Intratumor APOL3 delineates a distinctive immunogenic ferroptosis subset with prognosis prediction in colorectal cancer.

With the essential role of lipid transporting signaling in cancer-related immunity, apolipoprotein L3 (APOL3), a member of the apolipoprotein L gene family, demonstrated significant modulation ability in immunity. However, the expression profile and critical role of APOL3 in colorectal cancer (CRC) remain unclear. This study aimed to investigate the prognostic significance of APOL3 expression and its biological predictive value in CRC. The study enrolled multiple cohorts, consisting of 911 tumor microarray specimens of CRC patients from Zhongshan Hospital, 412 transcriptional data from The Cancer Genome Atlas, and 30 single-cell RNA sequencing (scRNA-seq) from internal and external CRC patients. APOL3 mRNA expression was directly acquired from public datasets, and APOL3 protein expression was detected using immunohistochemistry. Finally, the associations of APOL3 expression with clinical outcomes, immune context, and genomic and ferroptotic features were analyzed. Low APOL3 expression predicted poor prognosis and inferior responsiveness to 5-fluorouracil-based adjuvant chemotherapy (ACT) and targeted therapy. APOL3 fosters an immune-active microenvironment characterized by the promotion of ferroptosis, downregulation of macrophages, and upregulation of CD8+ T cell infiltration. Moreover, the expression of APOL3 in CD8+ T cells is intrinsically linked to ferroptosis and immune activation in CRC. In summary, APOL3 serves as an independent prognosticator and predictive biomarker for immunogenic ferroptosis, ACT, and targeted therapy in CRC. Furthermore, the APOL3 signaling activator could be a novel agent alone or in combination with current therapeutic strategies for CRC.

Genome-wide identification and expression analysis of GRAS gene family in Eucalyptus grandis.

BACKGROUND: The GRAS gene family is a class of plant-specific transcription factors with important roles in many biological processes, such as signal transduction, disease resistance and stress tolerance, plant growth and development. So far, no information available describes the functions of the GRAS genes in Eucalyptus grandis. RESULTS: A total of 82 GRAS genes were identified with amino acid lengths ranging from 267 to 817 aa, and most EgrGRAS genes had one exon. Members of the GRAS gene family of Eucalyptus grandis are divided into 9 subfamilies with different protein structures, while members of the same subfamily have similar gene structures and conserved motifs. Moreover, these EgrGRAS genes expanded primarily due to segmental duplication. In addition, cis-acting element analysis showed that this family of genes was involved involved in the signal transduction of various plant hormones, growth and development, and stress response. The qRT-PCR data indicated that 18 EgrGRAS genes significantly responded to hormonal and abiotic stresses. Among them, the expression of EgrGRAS13, EgrGRAS68 and EgrGRAS55 genes was significantly up-regulated during the treatment period, and it was hypothesised that members of the EgrGRAS family play an important role in stress tolerance. CONCLUSIONS: In this study, the phylogenetic relationship, conserved domains, cis-elements and expression patterns of GRAS gene family of Eucalyptus grandis were analyzed, which filled the gap in the identification of GRAS gene family of Eucalyptus grandis and laid the foundation for analyzing the function of EgrGRAS gene in hormone and stress response.

Nicotinamide riboside supplementation ameliorated post-ovulatory oocyte quality decline.

In brief: Oocyte quality and its NAD+ level decrease with time during in vitro culture. This study shows that nicotinamide riboside (NR) supplementation improves early embryonic development potential in post-ovulatory oocytes by decreasing the reactive oxygen species (ROS) levels and reducing DNA damage and apoptosis which could potentially increase the success rate of assisted reproductive technology (ART). Abstract: The quality of post-ovulatory oocytes deteriorates over time, impacting the outcome of early embryonic development during human ART. We and other groups have found that NAD+, a prominent redox cofactor and enzyme substrate, decreases in both aging ovaries and oocytes. In this study, we found that the NAD+ levels decreased in the post-ovulatory mouse oocytes during in vitro culture and this decrease was partly prevented by NR supplementation. NR treatmenty restored MII oocyte quality and enhanced the early embryonic development potential of post-ovulatory oocytes via alleviating mitochondrial dysfunction and maintaining normal spindle/chromosome structure. Also, treatment with NR decreased ROS levels and reduced DNA damage and apoptosis in post-ovulatory oocytes. Taken together, our findings indicated that NR supplementation increases the oocyte quality and early embryonic development potential in post-ovulatory oocytes which could potentially increase the success rate of ART.

Inhibition of vascular endothelial growth factor alleviates neovascular retinopathy with regulated neurotrophic/proinflammatory cytokines through the modulation of DBI-TSPO signaling.

Diazepam binding inhibitor (DBI)-translocator protein (18kDa) (TSPO) signaling in the retina was reported to possess coordinated macroglia-microglia interactions. We investigated DBI-TSPO signaling and its correlation with vascular endothelial growth factor (VEGF), neurotrophic or inflammatory cytokines in neovascular retinopathy, and under hypoxic conditions. The vitreous expression of DBI, VEGF, nerve growth factor (NGF), and interleukin-1beta (IL-1ß) were examined in proliferative diabetic retinopathy (PDR) patients with or without anti-VEGF therapy and nondiabetic controls. Retinal DBI-TSPO signaling and the effect of the anti-VEGF agent were evaluated in a mouse model of oxygen-induced retinopathy (OIR). Interactions between Müller cell-derived VEGF and DBI, as well as cocultured microglial cells under hypoxic conditions, were studied, using Western blot, real-time RT-PCR, enzyme-linked immunosorbent assay (ELISA), flow cytometry, and immunofluorescent labeling. Results showed that vitreous levels of DBI, VEGF, NGF, and IL-1ß were significantly higher in PDR patients compared with controls, which further changed after anti-VEGF therapy. A statistical association was found between vitreous DBI and VEGF, NGF, IL-1ß, and age. The application of the anti-VEGF agent in the OIR model induced retinal expression of DBI and NGF, and attenuated inflammation and microglial cell activation. Inhibition of Müller cell-derived VEGF could increase its DBI expression under hypoxic conditions, while the DBI-TSPO signaling pathway is essential for anti-VEGF agents exerting anti-inflammatory and neuroprotective effects, as well as limiting inflammatory magnitude, promoting its neurotrophin production and anti-inflammatory (M2) polarization in microglial cells. These findings suggest the beneficial effect of anti-VEGF therapy on inflammation and neurotrophy of retinal glial cells through modulation of the DBI-TSPO signaling pathway.

Malaria epidemiological characteristics and control in Guangzhou, China, 1950-2022.

BACKGROUND: Malaria was once widespread in Guangzhou, China. However, a series of control measures have succeeded in eliminating local malaria infections. Based on the analysis of the characteristics of malaria epidemics in Guangzhou, China, from 1950 to 2022, the changes and effectiveness of malaria control strategies and surveillance management in Guangzhou from 1950 to 2022 are described. METHODS: Data on malaria prevention and treatment in Guangzhou from 1950 to 2022 were collected, and descriptive epidemiological methods were used to analyse the prevalence of malaria, preventive and control measures taken, and the effectiveness of prevention and treatment in different periods. Data on malaria cases were obtained from the Guangzhou Centre for Disease Control and Prevention (CDC) and the China Communicable Disease Reporting System. RESULTS: The development of the malaria control system in Guangzhou has gone through four periods: 1. High malaria prevalence (1950-1979), 2. Intensive prevention and control stage (1980-2000), 3. Consolidating gains in malaria control (2001-2008), and 4. Preventing reestablishment of transmission (2009-2022). During Period 1, only medical institutions at all levels and the local CDCs, the Guangzhou CDC participated in the malaria prevention and control system, establishing a three-tier health system on malaria prevention and control. During Period 2, other types of organizations, including the agricultural sector, schools and village committees, the construction department and street committee, are involved in the malaria control system. During Period 3, more and more organizations are joining forces to prevent and control malaria. A well-established multisectoral malaria control mechanism and an improved post-elimination surveillance management system are in place. Between 1950 and 2022, a total of 420,670 cases of malaria were reported. During Period 1, there was an epidemic of malaria in the early 1950s, with an annual incidence rate of more than 10,000/100,000, including a high rate of 2887.98/100,000 in 1954. In Period 2 malaria was gradually brought under control, with the average annual malaria incidence rate dropping to 3.14/100,000. During Period 3, the incidence rate was kept below 1/100,000, and by 2009 local malaria infections were eliminated. CONCLUSION: For decades, Guangzhou has adopted different malaria control strategies and measures at different epidemic stages. Increased collaboration among civil organizations in Guangzhou in malaria control has led to a significant decline in the number of malaria cases and the elimination of indigenous malaria infections by 2009.The experience of Guangzhou can guide the development of malaria control strategies in other cities experiencing similar malaria epidemics.

Preoperative transarterial chemoembolization with drug-eluting beads (DEB-TACE) in patients undergoing conversional hepatectomy: a propensity-score matching analysis.

OBJECTIVES: Patients with colorectal liver metastases (CRLM) who underwent hepatic resection after conversion therapy had a high recurrence rate of nearly 90%. Preoperative DEB-TACE has the potential to prevent postoperative recurrence which has not been elucidated. The objective of this study was to evaluate the safety and efficacy of preoperative DEB-TACE. MATERIALS AND METHODS: Patients with CRLM who underwent liver resection from June 1, 2016, to June 30, 2021, were collected and those who received conversional hepatectomy were included in this study. Patients with preoperative DEB-TACE were propensity-score matched in a 1:1 ratio to patients without preoperative DEB-TACE. Short-term outcomes and recurrence-free survival (RFS) were compared between the two groups. RESULTS: After PSM, 44 patients were included in each group. The toxicities of DEB-TACE were mild and could be managed by conservative treatment. Overall response rate (ORR) of conversion therapy (75.0% vs. 81.2%, p = 0.437) and postoperative complication of hepatic resection (27.3% vs. 20.5%, p = 0.453) were similar between the two groups. The median RFS of the DEB-TACE group (10.7 months, 95%CI: 6.6-14.8 months) was significantly longer than that of the control group (8.1 months, 95%CI: 3.4-12.8 months) (HR: 0.60, 95%CI: 0.37-0.95, p = 0.027). CONCLUSIONS: In patients who became resectable after conversion therapy, preoperative DEB-TACE might be a safe option to achieve longer RFS. KEY POINTS: • This is a propensity-score matching study comparing patients who underwent conversional hepatectomy with or without preoperative DEB-TACE. • The preoperative DEB-TACE was safe and with mild toxicities (without toxicities more than CTCAE grade 3). • The preoperative DEB-TACE significantly prolonged the RFS of those patients who underwent conversional hepatectomy (10.7 vs. 8.1 months, p = 0.027).

Activation of miR-500a-3p/CDK6 axis suppresses aerobic glycolysis and colorectal cancer progression.

BACKGROUND: Colorectal cancer (CRC) is one of the lethal cancers with a high mortality rate worldwide and understanding the mechanisms behind its progression is critical for improving patients' prognosis and developing therapeutics. MiR-500a-3p has been demonstrated to be involved in the progression of several human cancers but its role in CRC remains unclear. The aim of this study is to uncover the expression pattern and mechanisms of action of miR-500a-3p during the CRC progression. METHODS: The expression of miR-500a-3p and Cyclin-dependent kinases 6 (CDK6) in 134 CRC tissues were tested by quantitative PCR (qPCR) and immunohistochemistry staining (IHC), respectively. The effect of miR-500a-3p on cell proliferation was explored in vitro and in vivo. The glycolysis of CRC cells was determined by Mass Spectrometry and Seahorse XF 96 Extracellular Flux Analyzer. A dual-luciferase reporter assay was performed to validate the relationship between miR-500a-3p and CDK6. RESULTS: miR-500a-3p was abnormally downregulated in CRC tissues and cell lines and was negatively associated with a worse prognosis. miR-500a-3p mimics impeded CRC cell proliferation in vitro and in vivo. miR-500a-3p inhibited glucose consumption, lactate and ATP production, and down-regulated the expression of hexokinase2 (HK2). In silico prediction combined with western blot and luciferase assay confirmed that CDK6 is a direct target of miR-500a-3p. Overexpression of CDK6 phenotypically rescued the inhibitory effect of miR-500a-3p on the proliferation and glycolysis of CRC cells. CONCLUSIONS: Our study revealed a potential tumor-suppressive role of miR-500a-3p in CRC, specifically targeting CDK6 and inhibiting cancer cell proliferation and aerobic glycolysis, which may provide new insights into novel prognostic biomarkers and therapeutic targets for CRC.

Association of RAS/BRAF Status and Prognosis of Metastatic Colorectal Cancer: Analysis of 1002 Consecutive Cases.

BACKGROUND: This study aimed to analyze the association of RAS/BRAF status and the prognosis of patients with metastatic colorectal cancer (mCRC) based on multi-disciplinary team (MDT) treatment mode. METHODS: The study retrospectively analyzed 1002 consecutive mCRC patients with different tumor RAS/BRAF status at Zhongshan Hospital Fudan University from April 2012 to December 2018. The association of RAS/BRAF status with clinicopathologic features and prognosis was analyzed. RESULTS: The mutation rate was 42.3% (424/1002) for RAS and 5.0% (50/1002) for BRAF. The RAS and BRAF mutations were mutually exclusive of each other. An association of RAS/BRAF status with sex (P < 0.001), age (P = 0.021), primary tumor location (P < 0.001), pathologic type (P < 0.001), differentiation (P < 0.001), metastatic organ (P < 0.001), carcinoembryonic antigen (CEA) (P < 0.001), and cancer antigen (CA)19-9 (P < 0.001) was observed. Overall survival (OS) was better for the RAS/BRAF wild-type patients than for the RAS-mutant patients, whereas the BRAF-mutant patients had the worst OS (51.0 vs 34.9 vs 18.9 months; P < 0.001). Regardless of RAS/BRAF status, metastases resection significantly improved OS (64.0 vs. 21.3 months; P < 0.001). Among the initially unresectable patients, the RAS/BRAF wild-type patients had a better conversional resection rate (32.9% vs 19.1% vs 0; P < 0.001) and a better OS (33.8 vs 23.3 vs 13.2 months; P = 0.005) than the RAS- and BRAF-mutant patients. Similarly, among the initially resectable patients, the RAS/BRAF wild-type patients had a better OS than the RAS- or BRAF- mutant patients (not assessable vs 51.7 vs 35.4 months; P = 0.005). CONCLUSIONS: This large-sample study showed that regardless of metastases resection or no resection, RAS and BRAF mutations were associated with a poor prognosis. Resection of metastases could bring survival benefits for patients regardless of RAS/BRAF status.

Robotic versus laparoscopic abdominoperineal resections for low rectal cancer: A single-center randomized controlled trial.

BACKGROUND AND OBJECTIVES: Robotic surgery for rectal cancer is gaining popularity, but persuasive evidence on reducing surgical trauma is still lacking. This study compared robotic and laparoscopic abdominoperineal resections (APRs) for the risk of postoperative complications in low rectal cancer. METHODS: Between December 2013 and 2016, patients with rectal cancer ≤5 cm from anal verge, cT1-T3 N0-1, or ycT1-T3 Nx stage, and no distant metastases were enrolled in a single-center, randomized, controlled trial. Eligible patients were randomly allocated to robotic or laparoscopic APRs at 1:1 ratio. The primary outcome was 30-day postoperative complication rate (Clavien-Dindo grade II or higher) of the intent-to-treat population. The trial registration number is NCT01985698 (http://www. CLINICALTRIALS: gov). RESULTS: Totally 347 eligible patients were enrolled: 174 in robotic and 173 in laparoscopic group. Robotic APRs significantly reduced postoperative complication rate (13.2% vs. 23.7%, p = 0.013), also reduced open conversion rate (0% vs. 2.9%, p = 0.030), intraoperative hemorrhage (median, 100 vs. 130 ml; p < 0.001), 30-day readmission rate (2.3% vs. 6.9%; p = 0.044), postoperative hospital stay (median, 5.0 vs. 7.0 days; p < 0.001), and improved urinary and sexual function. No significant difference was observed in long-term oncological outcomes. CONCLUSIONS: Compared with laparoscopic APRs, robotic APRs significantly reduced surgical trauma and promoted postoperative recovery.

Unsupervised learning of cross-modal mappings in multi-omics data for survival stratification of gastric cancer.

Aims: This study presents a survival stratification model based on multi-omics integration using bidirectional deep neural networks (BiDNNs) in gastric cancer. Methods: Based on the survival-related representation features yielded by BiDNNs through integrating transcriptomics and epigenomics data, K-means clustering analysis was performed to cluster tumor samples into different survival subgroups. The BiDNNs-based model was validated using tenfold cross-validation and in two independent confirmation cohorts. Results: Using the BiDNNs-based survival stratification model, patients were grouped into two survival subgroups with log-rank p-value = 9.05E-05. The subgroups classification was robustly validated in tenfold cross-validation (C-index = 0.65 ± 0.02) and in two confirmation cohorts (E-GEOD-26253, C-index = 0.609; E-GEOD-62254, C-index = 0.706). Conclusion: We propose and validate a robust and stable BiDNN-based survival stratification model in gastric cancer.

Short-term outcomes of complete mesocolic excision versus D2 dissection in patients undergoing laparoscopic colectomy for right colon cancer (RELARC): a randomised, controlled, phase 3, superiority trial.

BACKGROUND: Whether extended lymphadenectomy for right colon cancer leads to increased perioperative complications or improves survival is still controversial. This trial aimed to compare the efficacy and safety of complete mesocolic excision (CME) versus D2 dissection in laparoscopic right hemicolectomy for patients with right colon cancer. This article reports the early safety results from the trial. METHODS: This randomised, controlled, phase 3, superiority, trial was done at 17 hospitals in nine provinces of China. Eligible patients were aged 18-75 years with histologically confirmed primary adenocarcinoma located between the caecum and the right third of the transverse colon, without evidence of distant metastases. Central randomisation was done by means of the Clinical Information Management-Central Randomisation System via block randomisation (block size of four). Patients were randomly assigned (1:1) to CME or D2 dissection during laparoscopic right colectomy. Central lymph nodes were dissected in the CME but not in the D2 procedure. Neither investigators nor patients were masked to their group assignment but the quality control committee were masked to group assignment. The primary endpoint was 3-year disease-free survival, but the data for this endpoint are not yet mature; thus, only the secondary outcomes-intraoperative surgical complications and postoperative complications within 30 days of surgery, graded according to the Clavien-Dindo classification, mortality (death from any cause within 30 days of surgery), and central lymph node metastasis rate in the CME group only-are reported in this Article. This early analysis of safety was preplanned. The outcomes were analysed according to a modified intention-to-treat principle (excluding patients who no longer met inclusion criteria after surgery or who did not have surgery). This study is registered with ClinicalTrials.gov, NCT02619942. Study recruitment is complete, and follow-up is ongoing. FINDINGS: Between Jan 11, 2016, and Dec 26, 2019, 1072 patients were enrolled and randomly assigned. After exclusion of 77 patients, 995 patients were included in the modified intention-to-treat population (495 in the CME group and 500 in the D2 dissection group). The postoperative surgical complication rate was 20% (97 of 495 patients) in the CME group versus 22% (109 of 500 patients) in the D2 group (difference, -2·2% [95% CI -7·2 to 2·8]; p=0·39); the frequency of Clavien-Dindo grade I-II complications were similar between groups (91 [18%] vs 92 [18%], difference, -0·0% [95% CI -4·8 to 4·8]; p=1·0) but Clavien-Dindo grade III-IV complications were significantly less frequent in the CME group than in the D2 group (six [1%] vs 17 [3%], -2·2% [-4·1 to -0·3]; p=0·022); no deaths occurred in either group. Of the intraoperative complications, vascular injury was significantly more common in the CME group than in the D2 group (15 [3%] vs six [1%], difference, 1·8 [95% CI 0·04 to 3·6]; p=0·045). Metastases in the central lymph nodes were detected in 13 (3%) of 394 patients who underwent central lymph node biopsy in the CME group; no patient had isolated metastases to central lymph nodes. INTERPRETATION: Although the CME procedure might increase the risk of intraoperative vascular injury, it generally seems to be safe and feasible for experienced surgeons. FUNDING: The Capital Characteristic Clinical Project of Beijing and the Chinese Academy of Medical Sciences.

Preoperative Hepatic and Regional Arterial Chemotherapy in Patients Who Underwent Curative Colorectal Cancer Resection: A Prospective, Multi-center, Randomized Controlled Trial.

OBJECTIVE: To evaluate the effects of the addition of preoperative hepatic and regional arterial chemotherapy (PHRAC) on prognosis of stage II and III colorectal cancer (CRC) in a multicenter setting. SUMMARY OF BACKGROUND DATA: Our previous single-center pilot trial suggested that PHRAC in combination with surgical resection could reduce the occurrence of liver metastasis (LM) and improve survival in CRC patients. METHODS: A prospective multi-center randomized controlled trial was conducted from December 2008 to December 2012 at 5 hospitals in China. Eligible patients with clinical stage II or III CRC who underwent curative resection were randomized to receive PHRAC plus adjuvant therapy (PHRAC arm) or adjuvant therapy alone (control arm). The primary endpoint was DFS. Secondary endpoints were cumulative LM rates, overall survival (OS), and safety (NCT00643877). RESULTS: A total of 688 patients from 5 centers in China were randomly assigned (1:1) to each arm. The five-year DFS rate was 77% in the PHRAC arm and 65% in the control arm (HR = 0.61, 95% CI 0.46-0.81; P = 0.001). The 5-year LM rates were 7% and 16% in the PHRAC and control arms, respectively (HR = 0.37, 95% CI 0.22-0.63; P < 0.001). The 5-year OS rate was 84% in the PHRAC arm and 76% in the control arm (HR = 0.61, 95% CI 0.43-0.86; P = 0.005). There were no significant differences regarding treatment related morbidity or mortality between the two arms. CONCLUSIONS: The addition of PHRAC could improve DFS in patients with stage II and III CRC. It reduced the incidence of LM and improved OS without compromising patient safety. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT00643877.

Comparison between robotic natural orifice specimen extraction surgery and traditional laparoscopic low anterior resection for middle and low rectal cancer: A propensity score matching analysis.

BACKGROUND AND OBJECTIVES: This study aimed to find the advantages of robotic natural orifice specimen extraction surgery (NOSES) for middle and low rectal cancer, compared with traditional laparoscopic low anterior resection (LAR). METHODS: Patients receiving robotic NOSES or traditional laparoscopic LAR were retrospectively enrolled from 2013-10 to 2019-06, with middle and low rectal cancer, maximum diameter ≤ 5 cm, pT1-3 or ypT1-3 stage, no distant metastases. The baseline of the two groups was balanced using the propensity score matching method. Surgical quality, postoperative recovery, and long-term oncological outcomes were compared. RESULTS: Totally 137 eligible patients with robotic NOSES and 137 matched patients with traditional laparoscopic LAR were enrolled. Robotic NOSES had a significantly lower open conversion rate (0 vs. 4.4%, p = .030), less intraoperative hemorrhage (50 ml vs. 80 ml, p < .001) and longer distance from distal resection margin of low rectal cancer (1.5 cm vs. 1.0 cm, p = .030). Robotic NOSES significantly reduced the 30-day postoperative complication rate of Clavien-Dindo grade II or higher (17.5% vs. 31.4%, p = .008), promoted gastrointestinal and urinary function recovery, reduced postoperative pain and hospital stay (6.0 vs. 7.0 d, p = .022). The two groups were similar in long-term survival. CONCLUSIONS: Compared with traditional laparoscopic LAR, robotic NOSES had significant advantages in improving surgical quality and promoting postoperative recovery.

The effect of non-curative endoscopic resection on cT1N0M0 colorectal carcinoma patients who underwent additional surgery.

BACKGROUND AND AIM: Radical surgery is recommended for T1 colorectal cancer with non-curative endoscopic resection. However, there is still insufficient evidence about whether the non-curative endoscopic resection prior to surgical resection affects the short-term and long-term outcomes of patients. The purpose of this study was to investigate the effect of non-curative endoscopic resection before surgical resection on short-term and long-term outcomes in patients with T1 colorectal cancer. PATIENTS AND METHODS: Patients with clinical T1N0M0 (cT1N0M0) colorectal cancer who underwent direct surgery or additional radical surgery after non-curative endoscopic resection were collected. We evaluated postoperative complications and long-term prognosis between the two groups. RESULTS: From 2011 to 2017, 779 patients were clinically diagnosed with T1N0M0 colorectal cancer at Zhongshan Hospital. We assessed patients who underwent additional surgery following the prior non-curative endoscopic resection (n = 145) and patients who underwent radical surgery directly (n = 336). There was no significant difference in 5-year OS (99.3% vs. 99.4%, P = 0.866) and 5-year DFS (97.2% vs. 97.3%, P = 0.909) between the two groups. The total complication rate was slightly higher in prior endoscopic resection group (15.2% vs. 9.5%, P = 0.111). The 5-year OS and 5-year DFS of patients who refused additional surgery (n = 95) were significantly lower than ER prior to surgery group (For OS, 92.6% vs. 99.3%, P = 0.017; for DFS, 91.2% vs. 97.2%, P = 0.021). CONCLUSION: In patients who underwent additional surgery, non-curative endoscopic resection of cT1 colorectal carcinoma did not have adverse effect on short-term and long-term outcomes. Additional surgery should be recommended in patients who received non-curative ER.

Robotic colorectal cancer surgery in China: a nationwide retrospective observational study.

BACKGROUND: Robotic colorectal cancer surgery is widely accepted and applied. However, there is still no objective and comprehensive assessment on the data of nationwide multicenter series. METHOD: A total of 28 medical centers in Mainland China participated in this nationwide retrospective observational study. From the first case performed in each center to the last until December 2017, patients with robotic resection for primary tumor and pathologically confirmed colorectal adenocarcinoma were consecutively enrolled. Clinical, pathological and follow-up data were collected and analyzed. RESULTS: A total of 5389 eligible patients were finally enrolled in this study, composing 72.2% of the total robotic colorectal surgery volume of Mainland China in the same period. For resections of one bowel segment of primary tumor, the postoperative mortality rate was 0.08% (4/5063 cases), and the postoperative complication rate (Clavien-Dindo grade II or higher) was 8.6% (434/5063 cases). For multiple resections, the postoperative mortality rate was 0.6% (2/326 cases), and the postoperative complication rate was 16.3% (53/326 cases). Out of 2956 patients receiving sphincter-preserving surgery in only primary resection, 130 (4.4%) patients had anastomotic leakage. Traditional low anterior resection (tumor at middle rectum) (OR 2.384, P < 0.001), traditional low anterior resection (tumor at low rectum) (OR 1.968, P = 0.017) and intersphincteric resection (OR 5.468, P = 0.006) were significant independent risk factors for anastomotic leakage. Female gender (OR 0.557, P = 0.005), age ≥ 60 years (OR 0.684, P = 0.040), and preventive stoma (OR 0.496, P = 0.043) were significant independent protective factors. Body mass index, preoperative chemotherapy/radiotherapy, tumor size, and TNM stage did not independently affect the occurrence of anastomotic leakage. CONCLUSION: Robotic colorectal cancer surgery was safe and reliable and might have advantages in patients at high risk of anastomotic leakage.

Analysis of relapse-associated alternative mRNA splicing and construction of a prognostic signature predicting relapse in I-III colon cancer.

The literature comprehensively analyzed alternative splicing (AS) events in colon cancer is little and corresponding prognostic signature is still a lack. Based on data of TCGA, the relapse-associated ASs were comprehensively analyzed and a signature was further constructed to predict the relapse in I-III colon cancer. In total 1912 ASs of 1384 mRNA were identified as relapse-associated ASs, protein-protein interactions (PPI) and ASs-splicing factors (SF) interactions network were identified. We finally built a robust signature to predict the relapse of I-III colon cancer with a considerable AUC value in both the training group and the test group. The AUC in the entire set at 1, 3 and 5 year was 0.85, 0.83 and 0.836. Our study provided a profile of relapse-associated ASs in I-III colon cancer and built a robust signature to predict the relapse of I-III colon cancer.

A signature predicting relapse based on integrated analysis on relapse-associated alternative mRNA splicing in I-III rectal cancer.

Researches focusing on the effects of alternative splicing (AS) on relapse of rectal cancer is little and signature based on the AS is blank. In this study, bioinformatic analysis was performed to identify and analyze the relapse-associated ASs, a signature was also constructed. In conclusion, 829 relapse-associated ASs of 676 mRNA were identified. 603 proteins with 2119 interactions were involved in the PPI (protein-protein interactions) network. 43 relapse-associated ASs and 64 SFs (splicing factors) with 160 interactions were indicated. Finally, we built a robust signature to predict the relapse of I-III rectal cancer with a high AUC (0.98) of ROC at 1 year. Based on the ASs involved in the signature, 4 molecular subgroups that could distinguish the relapse rate in diverse groups were identified. Our research provided an overview of relapse-associated ASs in I-III rectal cancer.

Comparative analysis the performance of electrochemical water softening between high frequency electric fields and direct current electric fields based on orthogonal experimental methods.

Electrochemical water softening has been widely used in industrial circulating cooling water systems; however, their low deposition efficiency is the main drawback that limits usage in medium to large enterprises. In this work, the effect of different parameters on the hardness removal efficiency and energy consumption of the electrochemical water softening system is experimentally studied, and the performance of water softening applied by high frequency electric fields and direct current electric fields are comparative analyzed. The impact factors of the electrochemical water softening system are as follows: initial feed concentration of solute, magnitude of voltage, inter-electrode distance, area of cathode and frequency of power supply. To improve the analysis efficiency, the L25 (55) orthogonal table is used to investigate the five different factors at five levels. The experimental results are shown that the initial feed concentration of solute is the most significant factor affecting the hardness removal efficiency. The optimal combination for water softening in the group applied by high frequency electric field and direct current electric field are A3B2C1D4E3 and A2B5C3D1 respectively. The energy utilization of the device applied by high frequency electric field is 3.2 times that applied by direct current electric field. The practice shows that direct current electric fields have a better softening effect, and are is more suitable for scaling ion removal. Particle image velocimetry (PIV) was used to observe the flow field induced by the electrolysis and found that the vertical and horizontal velocities of the flow field at low voltage are conducive to the migration of scaled ions to the cathode, and then the electrolytic reaction and deposition reaction synergy effect is the optimal.

Research on performance optimization and mechanism of electrochemical water softening applied by pulse power supply.

In order to promote the application of electrochemical water softening technology in industrial circulating cooling water systems, electric field type, cathode structure and solution residence time are selected for optimization analysis of an electrochemical water softening device. The experimental results show that the water softening performance per unit area of mesh cathode is better than that of a plate cathode. In addition, the softening amount per unit area of the mesh cathode can be further increased when the high-frequency (HF) power supply is applied. When the HF power supply is applied, the softening amount per unit area is 158.58 g/m2·h-1 more than when the direct current power supply is applied. In order to explore the growth mechanism of calcium carbonate, micro-analysis technology and high-speed bubble photography technology are used. The results show that the bubbles escape along the longitudinal direction of the electrode plate, and the main growth direction of calcium carbonate growth is consistent with the escape direction of the bubble; that is, the bubbles grow along the longitudinal direction of the electrode plate. The special structure of the diamond-shaped mesh cathode facilitates the growth of calcium carbonate crystals.

Comprehensive Evaluation of Relapse Risk (CERR) Score for Colorectal Liver Metastases: Development and Validation.

BACKGROUND: The calculation of the tumor burden score (TBS) is not perfect because the bilobar spread of colorectal liver metastasis (CRLM) is neglected. The identification of an ideal prognostic scoring system for CRLM remains controversial. MATERIALS AND METHODS: Patients who underwent curative intent liver resection for CRLM from one medical center were enrolled in cohort 1 (787 patients) and cohort 2 (162 patients). Tumor relapse-free survival (RFS) was the main outcome. A Cox regression model was used to identify independent predictors of prognosis. The time-dependent area under the curve, calibration curve, and C-index were employed to validate the predictive ability of the survival model. RESULTS: Modified TBS (mTBS) was established by a mathematical equation with parameters including CRLM size, CRLM number, and unilobar or bilobar metastasis. Five preoperative predictors of worse RFS were identified in cohort 1 and incorporated into the Comprehensive Evaluation of Relapse Risk (CERR) score: KRAS/NRAS/BRAF-mutated tumor (1 point); node-positive primary (1 point); extrahepatic disease (1 point); carcinoembryonic antigen level > 200 ng/mL or carbohydrate antigen 19-9 (CA19-9) >200 U/mL (1 point); and mTBS between 5 and 11 (1 point) or 12 and over (2 points). Patients in cohort 1 were stratified by their CERR score into risk groups: the high-risk group (CERR score 4 or more), the medium-risk group (CERR score 2-3), and the low-risk group (CERR score 0-1). Importantly, internal validation in cohort 1 and further validation in cohort 2 both showed the superior discriminatory capacity of the CERR score. CONCLUSION: mTBS should be promoted. The CERR score is a powerful prognostic tool that can help determine optimal clinical management strategies. IMPLICATIONS FOR PRACTICE: This work resulted in the successful modification of the tumor burden score and development of a comprehensive and practical prognostic scoring system-the Comprehensive Evaluation of Relapse Risk (CERR) score. The CERR score, with a better prognostic discriminatory ability, outperformed the Fong score. Perhaps more importantly, the CERR score is a powerful prognostic tool because it unified the most consistently reported prognostic factors. Therefore, the CERR score can assist doctors in determining optimal clinical management strategies.