Intestinal perforation caused by Epstein-Barr virus-positive primary diffuse large B-cell lymphoma in a patient with HIV.

We report the case of a 48-year-old male who presented with right lower abdominal pain and a mass for 2 weeks and got constipation for 5 days. An abdominal CT scan conducted before admission at other hospitals revealed an obstruction in the blind ascending colon, which was suspected to be a malignant tumor. Proctoscopy revealed peritoneal implantation metastasis and multiple pelvic lymph nodes. Physical examination was unremarkable except for multiple lymph node enlargements in the inguinal area, without pain. A whole-body contrast-enhanced FDG-PET/CT revealed lymphoma involvement in the ascending colon, peritoneum, bone marrow, and lymph nodes in multiple regions of the body, with DLBCL as a suspected diagnosis. Pathological findings from the colonoscopy revealed atypical lymphocyte infiltration and Immunostaining indicated the presence of atypical lymphocytes with Ki-67 (90%) and tested positive for CD20, CD19, CD10, and BCL-6. Based on the above findings, stage IV DLBCL was diagnosed. Furthermore, EBV-DNA amplification was positive. The patient received R-CHOP treatment for 2 days before experiencing symptoms of fevers, chills, and abdominal pain. He underwent emergency surgery due to intestinal perforation, and preoperative blood tests revealed HIV-positive. The prognosis for the patient is poor due to sepsis.

Construction and validation of a novel senescence-related risk score can help predict the prognosis and tumor microenvironment of gastric cancer patients and determine that STK40 can affect the ROS accumulation and proliferation ability of gastric cancer cells.

Background: In recent years, significant molecules have been found in gastric cancer research. However, their precise roles in the disease's development and progression remain unclear. Given gastric cancer's heterogeneity, prognosis prediction is challenging. This study aims to assess patient prognosis and immune therapy efficacy using multiple key molecules. Method: The WGCNA algorithm was employed to identify modules of genes closely related to immunity. A prognostic model was established using the Lasso-Cox method to predict patients' prognosis. Single-sample gene set enrichment analysis (ssGSEA) was conducted to quantify the relative abundance of 16 immune cell types and 13 immune functions. The relationship between risk score and TMB, MSI, immune checkpoints, and DNA repair genes was examined to predict the effectiveness of immune therapy. GO and KEGG analyses were performed to explore potential pathways and mechanisms associated with the genes of interest. Single-cell RNA sequencing was utilized to investigate the expression patterns of key genes in different cell types. Results: Through the WGCNA algorithm and Lasso-Cox algorithm selected KL, SERPINE1, and STK40 as key genes for constructing the prognostic model. The SSGSEA algorithm was employed to evaluate the infiltration of immune cells and immune functions in different patients, and their association with the risk score was investigated. The high-risk group exhibited lower TMB and MSI compared to the low-risk group. MMR and immune checkpoint analysis revealed a significant correlation between the risk score and multiple molecules. Finally, we also believe that STK40 is the most critical senescence-related gene affecting the progression of gastric cancer. In vitro experiments showed that ROS accumulation and cell proliferation ability of gastric cancer cells were impaired when STK40 was knocked down. Conclusion: In summary, we've constructed a prognostic model utilizing key genes for gastric cancer prognosis, while also showcasing its efficacy in predicting patient response to immunotherapy.

TMEM147 Correlates with Immune Infiltration and Serve as a Potential Prognostic Biomarker in Hepatocellular Carcinoma.

Background: Hepatocellular carcinoma (HCC) is one of the most prevalent malignancies and is associated with high mortality. Transmembrane protein 147 (TMEM147) is a seven-transmembrane protein that may mediate immune regulation. However, the relevance of TMEM147 to immune regulation in HCC and the prognosis of HCC patients are unclear. Methods: We analyzed TMEM147 expression in HCC by using the Wilcoxon rank-sum test. Real time quantitative PCR (RT-qPCR) and Western blot analysis of tumor tissues and cell lines were used to verify TMEM147 expression in HCC. The influence of TMEM147 on HCC prognosis was assessed using Kaplan-Meier analysis, Cox regression analysis, and a prognostic nomogram. The functions of the TMEM147-related differentially expressed genes (DEGs) were identified by Gene Ontology (GO)/Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses and gene set enrichment analysis (GSEA). In addition, we examined the associations between TMEM147 expression and immune infiltration using single-sample gene set enrichment analysis (ssGSEA) and immunofluorescence staining of HCC tissues. Results: Our results showed that the expression of TMEM147 was significantly higher in human HCC tissues than in adjacent normal liver tissues, with similar findings in human HCC cell lines. High TMEM147 expression was correlated with T stage, pathological stage, histological grade, race, alpha-fetoprotein level, and vascular invasion in HCC. Moreover, we revealed that high TMEM147 expression was associated with shorter survival times and that TMEM147 could be a risk factor for overall survival, along with T stage, M stage, pathological stage, and tumor status. Mechanistic studies revealed that high TMEM147 expression was linked to the B lymphocyte, antigen response, IL6 signaling pathway, cell cycle, Kirsten rat sarcoma viral oncogene homolog (KRAS) signaling pathway, and myelocytomatosis oncogene (MYC) targets. Correspondingly, TMEM147 expression was positively associated with the infiltration of immune cells, including Th2 cells, follicular helper T cells, macrophages, and NK CD56 bright cells in HCC. Conclusions: TMEM147 might be a biomarker for poor prognosis and is related to immune cell infiltration in HCC.

Peptidomic Analysis Reveals that Novel Peptide LDP2 Protects Against Hepatic Ischemia/Reperfusion Injury.

Background and Aims: Hepatic ischemia/reperfusion (I/R) injury has become an inevitable issue during liver transplantation, with no effective treatments available. However, peptide drugs provide promising regimens for the treatment of this injury and peptidomics has gradually attracted increasing attention. This study was designed to analyze the spectrum of peptides in injured livers and explore the potential beneficial peptides involved in I/R injury. Methods: C57BL/6 mice were used to establish a liver I/R injury animal model. Changes in peptide profiles in I/R-injured livers were analyzed by mass spectrometry, and the functions of the identified peptides were predicted by bioinformatics. AML12 cells were used to simulate hepatic I/R injury in vitro. After treatment with candidate liver-derived peptides (LDPs) 1-10, the cells were collected at various reperfusion times for further study. Results: Our preliminary study demonstrated that 6 h of reperfusion caused the most liver I/R injury. Peptidomic results suggested that 10 down-regulated peptides were most likely to alleviate I/R injury by supporting mitochondrial function. Most importantly, a novel peptide, LDP2, was identified that alleviated I/R injury of AML12 cells. It increased cell viability and reduced the expression of inflammation- and apoptosis-related proteins. In addition, LDP2 inhibited the expression of proteins related to autophagy. Conclusions: Investigation of changes in the profiles of peptides in I/R-injured livers led to identification of a novel peptide, LDP2 with potential function in liver protection by inhibiting inflammation, apoptosis, and autophagy.

Preoperative administration of branched-chain amino acids reduces postoperative insulin resistance in rats by reducing liver gluconeogenesis.

BACKGROUND: Postoperative insulin resistance (PIR) represents an important characteristic of metabolic response following surgical injury. Clinical outcomes are negatively correlated to postoperative insulin resistance and hyperglycemia, indicating a novel treatment for reducing postoperative insulin resistance is urgently needed. The current work aimed to assess the protective effects of branched-chain amino acids (BCAA) on glucose metabolism disorders induced surgically in a rat model, and to explore the underpinning mechanism. METHODS AND RESULTS: Rats were randomly assigned to 2 groups, including the control and BCAA groups. Rats were given a compulsory oral 3 mL load by gavage two hours before surgery. The results showed that BCAA remarkably reduced glycemia by suppressing liver gluconeogenesis via reduction of cAMP-response element-binding protein-regulated transcription coactivator 2 (CRTC2) and glucose-6-phosphatase (G6PC) gene and protein expression levels (all Ps < 0.05). CONCLUSIONS: This study revealed that BCAA lower blood glucose levels by reducing liver gluconeogenesis without significant elevation of plasma insulin levels. We anticipate that preoperative BCAA supplementation may be a means for preventing postoperative insulin resistance.

Ultrasound biomicroscopic features associated with angle closure in fellow eyes of acute primary angle closure after laser iridotomy.

PURPOSE: To investigate the frequency of appositional angle closure and related anatomic characteristics in fellow eyes of Chinese subjects with acute primary angle closure (APAC) after laser peripheral iridotomy (LPI). DESIGN: Cross-sectional study. PARTICIPANTS: Consecutive subjects with APAC presenting from April 2006 to September 2006 at the Glaucoma Service of Peking University Eye Center, Peking University Third Hospital. METHODS: Under dark conditions, fellow eyes were divided into 2 groups based on the detection of appositional angle closure by ultrasound biomicroscopy (UBM). For all subjects, UBM parameters were measured to evaluate the different anatomic features between the 2 groups. Darkroom provocative tests (DRPTs) and gonioscopy were performed to investigate the relationship between angle closure and intraocular pressure. MAIN OUTCOME MEASURES: Central anterior chamber depth (ACD); angle opening distance(500) (AOD(500)); angle recess area(750) (ARA(750)); trabecular-iris angle (T-I angle); trabecular-ciliary process distance (TCPD); peripheral iris thickness (IT(1)); iris-zonule distance (IZD); and the position of the iris insertion. RESULTS: Thirty-four post-LPI fellow eyes of 34 patients with APAC (8 men, 26 women; mean +/- standard deviation age 66.3+/-7.2 years, range 54-83) were included. Peripheral anterior synechiae (PAS) were not observed in any subject. Appositional angle closure was observed in at least 1 quadrant in 13 (38.2%) of the 34 patients. Compared with eyes without appositional closure, eyes with appositional closure showed significantly lower AOD(500), ARA(750), and T-I angle in 4 quadrants; shorter TCPD in the inferior and temporal quadrants; and thicker IT(1) in the superior and nasal quadrants (P<0.05). The DRPT results were positive in 3 (11.1%) of 27 eyes with appositional closure in 0 to 2 quadrants and in 3 (75.0%) of 4 eyes with appositional closure in 3 to 4 quadrants (P = 0.0164). CONCLUSIONS: Under dark conditions, more than one third of fellow eyes of APAC showed appositional angle closure after LPI. The anatomic findings indicate a narrower angle, a more anterior position of the ciliary body, and a thicker peripheral iris in fellow eyes of APAC after LPI may be associated with an increased risk for progressive angle closure.

[Polymorphism of vitamin D receptor Fok I and colorectal cancer risk in Chinese].

OBJECTIVE: To explore the frequency of vitamin D receptor (VDR) Fok I polymorphism in healthy Chinese and colorectal tumor patients,and to study the correlation between VDR Fok I polymorphism and the pathogenesis of colorectal tumor. METHODS: After the preparation of gDNA by common method,VDR genotypes were determined by Fok I restriction endonuclease digestion of PCR-amplified DNA in 69 colorectal cancer patients and 218 healthy persons. RESULTS: The F allele frequencies of VDR in healthy persons and in colorectal tumors patients were 61.5% and 49.3%, respectively, with statistical difference (P< 0.05). The genotype frequencies of FF, Ff and ff in healthy persons and in colorectal tumors patient were (39.5%,44%,16.5%) and (29.1%,40.5%,30.4%), respectively,with statistical differences (P< 0.05). The odds ratio of ff and Ff genotypes were 2.51 (95% confidence interval,1.21 approximately 5.18) and 2.00 (95% confidence intervals,1.01approximately 3.96), respectively (P< 0.01). CONCLUSION: Fok I polymorphism is a common single nucleotide polymorphism (SNP) of VDR in Chinese population,and the VDR Fok I polymorphism may lower the risk of colorectal tumor.