Gastric paraganglioma: a case report and review of literature.

Paragangliomas (PGLs) are rare neuroendocrine tumors which overproduce catecholamines (CAs). They are extra-adrenal, catecholamine-secreting tumors occurring outside the adrenal glands. Gastric PGLs originating from extra-adrenal paraganglia are exceptionally rare, and their presentation in geriatric patients further adds to the complexity of diagnosis and management. A 72-year-old male patient presented with enduring left upper abdominal pain and anemia persisting for over a year, and hypertension for six months. Physical examination revealed epigastric discomfort and pallor. Computed tomography scans revealed enlarged lymph nodes in the lesser curvature of the stomach and thickening of the gastric antrum wall with concavity. The patient underwent three cycles of neoadjuvant therapy before radical gastrectomy for gastric cancer. These imaging findings were confirmed during surgery and intraoperative blood pressure was in fluctuation. After the successful resection of the tumor, postoperative pathology confirmed paraganglioma. During postoperative examination, it was observed that the patient's CAs and their metabolites had returned to within the normal range. Combined with the existing ten literatures, we retrospective report the clinical and pathological characteristics and treatment strategies of the rare gastric paraganglioma.

Systematic review and meta-analysis of current evidence in endograft therapy for spontaneous isolated superior mesenteric artery dissection.

The role of endovascular stent therapy (EST) in the treatment of spontaneous isolated superior mesenteric artery dissection (SISMAD) has gained momentum in recent years but remains controversial. We gathered research examining the advantages and disadvantages of EST for SISMAD patients. Primary outcomes involved both immediate and long-term results. Random or fixed effect models were used for effect size (ES) calculation with 95% confidence interval (CI) based on 50% heterogeneity threshold. Our analysis incorporated data from 21 studies including 611 SISMAD cases treated by EST. Our findings show a complication rate of approximately 1% following EST (95%CI 0.01-0.02, I2 = 0%, P = 0.97), with a bare minimum mortality rate of < 1% (95%CI 0.00-0.01, I2 = 0%, P > 0.05) and a reintervention rate of < 1% (95%CI 0.00-0.01, I2 = 0%, P = 0.89). We also found technique success and symptom resolution approaching 94% and 99%, respectively, in the immediate postoperative phase. In the long run, we observed a recurrence of symptoms at 3% (95%CI 0.00-0.06, I2 = 58.6%, P < 0.01), creation of new dissections at 1% (95%CI 0.00-0.02, I2 = 0%, P = 0.73), aneurysm progression at 2% (95%CI 0.00-0.03, I2 = 42.7%, P = 0.12), reintervention due to complications at 3% (95%CI 0.00-0.05, I2 = 0%, P = 0.43) and stenotic stents at 12% (95%CI 0.04-0.23, I2 = 77.5%, P < 0.01). Nevertheless, high levels of stent patency 98% (95% CI 0.97-1.00, I2 = 0%, P = 0.51) and complete remodeling 88% (95% CI 0.82-0.94, I2 = 65.5%, P < 0.05) were observed postoperatively. Overall, EST presents minimal complications and promising long-term outcomes for SISMAD, although the prevalence of stent stenosis requires further attention.

Erratum: Author correction to 'Mevalonate improves anti-PD-1/PD-L1 efficacy by stabilizing CD274 mRNA' [Acta Pharmaceutica Sinica B 13 (2023) 2585-2600].

[This corrects the article DOI: 10.1016/j.apsb.2023.04.002.].

Mevalonate improves anti-PD-1/PD-L1 efficacy by stabilizing CD274 mRNA.

Mevalonate metabolism plays an important role in regulating tumor growth and progression; however, its role in immune evasion and immune checkpoint modulation remains unclear. Here, we found that non-small cell lung cancer (NSCLC) patients with higher plasma mevalonate response better to anti-PD-(L)1 therapy, as indicated by prolonged progression-free survival and overall survival. Plasma mevalonate levels were positively correlated with programmed death ligand-1 (PD-L1) expression in tumor tissues. In NSCLC cell lines and patient-derived cells, supplementation of mevalonate significantly up-regulated the expression of PD-L1, whereas deprivation of mevalonate reduced PD-L1 expression. Mevalonate increased CD274 mRNA level but did not affect CD274 transcription. Further, we confirmed that mevalonate improved CD274 mRNA stability. Mevalonate promoted the affinity of the AU-rich element-binding protein HuR to the 3'-UTR regions of CD274 mRNA and thereby stabilized CD274 mRNA. By in vivo study, we further confirmed that mevalonate addition enhanced the anti-tumor effect of anti-PD-L1, increased the infiltration of CD8+ T cells, and improved cytotoxic function of T cells. Collectively, our findings discovered plasma mevalonate levels positively correlated with the therapeutic efficacy of anti-PD-(L)1 antibody, and provided the evidence that mevalonate supplementation could be an immunosensitizer in NSCLC.

Butein suppresses PD-L1 expression via downregulating STAT1 in non-small cell lung cancer.

PD-L1 (programmed cell death ligand 1) is frequently up-regulated in tumors and is critical in tumor immune escape. In addition to antibodies that block the interaction between PD-L1 and PD-1 (programmed cell death protein 1), small-molecule compounds that suppress PD-L1 expression also exhibit significant anti-tumor effects, emerging as a new strategy targeting PD-L1. By using a cell-based screening model, we found that butein, a natural chalcone compound, significantly reduced the cytoplasm and cell surface expression of PD-L1. This effect was further validated in various non-small cell lung cancer (NSCLC) cell lines and primary cells derived from clinical NSCLC tissues. Butein inhibited PD-L1 transcription, but not the half-life of PD-L1 protein. Butein reduced STAT1 level and butein-induced PD-L1 suppression was eliminated by the absence of STAT1. By co-culture system, butein improved tumor elimination by increasing the killing ability of CD8+ T cells. By in vivo study, we further confirmed that butein downregulated PD-L1 expression and improved infiltration of CD8+ T cells in tumor tissues. Taken together, our study suggested that butein could suppress the transcription of PD-L1 via downregulating STAT1, providing a theoretical basis for the application of butein in anti-tumor therapy.

Construction and properties of the silk fibroin and polypropylene composite biological mesh for abdominal incisional hernia repair.

Background: In this study, a new composite biological mesh named SFP was prepared by combining silk fibroin with polypropylene mesh. The mechanism and clinical application value of the SFP composite mesh were explored. Methods: The fibrous membrane was prepared by electrospinning of silk fibroin. The silk fibrous membrane was adhered to the polypropylene mesh by fibrin hydrogel to make a new composite mesh. The characterizations were verified by structural analysis and in vitro cell experiments. A total of 40 Sprague-Dawley rats were randomly divided into two groups, and 20 rats in each group were implanted with the SFP mesh and pure polypropylene mesh, respectively. The rats were sacrificed in batches on the 3rd, 7th, 14th, and 90th days after surgery. The adhesion degree and adhesion area on the mesh surface were compared, and a histopathological examination was carried out. Results: In vitro cell function experiments confirmed that the SFP mesh had good cell viability. The control group had different degrees of adhesion on the 3rd, 7th, 14th, and 90th days after surgery. However, there was almost no intraperitoneal adhesions on the 3rd and 7th days after surgery, and some rats only had mild adhesions on the 14th and 90th days after surgery in the SFP group. There were statistically significant differences in the postoperative intraperitoneal adhesion area and adhesion degree between the two groups (p < 0.05). Histopathological examination confirmed that the mesenchymal cells were well arranged and continuous, and there were more new capillaries and adipocyte proliferation under the mesenchymal cells in the SFP group. Conclusion: The SFP mesh shows good biocompatibility and biofunction in vitro and in vivo. It can promote the growth of peritoneal mesenchymal cells. The formation of a new mesenchymal cell layer can effectively reduce the extent and scope of adhesion between the mesh and abdominal organs. The SFP mesh will have a good application prospect in the field of abdominal wall hernia repair.

Clinical Data Analysis for Treatment of Adult Inguinal Hernia by TAPP or TEP.

Background: Transabdominal preperitoneal (TAPP) repair and totally extraperitoneal (TEP) repair are the primary surgical methods for the treatment of adult inguinal hernia, but it remains necessary to consider which one to choose in clinical practice. Our study seeks to compare the efficacy of laparoscopic TAPP and laparoscopic TEP in the treatment of adult inguinal hernia and to explore which surgical method is a better choice. Methods: A retrospective analysis of 686 adult patients with inguinal hernia admitted to our hospital from the period January 2016 to December 2020 was conducted. According to different surgical methods, they were divided into two groups: a TAPP group (n = 361) and a TEP group (n = 325). These two groups of patients were statistically analyzed, and the operation time, postoperative pain, postoperative hospital stay length, postoperative complications, and recurrence rate were compared between them. Results: There were no significant differences in postoperative hospital stay, complications, and the recurrence rate between the two groups (p > 0.05). The duration of operation in the TEP group was significantly shorter than that in the TAPP group, and the difference was statistically significant (p < 0.001); in terms of postoperative pain, the TEP group fared better than the TAPP group, and the difference was statistically significant (p < 0.001). Conclusion: TAPP and TEP are safe and effective surgical methods in the treatment of adult inguinal hernia. However, compared with TAPP, TEP can significantly shorten the operative time, reduce intraoperative trauma, and limit postoperative pain in the treatment of adult inguinal hernia. Furthermore, it does not increase the rate of complications or recurrence, so it is worth popularizing.

MicroRNA-135b/CAMK2D Axis Contribute to Malignant Progression of Gastric Cancer through EMT Process Remodeling.

There is a continued need for investigating the roles of microRNAs (miRNAs) and their targets on the progression of gastric cancer (GC), especially metastasis. Here, we performed an integrated study to identify dysregulated miRNAs critical for GC development and progression. miR-135b was determined as a promising biomarker for GC. The expression level of miR-135b was increased among GC cell lines, patient tumor tissues, serum samples, and correlation with aggravation of the GC patients. The in vitro functional assays demonstrated overexpression of miR-135b promoted cell proliferation, migration and invasion in GC, while miR-135b inhibition led to the opposite results. CAMK2D was found to be the direct target of miR-135b, serving as a tumor suppressor in GC cells. Based on our and public datasets, we confirmed the attenuation of CAMK2D expression in GC tissues. And, the expression levels of miR-135b and CAMK2D were closely associated with prognosis of GC patients. Ectopic expression of miR-135b resulted in the down-regulation of CAMK2D. Additionally, CAMK2D was a prerequisite for miR-135b to promote GC cells proliferation and migration by regulating the EMT process, which was confirmed by the in vivo experiments. Importantly, in vivo injection of miR-135b antagomir significantly repressed the tumor growth and metastasis of xenograft models, which suggested that the miR-135b antagomir were promising for clinical applications. Taken together, these results indicate that miR-135b/CAMK2D axis drives GC progression by EMT process remodeling, suggesting that miR-135b may be utilized as a new therapeutic target and prognostic marker for GC patients.

An integrated classifier improves prognostic accuracy in non-metastatic gastric cancer.

The American Joint Committee on Cancer (AJCC) staging system is insufficiently prognostic for gastric cancer (GC) patients and complementary factors are in urgent need. Here we aimed to develop a comprehensive model, consisting of both immune signatures and cancer signaling molecules, which was expected to accurately improve survival prediction in non-metastatic gastric cancer (GC). We first validated the prognostic value of a combination of 18 immune features and 52 cancer-signaling molecules in The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) database. Then, their expression and distribution were analyzed in consecutive 1180 GC patients using immunohistochemistry. We developed and validated a novel protein-based prognostic classifier using CDH1, an epithelial-mesenchymal transition (EMT) marker, and five immune features (CD3, CD4, CD274, GZMB, and PAX5) by Cox regression model with group LASSO penalty. We observed significant differences in the overall survival of the high- and low-prognostic risk groups (66.8% VS 27.0%, P < .001). A combination of this classifier with age and pTNM stage had better prognostic value than pTNM alone. The model was further validated in both treatment-naive patients and those treated with neoadjuvant chemotherapy. Moreover, GC patients with high-risk score exhibited a favorable prognosis to adjuvant chemotherapy. This integrated classifier could be automatically analyzed and effectively predict survival of GC patients and may provide a new clinically applicable strategy to identify patients who are more likely to benefit from adjuvant chemotherapy.

TNFRSF11B activates Wnt/ß-catenin signaling and promotes gastric cancer progression.

Tumor necrosis factor receptor superfamily member 11B (TNFRSF11B) has been studied to be involved in the development and progression of several human malignancies. However, little is unveiled regarding the complex mechanisms of TNFRSF11B in human gastric cancer (GC). The clinical significance of TNFRSF11B was assessed in 70 and 160 GC tissues using immunohistochemistry method and gene microarray analysis, respectively. The biological function of TNFRSF11B was studied in vitro and in vivo assays. Immunofluorescence assay was used to evaluate the expression of ß-catenin in the nucleus. The expression of ß-catenin and related protein was determined by Western blot. The interaction between TNFRSF11B and GSK3ß was detected by co-immunoprecipitation. We demonstrated that TNFRSF11B was highly expressed in the cytoplasm of GC and associated with the patient poor outcome. Our studies showed that TNFRSF11B in GC cells significantly promoted cell proliferation, migration, invasion in vitro and tumorigenic ability in vitro and in vivo. Meanwhile, TNFRSF11B inhibited GC cell apoptosis. The proportion of nuclear active ß-catenin showed positively correlation with TNFRSF11B expression. TNFRSF11B directly combined with GSK-3ß upregulating its phosphorylation, and increased expression of ß-catenin and its downstream effectors. Collectively, these findings demonstrate that TNFRSF11B promote the aggressive phenotypes of GC cells and activated Wnt/ß-catenin signaling. Accordingly, TNFRSF11B had potential as a biomarker and inhibition of TNFRSF11B expression might offer a new therapeutic target for GC patients.

EIF3B is associated with poor outcomes in gastric cancer patients and promotes cancer progression via the PI3K/AKT/mTOR signaling pathway.

PURPOSE: Eukaryotic translation initiation factor (EIF) plays a vital role in protein synthesis. EIF3B is a core subunit of the EIF3 family, and is overexpressed in many tumors. EIF3B is associated with an unfavorable prognosis, as well as the genesis and development of tumors. However, the potential role of EIF3B in gastric cancer (GC) remains unknown. In the current study, we explored the clinical significance and the possible mechanism of EIF3B in the progression of GC. METHODS: EIF3B expression was analyzed in 78 GC tissue samples through quantitative PCR and in 94 GC tissue samples through immunohistochemistry (IHC) staining. The correlation between EIF3B and clinicopathological features was analyzed in GC tissues. The role of EIF3B in GC progression was investigated through in vitro and in vivo assays. RESULTS: EIF3B expression was upregulated in GC tissues (73.4%, IHC). High expression of EIF3B was significantly correlated with the depth of tumor invasion, lymph node metastasis and TNM stage (P=0.000, 0.000 and 0.000, respectively). Multivariate analysis indicated that GC patients with high EIF3B expression suffered a poorer 5-year survival. EIF3B promoted GC cell proliferation and was strongly associated with proliferating cell nuclear antigen (PCNA) expression in GC samples (P=0.009). It also enhanced tumor cell migration and invasion, which were affected through epithelial-mesenchymal transition (EMT) and the Stat3 signaling pathway. Knockdown of EIF3B in GC cells suppressed the growth of xenograft tumors and lung metastatic colonization in vivo. Furthermore, gene set enrichment analysis (GSEA) and Western blot results demonstrated that EIF3B activated the PI3K/AKT/mTOR signaling pathway. CONCLUSION: Our results suggest that EIF3B plays an oncogenic role in GC progression and serves as an independent prognostic factor for GC patients.

Animal experimental studies using small intestine endoscope.

AIM: To assess the feasibility and safety of a novel enteroscope, negative-pressure suction endoscope in examining the small intestine of a porcine model. METHODS: In vitro experiments in small intestinal loops from 20 pigs and in vivo experiments in 20 living pigs were conducted. RESULTS: In in vitro experiments, a negative pressure of > 0.06 MPa was necessary for optimal visualization of the intestine, and this pressure did not cause gross or histological damage to the mucosa. For satisfactory examination of the small intestine in vivo, higher negative pressure (> 1.00 MPa) was required. Despite this higher pressure, the small intestine did not show any gross or microscopic damage in the suctioned areas. The average time of examination in the living animals was 60 ± 7.67 min. The animals did not experience any apparent ill effects from the procedure. CONCLUSION: Small intestine endoscope was safely performed within a reasonable time period and enabled complete visualization of the intestine in most cases.

Homeobox B9 is overexpressed in hepatocellular carcinomas and promotes tumor cell proliferation both in vitro and in vivo.

HomeoboxB9 (HOXB9), a nontransforming transcription factor that is overexpressed in multiple tumor types, alters tumor cell fate and promotes tumor progression. However, the role of HOXB9 in hepatocellular carcinoma (HCC) development has not been well studied. In this paper, we found that HOXB9 is overexpressed in human HCC samples. We investigated HOXB9 expression and its prognostic value for HCC. HCC surgical tissue samples were taken from 89 HCC patients. HOXB9 overexpression was observed in 65.2% of the cases, and the survival analysis showed that the HOXB9 overexpression group had significantly shorter overall survival time than the HOXB9 downexpression group. The ectopic expression of HOXB9 stimulated the proliferation of HCC cells; whereas the knockdown of HOXB9 produced an opposite effect. HOXB9 also modulated the tumorigenicity of HCC cells in vivo. Moreover, we found that the activation of TGF-ß1 contributes to HOXB9-induced proliferation activities. The results provide the first evidence that HOXB9 is a critical regulator of tumor growth factor in HCC.

[Establishment of serum protein pattern model for screening pancreatic cancers by SELDI-TOF-MS technique].

OBJECTIVE: To detect the serum specific proteins in pancreatic cancer patients and establish diagnostic model by surface enhanced laser desorption/ionization time of flight mass spectrometry (SELDI-TOF-MS) technique. METHODS: Twenty-nine serum samples from patients of pancreatic cancer were collected before surgery and an additional 57 serum samples from age and sex matched individuals without cancer were used as controls, SELDI-TOF-MS technique and WCX magnetic beads were used to detect the protein fingerprint expression of all the serum samples and the resulting profiles between pancreatic cancer patients and controls were analyzed with biomarker wizard system, established the model using biomarker patterns system software. A double-blind test was used to determine the sensitivity and specificity of the classification model. RESULTS: A panel of four biomarkers (relative molecular weight are 5705, 4935, 5318 and 3243 Da) were selected to set up a decision trees as the classification model for screening pancreatic cancer effectively. The result yielded a sensitivity of 100%, specificity of 97.4%. The double-blind test challenged the model with a sensitivity of 88.9% and a specificity of 89.5%. CONCLUSIONS: SELDI-TOF-MS offers a unique platform for the proteomic detection of serum in pancreatic cancer patients. It also offers a noninvasive method to further study the proteomic changes in the development and progression of pancreatic cancer.

[The contribution for the diagnosis of the tumor-like polypoid lesions of the gallbladder by SELDI-TOF-MS].

OBJECTIVE: To detect the serum specific proteins in tumor-like polypoid lesions of the gallbladder patients and establish diagnostic model. METHODS: Surface enhanced laser desorption/ionization time of flight mass spectrometry (SELDI-TOF-MS) technique and WCX Magnetic Beads were used to detect the serum proteomic patterns of 23 patients with tumor-like PLG, 21 patients with non tumor-like PLG and 26 normal persons. Biomarker Wizard and Biomarker Patterns Software were used in combination to analyze the data. RESULTS: Preliminary screening out 22 representative specific proteins for the diagnosis of the tumor-like PLG. Analysis system under the conditions set selected 3 specific proteins to establish diagnostic model for the tumor-like PLG. The sensitivity and specificity of the model for the diagnosis of the tumor-like PLG were 100% and 89.4%, respectively. CONCLUSION: SELDI-TOF-MS technique can select specific protein of the tumor-like PLG, and establish diagnostic model of the tumor-like PLG.