Present situation and prospect of immunotherapy for unresectable locally advanced esophageal cancer during peri-radiotherapy.

Four major studies (Checkmate577, Keynote-590, Checkmate649 and Attraction-4) of locally advanced esophageal cancer published in 2020 have established the importance of immunotherapy, represented by anti-programmed death protein (PD)-1 in postoperative adjuvant treatment and advanced first-line treatment of locally advanced or advanced esophageal cancer and esophagogastric junction cancer, from the aspects of proof of concept, long-term survival, overall survival rate and progression-free survival. For unresectable or inoperable nonmetastatic esophageal cancer, concurrent radiotherapy and chemotherapy is the standard treatment recommended by various guidelines. Because its curative effect is still not ideal, it is necessary to explore radical radiotherapy and chemotherapy in the future, and it is considered to be promising to combine them with immunotherapeutic drugs such as anti-PD-1. This paper mainly discusses how to combine radical concurrent radiotherapy and chemotherapy with immunotherapy for unresectable local advanced esophageal cancer.

Prognostic nutritional index predicts the prognosis of patients with advanced esophageal cancer treated with immune checkpoint inhibitors: a retrospective cohort study.

Background: Immune checkpoint inhibitors (ICIs) play an important role in the treatment of esophageal cancer (EC). However, their efficacy is variable, and there are still no effective and convenient biomarkers to identify and assess their efficacy. In recent years, programmed cell death-ligand 1 (PD-L1) expression, tumor mutation burden (TMB) and other commonly used biomarkers still cannot meet clinical needs. PNI is easy to obtain and its predictive value for the prognosis of immunotherapy has been confirmed in many cancer species, but the relationship between PNI and the efficacy of immunotherapy for esophageal cancer is still unclear. Therefore, this study aims to explore the predictive value of PNI in advanced esophageal cancer treated with ICIs. Methods: The clinicopathological features of 78 patients with advanced EC who received immunotherapy in the 900th Hospital of the Joint Logistics Team from September 2018 to May 2022 were retrospectively analyzed. The laboratory test results within 10 days prior to the start of ICI treatment were recorded, including absolute lymphocyte count and albumin (ALB) level. Meanwhile, the effects of pre-treatment prognostic nutritional index (PNI) and body mass index (BMI) on the overall survival (OS) and progression-free survival (PFS) in patients with advanced EC were analyzed. Results: The median age of the enrolled patients was 58 years, and 38 patients (48.7%) received second-or-later-line therapy. The median progression-free survival (mPFS) and median overall survival (mOS) were 7.4 months and 13 months, respectively. The mPFS and mOS were 8.8 months and 15 months, respectively, in the high baseline PNI subgroup, which were significantly higher than those in the low baseline PNI subgroup (4.7 and 8.2 months, respectively; both P<0.05). Multivariate regression analysis showed that low baseline PNI was an independent predictor of poor PFS [hazard studio (HR) =0.35, 95% CI: 0.14-0.85, P=0.020) and poor OS (HR =0.41, 95% CI: 0.17-0.99, P=0.047) and treatment line was an independent predictor of PFS. Baseline BMI was not significantly associated with prognosis. Conclusions: PNI is a simple and effective biomarker for predicting the prognosis of immunotherapy in patients with advanced EC, although further prospective studies are warranted.

Real-world experience with anti-programmed cell death protein 1 immunotherapy in patients with esophageal cancer: A retrospective single-center study.

The "real-world" data of programmed cell death protein 1 (PD-1) inhibitors in esophageal cancer (EPC) are still an unmet medical need, including the clinical efficacy and safety. Seventy-seven EPC data were studied retrospectively; the progression-free survival (PFS), risk factors (clinical stages larger than stage II, metastatic sites larger than 2, treatment lines larger than the first line, previous surgical treatment, combined positive score [CPS] expression, etc.), and the safety were analyzed. The median PFS for all patients was 7.2 months, clinical stage > stage II; the number of treatment lines > first line was significantly correlated with prognosis (all P < 0.05). Subgroup analysis showed that the median PFS of patients with clinical stage ≤ II was better; the results were the same for the patients with ≤2 metastatic sites, first-line PD-1 inhibitors, and not previously received radical surgery (all P < 0.05). Meanwhile, the incidence of adverse events (AEs) of varying degrees was 25.97% (20/77) in 20 patients and 6.49% (5/77) of grade 3/4 AEs. The highest AE was myelosuppression (15.58%), followed by liver function injury (7.79%). In addition, ≥2 lines of treatment and >2 metastatic sites predicted poor outcomes for patients with EPC who had failed first-line therapy or progressed with the combined immunotherapy and chemotherapy treatment strategy (all P < 0.05).

Animal-Protein-Based and Synthetic-Based Foamed Mixture Lightweight Soil Doped with Bauxite Tailings: Macro and Microscopic Properties.

In order to explore the effect of the foaming agent type on the properties of foamed mixture lightweight soil mixed with bauxite tailings (FMLSB), low-density (437.5 kg/m3 and 670 kg/m3) and high-density (902.5 kg/m3 and 1170 kg/m3) FMLSB were prepared using protein-based and synthetic-based foaming agents (AF and SF, respectively). The foam stability, micro characteristics, compressive strength, fluidity, and volume of water absorption of the FMLSB were investigated. The results showed that the foam made from AF had better strength and stability compared to SF. The internal pore sizes of both AF- and SF-FMLSB at low density were large, but at high density the internal pore sizes and area porosity of AF-FMLSB were smaller than those of SF-FMLSB. In terms of compressive strength, the compressive strength of AF-FMLSB was improved by 17.5% to 43.2% compared to SF-FMLSB. At low density, the fluidity of AF- and SF-FMLSB is similar, while at high density the fluidity of AF-FMLSB is much higher than that of SF-FMLSB. In addition, the stable volume of water absorption of SF-FMLSB is smaller than that of AF-FMLSB at low density, and the corresponding water resistance is better, but the situation is reversed at high density.

[Expression and significance of Treg/Th17 and CD4+/CD8+ T lymphocytes in experimental periodontitis in rats].

PURPOSE: To explore the expression of helper T cell 17/regulatory T cell (Th17/Treg) and CD4+/CD8+ T lymphocyte in experimental periodontitis in rats, and analyze its clinical significance. METHODS: Twenty SPF male SD rats were randomly divided into experimental group (inoculate Porphyromonas gingivalis suspension into gingival sulcus) and control group, with 10 rats in each group. The experimental group was smeared with Porphyromonas gingivalis suspension every other day within 1 week after operation, and the two groups were caged for 8 weeks. After the rats were sacrifical under anesthesia, the jaw tissue of the left maxillary second molar was stained with methylene blue to observe and measure the loss of alveolar bone (ABL). Hematoxylin-eosin (H-E) staining was used to observe the histopathological changes of the jaw. Rat peripheral blood mononuclear cells (PBMC) and T cells were isolated and cultured, Treg, Th17 cells and CD4+, CD8+ T lymphocytes in peripheral blood were detected by flow cytometry. The levels of serum interleukin-17(IL-17), IL-10 and IL-4, INF-γ were detected by enzyme-linked immunosorbent assay (ELISA). Expression changes of retinoic acid related orphan nuclear receptor (RORγt), forkhead wing like transcription factor 3 (Foxp3) and gap junction protein(Cx40) in jaw tissue were detected by Western blot. The data were statistically analyzed by SPSS 19.0 software package. RESULTS: Compared with the control group, ABL, peripheral blood Th17 ratio, Th17/Treg ratio, CD4+ ratio, CD4+/CD8+ T lymphocyte ratio, serum IL-17, IL-10 and IL-4 level, Foxp3 and Cx40 protein in jaw tissue were signifinantly increased in the experimental group(P<0.05), while Treg ratio, INF-γ, RORγt protein in jaw tissue significantly decreased(P<0.05) in the experimental group. CONCLUSIONS: Imbalance of Treg/Th17 and CD4+/CD8+ T lymphocytes leads to the abnormal high expression of inflammatory factors IL-17, IL-10 and IL-4, which may be closely related to the pathogenesis of experimental periodontitis.

High Tiam1 expression predicts positive lymphatic metastasis and worse survival in patients with malignant solid tumors: a systematic review and meta-analysis.

BACKGROUND: Many studies have explored the prognostic value of T-cell lymphoma invasion and metastasis inducing factor 1 (Tiam1) and its association with lymphatic metastasis in malignant solid tumors, but the conclusions remain controversial. Therefore, we performed a meta-analysis to systematically assess the prognostic value of Tiam1 expression and its association with lymphatic metastasis in malignant solid tumors. METHODS: We searched eligible studies in PubMed, Web of Science and EMBASE databases (from inception up to October 2018). The combined HR with 95% CI was used to estimate the prognostic value of Tiam1 expression. The correlation between Tiam1 expression and lymphatic metastasis was assessed using the combined odds ratio (OR) with 95% CI. RESULTS: A total of 17 studies with 2,228 patients with solid tumors were included in this meta-analysis. The overall estimated results showed that high Tiam1 expression was significantly associated with shorter overall survival (HR= 2.08, 95% CI: 1.62-2.68, P<0.01), and disease-free survival (HR = 1.86, 95% CI: 1.49-2.32, P<0.01). Besides, we also found that there was a close relationship between high Tiam1 expression and positive lymphatic metastasis (OR=2.63; 95% CI: 1.79-3.84, P<0.01). CONCLUSION: High Tiam1 expression was significantly associated with shorter survival and positive lymphatic metastasis in patients with malignant solid tumors. Therefore, Tiam1 may be a promising prognostic biomarker and an effective therapeutic target for malignant solid tumors.