Atherogenic Index of Plasma as a Mediator in the association between Body Roundness Index and Depression: insights from NHANES 2005-2018.

BACKGROUND: Previous studies have shown a correlation between depression and obesity, as well as between depression and the Atherogenic Index of Plasma (AIP). However, there is limited research on the association between visceral obesity and depression, as well as the potential mediating role of AIP in this relationship. METHODS: This study included 13,123 participants from the 2005-2018 National Health and Nutrition Examination Survey. Visceral obesity was measured with the Body Roundness Index (BRI), while depression was evaluated with the Patient Health Questionnaire-9. The AIP served as a marker for lipid disorders. To investigate the association between the BRI and depression, multivariate logistic regressions, restricted cubic spline models, subgroup analyses, and interaction tests were used. Additionally, a mediation analysis was conducted to explore the role of AIP in mediating the effect of BRI on depression. RESULTS: There was a positive linear correlation between the BRI and depression. After controlling for all covariates, individuals in the highest BRI (Q4) group had an OR of 1.42 for depression (95% CI: 1.12-1.82) in comparison with individuals in the lowest BRI (Q1) group. Moreover, the AIP partially mediated the association between the BRI and depression, accounting for approximately 8.64% (95% CI: 2.04-16.00%) of the total effect. CONCLUSION: The BRI was positively associated with depression, with the AIP playing a mediating role. This study provides a novel perspective on the mechanism that connects visceral obesity to depression. Managing visceral fat and monitoring AIP levels may contribute to alleviating depression.

Exploring the L-shaped relationship between Atherogenic Index of Plasma and depression: Results from NHANES 2005-2018.

BACKGROUND: The Atherogenic Index of Plasma (AIP) is a novel metric linked to several diseases. However, there is inadequate evidence to investigate the relationship between AIP and depression. Therefore, we aim to elucidate the non-linear association between AIP and depression. METHODS: 12,453 participants from the National Health and Nutrition Examination Survey (NHANES) 2005-2018 were included. The AIP was calculated as log10 (triglycerides/high-density lipoprotein cholesterol). The Patient Health Questionnaire (PHQ-9) was used to identify depression (PHQ-9 ≥ 10). Weighted multivariate logistic regression, restricted cubic splines (RCS) models, subgroup analysis, and interaction tests were employed to reveal the relationship between AIP and depression. RESULTS: AIP was found to be significantly correlated with depression. In the fully adjusted model, elevated AIP levels were associated with higher odds of depression (odds ratio [OR] = 1.50; 95 % CI: 1.06-2.12). The RCS analysis indicated an L-shaped pattern in the relationship between depression and AIP, with inflection points at -0.289. Beyond this inflection point, individuals with elevated AIP levels were associated with higher odds of depression (OR = 2.25; 95 % CI: 1.49-3.39). Notably, the association was particularly pronounced among individuals with diabetes. LIMITATION: This cross-sectional study is unable to establish causal relationships. CONCLUSION: There was an L-shaped association between AIP and depression among US adults. AIP has the potential value as a biological marker for depression, and maintaining AIP values below a certain threshold may help in managing depression.

LDL-C and TC mediate the risk of PNPLA3 inhibition on cardiovascular diseases.

BACKGROUND: PNPLA3 is a promising target for the treatment of Metabolic Dysfunction-Associated Steatotic Liver Disease. ARO-PNPLA3 is a drug that efficiently lowers PNPLA3 expression in hepatocytes at the mRNA level, resulting in a significant reduction in liver fat in Phase I clinical trials. However, the long-term effects and potential side effects of ARO-PNPLA3 are not well understood. METHODS: We conducted a two-sample, two-step Mendelian randomization (MR) analysis to investigate the association between PNPLA3 inhibition and 10 cardiovascular diseases (CVDs), as well as the role of lipid traits as mediators. We identified genetic variants near the PNPLA3 gene, which are linked to liver fat percentage, as instrumental variables for inhibiting PNPLA3. Additionally, positive control analyses on liver diseases were conducted to validate the selection of the genetic instruments. RESULTS: Genetically predicted PNPLA3 inhibition significantly increased the risk of coronary atherosclerosis (1.14, 95% CI 1.06, 1.23), coronary heart disease (1.14, 95% CI 1.08, 1.21), and myocardial infarction (1.16, 95% CI 1.08, 1.26). Suggestive associations were observed for increased risk of heart failure (1.09, 95% CI 1.02, 1.17, P = 0.0143) and atrial fibrillation (1.17, 95% CI 1.00, 1.36, P = 0.0468). Blood low-density lipoprotein cholesterol (LDL-C) and total cholesterol (TC) mediated approximately 16-25%, 16-30%, and 14-22% of the associations between PNPLA3 inhibition and coronary atherosclerosis, myocardial infarction, and coronary heart disease, respectively. CONCLUSION: This study suggests that PNPLA3 inhibition increases the risk of major CVDs. Moreover, blood LDL-C and TC may mediate a significant proportion of the associations between PNPLA3 inhibition and coronary atherosclerosis, coronary heart disease, or myocardial infarction.

Nasal alar metastasis of advanced hepatocellular carcinoma misdiagnosed as reactive cutaneous capillary endothelial proliferation in a patient treated with camrelizumab and apatinib: a case report.

Background: Reactive cutaneous capillary endothelial proliferation (RCCEP) is a common adverse event of camrelizumab in the treatment of advanced hepatocellular carcinoma. Facial skin metastasis is an exceptionally uncommon occurrence in hepatocellular carcinoma (HCC). It can be easily mistaken for a prevalent complication known as RCCEP, particularly when it manifests as a persistently enlarging tumor-like mass. This case report highlights a prototypical instance where a metastasis in the nasal alar region of HCC was mistakenly diagnosed as RCCEP during immunotherapy. The findings of this report hold significant clinical value in guiding the management of larger RCCEP lesions encountered during immunotherapy. Case Description: In this case, the patient is a male with a history of hepatitis B. In October 2015, he was diagnosed with HCC. In April 2020, he commenced treatment with ramucirumab (200 mg every 3 weeks) as tumor progression. However, during the third treatment cycle, the patient experienced RCCEP, predominantly affecting the head, neck, trunk, and limbs. To address this, sequential administration of apatinib was initiated, resulting in the gradual regression of RCCEP in these areas. Unfortunately, the metastatic lesion in the nasal alar region continued to grow, exhibiting a tumor-like appearance. On January 25, 2021, surgical resection was performed to remove the nasal alar lesion, and subsequent pathological examination confirmed it as a liver metastasis. Post-surgery, radiation therapy was administered to effectively manage the remaining lesion in the nasal alar region. Importantly, the treatment of the nasal alar metastasis did not hinder the comprehensive management of HCC. The patient obtained excellent curative effect. Conclusions: During the course of immunotherapy for HCC, the emergence of a larger RCCEP lesion that does not show signs of regression even with vigorous treatment raises the suspicion of skin metastasis. It is difficult to distinguish metastatic tumor on the skin from morule- and tumor-like RCCEP that does not easily resolve. To obtain a definitive diagnosis, an early pathological biopsy is crucial. If confirmed as a metastatic tumor, prompt consideration should be given to implementing curative surgical resection.

Synchronous triple primary gastrointestinal malignant tumors treated with laparoscopic surgery: A case report.

Synchronous gastrointestinal multiple primary tumors including gastric, colonic, and rectal cancers are rare. Moreover, it was a challenge to find an appropriate procedure without negatively impacting the overall outcome. We described the case of a 63-year-old woman who presented with a 4 month history of upper abdominal pain, acid regurgitation, and anemia. Gastroscopy with biopsy suggested early cancer of gastric antrum. Abdominal contrast-enhanced computerized tomography and colonoscopy revealed ascending colon and rectum tumors. She had no family history of malignancy. Endoscopic submucosal dissection was performed for gastric cancer, and the pathological result presented that it was poorly differentiated and invaded into deep submucosa. The laparoscopy-assisted radical surgery combined with distal gastrectomy, right hemicolectomy, and anterior resection of rectum was performed for these three tumors via eight ports and a 7 cm midline upper-abdominal incision. No other perioperative complications were encountered except postoperative ileus. The patient was discharged on the 12th postoperative day. The pathological results revealed gastric cancer (T1N0M0), right colonic cancer (T3N1M0), and rectal cancer (T2N0M0), indicating complete surgical resection. We reported that our laparoscopic approach for synchronous triple primary gastrointestinal malignant tumors was feasible and minimally invasive.

Knockdown of METTL5 inhibits the Myc pathway to downregulate PD-L1 expression and inhibits immune escape of hepatocellular carcinoma cells.

The incidence of hepatocellular carcinoma (HCC) is raised annually, which causes a great harm to people's health. This research aimed to investigate the influence and mechanism of methyltransferase-like 5 (METTL5) in HCC. According to The Cancer Genome Atlas (TCGA) database, METTL5 levels and prognosis was analyzed in HCC. Next, in HCC tissues and cells, METTL5 expression was examined via quantitative real-time polymerase chain reaction (qRT-PCR). Biological behaviors of HCC cells were assessed by Cell Counting Kit-8 (CCK-8), colony formation, transwell and flow cytometry assays. Gene Set Enrichment Analysis (GSEA) was applied to predict METTL5 related pathway. The possible binding sites of programmed cell death 1 ligand 1 (PD-L1) and myelocytomatosis viral oncogene (Myc) was predicted by JASPAR database. Western blot was utilized to test the change of PD-L1 and Myc pathway related proteins [cellular (c)-Myc, chaperonin containing TCP1 subunit 2 (CCT2) and chromobox protein homolog 3 (CBX3)]. In HCC tissues and cells, METTL5 expression was increased. High METTL5 expression was associated with poor prognosis. Knockdown of METTL5 inhibited HCC cell proliferation and invasion, induced cell apoptosis and reduced the expression of PD-L1, c-Myc, CCT2 and CBX3. The bind between PD-L1 and the Myc promoter in HCC cells was confirmed using Chip and luciferase reporter assays. Moreover, the influences of knockdown of METTL5 on PD-L1 expression and HCC cell biological behaviors were reversed by overexpression of Myc. Knockdown of METTL5 inhibited PD-L1 expression and malignant cell behavior of HCC through inhibiting the Myc pathway.