Pan-cancer analysis of Sushi domain-containing protein 4 (SUSD4) and validated in colorectal cancer.

Sushi domain-containing protein 4 (SUSD4) is a complement regulatory protein whose primary function is to inhibit the complement system, and it is involved in immune regulation. The role of SUSD4 in cancer progression has largely remained elusive. SUSD4 was studied across a variety of cancer types in this study. According to the results, there is an association between the expression level of SUSD4 and prognosis in multiple types of cancer. Further analysis demonstrated that SUSD4 expression level was related to immune cell infiltration, immune-related genes, tumor heterogeneity, and multiple cancer pathways. Additionally, we validated the function of SUSD4 in colorectal cancer cell lines and found that knockdown of SUSD4 inhibited cell growth and impacted the JAK/STAT pathway. By characterizing drug sensitivity in organoids, we found that the expression of SUSD4 showed a positive correlation trend with IC50 of Selumetinib, YK-4-279, and Piperlongumine. In conclusion, SUSD4 is a valuable prognostic indicator for diverse types of cancer, and it has the potential to be a target for cancer therapy.

Fixed Yellow-to-Blue Intensity Ratio of Dy3+ in KY(CO3)2 Host for Emission Color Tuning.

Dy3+, Ce3+ co-doped KY(CO3)2 phosphors with a monoclinic structure were synthesized using the hydrothermal method to create a fixed yellow-to-blue ratio emission. The [YO8] polyhedron, consisting of a Y atom and eight oxygen atoms, forms a relatively independent microstructure within the KY(CO3)2 host. Y3+ ions are partially replaced by Ce3+ or Dy3+ ions to construct the [CeO8] or [DyO8] polyhedral fluorescence emission unit. The spectral measurements indicate that Ce3+ and Dy3+ can maintain relatively independent fluorescence emission characteristics in the KY(CO3)2 host. The yellow-to-blue intensity ratio of Dy3+ remains close to 1 and does not change with the variation in the doping concentration of KY(CO3)2:Dy3+ and KY(CO3)2:Dy3+,Ce3+ phosphors. When Ce3+ and Dy3+ are co-doped with KY(CO3)2, the emission intensities of Dy3+ under 339 nm and 365 nm excitation increase by 8.43 and 2.32 times, respectively, through resonance energy transfer and cross-relaxation. All Ce3+-doped KY(CO3)2:Dy3+ phosphors can emit white light. Among them, the emitted light of KY(CO3)2:3%Dy3+,5%Ce3+ is closest to standard daylight. Therefore, a stable [YO8] polyhedral structure can be used to achieve more color tuning of light.

Primary Surgery Followed by Selective Chemoradiotherapy Versus Preoperative Chemoradiotherapy Followed by Surgery for Locally Advanced Rectal Cancer: A Randomized Clinical Trial.

PURPOSE: The aim of this work was to determine whether locally advanced rectal cancer (LARC) with negative mesorectal fascia (MRF) predicted by magnetic resonance imaging (MRI) can be excluded from preoperative radiation therapy treatment. METHODS AND MATERIALS: This multicenter, open-label, non-inferiority, randomized clinical trial enrolled patients with LARC within 6 to 12 cm from the anal verge and with negative MRI-predicted MRF. Participants were randomized to the intervention group (primary surgery, in which the patients with positive pathologic [CRM] circumferential margins were subjected to chemoradiotherapy [CRT] and those with negative CRM underwent adjuvant chemotherapy according to pathologic staging) or the control group (preoperative CRT, in which all patients underwent subsequent surgery and adjuvant chemotherapy). The primary endpoint was 3-year disease-free survival (DFS). RESULTS: A total of 275 patients were randomly assigned to the intervention (n = 140) and control (n = 135) groups, in which 33.57% and 28.15% patients were at clinical T4 stage and 85.92% and 80.45% patients were at "bad" or "ugly" risk in the intervention and control groups, respectively. There were 2 patients (1.52%) and 1 patient (0.77%) with positive CRM in the intervention and control groups, respectively (P > .05). The non-adherence rates for the intervention and control groups were 3.6% and 23.7%, respectively. After a median follow-up of 34.6 months (IQR, 18.2-45.7), 43 patients had positive events (28 patients and 15 patients in the intervention and control groups, respectively). There were 6 patients (4.4%) with local recurrence in the intervention group and none in the control group, which led to the termination of the trial. The 3-year DFS rate was 81.82% in the intervention group (95% CI, 78.18%-85.46%) and 85.37% in the control group (95% CI, 81.75%-88.99%), with a difference of -3.55% (95% CI, -3.71% to -3.39%; hazard ratio, 1.76; 95% CI, 0.94-3.30). In the per-protocol data set, the difference between 3-year DFS rates was -5.44% (95% CI, -5.63% to -5.25%; hazard ratio, 2.02; 95% CI, 1.01-4.06). CONCLUSIONS: Based on the outcomes of this trial, in patients with LARC and MRI-negative MRF, primary surgery could negatively influence their DFS rates. Therefore, primary surgery was an inferior strategy compared with preoperative CRT followed by surgery and cannot be recommended for patients with LARC.

Quantum Cutting in KGd(CO3)2:Tb3+ Green Phosphor.

Phosphors with a longer excitation wavelength exhibit higher energy conversion efficiency. Herein, quantum cutting KGd(CO3)2:Tb3+ phosphors excited by middle-wave ultraviolet were synthesized via a hydrothermal method. All the KGd(CO3)2:xTb3+ phosphors remain in monoclinic structures in a large Tb3+ doping range. In the KGd(CO3)2 host, 6D3/2 and 6I17/2 of Gd3+ were employed for quantum cutting in sensitizing levels. The excited state electrons could easily transfer from Gd3+ to Tb3+ with high efficiency. There are three efficient excited bands for quantum cutting. The excited wavelengths of 244, 273, and 283 nm correspond to the transition processes of 8S7/2→6D3/2 (Gd3+), 8S7/2→6I17/2 (Gd3+), and 7F6→5F4 (Tb3+), and the maximum quantum yields of KGd(CO3)2:Tb3+ can reach 163.5, 119, and 143%, respectively. The continuous and efficient excitation band of 273-283 nm can well match the commercial 275 nm LED chip to expand the usage of solid-state light sources. Meanwhile, the phosphor also shows good excitation efficiency at 365 nm in a high Tb3+ doping concentration. Therefore, KGd(CO3)2:Tb3+ is an efficient green-emitting phosphor for ultraviolet-excited solid-state light sources.

Upregulation of HMGB1 in tumor-associated macrophages induced by tumor cell-derived lactate further promotes colorectal cancer progression.

BACKGROUND: Lactate accumulation leads to an acidic tumor microenvironment (TME), in turn promoting colorectal cancer (CRC) progression. Tumor-associated macrophages (TAMs) are the predominant cells in TME. This study aimed to reveal the regulation mechanism of CRC cell-derived lactate on TAMs and explore the mechanism underlying lactate accumulation-induced aggravation in CRC. METHODS: Cell growth and metastasis were evaluated by colony formation, Transwell, and wound healing assays. Western blot and RT-qPCR were applied to determine the protein and mRNA expression. Flow cytometry was used to analyze the polarization state and apoptotic rate of macrophages induced in THP-1 cells. The lactate in the cell supernatant was quantified using an ELISA kit. Immunofluorescence was performed to visualize the location of High Mobility Group Box 1 (HMGB1). H&E and Ki67 staining assays were used to assess tumorigenesis in nude mice bearing ectopic tumors. RESULTS: Cell growth and metastasis were promoted in the hypoxic CRC cells. The hypoxic cell supernatant stimulated the M2-type polarization of macrophages. The lactate level increased in hypoxic cancer cells. However, the inhibition of lactate using 3-hydroxy-butyrate (3-OBA) reversed the effects of hypoxia. Also, macrophages showed no promoting effect on cancer cell growth and migration in the presence of 3-OBA. HMGB1 was secreted into the extracellular space of lactate-induced macrophages, further enhancing the malignant behaviors of cancer cells. ERK, EMT, and Wnt signaling pathways were activated in cancer cells due to HMGB1 upregulation. CONCLUSIONS: The lactate metabolized by cancer cells stimulated M2 polarization and HMGB1 secretion by macrophages, aggravating the carcinogenic behaviors of cancer cells.

Computational Dissection of the Role of Trp305 in the Regulation of the Death-Associated Protein Kinase-Calmodulin Interaction.

Death-associated protein kinase 1 (DAPK1), as a calcium/calmodulin (CaM) regulated serine/threonine kinase, functions in apoptotic and autophagy pathways and represents an interesting drug target for inflammatory bowel disease and Alzheimer's disease. The crystal structure of the DAPK1 catalytic domain and the autoregulatory domain (ARD) in complex with CaM provides an understanding of CaM-dependent regulation of DAPK1 activity. However, the molecular basis of how distinct Trp305 (W305Y and W305D) mutations in the ARD modulate different DAPK1 activities remains unknown. Here, we performed multiple, µs-length molecular dynamics (MD) simulations of the DAPK1-CaM complex in three different (wild-type, W305Y, and W305D) states. MD simulations showed that the overall structural complex did not change significantly in the wild-type and W305Y systems, but underwent obvious conformational alteration in the W305D system. Dynamical cross-correlation and principal component analyses revealed that the W305D mutation enhanced the anti-correlated motions between the DAPK1 and CaM and sampled a broader distribution of conformational space relative to the wild-type and W305Y systems. Structural and energetical analyses further exhibited that CaM binding was unfavored in response to the W305D mutation, resulting in the decreased binding of CaM to the W305D mutant. Furthermore, the hydrogen bonds and salt bridges responsible for the loss of CaM binding on the interface of the DAPK1-CaM complex were identified in the W305D mutant. This result may provide insights into the key role of Trp305 in the regulation of CaM-mediated DAPK1 activity.

The lncRNA NEAT1 Inhibits miRNA-216b and Promotes Colorectal Cancer Progression by Indirectly Activating YY1.

Background: Nuclear Paraspeckle Assembly Transcript 1 (NEAT1) is commonly considered an oncogene in various cancers. The long noncoding RNA NEAT1 has been reported to be overexpressed in colorectal cancer (CRC). However, the exact role of NEAT1 in CRC remains unknown. Our research aimed to explore the function of NEAT1 in the tumorigenesis and the development of CRC. Methods: Real-time quantitative PCR (qRT-PCR) was used to detect the NEAT1, miR-216b, and YIN-YANG-1 (YY1) mRNA levels in CRC tissues and cells, then immunohistochemistry (IHC) was used to detect the expression of YY1 in CRC tissues. Luciferase reporter, qPCR, western blot, and DNA pulldown assays were conducted to study the relationships between NEAT1, miR-216b, and YY1. Flow cytometry analysis was performed for cell cycle and apoptosis analyses, and a colony formation assay was performed to test cell proliferation. Transwell assays were performed to detect cell invasion and migration. Results: The NEAT1 expression was significantly upregulated in CRC tissues compared with its expression in normal tissues, and downregulation of NEAT1 suppressed the proliferation, migration, and invasion of CRC cells. Moreover, we found NEAT1 decreased the miR-216b level directly, and the suppression of miR-216b could inhibit the function of downstream YY1. However, overexpression of YY1 accelerated CRC cell proliferation, migration, and invasion. Conclusion: Our results indicated that NEAT1 acted as an oncogene in CRC and promoted the progression of CRC by directly sponging miR-216 b expression to activate the expression of YY1. The NEAT1/miR-216b/YY1 axis may be a novel therapeutic target for CRC.

Quantum Cutting in Ultraviolet B-Excited KY(CO3)2:Tb3+ Phosphors.

Highly efficient quantum cutting KY(CO3)2:Tb3+ phosphors excited by ultraviolet B (UVB) and ultraviolet C (UVC) were investigated. The structural and spectroscopic properties were characterized by XRD analysis and fluorescence spectrophotometry, respectively. The results showed that the monoclinic crystal structure of KY(CO3)2:Tb3+ remained in the Tb3+ doping range of 0~100%. In the excitation spectrum, two intense excitation peaks were observed in the ultraviolet range. Under the excitation of 283 nm, the maximum quantum efficiency of KY(CO3)2:0.7Tb3+ could reach 119%. However, the most efficient quantum cutting occurred at the 5K8 excited state in the cross-relaxation of 5K8 + 7F65D4 + 5D4. The Tb3+ content could be selected arbitrarily in the KY(CO3)2 host without any concentration quenching. Optimal quantum cutting concentrations of Tb3+ in KY(CO3)2 were 0.7 and 0.3 for the excitation of UVB and UVC, respectively. UVB-excited phosphors are more popular with high transparency in products such as glass or resin. A quick response code was fabricated by resin to show the hidden information clearly. Therefore, the highly efficient phosphor could be a candidate material for the application in information identification technology.

The combination therapy with esomeprazole and flupenthixol/melitracen in symptom improvement of erosive gastritis complicated with negative feelings compared with Esomeprazole alone.

The purpose of this study was to evaluate the co-prescription efficacy of esomeprazole and flupenthixol/melitracen relative to that of solitary esomeprazole on erosive gastritis complicated with negative feelings. 140 erosive gastritis patients complicated with negative feelings enrolled in the present study. Seventy cases in the control group took esomeprazole, and 70 cases in the observation group received esomeprazole plus flupenthixol/Melitracen, both for 4 weeks. We gastroscopically checked the clinical symptoms, mucosal erosion, PGE2 and MDA levels in gastric mucosa, anxiety, depression, and recurrence before and after treatment in the groups. After treatment, the observation group had lower scores of clinical symptoms, mucosal erosions, Hamilton Depression Rating Scale (HAMD), and Hamilton Depression Rating Scale (HAMA) than the control group (p<0.05); as well, the observation group showed higher PGE2 and lower MDA levels than the control group (p<0.05); during six months of follow-up (100% follow-up rate), 16 and 34 recurrent cases occurred, respectively, in the observation and control groups (p<0.05).  Co-prescription of esomeprazole and flupenthixol/melitracen improved the clinical symptoms and mucosal erosions, relieved negative feelings and reduced the recurrence rate. The efficacy of the co-prescription is higher than that of the solitary prescription.

Integrative Analysis of the IQ Motif-Containing GTPase-Activating Protein Family Indicates That the IQGAP3-PIK3C2B Axis Promotes Invasion in Colon Cancer.

BACKGROUND: Colon cancer (CRC) is a common type of tumour, and IQGAP family proteins play an important role in many tumours. However, their roles in CRC remain unclear. METHODS: First, we searched many public databases to comprehensively analyze expression of IQGAPs in CRC. Next, real-time PCR, immunohistochemical (IHC), transwell, siRNA transfection and Western blot assays were used to evaluate relationships among IQGAP3 expression, clinical pathological parameters and CRC prognosis, and the underlying molecular mechanism was investigated. RESULTS: IQGAP3 was elevated in CRC tissues, whereas there was no significant change in expression of IQGAP1 or IQGAP2. Additionally, IQGAP3 expression in CRC tissues was associated with tumour progression, invasion and poor prognosis. In mechanistic studies, we found that IQGAP3 was positively coexpressed with PIK3C2B. In an in vitro assay, the PIK3C2B expression level was increased after exogenous overexpression of IQGAP3, resulting in the promotion of cell invasion, which was blocked by pretransfecting cells with PIK3C2B siRNA. Furthermore, we found that high expression of IQGAP3 and PIK3C2B correlated with tumour stage and vessel invasion in human CRC, whereby patients with high expression of both in tumours had a worse prognosis compared with patients with single-positive or double-negative tumours. CONCLUSION: The results of our current study and corresponding previous studies provide evidence that IQGAP3 is elevated in CRC and promotes colon cancer growth and metastasis by regulating PIK3C2B activation.

Parenteral nutrition effects of Omega-3 fatty acids on C-reactive protein, high-density lipoprotein, lymphocyte characteristics and the treatment of critically ill patients.

To study the effects of omega-3 fatty acid parenteral nutrition on the nutrition, inflammatory responses, immunity and prognoses of critically ill cancer patients. A total of 80 critically ill cancer patients were randomly divided into an observation group and a control group, 40 cases in each group. Both groups of patients received equal-nitrogen and equal-calorie enteral and parenteral nutrition. The observation group, on this basis, was added with omega-3 fatty acid parenteral nutrition. The weekly nutritional status measures, inflammatory response measures, immune function measures and prognosis measures (ICU mortality, ICU stay, infectious complications) of the two groups were observed. The nutrition, inflammatory response and immune measures of the observation group were improved compared with the control group. The ICU stay in the observation group was shorter than the control group. Compared with the control group, the ICU mortality rate and infectious complication rate were lower in the observation group, but the differences were not significant (P mortality = 0.13, P infection rate = 0.165). Omega-3 fatty acid parenteral nutrition could improve patients' nutritional status and immune function, reduce the body's inflammatory responses and shorten the length of hospital stay, but couldn't significantly improve ICU mortality and reduce the incidence of infectious complications.

Infectious hematopoietic necrosis virus truncated G protein effect on survival, immune response, and disease resistance in rainbow trout.

The major antigenic protein of infectious hematopoietic necrosis virus (IHNV) is the surface glycoprotein G, which contains neutralizing epitopes that induce the production of immune neutralizing antibodies. In this study, the IHNV G gene sequence was truncated according to bioinformatics principles and then recombinantly expressed via an E. coli expression system. We then assessed the specific antibody immunoglobin M (IgM) levels of rainbow trout immunized with recombinant truncated G protein (emulsified with Freund's incomplete adjuvant), and showed that antibody IgM levels of immunized fish were significantly higher than in the control group (p < 0.01). The mRNA expression levels of interferon 1 (IFN1) and interleukin-8 (IL-8) were also up-regulated significantly (p < 0.01) in head kidneys and spleens of rainbow trout immunized with recombinant truncated G protein. Also, after challenge with wild-type IHNV HLJ-09 virus on Day 28, rainbow trout immunized with recombinant truncated G protein showed cumulative survival rates of 60%. These results indicate that the truncated G protein of IHNV expressed by the E. coli prokaryotic expression system can be used as a candidate immunogen for an IHNV subunit vaccine, which lays a theoretical foundation for the study of further potential IHNV subunit vaccines.

Oral immunization with recombinant Lactobacillus casei displayed AHA1-CK6 and VP2 induces protection against infectious pancreatic necrosis in rainbow trout (Oncorhynchus mykiss).

Infectious pancreatic necrosis virus (IPNV) primarily infects larvae and young salmonid with serious economic losses, which causes haemorrhage and putrescence of hepatopancreas. To develop a more effective oral vaccine against IPNV infection, the aeromonas hydrophila adhesion (AHA1) gene was used as a targeting molecule for intestinal epithelial cells. A genetically engineered Lactobacillus casei (pPG-612-AHA1-CK6-VP2/L. casei 393) was constructed to express the AHA1-CK6-VP2 fusion protein. The expression of interest protein was confirmed by western blotting and the immunogenicity of pPG-612-AHA1-CK6-VP2/L. casei 393 was evaluated. And the results showed that more pPG-612-AHA1-CK6-VP2/L. casei 393 were found in the intestinal mucosal surface of the immunized group. The Lactobacillus-derived AHA1-CK6-VP2 fusion protein could induce the production of serum IgM and skin mucus IgT specific for IPNV with neutralizing activity in rainbow trouts. The levels of IL-1ß, IL-8 and TNF-α isolated from the lymphocytes stimulated by AHA1-CK6-EGFP produced were significantly higher than EGFP group. For transcription levels of IL-1ß, IL-8, CK6, MHC-II, Mx and TNF-1α in the spleen, the result indicated that the adhesion and target chemokine recruit more immune cells to induce cellular immunity. The level of IPNV in the immunized group of pPG-612-AHA1-CK6-VP2/L. casei 393 was significantly lower than that in the control groups. These data indicated that the adhesion and target chemokine could enhance antigen delivery efficiency, which provides a valuable strategy for the development of IPNV recombination Lactobacillus casei oral vaccine in the future.

Circulating guanylyl cyclase C (GCC) mRNA is a reliable metastatic predictor and prognostic index of colorectal cancer.

BACKGROUND: Currently, few specific biomarkers or standard cutoff values are available for circulating tumor cells (CTCs) detection and survival prediction in patients with early stage colorectal cancer (CRC). Guanylyl cyclase C (GCC) presents as a specific expression in intestinal tumor cells and during their metastases, indicating its potential application as a metastatic predictor of CRC. METHODS: The circulating GCC mRNA of 160 colorectal cancer patients at stage I-III was detected via quantitative real-time (qRT)-PCR in our study, and the correlation of GCC mRNA level with tumor metastasis and long-term survival was explored. RESULTS: GCC mRNA was found to be positive in 43 out of 160 CRC patients and negative in ten healthy controls. It was found that GCC mRNA over the baseline (>100 copies/µL and 200 copies/µL) showed a significant correlation with disease-free survival (DFS) and overall survival (OS) in the stage II subgroup. It was further revealed that GCC mRNA over 300 copies/µL or higher than the median value of copy numbers was significantly correlated with reduced OS and DFS in CRC patients. A nomogram model based on variables including GCC mRNA copy number was established for predicting the OS of CRC patients (AUC =0.98). CONCLUSIONS: Circulating GCC mRNA over baseline is a reliable predictor for tumor metastasis and can be a prognostic index in CRC patients.

The L-domains in M and G proteins of infectious hematopoietic necrosis virus (IHNV) affect viral budding and pathogenicity.

RNA viruses including many retroviruses encode "late-domain" motifs that can interact with host proteins to mediate viral assembly and affect viral budding and pathogenicity. For IHNV, our previous studies demonstrated that the respective interactions of the L domains of IHNV with host proteins could mediate viral assembly and budding. To our knowledge, the role of L domains of the IHNV in the budding and pathogenicity has not investigated yet. In this study, we generated two recombinant IHNV strains rIHNV-M(PH>A4) and rIHNV-G(PS>A4) with mutations in the L domains (PPPH to AAAA or PSAP to AARA) of IHNV by reverse genetics and explored the effect of the mutations on budding and pathogenicity of the two recombinant viruses. The RT-qPCR results showed that the production levels of the extracellular particles of rIHNV-M(PH>A4) or rIHNV-G(PS>A4) declined significantly, compared with those of wild-type (wt) IHNV HLJ-09. Furthermore, the challenge test showed that the survival rates of juvenile rainbow trout challenged with rIHNV-M(PH>A4) or rIHNV-G(PS>A4) were 90% or 87%, respectively; however, the survivability was zero in groups challenged with wtIHNV HLJ-09 or rIHNV HLJ-09 (recombinant IHNV). Additionally, the RT-qPCR results showed that the recombinant viruses induced higher expression levels of IFN1, IL-1ß, and IL-8 compared with those induced by wtIHNV HLJ-09 as well as the ELISA results showed that fish vaccinated with recombinant viruses produced high levels of specific IgM antibodies, demonstrating that the two recombinant viruses may induce immune responses to resist infection by IHNV. Also, these results demonstrated for the first time that the L domains of the M and G proteins of IHNV could affect the budding and pathogenicity of IHNV, which may be beneficial in the prevention and control of IHNV infections in fish. Taken together, our study as the first research provides the foundation for effect of rhabdovirus L domains on viral budding and pathogenicity.

The role of infectious hematopoietic necrosis virus (IHNV) proteins in recruiting the ESCRT pathway through three ways in the host cells of fish during IHNV budding.

In cytokinetic abscission, phagophore formation, and enveloped virus budding are mediated by the endosomal sorting complex required for transport (ESCRT). Many retroviruses and RNA viruses encode "late-domain" motifs that can interact with the components of the ESCRT pathway to mediate the viral assembly and budding. However, the rhabdovirus in fish has been rarely investigated. In this study, inhibition the protein expression of the ESCRT components reduces the extracellular virion production, which preliminarily indicates that the ESCRT pathway is involved in IHNV release. The respective interactions of IHNV proteins including M, G, L protein with Nedd4, Tsg101, and Alix suggest the underlying molecular mechanism by which IHNV gets access to the ESCRT pathway. These results are the first observation that rhabdovirus in fish gains access to the ESCRT pathway through three ways of interactions between viral proteins and host proteins. In addition, the results show that IHNV is released from host cells through the ESCRT pathway. Taken together, our study provides a theoretical basis for studying the budding mechanism of IHNV.

Perineural and lymphovascular invasion predicts for poor prognosis in locally advanced rectal cancer after neoadjuvant chemoradiotherapy and surgery.

Background: Perineural invasion (PNI) and lymphovascular invasion (LVI) are associated with poor prognosis in colorectal cancer, but their clinical significance is still controversial for patients with locally advanced rectal cancer (LARC) who had received neoadjuvant chemoradiotherapy (nCRT) and surgical resection. The aim of this study was to confirm the correlation between PNI and/or LVI and clinical prognosis and to further confirm whether PNI and/or LVI can be used as potential prognostic indicators of adjuvant chemotherapy after nCRT and surgery in LARC. Methods: From February 2002 to December 2012, a total of 181 patients with LARC who had received nCRT and surgical resection were retrospectively reviewed. Overall survival (OS) and disease-free survival (DFS) were determined by the Kaplan-Meier method, log-rank test, and Cox proportional hazard regression model. Results: The median follow-up time was 48 months (range, 3 to 162 months). All the PNI-positive and/or LVI-positive patients showed adverse DFS and OS (P<0.001). In multivariate analysis, PNI and LVI were independent prognostic factors for DFS. PNI, rather than LVI, was also an independent prognostic factor for OS. In a subgroup analysis, PNI-positive, rather than LVI-positive, may benefit from adjuvant chemotherapy. Conclusion: For patients with LARC undergoing nCRT and surgery, PNI-positive and/or LVI positive were associated with poorer DFS and OS. And PNI-positive, rather than LVI-positive, may benefit from adjuvant chemotherapy.

End-to-end intestinal anastomosis using a novel biodegradable stent for laparoscopic colonic surgery: a multicenter study.

PURPOSE: Our animal studies have demonstrated the safety and feasibility of end-to-end intestinal anastomosis using a stent for laparoscopic colonic surgery. Therefore, we designed a non-inferiority trial to investigate the outcomes of stent anastomosis (SA) vs. those of conventional hand-sewn anastomosis (CA). METHODS: A multicenter randomized controlled trial was conducted between December, 2016 and April, 2018. The primary outcome was the healing condition of the anastomoses, evaluated by endoscopy 6 months postoperatively. The secondary outcomes were the anastomotic completion time, anastomotic leak, intestinal obstruction, peritoneal effusion, and bleeding. Quality of life (QOL) was evaluated by questionnaires. RESULTS: The subjects of this study were 60 patients, randomly divided into a SA group (n = 30) and a CA group (n = 30). There were no differences in anastomotic healing conditions (P = 1.00). The stent procedure was associated with a significantly shorter anastomosis time than the hand-sewn anastomosis (13.517 ± 4.281 vs. 20.333 ± 2.998 min, respectively; P < 0.001). There were no significant differences in anastomotic leakage, intestinal obstruction, peritoneal effusion, or bleeding between the groups. Questionnaires revealed almost no discrepancy between baseline QOL scores and those assessed 2, 4, 8, 12, and 24 weeks postoperatively in either group. CONCLUSIONS: Intestinal anastomosis with a stent is a non-inferior strategy for laparoscopic colonic surgery, which requires less time for the anastomosis.

Expression and clinical significance of serum NT5E protein in patients with colorectal cancer.

OBJECTIVE: This study aimed to investigate the expression level and clinical significance of serum NT5E protein (ecto-5'-nucleotidase) in patients with colorectal cancer. METHODS: The expression level of serum NT5E protein in 232 patients with colorectal cancer and 158 normal controls was detected using enzyme-linked immunosorbent assay. Moreover, the relationship between the expression level of serum NT5E and the clinicopathological features of colorectal cancer was analyzed. RESULTS: The expression level of serum NT5E in patients with colorectal cancer was significantly higher compared with that in normal controls (P< 0.05). The expression level of serum NT5E in patients with colorectal cancer closely correlated with the family history of tumors (P= 0.001), expression level of CA19-9 (P= 0.031), lymph node metastasis (P= 0.001), distant metastasis (P= 0.010), nerve invasion (P= 0.049), degree of differentiation (P= 0.013), and TNM staging (P= 0.001), but not with gender, age, smoking and drinking histories, expression level of carcinoembryonic antigen (CEA), tumor locations, vascular tumor thrombus, cancer nodules, and pathological type (P> 0.05). Moreover, the overall survival rate of patients with colorectal cancer was significantly lower in the NT5E high-expression group, with statistical significance (χ2= 11.184, P= 0.001). CONCLUSIONS: The expression level of serum NT5E increased in patients with colorectal cancer, and closely correlated with the malignant evolution and clinical prognosis of colorectal cancer. NT5E might serve as a serological indicator for molecular diagnosis and prognosis of colorectal cancer clinically.

Immunity induced by recombinant attenuated IHNV (infectious hematopoietic necrosis virus)-GN438A expresses VP2 gene-encoded IPNV (infectious pancreatic necrosis virus) against both pathogens in rainbow trout.

Infectious hematopoietic necrosis virus (IHNV) and infectious pancreatic necrosis virus (IPNV) are important pathogens in rainbow trout farming worldwide. Their co-infection is also common, which causes great economic loss in juvenile salmon species. Development of a universal virus vaccine providing broadly cross-protective immunity will be of great importance. In this study, we generated two recombinant (r) virus (rIHNV-N438A-ΔNV-EGFP and rIHNV-N438A-ΔNV-VP2) replacing the NV gene of the backbone of rIHNV at the single point mutation at residue 438 with an efficient green fluorescent protein (EGFP) reporter gene and antigenic VP2 gene of IPNV. Meanwhile, we tested their efficacy against the wild-type (wt) IHNV HLJ-09 virus and IPNV serotype Sp virus challenge. The relative per cent survival rates of two recombinant viruses against (wt) IHNV HLJ-09 virus challenge were 84.6% and 81.5%, respectively. Simultaneously, the relative per cent survival rate of rIHNV-N438A-ΔNV-VP2 against IPNV serotype Sp virus challenge was 88.9%. It showed the two recombinant viruses had high protection rates and induced a high level of antibodies against IHNV or IPNV. Taken together, these results suggest the VP2 gene of IPNV can act as candidate gene for vaccine and attenuated multivalent live vaccines and molecular marker vaccines have potential application for viral vaccine.