Brachytherapy in craniopharyngiomas: a systematic review and meta-analysis of long-term follow-up.

OBJECTIVE: Brachytherapy has been indicated as an alternative option for treating cystic craniopharyngiomas (CPs). The potential benefits of brachytherapy for CPs have not yet been clarified. The purpose of this work was to conduct a meta-analysis to analyze the long-term efficacy and adverse reactions profile of brachytherapy for CPs. MATERIALS AND METHODS: The relevant databases were searched to collect the clinical trials on brachytherapy in patients with CPs. Included studies were limited to publications in full manuscript form with at least 5-year median follow-up, and adequate reporting of treatment outcomes and adverse reactions data. Stata 12.0 was used for data analysis. RESULTS: According to the inclusion and exclusion criteria, a total of 6 clinical trials involving 266 patients with CPs were included in this meta-analysis. The minimum average follow-up was 5 years. The results of the meta-analysis showed that 1-year, 2-3 years and 5 years progression free survival rates (PFS) are 75% (95%CI: 66-84%), 62% (95%CI: 52-72%) and 57% (95%CI: 22-92%), respectively. At the last follow-up, less than 16% of patients with visual outcomes worser than baseline in all included studies. While, for endocrine outcomes, less than 32% of patients worser than baseline level. CONCLUSION: In general, based on the above results, brachytherapy should be considered as a good choice for the treatment of CP.

[Review of clinical effects of disk-up sinus reamer(DSR)-based internal sinus floor elevation with implantation in 10 years].

PURPOSE: To analyze the bone remodeling around the implant 10 years after disk-up sinus reamer(DSR)-based internal sinus floor elevation with implantation and to investigate the influence of different factors on implant retention. METHODS: The clinical and imaging data of patients undergoing DSR-based sinus floor elevation with simultaneous implantation were collected from the Department of Dental Implantology, Affiliated Hospital of Qingdao University from January 2008 to December 2011. Panoramic film and CBCT were used to measure the changes of bone mass around implant in different periods. Kaplan-Meier and Log-rank tests were used to analyze the effects of different factors on implant retention with SPSS 26.0 software package. RESULTS: The study included 98 patients with a total of 128 implants. During the follow-up of 0-168 months, 7 implants failed, and the remaining formed good osseointegration and functioned, with a 10-year cumulative retention rate of 94.53%. The height of bone formation was (0.29±0.15) mm at the top and (2.74±0.66) mm in the sinus of 75 implant sites with complete imaging data obtained ten years after surgery. Kaplan-Meier and Log-rank tests showed that 8 factors including initial bone height, elevated bone height, mucosal perforation, implant length, implant torsion, diabetes, smoking and periodontitis had significant effects on implant retention. CONCLUSIONS: The DSR-based internal sinus floor elevation with implantation is a reliable and stable bone augmentation operation for vertical bone defect in maxillary posterior region, with a 10-year cumulative retention rate of no less than 94%. Initial bone height, elevated bone height, mucosal perforation, implant length, implant torsion, diabetes, smoking and periodontitis are the important factors affecting the long-term retention rate of implants.

TT-type resonator-based differential photoacoustic spectroscopy for trace gas detection.

A novel TT-type resonator was proposed for the first time, to our knowledge, to realize differential photoacoustic (PA) detection for trace gas measurement. The special design of the TT-type resonator allows us to install the microphone at the resonant center of the acoustic field to maximize the use of the absorption-induced PA signal. To meet the requirement of low gas consumption and easy integration, the TT-type resonator-based PA cell was fabricated as a fiber-coupled module with an inner volume of only 1.1 ml. For validation, the TT-type PA cell was integrated to a photoacoustic spectroscopy (PAS) system for acetylene detection. As a result, a linearity of 0.99999 was achieved in a concentration range from 0 to 5000 ppm with a noise equivalent sensitivity of 101 ppb. The proposed TT-type resonator contributes a new style of PA cell structure to the field of PAS gas detection, combining the advantages of easy integration, low gas consumption, differential detection, and photoacoustic enhancement together.

Effectiveness of fecal DNA syndecan-2 methylation testing for detection of colorectal cancer in a high-risk Chinese population.

BACKGROUND: Colorectal cancer (CRC) is among the most prevalent and life-threatening malignancies worldwide. Syndecan-2 methylation (mSDC2) testing has emerged as a widely used biomarker for early detection of CRC in stool and serum samples. Cancer (CRC) is among the most prevalent and life-threatening malignancies worldwide. mSDC2 testing has emerged as a widely used biomarker for early detection of CRC in stool and serum samples. AIM: To validate the effectiveness of fecal DNA mSDC2 testing in the detection of CRC among a high-risk Chinese population to provide evidence-based data for the development of diagnostic and/or screening guidelines for CRC in China. METHODS: A high-risk Chinese cohort consisting of 1130 individuals aged 40-79 years was selected for evaluation via fecal mSDC2 testing. Sensitivity and specificity for CRC, advanced adenoma (AA) and advanced colorectal neoplasia (ACN) were determined. High-risk factors for the incidence of colorectal lesions were determined and a logistic regression model was constructed to reflect the efficacy of the test. RESULTS: A total of 1035 high-risk individuals were included in this study according to established criteria. Among them, 16 suffered from CRC (1.55%), 65 from AA (6.28%) and 189 from non-AAs (18.26%); 150 patients were diagnosed with polyps (14.49%). Diagnoses were established based upon colonoscopic and pathological examinations. Sensitivities of the mSDC2 test for CRC and AA were 87.50% and 40.00%, respectively; specificities were 95.61% for other groups. Positive predictive values of the mSDC2 test for CRC, AA and ACN were 16.09%, 29.89% and 45.98%, respectively; the negative predictive value for CRC was 99.79%. After adjusting for other high-risk covariates, mSDC2 test positivity was found to be a significant risk factor for the occurrence of ACN (P < 0.001). CONCLUSION: Our findings confirmed that offering fecal mSDC2 testing and colonoscopy in combination for CRC screening is effective for earlier detection of malignant colorectal lesions in a high-risk Chinese population.

Phenotypic and genotypic characterization of Marinobacterium weihaiense sp. nov. and Marinobacterium marinum sp. nov., isolated from marine sediment, and genomic properties of the genus Marinobacterium.

In this study, two novel bacterial strains were isolated from coastal sediment of Weihai, China. The two strains were Gram-stain-negative and facultatively aerobic, designated 3-1745T and A346T. Based on phenotypic, genetic and phylogenetic properties, strains 3-1745T and A346T represent two novel species of the genus Marinobacterium. The results of genome analysis revealed many central carbohydrate metabolism pathways such as gluconeogenesis, pyruvate oxidation, tricyclic acid cycle, pentose phosphate pathway and PRPP biosynthesis in the genus Marinobacterium. The ability of strains 3-1745T and A346T to utilize volatile fatty acids was experimentally confirmed. Polyhydroxyalkanoate synthases (PhaA, PhaB and PhaC) for the synthesis of polyhydroxyalkanoates were prevalent in the genus Marinobacterium. Multiple BGCs (biosynthetic gene clusters) including betalactone, ectoine, ranthipeptide, redox-cofactor, RiPPs (ribosomally synthesized post-translationally modified peptides) and T3PKS (polyketide synthases) in the genome of the genus Marinobacterium were found. Additional genome analyses suggested that the genus Marinobacterium contained diverse potential mechanisms of salt tolerance and mainly utilized oligosaccharides. This is the first report on broad genomic analyses of the genus Marinobacterium with the description of two novel species and potential ecological and biotechnological implications.

Accuracy of the Yakebot dental implant robotic system versus fully guided static computer-assisted implant surgery template in edentulous jaw implantation: A preliminary clinical study.

AIMS: To compare the accuracy of the Yakebot dental implant robotic system with that of fully guided static computer-assisted implant surgery (CAIS) template in edentulous implantation. MATERIALS AND METHODS: Thirteen patients with edentulous were recruited and divided into two groups: the Yake robotic system group (experimental) (n = 5) and the CAIS group (control) (n = 8). Postoperative cone-beam computed tomography (CBCT) was performed immediately, and the 3-dimensional positions of implants were obtained and compared with that in the preoperative design. The comparison showed platform, apical, depth, and angular deviations. A value of p < 0.05 was considered statistically significant. RESULTS: A total of 84 implants (36 in the robotic group and 48 in the CAIS group) were placed. The mean deviation at the implant platform, apex, depth, and angle in the CAIS group was 1.37 ± 0.72 mm, 1.28 ± 0.68 mm, 0.88 ± 0.47 mm, and 3.47 ± 2.02°, respectively. However, the mean deviation at the implant platform, apex, depth, and angle in the robotic group was 0.65 ± 0.25 mm, 0.65 ± 0.22 mm, 0.49 ± 0.24 mm, and 1.43 ± 1.18°, respectively. Significant differences in the four types of deviation (p < 0.05) between the two groups were observed. CONCLUSION: The accuracy of robotic system in edentulous implant placement was superior to that of the CAIS template, suggesting that robotic system is more accurate, safe, and flexible, can be considered a promising treatment in clinical practice.

Intraindividual difference in estimated GFR by creatinine and cystatin C, cognitive trajectories and motoric cognitive risk syndrome.

BACKGROUND: Intraindividual differences between estimated glomerular filtration rate (eGFR) based on cystatin C (eGFRcys) and creatinine (eGFRcr) can convey important clinical information regarding the health status. However, the clinical implications of these differences (eGFRdiff) for risk of cognitive decline and motoric cognitive risk syndrome (MCR) remains unclear. We aimed to investigate the longitudinal associations of eGFRdiff with cognitive trajectories and incident MCR. METHODS: Based on the China Health and Retirement Longitudinal Study, we identified two study sub-cohorts: one for cognitive trajectory follow-up (6423 participants; years:2011-2018) and another for incident MCR follow-up (2477 participants; years:2011-2015). The eGFRdiff was defined as eGFRcys minus eGFRcr. Adjusted ordinal and binary logistics regression models were separately used to assess the associations of eGFRdiff with cognitive trajectories and incident MCR. We also performed discordance analyses for eGFRdiff vs eGFRcys, eGFRcr or eGFR based on both creatinine and cystatin C (eGFRcys-cr). RESULTS: In the first sub-cohort, four distinct 7-year cognitive trajectories were identified. Each 1-SD higher eGFRdiff (value for eGFRcys minus eGFRcr) was associated with a lower risk of poorer cognitive trajectories (OR: 0.909, 95% CI: 0.877-0.942). In the second sub-cohort, 121 participants developed incident MCR after a 4-year follow-up. Each 1-SD higher eGFRdiff (value for eGFRcys minus eGFRcr) was linked with a 25.3% (95%CI: 16.6%-33.2%) decreased risk for MCR. The above associations persisted in individuals with normal kidney function. Additionally, the risk for cognitive decline and incident MCR was more strongly associated with eGFRcys than eGFRcr and eGFRcys-cr. For the discordance analyses, 'discordantly high eGFRdiff/low eGFR' group, but not 'discordantly low eGFRdiff/high eGFR', exhibited a significantly lower risk of poorer cognitive trajectories and MCR compared to the concordant group. CONCLUSIONS: A large negative difference between eGFRcys and eGFRcr (eGFRcys lower than eGFRcr) was associated with higher risk of cognitive decline and incident MCR. The eGFRdiff could capture additional valuable risk information beyond eGFRcys, eGFRcr, and eGFRcys-cr.

Blood Lipid Disorders in Post-Operative Craniopharyngioma Children and Adolescents and the Improvement with Recombinant Human Growth Hormone Replacement.

Context: The high prevalence of hypothalamic obesity (HO) and dyslipidemia in individuals with craniopharyngioma (CP) following surgery is a cause for increasing concern. However, few studies have explored the lipid profile in pediatric CP patients, with inconsistent findings. In addition, the role of recombinant human growth hormone (rhGH) replacement remains unclear in these patients. Objective: To compare the blood lipid profile among post-operative craniopharyngioma children and adolescents with that among healthy controls and to reveal the effects of rhGH replacement. Methods: Data of 79 post-operative craniopharyngioma children and adolescents in our center were retrospectively collected. Sixty patients underwent rhGH replacement during the follow-ups. We selected 36 patients who received rhGH replacement therapy, while 20 patients received rhGH replacement for at least 1 year and had complete lipid data before and after treatment and compared them with 19 patients who did not receive rhGH replacement therapy. Results: Craniopharyngioma patients had higher total cholesterol (TC) (5.17 vs 3.77 mmol/L), triglyceride (TG) (1.51 vs 0.73 mmol/L), and low-density lipoprotein cholesterol (LDL-C) (3.14 vs 2.10 mmol/L), and lower high-density lipoprotein cholesterol (HDL-C) (1.06 vs 1.39 mmol/L) than controls (all p < 0.001). The lipid profile of obese and non-obese patients was not significantly different. After rhGH replacement, TC was 0.90 mmol/L lower (p = 0.002) and LDL-C was 0.73 mmol/L lower (p = 0.010) than baseline. Although the baseline LDL-C was higher, patients with rhGH replacement had lower LDL-C (-0.73 mmol/L adjusted for age and sex, p = 0.045) after the initiation of replacement compared with patients without rhGH replacement. Conclusion: The lipid profile of obese and non-obese children and adolescents with craniopharyngioma was unfavorable, and rhGH replacement could improve their lipid profile.

Cooperation between IRTKS and deubiquitinase OTUD4 enhances the SETDB1-mediated H3K9 trimethylation that promotes tumor metastasis via suppressing E-cadherin expression.

Elevated expression and genetic aberration of IRTKS, also named as BAIAP2L1, have been observed in many tumors, especially in tumor progression. however, the molecular and cellular mechanisms involved in the IRTKS-enhanced tumor progression are obscure. Here we show that higher IRTKS level specifically increases histone H3 lysine 9 trimethylation (H3K9me3) by promoting accumulation of the histone methyltransferase SETDB1. Furthermore, we reveal that IRTKS recruits the deubiquitinase OTUD4 to remove Lys48-linked polyubiquitination at K182/K1050 sites of SETDB1, thus blocking SETDB1 degradation via the ubiquitin-proteasome pathway. Interestingly, the enhanced IRTKS-OTUD4-SETDB1-H3K9me3 axis leads to a general decrease in chromatin accessibility, which inhibits transcription of CDH1 encoding E-cadherin, a key molecule essential for maintaining epithelial cell phenotype, and therefore results in epithelial-mesenchymal transition (EMT) and malignant cell metastasis. Clinically, the elevated IRTKS levels in tumor specimens correlate with SETDB1 levels, but negatively associate with survival time. Our data reveal a novel mechanism for the IRTKS-enhanced tumor progression, where IRTKS cooperates with OTUD4 to enhance SETDB1-mediated H3K9 trimethylation that promotes tumor metastasis via suppressing E-cadherin expression. This study also provides a potential approach to reduce the activity and stability of the known therapeutic target SETDB1 possibly through regulating IRTKS or deubiquitinase OTUD4.

Comparison of gastrointestinal ultrasound with capsule endoscopy in patients with small bowel Crohn's disease.

OBJECTIVE: We aimed to investigate the association between gastrointestinal ultrasound (GIUS) and capsule endoscopy (CE) in assessing disease activity in patients with small bowel Crohn's disease (CD). METHODS: Medical records of 74 patients with small bowel CD who were treated at our hospital between January 2020 and March 2022 were retrospectively reviewed, including 50 men and 24 women. All patients underwent both GIUS and CE within one week after their admissions. The Simple Ultrasound Scoring of Crohn's Disease (SUS-CD) and Lewis score were used to assess disease activity during GIUS and CE, respectively. P < 0.05 was considered as statistically significant. RESULTS: The area under the receiver operating characteristic curve (AUROC) of SUS-CD was 0.90 (95% confidence interval [CI] 0.81-0.99; P < 0.001). And the diagnostic accuracy of GIUS was 79.7%, with a sensitivity of 93.6%, a specificity of 81.8%, a positive predictive value of 96.7%, a negative predictive value of 69.2% in predicting active small bowel CD. Furthermore, the agreement between GIUS and CE was assessed using Spearman's correlation analysis and SUS-CD was correlated with Lewis score (r = 0.82, P < 0.001) CONCLUSION: Our findings demonstrate a strong correlation between GIUS and CE in assessing the disease activity in patients with CD affecting the small intestine.

Evaluation of a novel disposable esophagogastroduodenoscopy system in emergency, bedside, and intraoperative settings: Pilot study (with videos).

OBJECTIVES: The disposable esophagogastroduodenoscopy (EGD) system is a novel endoscopic device which is highly portable and is designed to eliminate the risk of cross-infection caused by reusable EGD. This study aimed to investigate the feasibility and safety of disposable EGD in emergency, bedside, and intraoperative settings. METHODS: This was a prospective, single-center, noncomparative study. Disposable EGD was used for emergency, bedside, and intraoperative endoscopies in 30 patients. The primary end-point was the technical success rate of the disposable EGD. Secondary end-points included technical performance indicators including clinical operability, image quality score, procedure time, the incidence of device malfunction and/or failure, and the incidence of adverse events. RESULTS: A total of 30 patients underwent diagnosis and/or treatment with disposable EGD. Therapeutic EGD was performed on 13/30 patients, including hemostasis (n = 3), foreign body retrieval (n = 6), nasoenteric tube placement (n = 3), and percutaneous endoscopic gastrostomy (n = 1). The technical success rate was 100%: all procedures and indicated interventions were completed without changing to a conventional upper endoscope. The mean image quality score obtained immediately after procedure completion was 3.72 ± 0.56. The mean (± SD) procedure time was 7.4 (± 7.6) min. There were no device malfunctions or failures, device-related adverse events, or overall adverse events. CONCLUSION: The disposable EGD may be a feasible alternative to the traditional EGD in emergency, bedside, and intraoperative settings. Preliminary data show that it is a safe and effective tool for diagnosis and treatment in emergency and bedside upper gastrointestinal cases. TRIAL REGISTRATION: Chinese Clinical Trial Registry (Trial ID: ChiCTR2100051452, https://www.chictr.org.cn/showprojen.aspx?proj=134284).

Long-term exposure to PM2.5 and PM10 and chronic kidney disease: the Beijing Health Management Cohort, from 2013 to 2018.

Long-term exposure to ambient particulate pollutants (PM2.5 and PM10) may increase the risk of chronic kidney disease (CKD), but the results of previous research were limited and inconsistent. The purpose of this study was to assess the relationships of PM2.5 and PM10 with CKD. This study was a cohort study based on the physical examination data of 2082 Beijing residents from 2013 to 2018 in the Beijing Health Management Cohort (BHMC). A land-use regression model was used to estimate the individual exposure concentration of air pollution based on the address provided by each participant. CKD events were identified based on self-report or medical evaluation (estimated glomerular filtration rate, eGFR less than 60 ml/min/1.73 m2). Finally, the associations of PM2.5 and PM10 with CKD were calculated using univariate and multivariate logistic regression models. During the research period, we collected potentially confounding information. After adjusting for confounders, each 10 µg/m3 increase in PM2.5 and PM10 exposure was associated with an 84% (OR: 1.84; 95% CI: 1.45, 2.33) and 37% (OR: 1.37; 95% CI: 1.15, 1.63) increased risk of CKD. Adjusting for the four common gaseous air pollutants (CO, NO2, SO2, O3), the effect of PM2.5 and PM10 on CKD was significantly enhanced, but the effect of PM10 was no longer significant in the multi-pollutant model. The results of the stratified analysis showed that PM2.5 and PM10 were more significant in males, middle-aged and elderly people over 45 years old, smokers, drinkers, BMI ≥ 24 kg/m2, and abnormal metabolic components. In conclusion, long-term exposure to ambient PM2.5 and PM10 was associated with an increased risk of CKD.

Accurate tumor clonal structures require single-cell analysis.

Tumor clonal structure is closely related to future progression, which has been mainly investigated as mutation abundance clustering in bulk samples. With relatively limited studies at single-cell resolution, a systematic comparison of the two approaches is still lacking. Here, using bulk and single-cell mutational data from the liver and colorectal cancers, we checked whether co-mutations determined by single-cell analysis had corresponding bulk variant allele frequency (VAF) peaks. While bulk analysis suggested the absence of subclonal peaks and, possibly, neutral evolution in some cases, the single-cell analysis identified coexisting subclones. The overlaps of bulk VAF ranges for co-mutations from different subclones made it difficult to separate them. Complex subclonal structures and dynamic evolution could be hidden under the seemingly clonal neutral pattern at the bulk level, suggesting single-cell analysis is necessary to avoid underestimation of tumor heterogeneity.

Radiomic analysis based on multi-phase magnetic resonance imaging to predict preoperatively microvascular invasion in hepatocellular carcinoma.

BACKGROUND: The prognosis of hepatocellular carcinoma (HCC) remains poor and relapse occurs in more than half of patients within 2 years after hepatectomy. In terms of recent studies, microvascular invasion (MVI) is one of the potential predictors of recurrence. Accurate preoperative prediction of MVI is potentially beneficial to the optimization of treatment planning. AIM: To develop a radiomic analysis model based on pre-operative magnetic resonance imaging (MRI) data to predict MVI in HCC. METHODS: A total of 113 patients recruited to this study have been diagnosed as having HCC with histological confirmation, among whom 73 were found to have MVI and 40 were not. All the patients received preoperative examination by Gd-enhanced MRI and then curative hepatectomy. We manually delineated the tumor lesion on the largest cross-sectional area of the tumor and the adjacent two images on MRI, namely, the regions of interest. Quantitative analyses included most discriminant factors (MDFs) developed using linear discriminant analysis algorithm and histogram analysis with MaZda software. Independent significant variables of clinical and radiological features and MDFs for the prediction of MVI were estimated and a discriminant model was established by univariate and multivariate logistic regression analysis. Prediction ability of the above-mentioned parameters or model was then evaluated by receiver operating characteristic (ROC) curve analysis. Five-fold cross-validation was also applied via R software. RESULTS: The area under the ROC curve (AUC) of the MDF (0.77-0.85) outperformed that of histogram parameters (0.51-0.74). After multivariate analysis, MDF values of the arterial and portal venous phase, and peritumoral hypointensity in the hepatobiliary phase were identified to be independent predictors of MVI (P < 0.05). The AUC value of the model was 0.939 [95% confidence interval (CI): 0.893-0.984, standard error: 0.023]. The result of internal five-fold cross-validation (AUC: 0.912, 95%CI: 0.841-0.959, standard error: 0.0298) also showed favorable predictive efficacy. CONCLUSION: Noninvasive MRI radiomic model based on MDF values and imaging biomarkers may be useful to make preoperative prediction of MVI in patients with primary HCC.

DLK1-directed chimeric antigen receptor T-cell therapy for hepatocellular carcinoma.

BACKGROUND: Delta-like homologue 1 (DLK1), a transmembrane protein, is highly expressed in hepatocellular carcinoma (HCC). We explored whether DLK1-directed chimeric antigen receptor (CAR) T cells can specifically eliminate DLK1-positive HCC cells and serve as a therapeutic strategy for HCC immunotherapy. METHODS: We first characterized a homemade anti-human DLK1 monoclonal antibody, sequenced the single-chain Fragment variable (scFv) and integrated it into the second-generation CAR lentiviral vector, and then developed the DLK1-directed CAR-T cells. The cytotoxic activities of DLK1-directed CAR-T cells against different HCC cells were evaluated in vitro and in vivo. RESULTS: The genetically modified human T cells with the DLK1-directed CARs produced cytotoxic activity against DLK1-positive HCC cells. Additionally, the DLK1-directed CARs enhanced T cell proliferation and activation in a DLK1-dependent manner. Interestingly, the DLK1-targeted CAR-T cells significantly inhibited both subcutaneous and peritoneal xenograft tumours derived from human liver cancer cell lines HepG2 or Huh-7. CONCLUSION: DLK1-directed CAR-T cells specifically suppresses DLK1-positive HCC cells in vitro and in vivo. This study provides a novel transmembrane antigen DLK1 as a potential therapeutic target appropriate for CAR-T cell therapy, which may be further developed as a clinical therapeutic strategy for HCC immunotherapy.

Inhibition of Arid1a increases stem/progenitor cell-like properties of liver cancer.

ARID1A, a key subunit of the SWI/SNF chromatin remodeling complex, exhibits recurrent mutations in various types of human cancers, including liver cancer. However, the function of ARID1A in the pathogenesis of liver cancer remains controversial. Here, we demonstrate that Arid1a knockout may result in states of different cell differentiation, as indicated by single-cell RNA sequencing (scRNA-seq) analysis. Bulk RNA-seq also revealed that Arid1a deficiency upregulated these genes related to cell stemness and differentiation, but downregulated genes related to the hepatic functions. Furthermore, we confirmed that deficiency of Arid1a increased the expression of hepatic stem/progenitor cell markers, such as Cd133 and Epcam, and enhanced the self-renewal ability of cells. Mechanistic studies revealed that Arid1a loss remodeled the chromatin accessibility of some genes related to liver functions. Thus, Arid1a deficiency might contribute to cancer development by increasing the number of stem/progenitor-like cells through dysregulating the expression of these genes related to cell stemness, differentiation and liver functions.

Endoscopic resection via antral submucosal tunneling for en bloc removal of tumors in the duodenal bulb.

To overcome difficulties in the removal of duodenal bulb lesions, especially those in anatomically challenging locations, we developed the endoscopic resection via antral submucosal tunneling (ERAST) technique. In this study, we evaluated the feasibility and safety of ERAST for the removal of superficial and subepithelial lesions in the duodenal bulb. This was a single-center retrospective study of 10 patients with lesions in the bulb. Submucosal tunneling from the gastric antrum to the duodenum was performed to facilitate en bloc tumor resection in the bulb. The en bloc resection rate, postoperative bleeding, and perforation were the primary endpoints. Ten lesions (four superficial and six subepithelial), with an average size of 19.1 ± 9.2 mm, were resected en bloc by ERAST. Esophagogastroduodenoscopy follow-up after 2 months indicated complete wound healing in all patients. In our primary experience, ERAST was found to be a feasible and safe endoscopic resection technique for the removal of lesions in the duodenal bulb, especially those that are difficult to access.

High Expression of CISD2 in Relation to Adverse Outcome and Abnormal Immune Cell Infiltration in Glioma.

Glioma is a serious disease burden globally, with high mortality and recurrence rates. CDGSH iron sulfur domain 2 (CISD2) is an evolutionarily conserved protein that is involved in several cancers. However, its role in the prognosis and immune infiltration in glioma remains unclear. In our research, RNA-seq matrix and clinicopathological relevant data for CISD2 were downloaded from The Cancer Genome Atlas (TCGA) and Genotype-Tissue Expression (GTEx) databases. Human Protein Atlas was used to verify the CISD2 protein level in glioma, and STRING was used to establish relative coexpression gene network. The Kaplan-Meier plotter was adopted to analyze the effect of CISD2 on prognosis. The connection between CISD2 expression and immune infiltration was analyzed using single-sample GSEA (ssGSEA), TIMER, and GEPIA. In contrast to normal tissues, CISD2 expression was significantly higher in glioma tissues, and CISD2 presented a certain diagnostic value in distinguishing glioma tissues from normal tissues. Furthermore, the CISD2 level was correlated with age, histologic grade, histological type, isocitrate dehydrogenase (IDH) status, 1p/19q codeletion status, and primary therapy outcome of glioma, while high CISD2 mRNA expression was correlated with grave overall survival. Multivariate analysis demonstrated that CISD2 was an independent risk factor for patients with glioma. Functional enrichment analysis indicated that CISD2 could regulate proliferation, immune reaction, and mitochondrial function. The results from the ssGSEA and TIMER databases confirmed that CISD2 acts a prominent role in immune cell infiltration in the tumor microenvironment, especially in low-grade glioma (LGG). Furthermore, CISD2 expression was observably correlated to M2 polarization in macrophages with glioma progression. This is the first research to investigate the immune role of CISD2 in glioma. CISD2 may be an innovative prognostic biomarker and can act as a potential target for future therapy for glioma.

Correlation Between Ultrasonographic Response and Anti-Tumor Necrosis Factor Drug Levels in Crohn's disease.

BACKGROUND: Ultrasound is valuable in tight control algorithms for Crohn's disease (CD). However, the correlation between ultrasonographic response and anti-tumor necrosis factor (TNF) drug levels remains unknown. Elucidating this correlation would be helpful in optimizing the use of anti-TNF drugs. Thus, the authors aimed to investigate this correlation. METHODS: Between June 2020 and June 2021, all patients with CD who completed anti-TNF induction therapy were retrospectively included. Ultrasound was performed at week 0 and week 14, and proactive therapeutic drug monitoring of anti-TNF drugs was performed at week 14. The receiver operating characteristic (ROC) curve was used in the correlation analysis. RESULTS: Ninety-two patients (60 treated with infliximab and 32 with adalimumab) were included. At week 14, an ultrasonographic response was detected in 43 patients. Patients with ultrasonographic response had significantly higher median drug levels (5.9 mcg/mL for infliximab; 18.2 mcg/mL for adalimumab) than those without (0.9 mcg/mL for infliximab, P < 0.001; 4.8 mcg/mL for adalimumab, P < 0.001). The ROC curve showed a significant correlation between ultrasonographic response and anti-TNF drug levels (area under the curve = 0.79 for infliximab, P < 0.001; area under the curve = 0.86 for adalimumab, P < 0.001). The optimal cut-off values for infliximab and adalimumab correlated with ultrasonographic response were 5.0 and 10.5 mcg/mL, respectively. An incremental increase was observed in ultrasonographic response with higher anti-TNF drug levels. CONCLUSIONS: Higher anti-TNF drug levels are associated with an increased likelihood of ultrasonographic response in patients with CD.

Exposure to aristolochic acid I is associated with poor prognosis of liver cancer patients.

The aristolochic acids (AAs), derived from Aristolochia and Asarum species used widely in herbal medicines, are closely associated with liver cancer. The major AA derivatives are aristolochic acid I (AAI) and II (AAII), which can bind DNA covalently to form AA-DNA adducts after metabolic activation in vivo. Among all these AA-DNA adducts, 7-(deoxyadenosine-N6-yl) aristolactam I (dA-AL-I) is the most abundant and persistent DNA lesion in patients. However, the direct evidence indicating AA exposure in human liver cancer is still missing. Here, we analyzed dA-AL-I adduct, the direct biomarker of AAI exposure, by ultra-performance liquid chromatography coupled with triple quadrupole mass spectrometry (UPLC-TQ/MS) in 209 liver cancer patients. Also, DNA samples from mice treated with/without AAI were used as positive and negative controls. dA-AL-I adduct was present in 110 of 209 (52.6%) patients, indicating that these patients were exposed to AAI prior to their clinical investigations and also had a worse prognosis. The relative high AA exposure rate and worse prognosis in our cohort of patients emphasize the significance to increase public awareness to avoid the use of herbal medicine containing AAs or their derivatives.