Yanyan Liu

Background Alterations of the gut microbiota play a key role in the pathogenesis and progression of chronic kidney disease (CKD), and their importance is becoming more widely recognized. However, the relationship between the Dietary Index for Gut Microbiota (DI-GM) and the prevalence of CKD has not been fully investigated. Methods This study employed data from the National Health and Nutrition Examination Survey (NHANES) from 2007 to 2018, which included 24,962 people, following the DI-GM's eligibility requirements. This study's statistical methodologies included multivariable logistic regression, restricted cubic splines (RCS), subgroup analysis, and interaction tests. Results Of the 24,962 participants, 4,342 had CKD, representing 17.39% of all participants. The prevalence of CKD exhibited an inverse relationship with CKD, low estimated glomerular filtration rate (low-eGFR), and albuminuria. Specifically, for every one-unit rise in DI-GM, there was a corresponding 5% reduction in CKD prevalence (OR 0.95, 95% CI 0.93 ~ 0.97). In addition, the strength of association between DI-GM and decreased renal function (OR = 0.92, 95% CI 0.89 ~ 0.95) was higher than that of albuminuria (OR = 0.96, 95% CI 0.93 ~ 0.98). Further analysis using RCS indicated a linear association between DI-GM and CKD, low-eGFR, and albuminuria. Moreover, subgroup evaluations revealed that this negative association between DI-GM and CKD, low-eGFR, and albuminuria remained statistically significant in most subgroups. Conclusion Our research revealed a negative correlation between DI-GM and CKD, low-eGFR, and albuminuria in American adults. This finding suggests that DI-GM may serve as a useful tool to help raise awareness among individuals at high risk for CKD.

Lymphangiogenesis is the formation of new lymphatic vessels from preexisting vessels and occurs during embryonic lymphatic development and under pathological conditions induced by internal or external stimuli. Emerging evidence suggests that neutrophils contribute to the construction and remodeling of new lymphatic vessels. Neutrophils migrate to lymph nodes through the lymphatic vessels or high endothelial venules, and neutrophil migration may depend on the phenotype of the neutrophil. The presence of unique neutrophil phenotypes in individuals with lymphangiogenesis has been reported. Neutrophils promote lymphangiogenesis mainly by secreting lymphotropic factors or increasing their bioavailability and by collaborating with various immune cells. Neutrophils mediate lymphangiogenesis and exert complex effects on tumors and inflammation. The selective inhibition of specific neutrophil and neutrophil lymphangiogenic molecules may provide a novel approach for the prevention and treatment of associated diseases.

The characteristics of the tumour cells, as well as how tumour cells interact with their surroundings, affect the prognosis of cancer patients. The resident cells in the tumour microenvironment are mast cells (MCs), which are known for their functions in allergic responses, but their functions in the cancer milieu have been hotly contested. Several studies have revealed a link between MCs and the development of tumours. Mast cell proliferation in colorectal cancer (CRC) is correlated with angiogenesis, the number of lymph nodes to which the malignancy has spread, and patient prognosis. By releasing angiogenic factors (VEGF-A, CXCL 8, MMP-9, etc.) and lymphangiogenic factors (VEGF-C, VEGF-D, etc.) stored in granules, mast cells play a significant role in the development of CRC. On the other hand, MCs can actively encourage tumour development via pathways including the c-kit/SCF-dependent signaling cascade and histamine production. The impact of MC-derived mediators on tumour growth, the prognostic importance of MCs in patients with various stages of colorectal cancer, and crosstalk between MCs and CRC cells in the tumour microenvironment are discussed in this article. We acknowledge the need for a deeper comprehension of the function of MCs in CRC and the possibility that targeting MCs might be a useful therapeutic approach in the future.

Renal lymphangiogenesis is a new field of international nephrology in recent years and plays an important role in the progression of chronic renal disease. CD137 was originally described as a surface molecule present on activated T and NK cells and detected on hypoxic endothelial cells and inflamed blood vessels, but its function on lymphatic endothelial cells remains unclear. We investigated the relationships among CD137, lymphangiogenesis and macrophages, which are involved in interstitial fibrosis. Similar to other chronic inflammatory diseases, we found lymphangiogenesis and expression of CD137 in the renal tissue of patients with IgA nephropathy. CD137-positive lymphatic vessels were involved in the development process of IgA nephropathy and positively correlated with serum creatinine, serum urea nitrogen, serum uric acid, and urinary 24 h total protein. The expression of these indicators was negatively correlated with eGFR, plasma albumin, and HB. In mouse models of UUO, we verified that CD137 expression was significantly elevated during lymphangiogenesis and that its ligand CD137L was released by macrophages after VEGF-C stimulation in the kidney. In vitro, recombinant CD137L significantly enhanced LEC proliferation, migration and tube formation, and these effects were inhibited by CD137 siRNA. Mechanistically, the CD137L interaction with CD137 induced the transition from LC3-I to LC3-II and the expression of Atg5, Atg7, Atg12 and p62 proteins by activating the PI3K/AKT/mTOR pathway to promote autophagy. Knockdown of Atg5 and Atg7 blocked CD137L-induced autophagy. Thus, we propose that CD137L secretion by macrophages interacts with CD137 on lymphatic endothelial cells to prompt lymphangiogenesis in the kidney, which further drives fibrogenic responses. Our findings suggest that inhibition of the CD137-CD137L pathway is a novel therapeutic approach for obstructive nephropathy.

Background: Inflammatory factors and nutritional status are critical to the prognosis of colorectal cancer patients. This study aimed to investigate the prognostic value of the combination of preoperative lymphocytes, albumin, and neutrophils (LANR) in patients with resectable colorectal cancer.Methods: A total of 753 patients with pathologically diagnosed primary colorectal cancer were included in the study. The value of LANR was defined as follows: LANR, lymphocyte × albumin/neutrophil. The ROC curve, subgroup analysis and Cox proportional hazard regression analysis were used to assess the prognostic value of LANR in overall survival and progression-free survival.Results: The median age of the patients was 60 years (range 52–67 years). In overall survival, the area under the curve of LANR was 0.6276, and the HR (95% CI) was 0.551 (0.393–0.772). And in progression-free survival, the area under the curve of LANR was 0.5963, and the HR (95% CI) was 0.697 (0.550–0.884). The results indicate that preoperative LANR may be a reliable predictor of overall and progression-free survival in resectable colorectal cancer patients.Conclusions: LANR is an important prognostic indicator for patients with resectable colorectal cancer, and it can also provide a reference for clinicians and patients to choose a treatment plan.

Inflammation plays a crucial role in the occurrence and development of renal fibrosis, which ultimately results in end-stage renal disease (ESRD). There is new focus on lymphangiogenesis in the field of inflammation. Recent studies have revealed the association between lymphangiogenesis and renal fibrosis, but the source of lymphatic endothelial cells (LECs) is not clear. It has also been reported that macrophages are involved in lymphangiogenesis through direct and indirect mechanisms in other tissues. We hypothesized that there was a close relationship between macrophages and lymphatic endothelial progenitor cells in renal fibrosis. In this study, we demonstrated that lymphangiogenesis occurred in a renal fibrosis model and was positively correlated with the degree of fibrosis and macrophage infiltration. Compared to resting (M0) macrophages and alternatively activated (M2) macrophages, classically activated (M1) macrophages predominantly transdifferentiated into LECs in vivo and in vitro. VEGF-C further increased M1 macrophage polarization and transdifferentiation into LECs by activating VEGFR3. It was suggested that VEGF-C/VEGFR3 pathway activation downregulated macrophage autophagy and subsequently regulated macrophage phenotype. The induction of autophagy in macrophages by rapamycin decreased M1 macrophage polarization and differentiation into LECs. These results suggested that M1 macrophages promoted lymphangiogenesis and contributed to newly formed lymphatic vessels in the renal fibrosis microenvironment, and VEGF-C/VEGFR3 signaling promoted macrophage M1 polarization by suppressing macrophage autophagy and then increased the transdifferentiation of M1 macrophages into LECs.

Background: Primary central nervous system lymphoma is a rare extra-nodal lymphoma of the central nervous system. Primary central nervous system lymphoma lesions usually appear in the vicinity of the ventricle, and there are few reports of primary central nervous system lymphoma with hypothalamic-pituitary lesions. Case presentation: We treated a 56-year-old male with primary central nervous system lymphoma with the primary lesion in the hypothalamus, which was found by magnetic resonance imaging after sudden onset of endocrinological abnormalities. Initially, he was hospitalized to our department for hyponatremia. Endocrinological examination in conjunction with head magnetic resonance imaging and endoscopic biopsy revealed hypothalamic hypopituitarism and tertiary hypoadrenocorticism caused by a rapidly growing, diffuse large B-cell lymphoma in the hypothalamus. Remission of the tumor was achieved by high-dose methotrexate with whole brain radiotherapy, and some of the hormone responses were normalized. Conclusions: While primary central nervous system lymphoma is rare, it is important to note that hypopituitarism can result and that the endocrinological abnormalities can be partially restored by its remission.

Objective: To investigate the potential mechanism underlying the effect of lung carcinoma cell-derived exosomes on dendritic cell function. Materials and Methods: C57BL/6 (B6) mice were randomly divided into five groups: control, dendritic cell (DC), DC-NC, DC-siMALAT1, and siMALAT1. Tumor cell proliferation was measured by Ki-67 staining. LLC cells were divided into control, NC, and si-MALAT1 groups, and exosomes secreted by each group were labeled as PEX, PEXN, and PEX-si, respectively. Exosomes and autophagic vacuoles were observed by transmission electron microscopy. MALAT1 expression in LLC, A549, and Beas-2b cells was examined by RT-PCR. The expression of IFN-γ, IL-12, IL-10, and TGF-β was observed by Elisa assay. Flow cytometry was used to observe the phagocytic function of DCs, costimulatory molecule expression, and T cell proliferation and differentiation. The protein expression of p-AKT, AKT, p-mTOR, mTOR, ALIX, TSG101, and CD63 was detected by Western blot. Results: Compared with Beas-2b cells, MALAT1 expression was significantly increased in both LLC and A549 cells and in their secreted exosomes, and LLC cells showed the highest expression of MALAT1 (P < 0.05). Tumor cell proliferation and tumor volume were significantly decreased in the siMALAT1 and DC-siMALAT1 groups compared to those in the control group. DC phagocytosis, inflammatory response, costimulatory molecule expression, and T cell proliferation in the siMALAT1 and PEX-si groups were significantly enhanced (P < 0.05), while DC autophagy and T cell differentiation were reduced (P < 0.05). The levels of p-AKT, AKT, p-mTOR, and mTOR in the PEX and PEXN groups were increased compared with those in the control group, while those in the siMALAT1 and PEX-si groups were significantly decreased (P < 0.05). Conclusion: Inhibition of MALAT1 expression in LLC-derived exosomes promoted DC function and T cell proliferation and suppressed DC autophagy and T cell differentiation, suggesting that MALAT1 inhibition may be a potential strategy for the clinical treatment of lung cancer.

Background. Urinary kidney injury molecule 1 (uKIM-1) is a proximal tubular injury biomarker for predicting acute kidney injury (AKI); its prognostic value varies depending on the clinical and population characteristics. However, the predictive value of uKIM-1 for diagnosis of contrast-induced acute kidney injury (CI-AKI) remains unclear.Method. Medline, Embase, ClinicalTrials.gov, Cochrane Library database, and the China National Knowledge Infrastructure (CNKI) were used to identify relevant studies from their inception to November 31, 2019. Studies that met the inclusion criteria were included. Relevant data were extracted to obtain pooled sensitivity (SEN) and specificity (SPE), summary receiver operating characteristic curve (ROC), and area under the ROC (AUC or AUROC). A bivariate mixed-effects regression model was used for data analysis.Results. A total of 946 patients from 8 eligible studies were included. Across all the studies, the diagnostic odds ratio (DOR) for uKIM-1 level to predict CI-AKI was 19 (95% CI 10–39), with SEN and SPE of 0.84 and 0.78, respectively. The AUROC for uKIM-1 in predicting CI-AKI was 0.88 (95% CI 0.85–0.90). There was a substantial heterogeneity across the studies (I²was 37.73% for the summary sensitivity and 69.31% for the summary specificity).Conclusion. Urinary KIM-1 has a high predictive value for diagnosis of CI-AKI in patients who have undergone cardiac catheterization.