The Clinical Association Between the Inflammation-Nutritional Condition and Prognosis of Locally Advanced Intrahepatic Cholangiocarcinoma After R0 Resection: Evidence from Competing Risk and Propensity Matching Analysis.

Background: Intrahepatic cholangiocarcinoma (ICC) correlates with poor outcomes, necessitating the identification of prognostic factors from an inflammation-nutritional perspective in locally advanced ICC patients after R0 resection. Methods: We retrospectively reviewed the medical records of 159 locally advanced ICC patients from Sun Yat-sen University Cancer Center. Univariate and multivariate Cox regression analysis, as well as competing risk analysis, were conducted to explore prognostic variables for locally advanced ICC following surgery. To validate the robustness of our findings, we performed propensity score matching (PSM) analyses to evaluate survival differences based on inflammation-nutritional indexes. Results: Considering non-cancer-specific death as competing risk factors, both systemic immune-inflammation index (SII, HR: 1.934) and prognostic nutrition index (PNI, HR: 0.604) emerged as significant prognostic variables for locally advanced ICC after R0 resection (P < 0.05). After PSM, the survival benefit between the low and high PNI sets remained clear (median survival time: 15.7 months vs 35.1 months, P = 0.002). Although the 5-year overall survival (OS) rate of the low SII group was higher than that of the high SII group, the difference was not statistically significant (17.5% VS 27.4%, P = 0.112). Other influencing factors included tumor number, tumor diameter, preoperative carcinoembryonic antigen (CEA)and carbohydrate antigen 19-9 (CA19-9) levels, and postoperative adjuvant therapy. Conclusion: Individual inflammatory and nutritional status significantly impact the prognosis of locally advanced ICC undergoing R0 hapectomy. Oncologists should consider incorporating inflammation-nutritional conditions into the decision-making process for this subset of advanced ICC.

ELMO1 ameliorates intestinal epithelial cellular senescence via SIRT1/p65 signaling in inflammatory bowel disease-related fibrosis.

Background: Intestinal fibrosis is a common complication in inflammatory bowel disease (IBD), which still lacks of reliable markers and therapeutic options. Cellular senescence has been considered an important mechanism of intestinal fibrosis, but the underlying molecular link remains elusive. Methods: Tissues were stained using α-smooth muscle actin (α-SMA), fibronectin, and collagen I as markers of myofibroblastic differentiation. Cellular senescence was confirmed through Lamin B1 staining, senescence-associated ß-galactosidase staining, and the expression of senescence-associated secretory phenotype (SASP) factors. We explored the relationship between senescence of intestinal epithelial cells (IECs) and intestinal fibrosis, as well as the molecular mechanism underlying this interaction. The effects of irisin on cellular senescence and fibrosis were determined. Results: Here, we identify engulfment and cell motility protein 1 (ELMO1) as a novel biomarker for intestinal cellular senescence and fibrosis. In fibrostrictured tissues from patients and murine models with IBD, significantly high levels of cellular senescence score and factors were noted, which positively correlated with the fibrotic regulator fibronectin. Senescent IECs, not fibroblast itself, released SASP factors to regulate fibroblast activation. Prolonging exposure to severe and persistent injurious stimuli decreased ELMO1 expression, which dampened SIRT1 deacetylase activity, enhanced NF-κB (p65) acetylation, and thereby accelerated cellular senescence. Deletion of ELMO1 led to senescent IECs accumulation and triggered premature fibrosis in murine colitis. Furthermore, irisin, inhibiting the degradation of ELMO1, could downregulate p65 acetylation, reduce IECs senescence, and prevent incipient intestinal fibrosis in murine colitis models. Conclusions: This study reveals ELMO1 downregulation is an early symbol of intestinal senescence and fibrosis, and the altered ELMO1-SIRT1-p65 pathway plays an important role in intestinal cellular senescence and IBD-related fibrosis.

The depth of perineural invasion is an independent prognostic factor for stage II colorectal cancer.

BACKGROUND: Perineural invasion (PNI) is the invasion of nerves by cancer cells and is associated with poor survival in stage II colorectal cancer. However, PNI can be further subdivided according to the depth of invasion, and the depth of PNI has not been clearly linked to prognosis. METHOD: This study aimed to assess the prognostic value of different depths of PNI in stage II colorectal cancer. We defined PNI in the submucosal plexus and myenteric plexus as superficial perineural invasion (sup-PNI) and PNI in the subserous plexus as deep perineural invasion (deep-PNI). Patients were divided into three groups based on the depth of PNI: sup-PNI, deep-PNI and non-PNI. Then, univariate and multivariate Cox regression analyses were conducted to evaluate the role of PNI in the prognosis of stage II colorectal cancer. RESULTS: This study enrolled 3508 patients with stage II colorectal cancer who underwent resection for primary colorectal lesions between January 2013 and September 2019. Clinicopathological features, including elevated carcinoembryonic antigen (CEA) levels, T4 stage, poor differentiation, deficient DNA mismatch repair (dMMR), and vascular invasion, were correlated with deep-PNI. Multivariate analyses revealed that deep-PNI was associated with worse overall survival (OS; hazard ratio [HR], 3.546; 95% confidence interval [CI], 2.307-5.449; P < 0.001) and disease-free survival (DFS; HR, 2.921; 95% CI, 2.032-4.198; P < 0.001), compared with non-PNI. Conversely, no significant difference in OS or DFS was observed between the sup-PNI and non-PNI groups in multivariate analyses. CONCLUSIONS: The study demonstrated that the depth of PNI was an independent prognostic factor for patients with stage II colorectal cancer, and patients with deep PNI had a worse prognosis. Thus, patients with PNI require further subdivision according to the depth of invasion.

Differential Water Conservation Capacity in Broadleaved and Mixed Forest Restoration in Latosol Soil-Eroded Region, Hainan Province, China.

The water conservation capacity of the litter and soil layers of forest ecosystems improves the function of forest ecosystems in conserving soil and water. Plantation restoration plays a key role in preventing soil erosion. In order to evaluate the water conservation capacity of plantation restoration in Latosol soil-eroded region, we analyzed the litter thickness and mass, water absorption process, water holding recovery process, and soil water holding capacity of five restoration types (Hevea brasiliensis, Acacia mangium, Eucalyptus robusta, Acacia-Eucalyptus, and Acacia-Hevea) in the Mahuangling Watershed, Hainan province. The results showed that the thickness of the litter ranged from approximately 3.42 ± 0.24 to 4.73 ± 0.81 cm, and the litter mass ranged from 5.04 ± 1.52 t·ha-1 to 13.16 ± 1.76 t·ha-1, with higher litter mass in the SL layer than in the UL layer. The litter mass of A. mangium was higher than that of H. brasiliensis, E. robusta, Acacia-Eucalyptus, and Acacia-Hevea, which was 3.16 ± 1.76 t·ha-1. A. mangium forest was significantly higher than other plantation restoration types in terms of the maximum water retention capacity (Qmax) and the effective water retention capacity (Qeff). The soil bulk weight ranged from approximately 1.52 ± 0.09 to 1.59 ± 0.08 g·cm-3, and porosity ranged from 31.77 ± 4.72 to 35.62 ± 3.02%, both of which increased with the depth of the soil layer. The water holding capacity of 0-60 cm soil varied from approximately 12.94 ± 7.91 to 45.02 ± 31.79 t·ha-1, with A. mangium having the best soil permeability and the strongest soil water holding capacity. The entropy weight method was used to conduct a comprehensive evaluation, and the results showed that the water conservation capacity of the soil layer was 1.26 times higher than that of the litter layer, in which the water conservation capacity of A. mangium was the strongest, with a comprehensive evaluation value of 0.2854, which effectively intercepted rainfall and reduced surface runoff. Hence, we suggest that the planting of A. mangium should be considered in future ecological restoration projects of the erosion area of Mahuangling in order to improve the function of conserving soil and water in a restoration forest ecosystem.

Fatty Acid Oxidation Promotes Apoptotic Resistance and Proinflammatory Phenotype of CD4+ Tissue-resident Memory T cells in Crohn's Disease.

BACKGROUND & AIMS: As the most abundant memory T cells and major source of tumor necrosis factor α in the intestinal mucosa of Crohn's disease (CD) patients, CD4+ tissue-resident memory T (TRM) cells play a critical role in CD pathogenesis. We investigated the role of metabolic reprogramming in the regulation of proinflammatory and apoptosis-resistant phenotype for CD4+ TRM cells. METHODS: CD4+ TRM cells were collected from intestinal resection tissues from control and CD patients. Transcriptomic and metabolomic analysis were performed to identify metabolic characteristics of CD4+ TRM cells. Enzyme-linked immunosorbent assay and quantitative polymerase chain reaction experiments were used to assess cytokines level in CD4+ TRM cells; activation-induced cell apoptosis rate was evaluated by flow cytometry. Transwell assay and wound healing assay were performed to detect the effect of CD4+ TRM cells on the migration of normal intestinal epithelial cells. RESULTS: Transcriptomic data combined with unbiased metabolomic analysis revealed an increased fatty acid oxidation (FAO) phenotype existed in CD4+ TRM cells from CD patients. The lipidomic data and stable isotope tracer experiments demonstrated that CD4+ TRM cells up-regulated their lipid lipolysis and fatty acid uptake to fuel FAO in CD patients. Mechanistically, the activated nuclear factor kappa B signaling increased transcription of genes involved in lipid lipolysis, fatty acid uptake, and oxidation in CD4+ TRM cells from CD patients. Targeting FAO of CD4+ TRM cells reversed their apoptosis-resistant and proinflammatory phenotype in CD patients. CONCLUSIONS: CD4+ TRM cells process an accelerated FAO mediated by activated nuclear factor kappa B signaling in CD patients; targeting FAO could reverse their apoptosis-resistant and proinflammatory phenotype. These findings shed a new light on the pathogenic mechanism investigation and novel therapy development in CD patients.

Thermal-Assisted Multiscale Patterning of Nonplanar Colloidal Nanostructures for Multi-Modal Anti-Counterfeiting.

Nanotransfer printing of colloidal nanoparticles is a promising technique for the fabrication of functional materials and devices. However, patterning nonplanar nanostructures pose a challenge due to weak adhesion from the extremely small nanostructure-substrate contact area. Here, the study proposes a thermal-assisted nonplanar nanostructure transfer printing (NP-NTP) strategy for multiscale patterning of polystyrene (PS) nanospheres. The printing efficiency is significantly improved from ≈3.1% at low temperatures to ≈97.2% under the glass transition temperature of PS. Additionally, the arrangement of PS nanospheres transitioned from disorder to long-range order. The mechanism of printing efficiency enhancement is the drastic drop of Young's modulus of nanospheres, giving rise to an increased contact area, self-adhesive effect, and inter-particle necking. To demonstrate the versatility of the NP-NTP strategy, it is combined with the intaglio transfer printing technique, and multiple patterns are created at both micro and macro scales at a 4-inch scale with a resolution of ≈2757 pixels per inch (PPI). Furthermore, a multi-modal anti-counterfeiting concept based on structural patterns at hierarchical length scales is proposed, providing a new paradigm of imparting multiscale nanostructure patterning into macroscale functional devices.

Market integration and economic growth.

This study empirically examines the interplay between market integration and economic growth across nine cities within the Pearl River Delta urban agglomeration. The findings indicate that the city cluster's market integration negatively impacts regional economic development and has a negligible effect on the surrounding areas. In response, the research recommends the elimination of market trade barriers and a reduction in local protectionism within the city cluster. Additionally, infrastructure enhancement is essential to leverage the distinct comparative advantages of each city within the Pearl River Delta urban agglomeration. An efficient collaboration mechanism is crucial to amplify the collective economic potency of the region.

Combining perineural invasion with staging improve the prognostic accuracy in colorectal cancer: a retrospective cohort study.

BACKGROUND: Current guidelines only propose the importance of perineural invasion(PNI) on prognosis in stage II colon cancer. However, the prognostic value of PNI in other stages of colorectal cancer (CRC) is ambiguous. METHODS: This single-center retrospective cohort study included 3485 CRC patients who underwent primary colorectal resection between January 2013 and December 2016 at the Sixth Affiliated Hospital of Sun Yat-sen University. Associations of PNI with overall survival (OS) and disease-free survival (DFS) were evaluated using multivariable Cox proportional hazards regression models. In addition, interaction analyses were performed to explore the prognostic effects of PNI in different clinical subgroups. RESULTS: After median follow-up of 61.9 months, we found PNI was associated with poorer OS (adjusted hazard ratio [aHR], 1.290; 95% CI, 1.087-1.531) and DFS (aHR, 1.397; 95% CI, 1.207-1.617), irrespective of tumor stage. Interestingly, the weight of PNI was found second only to incomplete resection in the nomogram for risk factors of OS and DFS in stage II CRC patients. Moreover, OS and DFS were insignificantly different between stage II patients with PNI and stage III patients (both P > 0.05). PNI was found to be an independent prognostic factor of DFS in stage III CRC (aHR: 1.514; 95% CI, 1.211-1.892) as well. Finally, the adverse effect of PNI on OS was more significant in female, early-onset, and diabetes-negative patients than in their counterparts (interaction P = 0.0213, 0.0280, and 0.0186, respectively). CONCLUSION: PNI was an important prognostic factor in CRC, more than in stage II. The survival of patients with stage II combined with perineural invasion is similar with those with stage III. PNI in stage III CRC also suggests a worse survival.

Prognostic Implications of Endoscopic Obstruction in Patients with Pathological Stage II Colon Cancers: a Single-Center Retrospective Cohort Study.

BACKGROUND: The prognostic effect of endoscopic obstruction (eOB) on the survival of stage II colon cancer patients and the role of eOB in guiding postoperative adjuvant chemotherapy of stage II colon cancer are little known. METHODS: In this retrospective, single-center cohort study, patients who had undergone curative surgery and preoperative colonoscope for stage II colon carcinoma were included. The eOB was defined as severe luminal colon obstruction that prevented the standard colonoscope from passing beyond the tumor. The association between eOB and stage II colon cancer survival and the predictive role of eOB for adjuvant chemotherapy were evaluated using multivariate Cox regression analysis. RESULTS: Of 1102 included patients, 616 (55.9%) had eOB and 486 (44.1%) had no eOB. The median follow-up was 49 months (interquartile range, 38-68 months). Kaplan-Meier curves showed that patients with eOB had poor 5-year overall survival (OS; 85.3% vs. 95.3%, p < 0.001) compared to patients without eOB. Five-year disease-free survival (DFS; 78.5% vs. 87.6%, p = 0.004) was also poor in these patients. Multivariate analysis demonstrated eOB was a significant prognostic factor for poor OS (hazard ratio [HR] = 2.531, p < 0.001), but not for DFS (p = 0.081). Even when patients with clinical colonic obstruction were excluded from the population with eOB, the worse OS (HR = 2.262, p = 0.001) was observed. The OS and DFS of eOB patients improved slightly after adjuvant chemotherapy, but there was no statistical significance. CONCLUSIONS: Stage II colon cancer patients with eOB have a poor prognosis. However, whether eOB can guide adjuvant chemotherapy still needs further study.

Clinicopathological and molecular characteristics of early-onset vs late-onset colorectal cancer according to tumor location.

BACKGROUND: The incidence of early-onset colorectal cancer (EOCRC) is rapidly increasing worldwide in decade when screening of colorectal cancer (CRC) is more prevalent. The clinicopathological and molecular characteristics of EOCRC have not yet been clarified. This study aims to evaluate clinicopathological and molecular features among EOCRC and late-onset colorectal cancer (LOCRC) patients according to different tumor locations. METHODS: We identified CRC patients from a prospectively maintained CRC database between January 2015 and December 2018. The clinicopathological and molecular characteristics including dMMR, mutation of PIK3CA, BRAF and KRAS were compared between EOCRC and LOCRC. The relationships according to different tumor locations were assessed. RESULTS: Totally 4468 patients were analyzed in this study. Compared to LOCRC patients, EOCRC patients were more likely to have status of dMMR (OR, 2.52; P < 0.001), regardless of tumor location. EOCRC patients were more likely to be detected with mutation of PIK3CA (OR, 1.24; P = 0.041), which only tended to exist in the left-side colon (OR, 1.51; P = 0.06), but not in the right-side colon or rectum. No significant difference was found for BRAF or KRAS mutation, but mutation of KRAS was more frequently found in left-side colon (OR, 1.34; P = 0.04) among EOCRC patients. CONCLUSION: Status of dMMR, mutation of PIK3CA, BRAF and KRAS was different between EOCRC and LOCRC patients according to different tumor locations, which implied that EOCRC might be a unique subgroup of CRC patients. Further investigations of molecular and genetic differences should be performed to help define new diagnosing and therapeutical strategies for EOCRC patients.

Endoscopic Stricturotomy for Patients With Postoperative Benign Anastomotic Stricture for Colorectal Cancer.

BACKGROUND: Postoperative benign anastomotic stricture is associated with colorectal anastomosis following surgery for colorectal cancer. Endoscopic stricturotomy is a novel technique that has been demonstrated to be safe and effective for the treatment of colorectal anastomotic stricture in several case reports and series. OBJECTIVE: We designed this study to investigate the efficacy of endoscopic stricturotomy for postoperative benign anastomotic stricture in patients for colorectal cancer. The primary outcomes were stricture-recurrence-free survival and reoperation-free survival. DESIGN: This is a retrospective study. SETTING: This study presents a single-center experience. PATIENTS: This retrospective study included patients with colorectal cancer who underwent surgical resection and developed anastomotic stricture between January 2014 and June 2019 and were treated with endoscopic stricturotomy. MAIN OUTCOME MEASURES: Immediate technical success of endoscopic stricturotomy and the factors associated with success and recurrence were investigated. RESULTS: Endoscopic stricturotomy was performed in 57 patients, and immediate technical success was achieved in 84% of the patients. The mean follow-up was 31.3 (15.8) months (range, 9-74 months). Postoperative benign anastomotic stricture recurred in 11 patients after initial successful endoscopic stricturotomy; 10 of the 11 recurrent patients accepted reoperation. Univariate and multivariate analysis indicated that length of stricture ≥1 cm was an independent risk factor for failure of the initial endoscopic stricturotomy (OR, 9.423; 95% CI, 1.729-51.350; p = 0.010) and the recurrence of postoperative benign anastomotic stricture after the initial endoscopic stricturotomy (OR, 13.521; 95% CI, 2.305-79.306; p = 0.004). LIMITATIONS: The study was limited by its small sample size and retrospective design. CONCLUSIONS: Endoscopic stricturotomy is a safe and effective technique for postoperative benign anastomotic stricture. However, if the length of the stricture is ≥1 cm, endoscopic stricturotomy may not be effective, and recurrence of postoperative benign anastomotic stricture is also likely. See Video Abstract at http://links.lww.com/DCR/B739. ESTRICTUROTOMA ENDOSCPICA PARA PACIENTES CON ESTRICCIN ANASTOMTICA BENIGNA POSTOPERATORIA PARA EL CNCER COLORRECTAL: ANTECEDENTES:La estenosis anastomótica benigna postoperatoria se asocia con anastomosis colorrectal después de la cirugía para el cáncer colorrectal. La estricturotomia endoscópica es una técnica novedosa que se ha demostrado que es segura y efectiva para el tratamiento de la estenosis anastomótica colorrectal en varios informes de casos o series.OBJETIVO:Diseñamos este estudio para investigar la eficacia de la estricturotomia endoscópica para la estenosis anastomótica benigna postoperatoria en pacientes con cáncer colorrectal. El resultado primario fue la supervivencia libre de restricción estricta y la supervivencia libre de reoperación.DISEÑO:Este es un estudio retrospectivo.CONFIGURACIÓN:Este estudio presenta una experiencia de un solo centro.PACIENTES:Este estudio retrospectivo incluyó pacientes con cáncer colorrectal que se sometieron a resección quirúrgica y desarrollaron estenosis anastomótica entre enero de 2014 y junio de 2019 y tratados con estricturotomia endoscópica.MEDIDAS PRINCIPALES DE RESULTADO:Éxito técnico inmediato y estenosurotomía endoscópica, los factores asociados con el éxito y la recurrencia.RESULTADOS:Se realizó estricturotomia endoscópica en 57 pacientes, y se logró un éxito técnico inmediato en el 84% de los pacientes. El seguimiento medio fue de 31,3 (15,8) meses (rango, 9 a 74 meses), el POBAS se repitió en 11 pacientes después del éxito inicial de ESt. 10 de los 11 pacientes recurrentes aceptaron la reoperación. El análisis univariado y multivariado indicó que la longitud de la estenosis ≥1 cm era un factor de riesgo independiente para el fracaso de la estricturotomia endoscópica inicial (odds ratio = 9,423; IC del 95% = 1.729-51.350; p = 0.010) y la recurrencia de estenosis anastomótica benigna postoperatoria después de la estricturotomia endoscópica inicial (odds ratio = 13,521; IC del 95% = 2,305-79,306; p = 0.004).LIMITACIONES:El estudio estuvo limitado por su pequeño tamaño de muestra y diseño retrospectivo.CONCLUSIONES:La estricturotomia endoscópica es una técnica segura y efectiva para la estructura anastomótica benigna postoperatoria. Sin embargo, si la longitud de la estenosis es ≥1 cm, la estricturotomia endoscópica puede no ser efectiva y también es probable que se repita la estenosis anastomótica benigna postoperatoria. Consulte Video Resumen en http://links.lww.com/DCR/B739.

Risk factors for metachronous adenoma in patients with stage I/II colorectal cancer after radical surgery.

BACKGROUND: It is important to implement a preventive strategy for early detection and endoscopic removal of metachronous adenoma in patients with colorectal cancer (CRC). Here, we retrospectively explored the associated factors of metachronous adenoma in these patients. METHODS: This study recruited 551 patients with stage I and II CRC who underwent radical surgery between January 1, 2012 and July 1, 2017 with postoperative colonoscopic surveillance. Data on clinicopathological characteristics and surveillance colonoscopies were obtained from medical records. Univariate analysis by Kaplan-Meier method and multivariate analysis by Cox proportional hazards model were used to identify the factors associated with metachronous adenoma. RESULTS: Metachronous adenoma was detected in 110 (20.0%) patients. In these patients, 94.5% (104/110) had metachronous adenoma within 3 years postoperatively. Age, synchronous adenoma, hypertension, tumor stage, and surgical resection were correlated with metachronous adenoma in patients with stage I-II CRC after radical resection (log rank test, P<0.05). Multivariate analyses showed that synchronous adenoma (HR =2.515, 95% CI: 1.691-3.742, P<0.01); stage II (HR =2.066, 95% CI: 1.329-3.210, P<0.01); and left-side colorectal resection (HR =2.207, 95% CI: 1.292-3.772, P<0.01) were independent risk factors. CONCLUSIONS: Synchronous adenoma, left-side colorectal resection, and stage II cancer are independent risk factors of metachronous adenoma in patients with previous stage I and II CRC. In patients with risk factors, an enhanced colonoscopic strategy might be needed for early detection and timely endoscopic removal of metachronous adenoma.

Simultaneous measurement of liquid-level and density by detecting buoyancy and hydraulic pressure: publisher's note.

This publisher's note contains corrections to Opt. Lett.45, 6843 (2020)OPLEDP0146-959210.1364/OL.412738.

A Novel Snare Traction-Assisted Method During Endoscopic Resection for Upper Gastrointestinal Submucosal Tumors.

Background: Traction-assisted endoscopic resection is an approach to provide better procedural outcomes than conventional endoscopic procedure in treating gastric or esophageal epithelial lesions. Submucosal tumors (SMTs) are challenging to resect endoscopically due to the difficulty in exposure and high incidence of full-thickness resection. In this study, we investigated the efficacy of snare traction-assisted method, served as an "extra hand," for upper gastrointestinal SMTs. Methods: From June 2019 to May 2020, we used the snare traction-assisted method to treat 11 patients with 12 upper gastrointestinal SMTs in the Sixth Affiliated Hospital, Sun Yat-sen University. The duration of the procedures and the outcomes were recorded. Results: A total of 11 patients with 12 lesions were treated by snare traction-assisted endoscopic resection. The mean procedure time was 26.8 ± 8.3 minutes. En bloc resection was achieved in all the 12 lesions. The mean length of the specimens was 11.5 ± 4.0 mm. Full-thickness resection was performed in four lesions. The patients were discharged in 5.0 days after procedures without delayed bleeding or other complication reported. Conclusion: Snare traction-assisted method is an effective tool for endoscopic resection of upper gastrointestinal SMTs. Further prospective studies comparing the snare traction-assisted method with the conventional procedure are necessary.

Simultaneous measurement of liquid-level and density by detecting buoyancy and hydraulic pressure.

In this Letter, we propose and experimentally demonstrate a method for simultaneous and complete discriminative measurement of liquid-level and density for the first time, to the best of our knowledge. The principle is to measure the responses of optical fiber sensing units caused by buoyancy and hydraulic pressure. By utilizing a designed steel diamond structure, the sensor sensitivity is significantly improved. The theoretical models and experimental methods are analyzed in detail. For large-range liquid-level measurement, a high sensitivity of 77.3 pm/cm with resolution of 0.129 mm (accuracy of 0.149‰) is achieved. As a trade-off between density measurement and sensor capability, a dual-parameter sensing is demonstrated experimentally, which features liquid-level sensitivity of 34.7 pm/cm and density sensitivity varying from 1 to 3.44nm/g/cm3. Taking advantage of the compact size, easy fabrication, and low cost, this method has great potential in real-time intelligent monitoring of reserves and quality for industrial storage of fuels and chemicals.

Effects of Huaier Extract on Ameliorating Colitis-Associated Colorectal Tumorigenesis in Mice.

BACKGROUND: Huaier extract has been a part of traditional Chinese medicine (TCM) for roughly 1600 years and may serve as a potential anti-cancer drug as it is associated with good efficacy and low toxicity. Individuals with inflammatory bowel disease (IBD) are at a higher chance of being diagnosed with colorectal cancer (CRC) and as Huaier extract may potentially influence tumorigenesis, we set out to determine the effect of Huaier extract on colitis-associated CRC. METHODS: The CRC mouse model, established through azoxymethane (AOM) and dextran sulfate sodium (DSS), was administered Huaier extract. Weight loss, colon length, tumor number and tumor size were evaluated macroscopically. Pro-inflammatory cytokine expression and STAT3 phosphorylation were assessed in the colon using ELISA, Western blot and/or immunohistochemistry. RESULTS: Huaier extract improved the severity of colitis-associated tumorigenesis compared with control group, with attenuated weight loss and longer colons. Tumor number, size and load were drastically decreased in mice treated with Huaier. Histological assessment suggested that Huaier could decrease histological injury of the colon tissue. Additionally, Huaier extract treatment led to reduced pro-inflammatory cytokine levels (TNF-α, IL-6, IFN-γ and IL-1ß) and a decrease of STAT3 phosphorylation in colon tissue. Additionally, present findings demonstrated that Huaier extract inhibited cell proliferation and induced apoptosis in CRC cells HCT116 and HCT8. The migration and invasion of CRC cells were markedly inhibited upon exposure to Huaier treatment. The apoptosis-associated protein levels (P53, Bax, Bcl-2, pro-caspase-3 and cleavage caspase-3) showed significant differences after the administration of Huaier extract in HCT116 and HCT8 cells. In vivo, the administration of Huaier extract to mice inhibited tumor growth and yielded a similar profile of apoptotic proteins expression p53, Bcl-2, pro-caspase-3 and cleaved caspase-3 while no significant differences in Bax were observed. Moreover, the ratio of TUNEL-positive/apoptotic cells was markedly increased in the Huaier-treated mice. CONCLUSION: Huaier extract may reduce the IBD-associated tumor development by suppressing pro-inflammatory cytokine levels and STAT3 stimulation.

Increase in CD4+FOXP3+ regulatory T cell number and upregulation of the HGF/c-Met signaling pathway during the liver metastasis of colorectal cancer.

Colorectal cancer (CRC) is the third and second most common type of cancer diagnosed in males and females, respectively, and is the fourth leading cause of cancer-associated mortality worldwide. Liver metastasis is the primary cause of mortality in patients with CRC, and therefore requires therapeutic focus. Regulatory T cells (Tregs) and hepatic stellate cells (HSCs) are potentially involved in regulating the immune response during liver metastasis. The aim of the present study was to evaluate the influence of CD4+ forkhead box p3 (Foxp3)+ Tregs and the HGF/c-Met signaling pathway in the liver metastasis of CRC. A model of the latter was established using Balb/c mice via splenic injection of human CRC cells (CT-26 line). The mice were monitored for 3 weeks after being injected, and the spleens and livers were removed on day 22 for further analysis. Moreover, the single-cell suspensions were labeled with CD4 and Foxp3 antibodies, and were analyzed using flow cytometry. Expression levels of α-smooth muscle actin (SMA), hepatocyte growth factor (HGF) and hepatocyte growth factor receptor (c-Met) were analyzed using immunohistochemistry. Mice injected with CT-26 cells exhibited signs of illness and significant weight loss, compared with the control mice (P=0.013), and they also developed liver metastases, at an average of 20.5 tumors per mouse. Pathological evaluation using hematoxylin and eosin staining confirmed the tumors as liver metastases of CRC. The numbers of CD4+ T cells were significantly decreased in the spleen (P<0.001) and liver (P=0.003) of tumor-bearing mice, while the proportions of CD4+FOXP3+ Tregs increased significantly in the spleen (P<0.001) and liver (P=0.026) compared with that in the controls. Additionally, α-SMA, HGF and c-Met levels increased significantly during metastatic growth in the liver. In conclusion, CD4+FOXP3+ Treg levels increased and the HGF/c-Met pathway was upregulated during the liver metastasis of CRC in mice, indicating the presence of potential therapeutic targets.

CD73 promotes colitis-associated tumorigenesis in mice.

Patients with inflammatory bowel disease (IBD) are at a higher risk of developing colitis-associated colorectal cancer. The aim of the present study was to investigate the role of CD73 in IBD-associated tumorigenesis. A mouse model of colitis-associated tumorigenesis (CAT) induced by azoxymethane and dextran sulfate sodium was successfully constructed. Model mice were injected with CD73 inhibitor or adenosine receptor agonist. Colon length, body weight loss and tumor formation were assessed macroscopically. Inflammatory cytokine measurement and RNA sequencing on colon tissues were performed. Inhibition of CD73 by adenosine 5'-(α,ß-methylene) diphosphate (APCP) suppressed the severity of CAT with attenuated weight loss, longer colons, lower tumor number and smaller tumor size compared with the model group. Activation of adenosine receptors using 1-(6-amino-9H-purin-9-yl)-1-deoxy-N-ethyl-ß-D-ribofuranuronamide (NECA) exacerbated CAT. Histological assessment indicated that inhibition of CD73 reduced, while activation of adenosine receptors exacerbated, the histological damage of the colon. Increased expression of pro-inflammatory cytokines (tumor necrosis factor-α and interleukin-6) in colonic tissue was detected in the NECA group. According to RNA sequencing results, potential oncogenes such as arachidonate 15-lipoxygenase (ALOX15), Bcl-2-like protein 15 (Bcl2l15) and N-acetylaspartate synthetase (Nat8l) were downregulated in the APCP group and upregulated in the NECA group compared with the model group. Therefore, inhibition of CD73 attenuated IBD-associated tumorigenesis, while activation of adenosine receptors exacerbated tumorigenesis in a C57BL/6J mouse model. This effect may be associated with the expression of pro-inflammatory cytokines and the regulation of ALOX15, Bcl2l15 and Nat8l.

Risk factor analysis for inaccurate pre-operative MRI staging in rectal cancer.

BACKGROUND: Various tumor characteristics might lead to inaccurate local MRI-defined stage of rectal cancer and the purpose of this study was to explore the clinicopathological factors that impact on the precision pre-treatment MRI-defined stage of rectal cancer. METHODS: A retrospectively analysis was conducted in non-metastatic rectal cancer patients who received radical tumor resection without neoadjuvant treatment during 2007-2015 in the Sixth Affiliated Hospital of Sun Yat-sen University. Clinical T stage and N stage defined by pelvic enhanced MRI and pathological stage were compared and patients were subdivided into accurate-staging, over-staging and under-staging subgroups. Logistic regressions were used to explore risk factors for over-staging or under-staging. RESULTS: Five hundred fifty-one cases of patients were collected. Among them, 109 cases (19.4%) of patients were over-T-staged and 50 cases (8.9%) were under-T-staged, while 78 cases (13.9%) were over-N-staged and 75 cases (13.3%) were under-N-staged. Logistic regression suggested that pre-operative bowel obstruction was risk factor for over-T-staging (OR = 3.120, 95%CI: 1.662-5.857, P < 0.001) as well as over-N-staging (OR = 3.494, 95%CI: 1.797-6.794, P < 0.001), while mucinous adenocarcinoma was a risk factor for under-N-staging (OR = 4.049, 95%CI: 1.876-8.772, P < 0.001). Patients with larger tumor size were at lower risk for over-T-staging (OR = 0.837, 95%CI: 0.717-0.976, P = 0.024) and higher risk for over-N-staging (OR = 1.434, 95%CI: 1.223-1.680, P < 0.001). CONCLUSION: Bowel obstruction, mucinous adenocarcinoma and tumor size might have impact on the pre-operative MRI T staging or N staging of rectal cancer. Our results reminded clinicians to assess clinical stage individually in such rectal cancer patients.

Risk factors for recurrence after bowel resection for Crohn's disease.

BACKGROUND: Complications of Crohn's disease such as intestinal obstruction, fistula or perforation often need surgical treatment. Nearly 70%-80% patients with Crohn's disease would receive surgical treatment during the lifetime. However, surgical treatment is incurable for Crohn's disease. The challenge of recurrence postoperatively troubles both doctors and patients. Over 50% patients would suffer recurrence postoperatively. Some certain risk factors are associated with recurrence of Crohn's disease. AIM: To evaluate the risk factors for endoscopic recurrence and clinical recurrence after bowel resection in Crohn's disease. METHODS: Patients diagnosed Crohn's disease and received intestinal resection between April 2007 and December 2013 were included in this study. Data on the general demographic information, preoperative clinical characteristics, surgical information, postoperative clinical characteristics were collected. Continuous data are expressed as median (inter quartile range), and categorical data as frequencies and percentages. Kaplan-Meier method was applied to estimate the impact of the clinical variables above on the cumulative rate of postoperative endoscopic recurrence and clinical recurrence, then log-rank test was applied to test the homogeneity of those clinical variables. Multivariate Cox proportional hazard regression analysis was performed to identify the risk factors of postoperative endoscopic recurrence and clinical recurrence. RESULTS: A total of 64 patients were included in this study. The median follow-up time for the patients was 17 (9.25-25.75) mo. In this period, 41 patients (64.1%) had endoscopic recurrence or clinical recurrence. Endoscopic recurrence occurred in 34 (59.6%) patients while clinical recurrence occurred in 28 (43.8%) patients, with the interval between the operation and recurrence of 13.0 (8.0-24.5) months and 17.0 (8.0-27.8) mo, respectively. In univariate analysis, diagnosis at younger age (P < 0.001), disease behavior of penetrating (P = 0.044) and preoperative use of anti-tumor necrosis factor (TNF) (P = 0.020) were significantly correlated with endoscopic recurrence, while complication with perianal lesions (P = 0.032) and preoperative use of immunomodulatory (P = 0.031) were significantly correlated with clinical recurrence. As to multivariate analysis, diagnostic age (P = 0.004), disease behavior (P = 0.041) and preoperative use of anti-TNF (P = 0.010) were independent prognostic factors for endoscopic recurrence, while complication with perianal lesions (P = 0.023) was an independent prognostic factor for clinical recurrence. CONCLUSION: Diagnostic age, disease behavior, preoperative use of anti-TNF and complication with perianal lesions were independent risk factors for postoperative recurrence in Crohn's disease.