PurposeThe aim of this study was to screen and establish independent prognostic models for primary and recurrent retroperitoneal liposarcoma (RLS).MethodsA total of 2,429 patients confirmed to have RLS were extracted from the Surveillance, Epidemiology and End Results (SEER) database. The 245 patients collected from the same period at First Medical Center, Chinese People Liberation Army General Hospital (CPLAGH), were used for external validations. Nomogram were built on the basis of clinical practicability, univariate and multivariate Cox analyses.ResultsAfter performing a stepwise analysis, the simplified predictive models for primary RLS were primarily based on tumor size (median size, 162 mm [range, 90–230], p < 0.001) and pathological subtypes (WDL vs. DDL, hazard ratio [HR] = 2.11; 95% confidence interval [CI] = 1.71–2.61; p < 0.001), both of which can be readily obtained in outpatient settings. In contrast, TNM stage (HR = 2.18; 95% CI = 1.49–3.20; p < 0.001), an important postoperative prognostic factor, emerged as a significant predictor for recurrent RLS. The area under the time-dependent receiver operating characteristic curve (time-dependent AUC) and the concordance index (C-index) for overall survival (OS) and cancer-specific survival (CSS) models both approached 0.75 in both training and validation cohorts. Moreover, calibration curves and decision curve analysis (DCA) demonstrated that the validated models were not only reliable but also clinically applicable.ConclusionWe have developed efficient and independent models for both primary and recurrent RLS. These models will provide invaluable clinical guidance, aiding in prognostication and facilitating personalized therapeutic decision-making.

Objective This study aimed to show the clinicopathological characteristics of large retroperitoneal liposarcoma (RLS) and to develop a customized nomogram model for patients with large RLS. Methods A total of 1735 patients diagnosed with RLS were selected from the public SEER database. Among them, 1113 patients with a maximum tumor diameter greater than 150 mm were included for further analysis. Nomogram models were developed based on Lasso and multivariate Cox regression analyses. A total of 166 patients that presented in the same period at our institution were used for external validations. Results A larger tumor size in RLS was associated with worse survival outcomes. Lasso and Cox regression analyses consistently identified age, TNM stage, occurrence pattern, histology, and surgery as important prognostic factors for OS. The constructed model demonstrated robust predictive performance, with better time-ROC (time-dependent receiver operating characteristic) for 1-year (83.1%), 3-year (83.8%), and 5-year (81.4%) survival in the training cohort. The concordance index (C-index) was approximately 0.80 in both the training and validation cohorts, reflecting excellent discriminatory ability of the model. Survival risk stratification analysis revealed significant differences in survival outcomes of large RLS (HR = 4.12 [3.31–5.12], p < 0.001, in the training cohort). Decision curve analysis (DCA) confirmed that the nomogram provided greater net benefits across a range of threshold probabilities. Conclusion This study identified important prognostic factors for survival in patients with large RLS and developed a reliable nomogram for predicting OS. The model’s strong predictive performance supports its use in personalized treatment strategies, improving prognosis assessment and clinical decision making for these patients.

Advanced gastric cancer (GC) is a malignant tumor with poor prognosis, which requires in-depth exploration of its malignant progression mechanism and the development of efficient therapeutic protocols. Serine hydroxymethyltransferase (SHMT), an important hub in serine-glycine-nucleotide metabolic pathways, plays a crucial role in the occurrence and progression of GC. Bioinformatics analysis and cytological experiments preliminary identified the important role of SHMTs in GC. Drug synergistic screening assays were used to build the therapeutic model in the study. The transcriptomic analysis was performed to clarify the underlying mechanism of combination treatment. Here, we found that the SHMT1 and SHMT2 promoted malignant progression and 5-Fu resistance on GC, and their targeted inhibitor SHIN1 is a promising antitumor drug for GC. The synergistic screening analysis showed that SHIN1 was an efficient synergist for 5-Fu, and combination therapy, alleviated 5-Fu resistance to GC. Mechanistically, The combination treatment induces cell cycle arrest, DNA damage and cellular senescence through the activation of the P53 signaling pathway. These unique characteristics of cell growth inhibition, which are induced via interfering with nucleotide synthesis, were validated by substantial in vitro and in vivo assays. The regimen of SHIN1 combination with 5-Fu may be an efficient preclinical model for the treatment of GC. Huan Deng, Yajie Wang, Lin Xiao, Yisheng Pan. The SHMT inhibitor SHIN1 augments the antitumor efficacy of 5-Fuin preclinical models of gastric cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 1670.

The aim of this study was to establish independent prognostic models for primary and recurrent retroperitoneal liposarcoma (RLS). A total of 2429 patients confirmed to have RLS were extracted from the Surveillance, Epidemiology and End Results (SEER) database. The 245 patients collected from the same period at First Medical Center, Chinese People Liberation Army General Hospital (CPLAGH), were used for external validations. Nomogram were built on the basis of clinical practicability, univariate and multivariate Cox analyses. The simplified predictive models for primary RLS was mainly based on tumor size (median size, 162 mm [range, 90-230], P < 0.001) and pathological subtypes (WDL vs DDL, hazard ratio[HR]=2.11; 95% confidence interval [CI]=1.71-2.61; P < 0.001), which can be acquired in the outpatient clinics. However, TNM stage (Stage 1 vs Stage 2, HR=2.18; 95% CI=1.49-3.20; P < 0.001) as an extremely important postoperative indicator was enrolled in the model for recurrent RLS. The area under the time-dependent receiver operating characteristic curve (time-dependent AUC) and concordance index (C-index) of models almost approach 0.75 in the training and validation cohorts. These results indicated favourable discrimination of the models. The calibration curves of the model illustrated good consistency between the predicted and observed survival probabilities in both the training and two validation cohorts. Furthermore, decision curve analysis (DCA) revealed that the nomogram models were clinically useful and had considerable practicability. Efficient and independent models for primary and recurrent RLS will providing clinical guidance for both prognostication and individualized therapeutic decision-making. Huan Deng, Zhenhau Lu, Binrui Wang, Yisheng Pan. v [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 4524.

Objective This study aimed to show the clinicopathological characteristics of large retroperitoneal liposarcoma (RLS) and to developed a customized nomogram model for those patients. Methods A total of 1735 patients diagnosed with RLS were selected from the Surveillance, Epidemiology, and End Results (SEER) database. Among them, 1113 patients with a maximum tumor diameter greater than 150 mm were included for further analysis. Nomogram models were developed based on lasso and multivariate cox regression analyses. The 166 patients collected from the same period at First Medical Center, Chinese People Liberation Army General Hospital (CPLAGH), were used for external validations. The model was further validated through multiple dimensions. Results Larger tumor size in RLS was associated with worse survival outcomes (hazard ratio [HR] = 0.66, 95% confidence interval [CI]: 0.53–0.81, P < 0.05). Lasso and Cox regression analyses consistently identified age, TNM stage, occurrence pattern, histology, and surgery as important prognostic factors for OS. The constructed model demonstrated robust predictive performance, with better time-ROC (Time-Dependent Receiver Operating Characteristic) for 1-year (83.1%), 3-year (83.8%), and 5-year (81.4%) survival in training cohort. The concordance index (C-index) was approximately 0.80 in both the training and validation cohorts, reflecting excellent discriminatory ability of the model. Survival risk stratification analysis revealed significant differences in survival outcomes between the groups (HR = 4.12 [3.31–5.12], P < 0.001 in training cohort). Decision curve analysis (DCA) confirmed that the nomogram provided greater net benefits across a range of threshold probabilities. Conclusion This study identified important prognostic factors for survival in patients with large RLS and developed a reliable nomogram for predicting OS. The model’s strong predictive performance supports its use in personalized treatment strategies, improving prognosis assessment and clinical decision-making for these patients.

Advanced gastric cancer (GC) represents a malignancy tumor with poor prognosis, which requires urgent exploration into its molecular drivers and innovative therapeutic strategies. This study investigates the oncogenic role of serine hydroxymethyltransferase isoforms (SHMT1/SHMT2), key regulators of serine-glycine-one-carbon metabolism, in GC progression and chemoresistanc. Bioinformatics analysis and cytological experiments preliminary identified the important role of SHMTs in GC. Drug synergistic screening assays were used to build the therapeutic model in the study. The transcriptomic analysis was performed to clarify the underlying mechanism of combination treatment. Our investigations demonstrate that SHMT1 and SHMT2 functionally drive malignant progression and confer 5-fluorouracil (5-Fu) resistance in GC, while their selective inhibitor SHIN1 emerges as a novel therapeutic candidate for GC treatment. The synergistic screening analysis showed that SHIN1 was an efficient synergist for 5-Fu, and the combinative therapy amplified their anticancer effects. Mechanistically, the combination treatment induced cell cycle arrest, DNA damage and cellular senescence by regulating the P53 signaling pathway. These unique characteristics of cell cycle arrest through interfering nucleotide synthesis were validated by substantial in vitro and in vivo assays. The present study revealed SHMT isforms as the potential promoter for malignant progression and chemoresistance in GC. The inhibitor SHIN1 alleviates chemoresistance of 5-Fu and augments both therapeutic effects on GC. In conclusion, the combination of SHIN1 with 5-Fu represents a promising preclinical model for GC treatment, offering a novel strategy to overcome drug resistance and improve therapeutic efficacy.

Department of Gastrointestinal Surgery, Peking University First Hospital Sponsorships or competing interests that may be relevant to content are disclosed at the end of this article. Published online ■ ■ *Corresponding author. Address: Department of Gastrointestinal Surgery, Peking University First Hospital, No.8 Xishku Street, Xicheng District, Beijing, China. E-mail address: [email protected] (Y. Pan). This is an open access article distributed under the Creative Commons Attribution-ShareAlike License 4.0, which allows others to remix, tweak, and build upon the work, even for commercial purposes, as long as the author is credited and the new creations are licensed under the identical terms. http://creativecommons.org/licenses/by-sa/4.0/

Background The clinical profiles of recurrent retroperitoneal liposarcoma (RLS) need to be explored. The recurrence patterns of RLS are controversial and ambiguous. Methods A total of 138 patients with recurrent RLS were finally recruited in the study. The analysis of overall survival (OS) and recurrence-free survival (RFS) was performed by Kaplan‒Meier analysis. To identify independent prognostic factors, all significant variables on univariate Cox regression analysis ( P ≤ 0.05) were subjected to multivariate Cox regression analysis. The corresponding nomogram model was further built to predict the survival status of patients. Results Among patients, the 1-, 3-, and 5-year OS rates were 70.7%, 35.9% and 30.9%, respectively. The 1-, 3- and 5-year RFS rates of the 55 patients who underwent R0 resection were 76.1%, 50.8% and 34.4%, respectively. The multivariate analysis revealed that resection method, tumor size, status of pathological differentiation, pathological subtypes and recurrence pattern were independent risk factors for OS or RFS. Patients with distant recurrence (DR) pattern usually had multifocal tumors (90.5% vs. 74.7%, P < 0.05); they were prone to experience changes of pathological differentiation (69.9% vs. 33.3%, P < 0.05) and had a better prognosis than those with local recurrence (LR) pattern. R0 resection and combined organ resection favored the survival of patients with DR pattern in some cases. Conclusions Patients with DR pattern had better prognosis, and they may benefit more from aggressive combined resection than those with LR pattern. Classifying the recurrence patterns of RLS provides guidance for individualized clinical management of recurrent RLS.

ObjectiveGastric cancer (GC) is one of the most malignant tumors worldwide. Thus, it is necessary to explore the underlying mechanisms of GC progression and develop novel therapeutic regimens. Long non-coding RNAs (lncRNAs) have been demonstrated to be abnormally expressed and regulate the malignant behaviors of cancer cells. Our previous research demonstrated that lncRNA colon cancer-associated transcript 2 (CCAT2) has potential value for GC diagnosis and discrimination. However, the functional mechanisms of lncRNA CCAT2 in GC development remain to be explored.MethodsGC and normal adjacent tissues were collected to detect the expression of lncRNA CCAT2, ESRP1 and CD44 inclinical specimens and their clinical significance for GC patients. Cell counting kit-8, wound healing and transwell assays were conducted to investigate the malignant behaviors in vitro. The generation of nude mouse xenografts by subcutaneous, intraperitoneal and tail vein injection was performed to examine GC growth and metastasis in vivo. Co-immunoprecipitation, RNA-binding protein pull-down assay and fluorescence in situ hybridization were performed to reveal the binding relationships between ESRP1 and CD44.ResultsIn the present study, lncRNA CCAT2 was overexpressed in GC tissues compared to adjacent normal tissues and correlated with short survival time of patients. lncRNA CCAT2 promoted the proliferation, migration and invasion of GC cells. Its overexpression modulates alternative splicing of Cluster of differentiation 44 (CD44) variants and facilitates the conversion from the standard form to variable CD44 isoform 6 (CD44v6). Mechanistically, lncRNA CCAT2 upregulated CD44v6 expression by binding to epithelial splicing regulatory protein 1 (ESRP1), which subsequently mediates CD44 alternative splicing. The oncogenicrole of the lncRNA CCAT2/ESRP1/CD44 axis in the promotion of malignant behaviors was verified by both in vivo and in vitro experiments. ConclusionsOur findings identified a novel mechanism by which lncRNA CCAT2, as a type of protein-binding RNA,regulates alternative splicing of CD44 and promotes GC progression. This axis may become an effective target for clinical diagnosis and treatment.

To the Editor: Retroperitoneal liposarcoma (RLS) pertains to one of the rare malignant tumors originated from the retroperitoneum. It is evaluated as the most common type of retroperitoneal sarcoma. RLS can be divided into four subtypes according to the pathological classification, which includes well-differentiated liposarcoma (WDL), dedifferentiated liposarcoma (DDL), myxoid cell liposarcoma (MLS), and pleomorphic liposarcoma (PLS).[1] Giant RLS refers to the RLS with long diameter two times larger than the specified length of pathologic tumor stage-4 (pT4) category (≥30 cm) according to the eighth version of the American Joint Committee on Cancer (AJCC) Staging Manual.[2] Despite relatively low incidence, it brings great health burdens for patients and the standard therapeutic strategies remain to be explored. There are specific features of giant RLS according to clinical experience. For instance, giant RLS can occupy almost the entire abdominal cavity, close to or even wrapping around the inferior vena cava. Due to its location in the deep abdomen, patients usually have untypical symptoms at the early stage. The obvious signs and symptoms can be perceived only when the tumor becomes giant. These features increase difficulties in achieving complete resection during surgery and satisfactory patient outcomes. In addition, there is a lack of comprehensive research on the characteristics of giant RLS, which hinders the further progress of its diagnosis and targeted therapies. Identification of giant RLS characteristics may have great significance in clinical practice. Herein, we conducted a single-center retrospective study to reveal the clinicopathological features and outcomes of patients with giant RLS. This study was approved by the Protection of Human Subjects Committee of the Chinese People's Liberation Army (PLA) General Hospital (No. S2015-106-01). Informed written consent was provided by all participants included in this study. A total of 61 patients with giant RLS who received treatment at the First Medical Center, PLA General Hospital from January 2000 to December 2015 were enrolled in this study. Those with remote metastasis or perioperative death, or who received chemoradiotherapy were excluded from this study. The complete surgical margin referred to the resected margin without observable tumors. The complete resection was defined as the operation that macroscopically resected RLS without residual tumors. The time point of recurrence was when the recurrent region of RLS was detected. Overall survival (OS) referred to the time from surgical complete resection to the end of 5-year follow-up or death. Recurrence-free survival (RFS) was defined as the time from surgical complete resection to the onset of recurrence or death within 5 years.[3] Univariate analysis was performed for the selection of factors that were correlated with OS or RFS. The candidate factors were next included in the multivariate analysis to determine independent prognostic factors using Cox regression model. The categorical data were expressed as number (percentage); continuous variables were expressed as median (Q1–Q3) since they are not normally distributed. All data were analyzed using IBM SPSS Statistics for Windows, Version 25.0 (IBM Corp, Armonk, New York, USA). A two-sided P-value < 0.05 was considered statistically significant. In this retrospective study, there were 34 male (56%) and 27 female (44%) patients. The median age of them was 55 (46–63) years. The median size of tumors was 35 (31–40) cm [Supplementary Table 1, https://links.lww.com/CM9/B211], and the giant tumors could occupy the entire abdominal cavity [Supplementary Figure 1, https://links.lww.com/CM9/B211]. Considering the proportions and differentiation status of the four pathological subtypes of giant RLS, the patients were divided into two subgroups: WDL and non-WDL groups. WDL group accounted for the largest proportions among the four subtypes (34/61, 56%); the remaining 27 cases with DDL, MLS, and PLS subtypes were classified as the non-WDL group (44%). A total of 41 patients underwent organ resection (67%) and 17 cases were subjected to the resection of three and more organs (28%) [Supplementary Table 1, https://links.lww.com/CM9/B211]. The colon was the most frequently removed organ [Supplementary Figure 2, https://links.lww.com/CM9/B211]. Postoperative complications were evaluated according to the Clavien–Dindo classification.[4] There were 19 cases scored as Grade I (31%); while 42 cases underwent more serious complications were scored as Grades II–IV (69%) [Supplementary Table 1, https://links.lww.com/CM9/B211]. Subgroup analysis showed that 52% of cases in WDL group who received complete resection suffered from the Grade II–IV complications (13/25), while 81% of cases in non-WDL group who received complete resection had the Grade II–IV complications (13/16) [Supplementary Figure 3, https://links.lww.com/CM9/B211]. The median OS of all patients was 40 months during the 5-year follow up. The 1-, 3-, and 5-year OS rates were 83.8%, 51.7%, and 31.3%, respectively [Figure 1A]. To explore prognostic factors of 5-year OS for patients with giant RLS, univariate analysis was performed and indicated that resection times, resection method, intraoperative bleeding volume, total transfusion volume, postoperative complication, tumor morphology, tumor number, completeness of tumor capsule, pathological subtype, and status of surgical margin had significant correlations with 5-year OS (all P < 0.05) [Supplementary Table 1, https://links.lww.com/CM9/B211]. Variables with statistical significance were further examined using multivariate analysis. The results showed that postoperative complication and status of surgical margin were the prognostic factors of 5-year OS (both P < 0.05) [Supplementary Table 1, https://links.lww.com/CM9/B211].Figure 1: The 5-year OS and RFS analysis of patients with giant RLS. (A) The 5-year OS analysis of all 61 giant RLS patients included in this study. (B and C) The 5-year OS analysis of patients with WDL subtype (B) and non-WDL subtype (C) undergoing complete and incomplete resection. (D and E) The 5-year OS analysis of patients based on postoperative complication grades (D) and surgical margin status (E). (F) The 5-year RFS analysis of all 41 patients who received complete resection. (G and H) The 5-year RFS analysis of patients based on tumor capsule completeness (G) and resection times (H). OS: Overall survival; RFS: Recurrence-free survival; RLS: Retroperitoneal liposarcoma; WDL: Well-differentiated liposarcoma.The patients were next stratified to investigate the 5-year OS of subpopulations. Patients with WDL subtype of giant RLS who received complete resection had significantly better 5-year OS than those who received incomplete resection (P < 0.05) [Figure 1B]; whereas, for those with non-WDL subtypes, the difference between the two groups with complete or incomplete resections was not significant (P > 0.05) [Figure 1C]. In addition, we found that the patients who had milder postoperative complications or negative surgical margins obtained better 5-year OS (P < 0.05) [Figures 1D and 1E]. For the investigations into prognostic factors of RFS, data of 41 of the 61 patients, who received complete resection, were analyzed [Supplementary Table 2, https://links.lww.com/CM9/B211]. A total of 33 patients experienced local recurrence within 5 years. The median RFS was 15 (8–25) months. The 1-, 3-, and 5-year RFS rates of patients were 61.6%, 18.7%, and 13.4%, respectively [Figure 1F]. According to the univariate analysis, resection times, pathological subtype, and completeness of tumor capsule were correlated with 5-year RFS (all P < 0.05). After multivariate analysis, only the pathological subtype (P < 0.05) showed as an independent prognostic factor of 5-year RFS [Supplementary Table 2, https://links.lww.com/CM9/B211]. In addition, we found that the 5-year RFS of patients who had incomplete tumor capsules or multiple surgeries (resection times >3) was worse (both P < 0.05) [Figures 1G and 1H]. Few studies focused on the clinicopathological characteristics and survival outcomes of patients with giant RLS. Our study aimed to investigate the clinical features and risk factors of giant RLS, providing basic evidence for the development of giant RLS therapy. Compared with the survival outcomes of patients with non-giant RLS reported by other studies, those who suffered from giant RLS may have a worse prognosis.[5] Moreover, the processes of giant RLS resection are complicated, which may increase the risks of postoperative complications. In this study, we found that serious postoperative complication was significantly associated with the poor prognosis of patients with giant RLS. The importance of postoperative management of complications should be emphasized for patients with giant RLS. The role of pathological subtype in predicting the survival time of patients with ordinary RLS has been revealed in recent years. In this study, however, the pathological subtype was not proved to be an independent prognostic factor of 5-year OS. This contradiction may be attributable to the progression of giant RLS. The pathological subtype presented in this study was identified during the last surgery before follow-up. Well-differentiated giant RLS may progress to poorly-differentiated subtype, promoting tumor invasion, and attenuating survival benefits of patients. Additionally, the follow-up endpoint for RFS is tumor recurrence or a patient's death. RFS can reflect the effects of detected pathological subtype on survival time, free from potential influences of subsequent progression. Our findings proved that pathological subtype served as an independent factor of 5-year RFS, which further verifies our assumption that giant RLS may have a natural tendency to malignant progression. The completeness of surgical resection has been reported as an independent prognostic factor of patients with RLS. Supported by this evidence, wide application of complete RLS resection has been recommended. However, this opinion may be inappropriate for the treatment of giant RLS. In this study, giant tumors in many cases were found wrapping around abdominal organs and large vessels, which increased difficulties in achieving complete resection. Rigid conduction of complete resection may conversely elevate surgical risks and impair benefits from operations. Hence, a complete resection strategy for a giant RLS requires cautious consideration. Patients with WDL subtype of giant RLS could obtain significant survival benefits from complete resection when compared with those receiving incomplete resection. However, there were no significant differences in survival time between non-WDL patients who received complete and incomplete resections, and they were more likely to have severe postoperative complications. This suggests that pathological subtype may serve as an indicator for surgical decision-making. Radical resection may fit for patients with WDL subtype of giant RLS, while the cases with non-WDL subtype may need staging or palliative operations. Further clinical investigations should be conducted to prove the effectiveness of this strategy. It has to be admitted that there are several limitations. First, the study only included the cases from one center and the sample size is small due to the extremely low incidence of giant RLS. It impairs the representativeness of this research. Second, as a retrospective study, the range of collected information is limited and some potential biases cannot be eliminated. Third, several indicators of pathological examination, such as tumor necrosis and mitotic count, were not reported in some cases. It increases difficulties in more deeply identifying mechanisms underlying giant RLS progression. In conclusion, the status of surgical margins and postoperative complications were independent factors of OS, and the pathological subtype was proved as an independent marker for the recurrence of giant RLS. Complete resection for the WDL subtype of giant RLS contributed to prognosis improvement. However, survival benefits from complete resection were not obtained for the patients with non-WDL subtype of giant RLS. The pathological subtype may serve as an important reference indicator for the surgical decision-making process of giant RLS. Funding This study was supported by the National Natural Science Foundation of China (No. 82073192) and the National Key Research and Development Project of China (No. 2019YFB1311505). Conflicts of interest None.

This study aimed to investigate the protective effects of S-adenosylmethionine (SAM) on irinotecan-induced intestinal barrier dysfunction and microbial ecological dysregulation in both mice and human colon cell line Caco-2, which is widely used for studying intestinal epithelial barrier function. Specifically, this study utilized Caco-2 monolayers incubated with 7-ethyl-10-hydroxycamptothecin (SN-38) as well as an irinotecan-induced diarrhea model in mice.Our study found that SAM pretreatment significantly reduced body weight loss and diarrhea induced by irinotecan in mice. Furthermore, SAM inhibited the increase of intestinal permeability in irinotecan-treated mice and ameliorated the decrease of Zonula occludens-1(ZO-1), Occludin, and Claudin-1 expression. Additionally, irinotecan treatment increased the relative abundance of Proteobacteria compared to the control group, an effect that was reversed by SAM administration. In Caco-2 monolayers, SAM reduced the expression of reactive oxygen species (ROS) and ameliorated the decrease in transepithelial electrical resistance (TER) and increase in fluorescein isothiocyanate-dextran 4000 Da (FD-4) flux caused by SN-38. Moreover, SAM attenuated changes in the localization and distribution of ZO-1and Occludin in Caco-2 monolayers induced by SN-38 and protected barrier function by inhibiting activation of the p38 MAPK/p65 NF-kappa B/MLCK/MLC signaling pathway. These findings provide preliminary evidence for the potential use of SAM in treating diarrhea caused by irinotecan.

We read with interest the excellent and meaningful research by Caminada et al.,1 which showed that invasive procedures and surgical interventions play an important role in hepatitis. They performed a case‒control study to investigate the influence of surgical procedures on the transmission of viral hepatitis. The study enrolled 8,176 patients with HBV infection and 2,179 with HCV infection from a national surveillance system in Italy. They found that invasive procedures were a significant risk factor for acquiring parenterally transmitted hepatitis viruses.

BackgroundRetroperitoneal liposarcoma (RLS) is a rare but severe disease. Repeated postoperative recurrence with multiple tumors is a therapeutic dilemma. The clinical outcomes and survival predictors of recurrent RLS with multiple tumors remain to be explored.MethodsPatients with recurrent RLS were retrospectively analyzed. Univariate and multivariate analysis was performed to find independent prognostic factors that were correlated with Overall survival (OS) or progression-free survival (PFS). Factors significant in univariate analysis were further included into multivariate Cox proportional hazards regression model. The nomogram model was built to predict the survival status of patients. Variables that were significant in multivariable analysis were added to the internally validated nomogram models. The analysis of OS and PFS was performed by Kaplan–Meier analysis and log-rank test.ResultsA total of 113 recurrent RLS patients with multiple tumors were enrolled in the study. The 1-, 3-, and 5-years OS (PFS) rates were 70.7% (76.1%), 35.9% (76.1%), and 30.9% (76.1%), respectively. Univariate and multivariate analyses showed that number of surgeries, resection methods, tumor size, status of pathological differentiation, pathological subtypes, and recurrence patterns were important prognostic factors for OS or PFS (each p < 0.05). Nomogram models were established to efficiently predict the prognostic status of patients. Patients with the local recurrence (LR) pattern had a poor prognosis and would derive no survival benefit from combined organ resection and R0/R1 resection (each p < 0.05).ConclusionRLS patients recurrence with multiple tumors had a poor prognosis. Those patients should be followed up more frequently after surgery. The strategies of aggressive resection may not improve the survival of patients with LR pattern in the retroperitoneum. Prognostic factors in the efficient nomogram models should be considered in the individualized clinical management of recurrent RLS with multiple tumors.

Objective:To analyze the perioperative clinical characteristics of patients with blunt abdominal trauma and open trauma，and to compare the differences during the clinical treatment process.Methods:A retrospective analysis method was used to collect clinical data of 87 patients with abdominal trauma between January 2011 and December 2017. Patients were divided into blunt trauma group（n=41 cases）and open trauma group（n=46 cases）according to whether there were open abdominal wounds. Statistical software SPSS26.0 was used for data analysis. Measurement data of normal distribution was expressed as（xˉ±s），and t-test was used for comparison between groups. Non-normally distribution quantitative data are showed by the median（interquartile range IQR），and the rank sum test was used for comparison between groups. P<0.05 was considered as statistically significant difference.Results:Among the injury factors，the main cause of injury in the blunt group was car accident injury，accounting for 46.3%，and the main cause of injury in the open group was knife stabbing，accounting for 56.5%. Multiple injuries were 58.5% in the blunt group and 23.9% in the open group，respectively. Compared with the open group，the ratio of neutrophils to lymphocytes before operation（3.31 vs. 2.35），hospitalization time（12 d vs.9 d），intraoperative blood loss（650 ml vs. 400 ml），and grade Ⅱ wound healing（34 cases vs. 28 cases），intraoperative blood transfusion（38 cases vs. 33 cases），intestinal-abdominal wall fistula（25 cases vs. 37 cases），postoperative complications ≤grade Ⅱ（23 cases vs. 36 cases），the differences were statistically significant（P<0.05）.Conclusion:Blunt abdominal trauma and open trauma have different clinical characteristics. In general，patients with blunt trauma are more severely injury，difficult to surgery，more serious postoperative complications，and more complicated during perioperative management. The diagnosis and treatment strategy of blunt trauma should be prepared differently.

Objective:To analyze the short-term outcomes between open and robotic gastrectomy for elderly gastric cancer patients and explore the independent factors which influenced postoperative complications after gastrectomy.Methods:A retrospective study was conducted. We collected clinical data of 161 elder patients (Age over 70 years) undergoing open or robotic gastrectomy in the department of general surgery, Chinese PLA General Hospital First Medical Center between May 2017 and May 2021 were collected. The characteristics of clinicopathological datas between two groups were not significantly different(P>0.05).Results:The operative time was significantly longer in the robotic group compared to the open group [(242.92±55.12) min vs. (170.37±43.15)min, P<0.001]. Although intraoperative bleeding was comparable between the robotic and open groups [100 ml (100-200) ml vs. 100 ml (10-200) ml, P=0.102], the proportion of bleeding ≥400 ml was significantly lower in the robotic group compared with the open group(4.8% vs. 15.4%), with a statistically significant difference (P=0.025). The difference between the robotic and open groups were not statistically significant in the aspect of the number of retrieved lymph nodes [(24.51±9.51) vs. (24.28±9.36), P=0.881], postoperative hospital stay [10.0 d (9.0-12.0) d vs. 9.1 d (8.6-11.0) d, P=0.094], 30 days postoperative complication rate (25.3% vs. 26.9%, P=0.815), severe complication rate (8.4% vs. 3.8%, P=0.228), anastomotic leakage rate (2.4% vs. 5.1%, P=0.363), and 30 days postoperative mortality (2.4% vs. 1.3%, P=0.597). Univariate and multifactorial analyses showed that age ≥80 years was an independent risk factor for postoperative complications in elderly patients with gastric cancer.Conclusions:Elderly patients who accepted robotic gastrectomy are safe and feasible. Over 80 years old is the independent risk factor of the postoperative complications after gastrectomy which needs to evaluate the surgical risk sufficiently.

Background Traumatic colon injury (TCI) is a common disease during wartime. Prolongation of posttraumatic survival time is an effective approach to patient outcome improvement. However, there is a lack of basic research in this field. This study aimed to elucidate the mechanisms underlying TCI progression and to develop novel regimens to buy time for TCI patients on the battlefield. Methods A total of 669 Sprague–Dawley rats were used in this study. Surgical colon incision was performed to generate the TCI rat model. The landscape of colon microbiota compositions was depicted using 16S rRNA sequencing and metabolites in the intestinal contents were detected by metabolomics profiling. The signaling transduction in the intestinal epithelium was investigated using antibody microarrays and Western blotting. The enzyme-linked immunosorbent assay was conducted to measure the levels of interleukin-6 and tumor necrosis factor-α in intestines and plasma for the detection of inflammatory responses. Diamine oxidase, D-lactate and endotoxin in plasma and protein expression of zonula occludens 1 and occludin were selected as the indicators of intestinal barrier permeability. To investigate alterations of microbiota symbiosis, the relative abundances of specific bacterial genera were detected using quantitative real-time PCR. Results As a type of lethal injury, TCI induced acute disruption of intestinal homeostasis, characterized by inflammatory responses, intestinal barrier hyperpermeability and microbiota dysbiosis ( P < 0.05). Significant alterations in bacterial metabolic patterns were detected with decreases in many metabolites. After a series of screenings, we found that oral administration of asparagine (Asn) and 3-indolepropionic acid (IPA) effectively prolonged posttraumatic survival time [Asn plus IPA vs. Vehicle: hazard ratio ( HR ) = 0.105, 95% CI 0.031–0.356, P = 0.0003] and restored intestinal homeostasis in TCI rats ( P < 0.05). Mechanistically, this combinational strategy protected the rats against TCI through synergistic activation of Akt signaling in the intestinal epithelium ( P < 0.05). Conclusions Abrupt dysregulation of intestinal homeostasis plays a critical role in the progression toward TCI-induced death. Oral administration of Asn plus IPA may serve as an effective regimen to restore intestinal functions and prolong the posttraumatic survival time.

Background:Circular RNAs (circRNAs) regulate multiple malignant behaviors of various types of cancer. The role of circDNMT1, a newly identified circRNA, remains unknown in gastric cancer (GC). This study aimed to elucidate the underlying mechanisms of circDNMT1 in regulating GC progression.Methods:microRNA (miRNA) and circRNA expression was detected by quantitative real-time PCR. Western blotting was performed to measure hypoxia inducible factor-1 alpha (HIF-1α) protein expression. Sanger sequencing, gel electrophoresis and fluorescence in situ hybridization were performed to identify the presence of circDNMT1. The clinicopathological features and overall survival of patients were analyzed based on circDNMT1 expression. The proliferation, migration and invasion of GC cells were determined by cell counting kit-8, 5-ethynyl-2'-deoxyuridine, wound healing and transwell assays. Glycolysis of GC cells was detected based on the levels of glucose uptake, the lactate acid, ATP and pyruvic acid production and the extracellular acidification and oxygen consumption rates. The binding sites between miR-576-3p and circDNMT1 or HIF-1α were predicted by online bioinformatic tools and were validated using RNA pull-down and luciferase reporter assays. Xenograft models were established to determine the effects of the circDNMT1/miR-576-3p/HIF-1α axis on GC growth and metastasis in vivo.Results:circDNMT1 was successfully identified and shown to be overexpressed in GC tissues and cell lines. The expression levels of circDNMT1 were correlated with pathological T stage, pathological TNM stage and shorter survival time of GC patients. circDNMT1 knockdown inhibited the proliferation, migration, invasion and glycolysis of GC cells. circDNMT1 functioned as an oncogenic factor by sponging miR-576-3p. HIF-1α was negatively regulated by miR-576-3p via binding its mRNA 3' untranslated region. circDNMT1 promoted malignant behaviors and metabolic reprogramming of GC by targeting the miR-576-3p/HIF-1α axis both in vitro and in vivo.Conclusion:These findings demonstrated that circDNMT1 knockdown inhibited GC proliferation, migration, invasion and glycolysis through sponging miR-576-3p/HIF-1α axis. circDNMT1 may be a novel target for GC treatment.