Development and validation of clinical-radiomics analysis for preoperative prediction of IDH mutation status and WHO grade in diffuse gliomas: a consecutive L-[methyl-11C] methionine cohort study with two PET scanners.

PURPOSE: Determination of isocitrate dehydrogenase (IDH) genotype is crucial in the stratification of diagnosis and prognostication in diffuse gliomas. We sought to build and validate radiomics models and clinical features incorporated nomogram for preoperative prediction of IDH mutation status and WHO grade of diffuse gliomas with L-[methyl-11C] methionine ([11C]MET) PET/CT imaging according to the 2016 WHO classification of tumors of the central nervous system. METHODS: Consecutive 178 preoperative [11C]MET PET/CT images were retrospectively studied for radiomics analysis. One hundred six patients from PET scanner 1 were used as training dataset, and 72 patients from PET scanner 2 were used for validation dataset. [11C]MET PET and integrated CT radiomics features were extracted, respectively; three independent predictive models were built based on PET features, CT features, and combined PET/CT features, respectively. The SelectKBest method, Spearman correlation analysis, Least Absolute Shrinkage and Selection Operator (LASSO) regression, and machine learning algorithms were applied for feature selection and model building. After filtering the satisfactory predictive model, key clinical features were incorporated for the nomogram establishment. RESULTS: The combined [11C]MET PET/CT radiomics model, which consisted of four PET features and eight integrated CT features, was significantly associated with IDH genotype (p < 0.0001 for both training and validation datasets). Nomogram based on the [11C]MET PET/CT radiomics score, patients' age, and dichotomous tumor location status showed satisfactory discrimination capacity, and the AUC was 0.880 (95% CI, 0.726-0.998) in the training dataset and 0.866 (95% CI, 0.777-0.956) in the validation dataset. In IDH stratified WHO grade prediction, the final radiomics model consists of four PET features and two CT features had reasonable and stable differential efficacy of WHO grade II and III patients from grade IV patients in IDH-wildtype patients, and the AUC was 0.820 (95% CI, 0.541-1.000) in the training dataset and 0.766 (95% CI, 0.612-0.921) in the validation dataset. CONCLUSION: [11C]MET PET radiomics features could benefit non-invasive IDH genotype prediction, and integrated CT radiomics features could enhance the efficacy. Radiomics and clinical features incorporation could establish satisfactory nomogram for clinical application. This non-invasive predictive investigation based on our consecutive cohort from two PET scanners could provide the perspective to observe the differential efficacy and the stability of radiomics-based investigation in untreated diffuse gliomas.

LncRNA MAFG-AS1 Upregulates Polo-Like Kinase-1 by Sponging miR-505 to Promote Gastric Adenocarcinoma Cell Proliferation.

Gastric cancer is a commonly diagnosed, often fatal malignancy and requires novel anticancer therapies and preventative approaches. This study described the involvement of MAFG-AS1, a lncRNA with important functions in cancer biology, in gastric adenocarcinoma (GA). Thirty-six male and forty-two female GA patients with an average age of 51.9 ± 5.7 years in the range of 35 to 68 years were enrolled. Paired gastric cancer (GC) and non-tumor tissues were collected from each patient. MAFG-AS1 expression was determined. RNA interaction prediction, dual luciferase reporter assay, RT-qPCR assay, Western blot, and CCK-8 assay were conducted. The results indicated that MAFG-AS1 was highly expressed in GA and closely correlated with poor survival. MAFG-AS1 interacted with miR-505, but MAFG-AS1 and miR-505 overexpression showed no significant effects on each other's expression. In addition, MAFG-AS1 increased the expression of PLK1, a miR-505 target. MAFG-AS1 and PLK1 overexpression increased GC cell proliferation rate. MiR-505 overexpression reduced the effects of MAFG-AS1 and PLK1 overexpression on cell proliferation. Therefore, MAFG-AS1 might upregulate PLK1 by sponging miR-505 to promote GA cell proliferation.

The multiple effects of fecal microbiota transplantation on diarrhea-predominant irritable bowel syndrome (IBS-D) patients with anxiety and depression behaviors.

BACKGROUND: Anxiety and depression are complications in Irritable bowel syndrome (IBS) patients. In this study, we recruited 18 IBS patients with mild-modest anxiety and depression behaviors, and after the screening, we defined the FMT treatment group (n = 9) and the control group (n = 9). The IBS symptom severity scale (IBS-SSS), Hamilton Anxiety Rating Scale (HAM-A), Hamilton Depression Rating Scale (HAM-D), Irritable Bowel Syndrome Quality of Life (IBS-QOL) and Bristol stool scale (BSS) were evaluated one week before FMT (baseline), one-week-, one-month-, two-month-, and three-month-following FMT. Meanwhile, we determined the SCFAs in the patient's feces and serum and continued the metagenomic analysis of the microorganisms in the patient's feces. RESULTS: The results showed that the patient's anxiety and depression behavior gradually improved with FMT treatment. Moreover, the illness and quality of life had also been relieved significantly. The content of isovaleric acid and valeric acid was significantly reduced in the FMT group compared to the Col group. Metagenomic analysis showed that FMT treatment decreased the abundance of Faecalibacterium, Eubacterium and Escherichia. From KEGG functional analysis, we confirmed that the top five abundant pathways were "bacterial chemotaxis, "flagellar assembly", "glycine, serine and threonine metabolism", "apoptosis", and "bacterial invasion of epithelial cells". CONCLUSIONS: FMT treatment can effectively alleviate the anxiety and depression behaviors of IBS-D patients and reduce the IBS-SSS score, indicating that FMT can improve patients' symptoms. The high throughput sequencing results show that Bifidobacterium and Escherichia play the most critical role in the formation and recovery of IBS-D patients. The GC/MS data indicated that faeces isovaleric acid and valeric acid might be more suitable as a metabolic indicator of IBS-D remission. Trial registration ChiCTR, ChiCTR1900024924, Registered 3 August 2019, https://www.chictr.org.cn/showproj.aspx?proj=41676 .

A comprehensive approach to stool donor screening for faecal microbiota transplantation in China.

BACKGROUND: Faecal microbiota transplantation (FMT) is an effective therapy for recurrent Clostridium difficile infections and chronic gastrointestional infections. However, the risks of FMT and the selection process of suitable donors remain insufficiently characterized. The eligibility rate for screening, underlying microbial basis, and core ethical issues of stool donors for FMT are yet to be elucidated in China. RESULTS: The potential stool donors were screened from December 2017 to December 2019 with the help of an online survey, clinical assessments, and stool and blood testing. Bioinformatics analyses were performed, and the composition and stability of gut microbiota in stool obtained from eligible donors were dynamically observed using metagenomics. Meanwhile, we build a donor microbial evaluation index (DoMEI) for stool donor screening. In the screening process, we also focused on ethical principles and requirements. Of the 2071 participants, 66 donors were selected via the screening process (3.19% success rate). Although there were significant differences in gut microbiota among donors, we found that the changes in the gut microbiota of the same donor were typically more stable than those between donors over time. CONCLUSIONS: DoMEI provides a potential reference index for regular stool donor re-evaluation. In this retrospective study, we summarised the donor recruitment and screening procedure ensuring the safety and tolerability for FMT in China. Based on the latest advances in this field, we carried out rigorous recommendation and method which can assist stool bank and clinicians to screen eligible stool donor for FMT.

LncRNA SUMO1P3 promotes proliferation and inhibits apoptosis in colorectal cancer by epigenetically silencing CPEB3.

Colorectal cancer (CRC) is a prevalent malignancy characterized with high morbidity and death rate. Due to late diagnosis, most CRC patients missed the proper timing for radical operation, which led to the high mortality in CRC. Therefore, identifying new prognostic and therapeutic targets is important. Long non-coding RNAs are reported as essential regulators for tumor progression, including in CRC. LncRNA SUMO1P3 has been documented as an oncogene promoting proliferation, cell cycle, and metastasis in several cancers, but its role in CRC has never been unveiled. The purpose of our study is to interrogate the functions and mechanism of SUMO1P3 in colorectal cancer. We validated the upregulation and the prognostic significance of SUMO1P3 in CRC. The loss-of-function assays suggested that SUMO1P3 provoked CRC cell proliferative ability, and retarded apoptotic ability. Cytoplasmic polyadenylation element binding protein 3 (CPEB3) has been newly acknowledged as a tumor suppressive gene in several cancers, and has been revealed to present low expression in CRC. We predicted through UCSC database and validated by ChIP assay that EZH2, a crucial regulator of trimethylation of histone H3 at lysine 27 (H3K27me3), bound to CPEB3 promoter. Further, we validated that SUMO1P3 epigenetically repressed CPEB3 through EZH2. Finally, rescue assays indicated that SUMO1P3 provoked proliferation, cell cycle, and retarded apoptosis through CPEB3. Consequently, current study showed that lncRNA SUMO1P3 promoted cell proliferative ability and inhibited apoptotic ability in CRC by epigenetically silencing CPEB3, providing a novel prognostic marker for CRC patients.

Long non-coding RNA LINC01314 represses cell migration, invasion, and angiogenesis in gastric cancer via the Wnt/ß-catenin signaling pathway by down-regulating KLK4.

BACKGROUND: In recent years, gastric cancer (GC) has become a major cause of mortality among various malignancies worldwide with high incidence rates. Long non-coding RNA (lncRNAs) may serve as oncogenes and tumor suppressors in cancers. Therefore, we investigated the effect of LINC01314 on the development of GC cells in relation to the Wnt/ß-catenin signaling pathway. METHODS: Microarray data analysis was conducted to screen GC-related differentially expressed lncRNAs, followed by determination of the binding interaction between LINC01314 and kallikrein 4 (KLK4). Human GC cell line SGC-7901 was treated with over-expressed or silenced LINC01314 or KLK4 to investigate the mechanism LINC01314 affecting GC cellular activities. The levels of KLK4, Wnt-1, ß-catenin, cyclin D1, N-cadherin and E-cadherin were measured, and cell invasion and migration were evaluated. Next, the tumor weight, micro-vessel density (MVD) and the expression of VEGF-C and VEGFR-3 in transplanted tumors were measured. RESULTS: LINC01314 was poorly expressed in GC cells and KLK4 was revealed to be a direct target gene of LINC01314. Overexpressed LINC01314 or silencing of KLK4 led to inhibited GC cell migration and invasion, corresponding to decreased Wnt-1, ß-catenin, cyclin D1 and N-cadherin while increased E-cadherin. Also, in response to over-expression of LINC01314 or silencing of KLK4, tumor weight and the MVD of transplanted tumors were reduced and angiogenesis was suppressed, which was indicated by down-regulated positive expression of VEGF-C and VEGFR-3. CONCLUSION: The findings indicated that over-expression of LINC01314 down-regulated KLK4 to inhibit the activation of the Wnt/ß-catenin signaling pathway, thus suppressing migration, invasion, and angiogenesis in GC cells, which provides new insight for the treatment of GC.

Effect of somatostatin on prevention of post-endoscopic retrograde cholangiopancreatography pancreatitis and hyperamylasemia: A systematic review and meta-analysis.

OBJECTIVE: To perform a meta-analysis of all available studies on the effect of prophylactic somatostatin administration on prevention of post-endoscopic retrograde cholangiopancreatography (ERCP) pancreatitis (PEP) and post-ERCP hyperamylasemia (PEHA). METHODS: Electronic databases, including PubMed, EMBASE, the Cochrane library, and the Science Citation Index were searched to retrieve relevant trials. Randomized, placebo-controlled trials in adult patients that compared somatostatin versus placebo in prevention of PEP were included. Meta-analysis was performed using a random-effects model to assess the ratios of PEP, PEHA and post-ERCP abdominal pain. RESULTS: Total ratio of PEP of somatostatin group was significantly lower than that of placebo group. For the short-term injection or bolus injection there were no heterogeneity and no significance between the ratio of PEP of somatostatin group and placebo group. For the long-term injection subgroup there was heterogeneity, and the ratio of PEP of somatostatin group was significantly lower than that of placebo group. There was no significance between the ratio of PEP of somatostatin group and placebo group for the low-risk PEP subgroup, while the ratio of PEP of somatostatin group was significantly lower than that of placebo group for the high-risk PEP subgroup. The ratio of PEP of somatostatin group was significantly lower than that of placebo group for the long-term injection high-risk PEP subgroup. There was no significance between the ratio of PEHA of somatostatin group and placebo group for the short-term injection subgroup or bolus injection subgroup. The ratio of PEHA of somatostatin group was significantly lower than that of placebo group for the long-term injection subgroup. The total ratio of post-ERCP abdominal pain of somatostatin group was significantly lower than that of placebo group. The funnel plot of incidence of PEP and PEHA showed no asymmetry with a negative slope. CONCLUSION: Prophylactic use of long-term injection of somatostatin can significantly reduce the incidence of PEP, PEHA and post-ERCP abdominal pain for the high-risk PEP patients, while it is not necessary to be used for the low-risk PEP patients.

Conventional and Diffusional Magnetic Resonance Imaging Features of Mitochondrial Encephalomyopathy, Lactic Acidosis, and Stroke-Like Episodes in Chinese Patients: A Study of 40 Cases.

PURPOSES: The aims of the study were to analyze the conventional and diffusion-weighted MRI (DWI) of mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS) and to investigate underlying mechanisms. METHODS: Features of 58 acute and 68 chronic stroke-like lesions as well as global brain abnormalities of 40 Chinese MELAS patients were analyzed. RESULTS: Gyriform DWI hyperintensity with decreased apparent diffusion coefficient (ADC) and patchy DWI hyperintensity with normal ADC were noted in 56 of 58 and 2 of 58 cortical regions of acute lesions, respectively. High ADC and mix of low and high ADC were observed in 51 of 58 and 5 of 58 affected subcortical white matters, respectively. Lacunar infarcts existed in 23 of 40 patients. Among 17 patients who have been followed, recurrence, progression, and progressive atrophy were noted in 8, 9, and 4 cases, respectively. CONCLUSIONS: This study demonstrates the conventional and diffusional MRI features of MELAS, suggesting a model of acute stroke-like lesions in which the cortex manifest with cytotoxic edema and the subcortical area with vasogenic edema.

Evaluation of the applicability of territorial arterial spin labeling in meningiomas for presurgical assessments compared with 3-dimensional time-of-flight magnetic resonance angiography.

OBJECTIVES: To prospectively evaluate the application of territorial arterial spin labelling (t-ASL) in comparison with unenhanced three-dimensional time-of-flight magnetic resonance angiography (3D-TOF-MRA) in the identification of the feeding vasculature of meningiomas. METHODS: Thirty consecutive patients with suspected meningiomas underwent conventional MR imaging, unenhanced 3D-TOF-MRA and t-ASL scanning. Four experienced neuro-radiologists assessed the feeding vessels with different techniques separately. RESULTS: For the identification of the origin of the feeding arteries on t-ASL, the inter-observer agreement was excellent (к = 0.913), while the inter-observer agreement of 3D-TOF-MRA was good (к = 0.653). The inter-modality agreement between t-ASL and 3D-TOF-MRA for the feeding arteries was moderate (к = 0.514). All 8 patients with motor or sensory disorders proved to have meningiomas supplied completely or partially by the internal carotid arteries, while all 14 patients with meningiomas supplied by the external carotid arteries or basilar arteries didn't show any symptoms concerning motor or sensory disorders (p = 0.003). CONCLUSION: T-ASL could complement unenhanced 3D-TOF-MRA and increase accuracy in the identification of the supplying arteries of meningiomas in a safe, intuitive, non-radioactive manner. The information about feeding arteries was potentially related to patients' symptoms and pathology, making it more crucial for neurosurgeons in planning surgery as well as evaluating prognosis. KEY POINTS: • A comprehensive understanding of feeding vasculature is helpful for optimized treatment decisions. • T-ASL could identify main supplying arteries of meningiomas with excellent inter-observer agreement. • The inter-modality agreement for identification of the main feeding arteries was moderate. • Blood supply from ICAs was related to motor or sensory disorders. • High-level meningiomas were found to have double main supplying arteries.

Differentiating Primary Central Nervous System Lymphomas From Glioblastomas and Inflammatory Demyelinating Pseudotumor Using Relative Minimum Apparent Diffusion Coefficients.

OBJECTIVE: Our purpose was to evaluate the diagnostic performance of diffusion-weighted imaging, the relative minimum apparent diffusion coefficient (rADCmin) in differentiating primary central nervous system lymphomas (PCNSLs) from glioblastomas (GBMs) and inflammatory demyelinating pseudotumors (IDPs). MATERIALS AND METHODS: Magnetic resonance images were reviewed retrospectively in 82 patients including 39 PCNSLs, 35 GBMs, and 8 IDPs. Regions of interest were drawn around the tumor on contrast-enhanced axial images; these images were transferred onto coregistered ADC maps to obtain the ADCmin, and the normalized ADCmin ratios (rADCmin) were calculated using the formula rADCmin = ADCmin of the lesion / ADCmin of the normal white matter. The rADCmin values were compared between PCNSLs, GBMs, and IDPs using the analysis of variance test. Receiver operating characteristic curves were constructed to evaluate the diagnostic performance of rADCmin values and to determine the optimum thresholds. Simple logistic regression was analyzed to evaluate the relationship between ADCs and tumor cellularity. RESULTS: The rADCmin value was significantly lower in PCNSLs (0.675 ± 0.113) than GBMs (0.765 ± 0.059) and IDPs (0.834 ± 0.067) (PCNSL vs GBM, P < 0.001; PCNSL vs IDP, P < 0.001). Relative ADCmin was a significant assessor for differentiating PCNSLs from non-PCNCLs (P < 0.001). The optimal cutoff value was 0.722 (sensitivity, 74.5%; specificity, 74.1%; area under the curve, 0.803) on receiver operating characteristic analysis. A stronger negative correlation (r = -0.755, P = 0.000) was obtained between the cytoplasm and rADCmin. CONCLUSIONS: Relative ADCmin value is helpful in differentiating PCNSL from GBM and IDP. Thus, ADC values may provide a useful supplement to the information obtained from conventional contrast-enhanced magnetic resonance imaging and assist in future treatment planning.

Combination of diffusion tensor imaging and conventional MRI correlates with isocitrate dehydrogenase 1/2 mutations but not 1p/19q genotyping in oligodendroglial tumours.

OBJECTIVES: To explore the correlations of conventional MRI (cMRI) and diffusion tensor imaging (DTI) values with the 1p/19 codeletion and IDH mutations in oligodendroglial tumours (OTs). METHODS: Eighty-four patients with OTs who underwent cMRI and DTI were retrospectively reviewed. The maximal fractional anisotropy and minimal apparent diffusion coefficient (ADC) were measured and compared using the Mann-Whitney U test. Receiver operating characteristic curves, logistic regression analysis and four-table statistics analysis were performed to predict genotypings. RESULTS: OTs with 1p/19q codeletion or IDH mutations were prone to locate in frontal (P = 0.106 and 0.005, respectively) and insular lobes and were associated with absent or blurry contrast enhancement (P = 0.040 and 0.013, respectively). DTI values showed significant differences between OTs with and without IDH mutations (P < 0.05) but not in OTs with and without 1p/19q loss. The Ki-67 index significantly correlated with IDH mutations (P = 0.002) but not with 1p/19q codeletion. A combination of DTI and cMRI for the identification of IDH mutations resulted in sensitivity, specificity, positive and negative predictive values of 92.2 %, 75.8 %, 93.8 % and 71.1 %, respectively. CONCLUSIONS: Combination of DTI and cMRI correlates with isocitrate dehydrogenase 1/2 mutations but not 1p/19q genotyping in OTs. KEY POINTS: • OTs with 1p/19q codeletion were associated with absent or blurry contrast enhancement • OTs with IDH mutations were also associated with absent or blurry contrast enhancement • OTs with IDH mutations were prone to locate in frontal and insular lobes • DTI values can provide a non-invasive method for assessing the IDH status of OTs • A combination of DTI and cMRI correlates with isocitrate dehydrogenase 1/2 mutations.

High selectivity of PI3Kß inhibitors in SETD2-mutated renal clear cell carcinoma.

PURPOSE: Clear cell renal cell carcinoma (ccRCC) is characterized with frequent mutations of SETD2 gene and our purpose was to explore targeted therapy for this entity. METHODS: By bioinformatic investigation of two major databases, the Genomics of Drug Sensitivity in Cancer (GDSC) database and The Cancer Genome Atlas (TCGA) database, we identified the selective PI3Kß inhibitors TGX221 and AZD6482 as selective inhibitors for ccRCC with SETD2 mutations, with AZD6482 additionally targeting PIK3CA and CDK6 mutations. RESULTS: Further investigation on AZD6482 profile revealed that mutations in RB1, KRAS, NRAS and APC contributed in drug resistance. Changes in both AZD6482-sensitive and -resistant gene sets showed limited impact on prognosis. Western blotting showed AZD6482 did not induce changes in a panel of major downstream effectors of AKT, but substantially increased PMS2 level. AZD6482 also selectively inhibited migration, invasiveness, and colony formation of ccRCC cells with SETD2 mutations. Integrative network analysis revealed complex interactions between these genes except SETD2. CONCLUSION: AZD6482 is a novel inhibitor with high selectivity for ccRCC SETD2 mutations. Increased activity of PI3K/AKT/PMS2 could play a role in SETD2 mutated ccRCC.

Serum HSP70 and VEGF levels are effective predictive factors of chemoradiosensitivity and prognosis of pancreatic cancer patients.

AIM: To evaluate the value of serum HSP70 and VEGF levels for predicting the chemoradiosensitivity of the pancreatic cancer patients. METHODS: A total of 255 patients with pancreatic cancer and 60 healthy subjects were enrolled in this study. Serum levels of HSP70 and VEGF were measured using enzyme-linked immunosorbent assay (ELISA) for the pre-treatment, during-treatment and post- chemoradiotherapy time-points. The results were analyzed to evaluate the potential of serum HSP70 and VEGF levels for predicting the chemoradiosensitivity of pancreatic cancer patients. RESULTS: The serum levels of both HSP70 and VEGF were found to be elevated in pancreatic cancer patients as compared to healthy subjects. After chemoradiotherapy treatment, 179 patients showed effective clinical response [complete response (CR) + partial response (PR)] while 76 patients showed ineffective clinical response [stable disease (SD) + progressive disease (PD)]. Compared with the pre-treatment levels, serum levels of HSP70 and VEGF were higher during chemoradiotherapy, and lower post-treatment in the effective group. However, serum levels of HSP70 and VEGF were higher during and after treatment in the ineffective group. At any given timepoint, serum levels of HSP70 and VEGF were higher in the ineffective group as compared to those of the effective group. The overall survival (OS) and progression free survival (PFS) trends were: HSP70 High/VEGFHigh < HSP70High/VEGFLow or HSP70Low/VEGFHigh < HSP70Low/VEGFLow. Serum levels of HSP70 and VEGF were individually effective, and their combination was even more effective in predicting the chemoradiosensitivity of pancreatic cancer patients. HSP70 and VEGF expression were independent risk factors for OS and PFS of pancreatic cancer patients. CONCLUSION: Higher levels of serum HSP70 and VEGF were associated with lower radiosensitivity and worse prognosis, while lower levels of serum HSP70 and VEGF were associated with improved radiosensitivity and better prognosis of pancreatic cancer patients.

Effect of enteral nutrition and ecoimmunonutrition on bacterial translocation and cytokine production in patients with severe acute pancreatitis.

BACKGROUND: Severe acute pancreatitis (SAP) with severe complications such as multiple organ failure, necrosis, abscess, and formation of pancreatic pseudocysts often gives rise to a high mortality despite intensive treatment. Parenteral nutrition (PN), elemental enteral nutrition, and ecoimmunonutrition (EIN) hastened the recovery of SAP patients, stimulated gastrointestinal motility, and alleviated the degree of systemic inflammatory response syndrome. This study aimed to examine the effects of enteral nutrition (EN) and EIN on bacterial translocation and cytokine production in patients with SAP. METHODS: One hundred eighty-three SAP patients were randomly divided into three groups receiving PN, EN, or EN + EIN. Acute Physiology and Chronic Health Evaluation II scores, complications (systemic inflammatory response syndrome, multiorgan failure, and infections), intestinal bacterial strains of stool, and plasma concentrations of endotoxin, tumor necrosis factor α (TNF-α), and interleukin (IL) 6 and IL-10 were evaluated. RESULTS: The percentage of pancreatic sepsis, multiple organ dysfunction syndrome, and mortality was significantly lower in the EN group and was further lower in the EN + EIN group than that in the PN group. The plasma concentrations of TNF-α and IL-6 and APACHE II scores were significantly decreased in the EN group and were further lowered in the EN + EIN group than those in the PN group. The plasma concentration of IL-10 was higher in the EN group and was further increased in the EN + EIN group than that in the PN group. CONCLUSIONS: EN plays effective roles in the treatment of SAP by decreasing the expression of endotoxin, TNF-α, and IL-6 and the bacterial translocation, enhancing the expression of IL-10, and the combination of EIN with EN results in more therapeutic benefits than EN alone.

SPI1 Mediates N-Myristoyltransferase 1 to Advance Gastric Cancer Progression via PI3K/AKT/mTOR Pathway.

Gastric cancer (GC) is a common digestive tract malignancy worldwide. N-myristoyltransferase 1 (NMT1) has been implicated in many cancers, but its association with gastric cancer remains to be clarified. Thus, this paper elucidated the role of NMT1 in GC. The NMT1 expression level in GC and normal tissue samples as well as the relationship between NMT1 high or low expression and overall survival in GC was analyzed via GEPIA. GC cells were transfected with NMT1 or SPI1 overexpression plasmid and short hairpin RNA against NMT1 (shNMT1) or shSPI1. NMT1, SPI1, p-PI3K, PI3K, p-AKT, AKT, p-mTOR, and mTOR levels were detected through qRT-PCR and western blot. MTT, wound healing, and transwell assays were applied to test cell viability, migration, and invasion. The binding relationship of SPI1 and NMT1 was determined through a dual-luciferase reporter assay and chromatin immunoprecipitation. NMT1 was upregulated in GC, the high level of which connected with a poor prognosis. Overexpressed NMT1 elevated viability, migration rate, and invasion rate of GC cells, whereas NMT1 knockdown leads to the opposite results. Besides, SPI1 could bind to NMT1. Overexpressed NMT1 reversed the effects of shSPI1 on decreasing viability, migration, invasion, p-PI3K/PI3K, p-AKT/AKT, and p-mTOR/mTOR in GC cells, and NMT1 knockdown reversed the effects of SPI1 overexpression on increasing viability, migration, invasion, p-PI3K/PI3K, p-AKT/AKT, and p-mTOR/mTOR. SPI1 upregulated NMT1 to facilitate the malignant behaviors of GC cells through the PI3K/AKT/mTOR pathway.

A Matching Strategy To Guide Donor Selection for Ulcerative Colitis in Fecal Microbiota Transplantation: Meta-Analysis and Analytic Hierarchy Process.

Fecal microbiota transplantation (FMT) targeting gut microbiota has recently been applied to the treatment of ulcerative colitis (UC). However, preliminary trials showed that only a subset of patients responded to FMT, and the heterogeneity in donor gut microbiota probably played important roles in patients' responses, implying the significance of matching an appropriate donor to a specified patient. We developed a strategy to build a donor-recipient matching model to guide rational donor selection for UC in FMT. We collected and uniformly reanalyzed 656 fecal 16S rRNA gene sequencing samples (350 from UC patients and 306 from healthy subjects) from 9 studies. Significantly lower α-diversity indexes were observed in UC patients by random effects model. Thirty-four bacterial genera and 34 predicted pathways were identified with significant odds ratios and classification potentials for UC patients. Based on six bacterial indicators, including richness, overall distance, genera, and pathways (beneficial and harmful), the analytic hierarchy process-based donor-recipient matching model was set to rank and select appropriate donors for patients with UC. Finally, the model showed favorable classification powers (>70%) for FMT effectiveness in two previous clinical trials. This study revealed the dysbiosis of fecal bacterial diversity, composition, and predicted pathways of patients with UC by meta-analysis and hereby developed a donor-recipient matching strategy to guide donor selection for UC in FMT. This strategy can also be applied to other diseases associated with gut microbiota. IMPORTANCE Modulation of gut microbiota by FMT from donors has been applied to the treatment of UC and yielded variable effectiveness in clinical trials. One possibility is that this variable effectiveness was related to donor selection, as a patient's response to FMT may rely on the capability of the used donor's microbiota to restore the specific gut disturbances of the patient. However, the biggest issues on the practical level are what should be considered in the selection process and how to set up such a donor-recipient matching model. In this study, we presented a bacterial profile-based donor-recipient matching strategy to guide donor selection for UC in FMT by first meta-analysis of 656 fecal 16S rRNA gene sequencing samples from 9 studies to identify significant indicators and then setting up the model by an analytic hierarchy process. The applicability and accuracy of this model were verified in the data sets from two previous FMT clinical studies. Our data indicate that the donor-recipient matching model built in this study enables researchers to rationally select donors for UC patients in FMT clinical practice, although it needs more samples and prospective trials for validation. The strategy adopted in this study to leverage existing data sets to build donor-recipient matching models for precision FMT is feasible for other diseases associated with gut microbiota.

The Relationship Between Systemic Immune Inflammatory Index and Prognosis of Patients With Non-Small Cell Lung Cancer: A Meta-Analysis and Systematic Review.

Background: The relationship between systemic immune inflammation index (SII) and the prognosis of cancer has always been a subject of intense interest. However, the prognostic value of SII in non-small cell lung cancer (NSCLC) patients remains a controversial topic. Objective: To evaluate the effect of SII index on prognosis of NSCLC. Methods: We conducted a comprehensive search of PubMed, EMBASE, and the Cochrane Library databases to determine correlation between SII index, clinicopathological features, overall survival (OS), and progression-free survival (PFS). Odds ratio (ORs) and 95% confidence interval (CIs) were used to assess the connection between SII and clinicopathological parameters, and HRs and 95% CIs were used to assess the connection between SII and survival. Results: Seventeen studies with 8,877 cases were included in the analysis. Compared with NSCLC patients with low SII level, patients with NSCLC with high SII level had a poor OS (HR = 1.75, 95% CI, 1.50-2.00; P < 0.001) and had a poor PFS (HR = 1.61, 95% CI, 1.25-1.96; P < 0.001). In addition, patients with higher pathological stage (II-III) had higher SII levels (OR = 2.32, 95% CI, 2.06-2.62; P < 0.001). Conclusions: The SII index is a promising prognostic biomarker for NSCLC and may help clinicians choose appropriate NSCLC treatments.

Identification of prognostic hypoxia-related genes signature on the tumor microenvironment in esophageal cancer.

BACKGROUND: Hypoxia is a crucial factor in the development of esophageal cancer. The relationship between hypoxia and immune status in the esophageal cancer microenvironment is becoming increasingly important in clinical practice. This study aims to clarify and investigate the possible connection between immunotherapy and hypoxia in esophageal cancer. METHODS: The Cancer Genome Atlas databases are used to find two types of esophageal cancer cases. Cox regressions analyses are used to screen genes for hypoxia-related traits. After that, the genetic signature is validated by survival analysis and the construction of ROC curves. GSEA is used to compare differences in enrichment in the two groups and is followed by the CIBERSORT tool to investigate a potentially relevant correlation between immune cells and gene signatures. RESULTS: We found that the esophageal adenocarcinoma hypoxia model contains 3 genes (PGK1, PGM1, SLC2A3), and the esophageal squamous cell carcinoma hypoxia model contains 2 genes (EGFR, ATF3). The findings demonstrated that the survival rate of patients in the high-risk group is lower than in the lower-risk group. Furthermore, we find that three kinds of immune cells (memory activated CD4+ T cells, activated mast cells, and M2 macrophages) have a marked infiltration in the tissues of patients in the high-risk group. Moreover, we find that PD-L1 and CD244 are highly expressed in high-risk groups. CONCLUSIONS: Our data demonstrate that oxygen deprivation is correlated with prognosis and the incidence of immune cell infiltration in patients with both types of esophageal cancer, which provides an immunological perspective for the development of personalized therapy.

Multiomics Study Reveals Enterococcus and Subdoligranulum Are Beneficial to Necrotizing Enterocolitis.

Necrotizing enterocolitis (NEC) is a life-threatening disease for premature infants with low body weight. Due to its fragile gut microbiome and successful treatment of fecal microbiota transplantation (FMT) for intestinal disease, we aimed to reveal the multiple-omics changes after FMT and/or sulperazone treatment. In this study, 2-week-old newborn rabbits were used to simulate the NEC model and grouped into healthy control, NEC, sulperazone treatment, FTM treatment, and FMT and sulperazone combination treatment. We evaluated the intestinal pathology and survival to define the benefit from each treatment and performed microbiome and transcriptome analysis to reveal the changes in microcosmic level, which could be helpful to understand the pathogenesis of NEC and develop new strategy. We found NEC rabbits benefit more from the combination of FMT and sulperazone treatment. Combination treatment reverses a lot of microorganisms dysregulated by NEC and showed the most similar transcript profiler with healthy control. Moreover, a combination of FMT and sulperazone significantly prolonged the survival of NEC rabbits. Function enrichment showed that metabolism and viral life cycle are the most significant changes in NEC. FMT is a common therapy method for NEC. Meanwhile, in the severe situation of NEC with intestinal infection, the first therapy strategy is preferred the third-generation cephalosporin, among which sulperazone is used widely and the effect is remarkable. So, we used sulperazone to treat the rabbits with the NEC. In this research, we aim to explore the different effects on NEC between FMT and sulperazone as well as the combination. Considering the microbiome and transcriptome result, we make a conclusion that the Enterococcus and Subdoligranulum benefits NEC by influencing the bacterial phages and butyrate production, respectively.

Integrated CT Radiomics Features Could Enhance the Efficacy of 18F-FET PET for Non-Invasive Isocitrate Dehydrogenase Genotype Prediction in Adult Untreated Gliomas: A Retrospective Cohort Study.

PURPOSE: We aimed to investigate the predictive models based on O-[2-(18F)fluoroethyl]-l-tyrosine positron emission tomography/computed tomography (18F-FET PET/CT) radiomics features for the isocitrate dehydrogenase (IDH) genotype identification in adult gliomas. METHODS: Fifty-eight consecutive pathologically confirmed adult glioma patients with pretreatment 18F-FET PET/CT were retrospectively enrolled. One hundred and five radiomics features were extracted for analysis in each modality. Three independent radiomics models (PET-Rad Model, CT-Rad Model and PET/CT-Rad Model) predicting IDH mutation status were generated using the least absolute shrinkage and selection operator (LASSO) regression analysis based on machine learning algorithms. All-subsets regression and cross validation were applied for the filter and calibration of the predictive radiomics models. Besides, semi-quantitative parameters including maximum, peak and mean tumor to background ratio (TBRmax, TBRpeak, TBRmean), standard deviation of glioma lesion standardized uptake value (SUVSD), metabolic tumor volume (MTV) and total lesion tracer uptake (TLU) were obtained and filtered for the simple model construction with clinical feature of brain midline involvement status. The area under the receiver operating characteristic curve (AUC) was applied for the evaluation of the predictive models. RESULTS: The AUC of the simple predictive model consists of semi-quantitative parameter SUVSD and dichotomized brain midline involvement status was 0.786 (95% CI 0.659-0.883). The AUC of PET-Rad Model building with three 18F-FET PET radiomics parameters was 0.812 (95% CI 0.688-0.902). The AUC of CT-Rad Model building with three co-registered CT radiomics parameters was 0.883 (95% CI 0.771-0.952). While the AUC of the combined 18F-FET PET/CT-Rad Model building with three CT and one PET radiomics features was 0.912 (95% CI 0.808-0.970). DeLong test results indicated the PET/CT-Rad Model outperformed the PET-Rad Model (p = 0.048) and simple predictive model (p = 0.034). Further combination of the PET/CT-Rad Model with the clinical feature of dichotomized tumor location status could slightly enhance the AUC to 0.917 (95% CI 0.814-0.973). CONCLUSION: The predictive model combining 18F-FET PET and integrated CT radiomics features could significantly enhance and well balance the non-invasive IDH genotype prediction in untreated gliomas, which is important in clinical decision making for personalized treatment.