Pretreatment lymphocyte-monocyte ratio (LMR) as a superior predictor of short-term progression outcomes in patients with gastric cancer receiving second- and later-line apatinib regimens.

PURPOSE: Lymphocyte-monocyte ratio (LMR) has previously been used as a prognostic predictor in various solid tumors. This research aims in comparing the prognostic predictive Please check and conability of several inflammatory parameters and clinical parameters to validate further the excellent prognostic value of LMR in patients with gastric cancer treated with apatinib. METHODS: Monitor inflammatory, nutritional parameters and tumor markers. Cutoff values of the parameters concerned were identified with the X-tile program. Subgroup analysis was made via Kaplan-Meier curves, and univariate and multivariate Cox regression analyses were used to find independent prognostic factors. The nomogram of logistic regression models was constructed according to the results. RESULTS: A total of 192 patients (115 divided into training group and 77 into validation group) who received the second- or later-line regimen of apatinib were retrospectively analyzed. The optimal cutoff value for LMR was 1.33. Patients with high LMR (LMR-H) were significantly longer than those with low LMR (LMR-L) in progression-free survival (median 121.0 days vs. median 44.5 days, P < 0.001). The predictive value of LMR was generally uniform across subgroups. Meanwhile, LMR and CA19-9 were the only hematological parameters with significant prognostic value in multivariate analysis. The area under the LMR curve (0.60) was greatest for all inflammatory indices. Adding LMR to the base model significantly enhanced the predictive power of the 6-month probability of disease progression (PD). The LMR-based nomogram showed good predictive power and discrimination in external validation. CONCLUSION: LMR is a simple but effective predictor of prognosis for patients treated with apatinib.

Nomograms Combining Clinical and Imaging Parameters to Predict Recurrence and Disease-free Survival After Concurrent Chemoradiotherapy in Patients With Locally Advanced Cervical Cancer.

PURPOSES: To investigate the value of nomograms based on clinical prognostic factors (CPF), intravoxel incoherent motion diffusion weighted imaging (IVIM-DWI) and MRI-derived radiomics in predicting recurrence and disease-free survival (DFS) after concurrent chemoradiotherapy (CCRT) for locally advanced cervical cancer (LACC). METHODS: Retrospective analysis of data from 115 patients with ⅠB-ⅣA cervical cancer who underwent CCRT and had been followed up consistently. All patients were randomized 2:1 into training and validation groups. Pre-treatment IVIM-DWI parameters (ADC-value, D-value, D*-value and f-value) and pre- and post-treatment three-dimensional radiomics parameters (from axial T2WI) of primary lesions were measured. The LASSO algorithm and Logistic regression analysis were used to filter texture features and calculate radiomics score (Rad-score). Multivariate Logistic and Cox regression analysis was used to construct nomograms to predict recurrence and DFS for patients with LACC after CCRT respectively, with internal and external validation. RESULTS: External beam radiotherapy dose, f-value, pre-treatment and post-treatment Rad-score were independent prognostic factors for recurrence and DFS in patients with cervical cancer, forming Model1 and Model2, with OR values of 0.480, 1.318, 3.071, 3.200 and HR values of 0.322, 3.372, 5.138, 7.204. The area under the curve (AUC) of Model1 for predicting recurrence of cervical cancer was 0.977, with internal and external validation C-indexes of 0.977 and 0.962. The AUC for Model2 predicting disease-free survival (DFS) at 1, 3, and 5 years was 0.895, 0.888 and 0.916 respectively, with internal and external C-indexes of 0.860 and 0.892. The decision curves analysis and clinical impact curves further indicate the high predictive efficiency and stability of nomograms. CONCLUSION: The nomograms based on clinical, IVIM-DWI and radiomics parameters have high clinical value in predicting recurrence and DFS of patients with LACC after CCRT and can provide a reference for prognostic assessment and individualized treatment of cervical cancer patients.

A Nomogram Combining Neutrophil-to-Lymphocyte Ratio and D-Dimer Predicts Chemosensitivity of Oxaliplatin-Based First-Line Chemotherapy in Patients with Unresectable Advanced Gastric Cancer.

Introduction: No effective peripheral blood predictors have been establoshed for first-line chemotherapy in patients with advanced gastric cancer. In this study, a nomogram combining the neutrophil-to-lymphocyte ratio/D-dimer with gender, number of metastases, and histological grade was established to predict progression-free survival in patients with unresectable advanced gastric cancer. Methods: We retrospectively collected baseline clinical characteristics and blood parameters from 153 patients diagnosed with advanced gastric cancer that underwent oxaliplatin-based first-line chemotherapy. Kaplan-Meier analysis and Cox regression analysis were used to determine the factors associated with progression-free survival. The concordance index (C-index) and calibration curve were used to determine the prediction accuracy and discriminative ability of the nomogram as a visual complement to the prognostic score system. Results: Determined by the X-tile software, the optimal cut-off points for the neutrophil-to-lymphocyte ratio and D-dimer were 3.18 and 0.56 mg/L, respectively. Multivariate analysis identified four independent prognostic factors: two or more metastatic organs (HR: 1.562, 95% CI: 1.009-2.418, P = .046), poor differentiation (HR: 0.308, 95% CI: 0.194-0.487, P < .001), neutrophil-to-lymphocyte ratio >3.18 (HR: 1.427, 95% CI: 1.024-1.989, P = .036), and D-dimer >0.56 mg/L (HR: 1.811, 95% CI: 1.183-2.773, P = .006). Receiver operating characteristic curves showed that the combination of the neutrophil-to-lymphocyte ratio and D-dimer in the prediction model exhibited the highest predictive performance (area under the curve, 0.800). The prognostic nomogram yielded a C-index of 0.800. Decision curve analysis demonstrated that the prognostic nomogram was clinically useful. A nomogram-based risk classification system was also constructed to facilitate risk stratification of advanced gastric cancer for optimal clinical management. Conclusion: We identified the neutrophil-to-lymphocyte ratio and D-dimer level as independent prognostic factors for advanced gastric cancer. The prognostic nomogram combining the neutrophil-to-lymphocyte ratio and D-dimer level can be applied in the individualized prediction of treatment outcome in patients with advanced gastric cancer.

Combining Clinicopathology, IVIM-DWI and Texture Parameters for a Nomogram to Predict Treatment Response to Neoadjuvant Chemoradiotherapy in Locally Advanced Rectal Cancer Patients.

Objectives: This study aimed to create a nomogram for the risk prediction of neoadjuvant chemoradiotherapy (nCRT) resistance in locally advanced rectal cancer (LARC). Methods: Clinical data in this retrospective study were collected from a total of 135 LARC patients admitted to our hospital from June 2016 to December 2020. After screening by inclusion and exclusion criteria, 62 patients were included in the study. Texture analysis (TA) was performed on T2WI and DWI images. Patients were divided into response group (CR+PR) and no-response group (SD+PD) according to efficacy assessment. Multivariate analysis was performed on clinicopathology, IVIM-DWI and texture parameters for screening of independent predictors. A nomogram was created and model fit and clinical net benefit were assessed. Results: Multivariate analysis of clinicopathology parameters showed that the differentiation and T stage were independent predictors (OR values were 14.516 and 11.589, resp.; P<0.05). Multivariate analysis of IVIM-DWI and texture parameters showed that f value and Rads-score were independent predictors (OR values were 0.855, 2.790, resp.; P<0.05). In this study, clinicopathology together with IVIM-DWI and texture parameters showed the best predictive efficacy (AUC=0.979). The nomogram showed good predictive performance and stability in identifying high-risk LARC patients who are resistant to nCRT (C-index=0.979). Decision curve analyses showed that the nomogram had the best clinical net benefit. Ten-fold cross-validation results showed that the average AUC value was 0.967, and the average C-index was 0.966. Conclusions: The nomogram combining the differentiation, T stage, f value and Rads-score can effectively estimate the risk of nCRT resistance in patients with LARC.

Prognostic Significance of Platelet (PLT) and Platelet to Mean Platelet Volume (PLT/MPV) Ratio During Apatinib Second-Line or Late-Line Treatment in Advanced Esophageal Squamous Cell Carcinoma Patients.

Background: Apatinib has a certain efficacy for advanced esophageal squamous cell carcinoma (ESCC). This study aimed to investigate the prognostic significance of platelet (PLT) and platelet to mean platelet volume (PLT/MPV) ratio for advanced ESCC patients with apatinib second-line or late-line treatment. Methods: A retrospective study included 80 patients with advanced ESCC who received Apatinib ≥ 2 lines targeted therapy. We collected baseline clinical characteristics and blood parameters from the patients. Kaplan-Meier plots and univariate and multivariate analysis were used to find the factors related to progression-free survival (PFS). Results: The optimal cut-off values of PLT and PLT/MPV ratio were determined by X-tile software. Kaplan-Meier analysis demonstrated that patients in the high PLT group had better PFS than those in the low PLT group (156 d vs 80 d, P <.001), and patients in the high PLT/MPV ratio group had better PFS than those in low PLT/MPV ratio group (157 d vs 85 d, P <.001). Univariate analysis revealed pretreatment PLT and PLT/MPV ratio were significantly correlated with PFS. Multivariate analysis revealed high levels of pretreatment PLT/MPV ratio was an independent predictor of longer PFS (HR: 0.257, 95% CI: 0.089-0.743, P = .012). Conclusion: High levels of baseline PLT and PLT/MPV may indicate a better prognosis in apatinib ≥ 2 lines treatment for advanced ESCC patients.

Modification of m5C regulators in sarcoma can guide different immune infiltrations as well as immunotherapy.

Background: Recent studies have found that 5-methylcytosine (m5C) modulators are associated with the prognosis and treatment of cancer. However, the relevance of m5C modulators in sarcoma prognosis and the tumour microenvironment is unclear. Methods: We selected 15 m5C regulators and performed unsupervised clustering to identify m5C modification patterns and differentially expressed genes associated with the m5C phenotype in The Cancer Genome Atlas (TCGA) sarcomas. The extent of immune cell infiltration in different clustering groups was explored using single-sample gene set enrichment analysis and estimation algorithms. A principal component analysis algorithm-based m5C scoring protocol was performed to assess the m5C modification patterns of individual tumors. Results: We identified two distinct m5C modification patterns in the TCGA sarcoma cohort, which possess different clinical outcomes and biological processes. Tumour microenvironment analysis revealed two groups of immune infiltration patterns highly consistent with m5C modification patterns, classified as immune inflammatory and immune desert types. We constructed m5C scores and found that high m5C scores were closely associated with leiomyosarcoma and other subtypes, and were associated with poorer prognosis, lower PD-L1 expression, and poorer immunotherapy outcomes. The best application was validated against the m5C database. Conclusion: We constructed an m5C score for sarcoma based on the TCGA database and identified a poorer prognosis in the high m5c score group. The stability and good prognostic predictive power of the m5C score was verified by an external database. We found that sarcomas in the low m5C score group may have a better response to immunotherapy.

Vlasoulides A and B, a pair of neuroprotective C32 dimeric sesquiterpenes with a hexacyclic 5/7/5/5/(5)/7 carbon skeleton from the roots of Vladimiria souliei.

Vlasoulides A and B (1 and 2), a pair of epimeric C32 sesquiterpene lactone dimers, featuring a 5/7/5/5/(5)/7 ring system were isolated from the roots of Vladimiria souliei. Their chemical structures were determined by comprehensive analysis of spectroscopic data, including HRESIMS and 1D and 2D NMR spectroscopic data. Their absolute configurations were established by Mosher's method and ECD experiments. Furthermore, biological studies showed that compound 1 showed prominent neuroprotective effects against glutamate-induced neurotoxicity in PC-12 cells, with EC50 values of 13.54 ± 0.33 µM, while, the EC50 value of compound 2 is greater than 30 µM.

A new bilobalide isomer and two cis-coumaroylated flavonol glycosides from Ginkgo biloba leaves.

A new bilobalide isomer (1), together with two flavonol glycosides (2, 3), have been isolated and elucidated from the extract of Ginkgo biloba leaves. Significantly, 1 was a new sesquiterpene lactone with two lactone ring groups, both 2 and 3 were two flavonol glycosides with a same cis-coumaroylated fragment. Their chemical structures were elucidated by NMR and MS spectroscopic date and the absolute configuration of 1 was specific established by Cu-Kα X-ray crystallographic analyses. However, 1-3 showed no obvious anti-platelet aggregation activity.

Lineariifolianoids M-O, three rare sesquiterpene lactone dimers inhibiting NO production from Inula lineariifolia.

Three rare squiterpene lactone dimers lineariifolianoids M-O (1-3) were isolated from Inula lineariifolia for the first time. Their structures and absolute configuration were established on the basis of by NMR and MS spectroscopic data and X-ray crystallography. Furthermore, those three compounds exhibited significant inhibitory activity against LPS-induced NO production in RAW 264.7 macrophages with IC50 values of 1.421, 1.087 and 1.243 µM, respectively.