Transcriptome analysis and the effects of polyunsaturated fatty acids on the immune responses of the critically endangered angtze sturgeon (Acipenser dabryanus).

The poor understanding of nutrition needed has become a significant obstruction to artificial conservation of Yangtze sturgeon (Acipenser dabryanus) and the relationship between ployunsaturated fatty acid nutrition and the immune response of Yangtze sturgeon is remains unclear. To explore this relationship, the immune response was determined by the activities of serum immune-related enzymes and the transcriptome pattern in the spleen after feeding different fat source diets for 7 weeks. In addition, the gene expression pattern after a lipopolysaccharide (LPS) challenge was investigated in the presence of docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA). Long-term feeding of the fish oil diets increased the serum immune-related enzyme activities, including lysozyme, acid phosphatase, and alkaline phosphatase of Yangtze sturgeon. More than 653,999 transcripts with an N50 length of 1047 bp were obtained and a final set of 280,408 unigenes was generated. After annotating the unigenes, 3549 genes were assigned to the immune system and 2839 were identified to participate in the response to the different fat sources. A transcriptome assay showed the fish oil diets moderately upregulated immune-related signaling pathways in the spleen of Yangtze sturgeon, including NLR signaling, platelet activation, Fc gamma R-mediated phagocytosis, Th17 cell differentiation, and Th1 and Th2 cell differentiation. The quantitative polymerase chain reaction (qPCR) results of candidate genes for these pathways showed similar results. The LPS challenge study revealed that DHA and EPA moderately upregulated the candidate immune-related genes and modulated excessive activation of the immune pathway by the pathogen. This study confirmed the immunomodulatory function of unsaturated fatty acids in Yangtze sturgeon. This research will provide a reference for the preparation of artificial diets for Yangtze sturgeon.

The clinical characteristics and treatment of intestinal hamartomas.

The study aims to investigate the intestinal (small and large intestine) clinical features and treatment of hamartoma. Nowadays, with the rapid development of new technologies, digestive system endoscopy has been proven to be an effective device for treatment, rather than just a diagnostic tool. Such development plays a revolutionary role in diagnosis and treatment for digestive diseases. And endoscopic treatment was used in this study (LED light source, wavelength 580 ∼ 595 nm, power 200 W). A retrospective analysis of 20 cases of intestinal hamartomas performed from January 2012 to January 2016 to summarize its clinical characteristics and follow-up study on the therapeutic effect of the patients. There were 8 cases for endoscopic operation, and 12 cases for surgical operation. Comparison of tumor size between endoscopic and surgical estimated by using Wilcoxon rank sum test for tumor length (Z = -3.134, p = 0.001), and for tumor diameter (Z = -2.920, p = 0.002). The results of this study showed that intestinal hamartomas and gender have no significant relationship. The incidence of the disease is concentrated under 60 years, the incidence of the small intestine is significantly higher than that of the large intestine, and the rate of misdiagnosis is high. Endoscopic and surgical treatment are the main treatment, the prognosis is good, and after the radical resection, the recurrence was less.

[Characteristics and Sources of PM2.5 Pollution in Typical Cities of the Central Plains Urban Agglomeration in Autumn and Winter].

To study the characteristics of PM2.5 pollution and the potential sources of its main components in the central plain urban agglomeration in autumn and winter, PM2.5 samples were collected continually in the four typical cities of Zhengzhou, Luoyang, Anyang, and Xinxiang from October 2018 to January 2019. X-ray fluorescence spectrometry, carbon analysis methods, and ion chromatography were used to determine 18 kinds of inorganic elements, organic carbon (OC)/elemental carbon (EC), and 9 kinds of water-soluble inorganic ions. According to the daily PM2.5 concentration, three pollution levels were divided, and the comparative analysis for the spatial and temporal variation of PM2.5 and its main components, i.e., NO3-, OC, and 18 kinds of inorganic elements, were studied via the calculation of the nitrogen oxidation rate (NOR), secondary organic carbon (SOC), and enrichment factor. The emission sources and their contribution rates of PM2.5 pollution level in the four cities were calculated by a chemical mass balance (CMB) model; the potential pollution sources of PM2.5 and its main components, NO3- and OC, in the four cities were analyzed by a backward trajectory model (HYSPLIT) and potential source contribution factor method (PSCF). The results showed that the means of PM2.5 in Zhengzhou, Luoyang, Anyang, and Xinxiang were (82.1±45.5), (84.7±39.8), (96.8±46.1), and (81.1±36.6) µg·m-3, respectively, during the sampling period, and the maximum daily mean values were 3.3, 2.6, 3.0, and 2.3 times, respectively, of the Chinese national secondary standard; the main components of PM2.5 in the four cities were NO3- and SOC, and the concentration of NO3-, the ratio of NO3-/EC, and NOR all increased significantly with the rising of pollution levels, generally showing that the mean values of NO3-/EC and NOR of Zhengzhou and Luoyang were a little higher than those of Anyang and Xinxiang; the concentration of SOC, the proportion of SOC in OC, and the ratio of SOC/EC all increased with the rising of pollution levels. From the concentration and enrichment degree of inorganic elements, As was the highest in Zhengzhou; Mn and Fe were the highest in Luoyang; Zn, Ni, and Cr were the highest in Anyang; and Cu and Pb were the highest in Xinxiang. Secondary nitrate, secondary sulfate, organic matter, coal combustion, motor vehicle, dust, biomass burning, and industrial processes were the main PM2.5 pollution sources in the four cities, with the highest contribution rate of secondary nitrate in Zhengzhou (37.7%), the highest contribution rate of vehicle sources in Xinxiang (14.1%), and a relatively high contribution rate of industrial process source in Luoyang (7.0%) and Anyang (6.8%). The northwest direction of airflow contributed 51.6%, 49.2%, 49.6%, and 46.3% of the total airflow in Zhengzhou, Luoyang, Anyang, and Xinxiang, respectively. From the potential pollution area of each city, the Zhengzhou area was mainly concentrated in Henan province, the Luoyang area was mainly concentrated in the south of Henan province and Fen-wei plain, and the Anyang and Xinxiang areas were mainly concentrated in Henan province and the Beijing-Tianjin-Hebei transport belt. The pollution levels of OC in Anyang and Xinxiang were also affected by the northwest Anhui, southwest Shandong, southeast Shanxi, and north Shaanxi.

[Characterization, Sources, and Health Risks of PM2.5-bound PAHs During Autumn and Winter in Luoyang City].

In this study, PM2.5 samples were collected synchronously at Gaoxin and Linxiao in Luoyang City during autumn and winter (4 October 2018 to 30 January 2019). Sixteen priority polycyclic aromatic hydrocarbons (PAHs) associated with fine particulate matter were analyzed by gas chromatography mass spectrometry (GC-MS). The concentrations and composition characteristics of the PAHs on clean and polluted days were studied. Diagnostic ratio analysis and principal component analysis (PCA) were used to identify the emission sources of PM2.5-bound PAHs and the equivalent carcinogenic concentration of benzo[a]pyrene (BaP) and incremental lifetime cancer risks (ILCRs) model were applied to evaluate health risks. During the sampling period, the concentrations of PAHs at Gaoxin and Linxiao ranged 24.33-90.26 ng·m-3 and 23.81-76.99 ng·m-3, respectively. With the increase in PM2.5 pollution, PAH concentrations increase significantly (the mean PAH concentration on polluted days was approximately 1.3 times higher than during clean days). PAH profiles at different polluting levels were similar; 4-ring PAHs (43%-48%) > 5-6 ring PAHs (32%-35%) > 2-3-ring PAHs (20%-22%). Diagnostic ratios and PCA demonstrated that PAHs in the study area were mainly derived from combustion sources including coal combustion, biomass burning, and motor vehicle emissions. The coal combustion was the main pollution source in the study area (clean days=49.28%-56.38%, polluted days=49.44%-60.60%). The results of the equivalent carcinogenic concentration of benzo[a]pyrene (BaP) and ILCR model revealed that the human health risk on polluted days was higher. Moreover, the cancer risks from adult exposure to PAHs were higher than those child exposure, which has an acceptable level of risk (<10-6).

Analysis of Immune Landscape Reveals Prognostic Significance of Cytotoxic CD4+ T Cells in the Central Region of pMMR CRC.

BACKGROUND: Mismatch repair proficient colorectal cancer (pMMR CRC) lacks effective treatments and has a poor prognosis, which can be attributed to the complexity of tumor microenvironment. The coordinated function of immune cells is vital to anti-tumor immunity. However, the spatial characteristics of immune cells in the pMMR CRC immune microenvironment and their relationship with clinical prognosis are not fully understood. Meanwhile, the immune modulatory effect of neoadjuvant chemotherapy (NCT), which is the first-line treatment of pMMR CRC, needs further investigation. Therefore, this study aims to explore the spatial dynamics of immune cells and its prognostic value in pMMR CRC. METHODS: We analyzed the various immune cells in formalin-fixed, paraffin-embedded tumor tissues which were collected from 77 patients with stage II/III of pMMR CRC, including 39 non-NCT treated and 38 NCT treated patients. We used the optimized multiplex immunohistochemistry (mIHC) to identify and quantify the density, type and location of immune cells in pMMR CRC. Multivariate survival analysis was performed to assess the relationship of immune profiles and clinical prognosis of pMMR CRC patients. RESULTS: The densities of most T cell subsets, B cells and macrophages were higher in the central region of the pMMR CRC than in the invasion margin. Tumor infiltrating lymphocytes (TILs), especially the infiltration of CD4+ GzmB+ T cells in the central region of the tumor was identified to be positively correlated with the prognosis of the patients. Multivariate analysis confirmed that CD4+ GzmB+ T cells population was an independent predictor of disease-free survival (DFS) in non-NCT group. Meanwhile, NCT enhanced the infiltration of CD4+ GzmB+ T cells in the central region of the pMMR CRC, which was also identified as an independent protective factor of overall survival (OS) and DFS in NCT group. CONCLUSION: We demonstrated that the level of CD4+ GzmB+ T cells located in the center of tumor could provide great prognostic value for pMMR CRC patients. And the application of neoadjuvant chemotherapy further improves the infiltration of CD4+ GzmB+ T cells in the central compartment. Further studies into the application of CD4+ GzmB+ T cells in tumor immunotherapy are needed.

Potentiating CD8+ T cell antitumor activity by inhibiting PCSK9 to promote LDLR-mediated TCR recycling and signaling.

Metabolic regulation has been proven to play a critical role in T cell antitumor immunity. However, cholesterol metabolism as a key component of this regulation remains largely unexplored. Herein, we found that the low-density lipoprotein receptor (LDLR), which has been previously identified as a transporter for cholesterol, plays a pivotal role in regulating CD8+ T cell antitumor activity. Besides the involvement of cholesterol uptake which is mediated by LDLR in T cell priming and clonal expansion, we also found a non-canonical function of LDLR in CD8+ T cells: LDLR interacts with the T-cell receptor (TCR) complex and regulates TCR recycling and signaling, thus facilitating the effector function of cytotoxic T-lymphocytes (CTLs). Furthermore, we found that the tumor microenvironment (TME) downregulates CD8+ T cell LDLR level and TCR signaling via tumor cell-derived proprotein convertase subtilisin/kexin type 9 (PCSK9) which binds to LDLR and prevents the recycling of LDLR and TCR to the plasma membrane thus inhibits the effector function of CTLs. Moreover, genetic deletion or pharmacological inhibition of PCSK9 in tumor cells can enhance the antitumor activity of CD8+ T cells by alleviating the suppressive effect on CD8+ T cells and consequently inhibit tumor progression. While previously established as a hypercholesterolemia target, this study highlights PCSK9/LDLR as a potential target for cancer immunotherapy as well.

Gastrointestinal stromal tumor with a PDGFRA mutation masquerading as gastric plexiform fibromyxoma: A comparative clinicopathological study of two cases.

Gastric plexiform fibromyxoma (PF) is a rare mesenchymal tumor with a histologically distinctive multinodular pattern, dissimilar to conventional gastrointestinal stromal tumor (GIST). The current study presents one case of gastric PF, and one case of GIST with a platelet-derived growth factor receptor α (PDGFRA) mutation mimicking PF, and discusses their differential diagnoses. The two patients were a 51-year-old male with PF and a 47-year-old female with GIST, each of whom presented with an occupying lesion in the gastric antrum. Histologically, the two cases shared a rare and approximately unanimous morphological pattern of a prominent multinodular and plexiform figuration in the gastric wall, including mucoid matrix, short spindle cells and small caliber vascular elements, and areas of stromal tumor cells exhibited an epithelioid appearance. Immunohistochemistry revealed that the PF tumor cells were positive for smooth muscle actin (SMA), but negative for mast/stem cell growth factor receptor (KIT), GIST-1 (DOG1), cluster of differentiation (CD) 34, S-100, desmin and cytokeratin AE1/AE3. The case of GIST expressed KIT and DOG1, but was negative for SMA, CD34, S-100, desmin and AE1/AE3. In addition, the GIST case, which was observed to harbor a D842V mutation in exon 18 of PDGFRA, was demonstrated to be genetically distinct from PF. The cases presented in the current study were uncommon in that GIST exhibited a plexiform appearance that mimicked the histology of the rare PF tumor; therefore, GIST must be considered and discounted first when determining a differential diagnosis for a gastrointestinal mesenchymal neoplasm.

Spindle cell/sclerosing rhabdomyosarcoma: case series from a single institution emphasizing morphology, immunohistochemistry and follow-up.

Spindle cell/sclerosing rhabdomyosarcoma is a rare skeletal-muscle tumor with distinctive clinicopathologic characteristics. 10 cases (6 cases of spindle cell rhabdomyosarcoma and 4 cases of scleroisng rhabdomyosarcoma) were composed of 6 males and 4 females aging from 5 months to 57 years, with median age 33 years, most of who represented a painless solid mass. Histologically, the tumors were composed of fascicles of spindle cells or primitive round cells embed in sclerotic matrix with presence of rhabdomyoblasts in varying proportion. Immunohistochemically, the tumor cells expressed MyoD1 (10/10), Desmin (10/10), myogenin (6/10), AE1/AE3 (2/10), EMA (2/10), but were negative for SMA, caldesmon, S-100. All of the patients underwent a complete surgical resection without or with chemotherapy (2/10) or radiotherapy (1/10). During the follow-up period (1 to 24 months), 1 patient was succumbed, and 2 cases showed in situ recurrence with 1 of them adopting metastasis. Our cases further demonstrate there do present some clincopathologic relations between spindle cells rhabdomyosarcoma and sclerosing rhabdomyosarcoma, but the latter seems to have a better prognosis. Exact grading and staging contribute to predict the outcome.