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Chemotherapeutic drugs are the mainstay of treatment on mid-advanced tumors. In recent years, more and more studies have shown that chemotherapeutic drugs also have immunomodulatory effects. Some chemotherapeutic drugs can enhance anti-tumor immunity by inducing tumor cell immunogenic cell death or performing "immunogenic modulation". In addition, chemotherapeutic drugs can also act on immune cells and even the intestinal flora. A number of clinical trials of chemotherapy combined with immune checkpoint inhibitors are currently underway. This article focuses on the immunomodulatory effect of chemotherapeutic drugs, as well as the potential of chemotherapy combined with ICI on cancer, to provide guidance for the clinical application of chemotherapeutic drugs.

Objective To analyze the expression of CEA, CA199 and CA724 in patients with urachal carcinoma, and to explore their correlation with disease diagnosis, staging, progression and treatment response. Methods Twelve urachal carcinoma patients with related tumor markers were selected as the research object and further divided into distant metastasis group (n=4) and non-metastasis group (n=8). We selected 40 patients with urothelial carcinoma of the bladder and 40 healthy people as the control groups. SPSS 23.0 and MedCalc 19 were used for data analysis. Results Twelve patients with urachal carcinoma were all adenocarcinomas. The expression of CEA in the urachal carcinoma group was significantly higher than that in urothelial carcinoma group and healthy control group (P=0.01). The positive rate of CA724 in the distant metastasis group was significantly higher than that in the non-metastasis group (75% vs. 0, P=0.018). In single test, CEA diagnosed urachal carcinoma with the highest AUC of 0.750 and 95%CI of 0.584 to 0.916. The AUC detected by the combination of both CEA and CA724 or three tumor markers were all larger than the AUC detected by single test, but without statistical significance (0.817 vs. 0.805, P=0.8509). Conclusion The expression of CEA in patients with urachal carcinoma is significantly increased. CA724 can be used as a predictor of distant metastasis of urachal carcinoma, and the combination detection of CA724 and CEA can provide an effective reference for the clinical diagnosis of urachal cancer.

Abstract Background The development of vectors for cell-specific gene delivery is a major goal of gene therapeutic strategies. Transferrin receptor (TfR) is an endocytic receptor and identified as tumor relative specific due to its overexpression on most tumor cells or tissues, and TfR binds and intakes of transferrin-iron complex. We have previously generated an anti-TfR single-chain variable fragments of immunoglobulin (scFv) which were cloned from hybridoma cell line producing antibody against TfR linked with a 20 aa-long linker sequence (G4S)4. In the present study, the anti-TfR single-chain antibody (TfRscFv) was fused to DNA-binding domain of the yeast transcription factor GAL4. The recombinant fusion protein, designated as TfRscFv-GAL4, is expected to mediate the entry of DNA-protein complex into targeted tumor cells. Results Fusion protein TfRscFv-GAL4 was expressed in an E. coli bacterial expression system and was recovered from inclusion bodies with subsequent purification by metal-chelate chromatography. The resulting proteins were predominantly monomeric and, upon refolding, became a soluble biologically active bifunctional protein. In biological assays, the antigen-binding activity of the re-natured protein, TfRscFv-GAL4, was confirmed by specific binding to different cancer cells and tumor tissues. The cell binding rates, as indicated by flow cytometry (FCM) analysis, ranged from 54.11% to 8.23% in seven different human carcinoma cell lines. It showed similar affinity and binding potency as those of parent full-length mouse anti-TfR antibody. The positive binding rates to tumor tissues by tissue microarrays (TMA) assays were 75.32% and 63.25%, but it showed weakly binding with hepatic tissue in 5 cases, and normal tissues such as heart, spleen, adrenal cortex blood vessel and stomach. In addition, the re-natured fusion protein TfRscFv-GAL4 was used in an ELISA with rabbit anti-GAL4 antibody. The GAL4-DNA functional assay through the GAL4 complementary conjugation with the GAL4rec-GFP-pGes plasmid to verify the GLA4 activity and GAL4rec-recognized specificity functions. It also shows the complex, TfRscFv-GAL4-GAL4rec-GFP-pGes, could be taken into endochylema to express the green fluorescent protein (GFP) with 8 to 10-fold transfection efficiency. Conclusions Results of our study demonstrated that the biofunctianality of genetically engineered fusion protein, TfRscFv-GAL4, was retained, as the fusion protein could both carry the plasmid of GAL4rec-pGes and bind TfR on tumour cells. This product was able to transfect target cells effectively in an immuno-specific manner, resulting in transient gene expression. This protein that can be applied as an effective therapeutic and diagnostic delivery to the tumor using endogenous membrane transport system with potential widespread utility.

Calcium oxalate (CaOx) crystals induce renal tubular epithelial cell injury and subsequent nephropathy. However, the underlying mechanisms remain unclear. In the present study, single‐cell transcriptome sequencing is performed on kidney samples from mice with CaOx nephrocalcinosis. Renal proximal tubular cells are identified as the most severely damaged cell population and are accompanied by elevated ferroptosis. Further studies demonstrated that sirtuin1 (Sirt1) effectively reduced ferroptosis and CaOx crystal‐induced kidney injury in a glutathione peroxidase 4 (GPX4)‐dependent manner. Mechanistically, Sirt1 relies on peroxisome proliferator‐activated receptor gamma coactivator 1α (PGC‐1α) to promote resistance to ferroptosis in the tubular epithelium, and PGC‐1α can recruit nuclear factor erythroid 2‐related factor 2 (NRF2) to the promoter region of GPX4 and co‐activate GPX4 transcription. This work provides new insight into the mechanism of CaOx crystal‐induced kidney injury and identifies Sirt1 and PGC‐1α as potential preventative and therapeutic targets for crystal nephropathies. [ABSTRACT FROM AUTHOR]

Rural e-commerce, as a new form of digital economy, is of great significance in promoting the income of rural households and realizing common prosperity. Based on the 2021 China Rural Revitalization Survey (CRRS), the impact of rural e-commerce on farmers' income and the intra-rural income gap is explored using quantile regression. The results found that (1) rural e-commerce can effectively promote the level of farm household income and alleviate the intra-rural income disparity, with this finding still holding after addressing the potential endogeneity problem and conducting robust-type tests. (2) Rural e-commerce has the most pronounced income-generating effect on low-income households in the southern region; participation in rural e-commerce has a more "center-expanding" effect on households in the secondary education and high material capital groups. (3) Saving production and operation costs, shortening the product circulation chain, and improving access to information are channels through which rural e-commerce affects households' income. It is recommended to actively promote the deep integration and development of rural e-commerce in rural areas, establish a sound mechanism for bridging the "digital divide", encourage e-commerce "leaders" to build a perfect industrial chain, and guide smallholders to integrate into the rural e-commerce industrial chain to enjoy the digital dividend. [ABSTRACT FROM AUTHOR]