survival (HR = 1.38, 95%CI = 1.22-1.55, P < 0.001). Sex, gastrointestinal symptoms, weight loss percentages (within and beyond 6 months), calf circumference, and body mass index were incorporated to develop the nomogram, which showed high performance to predict malnutrition (AUC = 0.972, 95%CI = 0.960-0.983). The decision curve analysis and independent external validation further demonstrated the effectiveness and clinical usefulness of the tool.

Conclusions: Nutritional features-based clustering analysis is a feasible approach to define malnutrition. The derived nomogram shows effectiveness for the early identification of malnutrition in patients with cancer.
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http://dx.doi.org/10.1038/s41430-020-00844-8DOI Listing
January 2021

Development and validation of a rapid-decision pathway to diagnose malnutrition in patients with lung cancer.

Nutrition 2021 04 5;84:111102. Epub 2020 Dec 5.

Department of Clinical Nutrition, Daping Hospital, Army Medical University (Third Military Medical University), Chongqing, China. Electronic address:

Objectives: Malnutrition is frequently developed and outcome-related in patients with lung cancer (LC). Making a rapid and accurate diagnosis of malnutrition is the major concern for dietitians and clinicians.

Methods: We performed a multicenter, observational cohort study including 1219 patients with LC. Malnutrition was diagnosed using the Global Leadership Initiative on Malnutrition criteria, and the study population was randomly divided into a training group (n = 914) and a validation group (n = 305). A nomogram (to diagnose malnutrition) and two decision trees (to diagnose and grade malnutrition, respectively) were independently developed and tested. A random forest algorithm was used to calculate relative variable importance.

Results: The Global Leadership Initiative on Malnutrition criteria identified 292 patients with malnutrition (24%). Sex, body mass index, weight loss within 6 mo, weight loss beyond 6 mo, calf circumference, and handgrip strength to weight ratio were screened for model development. The nomogram showed good discrimination with an area under the curve (AUC) of 0.982 (95% confidence interval, 0.969-0.995) and good calibration in the validation group. A decision curve analysis demonstrated that the nomogram was clinically useful. The diagnostic tree showed an accuracy of 0.98 (Kappa = 0.942; AUC = 0.978; 95% confidence interval, 0.964-0.992), and the classification tree showed an accuracy of 0.98 (Kappa = 0.955; AUC = 0.987) in the validation group. Weight loss within 6 mo contributed the largest importance to both trees.

Conclusions: This study presents a rapid-decision pathway, including a set of tools that can be conveniently used to facilitate the diagnosis and severity grading of malnutrition in patients with LC.
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http://dx.doi.org/10.1016/j.nut.2020.111102DOI Listing
April 2021

Classification Tree-Based Machine Learning to Visualize and Validate a Decision Tool for Identifying Malnutrition in Cancer Patients.

JPEN J Parenter Enteral Nutr 2021 Jan 8. Epub 2021 Jan 8.

Department of Clinical Nutrition, Daping Hospital, Army Medical University (Third Military Medical University), Chongqing, China.

Background: The newly proposed Global Leadership Initiative on Malnutrition (GLIM) framework is promising to gain global acceptance for diagnosing malnutrition. However, the role of machine learning in facilitating its application in clinical practice remains largely unknown.

Methods: We performed a multicenter, observational cohort study including 3998 patients with cancer. Baseline malnutrition was defined using the GLIM criteria, and the study population was randomly divided into a derivation group (n = 2998) and a validation group (n = 1000). A classification and regression trees (CART) algorithm was used to develop a decision tree for classifying the severity of malnutrition in the derivation group. Model performance was evaluated in the validation group.

Results: GLIM criteria diagnosed 588 patients (14.7%) with moderate malnutrition and 532 patients (13.3%) with severe malnutrition among the study population. The CART cross-validation identified 5 key predictors for the decision tree construction, including age, weight loss within 6 months, body mass index, calf circumference, and the Nutritional Risk Screening 2002 score. The decision tree showed high performance, with an area under the curve of 0.964 (κ = 0.898, P < .001, accuracy = 0.955) in the validation group. Subgroup analysis showed that the model had apparently good performance in different cancers. Among the 5 predictors constituting the tree, age contributed the least to the classification power.

Conclusion: Using the machine learning, we visualized and validated a decision tool based on the GLIM criteria that can be conveniently used to accelerate the pretreatment identification of malnutrition in patients with cancer.
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http://dx.doi.org/10.1002/jpen.2070DOI Listing
January 2021

Is hand grip strength a necessary supportive index in the phenotypic criteria of the GLIM-based diagnosis of malnutrition in patients with cancer?

Support Care Cancer 2021 Jul 4;29(7):4001-4013. Epub 2021 Jan 4.

Department of Clinical Nutrition, Daping Hospital, Army Medical University (Third Military Medical University), Changjiangzhilu 10#, Yuzhong District, Chongqing, 400042, China.

Background: The Global Leadership Initiative on Malnutrition (GLIM) has the potential to gain global acceptance for diagnosing malnutrition. Of which, calf circumference (CC) was proposed as an alternative to evaluate the reduced muscle mass (RMM). The present study aimed to evaluate whether including the hand grip strength (HGS) was helpful for diagnosing malnutrition under the GLIM framework.

Methods: We performed a multicenter, observational cohort study including 3998 patients with cancer at two teaching hospitals. The RMM criterion was separately assessed using the calf circumference (CC), or the CC and HGS combined. Accordingly, two methods of GLIM diagnosis were independently developed to determine the nutritional status of the patients. The diagnostic concordance, baseline characteristics, and outcomes of patients were compared across the malnourished-CC-HGS, malnourished-CC+HGS, and well-nourished groups. The Patient-Generated Subjective Global Assessment (PG-SGA) was used as a comparator to identify the optimal method.

Results: Malnutrition was identified in 1120 (28%) patients by the CC method and 1060 (26.5%) patients by the CC+HGS method. Compared to the well-nourished group, the malnourished-CC+HGS group (60 patients, 1.5%) had poorer nutritional characteristics, poorer Karnofsky Performance Status scores, poorer global quality of life scores, and higher Nutritional Risk Screening 2002 scores. The severity of malnutrition diagnosed using the CC method (Kappa = 0.136) showed higher agreement with the PG-SGA than the CC+HGS method (Kappa = 0.127).

Conclusion: Compared to CC+HGS, the CC alone appears to be adequate to evaluate RMM under the GLIM framework. A simpler method might facilitate the application of these criteria in clinical settings by increasing efficacy and minimizing missed diagnoses.
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http://dx.doi.org/10.1007/s00520-020-05975-zDOI Listing
July 2021

Effects of ionic strength and cation type on the transport of perfluorooctanoic acid (PFOA) in unsaturated sand porous media.

J Hazard Mater 2021 02 13;403:123688. Epub 2020 Aug 13.

State Key Laboratory of Pollution Control and Resource Reuse, Key Laboratory of Surficial Geochemisty, Ministry of Education, School of Earth Sciences and Engineering, Hydrosciences Department, Nanjing University, Nanjing 210023, China. Electronic address:

Current understanding of perfluorooctanoic acid (PFOA) transport in unsaturated porous media is still limited with significant variability in solution chemistry. Column experiments were conducted to systematically evaluate the impacts of ionic strength (1.5-30 mM) and cation type (Na and Ca) on PFOA transport in unsaturated quartz sand. The results showed that an increase in ionic strength (1.5-30 mM) led to greater PFOA retardation in unsaturated columns. Meanwhile, Ca caused more PFOA retardation than Na at the same unsaturated conditions. These findings were supported by bubble column experiments, which indicated greater PFOA adsorption at the air-water interface with increasing ionic strength or in the presence of Ca in comparison to Na. Furthermore, the air-water interfacial (AWI) adsorption coefficients calculated from surface tension isotherms also increased with increasing ionic strength or in the presence of Ca in comparison to Na. These results clearly confirm that higher ionic strength or cation valence significantly promoted PFOA adsorption at the air-water interface, and thus caused greater PFOA retardation during transport in unsaturated porous media. This work points out the importance of considering solution ionic strength and cation type in assessing the transport behavior of PFOA in unsaturated porous media.
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http://dx.doi.org/10.1016/j.jhazmat.2020.123688DOI Listing
February 2021

Polyphenol-cisplatin complexation forming core-shell nanoparticles with improved tumor accumulation and dual-responsive drug release for enhanced cancer chemotherapy.

J Control Release 2021 02 7;330:992-1003. Epub 2020 Nov 7.

Center for Bionanoengineering, College of Chemical and Biological Engineering, Zhejiang University, Hangzhou 310027, People's Republic of China; Hangzhou Global Scientific and Technological Innovation Center, Hangzhou 311215, People's Republic of China. Electronic address:

Cisplatin (CDDP) is a potent first-line antitumor drug but suffers severe side effects and poor pharmacokinetics. Its complexation with polycarboxylic acids, such as polyglutamic acids, is generally used to fabricate nanoformulations for CDDP delivery; however, the multiple strong complexations makes intracellular drug release slow. Herein, we report a novel polyphenol-metal coordination method to fabricate CDDP-incorporated core-shell nanoparticles, which are stable in blood circulation but dissociate in the tumor. Methoxyl-PEG terminated with one or two gallic acids (PEG-GA or PEG-GA2) complexed CDDP and produced well-defined nanoparticles (PEG-GAx/Pt) with CDDP loading contents as high as 17.7% to 29.8%. The PEG-GAx/Pt nanoparticles were very stable in the physiological conditions and had slow blood clearance and efficient tumor accumulation, but dissociated quickly and released CDDP in response to the tumor acidity or elevated levels of reactive oxygen species (ROS). PEG-GAx/Pt nanoparticles exhibited improved antitumor efficiency against 4 T1 breast cancer and A549 lung carcinoma with much-reduced toxicity compared to free CDDP. The work demonstrates a new strategy of cisplatin-polyphenol coordination for developing platinum drugs' nanomedicines.
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http://dx.doi.org/10.1016/j.jconrel.2020.11.006DOI Listing
February 2021

Genetic Liability to Smoking and Breast Cancer Risk.

Clin Epidemiol 2020 20;12:1145-1148. Epub 2020 Oct 20.

Department of Cardiology, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang 310003, People's Republic of China.

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http://dx.doi.org/10.2147/CLEP.S270509DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7585802PMC
October 2020

Isolation and complete genome sequencing of the virulent phage vB_EcoS_XY3 infecting multidrug-resistant Escherichia coli.

Arch Virol 2021 Jan 25;166(1):303-307. Epub 2020 Oct 25.

Hubei Clinical Research Center of Parkinson's Disease, Hubei Key Laboratory of Wudang Local Chinese Medicine Research, Xiangyang No.1 People's Hospital, Hubei University of Medicine, Shiyan, 442000, China.

A virulent phage, named vB_EcoS_XY3, was isolated from hospital wastewater in Xiangyang, China. Its morphological characteristics, growth parameters, adsorption rate, and pH and temperature stability were determined. Phage vB_EcoS_XY3 was found to be able to infect Escherichia coli laboratory strains and also some multidrug-resistant E. coli strains. Its complete genome consists of 51,345 base pairs of double-stranded DNA with an average GC content of 55.24% and 85 putative protein-coding genes. Forty-four genes were annotated with known functions. These results will not only provide further insights into E. coli phages but also have implications for the development of potential biocontrol agents.
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http://dx.doi.org/10.1007/s00705-020-04844-8DOI Listing
January 2021

Identification and characterization of two bacteriophages with lytic activity against multidrug-resistant Escherichia coli.

Virus Res 2021 01 21;291:198196. Epub 2020 Oct 21.

Center for Translational Medicine, Hubei Clinical Research Center of Parkinson's disease, Hubei Key Laboratory of Wudang Local Chinese Medicine Research, Xiangyang No.1 People's Hospital, Hubei University of Medicine, Xiangyang, 441000, China. Electronic address:

Escherichia coli is an opportunistic bacterial pathogen that causes a wide range of nosocomial infections. The emergence of multidrug resistance in E. coli poses a severe threat to global health. Phage therapies are an alternative method to control multidrug-resistant pathogens, which have been attracting increasing attention. Owing to their ability to lyse bacteria specifically and efficiently, bacteriophages are considered novel antimicrobial agents. In this study, we used multidrug-resistant E. coli as an indicator and isolated, characterized, and compared two new phages of the Siphoviridae family referred to as vB_EcoS_XF and vB_EcoS_XY2. These phages were able to infect several pathogenic multidrug-resistant E. coli strains. A short latent period and large burst size ensured their rapidly reproduction in host cells. Their tolerance of high temperatures and high pH levels meant that remained stable when used to control pathogenic E. coli strains. No obvious cytotoxicity was observed when either HEK293 T or A549 cells were incubated with these two phages. Mass spectrometry analysis allowed us to identify several phage-encoded proteins. Genomic analysis revealed that no toxic proteins or antibiotic proteins were encoded. Genome comparison and phylogenetic analysis indicated that the phages identified show high similarity with E. coli phages of the genus Kagunavirus. The desirable characteristics of the novel phages identified make them good potential therapeutic candidates, and components of phage cocktails to treat multidrug-resistant E. coli in the future.
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http://dx.doi.org/10.1016/j.virusres.2020.198196DOI Listing
January 2021

The Role of N6-Methyladenosine Methylation in the Progression of Endometrial Cancer.

Cancer Biother Radiopharm 2020 Oct 14. Epub 2020 Oct 14.

Department of Gynecology, Jining No. 1 People's Hospital, Jining City, China.

N6-methyladenosine (m6A) methylation was the most abundant internal modification on messenger RNAs in eukaryotes. This study intended to explore the role of m6A methylation in endometrial cancer (EC). The m6A-sequencing data "GSE93911" of human EC were downloaded from Gene Expression Omnibus database. Hisat2 software and MACS2 were used to perform the alignment of reads and m6A methylation peak calling, and the peaks were annotated using Chipseeker. Then, differential m6A methylation peaks between normal and tumor samples were analyzed, followed by the functional enrichment analysis of the differentially methylated genes in promoter and 3' untranslated region (UTR) using Clusterprofiler. Based on the 450K methylated chip data, gene expression and clinical data in The Cancer Genome Atlas, the differentially methylated genes were verified, followed by Cox univariate/multivariate regression analysis and survival analysis. Finally, a risk prognosis model was constructed. The m6A peak number was decreased in EC. The distribution of m6A peaks was highly enriched near transcriptional start site, in promoter, UTR, intron and exon, followed by distal intergenic. A total of 581 differentially methylated genes (361 hyper- and 220 hypomethylated genes) were identified in promoter and UTR regions that were enriched in insulin resistance (IR) and extracellular matrix (ECM). A total of 181 genes with significant differential expressions and differential methylation site in EC were selected. Of which, 31 genes were correlated with survival, and an 11-gene risk prognosis model was identified, including GDF7, BNC2, SLC8A1, B4GALNT3, DHCR24, ESRP1, HOXB9, IGSF9, KIAA1324, MSnX1, and PHGDH. The m6A methylation regulated EC progression by targeting the genes related to IR and ECM. A 11-gene risk prognosis model was identified to predict survival of patients with EC.
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http://dx.doi.org/10.1089/cbr.2020.3912DOI Listing
October 2020

Resveratrol suppresses the growth and metastatic potential of cervical cancer by inhibiting STAT3 phosphorylation.

Cancer Med 2020 11 10;9(22):8685-8700. Epub 2020 Oct 10.

Hubei Institute of Parkinson's Disease at Xiangyang No. 1 People's Hospital, Hubei Key Laboratory of Wudang Local Chinese Medicine Research, Hubei University of Medicine, Shiyan, People's Republic of China.

Aberrant signal transducer and activator of transcription 3 (STAT3) signaling promotes the initiation and progression of cancer in humans by either inhibiting apoptosis or inducing cell proliferation, angiogenesis, invasion, and metastasis. The role of resveratrol(RES)in inhibiting the STAT3 signaling pathway in vivo, particularly in cervical cancer is still unknown. This study aims to investigate the role of STAT3 and its phosphorylation in RES-mediated suppression of cervical cancer. The effects of RES on cervical cancer were determined by examining tumor tissues, their histological changes, and the volume and weight of tumor tissues grown from HeLa cells injected in female athymic BALB/C nude mice. The structure and target interaction of RES were virtually screened using the molecular docking program Autodock Vina. The status of phosphorylated STAT3, protein levels of epithelial-mesenchymal transition molecular markers and extracellular matrix degradation enzymes were determined through Western blot. We demonstrated that RES could suppress the proliferation and metastatic potential of cervical cancer cells by inactivating phosphorylation of STAT3 at Tyr705 but not Ser727. This effect was intensified by inhibition of the STAT3 signal pathway.
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http://dx.doi.org/10.1002/cam4.3510DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7666735PMC
November 2020
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