Publications by authors named "Shan Zhang"

312 Publications

Source or sink? A study on the methane flux from mangroves stems in Zhangjiang estuary, southeast coast of China.

Sci Total Environ 2021 Sep 15;788:147782. Epub 2021 May 15.

Key Laboratory of the Ministry of Education for Coastal and Wetland Ecosystems, College of the Environment and Ecology, Xiamen University, Xiamen, Fujian 361102, PR China. Electronic address:

Mangrove ecosystems are an important component of "blue carbon". However, it is not clear whether the stems play roles in the CH budget of mangrove ecosystems. This study investigated the CH emission from mangrove stems and its potential driving factors. We set up six sample plots in the Zhangjiang Estuary National Mangrove Nature Reserve, where Kandelia obovata, Avicennia marina and Aegiceras corniculata are the main mangrove tree species. Soil properties such as total carbon content, redox potential and salinity were determined in each plot. The dynamic chamber method was used to measure mangrove stems and soil CH fluxes. Combined field survey results with Principal Component Analysis (PCA) of soil properties, we divided the six plots into two sites (S1 and S2) to perform statistical analyses of stem CH fluxes. Then the CH fluxes from mangrove tree stems and soil were further scaled up to the ecosystem level through the mapping model. Under different backgrounds of soil properties, salinity and microbial biomass carbon were the main factors modified soil CH fluxes in the two sites, and further affected the stem CH fluxes of mangroves. The soil of both sites are sources of CH, and the soil CH emission of S2 was about twice higher than that of S1. Results of upscaling model showed that mangrove stems in S1 were CH sinks with -105.65 g d. But stems in S2 were CH sources around 1448.24 g d. Taken together, our results suggested that CH emission from mangrove soils closely depends on soils properties. And mangrove stems were found to act as both CH sources and CH sinks depend on soil CH production. Therefore, when calculating the CH budget of the mangrove ecosystem, the contribution of mangrove plant stems cannot be ignored.
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http://dx.doi.org/10.1016/j.scitotenv.2021.147782DOI Listing
September 2021

Complete genome and molecular characterization of genotype VII velogenic Newcastle disease virus isolated in China.

Acta Virol 2021 ;65(2):149-159

Circulation of dominant genotype VII of Newcastle disease virus (NDV) causes significant economic losses to the poultry industry in China. Although most of genotype VII NDV has frequently been isolated in China to date, the genome sequence difference between duck-origin and chicken-origin NDVs remains largely unknown. In this study, a NDV strain of Chicken/China/HB/2017 (HB), isolated during an outbreak in China, was subjected to genetic, biological, phylogenetic and the pathogenicity characterization. The complete genome of HB strain is 15,192 nucleotides (nt) long and consisting of six genes in the order of 3'-NP-P-M-F-HN-L-5'. Several amino acid mutations were identified in the functional domains of F and HN proteins, including fusion peptide, heptad repeat region, transmembrane domains, and neutralizing epitopes. Phylogenetic analysis based on the F gene revealed that the HB strain and three other duck-origin NDV strains in China were grouped under subgenotype VII.1.1 and shared 99.1~99.2% nucleotide identity. Additionally, the challenge experiment results showed that the strain was highly pathogenic with 100% morbidity and mortality. Virus shedding was detected from 2 days post-infection until the fifth day. In conclusion, this study offers our understanding of circulating strains of NDV and genes involved in virulence and evolution between different hosts. Keywords: Newcastle disease virus; China; complete genome; genotype VII; mutations.
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http://dx.doi.org/10.4149/av_2021_210DOI Listing
June 2021

[Efficacy and Safety of PEG-rhG-CSF in HSC Mobilization in 71 Normal Healthy Donors for Allogeneic Hematopoietic Stem Cell Transplantation].

Zhongguo Shi Yan Xue Ye Xue Za Zhi 2021 Jun;29(3):951-956

Department of Hematology, The General Hospital of Western Theater Command, Chengdu 610083, Sichuan Province, China.

Objective: To retrospectively analyze the efficacy and safety of pegylated recombinant human granulocyte colony-stimulating factor (PEG-rhG-CSF) in hematopoietic stem cell mobilization in 71 normal healthy donors for allogeneic hematopoietic stem cell transplantation (allo-HSCT).

Methods: From March 2018 to July 2019, 71 patients received allo-HSCT in The General Hospital of Western Theater Command were enrolled in the study, a single dose of PEG-rhG-CSF was injected subcutaneously at 12 mg to all the stem cell donors. After injection for 4 days, CD34 cell number were detected, stem cells were collected on day 4 or 5 according to the CD34 cell number. The successful collection criteria were CD34 cells≥2×10/kg, and the excellent collection criteria were CD34 cells≥4×10/kg. The side effects after mobilization were observed and the collection time, the success rate, excellent rate, and times of the collection were evaluated in the donors, as well as the infused cell number, the engraftment rate, the time of engraftment, and the incidence of acute graft-versus-host disease (aGVHD) of the recipients.

Results: Seventy-one healthy stem cell donors included 39 males and 32 females with a median age of 38 (16-58) years old. The median number of CD34 cells on day 4 was 46 (7.4-133)/μl, of which 39 cases with CD34 cells ≥ 40/μl were collected on day 4, 28 cases with CD34 cells 20-40/μl were collected on day 5, and 4 cases with CD34 cells <20/μl were collected on day 5 after a salvage treatment with rhG-CSF. Sixty-five cases were collected once, while 6 cases twice. The median number of collected CD34 cells was 6.1(3.1-18.1)×10/kg. The success collection rate was 100% (71/71), and the excellent collection rate was 81.6% (58/71). All the cases had varying degrees of muscle and bone soreness, 17 cases (23.9%) had headache, 11 cases (15.5%) had fatigue, and 3 cases (4.2%) had a mild fever. Among 71 recipients, the median number of infused mononuclear cells (MNC) was 8.3(5-23.3)×10/kg, the median number of infused CD34 cells and CD3 cells was 5.3(3.1-10.7)×10/kg and 1.9 (0.5-7.6)×10/kg, respectively. Among them, 68 cases (95.8%) had a stable engraftment, the median time of neutrophil engraftment was 11(8-19) days, and the median time of platelet engraftment was 12(8-23) days. Among the 68 cases who were engrafted, 15 cases (22%) had grade Ⅱ-Ⅳ aGVHD, including grade Ⅲ-Ⅳ aGVHD in 3 patients (4.4%), 2 cases (2.9%) died of severe aGVHD.

Conclusion: For allo-HSCT donor mobilization, PEG-rh-G-CSF is effective, safe, and convenient, providing more options for HSC mobilization.
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http://dx.doi.org/10.19746/j.cnki.issn.1009-2137.2021.03.047DOI Listing
June 2021

Development and Validation of the Win-Win Scale.

Front Psychol 2021 21;12:657015. Epub 2021 May 21.

Institute of Psychology and Behavior, Henan University, Kaifeng, China.

Accumulating evidence has shown that win-win is necessary for both individuals and the society. This research, including two studies, aimed to develop and validate a measurement of the win-win scale. In the first study, we screened the items by item analysis and extracted common factors using exploratory factor analysis (EFA), thus determining a total of 25 items in the initial scale consisted of five dimensions including integrity, advancement, altruism, harmoniousness, and coordination. In the second study, we used first- and second-order confirmatory factor analysis (CFA) to test the scale's construct validity. The results indicated a good fit between the five-factor model and the data. Based on our results, we have formed a win-win scale by keeping 16 items from the original project pool.
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http://dx.doi.org/10.3389/fpsyg.2021.657015DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8175639PMC
May 2021

KOBAS-i: intelligent prioritization and exploratory visualization of biological functions for gene enrichment analysis.

Nucleic Acids Res 2021 Jun 4. Epub 2021 Jun 4.

Center for Bioinformatics, State Key Laboratory of Protein and Plant Gene Research, School of Life Sciences, Peking University, Beijing 100871, China.

Gene set enrichment (GSE) analysis plays an essential role in extracting biological insight from genome-scale experiments. ORA (overrepresentation analysis), FCS (functional class scoring), and PT (pathway topology) approaches are three generations of GSE methods along the timeline of development. Previous versions of KOBAS provided services based on just the ORA method. Here we presented version 3.0 of KOBAS, which is named KOBAS-i (short for KOBAS intelligent version). It introduced a novel machine learning-based method we published earlier, CGPS, which incorporates seven FCS tools and two PT tools into a single ensemble score and intelligently prioritizes the relevant biological pathways. In addition, KOBAS has expanded the downstream exploratory visualization for selecting and understanding the enriched results. The tool constructs a novel view of cirFunMap, which presents different enriched terms and their correlations in a landscape. Finally, based on the previous version's framework, KOBAS increased the number of supported species from 1327 to 5944. For an easier local run, it also provides a prebuilt Docker image that requires no installation, as a supplementary to the source code version. KOBAS can be freely accessed at http://kobas.cbi.pku.edu.cn, and a mirror site is available at http://bioinfo.org/kobas.
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http://dx.doi.org/10.1093/nar/gkab447DOI Listing
June 2021

Whole genome, exon mutation and transcriptomic profiling of acute myeloid leukemia: A case report.

Oncol Lett 2021 Jul 25;22(1):559. Epub 2021 May 25.

Hematology Department and Hematopoietic Stem Cell Transplantation Center, The General Hospital of Western Theater Command, Chengdu, Sichuan 610083, P.R. China.

The present study aimed to observe previously unidentified gene mutation and expression profiles associated with acute myeloid leukemia (AML) at the individual level, based on the blood samples of a father-son pair. Genomic DNA and RNA samples from blood serum were collected. Whole-genome sequencing (WGS) and whole-exome sequencing (WES), as well as mRNA sequencing of the son, were performed. For the father's sample, a total of 3,897,164 single nucleotide polymorphisms (SNPs) and 780,834 insertion and deletions (indels) were identified. Regarding amino acid translation, there were 11,316 non-synonymous, 12 stop-loss, 12,033 synonymous, 92 stop-gain SNPs, 63 frameshift insertions, 73 frameshift deletions, 242 non-frameshift insertions, 248 non-frameshift deletions, four stop-gains and two stop-loss for indel variants. Among the AML-related genes that had been previously identified, 14 genes were found in the father's exon region. For WES of the son's DNA, 96,639 SNPs were identified, including 10,504 non-synonymous SNPs. Seven mutant genes were found in sons' exon region compared with 121 AML-related genes. Based on the transcriptomic sequencing, there were 54 differentially expressed mRNAs, including 31 upregulated and 23 downregulated mRNAs. In the exon region, 10,072 SNPs were detected, and different types of alternative splicing in the son's sample were observed. Overall, whole genome, exon mutation and transcriptomic profiling of the present two patients with AML may provide a new insight into the molecular events governing the development of AML.
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http://dx.doi.org/10.3892/ol.2021.12820DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8161460PMC
July 2021

Moment-to-Moment Continuous Attention Fluctuation Monitoring through Consumer-Grade EEG Device.

Sensors (Basel) 2021 May 14;21(10). Epub 2021 May 14.

National University of Singapore, Singapore 117417, Singapore.

While numerous studies have explored using various sensing techniques to measure attention states, moment-to-moment attention fluctuation measurement is unavailable. To bridge this gap, we applied a novel paradigm in psychology, the gradual-onset continuous performance task (gradCPT), to collect the ground truth of attention states. GradCPT allows for the precise labeling of attention fluctuation on an 800 ms time scale. We then developed a new technique for measuring continuous attention fluctuation, based on a machine learning approach that uses the spectral properties of EEG signals as the main features. We demonstrated that, even using a consumer grade EEG device, the detection accuracy of moment-to-moment attention fluctuations was 73.49%. Next, we empirically validated our technique in a video learning scenario and found that our technique match with the classification obtained through thought probes, with an average F1 score of 0.77. Our results suggest the effectiveness of using gradCPT as a ground truth labeling method and the feasibility of using consumer-grade EEG devices for continuous attention fluctuation detection.
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http://dx.doi.org/10.3390/s21103419DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8156270PMC
May 2021

Loss of C2orf69 defines a fatal autoinflammatory syndrome in humans and zebrafish that evokes a glycogen storage-associated mitochondriopathy.

Am J Hum Genet 2021 May 21. Epub 2021 May 21.

Institute of Molecular and Cell Biology, A(∗)STAR, Biopolis, Singapore 138673, Singapore.

Human C2orf69 is an evolutionarily conserved gene whose function is unknown. Here, we report eight unrelated families from which 20 children presented with a fatal syndrome consisting of severe autoinflammation and progredient leukoencephalopathy with recurrent seizures; 12 of these subjects, whose DNA was available, segregated homozygous loss-of-function C2orf69 variants. C2ORF69 bears homology to esterase enzymes, and orthologs can be found in most eukaryotic genomes, including that of unicellular phytoplankton. We found that endogenous C2ORF69 (1) is loosely bound to mitochondria, (2) affects mitochondrial membrane potential and oxidative respiration in cultured neurons, and (3) controls the levels of the glycogen branching enzyme 1 (GBE1) consistent with a glycogen storage-associated mitochondriopathy. We show that CRISPR-Cas9-mediated inactivation of zebrafish C2orf69 results in lethality by 8 months of age due to spontaneous epileptic seizures, which is preceded by persistent brain inflammation. Collectively, our results delineate an autoinflammatory Mendelian disorder of C2orf69 deficiency that disrupts the development/homeostasis of the immune and central nervous systems.
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http://dx.doi.org/10.1016/j.ajhg.2021.05.003DOI Listing
May 2021

Investigation of the association between imbalance of the intestinal flora and infantile spasms: a pilot case-control study.

Transl Pediatr 2021 Apr;10(4):819-833

Medical School of the Chinese PLA, Beijing, China.

Background: The intestinal flora (IF) regulates brain function the neuroendocrine and neuroimmune systems and influences the development of several neuropsychiatric diseases, including epilepsy. Here, we investigated the specific relationship between the IF and infantile spasms (IS), a specific form of epilepsy.

Methods: Twenty-three children suffering from IS were recruited from the Chinese PLA General Hospital. According to patient response to adrenocorticotropic hormone (ACTH) treatment, the cohort was subdivided into 2 groups: an ACTH-response group and an ACTH-no response (NR) group. A total of 21 healthy children were recruited as a control group (healthy controls: HCs) during the same time period. Fecal samples were collected from infants in the IS and HC groups, and the population of fecal microorganisms was analyzed by 16s ribosomal DNA sequencing. The α and β diversity of the fecal microflora was determined, and the relative abundance of each species was classified. Tax4Fun2 was used to analyze the metabolic pathways utilized by the microflora, and the Kyoto Encyclopedia of Genes and Genomes database was used to analyze differentially expressed genes and pathways.

Results: No significant differences existed in α or β diversity when compared between the IS and HC groups, nor between the ACTH-response and ACTH-NR groups which were separated before and after ACTH treatment. Although there was no significant difference between the ACTH-response and ACTH-NR groups with respect to α diversity, there was a significant difference in β diversity. Compared with that of the HCs, the IF of the IS group featured lower proportions of , , and , and a higher proportion of . In the IS group, the proportion of in the IF was higher before treatment than after treatment. Compared with the ACTH-NR group, the ACTH-response group had reduced populations of , , , , and . However, an increase was observed in the population of . A significant difference was also identified between the IS and HC groups with regard to the expression levels of genes associated with lipoic acid synthesis.

Conclusions: Our analysis demonstrated that imbalance of the IF may be involved in the pathogenesis of IS and is related to response to ACTH. Regulating the composition of the IF may pave the way to developing a potential adjuvant therapy for patients with IS.
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http://dx.doi.org/10.21037/tp-20-384DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8107841PMC
April 2021

A discovery about the positional distribution pattern among candidate homologous pixels and its potential application in aerial multi-view image matching.

Sci Rep 2021 May 12;11(1):10161. Epub 2021 May 12.

Key Laboratory of Virtual Geographic Environment (Nanjing Normal University), Ministry of Education, 1# WenYuan Road, Nanjing, 210023, People's Republic of China.

In aerial multi-view photogrammetry, whether there is a special positional distribution pattern among candidate homologous pixels of a matching pixel in the multi-view images? If so, can this positional pattern be used to precisely confirm the real homologous pixels? These problems have not been studied at present. Therefore, the study of the positional distribution pattern among candidate homologous pixels based on the adjustment theory in surveying is investigated in this paper. Firstly, the definition and computing method of pixel's pseudo object-space coordinates are given, which can transform the problem of multi-view matching for confirming real homologous pixels into the problem of surveying adjustment for computing the pseudo object-space coordinates of the matching pixel. Secondly, according to the surveying adjustment theory, the standardized residual of each candidate homologous pixel of the matching pixel is figured out, and the positional distribution pattern among these candidate pixels is theoretically inferred utilizing the quantitative index of standardized residual. Lastly, actual aerial images acquired by different sensors are used to carry out experimental verification of the theoretical inference. Experimental results prove not only that there is a specific positional distribution pattern among candidate homologous pixels, but also that this positional distribution pattern can be used to develop a new object-side multi-view image matching method. The proposed study has an important reference value on resolving the defects of existing image-side multi-view matching methods at the mechanism level.
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http://dx.doi.org/10.1038/s41598-021-89501-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8115172PMC
May 2021

GABAergic synapses suppress intestinal innate immunity via insulin signaling in .

Proc Natl Acad Sci U S A 2021 May;118(20)

State Key Laboratory of Chemo/Biosensing and Chemometrics, College of Biology, Hunan University, 410082 Changsha, China;

GABAergic neurotransmission constitutes a major inhibitory signaling mechanism that plays crucial roles in central nervous system physiology and immune cell immunomodulation. However, its roles in innate immunity remain unclear. Here, we report that deficiency in the GABAergic neuromuscular junctions (NMJs) of results in enhanced resistance to pathogens, whereas pathogen infection enhances the strength of GABAergic transmission. GABAergic synapses control innate immunity in a manner dependent on the FOXO/DAF-16 but not the p38/PMK-1 pathway. Our data reveal that the insulin-like peptide INS-31 level was dramatically decreased in the GABAergic NMJ GABAR-deficient mutant compared with wild-type animals. with knockdown or loss of function exhibited enhanced resistance to PA14 exposure. INS-31 may act downstream of GABAergic NMJs and in body wall muscle to control intestinal innate immunity in a cell-nonautonomous manner. Our results reveal a signaling axis of synapse-muscular insulin-intestinal innate immunity in vivo.
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http://dx.doi.org/10.1073/pnas.2021063118DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8157918PMC
May 2021

Mild hypothermia facilitates mitochondrial transfer from astrocytes to injured neurons during oxygen-glucose deprivation/reoxygenation.

Neurosci Lett 2021 06 7;756:135940. Epub 2021 May 7.

Department of Anesthesiology, Second Hospital of Hebei Medical University, Shijiazhuang, 050000, Hebei, China. Electronic address:

Mitochondrial dysfunction is now considered an important sign of neuronal death during cerebral ischemia/reperfusion (I/R) injury. Studies have shown that the transfer of mitochondria from astrocytes to injured neurons contributes to endogenous neuroprotection after stroke. Basic and clinical studies have shown that mild hypothermia exerts a clear protective effect on neurons after cerebral ischemic injury, but the role of mild hypothermia in this endogenous neuroprotective mechanism remains unclear. Here, we established a neuronal cell oxygen-glucose deprivation (OGD)/reoxygenation (OGD/R)-induced injury model and explored the effect of mild hypothermia on the transfer of mitochondria from astrocytes to injured neurons. Astrocytes in the hypothermia group (33 °C) released more functional mitochondria into the extracellular medium than those in the normal temperature group (37 °C). Compared with cells in the normal temperature group, OGD-injured neuronal cells in the mild hypothermia group exhibited an increased intracellular ATP content, mitochondrial membrane potential (MMP) and cellular viability and a decreased death rate after the addition of astrocyte-derived conditioned medium. Based on the results of this study, mild hypothermia promotes endogenous neuroprotective effects through a mechanism related to functional mitochondria released from astrocytes into the extracellular space and transferred into injured neurons.
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http://dx.doi.org/10.1016/j.neulet.2021.135940DOI Listing
June 2021

A novel ATP dependent dimethylsulfoniopropionate lyase in bacteria that releases dimethyl sulfide and acryloyl-CoA.

Elife 2021 May 10;10. Epub 2021 May 10.

College of Marine Life Sciences, Ocean University of China, Qingdao, China.

Dimethylsulfoniopropionate (DMSP) is an abundant and ubiquitous organosulfur molecule in marine environments with important roles in global sulfur and nutrient cycling. Diverse DMSP lyases in some algae, bacteria, and fungi cleave DMSP to yield gaseous dimethyl sulfide (DMS), an infochemical with important roles in atmospheric chemistry. Here, we identified a novel ATP-dependent DMSP lyase, DddX. DddX belongs to the acyl-CoA synthetase superfamily and is distinct from the eight other known DMSP lyases. DddX catalyses the conversion of DMSP to DMS via a two-step reaction: the ligation of DMSP with CoA to form the intermediate DMSP-CoA, which is then cleaved to DMS and acryloyl-CoA. The novel catalytic mechanism was elucidated by structural and biochemical analyses. DddX is found in several Alphaproteobacteria, Gammaproteobacteria, and Firmicutes, suggesting that this new DMSP lyase may play an overlooked role in DMSP/DMS cycles.
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http://dx.doi.org/10.7554/eLife.64045DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8163506PMC
May 2021

SphK2/S1P Promotes Metastasis of Triple-Negative Breast Cancer Through the PAK1/LIMK1/Cofilin1 Signaling Pathway.

Front Mol Biosci 2021 22;8:598218. Epub 2021 Apr 22.

Department of Hepatobiliary Surgery, The Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing, China.

Background: Triple-negative breast cancer (TNBC) features a poor prognosis, which is partially attributed to its high metastatic rate. However, there is no effective target for systemic TNBC therapy due to the absence of estrogen, progesterone, and human epidermal growth factor 2 receptors (ER, PR, and HER-2, respectively) in cancer. In the present study, we evaluated the role of sphingosine kinase 2 (SphK2) and its catalyst sphingosine-1-phosphate (S1P) in TNBC metastasis and the effect of the SphK2-specific inhibitor ABC294640 on TNBC metastasis.

Methods: The function of SphK2 and S1P in TNBC cell metastasis was evaluated using transwell migration and wound-healing assays. The molecular mechanism of SphK2/S1P mediating TNBC metastasis was investigated using Western blot, histological examination, and immunohistochemistry assays. The antitumor activity of ABC294640 was examined in an TNBC lung metastatic model.

Results: Sphingosine kinase 2 promoted TNBC cell migration through the generation of S1P. Targeting SphK2 with ABC294640 inhibited TNBC lung metastasis . p21-activated kinase 1 (PAK1), p-Lin-11/Isl-1/Mec-3 kinase 1 (LIMK1), and Cofilin1 were the downstream signaling molecules of SphK2/S1P. Inhibition of PAK1 suppressed SphK2/S1P-induced TNBC cell migration.

Conclusion: Sphingosine kinase 2/sphingosine-1-phosphate promotes TNBC metastasis through the activation of the PAK1/LIMK1/Cofilin1 signaling pathway. ABC294640 inhibits TNBC metastasis and could be developed as a novel agent for the clinical treatment of TNBC.
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http://dx.doi.org/10.3389/fmolb.2021.598218DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8100449PMC
April 2021

Erythropoietin Improves Poor Outcomes in Preterm Infants with Intraventricular Hemorrhage.

CNS Drugs 2021 Jun 6;35(6):681-690. Epub 2021 May 6.

Henan Key Laboratory of Child Brain Injury and Henan Pediatric Clinical Research Center, Institute of Neuroscience and Third Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, China.

Background: Intraventricular hemorrhage (IVH) is a common complication in preterm infants that has poor outcomes, especially in severe cases, and there are currently no widely accepted effective treatments. Erythropoietin has been shown to be neuroprotective in neonatal brain injury.

Objective: The objective of this study was to evaluate the protective effect of repeated low-dose recombinant human erythropoietin (rhEPO) in preterm infants with IVH.

Methods: This was a single-blinded prospective randomized controlled trial. Preterm infants ≤ 32 weeks gestational age who were diagnosed with IVH within 72 h after birth were randomized to receive rhEPO 500 IU/kg or placebo (equivalent volume of saline) every other day for 2 weeks. The primary outcome was death or neurological disability assessed at 18 months of corrected age.

Results: A total of 316 eligible infants were included in the study, with 157 in the rhEPO group and 159 in the placebo group. Although no significant differences in mortality (p = 0.176) or incidence of neurological disability (p = 0.055) separately at 18 months of corrected age were seen between the rhEPO and placebo groups, significantly fewer infants had poor outcomes (death and neurological disability) in the rhEPO group: 14.9 vs. 26.4%; odds ratio (OR) 0.398; 95% confidence interval (CI) 0.199-0.796; p = 0.009. In addition, the incidence of Mental Development Index scores of < 70 was lower in the rhEPO group than in the placebo group: 7.2 vs. 15.3%; OR 0.326; 95% CI 0.122-0.875; p = 0.026.

Conclusions: Treatment with repeated low-dose rhEPO improved outcomes in preterm infants with IVH.

Trial Registration: The study was retrospectively registered on ClinicalTrials.gov on 16 April 2019 (NCT03914690).
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http://dx.doi.org/10.1007/s40263-021-00817-wDOI Listing
June 2021

Integration of evidence across human and model organism studies: A meeting report.

Genes Brain Behav 2021 Apr 23:e12738. Epub 2021 Apr 23.

Department of Psychiatry, Yale University School of Medicine, West Haven, Connecticut, USA.

The National Institute on Drug Abuse and Joint Institute for Biological Sciences at the Oak Ridge National Laboratory hosted a meeting attended by a diverse group of scientists with expertise in substance use disorders (SUDs), computational biology, and FAIR (Findability, Accessibility, Interoperability, and Reusability) data sharing. The meeting's objective was to discuss and evaluate better strategies to integrate genetic, epigenetic, and 'omics data across human and model organisms to achieve deeper mechanistic insight into SUDs. Specific topics were to (a) evaluate the current state of substance use genetics and genomics research and fundamental gaps, (b) identify opportunities and challenges of integration and sharing across species and data types, (c) identify current tools and resources for integration of genetic, epigenetic, and phenotypic data, (d) discuss steps and impediment related to data integration, and (e) outline future steps to support more effective collaboration-particularly between animal model research communities and human genetics and clinical research teams. This review summarizes key facets of this catalytic discussion with a focus on new opportunities and gaps in resources and knowledge on SUDs.
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http://dx.doi.org/10.1111/gbb.12738DOI Listing
April 2021

Solid-Pseudopapillary Neoplasm of the Pancreas: A 63-Case Analysis of Clinicopathologic and Immunohistochemical Features and Risk Factors of Malignancy.

Cancer Manag Res 2021 15;13:3335-3343. Epub 2021 Apr 15.

Department of Pathology, Bengbu Medical College, Bengbu, Anhui Province, 233000, People's Republic of China.

Purpose: Solid-pseudopapillary neoplasm (SPN) of the pancreas, a rare tumor, has low malignant potential. However, some patients develop metastasis and recurrence after resection, with aggressive biological behaviors. This study aimed to explore the features and risk factors associated with the aggressive biological behaviors of SPNs.

Patients And Methods: We retrospectively analyzed the clinicopathological and long-term follow-up data of 63 patients diagnosed with SPN at the First Affiliated Hospital of Bengbu Medical College between January 2007 and February 2019.

Results: Sixty-three patients presented atypical clinical symptoms. The median tumor size was 7.0 cm (range, 2.4-17 cm), and imaging features were solid and cystic or solid tumors with uneven density. Frequent and diffuse nuclear LEF1 protein expression (94.2%) was observed with LEF1 having a higher sensitivity and specificity. Overall survival significantly correlated with tumor size, Ki-67 index, and lymph node metastasis ( < 0.05).

Conclusion: SPN is a rare low-grade malignancy with a specific pseudopapillary structure. LEF1 is an effective biomarker of SPNs. Although SPNs generally display indolent biological behavior, a large tumor size, high proliferation index, and lymph node metastasis may be risk factors for the aggressive behavior and poor prognosis of SPN.
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http://dx.doi.org/10.2147/CMAR.S304981DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8055352PMC
April 2021

Identification of small extracellular vesicle-linked miRNA specifically derived from intrafollicular cells in women with polycystic ovary syndrome.

Reprod Biomed Online 2021 May 8;42(5):870-880. Epub 2021 Feb 8.

Department of Reproductive Medicine Center, Henan Provincial People's Hospital, People's Hospital of Zhengzhou University, Henan Provincial People's Hospital of Henan University, Zhengzhou, Henan, China; Henan Joint International Research Laboratory of Reproductive Bioengineering, Zhengzhou Henan Province, China. Electronic address:

Research Question: This study aimed to identify small extracellular vesicle (sEV)-linked microRNAs (miRNA) specifically derived from intrafollicular cells in women with polycystic ovary syndrome (PCOS) and to investigate their biological functions.

Design: A total of 120 women were recruited from September 2017 to October 2018. To investigate miRNA profiles in sEV derived from follicular fluid and serum, 30 women with PCOS and 30 without PCOS were included for a miRNA microarray containing probes interrogating 2549 human miRNA. To study the expression levels of differentially expressed miRNA, sEV in follicular fluid obtained from another 30 PCOS and 30 non-PCOS patients were used for quantitative real-time polymerase chain reaction analysis.

Results: A total of 281 sEV-linked miRNA specifically derived from intrafollicular cells were identified, 179 of which were expressed in both the PCOS and non-PCOS groups. Twenty-six of the 179 intrafollicle-specific sEV-linked miRNA were predicted to target 1537 genes. Functional analysis suggested that these genes were involved in pathways related to folliculogenesis, including the MAPK, and PI3K-Akt signalling pathways. Quantitative real-time polymerase chain reaction analysis showed that the expression of seven intrafollicle-specific sEV-linked miRNA was significantly higher in follicular fluid-derived sEV in women with PCOS than in women without it. These miRNA and their corresponding target genes were identified as being involved in the MAPK signalling pathway and oocyte meiosis.

Conclusions: The data suggest that the aberrantly expressed miRNA and their target genes might be associated with PCOS, providing novel insights into the molecular mechanisms underlying regulation of folliculogenesis and oocyte maturation in PCOS.
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http://dx.doi.org/10.1016/j.rbmo.2021.02.002DOI Listing
May 2021

Coding and non-coding roles of MOCCI (C15ORF48) coordinate to regulate host inflammation and immunity.

Nat Commun 2021 04 9;12(1):2130. Epub 2021 Apr 9.

Institute of Medical Biology, A*STAR, Singapore, Singapore.

Mito-SEPs are small open reading frame-encoded peptides that localize to the mitochondria to regulate metabolism. Motivated by an intriguing negative association between mito-SEPs and inflammation, here we screen for mito-SEPs that modify inflammatory outcomes and report a mito-SEP named "Modulator of cytochrome C oxidase during Inflammation" (MOCCI) that is upregulated during inflammation and infection to promote host-protective resolution. MOCCI, a paralog of the NDUFA4 subunit of cytochrome C oxidase (Complex IV), replaces NDUFA4 in Complex IV during inflammation to lower mitochondrial membrane potential and reduce ROS production, leading to cyto-protection and dampened immune response. The MOCCI transcript also generates miR-147b, which targets the NDUFA4 mRNA with similar immune dampening effects as MOCCI, but simultaneously enhances RIG-I/MDA-5-mediated viral immunity. Our work uncovers a dual-component pleiotropic regulation of host inflammation and immunity by MOCCI (C15ORF48) for safeguarding the host during infection and inflammation.
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http://dx.doi.org/10.1038/s41467-021-22397-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8035321PMC
April 2021

Iatrogenic vs. Spontaneous Preterm Birth: A Retrospective Study of Neonatal Outcome Among Very Preterm Infants.

Front Neurol 2021 23;12:649749. Epub 2021 Mar 23.

Henan Key Laboratory of Child Brain Injury and Henan Pediatric Clinical Research Center, Institute of Neuroscience and Third Affiliated Hospital of Zhengzhou University, Zhengzhou, China.

Preterm birth is a leading contributor to childhood morbidity and mortality, and the incidence tends to increase and is higher in developing countries. The aim of this study was to analyze the potential impact of preterm birth in different etiology groups on neonatal complications and outcomes and to gain insight into preventive strategies. We performed a retrospective cohort study of preterm infants less than 32 weeks' gestation in the Third Affiliated Hospital of Zhengzhou University from 2014 to 2019. Preterm births were categorized as spontaneous or iatrogenic, and these groups were compared for maternal and neonatal characteristics, neonatal complications, and outcomes. All infants surviving at discharge were followed up at 12 months of corrected age to compare the neurodevelopmental outcomes. A total of 1,415 mothers and 1,689 neonates were included, and the preterm population consisted of 1,038 spontaneous preterm infants and 651 iatrogenic preterm infants. There was a significant difference in the incidence of small for gestational age between the two groups. Infants born following spontaneous labor presented with a higher risk of intraventricular hemorrhage, whereas iatrogenic preterm birth was associated with higher risk of necrotizing enterocolitis and coagulopathy and higher risk of pathoglycemia. There was no difference in mortality between the two groups. Follow-up data were available for 1,114 infants, and no differences in neurologic outcomes were observed between the two preterm birth subtypes. Preterm births with different etiologies were associated with some neonatal complications, but not with neurodevelopmental outcomes at 12 months of corrected age.
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http://dx.doi.org/10.3389/fneur.2021.649749DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8021792PMC
March 2021

Therapeutic Angiogenesis for Ovarian Transplantation through Ultrasound-Targeted Microbubble Destruction.

Ultrasound Med Biol 2021 Jul 6;47(7):1868-1880. Epub 2021 Apr 6.

Department of Echocardiography, First Affiliated Hospital of Xinjiang Medical University, Urumqi, China. Electronic address:

Timely angiogenesis and effective microcirculation perfusion are essential for the survival and functional recovery of transplanted ovaries. Ultrasound-targeted microbubble destruction (UTMD) can lead to angiogenesis and increase flow perfusion by causing transient inflammation. The purpose of this study was to evaluate the effects of UTMD on transplanted ovarian revascularization and survival. In vitro, for the criteria of cell viability and tube formation capability, the optimal exposure parameters were determined to be a microbubble concentration of 1 × 10/mL, mechanical index of 1 and exposure time of 30 s. After ovarian transplantation, 40 female Sprague Dawley rats were divided into four groups: transplantation alone, ultrasound alone, microbubbles alone and ultrasound and microbubbles (UTMD). At 7 d after transplantation, ovarian perfusion was assessed using qualitative and quantitative methods. The effect of angiogenesis was assessed by contrast-enhanced ultrasound, laser Doppler perfusion imaging and histologic analysis. The results, in which ovarian perfusion was highest in the UTMD group, suggest that UTMD can effectively improve ovarian perfusion. Compared with the other three groups, the number of follicles, microvascular density and rate of Ki-67-positive cells increased significantly in the UTMD group, while apoptosis decreased significantly (p < 0.05). The study indicates that UTMD promoted ovarian re-vascularization after ovarian transplantation and maintained follicular reserve.
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http://dx.doi.org/10.1016/j.ultrasmedbio.2021.02.025DOI Listing
July 2021

Tritonibacter aquimaris sp. nov. and Tritonibacter litoralis sp. nov., two novel members of the Roseobacter group isolated from coastal seawater.

Antonie Van Leeuwenhoek 2021 Jun 29;114(6):787-798. Epub 2021 Mar 29.

State Key Laboratory of Microbial Technology, Institute of Marine Science and Technology, Marine Biotechnology Research Center, Shandong University, Qingdao, 266237, China.

Two Gram-stain-negative bacterial strains, SM1969 and SM1979, were isolated from coastal surface seawater of Qingdao, China. They were taxonomically characterized by the phylogenetic, genomic, chemotaxonomic and phenotypic analyses. The two strains shared 97.0% 16S rRNA gene sequence similarity with each other and the highest similarity (96.8-97.5%) with type strains of six species in the genera Shimia, Tritonibacter and Tropicibacter in the Roseobacter group of the family Rhodobacteraceae. In the phylogenetic tree based on single-copy orthologous clusters (OCs), both strains clustered with known species of the genus Tritonibacter and together formed a separate branch adjacent to Tritonibacter ulvae. Although sharing many chemotaxonomic and phenotypic characteristics, the two strains could be differentiated from each other and closely related species by numerous traits. Particularly, strain SM1969 was found to have a DMSP lyase coding gene dddW in its genome and have the ability to produce DMS from DMSP while strain SM1979 was not. The average nucleotide identity and in silico DNA-DNA hybridization values between strains SM1969 and SM1979 and type strains of closely related species were all below the thresholds to discriminate bacterial species, demonstrating that they constitute two new species in the genus Tritonibacter. The names Tritonibacter aquimaris sp. nov. and Tritonibacter litoralis sp. nov. are proposed for the two new species, with type strains being SM1969 (= MCCC 1K04320 = KCTC 72843) and SM1979 (= MCCC 1K04321 = KCTC 72842), respectively.
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http://dx.doi.org/10.1007/s10482-021-01558-yDOI Listing
June 2021

Insight into Shared Properties and Differential Dynamics and Specificity of Secretory Phospholipase A Family Members.

J Phys Chem B 2021 04 29;125(13):3353-3363. Epub 2021 Mar 29.

Faculty of Environmental and Life Sciences, Beijing University of Technology, Beijing 100124, China.

Understanding generic mechanisms of functions shared by the secretory phospholipase A (sPLA) family involved in the lipid metabolism and cell signaling and the molecular basis of function specificity for family members is an intriguing but challenging problem for biologists. Here, we explore the issue through extensive analyses using a combination of structure-based methods and bioinformatics tools on130 sPLA family members. The principal component analysis of the structure ensemble reveals that the enzyme has an open-close motion which helps widen the substrate binding channel, facilitating its binding to phospholipid. Performing elastic network model and sequence analyses found that the residues critical for family functions, such as cysteine and catalytic residues, are highly conserved and undergo minimal movements, which is evolutionarily essential as their perturbation would impact the function, while the four residue regions involved in the association with the calcium ion/membrane are lowly conserved and of high mobility and large variations in low-to-intermediate frequency modes, which reflects the specificity of members. The analyses from perturbation response scanning also reveal that the above four regions with high sensitivity to an external perturbation are member-specific, suggesting their different roles in allosteric modulation, while the minimal sensitive residues are the shared characteristics across family members, which play an important role in maintaining structural stability as the folding core. This study is helpful for understanding how sequences, structures, and dynamics of sPLA family members evolve to ensure their common and specific functions and can provide a guide for accurate design of proteins with finely tuned activities.
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http://dx.doi.org/10.1021/acs.jpcb.1c01315DOI Listing
April 2021

A Self-test Prediction Model to Determine the Probability Risk of Non-alcoholic Fatty Liver Disease.

Biomed Environ Sci 2020 Nov;33(11):857-861

School of Public Health, Beijing Municipal Key Laboratory of Clinical Epidemiology, Capital Medical University, Beijing 100069, China.

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http://dx.doi.org/10.3967/bes2020.116DOI Listing
November 2020

High Glucose Causes Distinct Expression Patterns of Primary Human Skin Cells by RNA Sequencing.

Front Endocrinol (Lausanne) 2021 8;12:603645. Epub 2021 Mar 8.

Department of Vascular Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

Diabetes-related skin problems represent the most common long-term complications in diabetes mellitus patients. These complications, which include diabetic dermopathy, diabetic blisters, necrobiosis lipoidica diabeticorum, and eruptive xanthomatosis, may dramatically impair patients' quality of life and cause long-lasting disability. However, the cellular and molecular mechanisms linking diabetes-related hyperglycemia and skin complications are still incompletely understood. To assess the role of the various skin-cell types in hyperglycemia-induced skin disorders, we performed RNA sequencing-based transcriptome analysis, measuring gene expression patterns in biological replicates in normal- and high glucose-stimulated skin cells. Three primary human skin-cell types were examined, , epidermal keratinocytes, dermal fibroblasts, and dermal microvascular endothelial cells. For each separate cell type, we identified gene expression. Comparing gene abundances and expression levels revealed that transcription profiles exhibit distinct patterns in the three skin-cell types exposed to normal (, physiological) glucose treatment and high (, supraphysiological) glucose treatment. The obtained data indicate that high glucose induced differential gene expression and distinct activity patterns in signaling pathways in each skin-cell type. We are adding these data to the public database in the hope that they will facilitate future studies to develop novel targeted interventions for diabetic skin complications.
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http://dx.doi.org/10.3389/fendo.2021.603645DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7982678PMC
March 2021

Megarthrus of China. Part 3. Comments on the occurrence of Megarthrus nitidulus Kraatz, 1857 in China, and description of a new species, with notes on teratology and phoretic acari in the genus (Coleoptera: Staphylinidae: Proteininae).

Zootaxa 2021 Feb 2;4920(4):zootaxa.4920.4.6. Epub 2021 Feb 2.

Institute of Entomology, College of Plant Protection, Southwest University, Chongqing 400715, China..

A new species, Megarthrus heise Zhang, Cuccodoro, Chen Liu sp. nov., resembling Megarthrus nitidulus Kraatz, 1857 is described from Qinghai, Sichuan, Gansu, Shaanxi, Shanxi provinces and Beijing in China. The record of M. nitidulus in China was apparently based on a misidentification, and the species is thus removed from the list of Chinese Megarthrus. Phoresy of acari and teratological modification of the abdomen are also reported for the first time in the genus.
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http://dx.doi.org/10.11646/zootaxa.4920.4.6DOI Listing
February 2021

Linc00665 Can Predict the Response to Cisplatin-Paclitaxel Neoadjuvant Chemotherapy for Breast Cancer Patients.

Front Oncol 2021 2;11:604319. Epub 2021 Mar 2.

Department of Breast Surgery, Renji Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, China.

Objective: Linc00665 is a novel long non-coding RNA that can promote the progression of breast cancer, but its value in predicting the efficacy of neoadjuvant chemotherapy (NAC) for breast cancer has not been reported. We aim to analyze the correlation between Linc00665 expression and pathological complete response (pCR) in breast cancer patients.

Materials And Methods: The present study examined the predictive role of Linc00665 expression in pCR after NAC using both univariate and multivariate logistic regression analyses. Receiver operating characteristic (ROC) curve and area under curve (AUC) were utilized to evaluate the performance of Linc00665 in predicting pCR. The Kyoto Encyclopedia of Gene and Genome (KEGG) analysis and Gene Set Enrichment Analysis (GSEA) were also conducted to determine the biological processes where Linc00665 may participate in.

Results: The present study study totally enrolled 102 breast cancer patients. The univariate analysis showed that Linc00665 level, human epidermal growth factor receptor 2 (HER2) status and hormone receptor (HR) status were correlated with pCR. The multivariate analysis showed that Linc00665 expression was an independent predictor of pCR (OR = 0.351, 95% CI: 0.125-0.936, P = 0.040), especially in patients with HR-positive/HER2-negative subtype (OR = 0.272, 95% CI: 0.104-0.664, P = 0.005). The KEGG analysis indicated that Linc00665 may be involved in drug metabolism. The GSEA analysis revealed that Linc00665 is correlated to DNA damage repair.

Conclusion: Linc00665 may be a potential novel predictive biomarker for breast cancer in NAC, especially for HR-positive/HER2-negative patients.
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http://dx.doi.org/10.3389/fonc.2021.604319DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7961084PMC
March 2021

Long-term outcomes of Boston keratoprosthesis type I: the Chinese People's Liberation Army General Hospital experience.

Br J Ophthalmol 2021 Mar 5. Epub 2021 Mar 5.

Department of Ophthalmology, General Hospital of People's Liberation Army, Beijing, China

Purpose: To report the long-term outcomes of Boston keratoprosthesis type I (B-KPro type I) implantation in the management of severe ocular surface disorders.

Methods: Retrospective case series. Patients who underwent B-KPro type I implantation at the People's Liberation Army General Hospital were enrolled between March 2011 and September 2019. Data regarding visual acuity (VA), B-KPro type I retention and postoperative complications were recorded and analysed.

Results: A total of 103 eyes of 100 patients who underwent B-KPro type I implantation were included. The main indications were chemical burn (59.2%), ocular trauma (25.2%), herpetic keratitis (11.7%) and autoimmune diseases (3.9%). The percentage of eyes with postoperative VA of 10/200 or better was 82.7% at 6 months, 82.8% at 12 months, 77.9% at 2 years, 72.4% at 3 years, 71.1% at 4 years, 69.4% at 5 years, 58.9% at 6 years, 56.8% at 7 years and 42.9% at 8 years. Preoperatively, 8.7% eyes were diagnosed with new-onset glaucoma. Retroprosthetic membrane formation occurred in 19.4% eye. Corneal melting occurred in 18.4% eyes. Sterile vitritis was diagnosed in 4.9% eyes and infectious endophthalmitis in 2.9% eyes. Retinal detachment occurred in 0.9% eyes.

Conclusions: In a Chinese patient group, B-KPro type I is a viable option for treating severe ocular surface disorders in eyes where conventional keratoplasty would have a poor prognosis, especially in patients with chemical and thermal burns. Improved visual outcomes and high retention rate can be achieved and maintained in most cases.
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http://dx.doi.org/10.1136/bjophthalmol-2019-315617DOI Listing
March 2021

Dietary supplementation with Bacillus subtilis promotes growth performance of broilers by altering the dominant microbial community.

Poult Sci 2021 Mar 23;100(3):100935. Epub 2021 Jan 23.

Poultry Institute, Chinese Academy of Agricultural Sciences, Yangzhou, Jiangsu 225125, China; Jiangsu Co-innovation Center for the Prevention and Control of Important Animal Infectious Disease and Zoonosis, Yangzhou University, Yangzhou, Jiangsu 225009, China. Electronic address:

The purpose of this study was to investigate the effects of Bacillus subtilis on growth performance, intestinal morphology, and cecal microbial composition of broilers. A total of 270 healthy one-day-old Arbor Acres male broiler chicks were randomly divided into 3 dietary treatment groups, with 6 replicates per group and 15 chickens per replicate. The dietary treatment groups were as follows: 1) basal diet, negative control group; 2) basal diet +250 g/t of zinc bacitracin, positive control group; and 3) basal diet +750 g/t of B. subtilis, B. subtilis group. Results of this experiment showed that compared with the negative control group, body weight at 42 d, average daily gain and European Production Efficiency Factor over the 42 d phase in the B. subtilis group and positive control group were significantly increased (P < 0.05); feed conversion rates in the B. subtilis group and positive control group were significantly decreased (P < 0.05); and average daily feed intake and mortality were not significantly different (P > 0.05). The villus height to crypt depth ratio in the ileum of the B. subtilis group was significantly higher (P < 0.05) than that of the negative control group. The results of cecal microflora at genus level were as follows. As compared with the negative control group, the abundance of Blautia, Faecalibacterium, Flavonifractor, and Hydrogenoanaerobacterium of the B. subtilis group and positive control group was significantly higher (P < 0.05), whereas the abundance of Odoribacter was significantly lower (P < 0.05). Moreover, abundance of the genera Romboutsia in the B. subtilis group was higher (P < 0.05) than that in the positive control group. The abundance of Flavonifractor, Erysipelatoclostridium, and Hydrogenoanaerobacterium were positively correlated with body weight and average daily gain by Spearman correlation analysis. In conclusion, dietary supplementation with B. subtilis improved growth performance of broilers which may be related to the increased abundance of Blautia, Faecalibacterium, Flavonifractor, Hydrogenoanaerobacterium, and Romboutsia, along with the decreased abundance of Odoribacter. In addition, the effect of B. subtilis was superior to zinc bacitracin in improving intestinal microbial composition of broilers. Therefore, B. subtilis may act as an effective antibiotic substitute in broilers.
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http://dx.doi.org/10.1016/j.psj.2020.12.032DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7936199PMC
March 2021

Clinicopathological features and prognostic factors associated with gastroenteropancreatic mixed neuroendocrine non-neuroendocrine neoplasms in Chinese patients.

World J Gastroenterol 2021 Feb;27(7):624-640

Department of Pathology, The First Affiliated Hospital of Bengbu Medical College, Bengbu 233000, Anhui Province, China.

Background: The incidence of mixed neuroendocrine-non-neuroendocrine neoplasms (MiNEN) is low. To improve our understanding of this rare tumor type and optimally guide clinical treatment, associated risk factors, clinical manifestations, and prognosis must be explored.

Aim: To identify risk factors that influence the prognosis of patients with gastroenteropancreatic MiNEN (GEP-MiNEN).

Methods: We retrospectively analyzed the clinical data of 46 patients who were diagnosed with GEP-MiNEN at the First Affiliated Hospital of Bengbu Medical College (Anhui, China) between January 2013 and December 2017. Risk factors influencing the prognosis of the patients were assessed using Kaplan-Meier curves and cox regression models. We compared the results with 55 randomly selected patients with gastroenteropancreatic GEP neuroendocrine tumors, 47 with neuroendocrine carcinomas (NEC), and 58 with poorly differentiated adenocarcinoma.

Results: Among the 46 patients with GEP-MiNEN, thirty-five had gastric tumors, nine had intestinal tumors (four in the small intestine and five in the colon and rectum), and two had pancreatic tumors. The median age of the patients was 66 (41-84) years, and the male-to-female ratio was 2.83. Thirty-three (71.7%) patients had clinical stage III and IV cancers. Distant metastasis occurred in 14 patients, of which 13 had metastasis to the liver. The follow-up period was 11-72 mo, and the median overall survival was 30 mo. Ki-67 index ≥ 50%, high proportion of NEC, lymph node involvement, distant metastasis, and higher clinical stage were independent risk factors affecting the prognosis of patients with GEP-MiNEN. The median overall survival was shorter for patients with NEC than for those with MiNEN (14 mo 30 mo, = 0.001), but did not significantly differ from those with poorly differentiated adenocarcinoma and MiNEN (30 mo 18 mo, = 0.453).

Conclusion: A poor prognosis is associated with rare, aggressive GEP-MiNEN. Ki-67 index, tumor composition, lymph node involvement, distant metastasis, and clinical stage are important factors for patient prognosis.
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http://dx.doi.org/10.3748/wjg.v27.i7.624DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7901054PMC
February 2021