Survival outcome and prognostic factors for early-onset and late-onset metastatic colorectal cancer: a population based study from SEER database.

Colorectal cancer is the third most common cancer worldwide and there has been a concerning increase in the incidence rate of colorectal cancer among individuals under the age of 50. This study compared the survival outcome between early-onset and late-onset metastatic colorectal cancer to find the differences and identify their prognostic factors. We obtained patient data from SEER database. Survival outcome was estimated using Kaplan-Meier survival curves and compared using the log-rank test. Univariate and multivariate analyses were conducted utilizing COX models to identify their independent prognostic factors. A total of 10,036 early-onset metastatic colorectal (EOCRC) cancer patients and 56,225 late-onset metastatic colorectal cancer (LOCRC) patients between 2010 and 2019 were included in this study. EOCRC has more survival benefits than LOCRC. Tumor primary location (p < 0.001), the location of metastasis (p < 0.001) and treatment modalities (p < 0.001) affect the survival outcomes between these two groups of patients. Female patients had better survival outcomes in EOCRC group (p < 0.001), but no difference was found in LOCRC group (p = 0.57). In conclusion, our study demonstrated that EOCRC patients have longer survival time than LOCRC patients. The sex differences in survival of metastatic colorectal cancer patients are associated with patients' age. These findings contribute to a better understanding of the differences between metastatic EOCRC and LOCRC, and can help inform the development of more precise treatment guidelines to improve prognosis.

Survival benefits of palliative gastrectomy for gastric cancer patients with liver metastasis: a population-based propensity score-matched cohort analysis.

Background and aims: Palliative primary tumor resection (pPTR) can benefit colorectal cancer patients with liver metastasis. Whether pPTR benefiting gastric cancer (GC) patients with liver metastasis is still controversial. Methods: Data on patients with metastatic GC diagnosed between 2010 to 2019 was extracted from SEER database. Propensity score analysis with 1:1 matching was performed. The univariable and multivariable Cox proportional hazards regression models were used to explore prognostic factors. Kaplan-Meier method was used to analyze survival outcomes. Results: Of 5691 GC patients with liver metastasis, 468 were included in the matched cohorts. The results showed that the median survival time was 6 months in the non-surgery groups and 14.5 months in the surgery groups (p < 0.001). Multivariable analysis showed that surgery was a protective prognostic factor for overall survival [hazard ratio (HR) = 0.416] as well as cancer-specific survival (HR = 0.417). Also, pPTR was only recommended for GC patients with isolated liver metastasis. Moreover, pPTR combined with chemotherapy brought the greatest therapeutic effect. Conclusion: pPTR benefits GC patients with isolated liver metastasis, and GC patients with liver metastasis receiving pPTR combined with chemotherapy had the best survival outcomes than any other therapeutic model.

Capsaicin inhibits the migration, invasion and EMT of renal cancer cells by inducing AMPK/mTOR-mediated autophagy.

Capsaicin (CAP), extracted from Capsicum fruits, has been reported to exhibit antitumor effects in various lines of cancer cells. However, the mechanism underlying its antitumor efficiency is not fully understood. Autophagy is a fundamental self-degradation process of cells that maintains homeostasis and plays a controversial role in tumor initiation and progression. The EMT is defined as a system regulating cells transformed from an epithelial-like phenotype into a mesenchymal phenotype by several internal and external factors, following the metastatic performance of the cells developed. The present study aimed to investigate the potential role of autophagy in CAP-induced antitumor effects in renal cell carcinoma (RCC) 786-O and CAKI-1 cell lines. The results revealed that CAP remarkably inhibited the migration and invasion of RCC cells in vitro and metastasis in vivo. Moreover, we found that the CAP treatment increased the formation of autophagolysosome vacuoles and LC3 yellow and red fluorescent puncta in RCC cells and upregulated the expression of LC3, suggesting that autophagy was induced by CAP in 786-O and CAKI-1 cell lines. Our further results demonstrated that CAP-induced autophagy was mediated by the AMPK/mTOR pathway. In conclusion, our study provides new knowledge of the potential relationship between autophagy and metastasis inhibition induced by CAP, which might be a promising therapeutic strategy in RCC.

Adhesive anastomosis for organ transplantation.

The recent development of tough tissue adhesives has stimulated intense interests among material scientists and medical doctors. However, these adhesives have seldom been tested in clinically demanding surgeries. Here we demonstrate adhesive anastomosis in organ transplantation. Anastomosis is commonly conducted by dense sutures and takes a long time, during which all the vessels are occluded. Prolonged occlusion may damage organs and even cause death. We formulate a tough, biocompatible, bioabsorbable adhesive that can sustain tissue tension and pressurized flow. We expose the endothelial surface of vessels onto a gasket, press two endothelial surfaces to the adhesive using a pair of magnetic rings, and reopen the bloodstream immediately. The time for adhesive anastomosis is shortened compared to the time for sutured anastomosis. We have achieved adhesive anastomosis of a great vein in transplanting the liver of a pig. After the surgery, the adhesive is absorbed, the vein heals, and the pig lives for over one month.

Application of dental pulp stem cells in oral maxillofacial tissue engineering.

In the maxillofacial area, soft and hard tissue abnormalities are caused by trauma, tumors, infection, and other causes that expose the maxillofacial region to the surface of the human body. Patients' normal physiological function and appearance are interfered with, and their mental health is adversely impacted, reducing their overall life quality. The pursuit of appropriate medical treatments to correct these abnormalities is thus vital. Autologous stem cell regeneration technology mainly focused on tissues has lately emerged as a significant problem in the medical community. Because of the capacity of dental pulp stem cells (DPSCs) to self-renew, the use of DPSCs from the human pulp tissues of deciduous teeth or permanent teeth has gained popularity among scientists as a stem cell-based therapy option. Aside from that, they are simple to extract and have minimal immunogenicity. As a result, bone tissue engineering may be a critical component in treating maxillofacial and periodontal bone abnormalities. DPSCs activity in maxillofacial and periodontal tissue-engineered bone tissue was investigated in this research.

Magnetic-assisted laparoscopic liver transplantation in swine.

BACKGROUND: Although laparoscopic technology has achieved rapid development in the surgical field, it has not been applied to liver transplantation, primarily because of difficulties associated with laparoscopic vascular anastomosis. In this study, we introduced a new magnetic-assisted vascular anastomosis technique and explored its application in laparoscopic liver transplantation in pigs. METHODS: Two sets of magnetic vascular anastomosis rings (MVARs) with different diameters were developed. One set was used for anastomosis of the suprahepatic vena cava (SHVC) and the other set was used for anastomosis of the infrahepatic vena cava (IHVC) and portal vein (PV). Six laparoscopic orthotopic liver transplantations were performed in pigs. Donor liver was obtained via open surgery. Hepatectomy was performed in the recipients through laparoscopic surgery. Anastomosis of the SHVC was performed using hand-assisted magnetic anastomosis, and the anastomosis of the IHVC and PV was performed by magnetic anastomosis with or without hand assistance. RESULTS: Liver transplants were successfully performed in five of the six cases. Postoperative ultrasonographic examination showed that the portal inflow was smooth. However, PV bending and blood flow obstruction occurred in one case because the MVARs were attached to each other. The durations of loading of MVAR in the laparoscope group and manual assistance group for IHVC and PV were 13 ± 5 vs. 5 ± 1 min (P < 0.01) and 10 ± 2 vs. 4 ± 1 min (P < 0.05), respectively. The durations of MVAR anastomosis in the laparoscope group and manual assistance group for IHVC and PV were 5 ± 1 vs. 1 ± 1 min (P < 0.01), and 5 ± 1 vs. 1 ± 1 min (P < 0.01), respectively. The anhepatic phase was 43 ± 4 min in the laparoscope group and 23 ± 2 min in the manual assistance group (P < 0.01). CONCLUSIONS: Our study showed that magnetic-assisted laparoscopic liver transplantation can be successfully carried out in pigs.

Transcriptomic profiling of mice brain under Bex3 regulation.

BEX family genes are expressed in various tissues and play significant roles in neuronal development. A mouse model of Bex3 gene knock-out was generated in this study, using the CRISPR-Cas9 system. Transcriptomic analysis of the brain was performed to identify genes and pathways under Bex3 regulation. Essential biological functions under the control of Bex3 related to brain development were identified. Ninety-five genes were differentially expressed under Bex3-/- regulation, with 53 down and 42 up. Among down-regulated genes, LOC102633156 is a member of zf-C2H2, Xlr3a is an X-linked lymphocyte regulated gene, LOC101056144 is a hippocampal related gene, 2210418O10Rik and Fam205a3 are cortex related genes. Among the upregulated genes, Zfp967 is a zf protein, Tgtp2 is a T cell-specific regulator, Trpc2 is a neuron-related gene, and Evi2 is related to NF1. A total of 34 KEGG disease terms were identified under the Bex3-/- regulation. The most prominent is non-syndromic X-linked mental retardation, where Fgd1 is enriched. Similarly, IRF, MBD, SAND, zf-BED, and zf-C2H2 were significantly enriched transcription factors. A further study is required to confirm and explain each aspect that has been identified in this study.

ß-ionone Inhibits Epithelial-Mesenchymal Transition (EMT) in Prostate Cancer Cells by Negatively Regulating the Wnt/ß-Catenin Pathway.

BACKGROUND: ß-ionone is a terminal cyclic analog of beta-carotenoids widely found in plants. In recent years, accumulating evidence has shown that ß-ionone exerts antitumor effects on various malignant tumors. However, limited studies have revealed the role of ß-ionone in regulating the epithelial-mesenchymal transition (EMT) of prostate cancer (PCa) cells. This study aimed to investigate the effect of ß-ionone on the EMT process of PCa, focusing on Wnt/ß-catenin signaling pathway. METHODS: After exposure to ß-ionone, cell viability was determined by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and the Brdu proliferation assay. The Transwell and wounding healing were used to investigate the migration and invasion abilities of PCa cells. Expression of proteins involved in the EMT process (E-cadherin, N-cadherin, vimentin) and proteins in the Wnt/ß-catenin pathway (ß-catenin, GSK3-ß, and p-GSK3-ß) were explored by western blotting. The effects of ß-ionone on ß-catenin degradation were explored by cycloheximide tracking assay and in vitro ubiquitination assay. Nude mouse xenograft model was served as the model system in vivo. RESULTS: The migration, invasion, and EMT process of PCa Human PC-3 prostate adenocarcinoma cells (PC3) and Human 22RV1 prostate adenocarcinoma cells (22RV1) cells were significantly inhibited after ß-ionone treatment. In addition, ß-ionone also inhibited the growth and EMT process of subcutaneous xenograft tumors in nude mice. The study also found that ß-catenin, which promotes EMT, was downregulated after ß-ionone treatment. Further mechanistic studies revealed that ß-ionone inhibited the Wnt/ß-catenin pathway by accelerating the ubiquitination and degradation of ß-catenin in PCa, thus inhibiting the downstream migration, invasion, and EMT processes. CONCLUSIONS: These findings demonstrate that ß-ionone may be a potential natural compound targeting the Wnt/ß-catenin pathway for the treatment of PCa.

Prognostic nomogram for cancer-specific survival in patients with intrahepatic cholangiocarcinoma after hepatectomy: A population study of 919 patients.

Background and Aims: Intrahepatic cholangiocarcinoma has an increasing global incidence and mortality rate. Hepatectomy is still the most effective curative treatment for patients with ICC, but the prognosis of patients with ICC is still poor even after curative resection. This study aimed to incorporate important factors obtained from SEER database to construct and validate a nomogram for predicting the cancer-specific survival of patients with ICC after hepatectomy. Methods: We obtained patient data from SEER database. The nomogram was constructed base on six prognostic factors for predicting CSS rates in ICC patients. The nomogram was validated by C-index, ROC curve and calibration curves. Results: A total of 919 patients with ICC after hepatectomy between 2000 and 2018 were included in this study. A nomogram based on six independent prognostic factors (Black race, AJCC T, AJCC N, AJCC M, chemotherapy and PLNR ≥ 0.15) was developed for the prediction of CSS at 3 and 5 years. The C-index of the nomogram and AJCC stage system were 0.709 and 0.657 in the training cohort respectively. The 3- and 5-year AUCs of nomogram were 0.744 and 0.75 in the training cohort. The calibration plots indicated that there was good agreement between the actual observations and predictions. Conclusions: In conclusion, we constructed and validated a nomogram for predicting the 3- and 5-year CSS in ICC patients after hepatectomy. We have confirmed the precise calibration and acceptable discrimination power of our nomogram. The predictive power of this nomogram may be improved by considering other potential important factors and also by external validation.