Engineered microparticles modulate arginine metabolism to repolarize tumor-associated macrophages for refractory colorectal cancer treatment.

BACKGROUND: Arginase is abundantly expressed in colorectal cancer and disrupts arginine metabolism, promoting the formation of an immunosuppressive tumor microenvironment. This significant factor contributes to the insensitivity of colorectal cancer to immunotherapy. Tumor-associated macrophages (TAMs) are major immune cells in this environment, and aberrant arginine metabolism in tumor tissues induces TAM polarization toward M2-like macrophages. The natural compound piceatannol 3'-O-glucoside inhibits arginase activity and activates nitric oxide synthase, thereby reducing M2-like macrophages while promoting M1-like macrophage polarization. METHODS: The natural compounds piceatannol 3'-O-glucoside and indocyanine green were encapsulated within microparticles derived from tumor cells, termed PG/ICG@MPs. The enhanced cancer therapeutic effect of PG/ICG@MP was assessed both in vitro and in vivo. RESULTS: PG/ICG@MP precisely targets the tumor site, with piceatannol 3'-O-glucoside concurrently inhibiting arginase activity and activating nitric oxide synthase. This process promotes increased endogenous nitric oxide production through arginine metabolism. The combined actions of nitric oxide and piceatannol 3'-O-glucoside facilitate the repolarization of tumor-associated macrophages toward the M1 phenotype. Furthermore, the increase in endogenous nitric oxide levels, in conjunction with the photodynamic effect induced by indocyanine green, increases the quantity of reactive oxygen species. This dual effect not only enhances tumor immunity but also exerts remarkable inhibitory effects on tumors. CONCLUSION: Our research results demonstrate the excellent tumor-targeting effect of PG/ICG@MPs. By modulating arginine metabolism to improve the tumor immune microenvironment, we provide an effective approach with clinical translational significance for combined cancer therapy.

Mitochondrial DNA Copy Number as a Biomarker for Guiding Adjuvant Chemotherapy in Stages II and III Colorectal Cancer Patients with Mismatch Repair Deficiency: Seeking Benefits and Avoiding Harms.

BACKGROUND: Colorectal cancer (CRC) patients with mismatch repair-deficient/microsatellite instability-high (dMMR/MSI-H) status are conventionally perceived as unresponsive to adjuvant chemotherapy (ACT). The mitochondrial transcription factor A (TFAM) is required for mitochondrial DNA copy number (mtDNA-CN) expression. In light of previous findings indicating that the frequent truncating-mutation of TFAM affects the chemotherapy resistance of MSI CRC cells, this study aimed to explore the potential of mtDNA-CN as a predictive biomarker for ACT efficacy in dMMR CRC patients. METHODS: Levels of MtDNA-CN were assessed using quantitative real-time polymerase chain reaction (qRT-PCR) in a cohort of 308 CRC patients with dMMR comprising 180 stage II and 128 stage III patients. Clinicopathologic and therapeutic data were collected. The study examined the association between mtDNA-CN levels and prognosis, as well as the impact of ACT benefit on dMMR CRC patients. Subgroup analyses were performed based mainly on tumor stage and mtDNA-CN level. Kaplan-Meier and Cox regression models were used to evaluate the effect of mtDNA-CN on disease-free survival (DFS) and overall survival (OS). RESULTS: A substantial reduction in mtDNA-CN expression was observed in tumor tissue, and higher mtDNA-CN levels were correlated with improved DFS (73.4% vs 85.7%; P = 0.0055) and OS (82.5% vs 90.3%; P = 0.0366) in dMMR CRC patients. Cox regression analysis identified high mtDNA-CN as an independent protective factor for DFS (hazard ratio [HR] 0.547; 95% confidence interval [CI] 0.321-0.934; P = 0.0270) and OS (HR 0.520; 95% CI 0.272-0.998; P = 0.0492). Notably, for dMMR CRC patients with elevated mtDNA-CN, ACT significantly improved DFS (74.6% vs 93.4%; P = 0.0015) and OS (81.0% vs 96.7%; P = 0.0017), including those with stage II or III disease. CONCLUSIONS: The mtDNA-CN levels exhibited a correlation with the prognosis of stage II or III CRC patients with dMMR. Elevated mtDNA-CN emerges as a robust prognostic factor, indicating improved ACT outcomes for stages II and III CRC patients with dMMR. These findings suggest the potential utility of mtDNA-CN as a biomarker for guiding personalized ACT treatment in this population.

Perineural invasion affects prognosis of patients undergoing colorectal cancer surgery: a propensity score matching analysis.

BACKGROUND: Tumour perineural invasion (PNI) is a predictor of poor prognosis, but its effect on the prognosis of patients with colorectal cancer (CRC) has not yet been elucidated. METHODS: This retrospective study used propensity score matching (PSM). The clinical case data of 1470 patients with surgically treated stage I-IV CRC at Wuhan Union Hospital were collected. PSM was used to analyse and compare the clinicopathological characteristics, perioperative outcomes, and long-term prognostic outcomes of the PNI(+) and PNI(-) groups. The factors influencing prognosis were screened using Cox univariate and multivariate analyses. RESULTS: After PSM, 548 patients were included in the study (n = 274 in each group). Multifactorial analysis showed that neurological invasion was an independent prognostic factor affecting patients' OS and DFS (hazard ratio [HR], 1.881; 95% confidence interval [CI], 1.35-2.62; P = 0.0001; HR, 1.809; 95% CI, 1.353-2.419; P < 0.001). Compared to PNI(+) patients without chemotherapy, those who received chemotherapy had a significant improvement in OS (P < 0.01). The AUROC curve of OS in the PNI(+) subgroup (0.802) was higher than that after PSM (0.743), while that of DFS in the PNI(+) subgroup (0.746) was higher than that after PSM (0.706). The independent predictors of PNI(+) could better predict the prognosis and survival of patients with PNI(+). CONCLUSIONS: PNI significantly affects the long-term survival and prognosis of patients with CRC undergoing surgery and is an independent risk factor for OS and DFS in patients with CRC undergoing surgery. Postoperative chemotherapy significantly improved the OS of PNI(+) patients.

Modified Naples prognostic score for evaluating the prognosis of patients with obstructive colorectal cancer.

BACKGROUND: Inflammatory, immune, and nutritional status are key factors in obstructive colorectal cancer (OCRC). This study aims to investigate the value of modified Naples prognostic score (M-NPS) in evaluating OCRC prognosis. METHODS: A total of 196 OCRC patients were retrospectively analyzed to construct M-NPS based on serum albumin (ALB), total cholesterol (CHOL), neutrophil:lymphocyte ratio (NLR), and lymphocyte:monocyte ratio (LMR), and then they were divided into three groups. The Kaplan-Meier (KM) method and Cox proportional hazard regression analysis were performed for overall survival (OS) and disease-free survival (DFS) of OCRC patients. RESULTS: Patients with high M-NPS had worse OS and DFS (P = 0.0001, P = 0.0011). Multivariate COX analysis showed that M-NPS was an independent prognostic factor for OCRC patients. Patients in the M-NPS 2 group had significantly worse OS (hazard ratio [HR] = 4.930 (95% confidence interval [95% CI], 2.217-10.964), P < 0.001) and DFS (HR = 3.508 (95% CI, 1.691-7.277), P < 0.001) than those in the 0 group. CONCLUSION: M-NPS was an independent prognostic factor for OCRC patients; it might provide a potential reference for immunonutritional intervention in patients with obstruction.

Endoscopic fully covered self-expandable metal stent and vacuum-assisted drainage to treat postoperative colorectal cancer anastomotic stenosis with fistula.

BACKGROUND: Digestive tract reconstruction is required after the surgical resection of a colorectal malignant tumor. Some patients may have concomitant anastomotic complications, such as anastomotic stenosis with fistula (ASF), postoperatively. Therefore, we evaluated the efficacy and safety of endoscopic fully covered self-expandable metal stent and homemade vacuum sponge-assisted drainage (FSEM-HVSD) for the treatment of ASF following the radical resection of colorectal cancer. METHODS: Patients treated with FESM-HVSD were prospectively analyzed and followed up for ASF following colorectal cancer treatment in our medical center from 2017 to 2021 for the observation and evaluation of its safety and efficacy. RESULTS: Fifteen patients with a mean age of 55.80 ± 11.08 years were included. Nine patients (60%) underwent protective ileostomy. All 15 patients were treated with endoscopic FSEM-HVSD. The median time from the index operation to the initiation of FSEM-HVSD was 80 ± 20.34 days in patients who underwent protective ileostomy versus 11.4 ± 4.4 days in those who did not. The average number of endoscopic treatments per patient was 5.70 ± 1.25 times. The mean length of hospital stay was 27.60 ± 4.43 days. FSEM-HVSD treatment was successful in 13 patients, and no patients had any complications. The follow-up time was 1 year. Twelve of 15 (80%) patients achieved prolonged clinical success after FSEM-HVSD treatment, 1 experienced anastomotic tumor recurrence and underwent surgery again, and 1 patient required balloon dilation for anastomotic stenosis recurrence. CONCLUSIONS: FSEM-HVSD is an effective, safe, and minimally invasive treatment for ASF following colorectal cancer treatment. This technique could be the preferred treatment strategy for patients with ASF.

Development and validation of a prognostic scoring system for patients with colorectal cancer hepato-pulmonary metastasis: a retrospective study.

BACKGROUND: Hepato-pulmonary metastasis of colorectal cancer (CRC) is a rare disease with poor prognosis. This study aims to establish a highly efficient nomogram model to predict overall survival (OS) and cancer-specific survival (CSS) in patients with colorectal cancer hepato-pulmonary metastasis (CRCHPM). METHODS: We retrospectively analyzed the data of patients with CRCHPM from SEER database and Wuhan Union Hospital Cancer Center (WUHCC). A total of 1250 CRCHPM patients were randomly assigned to the training, internal validation, and external validation cohorts from 2010 to 2016.Univariate and multivariate cox analysis were performed to identify independent clinicopathological predictors of OS and CSS, and a nomogram was constructed to predict OS and CSS in CRCHPM patients. RESULTS: A nomogram of OS was constructed based on seven independent predictors of age, degree of differentiation, T stage, chemotherapy, number of lsampled lymph nodes, number of positive lymph nodes, and tumor size. Nomogram showed favorable sensitivity in predicting OS at 1, 3 and 5 years, with area under the receiver operating characteristic curve (AUROC) values of 0.802, 0.759 and 0.752 in the training cohort;0.814, 0.769 and 0.716 in the internal validation cohort;0.778, 0.756 and 0.753 in the external validation cohort, respectively. A nomogram of CSS was constructed based on three independent predictors of T stage, chemotherapy, and tumor size. The AUROC values of 1, 3 and 5 years were 0.709,0.588,0.686 in the training cohort; 0.751, 0.648,0.666 in the internal validation cohort;0.781,0.588,0.645 in the external validation cohort, respectively. Calibration curves, Concordance index (C-index), and decision curve analysis (DCA) results revealed that using our model to predict OS and CSS is more efficient than other single clinicopathological characteristics. CONCLUSION: A nomogram of OS and CSS based on clinicopathological characteristics can be conveniently used to predict the prognosis of CRCHPM patients.

Application of nanotechnology in the early diagnosis and comprehensive treatment of gastrointestinal cancer.

Gastrointestinal cancer (GIC) is a common malignant tumour of the digestive system that seriously threatens human health. Due to the unique organ structure of the gastrointestinal tract, endoscopic and MRI diagnoses of GIC in the clinic share the problem of low sensitivity. The ineffectiveness of drugs and high recurrence rates in surgical and drug therapies are the main factors that impact the curative effect in GIC patients. Therefore, there is an urgent need to improve diagnostic accuracies and treatment efficiencies. Nanotechnology is widely used in the diagnosis and treatment of GIC by virtue of its unique size advantages and extensive modifiability. In the diagnosis and treatment of clinical GIC, surface-enhanced Raman scattering (SERS) nanoparticles, electrochemical nanobiosensors and magnetic nanoparticles, intraoperative imaging nanoparticles, drug delivery systems and other multifunctional nanoparticles have successfully improved the diagnosis and treatment of GIC. It is important to further improve the coordinated development of nanotechnology and GIC diagnosis and treatment. Herein, starting from the clinical diagnosis and treatment of GIC, this review summarizes which nanotechnologies have been applied in clinical diagnosis and treatment of GIC in recent years, and which cannot be applied in clinical practice. We also point out which challenges must be overcome by nanotechnology in the development of the clinical diagnosis and treatment of GIC and discuss how to quickly and safely combine the latest nanotechnology developed in the laboratory with clinical applications. Finally, we hope that this review can provide valuable reference information for researchers who are conducting cross-research on GIC and nanotechnology.

Application of endoscopic technique in completely occluded anastomosis with anastomotic separation after radical resection of colon cancer: a case report and literature review.

BACKGROUND: Anastomosis-related complications are common after the radical resection of colon cancer. Among such complications, severe stenosis or completely occluded anastomosis (COA) are uncommon in clinical practice, and the separation of the anastomosis is even rarer. For such difficult problems as COA or anastomotic separation, clinicians tend to adopt surgical interventions, and few clinicians try to solve them through endoscopic operations. CASE PRESENTATION: In this article, we present a case of endoscopic treatment of anastomotic closure and separation after radical resection for sigmoid carcinoma. After imaging examination and endoscopic evaluation, we found that the patient had a COA accompanied by a 3-4 cm anastomotic separation. With the aid of fluoroscopy, we attempted to use the titanium clip marker as a guide to perform an endoscopic incision and successfully achieved recanalization. We used a self-expanding covered metal stent to bridge the intestinal canal to resolve the anastomotic separation. Finally, the patient underwent ileostomy takedown, and the postoperative recovery was smooth. The follow-up evaluation results showed that the anastomotic stoma was unobstructed. CONCLUSIONS: We reported the successful application of endoscopic technique in a rare case of COA and separation after colon cancer surgery, which is worth exploring and verifying through more clinical studies in the future.

The value of haematological parameters and serum tumour markers for predicting KRAS mutations in 784 Chinese colorectal cancer patients: a retrospective analysis.

BACKGROUND: Identifying the mutation status of KRAS is important for optimizing treatment in patients with colorectal cancer (CRC). The aim of this study was to investigate the predictive value of haematological parameters and serum tumour markers (STMs) for KRAS gene mutations. METHODS: The clinical data of patients with colorectal cancer from January 2014 to December 2018 were retrospectively collected, and the associations between KRAS mutations and other indicators were analysed. Receiver operating characteristic (ROC) curve analysis was performed to quantify the predictive value of these factors. Univariate and multivariate logistic regression models were applied to identify predictors of KRAS mutations by calculating the odds ratios (ORs) and their corresponding 95% confidence intervals (CIs). RESULTS: KRAS mutations were identified in 276 patients (35.2%). ROC analysis revealed that age, CA12-5, AFP, SCC, CA72-4, CA15-3, FERR, CYFRA21-1, MCHC, and tumor location could not predict KRAS mutations (P = 0.154, 0.177, 0.277, 0.350, 0.864, 0.941, 0.066, 0.279, 0.293, and 0.053 respectively), although CEA, CA19-9, NSE and haematological parameter values showed significant predictive value (P = 0.001, < 0.001, 0.043 and P = 0.003, < 0.001, 0.001, 0.031, 0.030, 0.016, 0.015, 0.019, and 0.006, respectively) but without large areas under the curve. Multivariate logistic regression analysis showed that CA19-9 was significantly associated with KRAS mutations and was the only independent predictor of KRAS positivity (P = 0.016). CONCLUSIONS: Haematological parameters and STMs were related to KRAS mutation status, and CA19-9 was an independent predictive factor for KRAS gene mutations. The combination of these clinical factors can improve the ability to identify KRAS mutations in CRC patients.

Colon metal stents as a bridge to surgery had no significant effects on the perineural invasion: a retrospective study.

PURPOSE: The long-term oncological effects of self-expandable metallic stent (SEMS) as a "bridge to surgery" are contradictory, and perineural invasion was supposed to be enhanced by the stenting. In this retrospective study, we compared the perineural invasion and the oncological outcomes between the stent as a bridge to surgery (SBTS)- and emergency surgery (ES)-treated patients to evaluate the results of stenting on the perineural invasion. METHODS: The clinical data of patients with acute intestinal obstruction caused by colorectal cancer from January 2013 to January 2017 were retrospectively collected. Forty-three patients underwent semi-elective curative resection after endoscopic SEMS insertion, and sixty-three underwent ES. The adverse events and long-term follow-up outcomes were assessed. The clinicopathological characteristics, perineural invasion rates, and survival rates were compared between the two patient groups. RESULTS: Stent insertion resulted in significantly lower stoma rate (32.6% vs 46%; P = 0.03), post-operative overall complication rate (11.6% vs 28.6%, P = 0.038), and total hospital stay (17.07 ± 5.544 days vs 20.48 ± 7.372 days, P = 0.042). Compared with the ES group, there was no significant increase in the incidence of peripheral invasion in the SBTS group (39.5% vs 47.6%, P = 0.411). No significant difference was noted in the survival rate and long-term prognosis between the SEMS and ES groups (P = 0.964). The technical success rate was 95.6%, and the clinical success rate was 97.7%. CONCLUSIONS: Preoperative colon stenting was an effective transitional method for colorectal cancer patients with complete obstruction. Short-term stent implantation had no significant effect on perineural invasion in patients with CRC.

MYL9 expressed in cancer-associated fibroblasts regulate the immune microenvironment of colorectal cancer and promotes tumor progression in an autocrine manner.

BACKGROUND: The tumor microenvironment (TME) is an important factor that regulates the progression of colorectal cancer (CRC). Cancer-associated fibroblasts (CAFs) are the main mesenchymal cells in the TME and play a vital role in tumor progression; however, the specific underlying mechanisms require further study. METHODS: Multiple single-cell and transcriptome data were analyzed and validated. Primary CAFs isolation, CCK8 assay, co-culture assay, western blotting, multiple immunofluorescence, qRT-PCR, ELISA, immunoprecipitation, ChIP, double luciferase, and animal experiments were used to explore the potential mechanism of MYL9 regulation in CRC. RESULTS: Our findings revealed that MYL9 was predominantly localized and expressed in CAFs rather than in CRC cells, and bioinformatics analysis revealed that high MYL9 expression was strongly associated with poor overall and disease-free survival in various tumors. In addition, high MYL9 expression is closely associated with M2 macrophage infiltration, which can lead to an immunosuppressive microenvironment in CRC, making it insensitive to immunotherapy. Mechanically, MYL9 can regulate the secretion of CAFs on CCL2 and TGF-ß1, thus affecting the immune microenvironment and progression of CRC. In addition, MYL9 bounded with IQGAP1 to regulate CCL2 and TGF-ß1 secretion through the ERK 1/2 pathway, and CCL2 and TGF-ß1 synergistically promoted CRC cells progression through the PI3K-AKT pathway. Furthermore, MYL9 promotes epithelial-mesenchymal transition (EMT) in CRC. During the upstream regulation of MYL9 in CAFs, we found that the EMT transcription factor ZEB1 could bind to the MYL9 promoter in CAFs, enhancing the activity and function of MYL9. Therefore, MYL9 is predominantly expressed in CAFs and can indirectly influence tumor biology and EMT by affecting CAFs protein expression in CRC. CONCLUSIONS: MYL9 regulates the secretion of cytokines and chemokines in CAFs, which can affect the immune microenvironment of CRC and promote CRC progression. The relationship between MYL9 expression and CRC clinical staging and immunotherapy is closer in CAFs than in tumor cells; therefore, studies using CAFs as a model deserve more attention when exploring tumor molecular targets in clinical research.

Development and Interpretation of a Clinicopathological-Based Model for the Identification of Microsatellite Instability in Colorectal Cancer.

Chemotherapy is not recommended for patients with deficient mismatch repair (dMMR) in colorectal cancer (CRC); therefore, assessing the status of MMR is crucial for the selection of subsequent treatment. This study is aimed at building predictive models to accurately and rapidly identify dMMR. A retrospective analysis was performed at Wuhan Union Hospital between May 2017 and December 2019 based on the clinicopathological data of patients with CRC. The variables were subjected to collinearity, least absolute shrinkage and selection operator (LASSO) regression, and random forest (RF) feature screening analyses. Four sets of machine learning models (extreme gradient boosting (XGBoost), support vector machine (SVM), naive Bayes (NB), and RF) and a conventional logistic regression (LR) model were built for model training and testing. Receiver operating characteristic (ROC) curves were plotted to evaluate the predictive performance of the developed models. In total, 2279 patients were included in the study and were randomly divided into either the training or test group. Twelve clinicopathological features were incorporated into the development of the predictive models. The area under curve (AUC) values of the five predictive models were 0.8055 for XGBoost, 0.8174 for SVM, 0.7424 for NB, 8584 for RF, and 0.7835 for LR (Delong test, P value < 0.05). The results showed that the RF model exhibited the best recognition ability and outperformed the conventional LR method in identifying dMMR and proficient MMR (pMMR). Our predictive models based on routine clinicopathological data can significantly improve the diagnostic performance of dMMR and pMMR. The four machine learning models outperformed the conventional LR model.

Changes in Bacteroides and the microbiota in patients with obstructed colorectal cancer: retrospective cohort study.

BACKGROUND: The relationship between intestinal obstruction due to colorectal cancer (CRC) and the gut microbiota remains largely unknown. The aim of this study was to investigate the potential association between alterations in gut microbiota and CRC in the presence of intestinal obstruction. METHODS: Patients with CRC with or without obstruction were recruited and compared using 1:1 propensity score matching (PSM). Total DNA from tumours and adjacent normal tissues of 84 patients and 36 frozen tumour tissues was extracted and amplified. 16S RNA sequencing was used to uncover differences in microbiota composition between the two groups. RESULTS: A total of 313 patients with CRC were recruited. Survival analysis demonstrated that patients in the obstruction group had shorter overall survival time and disease-free survival (DFS) time than those in the non-obstruction group. Microbial richness and diversity in tumour tissues of patients with obstruction were significantly higher than those of patients with no obstruction. The alpha diversity indices and beta diversity exhibited were different between the two groups (P < 0.05). At the phylum and genus levels, Bacteroidetes were significantly enriched in the tumour tissues of patients with obstruction. Alpha diversity in tumour tissues was closely related to specific microbiota. These findings were replicated in the 16S rRNA analyses from frozen samples. There were more Bacteroidetes in CRC patients with obstruction. CONCLUSIONS: Patients with obstructed CRC have worse prognosis and have differences in their microbiota. Higher levels of Bacteroides were observed in patients with obstructed CRC.

The Prognostic Significance of RIMKLB and Related Immune Infiltrates in Colorectal Cancers.

RimK-like family member B (RIMKLB) is an enzyme that post-translationally modulates ribosomal protein S6, which can affect the development of immune cells. Some studies have suggested its role in tumor progression. However, the relationships among RIMKLB expression, survival outcomes, and tumor-infiltrating immune cells (TIICs) in colorectal cancer (CRC) are still unknown. Therefore, we analyzed RIMKLB expression levels in CRC and normal tissues and investigated the correlations between RIMKLB and TIICs as well as the impact of RIMKLB expression on clinical prognosis in CRC using multiple databases, including the Tumor Immune Estimation Resource (TIMER), Gene Expression Profiling Interactive Analysis (GEPIA), PrognoScan, and UALCAN databases. Enrichment analysis was conducted with the cluster Profiler package in R software to explore the RIMKLB-related biological processes involved in CRC. The RIMKLB expression was significantly decreased in CRC compared to normal tissues, and correlated with histology, stage, lymphatic metastasis, and tumor status (p < 0.05). Patients with CRC with high expression of RIMKLB showed poorer overall survival (OS) (HR = 2.5,p = 0.00,042), and inferior disease-free survival (DFS) (HR = 1.9,p = 0.19) than those with low expression of RIMKLB. TIMER analysis indicated that RIMKLB transcription was closely related with several TIICs, including CD4+ and CD8+ T cells, B cells, tumor-associated macrophages (TAMs), monocytes, neutrophils, natural killer cells, dendritic cells, and subsets of T cells. Moreover, the expression of RIMKLB showed significant positive correlations with infiltrating levels of PD1 (r = 0.223, p = 1.31e-06; r = 0.249, p = 1.25e-03), PDL1 (r = 0.223, p = 6.03e-07; r = 0.41, p = 5.45e-08), and CTLA4 (r = 0.325, p = 9.68e-13; r = 0.41, p = 5.45e-08) in colon and rectum cancer, respectively. Enrichment analysis showed that the RIMKLB expression was positively related to extracellular matrix and immune inflammation-related pathways. In conclusion, RIMKLB expression is associated with survival outcomes and TIICs levels in patients with CRC, and therefore, might be a potential novel prognostic biomarker that reflects the immune infiltration status.

Clinical effects of the combination of Traditional Chinese and Western Medicines on coronavirus disease 2019: a systematic review and Meta-analysi.

OBJECTIVE: To explore the clinical efficacy of the combination of Traditional Chinese and Western Medicines for the treatment of coronavirus disease 2019 (COVID-19). METHODS: Studies were identified in six popular medical databases. RESULTS: Thirteen studies were included. The results showed that combined treatment with Traditional Chinese and Western Medicines can reduce the probability of progression from mild to severe disease [RR = 0.34, 95% confidence interval (CI) (0.18, 0.65)] (P = 0.001) and improve the clinical cure rate [RR = 0.17, 95% CI (0.05, 0.28)] (P = 0.004). The use of an integrated treatment strategy shortened the time to the remission of fever [WMD = －1.27, 95% CI (－1.67, －0.92)](P < 0.001) and improved the incidences of the disappearance of fever and fatigue [RR = 1.25, 95% CI (1.06, 1.47) (P = 0.007); RR = 1.49, 95% CI (1.13, 1.97) (P = 0.004)]. CONCLUSION: A combined treatment strategy is effective for COVID-19.

Development and Validation of a Predictive Scoring System for Colorectal Cancer Patients With Liver Metastasis: A Population-Based Study.

Liver metastasis in colorectal cancer (CRC) is common and has an unfavorable prognosis. This study aimed to establish a functional nomogram model to predict overall survival (OS) and cancer-specific survival (CSS) in patients with colorectal cancer liver metastasis (CRCLM). A total of 9,736 patients with CRCLM from 2010 to 2016 were randomly assigned to training, internal validation, and external validation cohorts. Univariate and multivariate Cox analyses were performed to identify independent clinicopathologic predictive factors, and a nomogram was constructed to predict CSS and OS. Multivariate analysis demonstrated age, tumor location, differentiation, gender, TNM stage, chemotherapy, number of sampled lymph nodes, number of positive lymph nodes, tumor size, and metastatic surgery as independent predictors for CRCLM. A nomogram incorporating the 10 predictors was constructed. The nomogram showed favorable sensitivity at predicting 1-, 3-, and 5-year OS, with area under the receiver operating characteristic curve (AUROC) values of 0.816, 0.782, and 0.787 in the training cohort; 0.827, 0.769, and 0.774 in the internal validation cohort; and 0.819, 0.745, and 0.767 in the external validation cohort, respectively. For CSS, the values were 0.825, 0.771, and 0.772 in the training cohort; 0.828, 0.753, and 0.758 in the internal validation cohort; and 0.828, 0.737, and 0.772 in the external validation cohort, respectively. Calibration curves and ROC curves revealed that using our models to predict the OS and CSS would add more benefit than other single methods. In summary, the novel nomogram based on significant clinicopathological characteristics can be conveniently used to facilitate the postoperative individualized prediction of OS and CSS in CRCLM patients.

An Oxidative Stress Index-Based Score for Prognostic Prediction in Colorectal Cancer Patients Undergoing Surgery.

Oxidative stress plays an important role in the development of colorectal cancer (CRC). This study is aimed at developing and validating a novel scoring system, based on oxidative stress indexes, for prognostic prediction in CRC patients. A retrospective analysis of 1422 CRC patients who underwent surgical resection between January 2013 and December 2017 was performed. These patients were randomly assigned to the training set (n = 1022) or the validation set (n = 400). Cox regression model was used to analyze the laboratory parameters. The CRC-Integrated Oxidative Stress Score (CIOSS) was developed from albumin (ALB), direct bilirubin (DBIL), and blood urea nitrogen (BUN), which were significantly associated with survival in CRC patients. Furthermore, a survival nomogram was generated by combining the CIOSS with other beneficial clinical characteristics. The CIOSS generated was as follows: 0.074 × albumin (g/L), -0.094 × bilirubin (µmol/L), and -0.099 × blood urea nitrogen (mmol/L), based on the multivariable Cox regression analysis. Using 50% (0.1025) and 85% (0.481) of CIOSS as cutoff values, three prognostically distinct groups were formed. Patients with high CIOSS experienced worse overall survival (OS) (hazard ratio [HR] = 4.33; 95% confidence interval [CI], 2.80-6.68; P < 0.001) and worse disease-free survival (DFS) (HR = 3.02; 95% CI, 1.96-4.64; P < 0.001) compared to those with low CIOSS. This predictive nomogram had good calibration and discrimination. ROC analyses showed that the CIOSS possessed excellent performance (AUC = 0.818) in predicting DFS. The AUC of the OS nomogram based on CIOSS, TNM stage, T stage, and chemotherapy was 0.812, while that of the DFS nomogram based on CIOSS, T stage, and TNM stage was 0.855. Decision curve analysis showed that these two prediction models were clinically useful. CIOSS is a CRC-specific prognostic index based on the combination of available oxidative stress indexes. High CIOSS is a powerful indicator of poor prognosis. The CIOSS also showed better predictive performance compared to TNM stage in CRC patients.

Novel parameter based on lipid indicators ratio improves prognostic value of plasma lipid levels in resectable colorectal cancer patients.

BACKGROUND: At present, the value of lipid indicators in evaluating the prognosis of colorectal cancer is still relatively limited. AIM: To evaluate the value of a novel parameter for colorectal cancer (CRC) prognosis scoring based on preoperative serum lipid levels. METHODS: Four key serum lipid factors, namely, high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), apolipoprotein A1 (ApoA1), and apolipoprotein B (ApoB), were detected. Two representative ratios, HDL-C-LDL-C ratio (HLR) and ApoA1-ApoB ratio (ABR) were calculated. The relationship of these parameters with the prognosis of CRC patients including progression-free survival (PFS) and overall survival (OS) was analyzed by Kaplan-Meier plot and Cox proportional hazards regression. A novel lipoprotein cholesterol-apolipoprotein (LA) score based on HLR and ABR was established and its value in prognosis evaluation for CRC patients was explored. RESULTS: Multivariate Cox proportional hazards regression analysis of PFS and OS showed that HDL-C, ApoA1, HLR, and ABR were positively associated with the prognosis of CRC patients. LA score was independently associated with a good prognosis in resectable CRC patients. Data processing of a dummy variable showed that the prognosis of patients with higher LA scores is better than that with lower LA scores. CONCLUSION: The newly established LA score might serve as a better predictor of the prognosis of resectable CRC patients.

The Value of Haematological Parameters and Tumour Markers in the Prediction of Intestinal Obstruction in 1474 Chinese Colorectal Cancer Patients.

Intestinal obstruction, a life-threatening problem, often occurs in patients with advanced colorectal cancer (CRC). However, the cause of obstruction is still unknown. Very few prediction models for intestinal obstruction in CRC exist, and their results are unreliable. Therefore, we investigated whether preoperative serum tumour markers (STMs) combined with haematological and biochemical markers could be used as predictors. We retrospectively analysed 1474 patients with CRC who underwent radical resection after admission. Several clinical features, STMs, and serum biochemical and haematological indicators were analysed. Predictors of intestinal obstruction were analysed with univariate and multivariate logistic regression. The accuracy of the multivariate predictors of obstruction was measured by the area under the receiver operating characteristic (ROC) curve (AUC). The Kaplan-Meier method was used to create survival curves. Obstruction was found more in males (62.18%), never-smokers (73.95%), the left colon (54.20%), the tumour diameter > 4.5 cm (55.88%), high differentiation (89.50%), and negative nerve invasion (70.17%). The serum tumour markers (STMs) and peripheral blood routine indexes (PBRI) were significantly associated with obstructive status (p < 0.05). Multivariate analysis demonstrated that the neutrophil and lymphocyte counts, carcinoembryonic antigen, carbohydrate antigen 19-9, carbohydrate antigen 125, albumin, alkaline phosphatase, gamma-glutamyl transpeptidase, total protein, and neutrophil-to-lymphocyte ratio were predictors of intestinal obstruction (p < 0.05). The AUC for the curve with all the eight factors was 0.715 (95% confidence interval: 0.673-0.758). The STMs and PBRI were related to the obstruction status of the patients, and they could be used in combination with other clinical factors to significantly improve diagnosis and management of intestinal obstruction in CRC patients.