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The effect of substrate concentration, pH and cultivation time on the production of endoxylanase from Aspergillus awamori ZH-26 were optimized by statistical analysis using response surface methodology (RSM). Endoxylanase production was optimized by central composite rotary design. Statistical analysis of the results showed that the linear and quadratic terms of these three variables had significant effects. But no interactions between the three variables were found to contribute to the response at a significant level. The optimal conditions were: wheat bran 49.3 g/L, pH=4.14, and cultivation time 103.7 h. Under these conditions, the model predicted an endoxylanase activity of 28.25 U/mL. Verification of the optimization showed that endoxylanase production of 29.65 U/mL was observed under optimal conditions.

Abstract Background Accurate prediction of pathological complete response (pCR) and disease-free survival (DFS) in locally advanced rectal cancer (LARC) patients undergoing neoadjuvant chemoradiotherapy (NCRT) is essential for formulating effective treatment plans. This study aimed to construct and validate the machine learning (ML) models to predict pCR and DFS using pathomics. Method A retrospective analysis was conducted on 294 patients who received NCRT from two independent institutions. Pathomics from pre-NCRT H&E stains were extracted, and five ML models were developed and validated across two centers using ROC, Kaplan-Meier, time-dependent ROC, and nomogram analyses. Result Among the five ML models, the Xgboost (XGB) model demonstrated superior performance in predicting pCR, achieving an AUC of 1.000 (p

Abstract Background The prognostic value of Albumin and D-dimer has been established for multiple tumor types, indicating their potential for predicting tumor development. Nevertheless, the predictive capability of the DDI-to-albumin ratio (DAR) in locally advanced rectal cancer (LARC) remains uncertain. Purpose The objective of this study was to investigate the prognostic significance of the DAR in LARC. Methods A total of 513 patients who underwent neoadjuvant chemoradiotherapy (nCRT) prior to total mesorectal excision (TME) between March 2013 to October 2019 were included in this study. Patients were divided into high-level DAR (> 0.016) or low-level DAR (≤ 0.016) groups based on ROC curve analysis optimum cut-off value. The prognostic value of the DAR in LARC was analyzed. Results The study enrolled 513 patients. Patients were stratified into high-level DAR (> 0.016) and low-level DAR (≤ 0.016) cohorts according to the optimal cut-off value determined by ROC curve analysis. The 5-year overall survival (OS) rates for patients in the low DAR group (≤ 0.016) and the high DAR group (> 0.016) were 89.4% and 80.9%, respectively (p = 0.013). The 5-year disease-free survival (DFS) rates were 85.7% and 77.4% (p = 0.027). Multivariate analyses demonstrated that DAR were independent prognostic factors for OS (p = 0.02) and DFS (0.025). Predictive nomograms that included the DAR score group (C-index: OS-0.743, DFS-0.705) were superior to those without DAR scores (C-index: OS-0.721, DFS-0.697). Conclusion The DAR demonstrates high usability and prognostic value in predicting OS and DFS outcomes among patients diagnosed with LARC who undergo nCRT.

BackgroundThis study aimed to investigate the prognostic significance of the log odds of negative lymph nodes/T stage ratio (LONT) and develop an efficient prognostic staging system using LONT in patients with colon mucinous adenocarcinoma (MAC).MethodsThis study included 5,236 patients diagnosed with colon MAC obtained from the Surveillance, Epidemiology, and End Results database. The Kaplan–Meier method, subgroup analysis, receiver operating characteristic (ROC) curve, and Cox proportional hazard regression model were used to determine the clinical outcomes. Recursive partitioning analysis (RPA) was used to develop a novel prognostic system.ResultsThe 1-, 3-, and 5-year ROC curves, used to predict cancer-specific survival (CSS) and overall survival (OS), demonstrated that the areas under the ROC curve for LONT were superior to those of pT, pN, and pTNM stages. Additionally, a lower LONT was correlated with worse clinical outcomes. The LONT classification efficiently differentiated the prognosis of patients in terms of OS and CSS. Multivariate Cox analyses revealed that LONT was an independent prognostic factor for both CSS and OS. Based on the pT stage and LONT, a novel prognostic staging system was developed using RPA, demonstrating a good prognostic predictive performance.ConclusionA lower LONT was associated with worse survival in patients with colon MAC. The pT stage and LONT-based prognostic staging system facilitated risk stratification in these patients.

ABSTRACT Background The hiatal ligament, as the anatomical landmark for the completion of total mesorectal excision (TME) for ultra‐low rectal cancer, represents a continuation of the longitudinal muscle of the rectum. It receives vascular supply from the median sacral artery and contains lymphatic vessels. In cases where ultra‐low rectal cancer is located in the posterior rectal wall, the hiatal ligament may theoretically serve as an anatomical region susceptible to direct tumor cell spread or distant metastasis. Objective To evaluate the effect of circumferential tumor location (CTL) on postoperative survival of low rectal cancer and to determine the effect of total hiatal ligament excision (THLE) on the prognosis of patients with posterior rectal cancer. Methods Patients with ultra‐low rectal cancer who underwent laparoscopic surgery between March 2014 and October 2021 were enrolled in this study. Propensity score matching (PSM) analysis was used to compare the clinicopathological characteristics and prognosis of patients in the posterior group and the non‐posterior group. Prognostic factors were identified using COX regression. PSM analysis was also used in the posterior tumor subgroup to compare the clinicopathological characteristics and prognosis of patients in the hiatal ligament traditional transection (HLTT) and THLE groups. Results After PSM, OS, and DFS were comparable between the posterior and non‐posterior groups. Similarly, no difference was noted in the local recurrence rate between the two groups (p = 0.23). The prognosis of ultra‐low rectal cancer was not affected by CTL. However, the local recurrence rate was significantly lower in the THLE group compared with the HLTT group (p = 0.023). Multivariate analysis of the posterior group identified CRM, TNM stage III, and HLTT as independent risk factors for local recurrence‐free survival. Conclusions CTL is not a prognostic risk factor for low rectal cancer. In posterior wall tumors, THLE significantly reduces the local recurrence rate for low rectal cancer.

Colorectal cancer (CRC) is a common and malignant tumor, ranking as the third most common cancer in men and the second most common cancer in women. Pyroptosis, a recently described programmed cell death mechanism mediated by the GSDM family, has emerged as an immunogenic mechanism for chemotherapy drugs in tumor treatment. In this study, we discovered that Miltirone has the ability to reduce the viability of CRC cells (SW620 and HCT116) and cause the proteolytic cleavage of gasdermin E (GSDME) in CRC cells. It was also observed that inhibiting GSDME prevented pyroptotic cell death induced by Miltirone in SW620 and HCT116 cells. Furthermore, the main active component of Miltirone was found to effectively bind with caspase 3. SiRNA-mediated caspase 3 silencing and specific caspase 3 inhibitor Z-DEVD-FMK were shown to weaken Miltirone-induced GSDME-dependent cell death. The findings of the study suggest that Miltirone has the potential to inhibit the growth of CRC tumors in vivo by inducing pyroptotic cell death. This indicates that Miltirone could be a viable therapeutic agent for the treatment of CRC through GSDME-dependent pyroptosis. These results offer a promising new option for the clinical treatment of CRC.

Abstract Microvascular invasion (MVI) is a critical risk factor for postoperative recurrence of hepatocellular carcinoma (HCC). This study aimed to firstly develop and validate nomograms based on MVI grade for predicting recurrence, especially early recurrence, and overall survival in patients with early-stage HCC after curative resection. We retrospectively reviewed the data of patients with early-stage HCC who underwent curative hepatectomy in the First Affiliated Hospital of Fujian Medical University (FHFU) and Mengchao Hepatobiliary Hospital of Fujian Medical University (MHH). Kaplan–Meier curves and Cox proportional hazards regression models were used to analyse disease-free survival (DFS) and overall survival (OS). Nomogram models were constructed on the datasets from the 70% samples of and FHFU, which were validated using bootstrap resampling with 30% samples as internal validation and data of patients from MHH as external validation. A total of 703 patients with early-stage HCC were included to create a nomogram for predicting recurrence or metastasis (DFS nomogram) and a nomogram for predicting survival (OS nomogram). The concordance indexes and calibration curves in the training and validation cohorts showed optimal agreement between the predicted and observed DFS and OS rates. The predictive accuracy was significantly better than that of the classic HCC staging systems.

Abstract Purpose To identify genes associated with treatment response and prognosis for locally advanced rectal cancer (LARC) patients receiving neoadjuvant chemoradiotherapy (NCRT). Methods In our cohort, gene expression profiles of 64 tumor biopsy samples before NCRT were examined and generated. Weighted gene co-expression network analysis was performed to identify gene modules. External validation datasets included GSE3493, GSE119409, and GSE133057. The expression of candidate genes was evaluated using immunohistochemistry (IHC). TIMER was used to assess immune infiltration. Results We identified and validated the capability to predict the treatment response of CCT5 and ELF1 using our data and external validation datasets. The trends of survival differences of candidate genes in the GSE133057 dataset were similar to our cohort. High levels of CCT5 and ELF1 expression were associated with NCRT resistance and poor prognosis. Furthermore, the expression of CCT5 and ELF1 were also assessed in 117 LARC patients’ samples by the IHC method. Based on IHC results and Cox analysis, the risk score model with CCT5 and ELF1 was constructed and performed well. The risk score was an independent prognostic factor for progression-free survival and overall survival in LARC patients and was then used to build nomogram models. The underlying mechanisms of CCT5 and ELF1 were explored using gene set enrichment analysis. The underlying pathway including apoptosis, cell cycle, and other processes. CCT5 and ELF1 expressions were significantly correlated with immune cell infiltration. Conclusion CCT5 and ELF1 were determined as biomarkers for treatment response and prognosis in LARC patients. The risk score model and nomograms helped predict treatment response and survival outcomes for LARC patients undergoing NCRT.

Background: This study aimed to construct a nomogram based on CAF features to predict the cancer-specific survival (CSS) rates of locally advanced rectal cancer (LARC) patients. Methods: The EPIC algorithm was employed to calculate the proportion of CAFs. based on the differentially expressed genes between the high and low CAF proportion subgroups, prognostic genes were identified via LASSO and Cox regression analyses. They were then used to construct a prognostic risk signature. Moreover, the GSE39582 and GGSE38832 datasets were used for external validation. Lastly, the level of immune infiltration was evaluated using ssGSEA, ESTIMATE, CIBERSORTx, and TIMER. Results: A higher level of CAF infiltration was associated with a worse prognosis. Additionally, the number of metastasized lymph nodes and distant metastases, as well as the level of immune infiltration were higher in the high CAF proportion subgroup. Five prognostic genes (SMOC2, TUBAL3, C2CD4A, MAP1B, BMP8A) were identified and subsequently incorporated into the prognostic risk signature to predict the 1-, 3-, and 5-year CSS rates in the training and validation sets. Differences in survival rates were also determined in the external validation cohort. Furthermore, independent prognostic factors, including TNM stage and risk score, were combined to established a nomogram. Notably, our results revealed that the proportions of macrophages and neutrophils and the levels of cytokines secreted by M2 macrophages were higher in the high-risk subgroup. Finally, the prognostic genes were significantly associated with the level of immune cell infiltration. Conclusion: Herein, a nomogram based on CAF features was developed to predict the CSS rate of LARC patients. The risk model was capable of reflecting differences in the level of immune cell infiltration.

Abstract Background Gastrointestinal stromal tumor (GIST) is currently regarded as a potentially malignant tumor, and early diagnosis is the best way to improve its prognosis. Therefore, it will be meaningful to develop a new method for auxiliary diagnosis of this disease. Methods Here we try out a new means to detect GIST by combining two-photon imaging with automatic image processing strategy. Results Experimental results show that two-photon microscopy has the ability to label-freely identify the structural characteristics of GIST such as tumor cells, desmoplastic reaction, which are entirely different from those from gastric adenocarcinoma. Moreover, an image processing approach is used to extract eight collagen morphological features from tumor microenvironment and normal muscularis, and statistical analysis demonstrates that there are significant differences in three features—fiber area, density and cross-link density. The three morphological characteristics may be considered as optical imaging biomarkers to differentiate between normal and abnormal tissues. Conclusion With continued improvement and refinement of this technology, we believe that two-photon microscopy will be an efficient surveillance tool for GIST and lead to better management of this disease.

The prognosis of patients with locally advanced rectal cancer (LARC) has improved with the adoption of a multidisciplinary treatment approach combining neoadjuvant chemoradiotherapy (nCRT) and total mesorectal excision (TME). Developing real-time, sensitive biomarkers to monitor systemic changes during nCRT is of paramount importance. Although the association between albumin-derived neutrophil-to-lymphocyte ratio (Alb-dNLR) and prognosis in various cancers is established, its prognostic value in LARC patients undergoing nCRT is not well-studied. This study enrolled a cohort of 618 LARC patients, stratifying them into two groups according to their change in Alb-dNLR (∆Alb-dNLR) values, using an optimal cut-off point: a low ∆Alb-dNLR group (≤ 0.90) and a high ∆Alb-dNLR group (> 0.90). The prognostic significance of ∆Alb-dNLR was evaluated using a Cox proportional hazards model. The 5-year overall survival (OS) rates were 75.2% in the low ∆Alb-dNLR group (≤ 0.90) and 85.9% in the high ∆Alb-dNLR group (>0.90) (P < 0.001). The 5-year disease-free survival (DFS) rates were 71.2% and 80.6%, respectively (P = 0.016). Multivariate analyses demonstrated that both ∆Alb-dNLR and pre-Alb-dNLR were independent prognostic factors for OS (P ≤ 0.001), while ∆Alb-dNLR was demonstrated as an independent prognostic factor for DFS (P = 0.016). A predictive nomogram, incorporating the ∆Alb-dNLR subgroup, demonstrated enhanced performance (concordance index [C-index] of 0.720 for OS and 0.690 for DFS) compared to the pre-treatment Alb-dNLR subgroup (C-index of 0.700 for OS and of 0.680 for DFS). Therefore, ∆Alb-dNLR shows significant potential as a usable and prognostic biomarker for predicting OS and DFS in LARC patients undergoing nCRT.

Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal tumors arising in the digest tract. It brings a challenge to diagnosis because it is asymptomatic clinically. It is well known that tumor development is often accompanied by the changes in the morphology of collagen fibers. Nowadays, an emerging optical imaging technique, second-harmonic generation (SHG), can directly identify collagen fibers without staining due to its noncentrosymmetric properties. Therefore, in this study, we attempt to assess the feasibility of SHG imaging for detecting GISTs by monitoring the morphological changes of collagen fibers in tumor microenvironment. We found that collagen alterations occurred obviously in the GISTs by comparing with normal tissues, and furthermore, two morphological features from SHG images were extracted to quantitatively assess the morphological difference of collagen fibers between normal muscular layer and GISTs by means of automated image analysis. Quantitative analyses show a significant difference in the two collagen features. This study demonstrates the potential of SHG imaging as an adjunctive diagnostic tool for label-free identification of GISTs.

BackgroundTo explore the safety, efficacy, and survival benefits of laparoscopic digestive tract nutrition reconstruction (LDTNR) combined with conversion therapy in patients with unresectable gastric cancer with obstruction.MethodsThe clinical data of patients with unresectable gastric cancer with obstruction who was treated in Fujian Provincial Hospital from January 2016 to December 2019, were analyzed. LDTNR was performed according to the type and degree of obstruction. All patients received the epirubicin + oxaliplatin + capecitabine regimen as conversion therapy.ResultsThirty-seven patients with unresectable obstructive gastric cancer underwent LDTNR, while thirty-three patients received chemotherapy only. In LDTNR group patients, the proportion of nutritional risks gradually decreased, the rate of severe malnutrition decreased, the proportion of neutrophil-lymphocyte ratio (NLR)

Abstract Background To develop and evaluate the prognostic value of a comprehensive inflammatory biomarker for postoperative colorectal cancer (CRC) patients. Methods A total of 646 CRC patients were recruited between August 2017 and December 2019 from Fujian Medical University Union Hospital, with follow-up data up to 2021. The least absolute shrinkage and selection operator method (LASSO) was used to select inflammation indicators in order to construct a comprehensive biomarker (named NSAP). The Cox regression model was utilized to analyze the association between the NSAP and the disease-free survival (DFS) of CRC. Predictive performance and clinical utility of prognostic models were evaluated by area under the curve (AUC) and decision curve analyses (DCAs). Results During a median follow-up of 23 months, 95 clinical outcomes were observed, with a 1-year survival rate is 89.47%. A comprehensive inflammatory biomarker (NSAP) was established based on four blood indicators (including neutrophil-to-lymphocyte ratio (NLR), neutrophil×monocyte-to-lymphocyte ratio (SIRI), albumin-to-globulin ratio (AGR), and platelet-to-lymphocytes ratio (PLR)). Patients with a lower NSAP had significantly associated with better DFS of CRC (HR=0.53, 95%CI 0.32–0.89). Moreover, compared to a previously established model, the traditional TNM staging system or/and tumor markers, the nomogram based on NSAP displayed more excellent predictive ability (0.752 vs 0.597, 0.711 and 0.735, P < 0.05). DCAs also demonstrated that the established nomogram had better utility for decision making. Conclusions Our study suggests that NSAP may be a useful comprehensive prognostic biomarker for predicting the DFS of CRC patients. The nomogram based on NSAP can be considered a valuable tool to estimate the prognosis of patients with CRC.

Abstract Background The operative results of different approaches for the laparoscopic intersphincteric resection (LAISR) of low rectal cancer vary, and the patient characteristics associated with the best outcomes for each procedure have not been reported. We compared the efficacy of different approaches for LAISR of low rectal cancer and discussed the surgical indications for each approach. Methods We retrospectively reviewed data from 235 patients with low rectal cancer treated via LAISR from October 2010 to September 2016. Patients underwent either the transabdominal approach for ISR (TAISR, n = 142), the transabdominal perineal approach for ISR (TPAISR, n = 57), or the transanal pull-through approach for ISR (PAISR, n = 36). Results The PAISR and TAISR groups exhibited shorter operation times and less intraoperative blood loss than the TPAISR group. The anastomotic distance was shorter in the PAISR and TPAISR groups than in the TAISR group. No differences in the ability to perform radical resection, overall complications, postoperative recovery, Wexner score recorded 12 months after ostomy closure, 3-year disease-free survival, local recurrence-free survival, distant metastasis-free survival, or overall survival (OS) were observed among the three groups. Conclusions TAISR, TPAISR, and PAISR have unique advantages and do not differ in terms of operation safety, patient outcomes, or anal function. TPAISR requires a longer time to complete and is associated with more bleeding and a slower recovery of anal function. PAISR should be considered when TAISR cannot ensure a negative distal margin and the tumor and BMI are relatively small; otherwise, TPAISR is required.

Abstract Purpose To evaluate the impact of the log odds of positive lymph nodes (LODDS) on cancer‐specific survival (CSS) in colon mucinous adenocarcinoma (MAC) patients, compared with pN stage and the lymph nodes ratio (LNR). Methods A total of 10,182 colon MAC patients from the Surveillance, Epidemiology, and End Results database were divided into the training group. The external validation group included 153 patients from Fujian Medical University Union Hospital. The Cox regression method was used to identify prognostic risk factors. Nomograms were evaluated by Harrell's concordance index (C‐index) and calibration curves. Recursive partitioning analysis (RPA) was used to develop a novel staging system. Results Time‐dependent receiver operating characteristic curves (ROC) to predict CSS showed the areas under the ROC curve of LODDS were always higher than pN stage and LNR. LNR and LODDS classifications can well distinguish the prognosis of patients with the same pN stage. Cox analyses indicated that age, tumor size, pT stage, pN stage, LNR, and LODDS were independent predictors of CSS (p

Abstract Background Immunotherapies targeting ligand-receptor interactions (LRIs) are advancing rapidly in the treatment of colorectal cancer (CRC), and LRIs also affect many aspects of CRC development. However, the pattern of LRIs in CRC and their effect on tumor microenvironment and clinical value are still unclear. Methods We delineated the pattern of LRIs in 55,539 single-cell RNA sequencing (scRNA-seq) samples from 29 patients with CRC and three bulk RNA-seq datasets containing data from 1411 CRC patients. Then the influence of tumor microenvironment, immunotherapy and prognosis of CRC patients were comprehensively investigated. Results We calculated the strength of 1893 ligand-receptor pairs between 25 cell types to reconstruct the spatial structure of CRC. We identified tumor subtypes based on LRIs, revealed the relationship between the subtypes and immunotherapy efficacy and explored the ligand-receptor pairs and specific targets affecting the abundance of tumor-infiltrating lymphocytes. Finally, a prognostic model based on ligand-receptor pairs was constructed and validated. Conclusion Overall, through the comprehensive and in-depth investigation of the existing ligand-receptor pairs, this study provides new ideas for CRC subtype classification, a new risk screening tool for CRC patients, and potential ligand-receptor pair targets and pathways for CRC therapy.

BackgroundAnastomotic leakage (AL) is a major cause of postoperative morbidity and mortality in the treatment of colorectal cancer. The aim of this study was to investigate whether the resection of “dog-ears” in laparoscopic anterior resection of rectal cancer (called modified double-stapling technique, MDST) could reduce the rate of AL in patients with middle and high rectal cancer, as compared with the conventional double-stapling technique (DST).MethodsThe clinical data of 232 patients with middle and high rectal cancer were prospectively collected from September 2015 to October 2018. They were randomly divided into the MDST group (n = 116) and the DST group (n = 116) and the data were prospectively analyzed. Morbidity and AL rate were compared between the two groups.ResultsPatient demographics, tumor size, and time of first flatus were similar between the two groups. No difference was observed in the operation time between the two groups. The AL rate was significantly lower in the MDST group than in the DST group (3.4 vs. 11.2%, p = 0.032). The age and anastomotic technique were the factors associated with AL according to the multivariate analysis. The location of the AL in the DST group was further investigated, revealing that AL was in the same place as the “dog-ears” (11/13, 84.6%).ConclusionsOur prospective comparative study demonstrated that MDST have a better short-term outcome in reducing AL compared with DST. Therefore, this technique could be an alternative approach to maximize the benefit of laparoscopic anterior resection on patients with middle and high rectal cancer. The “dog-ears” create stapled corners potentially ischemic, since they represent the area with high incidence of AL.(NCT:02770911)

This paper proposes a dynamic synthetic inertia control method, considering the fatigue loads of the wind turbine. The control objectives include reducing the rate of change of frequency and frequency nadir of the power system and the fatigue load of the shaft and tower of the wind turbine. A frequency regulation model of the power system containing the primary operating dynamics of the wind turbine is established. The dynamic synthetic inertia control method is proposed according to the relationship between fatigue load, wind velocity, and frequency. Case studies are conducted with a wind turbine fatigue load under a synthetic inertia control with different weights for different wind velocities and system loads. Therefore, the dynamic weights are obtained. Comparing the rate of change of frequency and frequency nadir and equivalent damage load, the efficacy of the proposed method is verified.

Abstract Background D3 or complete mesocolic excision (CME) surgery has become a common surgical procedure for the treatment of colon cancer metastasis. Clinical misuse and overuse of lymph node dissection bring unnecessary burdens to patients. A detailed guidance for lymph node dissection in patients with T3 and T4 stage right colon cancer at different locations is urgently needed. Methods A retrospective study was performed. Patients received D3 or CME surgery were divided into ileocecal group, ascending colon group, and hepatic flexure group according to the 9th edition of the Japanese Society for Cancer of the Colon and Rectum guidelines. The distributions of lymph node metastases were analyzed according to tumor infiltration depth (T stage) and tumor location. Results The incidence of metastases in the paracolic area (or station), intermediate area, and main (or central) area was 38.4% (139/362), 12.7% (46/362), and 9.7% (35/362), respectively. The proportion of patients having No.206 and terminal ileum lymph nodes metastases was 7.7% (14/181) and 3.7% (9/244), respectively. No.206 lymph node metastasis is related to tumor location (χ 2 = 7.955, p = 0.019) and degree of differentiation (χ 2 = 18.99, p = 0.000), and terminal ileum lymph node metastasis is related to tumor location (χ 2 = 6.273, p = 0.043). Patients with T3/T4 hepatic flexure cancer received radical right hemicolectomy in addition to No.206 lymph node dissection. Conclusion Radical right hemicolectomy and No.206 group lymph node dissection are necessary for T3 and T4 stage colon cancer therapy.