Comparison of Short-term and Three-year Oncological Outcomes Between Robotic and Laparoscopic Gastrectomy for Gastric Cancer: A Large Multicenter Cohort Study.

OBJECTIVE: To compare the short-term and long-term outcomes between robotic gastrectomy (RG) and laparoscopic gastrectomy (LG) for gastric cancer. BACKGROUND: The clinical outcomes of RG over LG have not yet been effectively demonstrated. METHODS: This retrospective cohort study included 3599 patients with gastric cancer who underwent radical gastrectomy at eight high-volume hospitals in China from January 2015 to June 2019. Propensity score matching was performed between patients who received RG and LG. The primary end point was 3-year disease-free survival (DFS). RESULTS: After 1:1 propensity score matching, 1034 pairs of patients were enrolled in a balanced cohort for further analysis. The 3-year DFS in the RG and LG was 83.7% and 83.1% ( P =0.745), respectively, and the 3-year overall survival was 85.2% and 84.4%, respectively ( P =0.647). During 3 years of follow-up, 154 patients in the RG and LG groups relapsed (cumulative incidence of recurrence: 15.0% vs 15.0%, P =0.988). There was no significant difference in the recurrence sites between the 2 groups (all P >0.05). Sensitivity analysis showed that RG had comparable 3-year DFS (77.4% vs 76.7%, P =0.745) and overall survival (79.7% vs 78.4%, P =0.577) to LG in patients with advanced (pathologic T2-4a) disease, and the recurrence pattern within 3 years was also similar between the 2 groups (all P >0.05). RG had less intraoperative blood loss, lower conversion rate, and shorter hospital stays than LG (all P >0.05). CONCLUSIONS: For resectable gastric cancer, including advanced cases, RG is a safe approach with comparable 3-year oncological outcomes to LG when performed by experienced surgeons.

Robotic natural orifice specimen extraction surgery versus robotic transabdominal specimen extraction surgery for early-stage rectal cancer: a multicenter propensity score-matched analysis (in China).

BACKGROUND: Despite the global increase in the adoption of robotic natural orifice specimen extraction surgery (R-NOSES), its advantages over robotic transabdominal specimen extraction surgery (R-TSES) for treating early-stage rectal cancer remain debated. There is scant nationwide, multicenter studies comparing the surgical quality and short-term outcomes between R-NOSES and R-TSES for this condition. OBJECTIVE: This retrospective cohort study was conducted nationally across multiple centers to compare the surgical quality and short-term outcomes between R-NOSES and R-TSES in early-stage rectal cancer. DESIGN: Multicenter retrospective cohort trial. SETTING: Eight experienced surgeons from 8 high-volume Chinese colorectal cancer treatment centers. PATIENTS: The study included 1086 patients who underwent R-NOSES or R-TSES from October 2015 to November 2023 at the 8 centers. Inclusion criteria were: (1) histologically confirmed rectal adenocarcinoma; (2) robotic total mesorectal excision; (3) postoperative pathological staging of TisN0M0 or T1-2N0M0; (4) availability of complete surgical and postoperative follow-up data. Patients were matched 1:1 in the R-NOSES and R-TSES groups using the propensity score matching (PSM) technique. RESULTS: After PSM, 318 matched pairs with well-balanced patient characteristics were identified. The operation time for the R-NOSES group was significantly longer than that for the R-TSES group [140 min (125-170 min) vs. 140 min (120-160 min), P = 0.032]. Conversely, the times to first flatus and initial oral intake in the R-NOSES group were significantly shorter than those in the R-TSES group [48 h (41-56 h) vs. 48 h (44-62 h), P = 0.049 and 77 h (72-94 h) vs. 82 h (72-96 h), P = 0.008], respectively. Additionally, the length of postoperative hospital stay was shorter in the R-NOSES group compared with the R-TSES group [7 day (7-9 day) vs. 8 day (7-9 day), P = 0.005]. The overall postoperative complication rates were similar between the groups (10.7% in the R-NOSES group vs. 11.9% in the R-TSES group, P = 0.617). However, the R-NOSES group had a lower incidence of wound complications compared to the R-TSES group (0.0% vs. 2.2%, P = 0.015). Regarding surgical stress response, the R-NOSES group showed superior outcomes. Additionally, patients in the R-NOSES group required fewer additional analgesics on postoperative days 1, 3, and 5 and reported lower pain scores compared to the R-TSES group. The body image scale (BIS) and cosmetic scale (CS) scores were also significantly higher in the R-NOSES group. Furthermore, the R-NOSES group demonstrated significantly better outcomes in functional dimensions such as physical, role, emotional, social, and cognitive functioning, and in symptoms like fatigue and pain, when compared to the R-TSES group. LIMITATIONS: It is imperative to ensure the safe and standardized implementation of R-NOSES through the establishment of a uniform training protocol. CONCLUSIONS: These results affirm that R-NOSES is a safe and effective treatment for early-stage rectal cancer when meticulously executed by skilled surgeons.

Kinesin family member 11 promotes progression of hepatocellular carcinoma via the OCT4 pathway.

Hepatocellular carcinoma (HCC) is the tumor with the second highest mortality rate worldwide. Recent research data show that KIF11, a member of the kinesin family (KIF), plays an important role in the progression of various tumors. However, its expression and molecular mechanism in HCC remain elusive. Here, we evaluated the potential role of KIF11 in HCC. The effect of KIF11 was evaluated using the hepatocellular carcinoma cell lines, LM3 and Huh7, after genetic or pharmacological treatment. Evaluating the role of KIF11 in the xenograft animal models using its specific inhibitor. The role of KIF11 was systematically evaluated using specimens obtained from the aforementioned animal and cell models after various in vivo and in vitro experiments. The clinicopathological analysis showed that KIF11 was expressed at high levels in patients with hepatocellular carcinoma. Cell experiments in vitro showed that KIF11 deficiency significantly slowed the proliferation of liver tumor cells. And in the experiment using liver cancer cells overexpressing OCT4, overexpression of OCT4 substantially increased the proliferation of tumor cells compared with tumor cells with KIF11 knockdown alone. Both in vitro cell experiment and in vivo xenotransplantation tumor experiment showed that monastrol, an inhibitor of KIF11, could effectively delay the proliferation and migration of tumor cells. Based on these results, KIF11 is expressed at high levels in hepatocellular carcinoma and promotes tumor proliferation in an OCT4-dependent manner. KIF11 may become a therapeutic target for hepatocellular carcinoma, and its inhibitor monastrol may become a clinical antitumor drug.

Identification and validation of core genes in tumor-educated platelets for human gastrointestinal tumor diagnosis using network-based transcriptomic analysis.

Gastrointestinal (GI) tumors have increasing incidence worldwide with their underlying mechanisms still not being fully understood. The use of tumor-educated platelets (TEPs) in liquid biopsy is a newly-emerged blood-based cancer diagnostic method. Herein, we aimed to investigate the genomic changes of TEPs in GI tumor development and their potential functions using network-based meta-analysis combined with bioinformatic methods. We used a total of three eligible RNA-seq datasets, which were integrated using multiple meta-analysis methods on the NetworkAnalyst website, and identified 775 DEGs (differentially expressed genes; 51 up-regulated and 724 down-regulated genes) in GI tumor relative to healthy control (HC) samples. These TEP DEGs were mostly enriched in bone marrow-derived cell types and associated with gene ontology (GO) of "carcinoma" and could affect pathways of "Integrated Cancer Pathway" and "Generic transcription pathway" respectively for highly and lowly expressed DEGs. Combined network-based meta-analysis and protein-protein interaction (PPI) analysis identified cyclin dependent kinase 1 (CDK1) and heat shock protein family A (Hsp70) member 5 (HSPA5) to be the hub genes with the highest degree centrality (DC), being up-regulated and down-regulated in TEPs, respectively. GO and Kyoto Encyclopedia of Genes and Genomes (KEGG) results showed that the hub genes were primarily related to cell cycle and division, nucleobase-containing compound and carbohydrate transport, and endoplasmic reticulum unfolded protein response. Additionally, the nomogram model suggested that the two-gene signature owns extraordinary predictive power for GI tumor diagnosis. Further, the two-gene signature was demonstrated to have potential value for metastatic GI tumor diagnosis. The expression levels of CDK1 and HSPA5 in clinical platelet samples were verified to be consistent with the results from bioinformatic analysis. This study identified a two-gene signature encompassing CDK1 and HSPA5 that can be used as a biomarker for GI tumor diagnosis and maybe even cancer-associated thrombosis (CAT)-related prognosis.

What is the context? Gastrointestinal (GI) tumors are now responsible for the majority of cancer-related mortalities worldwide.In the majority of cases of cancer, curative treatments are not recommended at the time of diagnosis. In this case, early screening and diagnosis is very important for overall tumor prognosis. Liquid biopsy emerged as a newly introduced minimally invasive approach for cancer diagnosis by detecting blood analytes as tumor-educated platelets (TEPs). Compared to tissue-based biopsies, liquid biopsies are less invasive, easy to access, convenient for serial tracking and better in eliminating intratumoral spatial heterogeneity. In recent years, specific gene signatures have been identified for cancer diagnosis, prognosis and prediction based on gene profiling data of TEPs. However, most of these studies were performed on the independent platelet profile datasets published on the Gene Expression Omnibus (GEO) database, which may harbor enormous heterogeneity. Additionally, few study revealed TEP mRNA functions and roles in GI tumors. Therefore, there's the need of using an integrated method to re-analyze these data, so we can gain new insights for GI tumor diagnosis.What is new? Herein, through network-based RNA-seq meta-analysis, we identified the CDK1-HSPA5 signature in TEPs that has the potential as a biomarker for diagnosing GI tumors. This is the first time, to our knowledge, that a shared transcriptional signature of tumor-educated platelets has been identified in human GI tumor patients based on meta-analysis. Additionally, we found the two-gene signature has potential value for metastatic GI tumor diagnosis. We also demonstrated that HSPA5 may have different roles in blood and tumor cells, so its expression deregulation in distinct types of tissue may have opposing diagnostic and prognostic values.What is the impact? Our work provides a novel biomarker for platelet-based GI tumor prediction and diagnosis, which may also be used as novel targets for thrombosis prevention during cancer development in the future.

3D matrix promotes cell dedifferentiation into colorectal cancer stem cells via integrin/cytoskeleton/glycolysis signaling.

The potential for tumor occurrence triggered by cancer stem cells (CSCs) has emerged as a significant challenge for human colorectal cancer therapy. However, the underlying mechanism of CSC development remains controversial. Our study provided evidence that the bulk of tumor cells could dedifferentiate to CSCs and reacquire CSC-like phenotypes if cultured in the presence of extracellular matrix reagents, such as Matrigel and fibrin gels. In these 3D gels, CD133- colorectal cancer cells can regain tumorigenic potential and stem-like phenotypes. Mechanistically, the 3D extracellular matrix could mediate cytoskeletal F-actin bundling through biomechanical force associated receptors integrin ß1 (ITGB1), contributing to the release of E3 ligase tripartite motif protein 11 (TRIM11) from cytoskeleton and degradation of the glycolytic rate-limiting enzyme phosphofructokinase (PFK). Consequently, PFK inhibition resulted in enhanced glycolysis and upregulation of hypoxia-inducible factor 1 (HIF1α), thereby promoting the reprogramming of stem cell transcription factors and facilitating tumor progression in patients. This study provided novel insights into the role of the extracellular matrix in the regulation of CSC dedifferentiation in a cytoskeleton/glycolysis-dependent manner.

The safety and efficacy of laparoscopic surgery versus laparoscopic NOSE for sigmoid and rectal cancer.

BACKGROUND: Laparoscopic surgery with natural orifice specimen extraction (La-NOSE) is being performed more frequently for the minimally invasive management of sigmoid and rectal cancer. The objective of this meta-analysis was to compare the clinical and oncological safety and efficacy of La-NOSE versus conventional laparoscopy (CL). METHODS: A search of the PubMed, Web of Science, and Cochrane databases was performed for studies that compared clinical or oncological outcomes of conventional laparoscopic resection using NOSE with conventional laparoscopic resection for sigmoid and rectal cancer. RESULTS: Compared with CL group, the length of hospital stay and the pain score on the first day were shorter in the La-Nose group. The La-NOSE group had a lower incidence of total perioperative complications (OR 0.46; 95% CI [0.32 to 0.66]; I2 = 0%; P < 0.0001) and a lower incidence of surgical site infections (SSIs) (OR 0.11; 95% CI [0.04 to 0.29]; I2 = 0%; P < 0.0001) than the CL group, while the anastomotic leakage showed no significant difference between the La-Nose group and the CL group (P = 0.19). 5-year disease-free survival (DFS) and 5-year overall survival (OS) were no significant difference between the La-Nose group and the CL group (P = 0.43, P = 0.40, respectively). CONCLUSIONS: La-NOSE can achieve oncological and surgical safety comparable to that of CL for patients with sigmoid and rectal cancer. La-NOSE in patients was associated with a shorter hospital stay, shorter time to first flatus or defecation, less postoperative pain, and fewer surgical site infections (SSIs) and total perioperative complications. In general, the operative time in La-NOSE was longer than that in CL. The long-term oncological efficacy of La-NOSE seems to be equivalent to that of CL.

Inhibitor of apoptosis-stimulating p53 protein protects against inflammatory bowel disease in mice models by inhibiting the nuclear factor kappa B signaling.

Drugs and therapies available for the treatment of inflammatory bowel disease (IBD) are not satisfactory. Our previous study has established the inhibitor of apoptosis-stimulating p53 protein (iASPP) as an oncogenic regulator in colorectal cancer by forming a regulatory axis or feedback loop with miR-124, p53, or p63. As iASPP could target and inhibit nuclear factor kappa B (NF-κB) activation, in this study the role and mechanism of iASPP in IBD was investigated. The aberrant up-regulation of iASPP in IBD was subsequently confirmed, based on online data sets, clinical sample examinations and 2,4,6-trinitrobenzene sulfonic acid (TNBS)- and dextran sulfate sodium (DSS)-induced colitis mice models. TNBS or DSS stimulation successfully induced colon shortness, body weight loss, mice colon oxidative stress and inflammation. In both types of colitis mice models, iASPP over-expression improved, whereas iASPP knockdown aggravated TNBS or DSS stimulation-caused colon shortness, body weight loss and mice colon oxidative stress and inflammation. Meanwhile, in both types of colitis mice models, iASPP over-expression inhibited p65 phosphorylation and decreased the levels of tumor necrosis factor (TNF)-α, interleukin (IL)-1ß, IL-6, C-X-C motif chemokine ligand (CXCL)1 and CXCL2 in mice colons, whereas iASPP knockdown exerted opposite effects.

Totally Robotic Distal Gastrectomy: A Safe and Feasible Minimally Invasive Technique for Gastric Cancer Patients Who Undergo Distal Gastrectomy.

PURPOSES: To explore the safety and feasibility of totally robotic distal gastrectomy (TRDG) for gastric cancer patients who undergo distal gastrectomy. METHODS: Consecutive patients with gastric cancer who underwent TRDG (TRDG group) and robotic-assisted distal gastrectomy (RADG) (RADG group) were systematically reviewed at the Second Xiangya Hospital of Central South University from October 2015 to August 2018. Data were collected and statistically analyzed. RESULTS: A total of 161 consecutive patients were included in this study: 84 cases in the TRDG group and 77 in the RADG group. Clinical characteristics and pathological results were mostly similar in both groups. The TRDG group had a significantly longer anastomotic time (20.6 ± 3.3 vs. 17.5 ± 4.0 min, p ˂ 0.001) but showed no difference in total operating time (167.0 ± 18.0 vs. 162.9 ± 17.6 min, p = 0.159). The postoperative hospitalization in the TRDG group was shorter than that in the RADG group (6.7 ± 1.2 vs. 7.2 ± 1.7 days, p = 0.019). Conversion rate, estimated blood loss, and postoperative complications were similar in both groups. There were no statistical differences in the estimated 2-year disease-free survival and overall survival rate between both groups. CONCLUSIONS: Although our current results need to be verified in further studies, TRDG represents a safe and feasible approach to distal gastrectomy and embodies the theory of minimally invasive surgery.

Wip1 cooperates with KPNA2 to modulate the cell proliferation and migration of colorectal cancer via a p53-dependent manner.

Due to the increasing incidence and mortality, the early diagnosis, specific targeted therapies, and prognosis for colorectal cancer (CRC) attract more and more attention. Wild-type p53-induced phosphatase 1 (Wip1) and karyopherin α2 (KPNA2) have been regarded as oncogenes in many cancers, including CRC. Wip1 dephosphorylates p53 to inactivate it. TP53 activator and Wip1 inhibitor downregulate KPNA2 expression. Therefore, we speculate that Wip1 may co-operate with KPNA2 to modulate CRC progression in a p53-dependent manner. Here, Wip1 and KPNA2 messenger RNA expression and protein levels are significantly increased in CRC tissues and cell lines and are positively correlated with each other. Wip1 silence increases p53 phosphorylation while decreases KPNA2 protein. Wip1 knockdown remarkably suppresses CRC cell proliferation and migration while KPNA2 overexpression exerts an opposing effect. KPNA2 overexpression could partially rescue Wip1 silence-inhibited CRC cell proliferation and migration. Finally, Wip1 interacts with KPNA2 to modulate the activation of AKT/GSK-3ß signaling and metastasis-related factors. In summary, Wip1 could co-operate with KPNA2 to modulate CRC cell proliferation and migration, possibly via a p53-dependent manner, through downstream AKT/GSK-3ß pathway. We provided a novel mechanism of Wip1 interacting with KPNA2, therefore modulating CRC cell proliferation and migration.

Functional role of a long non-coding RNA LIFR-AS1/miR-29a/TNFAIP3 axis in colorectal cancer resistance to pohotodynamic therapy.

Colorectal Cancer (CRC) is one of the most common digestive system malignant tumors. Recently, PDT has been used as a first-line treatment for colon cancer; however, limited curative effect was obtained due to resistance of CRC to PDT. During the past decades, accumulating CRC-related long non-coding RNAs (lncRNAs), microRNAs (miRNAs) and mRNAs have been reported to exert diverse functions through various biological processes; their dysregulation might trigger and/or promote the pathological changes. Herein, we performed microarrays analysis to identify dysregulated lncRNAs, miRNAs and mRNAs in PDT-treated HCT116 cells to figure out the lncRNA-miRNA interactions related to the resistance of CRC to PDT treatment, and the downstream mRNA target, as well as the molecular mechanism. We found a total of 1096 lncRNAs dysregulated in PDT-treated CRC HCT116 cells; among them, LIFR-AS1 negatively interacted with miR-29a, one of the dysregulated miRNAs in PDT-treated CRC cells, to affect the resistance of CRC to PDT. LIFR-AS1 knockdown attenuated, whereas miR-29a inhibition enhanced the cellular effect of PDT on HCT116 cell proliferation and apoptosis. Furthermore, among the dysregulated mRNAs, TNFAIP3 was confirmed to be a direct target of miR-29a and exerted a similar effect to LIFR-AS1 on the cellular effects of PDT. In summary, LIFR-AS1 serves as a competitive endogenous RNA (ceRNA) for miR-29a to inhibit its expression and up-regulate downstream target TNFAIP3 expression, finally modulating the resistance of CRC to PDT. We provide an experimental basis for this lncRNA/miRNA/mRNA network being a promising target in CRC resistance to PDT treatment.

Combining albumin-bilirubin score with future liver remnant predicts post-hepatectomy liver failure in HBV-associated HCC patients.

BACKGROUND AND AIMS: Accurate assessment of liver functional reserve pre-operatively is vital for safe hepatic resection. The ALBI score is a new model for assessing liver function. This study aimed to evaluate the value of combining ALBI score with sFLR in predicting post-operative morbidity and PHLF in HCC patients who underwent hepatectomy. METHODS: Patients undergoing three-dimensional CT reconstruction prior to hepatectomy for HCC between January 2015 and January 2017 were enrolled. The values of the CP score, ALBI score and sFLR in predicting post-operative outcomes were evaluated. RESULTS: A total of 229 HCC patients were enrolled; 24 (10.5%) experienced major complications and 21 (9.2%) developed PHLF. The incidence of major complications and PHLF increased with increasing ALBI grade. The ALBI grade classified patients with CP grade A into two subgroups with different incidences of PHLF (P=.029). sFLR and ALBI scores were identified as independent predictors of PHLF. The AUC values for the CP score, ALBI score, sFLR and sFLR×ALBI for predicting major complications were 0.600, 0.756, 0.660 and 0.790 respectively. The AUC values of the CP score, ALBI score, sFLR and sFLR×ALBI for predicting PHLF were 0.646, 0.738, 0.758 and 0.884 respectively. CONCLUSIONS: The ALBI score showed superior predictive value of post-operative outcomes over CP score, and the combination of sFLR and ALBI score was identified as a stronger predictor of post-operative outcomes than the sFLR or ALBI score alone.

Robotic low anterior resection plus transanal natural orifice specimen extraction in a patient with situs inversus totalis.

BACKGROUND: Situs inversus totalis (SIT) refers to an unusual condition involving reversal of abdominal and thoracic viscera, with an incidence rate of 1/5000-20,000 adults. Minimally invasive surgeries for SIT patients are technically challenging, while the surgical experience for SIT patients is quite limited. CASE PRESENTATION: A 61-year-old man, previously diagnosed as SIT, came to our hospital for 6 months history of hematochezia and altered bowel habit. A diagnosis of rectal cancer was made in view of colonoscopic biopsy which confirmed an irregular circumferential lump of well differentiated adenocarcinoma at 10 cm from the anal verge. The computed tomography contrast-enhanced (thorax + abdomen + pelvis) scan revealed a total transposition of abdominal and thoracic organs and an enhanced eccentric mass of rectal but with no evidence of distant metastasis. Robotic low anterior resection (LAR) plus transanal natural orifice specimen extraction (NOSE) was performed after obtaining informed consent. The procedure was performed successfully and the patient convalesced nicely without any complications. The postoperative pathological diagnosis revealed a 4x4x0.6 cm3 moderately differentiated adenocarcinoma and circumferential clearance. CONCLUSIONS: Robotic LAR plus transanal NOSE for rectal cancer patients with SIT can be performed safely and may be an effective approach in contrast to open or laparoscopic approach, despite the unconventional anatomy.

Impact of a Eukaryotic Translation Initiation Factor 3a Polymorphism on Susceptibility to Gastric Cancer.

OBJECTIVE: To investigate single nucleotide polymorphisms in the eukaryotic translation initiation factor 3a (eIF3a) gene and the risk for gastric cancer within the Chinese population. SUBJECTS AND METHODS: A total of 322 patients with gastric cancer were selected as the patient group and 340 non-gastric cancer patients were selected as the control group using the case-control method. Polymerase chain reaction-sequence-specific primer technology was leveraged to genotype the rs77382849 single nucleotide polymorphism in the eIF3a gene. The demographic characteristics of the study population and other exposures to risk factors were collected. Unconditional logistic regression analysis was performed to determine the association between the risk factors and gastric cancer. RESULTS: A higher frequency of the eIF3a rs77382849 GG homozygote genotype was observed in the gastric cancer patients compared with the controls (63.98 vs. 54.41%, p < 0.05). After adjustment of exposure risks, such as age, gender, smoking, and drinking, the rs77382849 single nucleotide polymorphism was still associated with susceptibility to gastric cancer. When the eIF3a rs77382849 GG homozygote genotype was used as the reference group, the GA genotype (GA vs. GG: OR = 0.545, 95% CI: 0.386-0.769, p = 0.001) and AA genotype (AA vs. GG: OR = 0.245, 95% CI: 0.072-0.836, p = 0.025) were both correlated with a significantly decreased risk for gastric cancer development. CONCLUSION: An association between eIF3a rs77382849 polymorphism and susceptibility to gastric cancer was observed in these Chinese patients.

Biomimetic modification of macrophage membrane-coated prussian blue nanoparticles loaded with SN-38 to treat colorectal cancer by photothermal-chemotherapy.

SN-38 is the active metabolite of irinotecan and acts as an effective topoisomerase I inhibitor with therapeutic effects on many malignant tumors, including some drug-resistant cancers. However, the poor solubility, low bioavailability, and severe dose-dependent toxicity limits the clinical application of SN-38. Currently, emerging macrophage membrane-coated nanoparticles provide an efficient biomimetic approach to develop novel SN-38 formulations for the reduction of its side effects. Photothermal therapy (PTT) is a promising methods in tumor treatment to thermally ablate tumors using various materials such Prussian blue nanoparticles (NPs) and can combined with chemotherapy to synergistically work. There is no report that combined SN38 and photothermal therapy for the treatment of colorectal cancer (CRC). SN38-PB@CM NPs were constructed by loading SN-38 into macrophage cell membrane-coated hollow mesoporous Prussian blue (PB) NPs. The morphology, size and zeta potential were evaluated by transmission microscopy and dynamic light scatter (DLS). Coomassie bright blue staining was performed to assess total protein profile. The photothermal properties of it were also investigated via near-infrared imaging. CCK8 and calcein-AM/PI staining were used to evaluate cell viability. Flow cytometry was performed to assess cell apoptosis. The fluorescent microscopy was used to observe cellular uptake of SN38-PB@CM NPs to assess its internalization in vitro. The biodistribution, tumor-targeting efficacy, antitumor efficacy and safety of SN38-PB@CM NPs in vivo were assessed in CT26 tumor-bearing mice via In Vivo Imaging System. SN38-PB@CM NPs were successfully constructed and exhibited a uniform size distribution (140.5 ± 4.3 nm) and an excellent drug-loading capacity (5.61 ± 0.64%). SN38-PB@CM NPs showed stable release properties within 72 h. It can also enhance the selective intracellular delivery of SN38 in vitro and showed good near-infrared (NIR) photothermal properties. And the NPs showed excellent tumor targeting, effective photothermal therapy, improved biosafety and antitumor efficacy on CT26-bearing mice. Multifunctional SN38-PB@CM NPs could achieve improved biosafety, great tumor-targeting, high-efficiency PTT and excellent antitumor efficacy, which provided a promising and attractive combination therapy for the treatment of CRC.

Chronic exposure to BDE-47 aggravates acute pancreatitis and chronic pancreatitis by promoting acinar cell apoptosis and inflammation.

The effect of 2,2',4,4'-tetrabromodiphenyl ether (BDE-47), a persistent environmental pollutant commonly used as a flame retardant in various consumer products, on pancreatitis has not been clearly elucidated, although it has been reported to be toxic to the liver, nervous system, and reproductive system. Acute pancreatitis (AP) and chronic pancreatitis (CP) models were induced in this study by intraperitoneal injection of caerulein. The aim was to investigate the impact of BDE-47 on pancreatitis by exposing the animals to acute (1 week) or chronic (8 weeks) doses of BDE-47 (30 mg/kg in the low-concentration group and 100 mg/kg in the high-concentration group). Additionally, BDE-47 was utilized to stimulate mouse bone marrow-derived macrophages, pancreatic primary stellate cells, and acinar cells in order to investigate the impact of BDE-47 on pancreatitis. In vivo experiments conducted on mice revealed that chronic exposure to BDE-47, rather than acute exposure, exacerbated the histopathological damage of AP and CP, leading to elevated fibrosis in pancreatic tissue and increased infiltration of inflammatory cells in the pancreas. In vitro experiments showed that BDE-47 can promote the expression of the inflammatory cytokines Tnf-α and Il-6 in M1 macrophages, as well as promote acinar cell apoptosis through the activation of the PERK and JNK pathways via endoplasmic reticulum stress. The findings of this study imply chronic exposure to BDE-47 may exacerbate the progression of both AP and CP by inducing acinar cell apoptosis and dysregulating inflammatory responses.

Hspb1 protects against severe acute pancreatitis by attenuating apoptosis and ferroptosis via interacting with Anxa2 to restore the antioxidative activity of Prdx1.

Acute pancreatitis (AP) is a common abdominal disease that typically resolves on its own, but the mortality rate dramatically increases when it progresses to severe acute pancreatitis (SAP). In this study, we investigated the molecular mechanism underlying the development of SAP from AP. We utilized two SAP models induced by pancreatic duct ligation and caerulein administration. Transcriptomic and proteomic analyses were subsequently performed to determine the mRNA and protein expression profiles of pancreatic samples from SAP and AP model and normal mice. To explore the role of Hspb1 in SAP, we used Hspb1 knockout (KO) mice, a genetically engineered chronic pancreatitis strain (T7D23A), Anxa2 KO mice, and acinar cell-specific Prdx1 knockout mice. Additionally, various in vivo and in vitro assays were performed to elucidate the molecular events and direct targets of Hspb1 in acinar cells. We found that Hspb1 expression was upregulated in AP samples but significantly reduced in acinar cells from SAP samples. KO or inhibition of Hspb1 worsened AP, while AAV8-Hspb1 administration mitigated the severity of SAP and reduced remote organ damage in mice. Furthermore, AAV8-Hspb1 treatment prevented the development of chronic pancreatitis. We found that KO or inhibition of Hspb1 promoted acinar cell death through apoptosis and ferroptosis but not necroptosis or autophagy by increasing reactive oxygen species (ROS) and lipid ROS levels. Mechanistically, Hspb1 directly interacted with Anxa2 to decrease its aggregation and phosphorylation, interact with the crucial antioxidant enzyme Prdx1, and maintain its antioxidative activity by decreasing Thr-90 phosphorylation. Notably, the overexpression of Hspb1 did not have a protective effect on acinar-specific Prdx1 knockout mice. In summary, our findings shed light on the role of Hspb1 in acinar cells. We showed that targeting Hspb1/Anxa2/Prdx1 could serve as a potential therapeutic strategy for SAP.

Mechanism underlying the effect of Pulsatilla decoction in hepatocellular carcinoma treatment: a network pharmacology and in vitro analysis.

BACKGROUND: Currently, hepatocellular carcinoma (HCC) is associated with a poor prognosis. Moreover, there exist limited strategies for treating HCC. Pulsatilla decoction (PD), a traditional Chinese medicine formula, has been used to treat inflammatory bowel disease and several cancer types. Accordingly, we explored the mechanism of PD in HCC treatment via network pharmacology and in vitro experiments. METHODS: Online databases were searched for gene data, active components, and potential target genes associated with HCC development. Subsequently, bioinformatics analysis was performed using protein-protein interaction and Network Construction and Kyoto Encyclopedia of Genes and Genomes (KEGG) to screen for potential anticancer components and therapeutic targets of PD. Finally, the effect of PD on HCC was further verified by in vitro experiments. RESULTS: Network pharmacological analysis revealed that 65 compounds and 180 possible target genes were associated with the effect of PD on HCC. These included PI3K, AKT, NF-κB, FOS, and NFKBIA. KEGG analysis demonstrated that PD exerted its effect on HCC mainly via the PI3K-AKT, IL-17, and TNF signaling pathways. Cell viability and cell cycle experiments revealed that PD could significantly inhibit cancer cell proliferation and kill HCC cells by inducing apoptosis. Furthermore, western blotting confirmed that apoptosis was mediated primarily via the PI3K-AKT, IL-17, and TNF signaling pathways. CONCLUSION: To the best of our knowledge, this is the first study to elucidate the molecular mechanism and potential targets of PD in the treatment of HCC using network pharmacology.

A propensity score matching study of totally robotic right hemicolectomy versus robot-assisted right hemicolectomy.

To compare and analyze the differences in safety, feasibility and short-term efficacy between robot-assisted right hemicolectomy (RARH) and totally robotic right hemicolectomy (TRRH). We collected the information of 184 patients who underwent right hemicolectomy in the Second Xiangya Hospital of Central South University from July 2016 to December 2021. We matched 148 patients (74 with robot-assisted right hemicolectomy and 74 with totally robotic right hemicolectomy) to conduct a retrospective analysis of their clinical outcomes. The incision lengths were 5.14 ± 0.60 cm in the RARH group and 4.74 ± 0.55 cm in the TRRH (p < 0.001). The blood losses were 86.28 ± 52.57 mL in the RARH group and 69.19 ± 44.78 mL in the TRRH (p = 0.035). The operative times were 197.50 min (171.25-242.25) in the RARH group and 160.00 min (145.00-188.75) in the TRRH (p < 0.001). The postoperative hospital stays were 11.18 ± 4.32 days in the RARH group and 9.53 ± 4.42 days in the TRRH (p = 0.023). The NRS pain scores were 3.05 ± 0.23 in the RARH group and 2.96 ± 0.26 in the TRRH (p = 0.019). The abdominal drainage extraction times were 7.54 ± 1.44 days in the RARH group and 7.00 ± 1.25 days in the TRRH (p = 0.016). Postoperative complications in the RARH group are fewer than TRRH (p = 0.033). TRRH is safe and feasible. Compared with RARHs, the TRRHs resulted in shorter incision lengths, operative times, intraoperative blood losses, postoperative hospital stays, first flatus times, first liquid diet times, and drainage tube removal times, and they improved NRS pain scores and postoperative complication frequencies.

The anoikis-related gene signature predicts survival accurately in colon adenocarcinoma.

Colon adenocarcinoma (COAD) is a serious public health problem, the third most common cancer and the second most deadly cancer in the world. About 9.4% of cancer-related deaths in 2020 were due to COAD. Anoikis is a specialized form of programmed cell death that plays an important role in tumor invasion and metastasis. The presence of anti-anoikis factors is associated with tumor aggressiveness and drug resistance. Various bioinformatic methods, such as differential expression analysis, and functional annotation analysis, machine learning, were used in this study. RNA-sequencing and clinical data from COAD patients were obtained from the Gene expression omnibus (GEO) and The Cancer Genome Atlas (TCGA) databases. Construction of a prognostic nomogram for predicting overall survival (OS) using multivariate analysis and Lasso-Cox regression. Immunohistochemistry (IHC) was our method of validating the expression of seven genes that are linked to anoikis in COAD. We identified seven anoikis-related genes as predictors of COAD survival and prognosis, and confirmed their accuracy in predicting colon adenocarcinoma prognosis by KM survival curves and ROC curves. A seven-gene risk score consisting of NAT1, CDC25C, ATP2A3, MMP3, EEF1A2, PBK, and TIMP1 showed strong prognostic value. Meanwhile, we made a nomogram to predict the survival rate of COAD patients. The immune infiltration assay showed T cells. CD4 memory. Rest and macrophages. M0 has a higher proportion in COAD, and 11 genes related to tumor immunity are important. GDSC2-based drug susceptibility analysis showed that 6 out of 198 drugs were significant in COAD. Anoikis-related genes have potential value in predicting the prognosis of COAD and provide clues for developing new therapeutic strategies for COAD. Immune infiltration and drug susceptibility results provide important clues for finding new personalized treatment options for COAD. These findings also suggest possible mechanisms that may affect prognosis. These results are the starting point for planning individualized treatment and managing patient outcomes.

Robotic natural orifice specimen extraction surgery versus conventional robotic resection for patients with colorectal neoplasms.

Background: Laparoscopic natural orifice specimen extraction surgery (NOSES) has been widely used in colorectal neoplasms. However, only a few studies have focused on robotic NOSES. This study compared the short-term clinical outcomes and long-term survival outcomes between robotic NOSES and conventional robotic resection (CRR) groups. Methods: From March 2016 to October 2018, a consecutive of 143 patients who underwent robotic sigmoid and rectal resection at the Department of Gastrointestinal Surgery, The Second Xiangya Hospital, Central South University, were considered for inclusion in this study. Propensity-score matching (PSM) was conducted to account for differences in the baseline characteristics. After PSM, 39 patients were included in the robotic NOSES group, and 39 patients in the CRR group. The baseline characteristics between the two groups were all balanced and comparable. Results: Patients in the NOSES group experienced less intraoperative blood loss (p=0.001), lower requirements for additional analgesia (p=0.020), shorter time to first flatus (p=0.010), and a shorter time to first liquid diet (p=0.003) than the CRR group. The 3-year overall survival rates (NOSES: 92.3% vs. CRR: 89.7% p=1.000) and 3-year disease-free survival rates (NOSES: 82.1% vs. CRR: 84.6% p=0.761) between the two groups were comparable. Conclusion: Robotic natural orifice specimen extraction surgery is a safe and feasible surgery for patients with colorectal neoplasms. Robotic NOSES is associated with better short-term clinical outcomes and similar long-term survival outcomes to conventional robotic resection.