Advanced renal pelvis carcinoma patient with an ERBB2 insertion mutation: a case report.

The prognosis of renal pelvis cancer is poor and therapeutic options are limited, especially for patients with advanced disease. In this report, we present a case of advanced renal pelvis carcinoma in a male patient in his 60s, characterized by an activating mutation in ERBB2. Clinical evaluation resulted in a pathological diagnosis of renal pelvis carcinoma with liver metastasis. Immunohistochemistry staining results suggested that CK, P63, and PAX8 were positively expressed, while Sy, CK7, CK20, S100, PAX8, and HEP1 were negatively expressed. Furthermore, next-generation sequencing results showed an activating mutation in the ERBB2 gene. The patient initially received a trastuzumab-based combination therapy, which led to a significant reduction in ERBB2 mutation frequency and a stable condition after three treatment cycles. However, following continuous treatment for 4 months, the patient developed drug resistance that resulted in disease relapse. Subsequently, the patient received apatinib treatment, but the therapeutic response was not satisfactory. The patient's condition underwent rapid deterioration and he ultimately succumbed to the disease. This case underscores the potential benefit of trastuzumab for treating ERBB2-mutated advanced renal pelvis cancer, but further highlights that overcoming drug resistance remains a crucial challenge for long-term efficacy.

RNF43 is associated with genomic features and clinical outcome in BRAF mutant colorectal cancer.

Background: Colorectal cancer (CRC) patients with BRAF mutation have very poor prognosis. It is urgent to search for prognostic factors of BRAF mutant CRC. RNF43 is a ENF ubiquitin ligase of Wnt signaling. Mutation of RNF43 has been observed frequently in various types of human cancers. However, few studies have evaluated the role of RNF43 in CRC. The present study aimed to explore the impact of RNF43 mutations on molecular characteristics and prognosis in BRAF mutant CRC. Methods: Samples of 261 CRC patients with BRAF mutation were retrospectively analyzed. Tumor tissue and matched peripheral blood samples were collected and subjected to targeted sequencing with a panel of 1021 cancer-related genes. The association of molecular characteristics and survival in patients were then analyzed. 358 CRC patients with BRAF mutation from the cBioPortal dataset were used for further confirmation. Results: This study was inspired by a CRC patient with BRAF V600E and RNF43 co-mutation, who achieved a best remission of 70% and a progression free survival (PFS) of 13 months. Genomic analysis indicated that RNF43 mutation affected the genomic characteristics of patients with BRAF mutation, including microsatellite instability (MSI), tumor mutation burden (TMB) and the proportion of common gene mutations. Survival analysis showed that RNF43 mutation was a predictive biomarker for better PFS and OS in BRAF mutant CRC. Conclusion: Collectively, we identified that RNF43 mutations were correlated with favorable genomic features, resulting in a better clinical outcome for BRAF mutant CRC patients.

Natural gas spot price prediction research under the background of Russia-Ukraine conflict - based on FS-GA-SVR hybrid model.

The ongoing Russia-Ukraine conflict has led to significant upheaval in the worldwide natural gas sector. Accurate natural gas price forecasting, as an essential tool for mitigating market uncertainty, plays a crucial role in commodity trading and regulatory decision-making. This study aims to develop a hybrid forecasting model, the FS-GA-SVR model, which integrates feature selection (FS), genetic algorithm (GA), and support vector regression (SVR) to investigate Henry Hub natural gas price prediction amidst the Russia-Ukraine conflict. The results show that: (1) The feature selection automates model input variable selection, decreasing the time required while improving the model's accuracy. (2) The use of genetic algorithm for selecting support vector regression hyperparameters significantly improves the accuracy of natural gas price predictions. The algorithm leads to a decrease of approximately 70% in measurement indicators. (3) During the Russia-Ukraine conflict, the FS-GA-SVR hybrid model demonstrates more consistent and accurate predictions for natural gas spot prices than the base SVR model. This study serves as a valuable theoretical reference for energy policymakers and natural gas market investors worldwide, supporting their ability to anticipate fluctuations in natural gas prices.

Clinical and biomarker analyses of sintilimab plus gemcitabine and cisplatin as first-line treatment for patients with advanced biliary tract cancer.

The prognosis of biliary tract cancer (BTC) remains unsatisfactory. This single-arm, phase II clinical trial (ChiCTR2000036652) investigated the efficacy, safety, and predictive biomarkers of sintilimab plus gemcitabine and cisplatin as the first-line treatment for patients with advanced BTCs. The primary endpoint was overall survival (OS). Secondary endpoints included toxicities, progression-free survival (PFS), and objective response rate (ORR); multi-omics biomarkers were assessed as exploratory objective. Thirty patients were enrolled and received treatment, the median OS and PFS were 15.9 months and 5.1 months, the ORR was 36.7%. The most common grade 3 or 4 treatment-related adverse events were thrombocytopenia (33.3%), with no reported deaths nor unexpected safety events. Predefined biomarker analysis indicated that patients with homologous recombination repair pathway gene alterations or loss-of-function mutations in chromatin remodeling genes presented better tumor response and survival outcomes. Furthermore, transcriptome analysis revealed a markedly longer PFS and tumor response were associated with higher expression of a 3-gene effector T cell signature or an 18-gene inflamed T cell signature. Sintilimab plus gemcitabine and cisplatin meets pre-specified endpoints and displays acceptable safety profile, multiomics potential predictive biomarkers are identified and warrant further verification.

Therapeutic Effect and Prognosis of Biliary Tract Tumor Transformation.

Biliary tract tumor is a common malignant disease in clinical practice. Its incidence rate and mortality rate are high, which seriously endangers the health of the people. At present, gastrointestinal surgery is mainly used to treat patients at home and abroad. This paper discusses the main risk factors of biliary tract cancer transformation, analyzes its prognostic characteristics and clinical efficacy, and compares them by comprehensive evaluation methods such as observation group control method, blood routine examination and treatment. The results are as follows: the postoperative adverse reactions in the control group are more obvious than those in the experimental group. There were no obvious clinical manifestations or adverse reactions in the experimental group. The therapeutic effect of biliary tumor transformation can effectively help patients improve their quality of life. Through the prognosis recovery of biliary tract tumor transformation treatment, the health level of patients in the experimental group was higher than that in the control group.

Feasibility of peaking carbon emissions of the power sector in China's eight regions: decomposition, decoupling, and prediction analysis.

Carbon emissions in the power sector are an important part of China's total carbon emissions and have a significant impact on whether China can achieve the 2030 carbon peak target. Based on the three perspectives of decomposition, decoupling, and prediction, this paper studies the feasibility of carbon emission peaks in eight major regional power sectors in China. First, the generalized Divisia index model (GDIM) is used to decompose the carbon emissions of the eight regional power sectors, and the driving factors and their effects on carbon emissions in the power sector of each region are compared. Then, the decoupling index based on the generalized Divisia index model (GDIM-D) is used to study the decoupling relationship between the carbon emissions of the eight regional power sectors and economic growth. Finally, the carbon emissions and decoupling indices of the power sector from 2017 to 2030 are predicted. The results show the following. First, the gross domestic product (GDP) and output scale are the main factors contributing to the carbon emissions of the eight regional power sectors. The carbon intensity of the power sector in GDP (C/G) and output carbon intensity(C/E) are the main factors that contribute to the reduction. Second, the carbon emissions of the southern coast, the middle Yellow River, and the Southwest peaked in 2013 and have been decoupled from economic growth, while those in the other regions have not peaked or decoupled. Third, if the carbon emissions of the power sector in the Northeast, northern coast, eastern coast, middle Yangtze River, and Northwest reach a peak in 2030, they will face many emission reduction pressures. This paper provides a reference for studying the carbon emissions of China's regional power sectors and their relationship with economic growth and has important implications for peak carbon emissions at the national level.

Interregional carbon compensation cost forecast and priority index calculation based on the theoretical carbon deficit: China as a case.

Interregional carbon compensation is an important part of ecological compensation. An accurate accounting of the interregional carbon compensation cost is the foundation for establishing a carbon compensation mechanism. Corresponding to the actual carbon deficit, this paper advances, for the first time, the concept of the theoretical carbon deficit and, improves the calculation method of the interregional carbon compensation cost based on the theoretical carbon deficit. Additionally, this paper, forecasts the carbon compensation cost among 30 provinces in China from 2017 to 2026 by using the Stochastic Impacts by Regression on Population, Affluence, and Technology (STIRPAT) model and the gray prediction model GM (1, 1). Finally, this paper calculates the priority indexes of the carbon compensation among provinces. The results indicate that, first, from 2017 to 2026, the carbon emissions and carbon absorption in 30 provinces in China are generally on the rise, and the increase rate of carbon absorption is less than the increase rate of carbon emissions. Second, from 2017 to 2026, China's carbon compensation cost payment provinces and carbon compensation cost recipient provinces do not change position, and the flow of the carbon compensation cost is stable. The carbon compensation cost payment provinces are mainly located in the central and eastern regions, and the carbon compensation cost recipient provinces are mainly located in the northwestern region. Third, the priority indexes of carbon compensation in China's provinces are all small and declining, and the carbon compensation among regions has little impact on regional economic development. The research results in this paper can provide a reasonable reference for the cost calculation of interregional carbon compensation and the establishment and improvement of an interregional carbon compensation mechanism.

Optimization of an amplification protocol for misfolded proteins by using relaxed control.

We investigate an optimal control problem which arises in the optimization of an amplification technique for misfolded proteins. The improvement of this technique may play a role in the detection of prion diseases. The model consists in a linear system of differential equations with a nonlinear control. The appearance of oscillations in the numerical simulations is understood by using the Perron and Floquet eigenvalue theory for nonnegative irreducible matrices. Then to overcome the unsolvability of the optimal control, we relax the problem. In the two dimensional case, we solve explicitly the optimal relaxed control problem when the final time is large enough.

Transfection of chimeric anti-CD138 gene enhances natural killer cell activation and killing of multiple myeloma cells.

Reprogramming of NK cells with a chimeric antigen receptor (CAR) proved an effective strategy to increase NK cell reactivity and recognition specificity toward tumor cells. To enhance the cytotoxicity of NK cells against CD138-positive multiple myeloma (MM) cells, we generated genetically modified NK-92MI cells carrying a CAR that consists of an anti-CD138 single-chain variable fragment (scFv) fused to the CD3ζ chain as a signaling moiety. The genetic modification through a lentiviral vector did not affect the intrinsic cytolytic activity of NK-92MI toward human erythroleukemic cell line K562 cells or CD138-negative targets. However, these retargeted NK-92MI (NK-92MI-scFv) displayed markedly enhanced cytotoxicity against CD138-positive human MM cell lines (RPMI8226, U266 and NCI-H929) and primary MM cells at various effector-to-target ratios (E:T) as compared to the empty vector-transfected NK-92MI (NK-92MI-mock). In line with the enhanced cytotoxicity of NK-92MI-scFv, significant elevations in the secretion of granzyme B, interferon-γ and proportion of CD107a expression were also found in NK-92MI-scFv in response to CD138-positive targets compared with NK-92MI-mock. Most importantly, the enhancement in the cytotoxicity of NK-92MI-scFv did not attenuate with 10Gy-irradiation that sufficiently blocked cell proliferation. Moreover, the irradiated NK-92MI-scFv exerted definitely intensified anti-tumor activity toward CD138-positive MM cells than NK-92MI-mock in the xenograft NOD-SCID mouse model. This study provides the rationale and feasibility for adoptive immunotherapy with CD138-specific CAR-modified NK cells in CD138-positive plasmacytic malignancies, which potentially further improves remission quality and prolongs the remission duration of patients with MM after upfront chemotherapy.