Fangfang Xu

Although obesity is a well-established risk factor for metabolic dysfunction-associated steatotic liver disease (MASLD), the impact of long-term weight trajectories on MASLD risk remains unclear. We aimed to examine the association between weight change trajectories across adulthood and the risk of ultrasound-defined MASLD. We analysed data from 4999 participants from the Healthy Happy Aging Community Cohort. Weight trajectories were assessed using body mass index (BMI) at age 25 years, ten years before baseline, one year before baseline, and at baseline. MASLD was defined as a median (MD) controlled attenuation parameter (CAP) of ≥274 dB/m and severe steatosis as a MD CAP of ≥302 dB/m via vibration-controlled transient elastography. There were 2247 (44.9%) patients with MASLD, of whom 1468 (29.4%) had severe steatosis. Compared with stable normal weight, sustained obesity (BMI ≥ 30 kg/m² at all time points) demonstrated a strong association with MASLD risk (adjusted odds ratio (aOR) = 2.17; 95% confidence interval (CI) = 1.64-2.86), particularly for severe steatosis (aOR = 2.52; 95% CI = 1.74-3.66). The transition from non-obese to obese status was associated with a 2.5-fold increase in risk (aOR = 2.51; 95% CI = 1.81-3.48), with a more pronounced effect observed in men (P-interaction 2) remained the strongest independent predictor (aOR = 4.12; 95% CI = 2.70-6.29). Long-term obesity and weight gain, especially in early adulthood, significantly increase MASLD risk. Sustained obesity and progression to obesity were key risk factors, with severe obesity showing the strongest association. Early weight management is crucial for MASLD prevention.

Background: Good knowledge of and attitudes toward hemodialysis and its complications might be expected to promote good practices and improve adherence. This study investigated, the knowledge, attitude, and practice of patients receiving hemodialysis regarding hemodialysis and its complications. Methods: This cross-sectional study enrolled patients with uremia who were receiving hemodialysis at the Second Affiliated Hospital of Nanjing Medical University (China) between January 9, 2023, and January 16, 2023. A questionnaire was designed that included the following dimensions: demographic/clinical information, knowledge, attitude, and practice. Correlations between knowledge, attitude, and practice scores were evaluated by Pearson correlation analysis. Results: The analysis included 493 patients (305 males, 61.87%). The average knowledge, attitude, and practice score was 19.33 ± 7.07 (possible range, 0–31), 28.77 ± 3.58 (possible range, 8–40), and 43.57 ± 6.53 (possible range, 11–55) points, respectively. A higher knowledge score was associated with younger age (P < 0.001), a higher education level (P < 0.001), and not living alone (P < 0.001), while a higher practice score was associated with a shorter history of hemodialysis (P < 0.001). There were positive correlations between the knowledge and practice scores (r = 0.220, P < 0.001) and between the attitude and practice scores (r = 0.453, P < 0.001), although the knowledge and attitude scores were not significantly correlated. Conclusions: The results provide important insights into the knowledge, attitudes, and practices of patients with uremia in Nanjing (China) regarding hemodialysis and its complications. These findings may facilitate education programs to improve self-care practices in patients receiving maintenance hemodialysis in Nanjing (China).

Background: ANGPTL3, 4 and 8 have been reported to be involved in the regulation of lipid and glucose metabolism. The aim of this study was to investigate the expression of ANGPTL3, 4, 8 in hypertensive patients with or without overweight/obesity, T2D, and hyperlipidemia, and the possible association between their expression and the status of the aforementioned comorbidities. Methods: Plasma levels of ANGPTL3, 4, and 8 in 87 hospitalized patients with hypertension were measured using ELISA kits. Associations between circulating ANGPTLs levels and the most common additional cardiovascular risk factors were assessed using multivariate linear regression analyses. Pearson’s correlation analysis was used to examine the association between ANGPTLs and clinical parameters. Results: In the context of hypertension, (1) although not statistically significant, circulating ANGPTL3 levels were higher in the overweight/obese group than in the normal weight group; (2) circulating levels of ANGPTL3 and ANGPTL8 were significantly lower in patients with T2D than in non-diabetic patients; (3) circulating ANGPTL3 levels were significantly higher in the hyperlipidemic group than in the non-hyperlipidemic group. ANGPTL3 was associated with T2D and hyperlipidemia status, whereas ANGPTL8 was independently associated with T2D status. In addition, circulating ANGPTL3 levels were positively correlated with TC, TG, LDL-C, HCY, and ANGPTL8, and circulating ANGPTL4 levels were positively correlated with UACR and BNP. Conclusion: Changes in circulating ANGPTL3 and ANGPTL8 levels have been observed in hypertensive patients with the most common additional cardiovascular risk factors, suggesting a role in the common comorbidities of hypertension and cardiovascular disease. Hypertensive patients with overweight/obesity or hyperlipidemia may benefit from therapies targeting ANGPTL3.

Background: Insulin resistance is a determining factor in the pathophysiology of type 2 diabetes mellitus (T2DM). Angiopoietin-like protein 8 (ANGPTL8, also known as betatrophin), associated with glucose homeostasis and lipid metabolism, has attracted attention. But its mechanism in glucose metabolism remains unclear. This study aimed to explore the effect of ANGPTL8/betatrophin on glucose tolerance in Kunming (KM) mice of different ages and metabolic profiles in insulin-resistant HepG2 cells. Our study may provide a new perspective of ANGPTL8/betatrophin in insulin resistance from the metabolic changes. Methods: Oral glucose tolerance test was performed in KM mice of different ages. Insulin concentration was measured by using a quantitative enzyme-linked immunosorbent assay (ELISA). ANGPTL8/betatrophin knockouts in HepG2 cells were established with clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated (Cas) protein 9 (CRISPR/Cas9) system. Cell counting kit-8 (CCK-8) assay was used to determine cell viability after gene knockout. The effect of ANGPTL8/betatrophin on the metabolomic changes was evaluated in high insulin-induced insulin-resistant HepG2 cells by an ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method. Results: ANGPTL8/betatrophin improved glucose tolerance in older mice not by altering the concentration of insulin. Cell growth was affected in ANGPTL8/betatrophin knockout HepG2. Based on UPLC-MS/MS, compared with wild type insulin-resistant HepG2 cells, we identified 83 differential metabolites in ANGPTL8/betatrophin knockout HepG2 cells after high insulin induction. Among the 14 differential up-regulated metabolites, D-mannose had the highest fold change. In insulin-resistant HepG2 cells, ANGPTL8/betatrophin knockout exerted an effect on the amino acid metabolism, carbohydrate metabolism, metabolism of cofactors and vitamins, lipid metabolism, nucleotide metabolism, and genetic information processing pathway. Conclusion: This study identified the effect of ANGPTL8/betatrophin on glucose tolerance in mice of different ages and metabolic profiles in insulin-resistant HepG2 cells. These findings may contribute to a new understanding of its role in glucose metabolism in the context of insulin resistance.

Background: Hemorrhagic complications are the most common cause of early death in patients with APL and remain a major challenge in the management of APL. Early fatal bleeding events occur not only in high-risk but also in non-high-risk acute promyelocytic leukemia (APL) patients with normal or low WBC counts. Objectives and Methods: To demonstrate the role of the absolute number of circulating leukemic cells in early bleeding events in APL patients. Clinical and laboratory characteristics of 149 patients newly diagnosed with APL were obtained from medical records and retrospectively investigated. Results: In this study, circulating absolute leukemic cells were positively correlated with the WBC count (r=0.9813, p< 0.001) in all patients with APL, and importantly, they were strongly associated with significant bleeding events in non-high-risk patients. Multivariate logistic regression analysis showed that the absolute number of leukemia cells was an independent risk factor for significant bleeding events in APL patients. A cut-off value of 2.59× 10⁹/L for circulating leukemic cells to predict significant bleeding events in APL patients was obtained by ROC curve analysis. We further confirmed that the significant bleeding rate of patients with non-high-risk APL was statistically increased when the absolute number of circulating leukemic cells was ≥ 2.59× 10⁹/L. Conclusion: Circulating leukemic cell content has great clinical value for predicting early bleeding events in APL patients, especially in non-high-risk APL.

Purpose: Red blood cell distribution width (RDW), neutrophil-to-lymphocyte ratio (NLR), and platelet count (PLT) have been reported to be associated with the prognosis of malignancies; this study aimed to evaluate the prognostic significance of the inflammatory prognostic scoring index (IPSI), comprised of RDW, N LR, and PLT for overall survival (OS) in newly diagnosed multiple myeloma patients in the bortezomib-based chemotherapy era. Patients and methods: The prognostic significance of variables associated with the OS of 175 newly diagnosed multiple myeloma patients was evaluated through univariate and multivariate analyses. The cut-off values of RDW, NLR, and PLT were obtained from references. Patients with high RDW (RDW>14) were given a score of 1; patients with high NLR (NLR>2) or low PLT (PLT≤150) were given a score of 2. According to the obtained scores, the inflammatory prognostic scoring index (IPSI) was formed, in which patients were grouped into high-risk group (4–5 points), intermediate-risk group (3 points) and low-risk group (0–2 points). Results: OS varied significantly in different IPSI groups (P< 0.001). On multivariate analysis, the IPSI was an independent prognostic factor for OS (intermediate-risk group HR 2.89, 95% CI 1.60–5.22, high risk-group HR 14.50, 95% CI 7.26–28.93, P<0.001). Importantly, with IPSI as supplement to the International Staging System (ISS), a significant difference in OS was observed among IPSI subgroups (ISS I, P<0.001; ISS II, P=0.008; ISS III, P<0.001). Conclusion: The IPSI, comprised of RDW, NLR, and PLT, played specific role in the prognosis of patients preliminarily diagnosed with multiple myeloma in the bortezomib-based chemotherapy era and could be a beneficial supplement for ISS staging.

Background: Hypomethylating agents (HMAs), such as decitabine (DAC), are currently used as first-line therapy for patients with high-risk myelodysplastic syndromes (MDS) and acute myelogenous leukemia (AML) not eligible for standard chemotherapies. Exacerbation of thrombocytopenia is one of the prevalent complications after HMA treatment. Eltrombopag (EP), an oral thrombopoietin receptor agonist, can efficiently stimulate megakaryopoiesis and elevate platelet counts in MDS/AML patients. However, the significance of combining EP with HMAs in patients with high-risk MDS/AML has not been determined. Purpose: To explore the impacts and mechanisms of EP and/or DAC on leukemia cell growth and to explore whether EP exhibits antileukemic effects in the context of DAC treatment in human myeloid leukemia cell lines. Methods: In our study, we assessed the anti-leukemic effect of EP in the context of DAC treatment by measuring cell proliferation, apoptosis, cell-cycle distribution, and intracellular reactive oxygen species (ROS) levels. Results: Our results showed that the combination of EP and DAC had a more obvious antiproliferative effect than that of DAC as a single agent. EP mainly induced S or G0/G1 phase cell cycle arrest, and DAC arrested the cell cycle in the S or G2/M phase. The combination of EP and DAC had a synergistic effect on cell cycle arrest. Furthermore, single-agent treatment with EP or DAC induced a change in intracellular ROS levels, and the combination of EP and DAC had a synergistic effect on ROS levels, exacerbating leukemia cell death. Conclusion: Our study provides in vitro evidence of the synergistic antileukemic effect and potential mechanisms of the combination of DAC and EP on myeloid leukemia cells.

ANGPTL8/Betatrophin has been implicated in the regulation of both glucose and triglyceride metabolism. However, its role in regulating glucose metabolism by promoting β cell proliferation remains controversial, and its physiological functions and molecular targets are largely unknown. Hence, it is of great importance to make recombinant protein and test its effects on β cell mass directly. In this study, the mature form gene of human ANGPTL8/betatrophin was obtained through chemical synthesis on to the vector pUCE, and the fusion protein was expressed in the Transetta (DE3)/pEASY-E2-betatrophin strain. The inclusion bodies were solubilized in urea and purified by Ni–NTA affinity chromatography. The yield of purified ANGPTL8/betatrophin was approximately 20 mg per liter of culture medium. In vitro studies revealed that the recombinant ANGPTL8/betatrophin had no proliferation effect on MIN6 cells but promoted TG levels in HepG2 cells. This method to generate bioactive ANGPTL8/betatrophin is a simple, practical and user-friendly protocol.