Metastasis patterns and prognosis in young gastric cancer patients: A propensity score­matched SEER database analysis.

BACKGROUND: Whether young patients with metastatic gastric cancer (GC) had distinct metastasis patterns and survival outcomes from older patients remains controversial. The aim of the present study was to explore the metastasis patterns and prognostic factors in young patients and evaluate the survival outcome in comparison to their older counterparts. MATERIALS AND METHODS: We identified patients with metastatic GC in the surveillance, epidemiology, and end results (SEER) database from 2010 to 2015. The patients were divided into two groups based on age at diagnosis: younger (≤40 years old) and older (>40 years old). We employed the chi-squared test to compare the clinicopathological characteristics between the two age groups. Furthermore, we conducted survival analyses using Kaplan-Meier and Cox regression analyses. To balance disparities in baseline characteristics, we employed propensity score matching (PSM). RESULTS: We identified 5,580 metastatic GC patients from the SEER database, with 237 (4.2%) classified as younger and 5343 (95.8%) as older patients. A total of 237 pairs of patients were generated after adjustment by PSM. Patients in the younger group exhibited a higher proportion of bone-only metastases and a lower proportion of liver-only metastases compared with patients in the older group. Multivariate Cox regression analysis demonstrated that youth was an independent protective factor for overall survival (OS) before and after PSM, but not for gastric cancer-specific survival (GCSS). Among the younger group, patients with liver-only metastasis demonstrated the best prognosis, whereas patients with lung-only metastasis exhibited significantly worse survival outcomes compared with liver-only metastases, even comparable to that of bone metastasis. CONCLUSIONS: Compared with the older group, the metastatic GC patients in the younger group exhibited more aggressive tumors but better prognoses. The metastasis pattern and its effect on the prognosis of GC varied by age group.

Sodium-glucose cotransporter 2 inhibitors, inflammation, and heart failure: a two-sample Mendelian randomization study.

BACKGROUND: Sodium-glucose cotransporter 2 (SGLT-2) inhibitors are increasingly recognized for their role in reducing the risk and improving the prognosis of heart failure (HF). However, the precise mechanisms involved remain to be fully delineated. Evidence points to their potential anti-inflammatory pathway in mitigating the risk of HF. METHODS: A two-sample, two-step Mendelian Randomization (MR) approach was employed to assess the correlation between SGLT-2 inhibition and HF, along with the mediating effects of inflammatory biomarkers in this relationship. MR is an analytical methodology that leverages single nucleotide polymorphisms as instrumental variables to infer potential causal inferences between exposures and outcomes within observational data frameworks. Genetic variants correlated with the expression of the SLC5A2 gene and glycated hemoglobin levels (HbA1c) were selected using datasets from the Genotype-Tissue Expression project and the eQTLGen consortium. The Genome-wide association study (GWAS) data for 92 inflammatory biomarkers were obtained from two datasets, which included 14,824 and 575,531 individuals of European ancestry, respectively. GWAS data for HF was derived from a meta-analysis that combined 26 cohorts, including 47,309 HF cases and 930,014 controls. Odds ratios (ORs) and 95% confidence interval (CI) for HF were calculated per 1 unit change of HbA1c. RESULTS: Genetically predicted SGLT-2 inhibition was associated with a reduced risk of HF (OR 0.42 [95% CI 0.30-0.59], P < 0.0001). Of the 92 inflammatory biomarkers studied, two inflammatory biomarkers (C-X-C motif chemokine ligand 10 [CXCL10] and leukemia inhibitory factor) were associated with both SGLT-2 inhibition and HF. Multivariable MR analysis revealed that CXCL10 was the primary inflammatory cytokine related to HF (MIP = 0.861, MACE = 0.224, FDR-adjusted P = 0.0844). The effect of SGLT-2 inhibition on HF was mediated by CXCL10 by 17.85% of the total effect (95% CI [3.03%-32.68%], P = 0.0183). CONCLUSIONS: This study provides genetic evidence supporting the anti-inflammatory effects of SGLT-2 inhibitors and their beneficial impact in reducing the risk of HF. CXCL10 emerged as a potential mediator, offering a novel intervention pathway for HF treatment.

Relationship between the health poverty vulnerability and multimorbidity patterns identified with latent class analysis aged 45 years or more adults in Northwestern China: A cross-section study.

This study aims to identify multimorbidity patterns and examine whether health poverty vulnerability (HPV) varies among adults aged 45 years or more. Data from 4338 participants were extracted from a Chinese cross-sectional study. Latent class analysis was used to identify multimorbidity patterns based on 11 self-reported chronic diseases. A 3-stage feasible generalized least-squares method was used to measure the HPV. The associations and influencing factors were analyzed using the Tobit model. The mean HPV values were 0.105 ±â€…0.225 and 0.329 ±â€…0.357, based on extreme poverty and those of low- and middle-income countries' poverty line, respectively. Four latent multimorbidity patterns were identified, comprising hypertension (57.33%), cardiovascular diseases (19.94%), the musculoskeletal system (13.09%), and spine (9.64%). The HPV value from hypertension (coefficient [Coef] =0.03, 95% confidence interval (CI) = 0.00-0.05) was significantly higher than that of the musculoskeletal system based on extreme poverty. In addition, the HPV values for hypertension (Coef =0.08, 95% CI = 0.05-0.11), spine (Coef =0.06, 95% CI = 0.02-0.11), and cardiovascular diseases (Coef =0.07, 95% CI = 0.03-0.11) were significantly high based on low- and middle-income countries' poverty line. Age ≥75 years, registered poor households, catastrophic medical expenditure, and toilet style were major risk factors. Although the multimorbidity pattern-induced HPV has been significant improved on extreme poverty, it still poses a very serious challenge with regard to low- to middle-income countries' poverty line. The sensitivity analysis proved the robustness of the results. Policymakers should focus on adults with 3 multimorbidity patterns, namely, registered poor households, age ≥75 years, and catastrophic health expenditure, to adopt targeted interventions to prevent and eliminate HPV.

Jiawei Taohe Chengqi decoction inhibition of the notch signal pathway affects macrophage reprogramming to inhibit HSCs activation for the treatment of hepatic fibrosis.

ETHNOPHARMACOLOGICAL RELEVANCE: Jiawei Taohe Chengqi Tang (JTCD) is a modified formulation of Traditional Chinese Medicine (TCM) known as Taohe Chengqi Decoction, which has been described in the ancient TCM literature "Treatise on Febrile Diseases". As a formula that can activate blood circulation and eliminate blood stasis and regulate Yin and Yang in traditional Chinese medicine applications, JTCD has been reported to be effective in the treatment of chronic liver disease and hepatic fibrosis (HF). AIM OF STUDY: The current study aimed to evaluate the effectiveness of JTCD in modulating hepatic macrophages by regulating the Notch signal pathway, and to further investigate the mechanisms underlying macrophage reprogramming that leads to HF. MATERIALS AND METHODS: Molecular assays were performed using in vitro cultures of human mononuclear THP-1 cells and human-derived hepatic stellate cells LX-2. CCl4-induced mice were utilized as an in vivo model to simulate HF. RESULTS: Our results demonstrated that JTCD exhibited dual effects by inhibiting hepatic stellate cell (HSCs) activation and modulating the polarisation of macrophages towards the M2 phenotype while decreasing the M1 phenotype. Network pharmacological analyses and molecular docking studies revealed that the Notch signal pathway was significantly enriched and played a crucial role in the therapeutic response of JTCD against HF. Moreover, through the establishment of a co-culture model, we validated that JTCD inhibited the Notch signal pathway in macrophages, leading to alterations in macrophage reprogramming, subsequent inhibition of HSC activation, and ultimately exerting anti-HF effects. CONCLUSION: In conclusion, our findings provide solid evidence for JTCD in treating HF, as it suppresses the Notch signal pathway in macrophages, regulates macrophage reprogramming, and inhibits HSC activation.

New Perspectives on Chinese Medicine in Treating Hepatic Fibrosis: Lipid Droplets in Hepatic Stellate Cells.

Hepatic fibrosis (HF) is a wound healing response featuring excessive deposition of the extracellular matrix (ECM) and activation of hepatic stellate cells (HSCs) that occurs during chronic liver injury. As an initial stage of various liver diseases, HF is a reversible pathological process that, if left unchecked, can escalate into cirrhosis, liver failure, and liver cancer. HF is a life-threatening disease presenting morbidity and mortality challenges to healthcare systems worldwide. There is no specific and effective anti-HF therapy, and the toxic side effects of the available drugs also impose a heavy financial burden on patients. Therefore, it is significant to study the pathogenesis of HF and explore effective prevention and treatment measures. Formerly called adipocytes, or fat storage cells, HSCs regulate liver growth, immunity, and inflammation, as well as energy and nutrient homeostasis. HSCs in a quiescent state do not proliferate and store abundant lipid droplets (LDs). Catabolism of LDs is characteristic of the activation of HSCs and morphological transdifferentiation of cells into contractile and proliferative myofibroblasts, resulting in the deposition of ECM and the development of HF. Recent studies have revealed that various Chinese medicines (e.g., Artemisia annua, turmeric, Scutellaria baicalensis Georgi, etc.) are able to effectively reduce the degradation of LDs in HSCs. Therefore, this study takes the modification of LDs in HSCs as an entry point to elaborate on the process of Chinese medicine intervening in the loss of LDs in HSCs and the mechanism of action for the treatment of HF.

Thymosin Beta 15 Alters the Spatial Development of Thymic Epithelial Cells.

The thymus is the most sensitive organ under various pathophysiological conditions, such as aging, starvation, and infection. As a key stromal cell for T cell development, it is well-known that thymic epithelial cells (TECs) play an important role in the thymus response to the external environment. Thymosin beta 15 (Tß15) is a G-actin binding protein secreted by TECs, it plays an important role in maintaining the dynamic balance of actin, angiogenesis, axonal formation, and wound healing, but the relationship between Tß15 and TECs is not clear yet. Here, we show the impact of Tß15 on the TEC's spatial development, as well as the T-cell differentiation and thymic output. As a result, TEC is the main effector cell of Tß15 in the thymus. Tß15 OX inhibits the chemotaxis of TECs to the medulla and subsequently blocks the positive selection of thymocytes from CD3+TCRß+CD4+CD8+ double positive cells to CD3+TCRß+CD4+CD8- single-positive (CD4SP) cells. Tß15-knockdown accelerates the reticular differentiation of astral TECs and medullary TECs. Importantly, mice implanted with Tß15-knockdown iTECs show high thymic output but low peripheral T cell maturity and activity. In a word, our results explain the role of Tß15 on the differentiation and function of TECs and provide a new perspective for understanding the process of thymus development and degeneration.

20(S)-Protopanaxdiol Suppresses the Abnormal Granule-Monocyte Differentiation of Hematopoietic Stem Cells in 4T1 Breast Cancer-Bearing Mouse.

Panax notoginseng (PN) has been used as a qi- and blood-activating (Huoxue) drug for thousands of years in China. It has also been widely used as an anticancer drug at present. As a Huoxue drug, the effect of PN on hematopoietic differentiation in tumor-bearing body has been paid more and more attention. Our research found that panax notoginseng saponins (PNS), especially panaxadiol saponins (PDS) and its aglucon 20(S)-Protopanaxdiol (PPD), could improve the immunosuppressive state by regulating the abnormal hematopoietic differentiation in a tumor-bearing body by multiple ways. An interesting phenomenon is that PDS reduced the neutrophil-lymphocyte ratio (NLR) via its inhibition effect on the granule-monocyte differentiation of spleen cells, which is associated with a decrease in the secretion of tumor MPO, G-CSF, PU.1, and C/EBPα. Otherwise, PDS increased the proportion of both hematopoietic stem cells and erythroid progenitor cells in the bone marrow, but inhibited spleen erythroid differentiation via inhibiting secretion of tumor EPO, GATA-1, and GATA-2. This study suggests that PNS regulated the tumor-induced abnormal granule-monocyte differentiation of hematopoietic stem cells, affecting the distribution and function of haemocytes in tumor-bearing mice.

Identification and functional study of immortalized mouse thymic epithelial cells.

As the key cells in a three-dimensional scaffold within the thymus, Thymic epithelial cells (TECs) play critical roles in the homing, migration and differentiation of T cell precursors through adhesive interactions and the release of various cytokines. In this study, primary cultures of mouse TECs were isolated and identified with TEC-specific antibodies CK5 and CK8. These TECs were immortalized by retroviral transduction of simian virus (SV) 40 large T antigen. We then compared the functions of TECs and immortalized TECs (iTECs). Cell morphology and the proliferative capacity of TECs and iTECs were observed by inverted microscope photography and crystal violet assay after passage. A soft agar assay was then performed to observe their clone formation ability. The expression levels of epithelial cell related factors, such as IL-7, Lptin, Pax-9, Sema3A and et al., were detected by IF and qPCR. TECs were co-cultured with human acute monocytic leukemia cells (THP-1), and the effect of TECs on promoting THP-1 proliferation was observed with flow cytometry and CFSE labeling. Senescence-associated ß-galactosidase assay was measured to detect the anti-aging capabilities of the cells. Cell cycle distribution was analyzed by propidium iodide (PI) staining, and paclitaxel (PTX)-induced apoptosis was detected by Annexin V-PI staining to evaluate the anti-apoptotic ability of the cells. Throughout, we found that the immortalized TECs still retain the characteristics of primary TECs, such as the morphology, function and epithelial characteristics; however, iTECs have stronger capabilities in proliferation and anti-aging. Our research suggests that the iTECs were successfully immortalized by SV40 large T antigen, and that the biological characteristics and functions of iTECs were similar to the original TECs. This immortalized cell can be used as an efficient cell model in functional research of the thymus substituting primary TECs with iTECs.

Clinical effect of trimetazidine on prevention of contrast-induced nephropathy in patients with renal insufficiency: An updated systematic review and meta-analysis.

BACKGROUND: With the continuous development of cardiac interventional medicine, the incidence of contrast-induced nephropathy (CIN) is increasing every year, which is a serious threat to people's physical and mental health. Trimetazidine (TMZ) is a type of anti-ischemic drug developed in recent years, which can significantly reduce the incidence of CIN. At present, a systematic review and meta-analysis was conducted to evaluate the clinical effect of TMZ on prevention of CIN in patients with renal insufficiency. However, the study did not include patients from other countries and speaking different languages. So we conducted this study to update the previous meta-analysis that investigated the effects of TMZ on prevention of CIN in patients with renal insufficiency, and provided some theoretical reference for clinical. METHODS: By searching PubMed, Embase, the Cochrane Library, Web of Science, CBM, CNKI, VIP database, and Wang Fang database for randomized controlled trial, which is comparing TMZ versus conventional hydration for prevention of CIN. Two researchers independently screened literature, and then evaluated the quality of literature and extracted the relevant data. Stata 11.0 software was used for statistical analysis. RESULTS: Finally, this updated review showed that 3 studies that were not included in the previous meta-analysis were included in our study (3 articles were published in the Chinese Journal, 1 study for CIN, 1 study for CIN, serum creatinine (Scr), and superoxide dismutase, 1 study for CIN and Scr), and 1 outcome (Scr) reflecting the change of renal function was additionally included in our study. Of the 932 studies, 6 randomized controlled trials met the criteria, including 377 patients in TMZ group and 387 patients in control group. This meta-analysis for all studies showed that TMZ can significantly reduce the incidence of CIN (relative risk 0.27, 95% confidence interval [CI] 0.16, 0.46, P = 0.000), and can decrease the level of Scr after operation, including Scr of postoperative 24 hours (standardized mean difference [SMD] -0.30, 95% CI -0.51, -0.09, P = 0.005), Scr of postoperative 48 hours (SMD -0.66, 95% CI -1.23, -0.10, P = 0.022), and Scr of postoperative 7 days (SMD -0.74, 95% CI -1.36, -0.11, P = 0.021). However, the Scr of postoperative 72 hours between TMZ group and control group has no statistical significance (P = 0.362). CONCLUSION: Our study showed that when comparing with conventional hydration, TMZ can significantly reduce the incidence of CIN and the level of postoperative Scr. Therefore, we could suggest that TMZ was superior to conventional hydration for the treatment of CIN in patients with renal insufficiency. However, due to the restriction of quality and number of included articles, it still needs to carry out multicenter, randomized, double-blind clinical trials to confirm this conclusion in the future.

The effect of alprostadil on preventing contrast-induced nephropathy for percutaneous coronary intervention in diabetic patients: A systematic review and meta-analysis.

BACKGROUND: At present, there are a lot of research about the effect of Alprostadil on preventing contrast-induced nephropathy for percutaneous coronary intervention (PCI) in diabetic patients, but the clinical efficacy is not consistent, so we conduct this study and therefore determine the dominant strategy for the treatment of PCI in diabetic patients based on the best evidence currently. METHODS: An electronic database search was conducted in MEDLINE, Embase, Cochrane library, CBM, CNKI, VIP, and WanFang to retrieve randomized controlled trial (RCT) comparing Alprostadil versus hydration on preventing CIN for PCI in diabetic patients. Reference lists of relevant articles were also screened manually to retrieve additional ones. Two investigators independently assessed the eligibility of retrieved articles using predefined inclusion and exclusion criteria. All characteristics as well as outcome variables including incidence of CIN, blood urea nitrogen (BUN), cystatin C (CysC), glomerular filtration rate (GFR), serum creatinine (Scr), serum beta 2-microspheres (ß2-MG) presented in each included study were extracted. Heterogeneity was thought to be significant when I > 50%. All of the meta-analytic procedures were performed by using Review Manager software, version 5.3. RESULTS: Finally, data from 8 articles including 969 patients were included into this meta-analysis, among them, 487 patients in the experience group, and 482 patients in the control group. Meta analysis showed that the incidence of CIN in the experimental group was significantly lower than that in the control group (OR = 0.28,95%CI[0.18,0.42]). The incidence of adverse reactions in the experimental group was significantly lower than that in the control group (OR = 0.46,95%CI[0.24,0.85]). The BUN of 24 hours, 48 hours, and 72 hours in the experimental group were significantly lower than that of control group (MD = -0.77, 95%CI [-1.22, -0.32]; MD = -1.38, 95%CI [-1.83,-0.92]; MD = -2.43, 95%CI [-2.68,-2.19], respectively). The CysC of 24 hours, 48 hours, and 72 hours in the experimental group were significantly lower than that of control group (MD = -0.30, 95%CI [-0.40, -0.21]; MD = -0.54, 95%CI [-0.68,-0.41]; MD = -0.49, 95%CI [-0.63, -0.35], respectively). The GFR of 24 hours, 48 hours, and 72 hours in the experimental group were significantly higher than that of control group (MD = 7.86, 95%CI [4.44, 11.29], MD = 18.23, 95%CI [13.76,22.69], MD = 12.81, 95%CI [8.51,17.11], respectively). The Scr of 24 hours, 48 hours, and 72 hours in the experimental group were significantly lower than that of control group (MD = -9.09, 95%CI [-12.67, -5.51], MD = -19.14, 95%CI [-23.61, -14.66], MD = -6.50, 95%CI [-8.29, -4.71], respectively). The ß2-MG of 24 hours, 48 hours, and 72 hours in the experimental group were significantly lower than that of control group (MD = -0.12, 95%CI [-0.27, 0.03], MD = -0.55, 95%CI [-0.71, -0.39], MD = -0.50, 95%CI [-0.60, -0.39], respectively). CONCLUSION: Our result suggested that comparing with conventional Hydration, Alprostadil can significantly reduce the incidence of CIN, adverse reaction, and protect renal function in PCI in diabetic patients. Due to the limitations of the quality and quantity of the articles, this conclusion still needs further research to confirm.