Progress on immuno-microenvironment and immune-related therapies in patients with pseudomyxoma peritonei.

Pseudomyxoma peritonei (PMP) is an indolent malignant syndrome. The standard treatment for PMP is cytoreductive surgery plus intraperitoneal hyperthermic chemotherapy (CRS + HIPEC). However, the high recurrence rate and latent clinical symptoms and signs are major obstacles to further improving clinical outcomes. Moreover, patients in advanced stages receive little benefit from CRS + HIPEC due to widespread intraperitoneal metastases. Another challenge in PMP treatment involves the progressive sclerosis of PMP cell-secreted mucus, which is often increased due to activating mutations in the gene coding for guanine nucleotide-binding protein alpha subunit (GNAS). Consequently, the development of other PMP therapies is urgently needed. Several immune-related therapies have shown promise, including the use of bacterium-derived non-specific immunogenic agents, radio-immunotherapeutic agents, and tumor cell-derived neoantigens, but a well-recognized immunotherapy has not been established. In this review the roles of GNAS mutations in the promotion of mucin secretion and disease development are discussed. In addition, the immunologic features of the PMP microenvironment and immune-associated treatments are discussed to summarize the current understanding of key features of the disease and to facilitate the development of immunotherapies.

Incidence and prognostic nomogram for resected non-small cell neuroendocrine tumor: A population-based respective study in China and the SEER database.

Background: Pulmonary neuroendocrine tumors, including small cell lung cancer (SCLC) and non-small cell neuroendocrine tumor (NSCLC-NET), have obvious heterogeneity. The comparison between SCLC and NSCLC-NET, and prognostic nomogram of resected NSCLC-NET have not been performed. Methods: We retrieved data from SEER database. The incidence and prognostic factors were compared between SCLC and NSCLC-NET. By Cox regression, we constructed prognostic nomogram of resected NSCLC-NET. The nomogram was evaluated by ROC, calibration plot and decision curve analysis (DCA) and compared with 8th TNM staging system. A Chinese cohort was used for external validation. Results: The age-adjusted incidence of SCLC declined after 1991 but the incidence of NSCLC-NET continuously rose. Patients with typical carcinoid had the best prognosis in both overall survival and lung cancer specific survival, followed by atypical carcinoid, large cell neuroendocrine tumor and SCLC after operation. Patients receiving sleeve resection in NSCLC-NET had longer survival but segmental resection was more recommended in SCLC. High-smoking index was associated with worse overall survival in both SCLC and NSCLC-NET. Histological subtype, age, surgery type, N, M stage and chemotherapy were independent prognostic factors and used to construct prognostic nomogram of resected NSCLC-NET. The nomogram performed well with good discrimination, calibration and clinical usefulness, which was validated by a Chinese cohort (1, 3, 5-year AUC: SEER cohort 0.873, 0.901, 0.875; Chinese cohort 0.867, 0.892, 0.874). Compared to the 8th staging system, the nomogram had higher C-index (0.87 vs 0.728, P < 0.001), clinical usefulness, increasing AUC value over time and improved 68%. Conclusion: The prognostic nomogram of resected NSCLC-NET performed better than the 8th TNM staging system. It may have certain value in risk stratification and survival prediction of patients with resected NSCLC-NET and help clinicians to take measures for high-risk patients in advance.

Dynamic Seed Emission, Dispersion, and Deposition from Horseweed (Conyza canadensis (L.) Cronquist).

The wide dispersion of glyphosate-resistant (GR) horseweed (Conyza canadensis (L.) Cronquist: synonym Erigeron canadensis L.) biotypes has been reported in agricultural fields in many states. GR traits may be transferred through seeds or pollen from fields with existing GR horseweed prevalence to surrounding fields. Understanding seed production and movement is essential when characterizing and predicting the spread of GR horseweed, yet a literature review indicates that there are no experimental data on dynamic (hourly) seed production and horizontal dispersion and deposition from horseweed. To obtain the dynamic data, two field experiments were performed, one in Illinois and one in Tennessee, USA in 2013 and 2014, respectively. Seed concentration and deposition along with atmospheric conditions were measured with samplers in the Illinois (184 m × 46 m, natural plants, density = 9.5 plants/m2) and Tennessee (6 m × 6 m, cultivated plants, density = 4 plants/m2) experimental fields and their surrounding areas along the downwind direction up to 1 km horizontally and 100 m vertically in the Illinois field and up to 32 m horizontally and 5 m vertically in the Tennessee field. The dynamic seed source strengths (emission rates) measured during two entire seed-shedding seasons were reported, ranging from 0 to 0.41 grains/plant/s for Illinois and ranging from 0 to 0.56 grains/plant/s for Tennessee. The average total seed production was an estimated 122,178 grains/plant for the duration of the Illinois experiment and 94,146 grains/plant for Tennessee. Seeds trapped by Rotorod samplers attached beneath two balloons in the Illinois field experiment were observed at heights of 80 to 100 m, indicating the possibility of long-distance transport. Normalized (by source data) seed deposition with distance followed a negative power exponential function. Seed emission and transport were affected mainly by wind speed. This study is the first to investigate dynamic horseweed seed emission, dispersion, and deposition for an entire seed-shedding season. The results will aid in the management of GR horseweed. The potential for regional effects of horseweed invasion may require all farmers to control horseweed in their individual fields.

The Prognostic Value of Multiple Systemic Inflammatory Biomarkers in Preoperative Patients With Non-small Cell Lung Cancer.

Introduction: The preoperative inflammatory and nutrient status of the patient are closely correlated to the outcome of surgery-based treatment for non-small cell lung cancer (NSCLC). We aimed to investigate the prognostic value of inflammation and nutrient biomarkers in preoperative patients with non-small cell lung cancer (NSCLC) by constructing a prognostic predictive model. Methods: We retrospectively studied 995 patients with NSCLC who underwent surgery in the Shandong Provincial Hospital and randomly allocated them into the training and validation group with a ratio of 7:3. We then compared their prognostic performance and conducted univariate Cox analyses with several clinicopathological variables. Based on the performance of the receiver operating characteristic (ROC) curves and decision curves analysis (DCA), the prognostic model was optimized and validated. Result: The median overall overall survival (OS) of patients was 74 months. Univariate Cox analysis indicated that fifteen inflammatory biomarkers were significantly correlated with OS (p < 0.100). Multivariate Cox analysis revealed that the model incorporating grade, age, stage, basophil-to-lymphocyte ratio (BLR, ≥0.00675 vs. < 0.00675) and albumin-to-globulin ratio (AGR, ≥1.40 vs. <1.40) showed the maximum area under the curve (AUC, 0.744). The C-index in the training and validation group was 0.690 and 0.683, respectively. The 3-year integrated discrimination improvement (IDI) compared to TNM (Tumor Node Metastasis) stage was 0.035 vs. 0.011 in the training and validation group, respectively. Conclusions: Lower AGR, ANRI, and higher BLR were associated with a worse outcome for patients with NSCLC. We constructed a prognostic nomogram with risk stratification based on inflammatory and nutrient biomarkers. The discrimination and calibration abilities of the model were evaluated to confirm its validity, indicating the potential utility of this prognostic model for clinical guidance.

Gender specific eRNA TBX5-AS1 as the immunological biomarker for male patients with lung squamous cell carcinoma in pan-cancer screening.

As an innate feature of human beings, gender differences have an influence on various biological phenotypes, yet it does not attract enough attention in genomics studies. The prognosis of multiple carcinomas usually exhibits a favorable ending for female patients, but the neglect of gender differences can cause serious bias in survival analysis. Enhancer RNAs (eRNAs) are mostly downstream of androgens or estrogen. The present study was aimed to screen eRNAs in patients with non-small-cell lung cancer. The findings revealed that eRNA TBX5-AS1 was expressed differently between female and male patients. Meanwhile, its prognostic significance appeared only in male patients with squamous cell carcinoma (SCC) type. The Gene Set Enrichment Analysis proved that the expression level of TBX5-AS1 increased following the activation of the androgen signaling pathway. In pan-cancer analysis, the prognostic prediction based on gender grouping obtained more meaningful results, and the synergy between TBX5-AS1 and its homologous target was more consistent. Furthermore, immunity variations between sexes prompted us to explore the role that TBX5-AS1 played in tumor microenvironment and immunotherapy. The robust evidence proved that male patients with high expression of TBX5-AS1 possessed a malignant immune microenvironment and urgently needed immune checkpoint inhibitor treatment. In conclusion, TBX5-AS1 may be one of the strongest candidates to predict prognosis for male patients with SCC and provide a reference for immunotherapy.

Biological calcium carbonate with a unique organic-inorganic composite structure to enhance biochar stability.

Biochar stability is a key factor affecting the efficiency of soil carbon sequestration. Mineral calcium carbonate (M-CaCO3) can enhance the stability of biochar, and the mechanism has been extensively studied; however, similar studies on biological calcium carbonate (Bio-CaCO3), another natural form of calcium carbonate, are lacking. In this work, Bio-CaCO3 was used as an additive to explore the mechanism by which it enhances the stability of biochar. The results showed that Bio-CaCO3 improved the stability of biochar at pyrolysis temperatures ranging from 250 to 700 °C, and the enhancement effects increased upon increasing the pyrolysis temperature. The enhancement effects of M-CaCO3 were better at lower temperatures (250 and 400 °C) while Bio-CaCO3 was better at higher temperatures (550 and 700 °C). Mechanistic studies showed that the enhanced stability of Bio-CaCO3 at 250 °C was due to the fact that the inorganic component in Bio-CaCO3 promoted the deoxidation of the carbon matrix and the aromatization of aliphatic carbon at 400 °C. The reasons for the increased stability using Bio-CaCO3 at high temperatures included two mechanisms. One is that the inorganic components in Bio-CaCO3 promoted the aromatization of the carbon matrix. The other is that the unique organic nitrogen-containing functional groups in Bio-CaCO3 underwent dimerization and cyclization with the organic carbon components in biomass to form a more stable pyridinic-N structure. This work provides novel ideas for enhancing biochar stability using Bio-CaCO3.

Is Preoperative Fibrinogen Associated with the Survival Prognosis of Gastric Cancer Patients? A Multi-centered, Propensity Score-Matched Retrospective Study.

BACKGROUND: The prognostic significance of preoperative plasma fibrinogen in patients with operable gastric cancer remains under debate. This study aimed to elucidate the prognostic value of fibrinogen in gastric cancer patients underwent gastrectomy. METHODS: A total of 4351 patients with gastric cancer collected from three comprehensive medical centers were retrospectively evaluated. Patients were categorized by minimum P value using X-tile, while the baseline confounders for fibrinogen was balanced through propensity score matching (PSM). The relationships between fibrinogen and other clinicopathologic features were evaluated, and nomogram was constructed to assess its prognostic improvement compared with TNM staging system. RESULTS: Fibrinogen was significantly correlated with macroscopic type, tumor differentiation, tumor size, and T and N stage. The factors, fibrinogen and T stage as well as N stage, were identified to be independent prognostic factors after PSM. Nomogram based on fibrinogen demonstrated a smaller Akaike information criterion (AIC) and a larger concordance index (C-index) than TNM staging system, illustrating that fibrinogen might be able to improve the prognostic accuracy. CONCLUSIONS: Preoperative plasma fibrinogen levels in gastric cancer patients were significantly correlated with tumor progression, which could be regarded as a reliable marker for survival prognostic prediction.