Development of a tongue image-based machine learning tool for the diagnosis of gastric cancer: a prospective multicentre clinical cohort study.

Background: Tongue images (the colour, size and shape of the tongue and the colour, thickness and moisture content of the tongue coating), reflecting the health state of the whole body according to the theory of traditional Chinese medicine (TCM), have been widely used in China for thousands of years. Herein, we investigated the value of tongue images and the tongue coating microbiome in the diagnosis of gastric cancer (GC). Methods: From May 2020 to January 2021, we simultaneously collected tongue images and tongue coating samples from 328 patients with GC (all newly diagnosed with GC) and 304 non-gastric cancer (NGC) participants in China, and 16 S rDNA was used to characterize the microbiome of the tongue coating samples. Then, artificial intelligence (AI) deep learning models were established to evaluate the value of tongue images and the tongue coating microbiome in the diagnosis of GC. Considering that tongue imaging is more convenient and economical as a diagnostic tool, we further conducted a prospective multicentre clinical study from May 2020 to March 2022 in China and recruited 937 patients with GC and 1911 participants with NGC from 10 centres across China to further evaluate the role of tongue images in the diagnosis of GC. Moreover, we verified this approach in another independent external validation cohort that included 294 patients with GC and 521 participants with NGC from 7 centres. This study is registered at ClinicalTrials.gov, NCT01090362. Findings: For the first time, we found that both tongue images and the tongue coating microbiome can be used as tools for the diagnosis of GC, and the area under the curve (AUC) value of the tongue image-based diagnostic model was 0.89. The AUC values of the tongue coating microbiome-based model reached 0.94 using genus data and 0.95 using species data. The results of the prospective multicentre clinical study showed that the AUC values of the three tongue image-based models for GCs reached 0.88-0.92 in the internal verification and 0.83-0.88 in the independent external verification, which were significantly superior to the combination of eight blood biomarkers. Interpretation: Our results suggest that tongue images can be used as a stable method for GC diagnosis and are significantly superior to conventional blood biomarkers. The three kinds of tongue image-based AI deep learning diagnostic models that we developed can be used to adequately distinguish patients with GC from participants with NGC, even early GC and precancerous lesions, such as atrophic gastritis (AG). Funding: The National Key R&D Program of China (2021YFA0910100), Program of Zhejiang Provincial TCM Sci-tech Plan (2018ZY006), Medical Science and Technology Project of Zhejiang Province (2022KY114, WKJ-ZJ-2104), Zhejiang Provincial Research Center for Upper Gastrointestinal Tract Cancer (JBZX-202006), Natural Science Foundation of Zhejiang Province (HDMY22H160008), Science and Technology Projects of Zhejiang Province (2019C03049), National Natural Science Foundation of China (82074245, 81973634, 82204828), and Chinese Postdoctoral Science Foundation (2022M713203).

BIX-01294 enhanced chemotherapy effect in gastric cancer by inducing GSDME-mediated pyroptosis.

Adjuvant chemotherapy in combination with surgery is expected to be a curative strategy for gastric cancer. However, drug resistance remains an obstacle in effective chemotherapy. Therefore, understanding the potential mechanisms of chemotherapy induced gastric cancer cell death is of great importance. We demonstrated that BIX-01294 (BIX) at low concentration could induce autophagic flux by converting LC3B-I to LC3B-II and directly activate autophagy associated cell death in gastric cancer cell lines at high concentration. BIX at low concentration could help obtain sensitivity of gastric cancer cells to chemotherapy with significantly reduced cell viability. Interestingly, BIX combined Cis (BIX + Cis) treated SGC-7901 cells display pyroptosis related cell death with large bubbles blown around the membrane, significantly decreased cell viability, elevated lactate dehydrogenase release and increased percentage of propidium iodide and Annexin-V double positive cells. Furthermore, the cleavage of gasdermin E (GSDME) and caspase-3 but not GSDMD was detected by immunoblotting and the knockout of GSDME switched pyroptosis into apoptosis in the BIX + Cis combined treated group. Furthermore, the deficiency of Beclin-1 to inhibit BIX induced autophagic flux completely blocked BIX + Cis combined treated induced cell pyroptosis related cell death. Additionally, BIX + Cis in vivo treatment could inhibit tumor growth, which could be reversed by the deficiency of Beclin-1 and be delayed by the deficiency of GSDME. In conclusion, our data was the first to reveal that BIX enhanced the anticancer chemotherapy effect by induced GSDME-mediated pyroptosis through the activation of autophagic flux in gastric cancer cells.

Primary low grade myxofibrosarcoma of the liver with benign presentation but malignant outcome: a case report.

BACKGROUND: Myxofibrosarcoma (MFS) is most often found on the limbs of aged male people, but extremely uncommon in the liver. CASE PRESENTATION: A 52-year-old female patient with a liver mass was diagnosed as a primary MFS. It had no obvious abdominal symptoms, and the tumor was resected with an extended margin. Three years after the surgery, the patient was readmitted for peritoneal metastasis and passed away 4 months later. The tumor has a benign presentation, but malignant outcome. CONCLUSIONS: Comprehensive radiological inspection, intensive preoperative evaluation, careful design of operating procedures, wide margin resection, consecutive treatment, and strict periodical follow-ups should be taken to ensure a better prognosis of this kind of neoplastic disease.

Reactivation of microRNA-506 inhibits gastric carcinoma cell metastasis through ZEB2.

MicroRNAs (miRNAs) are frequently dysregulated in a variety of human cancers, including gastric carcinoma. To improve our understanding of the role of miRNAs in gastric carcinoma and potential identify novel biomarkers or therapeutic agents, we performed microarray analysis to identify differentially expressed miRNAs in gastric carcinoma, compared with paired non-cancerous gastric tissues. We identified significantly differentially expressed miRNAs in gastric carcinoma tissues, including miR-506. We validated the microarray results by quantitative reverse transcription polymerase chain reaction in 26 specimens and confirmed significant downregulation of miR-506 in gastric carcinoma. Bioinformatics analysis predicted ZEB2 (zinc finger E-box-binding homeobox 2) as a potential target of miR-506. MiR-506 levels and ZEB2 levels were inversely correlated in gastric carcinoma, and low miR-506 levels in gastric carcinoma were associated with poor prognosis. Overexpression of miR-506 in gastric carcinoma cells significantly inhibited cell migration and invasion, while depletion of miR-506 in gastric carcinoma cells significantly increased cell migration and invasion. Transplantation of miR-506-overexpressing gastric carcinoma cells developed significantly smaller tumor, compared to the control. Thus, our results suggest that miR-506 may function as a tumor suppressor and targets and inhibits ZEB2 in gastric carcinoma.

Prevention of TLR9 Pathway in Warm Ischemia in Porcine Donor Liver after Cardiac Death.

OBJECTIVE: To investigate effect of warm ischemia after cardiac death on activation of TLR9 pathway in porcine liver. METHODS: Donor of cardiac death (DCD) model was established with Duroc, Landrace, Large White crossbred pigs. Liver tissues from the animals were harvested at 0, 5, 10, 15, 25 and 30 minutes after warm ischemia for analysis of expression of TLR9, IRF7, IFN-ß, and TNF-α at mRNA and protein levels by real-time PCR and western blot, respectively, and for assessment of NF-κB/DNA binding activity by western blot detection of p65 protein. RESULTS: Ischemia induced TLR9, IRF7, IFN-ß, and TNF-α expression at both mRNA and protein levels in an ischemic time dependent manner. Among them, expression of TNF-α and IFN- ß was induced later than TLR9 and IRF7 did. Ischemia also enhanced NF-κB binding to DNA in the DCD liver tissue. Pretreatment with iCpG specifically blocked activation of TLR9 pathway triggered by ischemia in liver and protected the animals from ischemia-caused liver tissue damage. CONCLUSION: Warm ischemia activates TLR9 pathways in the porcine liver tissue. Blocking TLR9 pathway could offer protection from ischemia-caused liver tissue in DCD liver transplantation.

TAK-242 treatment ameliorates liver ischemia/reperfusion injury by inhibiting TLR4 signaling pathway in a swine model of Maastricht-category-III cardiac death.

OBJECTIVES: This study aims to test the effects of TAK-242 on liver transplant viability in a model of swine Maastricht-category-III cardiac death. METHODS: A swine DCD Maastricht-III model of cardiac death was established, and TAK-242 was administered prior to the induction of cardiac death. The protein and mRNA level of TLR4 signaling pathway molecules and cytokines that are important in mediating immune and inflammatory responses were assessed at different time points following the induction of cardiac death. RESULTS: After induction of cardiac death, both the mRNA and protein levels of key molecules (TLR4, TRAF6, NF-Ï°B, ICAM-1, MCP-1 and MPO), TNF-α and IL-6 increased significantly. Infusion of TAK-242 1h before induction of cardiac death blocked the increase of immune and inflammatory response molecules. However, the increase of TLR4 level was not affected by infusion of TAK-242. Histology study showed that infusion of TAK-242 protect liver tissue from damage during cardiac death. CONCLUSIONS: These results indicates that TLR4 signaling pathway may contribute to ischemia/reperfusion injury in the liver grafts, and blocking TLR4 pathway with TAk-242 may reduce TLR4-mediated tissue damage.

Hypothermic machine perfusion reduces delayed graft function and improves one-year graft survival of kidneys from expanded criteria donors: a meta-analysis.

BACKGROUND: Expanded criteria donors (ECDs) are currently accepted as potential sources to increase the donor pool and to provide more chances of kidney transplantation for elderly recipients who would not survive long waiting periods. Hypothermic machine perfusion (HMP) is designed to mitigate the deleterious effects of simple cold storage (CS) on the quality of preserved organs, particularly when the donor is in a marginal status. METHODS: We compared the transplant outcomes in patients receiving ECD kidneys with either HMP or CS graft preservation. Articles from the MEDLINE, EMBASE and Cochrane Library databases were searched and all studies reporting outcomes from HMP versus CS methods of kidney preservation were included in this meta-analysis. The parameters analyzed included the incidence of delayed graft function (DGF), primary non-function (PNF) and one-year graft and patient survival. RESULTS: A total of seven studies qualified for the review, involving 2374 and 8716 kidney grafts with HMP or CS preservation respectively, all from ECD donors. The incidence of delayed graft function (DGF) was significantly reduced with an odd ratio(OR) of 0.59 (95% CI 0.54-0.66, P<0.001) and one-year graft survival was significantly improved with an OR of 1.12 (95% CI 1.03-1.21, P = 0.005) in HMP preservation compared to CS. However, there was no difference in the incidence of PNF (OR 0.54, 95% CI 0.21-1.40, P = 0.20), and one-year patient survival (OR 0.98, 95% CI 0.94-1.02, P = 0.36) between HMP and CS preservation. CONCLUSIONS: HMP was associated with a reduced incidence of DGF and an with increased one-year graft survival, but it was not associated with the incidence of PNF and one-year patient survival.

Clinical outcomes of radiofrequency ablation and surgical resection for small hepatocellular carcinoma: a meta-analysis.

BACKGROUND AND AIM: To evaluate the evidence comparing radiofrequency ablation (RFA) and surgical resection (RES) on the treatment of hepatocellular carcinoma (HCC) using meta-analytical techniques. METHODS: Literature search was undertaken until March 2011 to identify comparative studies evaluating survival rates, recurrence rates, and complications. Pooled odds ratios (OR) and 95% confidence intervals (95% CI) were calculated with either the fixed or random effect model. RESULTS: These studies included a total of 877 patients: 441 treated with RFA and 436 treated with RES. The overall survival was significantly higher in patients treated with RES than RFA at 1, 3 and 5 years (respectively: OR: 0.50, 95% CI: 0.29-0.86; OR: 0.51, 95% CI: 0.28-0.94; OR: 0.62, 95% CI: 0.45-0.84). In the RES group the 1, 3, and 5 years recurrence-free survival rates were significantly higher than the RFA group (respectively: OR: 0.65, 95% CI: 0.44-0.97; OR: 0.65, 95% CI: 0.47-0.89; OR: 0.52, 95% CI: 0.35-0.77). RFA had a higher rate of local recurrence (OR: 4.08, 95% CI: 2.03-8.20). For tumors ≤ 3 cm RES was better than RFA in the 3-year overall survival rates (OR: 0.38, 95% CI: 0.16-0.89). CONCLUSIONS: Surgical resection was superior to RFA in the treatment of HCC. However, the findings have to be carefully interpreted due to the lower level of evidence.