CTHRC1 promotes colorectal cancer progression by recruiting tumor-associated macrophages via up-regulation of CCL15.

Tumor-associated macrophages (TAMs) represent a key factor in the tumor immune microenvironment (TME), exerting significant influence over tumor migration, invasion, immunosuppressive features, and drug resistance. Collagen triple helix repeat containing 1 (CTHRC1), a 30 KDa protein which was secreted during the tissue-repair process, is highly expressed in several malignant tumors, including colorectal cancer (CRC). Previous studies demonstrated that CTHRC1 expression in TAMs was positively correlated to M2 macrophage polarization and liver metastasis, while our discovery suggesting a novel mechanism that CTHRC1 secreted from cancer cell could indirectly interplay with TAMs. In this study, the high expression level of CTHRC1 was evaluated in CRC based on GEO and TCGA databases. Further, CTHRC1 was detected high in all stages of CRC patients by ELISA and was correlated to poor prognosis. Multispectral imaging of IHC demonstrated that M2 macrophage infiltration was increased accompanied with CTHRC1 enrichment, suggesting that CTHRC1 may have chemotactic effect on macrophages. In vitro, CTHRC1 could have chemotactic ability of macrophage in the presence of HT-29 cell line. Cytokine microarray revealed that CTHRC1 could up-regulate the CCL15 level of HT-29, pathway analysis demonstrated that CTHRC1 could regulate CCL15 by controlling the TGFß activation and Smad phosphorylation level. In vivo, knocking down of CTHRC1 from CT-26 also inhibits tumor formation. In conclusion, CTHRC1 could promote the chemotactic ability of macrophages by up-regulating CCL15 via TGFß/Smad pathway; additionally, a high level of CTHRC1 could promote macrophage's M2 polarization. This discovery may be related to tumor immune tolerance and tumor immunotherapy resistance in CRC. KEY MESSAGES: CTHRC1 promotes CRC progression by up-regulating CCL15 via TGF-ß/Smad pathways to further recruit tumor-associated macrophages. By the means of autocrine or paracrine, CTHRC1 can indeed promote macrophage chemotaxis and enhance the infiltration of macrophages in tumor tissues but in the presence of tumor cells. CAFs were another source of CTHRC1, indicating CTHRC1 can infiltrate tumor islet as well as the stomal and be secreted from both tumor cells and CAFs. This study validated CTHRC1 as a potential immune therapy target CRC.

Prediction of symptomatic anastomotic leak after rectal cancer surgery: A machine learning approach.

INTRODUCTION: Anastomotic leakage (AL) remains the most dreaded and unpredictable major complication after low anterior resection for mid-low rectal cancer. The aim of this study is to identify patients with high risk for AL based on the machine learning method. METHODS: Patients with mid-low rectal cancer undergoing low anterior resection were enrolled from West China Hospital between January 2008 and October 2019 and were split by time into training cohort and validation cohort. The least absolute shrinkage and selection operator (LASSO) method and stepwise method were applied for variable selection and predictive model building in the training cohort. The area under the receiver operating characteristic curve (AUC) and calibration curves were used to evaluate the performance of the models. RESULTS: The rate of AL was 5.8% (38/652) and 7.2% (15/208) in the training cohort and validation cohort, respectively. The LASSO-logistic model selected almost the same variables (hypertension, operating time, cT4, tumor location, intraoperative blood loss) compared to the stepwise logistic model except for tumor size (the LASSO-logistic model) and American Society of Anesthesiologists score (the stepwise logistic model). The predictive performance of the LASSO-logistics model was better than the stepwise-logistics model (AUC: 0.790 vs. 0.759). Calibration curves showed mean absolute error of 0.006 and 0.013 for the LASSO-logistics model and stepwise-logistics model, respectively. CONCLUSION: Our study developed a feasible predictive model with a machine-learning algorithm to classify patients with a high risk of AL, which would assist surgical decision-making and reduce unnecessary stoma diversion. The involved machine learning algorithms provide clinicians with an innovative alternative to enhance clinical management.

Clinical evaluation of a multitarget fecal immunochemical test-sDNA test for colorectal cancer screening in a high-risk population: a prospective, multicenter clinical study.

Colorectal cancer (CRC) is a major malignancy threatening the health of people in China and screening could be effective for preventing the occurrence and reducing the mortality of CRC. We conducted a multicenter, prospective clinical study which recruited 4,245 high-risk CRC individuals defined as having positive risk-adapted scores or fecal immunochemical test (FIT) results, to evaluate the clinical performance of the multitarget fecal immunochemical and stool DNA (FIT-sDNA) test for CRC screening. Each participant was asked to provide a stool sample prior to bowel preparation, and FIT-sDNA test and FIT were performed independently of colonoscopy. We found that 186 (4.4%) were confirmed to have CRC, and 375 (8.8%) had advanced precancerous neoplasia among the high CRC risk individuals. The sensitivity of detecting CRC for FIT-sDNA test was 91.9% (95% CI, 86.8-95.3), compared with 62.4% (95% CI, 54.9-69.3) for FIT (P < 0.001). The sensitivity for detecting advanced precancerous neoplasia was 63.5% (95% CI, 58.3-68.3) for FIT-sDNA test, compared with 30.9% (95% CI, 26.3-35.6) for FIT (P < 0.001). Multitarget FIT-sDNA test detected more colorectal advanced neoplasia than FIT. Overall, these findings indicated that in areas with limited colonoscopy resources, FIT-sDNA test could be a promising further risk triaging modality to select patients for colonoscopy in CRC screening.

Closure of pelvic peritoneum with bladder peritoneum flap reconstruction after laparoscopic extralevator abdominoperineal excision: A prospective stage II study.

BACKGROUND: Extralevator abdominoperineal resection (ELAPE) has increased perineal wound complications due to the extended resection area. Closure of the pelvic peritoneum (CPP) may exclude the abdominal content from descending into the pelvic cavity and reduce the incidence of perineal complications after ELAPE. We have previously introduced bladder peritoneum flap reconstruction (BLAPER) as a novel method for patients in whom traditional CPP is not possible. The aim of the present study was to report the development and preliminary outcomes of BLAPER. METHODS: This is a prospective single-arm study at the development and exploration phase and fulfills the IDEAL framework stage II. Ultralow rectal cancer patients with rigid pelvis who underwent ELAPE with BLAPER were enrolled. Primary outcomes were intraoperative complications and postoperative complications within 1 month after surgery. RESULTS: Among 27 patients included, the overall success rate of BLAPER was 96.3% (26/27). Indocyanine green fluorescence imaging and antiadhesive barrier placement were introduced to improve the BLAPER technique. The incidence of major pelvic wound complications was 7.7%. No patient who underwent BLAPER has suffered small bowel obstruction (SBO), presence of small bowel in the retrourogenital space, or perineal hernia (PH). CONCLUSIONS: BLAPER is safe and may prevent the small bowel from descending into the retrourogenital space and subsequently developing PH and SBO without increasing the intraoperative and postoperative complications. BLAPER may serve as an option when the primary suture of the pelvic peritoneum is not feasible.

Facile Fabrication of a Robust Superhydrophilic/Underwater Superoleophobic Material for Oil-Fouling Expulsion.

The reduction of oil fouling in pipes and tanks is essential for the oil storage and transportation industry. In this study, a superhydrophilic/underwater superoleophobic surface (SUSS) with high wearability, weatherability, and durability was developed using a facile two-step synthesis method and used to expel fouled oil from the surface using water without a surfactant. Some typical oils, including kerosene and white oil, can be spontaneously expelled by static water; however, rapeseed oil requires motive water for expulsion because of its high affinity for the SUSS. Different occurrences can be estimated based on a correlated parameter, φ(Pe), which is calculated using an introduced dimensionless number, Pe=σLVuµ. A positive value of φ indicates the occurrence of fouled-oil expulsion by water replacement, whereas a negative value indicates no occurrence of this phenomenon. This study provides a facile strategy for the rapid cleansing of oil-fouled pipes and tanks without using a detergent, thereby lowering costs and environmental risks.

Superhydrophobic/Superoleophilic PDMS/SiO2 Aerogel Fabric Gathering Device for Self-Driven Collection of Floating Viscous Oil.

The persistent challenge of removing viscous oil on water surfaces continues to pose a major concern and requires immediate attention. Here, a novel solution has been introduced in the form of a superhydrophobic/superoleophilic PDMS/SiO2 aerogel fabric gathering device (SFGD). The SFGD is based on the adhesive and kinematic viscosity properties of oil, enabling self-driven collection of floating oil on the water surface. The SFGD is able to spontaneously capture the floating oil, selectively filter it, and sustainably collect it into its porous fabric interior through the synergistic effects of surface tension, gravity, and liquid pressure. This eliminates the need for auxiliary operations such as pumping, pouring, or squeezing. The SFGD demonstrates exceptional average recovery efficiencies of 94% for oils with viscosities ranging from 10 to 1000 mPa·s at room temperature, including dimethylsilicone oil, soybean oil, and machine oil. With its facile design, ease of fabrication, high recovery efficiency, excellent reclaiming capabilities, and scalability for multiple oil mixtures, the SFGD represents a significant advancement in the separation of immiscible oil/water mixtures of various viscosities and brings the separation process one step closer to practical application.

Surgical Intervention Could Relieve Obstruction-Related Symptoms of Refractory Superior Mesenteric Artery Syndrome: Long-Term Follow-up Results.

PURPOSE: Superior mesenteric artery syndrome (SMAS) is one of the rare causes of chronic duodenal obstruction. The aim of our study was to evaluate the outcomes of surgical management of refractory SMAS (Re-SMAS) in our institution during the last decade. MATERIALS AND METHODS: Consecutive patients diagnosed as Re-SMAS and underwent surgical intervention were retrospectively enrolled. A modified Likert-scale-based questionnaire was used to quantify the symptoms of SMAS. The primary outcome was the increase of BMI and symptomatic relief after surgery. RESULTS: From January 2010 to January 2020, 22 patients diagnosed with Re-SMAS and underwent surgery were included. Age distribution of included patients were < 19 (10/22, 45%), 19-45 (11/22, 50%), and > 45 (1/22, 5%). A significant BMI increase was recorded, [16.1 (14.6-23.7) kg/m2 vs 21.9 (15.6-29.5) kg/m2 before and after surgery, respectively, p < 0.001]. Up to 20 patients (20/22, 91%) reported symptomatic relief. The obstruction-related symptom score decreasing significantly (p < 0.001), with reported nausea, vomiting, and regurgitation incidences dropping from 77 to 41% (p = 0.031), 68 to 23% (p = 0.006), and 32 to 5% (p = 0.046), respectively. CONCLUSION: Surgical interventions could relieve obstruction-related symptoms of Re-SMAS and promote weight gain. For patients who suffered from Re-SMAS and referred to surgeons mainly for obstruction-related symptoms, surgical intervention is recommended.

DOG1 as a novel antibody-drug conjugate target for the treatment of multiple gastrointestinal tumors and liver metastasis.

Discovered On Gastrointestinal stromal tumors protein 1 (DOG1), a major calcium-activated chloride channel, has been used as a common diagnostic marker for gastrointestinal stromal tumors. However, the therapeutic application of DOG1 was not well defined. Here, we aim to investigate its potential as a therapeutic target for an antibody-drug conjugate (ADC) in various cancers of the alimentary tract and metastasis. The DOG1 expression profile was determined among TCGA samples and tissue microarrays. High levels of DOG1 expression were ubiquitously observed in multiple cancer samples from the alimentary tract determined by TCGA samples and tissue microarrays. Circulating tumor cells isolated from metastatic colon cancer patients were also positive for DOG1 expression. The mechanisms of anti-DOG1 antibody were investigated by dual-luciferase reporter assay. The anti-DOG1 antibody could inhibit proliferation and metastasis via p53 signaling in limited cancer cell lines. The anti-DOG1 antibody was conjugated with a microtubule inhibitor DM4, to construct a new anti-DOG1-DM4-ADC to strengthen its activity. The anti-DOG1-DM4-ADC showed cytotoxicity at the nanomolar level in vitro. In the murine xenograft tumor models, treatment of anti-DOG1-DM4-ADC achieved a significant tumor growth inhibition rate. Our study indicates that anti-DOG1-DM4-ADC may be promising therapeutic molecules for DOG1-positive alimentary tract tumors and may be effective in inhibiting recurrence after curative resection of liver metastases of colorectal origin.

Day-case loop ileostomy reversal based on the community hospital joined enhanced recovery after surgery (CHJ-ERAS) program in China: Safe and feasible.

BACKGROUND: This study was performed to determine the feasibility of Day-case loop ileostomy reversal (DLIR) in China based on the community hospital joined enhanced recovery after surgery (CHJ-ERAS) program. METHOD: Patients who underwent loop ileostomy were enrolled in the CHJ-ERAS program for DLIR after rigorous evaluation. The primary outcome was the results of short-term follow-ups. RESULTS: From August 2017 to April 2022, 216 patients have been enrolled in the CHJ-ERAS program for DLIR. After DLIR, 14 patients (14/216, 6.5%) have recorded 17 episodes of postoperative complications within 1 month after surgery, including 10 readmission and 2 reoperation. Compared with in-patient loop ileostomy reversal, DLIR based on CHJ-ERAS did not increase the postoperative complications and reoperations. CONCLUSION: The CMJ-ERAS program for DLIR in our center is a safe and feasible alternative option for inpatient LIR and an acceptable transitional approach for the development of day-case DLIR in developing countries.

Survival outcomes of stage I colorectal cancer: development and validation of the ACEPLY model using two prospective cohorts.

BACKGROUND: Approximately 10% of stage I colorectal cancer (CRC) patients experience unfavorable clinical outcomes after surgery. However, little is known about the subset of stage I patients who are predisposed to high risk of recurrence or death. Previous evidence was limited by small sample sizes and lack of validation. METHODS: We aimed to identify early indicators and develop a risk stratification model to inform prognosis of stage I patients by employing two large prospective cohorts. Prognostic factors for stage II tumors, including T stage, number of nodes examined, preoperative carcinoma embryonic antigen (CEA), lymphovascular invasion, perineural invasion (PNI), and tumor grade were investigated in the discovery cohort, and significant findings were further validated in the other cohort. We adopted disease-free survival (DFS) as the primary outcome for maximum statistical power and recurrence rate and overall survival (OS) as secondary outcomes. Hazard ratios (HRs) were estimated from Cox proportional hazard models, which were subsequently utilized to develop a multivariable model to predict DFS. Predictive performance was assessed in relation to discrimination, calibration and net benefit. RESULTS: A total of 728 and 413 patients were included for discovery and validation. Overall, 6.7% and 4.1% of the patients developed recurrences during follow-up. We identified consistent significant effects of PNI and higher preoperative CEA on inferior DFS in both the discovery (PNI: HR = 4.26, 95% CI: 1.70-10.67, p = 0.002; CEA: HR = 1.46, 95% CI: 1.13-1.87, p = 0.003) and the validation analysis (PNI: HR = 3.31, 95% CI: 1.01-10.89, p = 0.049; CEA: HR = 1.58, 95% CI: 1.10-2.28, p = 0.014). They were also significantly associated with recurrence rate. Age at diagnosis was a prominent determinant of OS. A prediction model on DFS using Age at diagnosis, CEA, PNI, and number of LYmph nodes examined (ACEPLY) showed significant discriminative performance (C-index: 0.69, 95% CI:0.60-0.77) in the external validation cohort. Decision curve analysis demonstrated added clinical benefit of applying the model for risk stratification. CONCLUSIONS: PNI and preoperative CEA are useful indicators for inferior survival outcomes of stage I CRC. Identification of stage I patients at high risk of recurrence is feasible using the ACEPLY model, although the predictive performance is yet to be improved.

Spatial and interspecific differences in coral-associated bacterial diversity in Hainan, China.

Coral reefs are suffering from environmental change and anthropogenic disturbances. It is well known that microbes play an indispensable role in the stable state of coral reef health. Furthermore, the coral reef microbial database helps to understand the connections among microbiomes shifts and ecosystem stress. Hainan Province is the main coral reef distribution area in China. Therefore, targeted microbial reference information from Hainan, including several coral microbiomes, was generated by 16S rRNA gene sequencing in this study. This study focused on a small range of coral-associated bacterial information and found a relationship between microbes and the surrounding environment based on coral interspecific and environmental factors. Interestingly, compared with species, the differences of bacterial community structures are best explained by site. It seems that various environmental factors contribute more to the microbial structure of corals than interspecific influences.

Is it worthwhile to perform closure of the pelvic peritoneum in laparoscopic extralevator abdominoperineal resection?

PURPOSE: There is no uniformity in the use of closure of the pelvic peritoneum (CPP) after laparoscopic extralevator abdominoperineal excision (ELAPE). This study aimed to evaluate the short-term outcomes of CPP after ELAPE and provide supporting evidence for the performance of CPP in laparoscopic ELAPE. METHODS: Patients with rectal cancer who underwent ELAPE from January 2014 to April 2019 were retrospectively investigated. CPP was routinely performed unless it was not feasible. The main outcome was the difference in the occurrence of perineal hernia (PH), small bowel obstruction (SBO) and perineal wound complications between laparoscopic and open ELAPE, which were compared using Kaplan-Meier curves. RESULTS: Of the 244 patients included, 104 received laparoscopic ELAPE, and 140 received open ELAPE. Patients in the laparoscopic group suffered a higher incidence of PH (11.5% (12/104) vs. 5.0% (7/140), p = 0.049), SBO (10.6% (11/104) vs. 7.9% (11/140), p = 0.433) and major perineal wound complications (12.5% (13/104) vs. 7.9% (11/140), p = 0.228) than those in the open group. Multivariate analysis showed that no-CPP was an independent risk factor for the occurrence of PH (p = 0.022, OR 3.436, 95% CI 1.199-9.848) and major perineal wound complications (p = 0.012, OR 3.683, 95% CI 1.337-10.146). CONCLUSION: In this comparative cohort study with a risk of allocation bias, CPP was associated with a lower incidence of radiological PH and major perineal wound complications regardless of the surgical approach. Thus, we believe CPP could serve as an option L-ELAPE for the prevention of perineal complications. To further determine the impact of CPP on postoperative complications after ELAPE, a prospective multicentre study is needed.

Claudin-2 promotes colorectal cancer growth and metastasis by suppressing NDRG1 transcription.

Colorectal cancer (CRC) is one of the most common malignant tumours, with multiple driving factors and biological transitions involved in its development. Claudin-2 (CLDN2), a well-defined component of cellular tight junction, has been indicated to associate with CRC progression. However, the function of CLDN2 and the underlying mechanism whereby the downstream signalling transduction is regulated in CRC remains largely unclear. In this study, we demonstrated that CLDN2 is upregulated in CRC samples and associated with poor survival. And CLDN2 depletion significantly promotes N-myc downstream-regulated gene 1 (NDRG1) transcription, leading to termination of the CRC growth and metastasis in vitro and in vivo. Mechanistically, this process promotes CLDN2/ZO1/ZONAB complex dissociation and ZONAB shuttle into nucleus to enrich in the promoter of NDRG1. Thus, this study reveals a novel CLDN2/ZO1/ZONAB-NDRG1 axis in CRC by regulating the expression of EMT-related genes and CDKIs, suggesting CLDN2 may serve as a promising target for CRC treatment.

Efficacy of Pelvic Peritoneum Closure After Laparoscopic Extralevator Abdominoperineal Excision for Rectal Cancer.

BACKGROUND: The descent of the small bowel into the pelvic dead space after extralevator abdominoperineal excision (ELAPE) presents a higher risk for postoperative complications. The aim of the present study was to evaluate the efficacy of pelvic peritoneum closure in preventing the small bowel from descending into the pelvic dead space and the potential consequences of this approach. METHODS: Patients with rectal cancer undergoing laparoscopic ELAPE from March 2014 to January 2019 were retrospectively investigated. Closure of the pelvic peritoneum (CPP) was routinely performed unless it was not feasible. All patients with pelvic peritoneum reconstruction were included in the CPP group, and patients without pelvic peritoneum reconstruction were included in the no-CPP group. The main outcomes included the incidences of the small bowel descending into the retro-urogenital space (space between the bladder/uterus and the sacrum on axial CT scans), perineal wound complications, perineal hernia, and small bowel obstruction (SBO). RESULTS: Of the 100 patients included, 79 received CPP, and 21 did not. Fewer patients with pelvic peritoneum closure had small bowels residing in the retro-urogenital space than patients without closure (17.7% vs 42.9%, p=0.014). The incidence of SBO was also lower in the CPP group (7.6% vs. 23.8%, p=0.034). Multivariable analysis showed that no-CPP (p=0.014) was an independent risk factor for the small bowel descending into the retro-urogenital space. CONCLUSION: CPP may prevent the small bowel from descending into the retro-urogenital dead space in patients undergoing laparoscopic ELAPE without increasing the incidence of perineal wound complications. Prospective studies are warranted to confirm the efficacy of CPP in preventing SBO and perineal hernia.

AirSign: Smartphone Authentication by Signing in the Air.

In this paper, we propose AirSign, a novel user authentication technology to provide users with more convenient, intuitive, and secure ways of interacting with smartphones in daily settings. AirSign leverages both acoustic and motion sensors for user authentication by signing signatures in the air through smartphones without requiring any special hardware. This technology actively transmits inaudible acoustic signals from the earpiece speaker, receives echoes back through both built-in microphones to "illuminate" signature and hand geometry, and authenticates users according to the unique features extracted from echoes and motion sensors. To evaluate our system, we collected registered, genuine, and forged signatures from 30 participants, and by applying AirSign on the above dataset, we were able to successfully distinguish between genuine and forged signatures with a 97.1% F-score while requesting only seven signatures during the registration phase.