Cuproptosis-related long non-coding RNAs model that effectively predicts prognosis in hepatocellular carcinoma.

BACKGROUND: Cuproptosis has recently been considered a novel form of programmed cell death. To date, long-chain non-coding RNAs (lncRNAs) crucial to the regulation of this process remain unelucidated. AIM: To identify lncRNAs linked to cuproptosis in order to estimate patients' prognoses for hepatocellular carcinoma (HCC). METHODS: Using RNA sequence data from The Cancer Genome Atlas Live Hepatocellular Carcinoma (TCGA-LIHC), a co-expression network of cuproptosis-related genes and lncRNAs was constructed. For HCC prognosis, we developed a cuproptosis-related lncRNA signature (CupRLSig) using univariate Cox, lasso, and multivariate Cox regression analyses. Kaplan-Meier analysis was used to compare overall survival among high- and low-risk groups stratified by median CupRLSig risk score. Furthermore, comparisons of functional annotation, immune infiltration, somatic mutation, tumor mutation burden (TMB), and pharmacologic options were made between high- and low-risk groups. RESULTS: Three hundred and forty-three patients with complete follow-up data were recruited in the analysis. Pearson correlation analysis identified 157 cuproptosis-related lncRNAs related to 14 cuproptosis genes. Next, we divided the TCGA-LIHC sample into a training set and a validation set. In univariate Cox regression analysis, 27 LncRNAs with prognostic value were identified in the training set. After lasso regression, the multivariate Cox regression model determined the identified risk equation as follows: Risk score = (0.2659 × PICSAR expression) + (0.4374 × FOXD2-AS1 expression) + (-0.3467 × AP001065.1 expression). The CupRLSig high-risk group was associated with poor overall survival (hazard ratio = 1.162, 95%CI = 1.063-1.270; P < 0.001) after the patients were divided into two groups depending upon their median risk score. Model accuracy was further supported by receiver operating characteristic and principal component analysis as well as the validation set. The area under the curve of 0.741 was found to be a better predictor of HCC prognosis as compared to other clinicopathological variables. Mutation analysis revealed that high-risk combinations with high TMB carried worse prognoses (median survival of 30 mo vs 102 mo of low-risk combinations with low TMB group). The low-risk group had more activated natural killer cells (NK cells, P = 0.032 by Wilcoxon rank sum test) and fewer regulatory T cells (Tregs, P = 0.021) infiltration than the high-risk group. This finding could explain why the low-risk group has a better prognosis. Interestingly, when checkpoint gene expression (CD276, CTLA-4, and PDCD-1) and tumor immune dysfunction and rejection (TIDE) scores are considered, high-risk patients may respond better to immunotherapy. Finally, most drugs commonly used in preclinical and clinical systemic therapy for HCC, such as 5-fluorouracil, gemcitabine, paclitaxel, imatinib, sunitinib, rapamycin, and XL-184 (cabozantinib), were found to be more efficacious in the low-risk group; erlotinib, an exception, was more efficacious in the high-risk group. CONCLUSION: The lncRNA signature, CupRLSig, constructed in this study is valuable in prognostic estimation of HCC. Importantly, CupRLSig also predicts the level of immune infiltration and potential efficacy of tumor immunotherapy.

Application of a New Mesh Fixation Method in Laparoscopic Incisional Hernia Repair.

Laparoscopic incisional hernia repair using intraperitoneal onlay mesh (IPOM) is one of the most widely used minimally invasive methods for repairing incisional hernias. The laparoscopic IPOM involves implanting the mesh into the abdominal cavity through laparoscopy to repair an abdominal wall hernia. In the IPOM surgery, after the closure of the hernia ring, an anti-adhesion mesh is placed laparoscopically. The correct placement of this mesh is critical to the success of the method, and surgical skills are required to achieve perfect placement. If the mesh placement is not mastered properly, the operation and anesthesia time will be prolonged. In addition, improper placement of the mesh can lead to serious consequences, such as intestinal obstruction and mesh infection. A "contraposition and alignment" mesh fixation method is described in this study, which involves pre-marking the fixation position of the mesh to reduce the difficulty of mesh placement. A properly placed mesh is completely flat on the peritoneum, the edges are not curled or wrapped, and the mesh is adhered firmly such that there is no displacement after removing the pneumoperitoneum pressure. The "contraposition and alignment" mesh fixation technique offers the advantages of reliable placement of the mesh and fewer complications than other techniques, and it is easy to learn and master. It also allows for positioning the nail gun in advance based on the anatomy of the incisional hernia. This enables the use of the minimum number of nails possible while still ensuring good fixation, which can reduce the occurrence of complications and reduce the cost of surgery. Thus, the mesh fixation method described here is highly suitable for clinical applications based on the aforementioned advantages.

Botulinum Toxin A Facilitated Laparoscopic Repair of Complex Ventral Hernia.

Background: Complex ventral hernia repair can be challenging despite the recent advances in surgical techniques. Here, we aimed to examine the effectiveness of preoperative combined use of botulinum toxin A (BTA) and preoperative progressive pneumoperitoneum (PPP) for surgical preparation of patients with complex ventral hernia. Methods: In this prospective, observational study, we included 22 patients with complex ventral hernia between January 2018 and May 2021. All patients were treated with BTA injections into the lateral abdominal muscles and PPP before hernia repair. The lengths of abdominal wall muscles, the volumes of the incisional hernia (VIH), the volumes of the abdominal cavity (VAC), and the VIH/VAC ratio were measured before and after BTA and PPP using abdominal CT scan. All Hernias were repaired using laparoscopic intra-peritoneal onlay mesh (IPOM) or laparoscopic-open-laparoscopic (LOL) techniques. Results: Imaging showed a significant increase in the mean lateral abdominal muscle length from 13.1 to 17.2 cm/side (p < 0.01). Before and after BTA and PPP, the mean VIH was 894 cc and 1209 cc (P < 0.01), and the mean VAC was 6,692 cc and 9,183 cc (P < 0.01). The VAC increased by 2,491 cc (P < 0.01) and was greater than the mean VIH before PPP. An average reduction of 0.9% of the VIH/VAC ratio after BTA and PPP was obtained (p > 0.05). All hernias were surgically reduced with mesh, hernia recurrence occurred in only two patients. Conclusions: The preoperative combined use of PPP and BTA increased the abdominal volume, lengthened the laterally retracted abdominal muscles, and facilitated laparoscopic closure of large complex ventral hernia.