Publications by authors named "Xin Guan"

321 Publications

Humidity sensors based on metal organic frameworks derived polyelectrolyte films.

J Colloid Interface Sci 2021 Jun 13;602:646-653. Epub 2021 Jun 13.

State Key Laboratory of Integrated Optoelectronics, College of Electronic Science and Engineering, Jilin University, Changchun 130012, PR China. Electronic address:

Application of metal organic frameworks (MOFs) on sensors is of great interest for researchers. Film forming ability of the sensing material is very important for both the preparation process and sensing properties of the devices. Humidity sensors based on UIO-66 derived polyelectrolyte films were well prepared by in situ thiol-ene click cross-linking polymerization in this work. The hydrophilicity of the sensing film could be controlled by the feed ratios. The optimized humidity sensor shows a fast response to RHs change (Res/Rec time is 3.1 s/1.5 s, respectively) with ∼1.2% RH of humidity hysteresis. The water molecules adsorption behavior of the film and the sensing mechanism were also be investigated. The humidity sensor with good water and thermal stability and repeatability was applied in breath monitoring, which can well distinguish different breath states.
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http://dx.doi.org/10.1016/j.jcis.2021.06.064DOI Listing
June 2021

Health-related quality of life outcomes and influencing factors in patients with unruptured intracranial aneurysms after endovascular treatment.

Qual Life Res 2021 Jun 21. Epub 2021 Jun 21.

Department of Neurosurgery, Xuanwu Hospital, Capital Medical University, No. 45 Changchun Street, Xicheng District, Beijing, China.

Background: Health-related quality of life (HRQoL) is an important indicator when evaluating prognosis and disease-related treatments. Our current knowledge of the HRQoL outcomes of unruptured intracranial aneurysm (UIA) patients treated by the endovascular intervention appeared to be very limited. To fill this gap, the present study investigated the HRQoL outcomes and identified the influencing factors in UIA patients treated by endovascular intervention.

Methods: We conducted a single-center cross-sectional study on patients who underwent endovascular treatment for UIAs. HRQoL outcomes were assessed by the 36-item Short Form Health Survey (SF-36). The SF-36 results of the Chinese reference population were used as the reference data. The independent variables with a univariate analysis result of P < 0.05 were included in the multivariate analysis. Finally, multivariable linear regression analysis was performed to identify the factors influencing HRQoL. Bonferroni correction was utilized for multiple testing correction.

Results: A total of 200 patients (83 males and 117 females, mean age of 55.2 ± 9.48 years) with UIAs treated by endovascular intervention were enrolled. The scores of SF-36 in 8 domains for UIA patients treated by endovascular intervention did not all reach the average level of the Chinese reference population after an average recovery period of 30.67 ± 8.6 months. Ischemic cerebrovascular disease history, advanced age, and mRS progression at discharge were independent risk factors of HRQoL for UIA patients treated by endovascular intervention, but physical exercise at least once a week and daily sleep time no < 6 h were independent protective factors.

Conclusion: The HRQoL of UIA patients treated by the endovascular intervention was decreased to varying degrees compared with those of the Chinese reference population. The influencing factors of HRQoL explored by this study provide insights for improving the clinical management and daily lives of these patients. HRQoL assessment should be included in future aneurysm prognostic studies to provide better evidence.
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http://dx.doi.org/10.1007/s11136-021-02904-3DOI Listing
June 2021

Cost-Effectiveness Analysis of Abemaciclib Plus Fulvestrant in the Second-Line Treatment of Women With HR+/HER2- Advanced or Metastatic Breast Cancer: A US Payer Perspective.

Front Med (Lausanne) 2021 2;8:658747. Epub 2021 Jun 2.

School of International Pharmaceutical Business, China Pharmaceutical University, Nanjing, China.

This study evaluated the cost-effectiveness of abemaciclib plus fulvestrant (ABE + FUL) vs. palbociclib plus fulvestrant (PAL + FUL), ribociclib plus fulvestrant (RIB + FUL) and fulvestrant monotherapy (FUL) as second-line treatment for hormone receptor-positive and human epidermal growth factor receptor 2- negative advanced or metastatic breast cancer in the US. The 3 health states partitioned survival (PS) model was used over the lifetime. Effectiveness and safety data were derived from the MONARCH 2 trial, MONALEESA-3 trial, and PALOMA-3 trial. Parametric survival models were used for four treatments to explore the long-term effect. Costs were derived from the pricing files of Medicare and Medicaid Services, and utility values were derived from published studies. Sensitivity analyses including one-way sensitivity analysis, probabilistic sensitivity analysis and scenario analysis were performed to observe model stability. In the PS model, compared with PAL + FUL, ABE + FUL yielded 0.44 additional QALYs at an additional cost of $100,696 for an incremental cost-utility ratio (ICUR) of $229,039/QALY. Compared with RIB + FUL, ABE + FUL yielded 0.03 additional QALYs at an additional cost of $518 for an ICUR of $19,314/QALY. Compared with FUL, ABE + FUL yielded 0.68 additional QALYs at an additional cost of $260,584 for ICUR of $381,450/QALY. From the PS model, the ICUR was $270,576 /QALY (ABE + FUL vs. PAL + FUL), dominated (ABE + FUL vs. RIB + FUL) and $404,493/QALY (ABE + FUL vs. FUL) in scenario analysis. In the probabilistic sensitivity analysis, the probabilities that ABE + FUL was cost-effective vs. PAL + FUL, RIB + FUL and FUL at thresholds of $50,000, $100,000, and $200,000 per QALY gained were 0% and the probabilities that ABE + FUL was cost-effective vs. PAL + FUL and RIB + FUL at thresholds of $50,000, $100,000, and $200,000 per QALY gained were 0.2, 0.6, and 7.3%. The findings from the present analysis suggest that ABE + FUL might be cost-effective compared with RIB + FUL and not cost-effective compared with PAL + FUL and FUL for second-line treatment of patients with HR+/HER2- advanced or metastatic breast cancer in the US.
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http://dx.doi.org/10.3389/fmed.2021.658747DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8206485PMC
June 2021

Comprehensive analysis of tumor microenvironment and identification of an immune signature to predict the prognosis and immunotherapeutic response in lung squamous cell carcinoma.

Ann Transl Med 2021 Apr;9(7):569

Department of Thoracic Surgery, Shanghai Ninth People's Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China.

Background: Tumor mutation burden (TMB) and immune microenvironment are important determinants of prognosis and immunotherapeutic efficacy for cancer patients. The aim of the present study was to develop an immune signature to effectively predict prognosis and immunotherapeutic response in patients with lung squamous cell carcinoma (LUSC).

Methods: TMB and immune microenvironment characteristics were comprehensively analyzed by multi-omics data in LUSC. The immune signature was further constructed and validated in multiple independent datasets by LASSO Cox regression analysis. Next, the value of immune signature in predicting the response of immunotherapy was evaluated. Finally, the possible mechanism of immune signature was also investigated.

Results: A novel immune signature based on 5 genes was constructed and validated to predict the prognosis of LUSC patients. These genes were filamin-C, Rho family GTPase 1, interleukin 4-induced gene-1, transglutaminase 2, and prostaglandin I2 synthase. High-risk patients had significantly poorer survival than low-risk patients. A nomogram was also developed based on the immune signature and tumor stage, which showed good application. Furthermore, we found that the immune signature had a significant correlation with immune checkpoint, microsatellite instability, tumor infiltrating lymphocytes, cytotoxic activity scores, and T-cell-inflamed score, suggesting low-risk patients are more likely to benefit from immunotherapy. Finally, functional enrichment and pathway analyses revealed several significantly enriched immune-related biological processes and metabolic pathways.

Conclusions: In the present study, we developed a novel immune signature that could predict prognosis and immunotherapeutic response in LUSC patients. The results not only help identify LUSC patients with poor survival, but also increase our understanding of the immune microenvironment and immunotherapy in LUSC.
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http://dx.doi.org/10.21037/atm-21-463DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8105790PMC
April 2021

Medioresinol as a novel PGC-1α activator prevents pyroptosis of endothelial cells in ischemic stroke through PPARα-GOT1 axis.

Pharmacol Res 2021 Jul 27;169:105640. Epub 2021 Apr 27.

State Key Laboratory of Natural Medicines, Jiangsu Key Laboratory of Drug Discovery for Metabolic Diseases, Jiangsu Key Laboratory of Druggability of Biopharmaceuticals, New drug screening center, Jiangsu Center for Pharmacodynamics Research and Evaluation, Institute of Pharmaceutical Sciences, China Pharmaceutical University, Nanjing 210009, PR China; Key Laboratory of Drug Quality Control and Pharmacovigilance (China Pharmaceutical University), Ministry of Education, Nanjing 210009, PR China. Electronic address:

Aim: Brain microvascular endothelial cells (BMVECs), as the important structure of blood-brain barrier (BBB), play a vital role in ischemic stroke. Pyroptosis of different cells in the brain may aggravate cerebral ischemic injury, and PGC-1α plays a major role in pyroptosis. However, it is not known whether BMVECs undergo pyroptosis after ischemic stroke and whether PGC-1α activator Medioresinol (MDN) we discovered may be useful against pyroptosis of endothelial cells and ischemic brain injury.

Methods: For in vitro experiments, the bEnd.3 cells and BMVECs under oxygen and glucose-deprivation (OGD) were treated with or without MDN, and the LDH release, tight junction protein degradation, GSDMD-NT membrane location and pyroptosis-associated proteins were evaluated. For in vivo experiments, mice underwent transient middle cerebral artery occlusion (tMCAO) for ischemia model, and the neuroprotective effects of MDN were measured by infarct volume, the permeability of BBB and pyroptosis of BMVECs. For mechanistic study, effects of MDN on the accumulation of phenylalanine, mitochondrial reactive oxygen species (mtROS) were tested by untargeted metabolomics and MitoSOX Red probe, respectively.

Results: BMVECs underwent pyroptosis after ischemia. MDN dose-dependently activated PGC-1α, significantly reduced pyroptosis, mtROS and the expressions of pyroptosis-associated proteins (NLRP3, ASC, cleaved caspase-1, IL-1β, GSDMD-NT), and increased ZO-1 and Occludin protein expressions in BMVECs. In tMCAO mice, MDN remarkably reduced brain infarct volume and the permeability of BBB, inhibited pyroptosis of BMVECs, and promoted long-term neurobehavioral functional recovery. Mechanistically, MDN promoted the interaction of PGC-1α with PPARα to increase PPARα nuclear translocation and transcription activity, further increased the expression of GOT1 and PAH, resulting in enhanced phenylalanine metabolism to reduce the ischemia-caused phenylalanine accumulation and mtROS and further ameliorate pyroptosis of BMVECs.

Conclusion: In this study, we for the first time discovered that pyroptosis of BMVECs was involved in the pathogenesis of ischemic stroke and MDN as a novel PGC-1α activator could ameliorate the pyroptosis of endothelial cells and ischemic brain injury, which might attribute to reduction of mtROS through PPARα/GOT1 axis in BMVECs. Taken together, targeting endothelial pyroptosis by MDN may provide alternative therapeutics for brain ischemic stroke.
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http://dx.doi.org/10.1016/j.phrs.2021.105640DOI Listing
July 2021

Exposure to oxidized soybean oil induces mammary mitochondrial injury in lactating rats and alters the intestinal barrier function of progeny.

Food Funct 2021 Apr;12(8):3705-3719

Department of Food Science, Northeast Agricultural University, Harbin 150030, P. R. China.

Similar to other food contaminants, dietary oxidized soybean oil (OSO) is also a toxic xenobiotic for animal and human nutrition. This research evaluated the effects of maternal OSO exposure during lactation on mammary mitochondrial injury and intestinal barrier of sucking progeny. Twenty-four female adult SD rats were fed a fresh soybean oil (FSO) homozygous diet (7%) or an OSO homozygous diet (7%) during lactation. On day 21 of lactation, upregulated mRNA expression of Sirt3 and PRDX3 and downregulated mRNA expression of Mfn2 were observed in mammary tissues in the OSO group compared to the control group (P < 0.05). Maternal OSO consumption increased the FasL transcriptional level in the mammary glands of rat dams (P < 0.05), while the mRNA expression of Bax, Bcl-2, Caspase3, and Fas was not different from that in the control group (P > 0.05). OSO enhanced the Nrf2 transcriptional level and decreased the expression of Keap1 and PPARα in mammary tissues (P < 0.05). In addition, the contents of CAT, MDA, SOD were not affected by dietary OSO (P > 0.05), while the concentration of H2O2 was significantly decreased in the OSO-treated mammary glands of rat dams (P < 0.05). Maternal OSO exposure during lactation did not affect the organ coefficients of pups (P > 0.05). However, maternal OSO consumption influenced the intestinal tight junction protein expression of progeny (P < 0.05). In summary, the present study demonstrated that dietary OSO may aggravate mammary injury and mitochondria dysfunction, but the OSO-induced damage was self-alleviating via the promotion of Sirt3 and PRDX3 expression and further scavenging of oxidative products.
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http://dx.doi.org/10.1039/d1fo00423aDOI Listing
April 2021

Epigenome-wide DNA methylation signature of benzo[a]pyrene exposure and their mediation roles in benzo[a]pyrene-associated lung cancer development.

J Hazard Mater 2021 Apr 8;416:125839. Epub 2021 Apr 8.

Department of Occupational and Environmental Health, State Key Laboratory of Environmental Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China. Electronic address:

Benzo[a]pyrene (B[a]P) is a typical carcinogen associated with increased lung cancer risk, but the underlying mechanisms remain unclear. This study aimed to investigate epigenome-wide DNA methylation associated with B[a]P exposure and their mediation effects on B[a]P-lung cancer association in two lung cancer case-control studies of 462 subjects. Their plasma levels of benzo[a]pyrene diol epoxide-albumin (BPDE-Alb) adducts and genome-wide DNA methylations were separately detected in peripheral blood by using enzyme-linked immunosorbent assay (ELISA) and genome-wide methylation arrays. The epigenome-wide meta-analysis was performed to analyze the associations between BPDE-Alb adducts and DNA methylations. Mediation analysis was applied to assess effect of DNA methylation on the B[a]P-lung cancer association. We identified 15 CpGs associated with BPDE-Alb adducts (P < 1.0 × 10), among which the methylation levels at five loci (cg06245338, cg24256211, cg15107887, cg02211741, and cg04354393 annotated to UBE2O, SAMD4A, ACBD6, DGKZ, and SLFN13, respectively) mediated a separate 38.5%, 29.2%, 41.5%, 47.7%, 56.5%, and a joint 58.2% of the association between BPDE-Alb adducts and lung cancer risk. Compared to the traditional factors [area under the curve (AUC) = 0.788], addition of these CpGs exerted improved discriminations for lung cancer, with AUC ranging 0.828-0.861. Our results highlight DNA methylation alterations as potential mediators in lung tumorigenesis induced by B[a]P exposure.
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http://dx.doi.org/10.1016/j.jhazmat.2021.125839DOI Listing
April 2021

Distinguishing Rectal Cancer from Colon Cancer Based on the Support Vector Machine Method and RNA-sequencing Data.

Curr Med Sci 2021 Apr 20;41(2):368-374. Epub 2021 Apr 20.

Jiangsu Cancer Hospital, Jiangsu Institute of Cancer Research, The Affiliated Cancer Hospital of Nanjing Medical University, Nanjing, 210009, China.

Colorectal cancer (CRC) is the third most commonly diagnosed cancer worldwide. Several studies have indicated that rectal cancer is significantly different from colon cancer in terms of treatment, prognosis, and metastasis. Recently, the differential mRNA expression of colon cancer and rectal cancer has received a great deal of attention. The current study aimed to identify significant differences between colon cancer and rectal cancer based on RNA sequencing (RNA-seq) data via support vector machines (SVM). Here, 393 CRC samples from the The Cancer Genome Atlas (TCGA) database were investigated, including 298 patients with colon cancer and 95 with rectal cancer. Following the random forest (RF) analysis of the mRNA expression data, 96 genes such as HOXB13, PRAC, and BCLAF1 were identified and utilized to build the SVM classification model with the Leave-One-Out Cross-validation (LOOCV) algorithm. In the training (n=196) and the validation cohorts (n=197), the accuracy (82.1 % and 82.2 %, respectively) and the AUC (0.87 and 0.91, respectively) indicated that the established optimal SVM classification model distinguished colon cancer from rectal cancer reasonably. However, additional experiments are required to validate the predicted gene expression levels and functions.
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http://dx.doi.org/10.1007/s11596-021-2356-8DOI Listing
April 2021

EZH2-Mediated microRNA-375 Upregulation Promotes Progression of Breast Cancer the Inhibition of FOXO1 and the p53 Signaling Pathway.

Front Genet 2021 29;12:633756. Epub 2021 Mar 29.

Department of Breast Surgery, The First Hospital of Jilin University, Changchun, China.

Breast cancer (BC) is the most common gynecologic tumor worldwide where aberrant expression of microRNAs (miRNAs) is frequently involved. Here, we evaluated the function of miR-375 on BC development and the molecules implicated. Differentially expressed genes between tumor and paired normal tissues from BC patients were screened out by microarray analyses. miR-375 was abundantly expressed in BC tissues and cells, and it was correlated with the poor prognosis of patients. Downregulation of miR-375 was introduced into BC cell lines MCF-7 and HCC1954, after which the viability, colony formation, migration, and invasion were suppressed, while the apoptosis of cells was increased, and the xenograft tumors in nude mice were reduced as well. EZH2 increased methylation and phosphorylation of signal transducer and activator of transcription 3 (STAT3) and increased transcription activity of miR-375, while miR-375 directly targeted FOXO1. Either overexpression of EZH2 or downregulation of FOXO1 blocked the functions of anti-miR-375 in cells and animals. FOXO1 was found as an activator of the p53 signaling pathway. This study showed that miR-375 is an important oncogene in BC. EZH2 is an upstream regulator of miR-375 through mediating the methylation of STAT3, while FOXO1 is a downstream target mRNA of miR-375 that activates the p53 signaling pathway to suppress BC development.
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http://dx.doi.org/10.3389/fgene.2021.633756DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8041054PMC
March 2021

Clinicopathologic features and treatment of thymic lymphoepithelioma-like carcinoma: two case reports and literature review.

Am J Transl Res 2021 15;13(3):1896-1903. Epub 2021 Mar 15.

Department of Pathology, The First Affiliated Hospital and College of Basic Medical Sciences, China Medical University No. 155 Nanjing North Street, Heping District, Shenyang 110001, Liaoning, China.

Lymphoepithelioma-like carcinoma (LELC) is rare in the thymus, and easily misdiagnosed. To improve its clinicopathologic knowledge, we describe two cases of thymic LELC, and investigate their microscopic and immunohistochemical features, treatment, and follow-up with a review of previously published cases. Two patients in the First Affiliated Hospital of China Medical University underwent complete surgical resection for thymic LELC. They were treated with chemotherapy or radiotherapy after operation. Histologically, tumor cells exhibited nest patterns or showed stripe-shaped infiltration in fibrous tissue containing lymphocytes. Tumor was diffusely positive for pan-cytokeratin (CK), CK19, cluster of differentiation 5 (CD5), CD117, epithelial membrane antigen (EMA), and p63, and negative for TdT. Recent follow-up showed that the two patients were alive with no signs of recurrence. We report two cases of thymic LELC with a review of previously published cases to summarize knowledge of their clinicopathological characteristics, which is necessary for accurate diagnosis and clinical treatment.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8014405PMC
March 2021

Inflammatory Markers Predict Survival in Patients With Advanced Gastric and Colorectal Cancers Receiving Anti-PD-1 Therapy.

Front Cell Dev Biol 2021 15;9:638312. Epub 2021 Mar 15.

Department of Gastrointestinal Medical Oncology, Harbin Medical University Cancer Hospital, Harbin, China.

There is a lack of useful biomarkers for predicting the efficacy of anti-programmed death-1 (PD-1) therapy for advanced gastric and colorectal cancer. To address this issue, in this study we investigated the correlation between inflammatory marker expression and survival in patients with advanced gastric and colorectal cancer. Data for 111 patients with advanced gastric and colorectal cancer treated with anti-PD-1 regimens were retrospectively analyzed. Neutrophil-to-lymphocyte ratio (NLR), monocyte-to-lymphocyte ratio (MLR), platelet-to-lymphocyte ratio (PLR), and clinical characteristics of each patient were selected as the main variables. Overall response rate, disease control rate, and progression-free survival were primary endpoints, and overall survival and immune-related adverse events (irAEs) were secondary endpoints. The chi-squared test and Fisher's exact test were used to evaluate relationships between categorical variables. Uni- and multivariate Cox regression analyses were performed, and median progression-free survival and overall survival were estimated with the Kaplan-Meier method. The overall response rate and disease control rate of anti-PD-1therapy in advanced gastric and colorectal tumors were 12.61 and 66.66%, respectively. The patients with MLR < 0.31, NLR < 5, and PLR < 135 had a significantly higher disease control rate than those with MLR > 0.31, NLR > 5, and PLR > 135 ( < 0.05). The multivariate analysis revealed that MLR < 0.31, BMI > 18.5, and anti-PD-1 therapy in first-line were associated with prolonged PFS. MLR < 0.31 and BMI > 18.5 were associated with prolonged overall survival. The irAE rate differed significantly between PLR groups, and PLR < 135 was associated with an increased rate of irAEs ( = 0.028). These results indicate that the inflammatory markers NLR, MLR, and PLR have clinical utility for predicting survival or risk of irAEs in patients with advanced gastric cancer and colorectal cancer.
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http://dx.doi.org/10.3389/fcell.2021.638312DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8005614PMC
March 2021

[Electroacupuncture in the prevention and treatment of sore throat and nausea and vomiting after gastrointestinal surgery: a randomized controlled trial].

Zhen Ci Yan Jiu 2021 Feb;46(2):164-7

Department of Anesthesiology, Guang'anmen Hospital of China Academy of Chinese Medical Sciences, Beijing 100053, China.

Objective: To observe the effect of electroacupuncture (EA) intervention on postoperative sore throat (POST) and postoperative nausea and vomiting (PONV) after endotracheal intubation and general anesthesia.

Methods: According to the random number table, 60 patients of gastrointestinal surgery under general anesthesia with tracheal intubation were randomly divided into EA group (30 cases) and control group (30 cases). Patients in the EA group were given acupuncture at Shaoshang (LU11) 30 minutes before general anesthesia, and EA at Chize (LU5) and Hegu (LI4) continued until the operation was completed. The incidence and severity of POST and visual analogue scale (VAS) score at 12, 24, and 48 h after surgery, and the incidence and severity of PONV at 12, 24 h after surgery were analyzed, respectively.

Results: The incidence and severity of POST and PONV, and VAS score in the EA group were significantly lower than those in the control group 12 h and 24 h after surgery (P<0.05). Both groups had significant reductions in VAS score at 24 h and 48 h after surgery compared with that at 12 h (P<0.05).

Conclusion: EA can significantly improve the prognosis of patients on sore throat and reduce the incidence of PONV.
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http://dx.doi.org/10.13702/j.1000-0607.200464DOI Listing
February 2021

PGC-1α-siRNA suppresses inflammation in substantia nigra of PD mice by inhibiting microglia.

Int J Neurosci 2021 Jun 1:1-9. Epub 2021 Jun 1.

Department of Physiology, College of Life Sciences, Hebei Normal University, Shijiazhuang, Hebei, PR China.

Parkinson's disease is a common degenerative disease of the central nervous system with complex pathogenesis. More and more studies have found that inflammatory response promotes the occurrence and development of the disease, in which the activation of microglia plays an important role. PGC-1α (peroxisome proliferator activated receptor-γ coactivator-1α) is the main factor in mitochondrial biogenetic, and is closely related to the inflammatory response. Our immunofluorescence test results showed that PGC-1α and microglia (Iba1) have double-labeled phenomenon. The expression of microglia in the MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine) group increased, and PGC-1α/Iba1 double label increased. To test whether lowering the expression of PGC-1α can reduce the activation of microglia and protect the substantia nigra dopaminergic neurons, we constructed PGC-1α interference lentivirus. Immunofluorescence, western blot, and ELISA were used to detect microglial phenotype. The results showed that PGC-1α interfering with lentivirus can transfect microglial cells in substantia nigra, and the PGC-1α protein level decreased in substantia nigra accordingly; TH protein expression had no statistical difference compared with MPTP group; PGC-1α interfering lentivirus reduced microglia number and activation, and at the same time the expression of iNOS and Arg1 significantly reduced compared with MPTP group. The IL-6 expression in blood detected using ELISA was significantly reduced compared with MPTP group. PGC-1α downregulation inhibited microglia activity, and both M1 and M2 microglial activities are reduced.
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http://dx.doi.org/10.1080/00207454.2021.1910257DOI Listing
June 2021

YAF2 exerts anti-apoptotic effect in human tumor cells in a FANK1- and phosphorylation-dependent manner.

Biochem Biophys Res Commun 2021 05 27;554:99-106. Epub 2021 Mar 27.

Department of Biochemistry and Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences and School of Basic Medicine, Peking Union Medical College, Beijing, 100005, China. Electronic address:

YY1-associated factor 2 (YAF2) was frequently reported to modulate target gene transcription through both epigenetic and non-epigenetic means. However, other mechanisms were also utilized by YAF2 to carry out its biological functions. Here, we demonstrated that YAF2 from human tumor and non-tumor cells were mainly expressed as Serine 167 phosphorylated form. Further studies showed that the phosphorylated YAF2 up-regulated while its knockdown by specific siRNAs reduced fibronectin type III and ankyrin repeat domains 1 (FANK1) protein level. Mechanistic exploration disclosed that phosphorylated YAF2 inhibit proteasomal degradation of polyubiquitinated FANK1, leading to its increased stability. We then validated their interaction, and displayed that the FN3 domain of FANK1 binds to amino-terminal of YAF2. Functional studies showed that phosphorylated YAF2 inhibits tumor cell apoptosis in a FANK1-dependent manner. Taken together, our current findings demonstrated that phosphorylated YAF2 exhibits anti-apoptotic activity through targeting FANK1 expression in human tumor cells.
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http://dx.doi.org/10.1016/j.bbrc.2021.03.105DOI Listing
May 2021

A novel SIRT6 activator ameliorates neuroinflammation and ischemic brain injury EZH2/FOXC1 axis.

Acta Pharm Sin B 2021 Mar 7;11(3):708-726. Epub 2020 Nov 7.

State Key Laboratory of Natural Medicines, Jiangsu Key Laboratory of Drug Screening, Jiangsu Key Laboratory of Drug Discovery for Metabolic Diseases, China Pharmaceutical University, Nanjing 210009, China.

Ischemic stroke is the second leading cause of death worldwide with limited medications and neuroinflammation was recognized as a critical player in the progression of stroke, but how to control the overactive neuroinflammation is still a long-standing challenge. Here, we designed a novel SIRT6 activator MDL-811 which remarkably inhibited inflammatory response in lipopolysaccharide (LPS)-stimulated RAW264.7 macrophages and primary mouse microglia, which were abolished by silencing SIRT6. RNA-seq screening identified the forkhead box C1 () is a key gene evoked by MDL-811 stimulation and is required for the anti-inflammatory effects of MDL-811. We found MDL-811-activated SIRT6 directly interacted with enhancer of zeste homolog 2 (EZH2) and promoted deacetylation of EZH2 which could bind to the promoter of and upregulate its expression to modulate inflammation. Moreover, our data demonstrated that MDL-811 not only ameliorated sickness behaviors in neuroinflammatory mice induced by LPS, but also markedly reduced the brain injury in ischemic stroke mice in addition to promoting long-term functional recovery. Importantly, MDL-811 also exhibited strong anti-inflammatory effects in human monocytes isolated from ischemic stroke patients, underlying an interesting translational perspective. Taken together, MDL-811 could be an alternative therapeutic candidate for ischemic stroke and other brain disorders associated with neuroinflammation.
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http://dx.doi.org/10.1016/j.apsb.2020.11.002DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7982432PMC
March 2021

Metformin improves survival in patients with concurrent diabetes and small cell lung cancer: a meta-analysis.

Minerva Endocrinol (Torino) 2021 Mar 16. Epub 2021 Mar 16.

Department of Oncology and Hematology, People's Hospital of Leshan,Leshan City, P.R China -

Objective: To compare survival outcome among the patients with concurrent small cell lung cancer (SCLC) and diabetes mellitus (DM) using metformin or without metformin.

Methods: A systematic literature search for relevant studies up to Oct 2020 was conducted. Outcome of the included studies included overall survival (OS) or disease-free survival (DFS). HR values were pooled to estimate the effect of metformin on survival outcomes.

Results: 6 studies with 539 participants with both SCLC and diabetes were included in the analysis. The patients with metformin usage had significantly longer OS and DFS than those without metformin usage [OS: HR=0.72 (0.53-0.98), p=0.04; DFS: HR= 0.59 (0.45-0.76), p<0.0001)]. The studies included were not significantly different in the two analyses by heterogeneity test. There was no obvious publication bias.

Conclusions: Metformin may improve survival among patients with concurrent SCLC and DM. Further investigations especially randomized control trials are warranted, especially among the patients who do not have diabetes.
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http://dx.doi.org/10.23736/S2724-6507.21.03289-2DOI Listing
March 2021

A new classification of descending necrotizing mediastinitis and surgical strategies.

Ann Transl Med 2021 Feb;9(4):356

Department of Oral Surgery, Shanghai Ninth People's Hospital, College of Clinical Medicine, Shanghai Jiao Tong University School of Medicine, Shanghai, China.

Background: Descending necrotizing mediastinitis (DNM) is an inflammation occurring in the oropharynx and descending to the deep cervical space and mediastinum, which is a serious infectious disease. The investigation of a new classification system and treatment methods for DNM is still necessary.

Methods: A total of 139 patients with DNM caused by odontogenic or pharyngeal infection were retrospectively analyzed in last 20 years in the Ninth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine. The patients were divided into the traditional treatment Group T (Group T: 43 patients) and the new classification Group N (Group N: 96 patients). A new DNM classification was developed based on the progression of mediastinal infection as follows: type Ia: infection in the anterosuperior mediastinum; type I: infection in the anterior mediastinum; type II: infection in the posterior mediastinum; and type III: infection of the whole mediastinum.

Results: There were 49, 8, 10, and 29 patients classified as type Ia, I, II, and III, respectively in the Group N. The type Ia DNM patients were managed with transcervical mediastinal drainage, and the patients with types I and II DNM underwent open (thoracoscopic) surgery, 1 patient within types I died. The 29 patients with type III were managed with unilateral or bilateral open (thoracoscopic) surgery, among them, 8 patients died. The mortality rate for patients with type III DNM was 27.6%. The overall mortality rate in Group N was 9.4%. The mortality rate for patients in the Group T was 25.6%. The mortality rate of Group N was significantly lower than that of Group T (P<0.05).

Conclusions: We have carried out a new clinical classification of DNM, and selected the appropriate treatment method according to the classification, and achieved a better effect than the traditional treatment method.
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http://dx.doi.org/10.21037/atm-21-121DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7944333PMC
February 2021

Effects of polycyclic aromatic hydrocarbons and multiple metals co-exposure on the mosaic loss of chromosome Y in peripheral blood.

J Hazard Mater 2021 07 24;414:125519. Epub 2021 Feb 24.

Department of Occupational and Environmental Health, State Key Laboratory of Environmental Health (Incubating), School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China. Electronic address:

Mosaic loss of chromosome Y (mLOY) is an indicator of genome instability, but the environmental stressors of mLOY remained largely unknown. In this study, we detected the internal exposure levels of 11 polycyclic aromatic hydrocarbon (PAH) metabolites and 22 metals among 888 coke-oven workers, and calculated their blood mLOY based on genome-wide SNP genotyping data and presented as median log R ratio (mLRR-Y). The generalized linear model (GLM), LASSO, and Bayesian kernel machine regression (BKMR), were used to select mLOY-relevant chemicals. The results of these models consistently suggested the negative dose-response relationships of urinary 1-hydroxynaphthalene (1-OHNa), antimony (Sb), and molybdenum (Mo) with mLRR-Y. There were no pairwise interactions between these three chemicals (P > 0.05), but subjects with high exposure to ≥ 2 kinds of these chemicals showed reducing mLRR-Y [β(95%CI) = - 0.015(- 0.023, - 0.008)], increasing oxidative DNA damage (marked by 8-hydroxydeoxyguanosine) [β(95%CI) = 0.625(0.454, 0.796)] and chromosome damage (marked by micronucleus frequency in lymphocytes) [frequency ratio (FR) and 95%CI = 1.146(1.047, 1.225)] than those with low exposure to all these chemicals. The combined effects of 1-OHNa, Sb, and Mo on elevating DNA damage may partly explain their joint effects on increased blood mLOY. These results provided a new insight into environmental hazards co-exposure on chromosome-Y deletions.
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http://dx.doi.org/10.1016/j.jhazmat.2021.125519DOI Listing
July 2021

Chloroplast phylogenomic analysis provides insights into the evolution of sp. nov.

Mitochondrial DNA B Resour 2021 Feb 8;6(2):346-348. Epub 2021 Feb 8.

College of Pharmaceutical Science, Dali University, Dali, PR China.

sp. nov is a species of flowering herb of the genus and widely distributed in the southwest of China. In this study, we sequenced the complete chloroplast (cp) genome of sp. nov to investigate its phylogenetic relationship in genus . The cp genome of sp. nov was 163,860 bp in length, containing a large single-copy (LSC) region of 84,415 bp, a small single-copy (SSC) region of 12,947 bp, and a pair of inverted repeats (IRs) region of 33,249 bp. The overall GC content was 37.0%. The genome comprises of 135 genes, including 91 protein-coding genes, 37 tRNA genes, and 4 rRNA genes. Phylogenetic relationship analysis based on complete cp genome sequences exhibited that sp. nov was most related to var. .
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http://dx.doi.org/10.1080/23802359.2020.1867016DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7872569PMC
February 2021

Restoration of NRF2 attenuates myocardial ischemia reperfusion injury through mediating microRNA-29a-3p/CCNT2 axis.

Biofactors 2021 May 18;47(3):414-426. Epub 2021 Feb 18.

Department of Cardiology, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, China.

Accumulated studies have been implemented for comprehending the mechanism of myocardial ischemia reperfusion injury (MI/RI). Nuclear factor erythroid-2 related factor 2 (NRF2)-mediated transcription activity in MI/RI has not been completely interpreted from the perspective of microRNA-29a-3p (miR-29a-3p) and cyclin T2 (CCNT2). Therein, this study intends to decode the mechanism of NRF2/miR-29a-3p/CCNT2 axis in MI/RI. Rat MI/RI models were established by left anterior descending artery ligation. Rats were injected with NRF2 or CCNT2 overexpression plasmids or miR-29a-3p agomir to explore their effects on MI/RI. Hypoxia/reoxygenation (H/R) cardiomyocytes were established and transfected with restored NRF2 or miR-29a-3p or CCNT2 for further exploration of their roles. NRF2, miR-29a-3p, and CCNT2 expression in myocardial tissues in rats with MI/RI and in cardiomyocytes in H/R injury were detected. ChIP assay verified the relationship between miR-29a-3p and NRF2, and the bioinformatics software and dual-luciferase reporter experiment verified the interaction between miR-29a-3p and CCNT2. NRF2 and miR-29a-3p were down-regulated while CCNT2 was up-regulated in myocardial tissues in rats with MI/RI and in H/R-treated cardiomyocytes. Restoration of NRF2 or miR-29a-3p improved hemodynamics and myocardial injury and suppressed serum inflammation and cardiomyocyte apoptosis via CCNT2 in rats with MI/RI. Upregulation of NRF2 or miR-29a-3p inhibited LDH and CK-MB activities, oxidative stress, and apoptosis and promoted viability of cardiomyocytes with H/R injury. NRF2 bound to the promoter of miR-29a-3p and CCNT2 was targeted by miR-29a-3p. This study elucidates that up-regulating NRF2 or miR-29a-3p attenuates MI/RI via inhibiting CCNT2, which may renew the existed knowledge of MI/RI-related mechanism and provide a novel guidance toward MI/RI treatment.
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http://dx.doi.org/10.1002/biof.1712DOI Listing
May 2021

pH-Sensitive W/O Pickering High Internal Phase Emulsions and W/O/W High Internal Water-Phase Double Emulsions with Tailored Microstructures Costabilized by Lecithin and Silica Inorganic Particles.

Authors:
Xin Guan To Ngai

Langmuir 2021 Mar 17;37(8):2843-2854. Epub 2021 Feb 17.

Department of Chemistry, The Chinese University of Hong Kong, Shatin, N.T., Hong Kong, China.

Synergistic stabilization of Pickering emulsions by a mixture of surfactants and colloidal particles has received increasing interest in recent years but only a few of them can produce high internal phase double emulsions (HIPDEs) with good stability. In this study, we present a feasible and common method of preparing Pickering high internal phase emulsions (HIPEs) with tunable inner morphology costabilized by a biosurfactant lecithin and silica nanoparticles. We investigate the influence of the pH value on the interfacial behavior of lecithin and elucidate the synergistic mechanism between lecithin and silica nanoparticles in different conditions in the stability of as-prepared emulsions. Specifically, water-in-oil (W/O) Pickering HIPEs can be successfully stabilized by lecithin and hydrophobic silica nanoparticles in a wide pH range (pH 1-10), while catastrophic phase inversion occurred at high pH values (pH ≥ 11). Interestingly, stable water-in-oil-in-water (W/O/W) high internal phase double emulsions (HIPDEs) can also be prepared via a two-step method by the cooperation of lecithin and silica nanoparticles. Moreover, functional interconnected porous monoliths and microspheres are facilely fabricated by emulsion templates and their potential applications are explored.
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http://dx.doi.org/10.1021/acs.langmuir.0c03658DOI Listing
March 2021

Cost-effectiveness analysis of fruquintinib versus regorafenib as the third-line therapy for metastatic colorectal cancer in China.

J Med Econ 2021 Jan-Dec;24(1):339-344

School of International Pharmaceutical Business, China Pharmaceutical University, Nanjing, China.

Objectives: The aim of this study is to assess the cost-effectiveness of fruquintinib compared to regorafenib as third-line treatment for patients with metastatic colorectal cancer (mCRC) in China.

Methods: A three-state Markov model with monthly cycle was constructed to estimate lifetime incremental cost-effectiveness ratio (ICER) of fruquintinib versus regorafenib as third-line treatment for patients with mCRC from Chinese health care perspective. Survival analysis was applied to calculate transition probabilities using the data from the clinical trials FRESCO and CONCUR, which were also the data sources accessing probabilities of adverse events. Background mortality rate and drug costs were derived from government published data. Costs for medical services were obtained from real-world data and published literatures. Utilities applied to calculate the quality-adjusted life years (QALYs) were obtained from literature review. One-way sensitivity analysis and probabilistic sensitivity analysis were adopted to verify the robustness of the results.

Results: Fruquintinib provided 0.74 QALYs at a cost of CNY 151,058 (USD 22,888), whereas regorafenib provided 0.79 QALYs at a cost of CNY 226,657 (USD 32,224). Compared to fruquintinib, the ICER of regorafenib was CNY 1,529,197/QALY (USD 231,697/QALY) from Chinese health care perspective, which was above the triple GDP per capita of China in 2019 (CNY 212,676) (USD 32,224) as the threshold to define the cost-effectiveness. One-way sensitivity analysis showed the results were generally robust. Cost-effectiveness acceptability curves derived from probabilistic sensitivity analysis demonstrated the probability that fruquintinib was more cost-effective was 100% when the threshold was the triple GDP per capita of China.

Conclusions: Compared to regorafenib, fruquintinib, which leads to forego about 0.05 QALYs and save about CNY 75,599 (USD 11,454), is a cost-effective choice as the third-line treatment for patients with mCRC in China.
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http://dx.doi.org/10.1080/13696998.2021.1888743DOI Listing
March 2021

Copper-Containing Alloy as Immunoregulatory Material in Bone Regeneration via Mitochondrial Oxidative Stress.

Front Bioeng Biotechnol 2020 14;8:620629. Epub 2021 Jan 14.

Division of Orthopedic Surgery, Department of Orthopedics, Nanfang Hospital, Southern Medical University, Guangzhou, China.

In the mammalian skeletal system, osteogenesis and angiogenesis are closely linked by type H vessels during bone regeneration and repair. Our previous studies confirmed the promotion of these processes by copper-containing metal (CCM) and . However, whether and how the coupling of angiogenesis and osteogenesis participates in the promotion of bone regeneration by CCM is unknown. In this study, M2a macrophages but not M2c macrophages were shown to be immunoregulated by CCM. A CCM, 316L-5Cu, was applied to drilling hole injuries of the tibia of C57/6 mice for comparison. We observed advanced formation of cortical bone and type H vessels beneath the new bone in the 316L-5Cu group 14 and 21 days postinjury. Moreover, the recruitment of CD206-positive M2a macrophages, which are regarded as the primary source of platelet-derived growth factor type BB (PDGF-BB), was significantly promoted at the injury site at days 14 and 21. Under the stimulation of CCM, mitochondria-derived reactive oxygen species were also found to be upregulated in CD206 M2a macrophages , and this upregulation was correlated with the expression of PDGF-BB. In conclusion, our results indicate that CCM promotes the evolution of callus through the generation of type H vessels during the process of bone repair by upregulating the expression of PDGF-BB derived from M2a macrophages.
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http://dx.doi.org/10.3389/fbioe.2020.620629DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7869892PMC
January 2021

Dynamic modulation of gut microbiota improves post-myocardial infarct tissue repair in rats via butyric acid-mediated histone deacetylase inhibition.

FASEB J 2021 Mar;35(3):e21385

Department of Pharmacology, College of Basic Medical Sciences, Jilin University, Changchun, China.

The complex and dynamic population of gut microbiota exerts a marked influence on the host during homeostasis and disease. Imbalance of gut microbiota metabolites may lead to cardiac dysfunction in patients with heart failure, which is related to myocardial infarction(MI) severity. However, the role of gut microbiota in the repair process after MI has rarely been reported. To explore the role of gut microbiota in MI repair and its underlying mechanism, we mixed antibiotics in drinking water to interfere with gut microbiota in rats. Hematoxylin and eosin staining, Sirius red staining, western blotting, and immunohistochemistry were used to detect tissue repair and fibrosis. We found that the expressions of alpha-smooth muscle actin, collagen, and histone deacetylase (HDAC) activities were significantly increased. We detected gut microbiota at different time points after MI using 16S ribosomal RNA sequencing and detected that Prevotellaceae, Clostridiaceae, and Lachnospiraceae were significantly altered among the butyric acid producers. We administered sodium butyrate via drinking water and discovered that sodium butyrate reduced HDAC activities and adverse repair. Therefore, we speculated that gut microbiota influences the acetylation level and tissue repair process after MI by affecting butyric acid production.
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http://dx.doi.org/10.1096/fj.201903129RRRDOI Listing
March 2021

Transcriptome Analysis and Cell Morphology of Cells to Botryosphaeria Dieback Pathogen .

Genes (Basel) 2021 Jan 27;12(2). Epub 2021 Jan 27.

College of Horticulture and Landscape Architecture, Southwest University, Chongqing 400716, China.

, one of the major causal agents of Botryosphaeria dieback, spreads worldwide causing cankers, leaf spots and fruit black rot in grapevine. is an American wild grapevine widely used for resistance and rootstock breeding and was found to be highly resistant to Botryosphaeria dieback. The defence responses of to 98.1 were analysed by RNA-seq in this study. There were 1365 differentially expressed genes (DEGs) annotated with gene ontology (GO) and enriched by the Kyoto Encyclopedia of gene and genome (KEGG) database. The DEGs could be allocated to the flavonoid biosynthesis pathway and the plant-pathogen interaction pathway. Among them, 53 DEGs were transcription factors (TFs). The expression levels of 12 genes were further verified by real-time quantitative reverse transcription polymerase chain reaction (qRT-PCR). The aggregation of proteins on plasma membrane, formation variations in cytoskeleton and plasmodesmata, as well as hormone regulations revealed a declined physiological status in suspension cells after incubation with the culture filtrates of 98.1. This study provides insights into the molecular mechanisms in grapevine cells response to 98.1, which will be valuable for the control of Botryosphaeria dieback.
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http://dx.doi.org/10.3390/genes12020179DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7910889PMC
January 2021

Blocking IL-17A enhances tumor response to anti-PD-1 immunotherapy in microsatellite stable colorectal cancer.

J Immunother Cancer 2021 Jan;9(1)

Department of Gastrointestinal Medical Oncology, Harbin Medical University Cancer Hospital, Harbin, China

Background: Immune checkpoint inhibitors (ICIs), including anti-PD-1 therapy, have limited efficacy in patients with microsatellite stable (MSS) colorectal cancer (CRC). Interleukin 17A (IL-17A) activity leads to a protumor microenvironment, dependent on its ability to induce the production of inflammatory mediators, mobilize myeloid cells and reshape the tumor environment. In the present study, we aimed to investigate the role of IL-17A in resistance to antitumor immunity and to explore the feasibility of anti-IL-17A combined with anti-PD-1 therapy in MSS CRC murine models.

Methods: The expression of programmed cell death-ligand 1 (PD-L1) and its regulation by miR-15b-5p were investigated in MSS CRC cell lines and tissues. The effects of miR-15b-5p on tumorigenesis and anti-PD-1 treatment sensitivity were verified both in vitro and in colitis-associated cancer (CAC) and APC murine models. In vivo efficacy and mechanistic studies were conducted using antibodies targeting IL-17A and PD-1 in mice bearing subcutaneous CT26 and MC38 tumors.

Results: Evaluation of clinical pathological specimens confirmed that mRNA levels are associated with CD8+ T cell infiltration and better prognosis. miR-15b-5p was found to downregulate the expression of PD-L1 at the protein level, inhibit tumorigenesis and enhance anti-PD-1 sensitivity in CAC and APC CRC models. IL-17A led to high PD-L1 expression in CRC cells through regulating the P65/NRF1/miR-15b-5p axis. Combined IL-17A and PD-1 blockade had efficacy in CT26 and MC38 tumors, with more cytotoxic T lymphocytes cells and fewer myeloid-derived suppressor cells in tumors.

Conclusions: IL-17A increases PD-L1 expression through the p65/NRF1/miR-15b-5p axis and promotes resistance to anti-PD-1 therapy. Blocking IL-17A improved the efficacy of anti-PD-1 therapy in MSS CRC murine models. IL-17A might serve as a therapeutic target to sensitize patients with MSS CRC to ICI therapy.
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http://dx.doi.org/10.1136/jitc-2020-001895DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7813395PMC
January 2021

Clinical and inflammatory features based machine learning model for fatal risk prediction of hospitalized COVID-19 patients: results from a retrospective cohort study.

Ann Med 2021 12;53(1):257-266

Department of Laboratory Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

Objectives: To appraise effective predictors for COVID-19 mortality in a retrospective cohort study.

Methods: A total of 1270 COVID-19 patients, including 984 admitted in Sino French New City Branch (training and internal validation sets randomly split at 7:3 ratio) and 286 admitted in Optical Valley Branch (external validation set) of Wuhan Tongji hospital, were included in this study. Forty-eight clinical and laboratory features were screened with LASSO method. Further multi-tree extreme gradient boosting (XGBoost) machine learning-based model was used to rank importance of features selected from LASSO and subsequently constructed death risk prediction model with simple-tree XGBoost model. Performances of models were evaluated by AUC, prediction accuracy, precision, and F1 scores.

Results: Six features, including disease severity, age, levels of high-sensitivity C-reactive protein (hs-CRP), lactate dehydrogenase (LDH), ferritin, and interleukin-10 (IL-10), were selected as predictors for COVID-19 mortality. Simple-tree XGBoost model conducted by these features can predict death risk accurately with >90% precision and >85% sensitivity, as well as F1 scores >0.90 in training and validation sets.

Conclusion: We proposed the disease severity, age, serum levels of hs-CRP, LDH, ferritin, and IL-10 as significant predictors for death risk of COVID-19, which may help to identify the high-risk COVID-19 cases. KEY MESSAGES A machine learning method is used to build death risk model for COVID-19 patients. Disease severity, age, hs-CRP, LDH, ferritin, and IL-10 are death risk factors. These findings may help to identify the high-risk COVID-19 cases.
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http://dx.doi.org/10.1080/07853890.2020.1868564DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7799376PMC
December 2021

Kinesin Family Member C1 (KIFC1) Regulated by Centrosome Protein E (CENPE) Promotes Proliferation, Migration, and Epithelial-Mesenchymal Transition of Ovarian Cancer.

Med Sci Monit 2020 Dec 28;26:e927869. Epub 2020 Dec 28.

Department of Gynecology, The Third People's Hospital of Dalian, Dalian, Liaoning, China (mainland).

BACKGROUND Centrosome amplification is recognized as a hallmark of cancer. Kinesin family member C1 (KIFC1), a centrosome-clustering molecule, is essential for the viability of extra centrosome-bearing cancer cells and may be the basis for the progression of ovarian cancer. However, its biological function and mechanism in ovarian cancer have not yet been studied. MATERIAL AND METHODS Quantitative reverse-transcription polymerase chain reaction was performed to detect the levels of KIFC1 and centrosome protein E (CENPE). Further, cell viability was analyzed with CCK-8 assay, and immunofluorescence was used to measure the expression of Ki67 and PCNA. Cell migration was analyzed with wound healing and transwell assays. Western blot analysis was performed to measure the expression of proteins in ovarian cancer cells. The relationship between KIFC1 and CENPE was investigated by performing co-immunoprecipitation. RESULTS KIFC1 was upregulated in ovarian cancer cells, especially in SKOV3 cells. Additionally, we found that KIFC1 silencing in SKOV3 cells inhibited cell proliferation and downregulated the expression of Ki67 and PCNA. Further, the knockdown of KIFC1 suppressed cell migration and epithelial-mesenchymal transition (EMT) and regulated the expression of matrix metalloproteinase (MMP)2, MMP9, E-cadherin, N-cadherin, Snail, and ZEB1. Next, we found that KIFC1 bound to and positively regulated CENPE, a tumor promoter in certain human cancers. All the suppressive effects triggered by KIFC1 inhibition were reversed by CENPE overexpression. CONCLUSIONS KIFC1 contributed to cell proliferation, migration, and EMT via interacting with CENPE in ovarian cancer. KIFC1 might be a potential biomarker and therapeutic target in ovarian cancer patients.
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http://dx.doi.org/10.12659/MSM.927869DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7780892PMC
December 2020

Comparison of clinicopathological characteristics and prognosis among patients with pure invasive ductal carcinoma, invasive ductal carcinoma coexisted with invasive micropapillary carcinoma, and invasive ductal carcinoma coexisted with ductal carcinoma in situ: A retrospective cohort study.

Medicine (Baltimore) 2020 Dec;99(50):e23487

The Second Breast Surgery Department of Jilin Cancer Hospital.

This paper aimed to analyze the clinicopathological characteristics of invasive ductal carcinoma with an invasive micropapillary carcinoma component (IDC + IMPC), invasive ductal carcinoma with a ductal carcinoma in situ component (IDC + DCIS), and compare the clinicopathological characteristics and prognosis to those of IDC.A total of 1713 patients (130 IDC + IMPC cases, 352 IDC + DCIS cases, and 1231 pure IDC cases) who underwent appropriate surgery from June 2011 to September 2017 were retrospectively selected.Compared to the pure IDC and IDC + DCIS patients, the IDC + IMPC patients presented with more aggressive characteristics, such as a higher proportion of vascular invasion (P < .001), fewer progesterone receptor (PR)-positive patients (P < .001), a lower proportion of cases in American Joint Committee on Cancer stage I (P < .001), a higher recurrence risk (P < .001), more deaths (P < .001), and more metastatic cases (P < .001). Compared to the pure IDC and IDC + IMPC patients, the IDC+DCIS patients presented with less aggressive characteristics, such as a higher proportion of estrogen receptor-positive patients (P < .001) and PR-positive patients (P < .001), a lower proportion of cases with nerve invasion (P < .001) and vascular invasion (P < .001), a higher proportion of cases in American Joint Committee on Cancer stage I (P < .001), fewer deaths (P < .001), and fewer metastatic cases (P < .001). The patients with IDC + DCIS had significantly better disease-free survival (DFS) and overall survival (OS) compared to those with pure IDC and IDC + IMPC (P < .001). The patients with IDC + IMPC had significantly worse DFS and OS compared to those with pure IDC and IDC + DCIS (P < .001). In univariate analysis, the presence of an IMPC component in IDC (P = .007), estrogen receptor status (P = .05), and PR status (P = .003) were factors associated with OS. In multivariate analysis, coexisting IMPC (P = .04) was the only independent prognostic factor associated with OS.Compared to IDC and IDC + DCIS, IDC + IMPC had more aggressive characteristics and significantly worse DFS and OS. Compared to IDC and IDC + IMPC, IDC + DCIS had less aggressive characteristics and significantly better DFS and OS.
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http://dx.doi.org/10.1097/MD.0000000000023487DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7738125PMC
December 2020