Coral-like CoSe2@N-doped carbon with a high initial coulombic efficiency as advanced anode materials for Na-ion batteries.

Na-ion batteries (NIBs) have attracted great interest as a possible technology for grid-scale energy storage for the past few years owing to the wide distribution, low cost and environmental friendliness of sodium resources and similar chemical mechanisms to those of established Li-ion batteries (LIBs). Nonetheless, the implementation of NIBs is seriously hindered because of their low rate capability and cycling stability. This is mainly because the large ionic size of Na+ can reduce the structural stability and cause sluggish reaction kinetics of electrode materials. Herein, three-dimensional nanoarchitectured coral-like CoSe2@N-doped carbon (CL-CoSe2@NC) was synthesized through solvothermal and selenizing techniques. As a result, CL-CoSe2@NC for NIBs at 2 A g-1 exhibits an ultrahigh specific capacity of 345.4 mA h g-1 after 2800 cycles and a superhigh initial coulombic efficiency (ICE) of 93.1%. Ex situ XRD, HRTEM, SAED and XPS were executed to study the crystal structure evolution between Na and CoSe2 during sodiation/de-sodiation processes. The aforementioned results indicate that the improved sodium storage property of CL-CoSe2@NC could be attributed to better electrode kinetics and a stable SEI film because of the 3D nanoarchitecture and the existence of the NC layer.

The use of non-steroid anti-inflammatory drugs during radical resection correlated with the outcome in non-small cell lung cancer.

AIMS: The use of non-steroid anti-inflammatory drugs (NSAIDs) is conventional in management of postoperative pain in cancer patients, and further investigations have reported that some of these drugs correlated with the outcome in cancers. However, the prognostic value of the use of NSAIDs during surgery in non-small cell lung cancer (NSCLC) patients has been less addressed. METHODS: NSCLC patients staged I-III are retrospectively enrolled, and the data of the use of NSAIDs during surgery are collected. Patients are divided into two subgroups according to the use intensity (UI) (low or high) of the NSAIDs, which was calculated by the accumulate dosage of all the NSAIDs divided by the length of hospitalization. The differences of the clinical features among these groups were checked. And the disease-free survival (DFS) and overall survival (OS) differences in these groups were compared by Kaplan-Meier analysis; risk factors for survival were validated by using a Cox proportional hazards model. RESULTS: The UI was significant in predicting the DFS (AUC = 0.65, 95% CI: 0.57-0.73, P = 0.001) and OS (AUC = 0.70, 95% CI: 0.59-0.81, P = 0.001). Clinical features including type of resection (P = 0.001), N stages (P < 0.001), and TNM stages (P = 0.004) were significantly different in UI low (< 74.55 mg/day) or high (≥ 74.55 mg/day) subgroups. Patients in UI-high subgroups displayed significant superior DFS (log rank = 11.46, P = 0.001) and OS (log rank = 7.63, P = 0.006) than the UI-low ones. At last, the UI was found to be an independent risk factor for DFS (HR: 0.52, 95% CI: 0.28-0.95, P = 0.034). CONCLUSIONS: The use of NSAIDs during radical resection in NSCLC patients correlated with the outcome and patients with a relative high UI has better outcome.

Multifunctional properties of the transmembrane LPxTG-motif protein derived from Limosilactobacillus reuteri SH-23.

The LPxTG-motif protein is an important transmembrane protein with high hydrophilicity and stability, as evidenced by its stress tolerance and adhesion ability. In this study, a novel LPxTG-motif protein with esterase activity (LEP) was expressed, and the multifunctional properties such as adhesion properties and esterase activity were also investigated. When cocultured with Limosilactobacillus reuteri SH-23, the adhesion ability of L. reuteri SH-23 to HT-29 cells was improved, and this adhesion was further found relating to the potential target protein Pyruvate kinase M1/2 (PKM) of HT-29 cells. In addition, as a multifunctional protein, LEP can promote the hydrolysis of bovine milk lipids with its esterase activity, and the activity was enhanced in the presence of Zn2+ and Mn2+ at pH 7. Furthermore, the polyunsaturated fatty acids (PUFA) such as linoleic acid and eicosapentaenoic acid were found to increase during the hydrolyzing process. These unique properties of LEP provide a comprehensive understanding of the adhesion function and PUFA releasing properties of the multifunctional protein derived from L. reuteri SH-23 and shed light on the beneficial effect of this Lactobacillus strain on the colonization of the gastrointestinal tract.

The Value of Targeting CXCR4 With 68Ga-Pentixafor PET/CT for Subtyping Primary Aldosteronism.

CONTEXT: Primary aldosteronism (PA) is one of the leading causes of secondary hypertension, and its diagnostic subtyping consistently presents a clinical challenge. OBJECTIVE: This study aimed to investigate the potential of 68Ga-Pentixafor positron emission tomography/computed tomography (PET/CT) in PA classification and its applicability in guiding the development of clinical treatment plans by increasing the sample size. METHODS: We prospectively enrolled 120 patients with either PA or nonfunctional adenoma (NFA) for analysis. All patients underwent 68Ga-Pentixafor PET/CT. Of these, 11 patients underwent adrenal venous sampling (AVS), 77 underwent adrenalectomy, 76 received pathological diagnoses, and 71 underwent immunohistochemical detection of aldosterone synthase (CYP11B2). Immunohistochemistry for C-X-C chemokine receptor 4 (CXCR4) was performed in 62 cases. Follow-up was conducted for all patients. RESULTS: Among the 120 patients, 66 were diagnosed with aldosterone-producing adenoma (APA), 33 with idiopathic hyperaldosteronism (IHA), and 21 with NFA. For APA patients, the sensitivity, specificity, and accuracy of visual analysis using 68Ga-Pentixafor PET/CT were 92.40%, 94.40%, and 93.33%, respectively. Furthermore, for APA patients with a nodule greater than 1 cm in diameter, when the maximum standard uptake value was 7.3 or greater, the specificity was 100%; and for APA patients with a nodule less than 1 cm in diameter, 68Ga-Pentixafor PET/CT also exhibited high sensitivity. AVS was successfully performed in 5 patients. Among the 5 patients, the concordance rate between the AVS and 68Ga-Pentixafor PET/CT for PA subtyping was 60%. In the 77 patients who underwent adrenalectomy, 61 PET/CT scans displayed positive lesions, all of which benefited from the surgery. Additionally, the concordance rate between 68Ga-Pentixafor PET/CT imaging and CYP11B2 was 81.69%. CONCLUSION: 68Ga-Pentixafor PET/CT is a reliable and noninvasive functional imaging technique that demonstrates high accuracy in classifying PA and provides valuable guidance for clinical treatment decision-making.

Postoperative serum interleukin-6 levels correlate with survival in stage I-III colorectal cancer.

AIMS: The preoperative serum levels of inflammatory mediators, including C-reactive protein (CRP), procalcitonin (PCT) and interleukin-6 (IL-6), have been demonstrated to be correlated with patient outcomes in colorectal cancer (CRC); however, the prognostic role of these levels has been less well-studied in postoperative settings. MATERIALS AND METHODS: A total of 122 stage I-III CRC patients were retrospectively enrolled. Serum levels of CRP, PCT and IL-6 were measured after surgery, and their prognostic value was evaluated. Kaplan-Meier analysis was used to determine the differences in disease-free survival (DFS) and overall survival (OS) between patients with different levels of these mediators, and the Cox proportional hazards model was used to estimate the risk factors. RESULTS: In contrast to CRP and PCT, only the level of IL-6 was significant in predicting DFS (P = 0.01) but not OS (P = 0.07). A total of 66.39% (81/122) of patients were assigned to the low IL-6 group and no significant differences were found in the collected clinicopathological parameters among the low or high IL-6 subgroups. The level of IL-6 was negatively correlated with postoperative (1 w) (R=-0.24, P = 0.02) absolute lymphocyte counts. Patients with low levels of IL-6 had better DFS (log rank = 6.10, P = 0.01) but not OS (log rank = 2.28, P = 0.13). Finally, the level of IL-6 was an independent risk factor for DFS (HR: 1.81, 95% CI: 1.03-3.15, P = 0.04). CONCLUSIONS: Compared to CRP and PCT, the level of IL-6 was observed to be the only significant factor in predicting the prognosis of stage I-III CRC patients after surgery, and a low level of IL-6 was associated with good DFS.

Development and validation of an ensemble machine-learning model for predicting early mortality among patients with bone metastases of hepatocellular carcinoma.

Purpose: Using an ensemble machine learning technique that incorporates the results of multiple machine learning algorithms, the study's objective is to build a reliable model to predict the early mortality among hepatocellular carcinoma (HCC) patients with bone metastases. Methods: We extracted a cohort of 124,770 patients with a diagnosis of hepatocellular carcinoma from the Surveillance, Epidemiology, and End Results (SEER) program and enrolled a cohort of 1897 patients who were diagnosed as having bone metastases. Patients with a survival time of 3 months or less were considered to have had early death. To compare patients with and without early mortality, subgroup analysis was used. Patients were randomly divided into two groups: a training cohort (n = 1509, 80%) and an internal testing cohort (n = 388, 20%). In the training cohort, five machine learning techniques were employed to train and optimize models for predicting early mortality, and an ensemble machine learning technique was used to generate risk probability in a way of soft voting, and it was able to combine the results from the multiply machine learning algorithms. The study employed both internal and external validations, and the key performance indicators included the area under the receiver operating characteristic curve (AUROC), Brier score, and calibration curve. Patients from two tertiary hospitals were chosen as the external testing cohorts (n = 98). Feature importance and reclassification were both operated in the study. Results: The early mortality was 55.5% (1052/1897). Eleven clinical characteristics were included as input features of machine learning models: sex (p = 0.019), marital status (p = 0.004), tumor stage (p = 0.025), node stage (p = 0.001), fibrosis score (p = 0.040), AFP level (p = 0.032), tumor size (p = 0.001), lung metastases (p < 0.001), cancer-directed surgery (p < 0.001), radiation (p < 0.001), and chemotherapy (p < 0.001). Application of the ensemble model in the internal testing population yielded an AUROC of 0.779 (95% confidence interval [CI]: 0.727-0.820), which was the largest AUROC among all models. Additionally, the ensemble model (0.191) outperformed the other five machine learning models in terms of Brier score. In terms of decision curves, the ensemble model also showed favorable clinical usefulness. External validation showed similar results; with an AUROC of 0.764 and Brier score of 0.195, the prediction performance was further improved after revision of the model. Feature importance demonstrated that the top three most crucial features were chemotherapy, radiation, and lung metastases based on the ensemble model. Reclassification of patients revealed a substantial difference in the two risk groups' actual probabilities of early mortality (74.38% vs. 31.35%, p < 0.001). Patients in the high-risk group had significantly shorter survival time than patients in the low-risk group (p < 0.001), according to the Kaplan-Meier survival curve. Conclusions: The ensemble machine learning model exhibits promising prediction performance for early mortality among HCC patients with bone metastases. With the aid of routinely accessible clinical characteristics, this model can be a trustworthy prognostic tool to predict the early death of those patients and facilitate clinical decision-making.

Combined preoperative prognostic nutritional index and D-dimer score predicts outcome in colorectal cancer.

BACKGROUND: The prognostic nutritional index (PNI) and D-dimer (DD) levels represent useful prognostic indicators in colorectal cancer (CRC); however, a combination of these indicators, namely, the PNI and DD score (PDS) was less addressed. METHODS: A retrospective study with 183 patients after curative surgery was conducted. Patients were divided into 3 subgroups: PDS 0, decreased PNI and increased DD levels; PDS 1, decreased or increased PNI and DD levels; PDS 2, increased PNI and decreased DD levels. The differences in disease-free survival (DFS) and overall survival (OS) were compared among these subgroups, and risk factors for outcome were determined. RESULTS: A total of 56, 65 and 62 patients were assigned to the PDS 0, 1 and 2 subgroups, respectively. PDS was significant in predicting both the DFS (area under the curve (AUC) = 0.68, P < 0.001) and OS (AUC = 0.74, P < 0.001). PDS 0 patients were more likely to be associated with old age (P = 0.032), laparotomy (P < 0.001), elevated CEA (P = 0.001), T3 + T4 (P = 0.001) and advanced TNM stage (P = 0.031). PDS 0 patients had significantly inferior DFS (log rank = 18.35, P < 0.001) and OS (log rank = 28.34, P < 0.001) than PDS 1 or 2 patients. PDS was identified as an independent risk factor for both DFS (PDS 1: HR = 0.54, 95% CI: 0.30-1.00, P = 0.049; PDS 2: HR = 0.40, 95% CI: 0.20-0.79, P = 0.009) and OS (PDS 1: HR = 0.44, 95% CI: 0.22-0.88, P = 0.020; PDS 2: HR = 0.17, 95% CI: 0.06-0.45, P < 0.001). CONCLUSION: The PDS is a useful prognostic indicator for CRC patients after curative surgery, and PDS 0 patients have inferior survival. Additional future studies are needed to validate these findings.

A combined preoperative red cell distribution width and carcinoembryonic antigen score contribute to prognosis prediction in stage I lung adenocarcinoma.

AIMS: Hematological markers that can be used for prognosis prediction for stage I lung adenocarcinoma (LUAD) are still lacking. Here, we examined the prognostic value of a combination of the red cell distribution width (RDW) and carcinoembryonic antigen (CEA), namely, the RDW-CEA score (RCS), in stage I LUAD. MATERIALS AND METHODS: A retrospective study with 154 patients with stage I LUAD was conducted. Patients were divided into RCS 1 (decreased RDW and CEA), RCS 2 (decreased RDW and increased CEA, increased RDW and decreased CEA), and RCS 3 (increased RDW and CEA) subgroups based on the best optimal cutoff points of RDW and CEA for overall survival (OS). The differences in other clinicopathological parameters among RCS subgroups were calculated. Disease-free survival (DFS) and OS among these groups were determined by Kaplan-Meier analysis, and risk factors for outcome were calculated by a Cox proportional hazards model. RESULTS: Seventy, 65, and 19 patients were assigned to the RCS 1, 2, and 3 subgroups, respectively. Patients ≥ 60 years (P < 0.001), male sex (P = 0.004), T2 stage (P = 0.004), and IB stage (P = 0.006) were more significant in the RCS 2 or 3 subgroups. The RCS had a good area under the curve (AUC) for predicting DFS (AUC = 0.81, P < 0.001) and OS (AUC = 0.93, P < 0.001). The DFS (log-rank = 33.26, P < 0.001) and OS (log-rank = 42.05, P < 0.001) were significantly different among RCS subgroups, with RCS 3 patients displaying the worst survival compared to RCS 1 or 2 patients. RCS 3 was also an independent risk factor for both DFS and OS. CONCLUSIONS: RCS is a useful prognostic indicator in stage I LUAD patients, and RCS 3 patients have poorer survival. However, randomized controlled trials are needed to validate our findings in the future.

Development of a web-based calculator to predict three-month mortality among patients with bone metastases from cancer of unknown primary: An internally and externally validated study using machine-learning techniques.

Background: Individualized therapeutic strategies can be carried out under the guidance of expected lifespan, hence survival prediction is important. Nonetheless, reliable survival estimation in individuals with bone metastases from cancer of unknown primary (CUP) is still scarce. The objective of the study is to construct a model as well as a web-based calculator to predict three-month mortality among bone metastasis patients with CUP using machine learning-based techniques. Methods: This study enrolled 1010 patients from a large oncological database, the Surveillance, Epidemiology, and End Results (SEER) database, in the United States between 2010 and 2018. The entire patient population was classified into two cohorts at random: a training cohort (n=600, 60%) and a validation cohort (410, 40%). Patients from the validation cohort were used to validate models after they had been developed using the four machine learning approaches of random forest, gradient boosting machine, decision tree, and eXGBoosting machine on patients from the training cohort. In addition, 101 patients from two large teaching hospital were served as an external validation cohort. To evaluate each model's ability to predict the outcome, prediction measures such as area under the receiver operating characteristic (AUROC) curves, accuracy, and Youden index were generated. The study's risk stratification was done using the best cut-off value. The Streamlit software was used to establish a web-based calculator. Results: The three-month mortality was 72.38% (731/1010) in the entire cohort. The multivariate analysis revealed that older age (P=0.031), lung metastasis (P=0.012), and liver metastasis (P=0.008) were risk contributors for three-month mortality, while radiation (P=0.002) and chemotherapy (P<0.001) were protective factors. The random forest model showed the highest area under curve (AUC) value (0.796, 95% CI: 0.746-0.847), the second-highest precision (0.876) and accuracy (0.778), and the highest Youden index (1.486), in comparison to the other three machine learning approaches. The AUC value was 0.748 (95% CI: 0.653-0.843) and the accuracy was 0.745, according to the external validation cohort. Based on the random forest model, a web calculator was established: https://starxueshu-codeok-main-8jv2ws.streamlitapp.com/. When compared to patients in the low-risk groups, patients in the high-risk groups had a 1.99 times higher chance of dying within three months in the internal validation cohort and a 2.37 times higher chance in the external validation cohort (Both P<0.001). Conclusions: The random forest model has promising performance with favorable discrimination and calibration. This study suggests a web-based calculator based on the random forest model to estimate the three-month mortality among bone metastases from CUP, and it may be a helpful tool to direct clinical decision-making, inform patients about their prognosis, and facilitate therapeutic communication between patients and physicians.

Preoperative carcinoembryonic antigen to body mass index ratio contributes to prognosis prediction in colorectal cancer.

Both carcinoembryonic antigen (CEA) level and body mass index (BMI) are traditional prognostic markers in colorectal cancer (CRC); however, to the best of our knowledge, the value of the CEA to BMI ratio (CBR) has never been addressed. In the present study, 191 patients with CRC treated using radical resection were retrospectively included, and the significance of the CBR in predicting disease-free survival (DFS) or overall survival (OS) rates was calculated. The prognostic efficacy of the CBR in predicting OS was compared with individual CEA and BMI values. The survival differences of the subgroups were calculated by Kaplan-Meier analysis, and corresponding risk factors were then estimated by a Cox proportional hazards model. As a result, 29.84% (57/191) of the patients were assigned to the high CBR group (cut-off, ≥0.28); the CBR had a sensitivity of 56.50 and 68.90%, and a specificity of 80.60 and 80.10% for DFS and OS, respectively. Patients with a high CBR more commonly underwent laparotomy and exhibited advanced T stages, the presence of tumor deposits and advanced Tumor-Node-Metastasis stages (stage II or III). The CBR was more efficient than the CEA or BMI alone in predicting OS. In addition, patients with a high CBR presented with a significantly worse outcome than patients with a low CBR. Finally, the CBR was an independent risk factor for both DFS and OS. In conclusion, the CBR was a more robust prognostic factor in CRC, and patients with a relatively high CBR exhibited poorer survival.

Preoperative Absolute Lymphocyte Count to Carcinoembryonic Antigen Ratio Is a Superior Predictor of Survival in Stage I to III Colorectal Cancer.

Background: Preoperative absolute lymphocyte count (ALC) and carcinoembryonic antigen (CEA) are useful prognostic indicators in colorectal cancer (CRC); however, the role of the ALC-to-CEA ratio (LCR) has been less addressed. Methods: A total of 189 stage I to III CRC patients who underwent radical resection were enrolled retrospectively. The significance of the LCR in predicting disease-free survival (DFS) and overall survival (OS) was calculated and compared with other markers based on ALC. The DFS and OS differences among the low- and high-LCR subgroups and risk factors for the outcome were estimated by Kaplan-Meier analysis and the Cox proportional hazards model, respectively. Results: Taking 0.28 as the cutoff point, the LCR has a sensitivity and a specificity of 75.60% and 77.00%, respectively, in predicting OS. The prognostic efficacy of LCR was significantly superior to that of other markers based on ALC for predicting DFS and OS. A total of 34.92% (66/189) of patients displayed a low LCR (<0.28), and these patients were more likely to present poor cell differentiation (P = .03), tumor deposits (P < .01) and advanced T (P < .01) and liver metastasis (P = .02). Patients with a low LCR had significantly worse DFS (Log Rank = 34.98, P < .01) and OS (Log Rank = 43.17, P < .01) than those with a high LCR. The LCR was an independent prognostic factor for both DFS (hazard ratio (HR) = 0.35, 95% confidence interval (CI): 0.20-0.62, P < .01) and OS (HR = 0.18, 95% CI: 0.08-0.37, P < .01). Conclusions: The LCR is a superior predictor of survival in stage I to III CRC, and patients with a low LCR have an inferior outcome; however, additional studies are required to validate its prognostic role.

Preoperative low absolute lymphocyte count to fibrinogen ratio correlated with poor survival in nonmetastatic colorectal cancer.

BACKGROUND: Preoperative absolute lymphocyte count (LC) and fibrinogen (FIB) are useful prognostic indicators in colorectal cancer (CRC). However, the prognostic value of the LC to FIB ratio (LFR) has never been addressed. METHODS: A total of 189 nonmetastatic CRC patients after resection were enrolled retrospectively. The significance of the LFR in predicting disease-free survival (DFS) and overall survival (OS) was estimated by receiver operating characteristic curve analysis, and the prognostic efficacy was compared with individual LC and FIB. Patients were assigned to LFR low or high subgroups. Differences in clinicopathological features among these subgroups were calculated, and the survival differences of these subgroups were determined by the Kaplan-Meier analysis. A Cox proportional hazards model was applied to test the risk factors for survival. RESULTS: Taking 0.54 as the optimal cutoff point, the LFR had sensitivities of 79.70% and 86.40% and specificities of 52.30% and 51.00% in predicting the DFS and OS, respectively. A total of 109/189 (57.67%) patients were assigned to the LFR low group, and these patients were more likely to be characterized by criteria such as T3 + T4 (P < 0.01), stage 3 (P < 0.01), tumor deposits (P = 0.01), high CEA (P < 0.01), or CA19-9 levels (P = 0.04). And they also displayed worse DFS (log rank = 18.57, P < 0.01) and OS (log rank = 20.40, P < 0.01) than the high LFR group. Finally, the LFR was independently associated with inferior DFS (HR = 0.32, 95% CI: 0.16-0.61, P < 0.01) and OS (HR = 0.23, 95% CI: 0.09-0.55, P < 0.01). CONCLUSIONS: The LFR is a useful prognostic indicator in nonmetastatic CRC, and patients with a relatively low LFR had poor survival.

An analysis of the significance of the Tre2/Bub2/CDC 16 (TBC) domain protein family 8 in colorectal cancer.

The TBC (Tre-2/Bub2/Cdc16, TBC) structural domain is now considered as one of the factors potentially regulating tumor progression. However, to date, studies on the relationship between TBC structural domains and tumors are limited. In this study, we identified the role of TBC1 domain family member 8 (TBC1D8) as an oncogene in colorectal cancer (CRC) by least absolute shrinkage and selection operator (LASSO) and Cox regression analysis, showing that TBC1D8 may independently predict CRC outcome. Functional enrichment and single-cell analysis showed that TBC1D8 levels were associated with hypoxia. TBC1D8 levels were also positively correlated with M2 macrophage infiltration, which may have a complex association with hypoxia. Taken together, these results show that the TBC1D8 gene is involved in colorectal carcinogenesis, and the underlying molecular mechanisms may include hypoxia and immune cell infiltration.

Low VGF is associated with executive dysfunction in patients with major depressive disorder.

OBJECTIVES: Executive dysfunction is considered to be one of the cognitive impairment dimensions that are easily observed in depression, but its underlying molecular mechanism is still unclear. Study have shown that the neuropeptide VGF (non-acronymic) plays an important role in the regulation of hippocampal neurogenesis and neuroplasticity. Previous studies have shown that VGF may be related to the psychopathology of depression and cognitive impairment. However, the correlation between VGF and executive dysfunction in MDD has not been investigated. METHODS: A total of 35 MDD patients and 31 healthy control patients were enrolled in this study. The 17-item Hamilton Depression Rating Scale (HDRS) was used to measure the severity of depression, and the Wisconsin Card Sorting Test (WCST) was used to assess executive dysfunction. Double antibody sandwich enzyme-linked immunosorbent assay (ELISA) was used to determine serum VGF in peripheral blood. RESULTS: The level of serum VGF in MDD patients was significantly lower compared to that in the healthy control group (p < 0.001). Moreover, Response Administered (RA) scores, Response preservative errors (RPE), and Non-response preservative errors (NRPE) were all higher in the MDD group (all p < 0.05). In contrast, Categories Completed (CC) and Response Correct (RC) scores were lower (all p < 0.05). Further results showed a significant correlation between serum VGF with RA (r = -0.372, p = 0.028) and RPE scores (r = 0.507, p = 0.002) in patients with depression, while serum VGF showed no correlation with the severity of depression in either group. CONCLUSIONS: VGF may play an important role in executive function dysfunction in MDD patients, and VGF levels may become a new marker for predicting executive function dysfunction in depression.

Irregular delay of adjuvant chemotherapy correlated with poor outcome in stage II-III colorectal cancer.

AIMS: Adjuvant chemotherapy (ACT) plays an important role in improving the survival of stage II-III colorectal cancer (CRC) patients after curative surgery. However, the prognostic role of irregular delay of ACT (IDacT) for these patients has been less studied. MATERIALS AND METHODS: A total of 117 stage II-III CRC patients who underwent radical resection and received at least 3 months ACT were enrolled retrospectively. The significance of IDacT, including total delay (TD) and delay per cycle (DpC), in predicting disease-free survival (DFS) was determined using receiver operating characteristic curve (ROC) analysis. The survival differences between the TD, DpC-short and DpC-long subgroups were tested using Kaplan-Meier analysis, and risk factors for prognosis were determined using a Cox proportional hazards model. RESULTS: Using 35.50 and 3.27 days as the optimal cut-off points for TD and DpC, respectively, ROC analysis revealed that TD and DpC had sensitivities of 43.60% and 59.00% and specificities of 83.30% and 62.80%, respectively, in predicting DFS (both P < 0.05). No differences in the clinicopathological parameters were found between the TD, DpC-short or -long subgroups except histological differentiation in different TD subgroups and combined T stages in different DpC subgroups (both P = 0.04). Patients in the TD or DpC-long group exhibited significantly worse survival than in the -short group (TD: Log rank = 9.11, P < 0.01; DpC: Log rank = 6.09, P = 0.01). DpC was an independent risk factor for prognosis (HR = 2.54, 95% CI: 1.32-4.88, P = 0.01). CONCLUSIONS: IDacT had a profound effect on the outcome for stage II-III CRC. Although TD and DpC were significant for the prognosis, DpC was more robust, and patients who presented DpC for a long time had a significantly worse DFS.

An Analysis Regarding the Association Between Connexins and Colorectal Cancer (CRC) Tumor Microenvironment.

Background: Gap junctions, as one of the major ways to maintain social connections between cells, are now considered as one of the potential regulators of tumor metastasis. However, to date, studies on the relationship between gap junctions and colorectal cancer (CRC) are limited. Methods: We synthesized connexins-coding gene expression data from public Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA) databases. Bioinformatics analysis was performed using R software and several database resources such as MEXPRESS database, Gene Set Cancer Analysis (GSCA) database, Human Protein Atlas (HPA) database, Tumor Immune Single Cell Hub (TISCH) database, Search Tool for Retrieval of Gene Interaction Relationships (STRING), and Cytoscape software, etc., to investigate the biological mechanisms that may be involved in connexins. Immunofluorescence and immunohistochemical staining were used to validate the expression and localization of GJA4. Results: We found that CRC patients can be divided into two connexin clusters and that patients in cluster C1 had shorter survival than in cluster C2. The infiltration of M1 macrophages and NK cells was lower in cluster C1, while the levels of M2 macrophages and immune checkpoints were higher, indicating an immunosuppressed state in cluster C1. In addition, the epithelial-mesenchymal transition (EMT) phenotype was significantly activated in cluster C1. We observed that GJA4 was up-regulated in colorectal cancer tissues, which was related to poor prognosis. It was mainly expressed in fibroblasts, but the expression levels in normal intestinal epithelial cells were low. Finally, we found that GJA4 was associated with M2 macrophages and may be a potential immunosuppressive factor. Conclusion: We found that there is a significant correlation between abnormal connexins expression and patients' prognosis, and connexins play an important role in stromal-tumor interactions. Connexins, especially GJA4, can help enhance our understanding of tumor microenvironment (TME) and may guide more effective immunotherapeutic strategies.

Prognostic Implication of Preoperative Serum Albumin to Carcinoembryonic Antigen Ratio in Colorectal Cancer Patients.

Background: Preoperative serum albumin (ALB) and carcinoembryonic antigen (CEA) were useful prognostic factors in colorectal cancer (CRC); however, the ALB to CEA ratio (ACR) and their individual prognostic efficacies have been less studied. Methods: A retrospective study with 156 CRC patients staged I to IV was performed. The prognostic efficacy of ACR was estimated and subsequently compared with ALB, CEA, and other systemic inflammation markers, including the neutrophil-to-lymphocyte ratio (NLR), lymphocyte-to-monocyte ratio (LMR), and platelet-to-lymphocyte ratio (PLR). Differences in progression-free survival (PFS) and overall survival (OS) were determined by Kaplan-Meier (K-M) analysis, and the risk factors for survival were calculated by the Cox proportional hazards model. Results: A total of 31.41% (49 of 156) of patients presented with ACR-low disease, and these patients had tumors with advanced T stages, larger tumor diameters and distant metastases, and a lower LMR. When 5.98 was used as the cut-off point, it had a sensitivity of 58.50% and 61.50% and a specificity of 83.50% and 80.50% for PFS and OS, respectively. ACR displayed a superior prognostic efficacy than individual ALB, CEA and NLR, LMR, and PLR for both PFS and OS (except LMR). Patients in the ACR-low group displayed significantly worse PFS and OS than those in the ACR-high group. Finally, ACR was an independent prognostic factor for both PFS (HR = 0.31, 95% CI: 0.17-0.56, P < .01) and OS (HR = 0.33, 95% CI: 0.16-0.66, P < .01). Conclusions: ACR was a robust prognostic factor in CRC, and patients with a relatively low preoperative ACR would have significantly worse survival.

Correlation and prognostic implications of intratumor and tumor draining lymph node Foxp3+ T regulatory cells in colorectal cancer.

BACKGROUND: The prognostic value of intratumor T regulatory cells (Tregs) in colorectal cancer (CRC) was previously reported, but the role of these cells in tumor draining lymph nodes (TDLNs) was less addressed. METHODS: A total of 150 CRC stages I-IV were retrospectively enrolled. Intratumor and TDLN Tregs were examined by immunohistochemical assay. The association of these cells was estimated by Pearson correlation. Survival analyses of subgroups were conducted by Kaplan-Meier curves, and the log-rank test and risk factors for survival were tested by the Cox proportional hazard model. RESULTS: High accumulation of Tregs in tumors was significant in patients with younger age and good histological grade, where enrichment of these cells in TDLNs was more apparent in those with node-negative disease and early TNM stage disease, both of which were more common in early T stage cases. A significant correlation of intratumoral and TDLN Tregs was detected. Patients with higher intratumoral Tregs displayed significantly better PFS and OS than those with lower Tregs. However, no such differences were found, but a similar prognostic prediction trend was found for these cells in TDLNs. Finally, intratumoral Tregs were an independent prognostic factor for both PFS (HR = 0.97, 95% CI 0.95-0.99, P < 0.01) and OS (HR = 0.98, 95% CI 0.95-1.00, P = 0.04) in the patients. CONCLUSIONS: Higher intratumor Tregs were associated with better survival in CRC. Although no such role was found for these cells in TDLNs, the positive correlation and similar prognostic prediction trend with their intratumoral counterparts may indicate a parallelized function of these cells in CRC.

MiR-34b-3p Impaired HUVECs Viability and Migration via Targeting PDK1 in an In Vitro Model of Gestational Diabetes Mellitus.

Gestational diabetes mellitus (GDM) leads to poor pregnancy outcomes. The methods for GDM early diagnosis and treatment are still unknown. This study aimed to investigate the expression and diagnostic potential of miR-34b-3p in GDM patients and further analyzed the effects of miR-34b-3p on HUVECs viability and migration. The expression of miR-34b-3p was detected in HUVECs of GDM and normal pregnant women by qRT-PCR. Then the HUVECs were isolated from normal pregnant women. High glucose (HG) was used to treat the HUVECs to mimic the GDM in vitro. The cell viability and migration were determined by MTT, wound healing assay, and transwell assay. The interaction between miR-34b-3p and PDK1 was evaluated by luciferase activity assay. Our results showed that miR-34b-3p was up-regulated in HUVECs of GDM patients. Then the HUVECs were isolated from normal pregnant women and they were treated with HG to mimic the GDM in vitro. Interestingly, knockdown of miR-34b-3p restored the impairment of HG treatment-induced effects in HUVECs. More importantly, PDK1 was proved to be a potential target of miR-34b-3p. Finally, the rescue experiments confirmed that miR-34b-3p impaired cell viability and migration ability in HUVECs by targeting PDK1. These findings concluded that miR-34b-3p impaired HUVECs viability and migration in GDM by targeting PDK1, which might provide a novel perspective for the pathogenesis and underlying therapeutic target for GDM.