BACKGROUND:Both calorie restriction and time-restricted feeding,as two common dietary patterns,have been shown to improve health by regulating metabolism.However,the difference between these dietary patterns,metabolic indices,as well as the gut microbiota still requires further attention.OBJECTIVE:To explore the differences of calorie restriction and time-restricted feeding on the metabolic indices and gut microbiota of mice.METHODS:The C57BL/6J mice were randomly divided into three groups of ad libitum,calorie restriction,and time-restricted feeding(n=6 per group)for 28 weeks of dietary intervention.Various parameters such as body weight,food intake,glucose tolerance,serum fasting insulin,Homeostasis Model Assessment of Insulin Resistance,and leptin were measured.The impact of different interventions on the gut microbiota structure in mice was explored using 16S rRNA sequence analysis.Key operational taxonomic units responsive to dietary interventions were identified through LEfSe analysis.RESULTS AND CONCLUSION:(1)Compared with the ad libitum group,the body weight,food intake,area under the glucose tolerance curve of the calorie restriction and time-restricted feeding groups were decreased(P＜0.01),and the serum leptin was decreased(P＜0.05).The fasting insulin level and serum leptin level of the calorie restriction group were decreased(P＜0.05)and were significantly lower than those of the time-restricted feeding group(P＜0.05);homeostasis model assessment of insulin resistance decreased in the calorie restriction group(P＜0.01).(2)Compared with the ad libitum group,the αdiversity of gut microbiota in the calorie restriction group and the time-restricted feeding group was decreased(P＜0.05),but the diversity of the time-restricted feeding group was slightly lower than that in the calorie restriction group.(3)There were 15 key operational taxonomic units related to calorie restriction and the time-restricted feeding intervention,of which 8 were positively correlated with metabolic phenotypes and their abundance decreased,and 3 were negatively correlated with metabolic phenotypes and their abundance increased(P＜0.05).OTU819 Lachnospiraceae_UCG-006 was positively correlated with body weight,area under the glucose tolerance curve,homeostasis model assessment of insulin resistance,and fasting insulin,while OTU1397 Muribaculaceae was negatively correlated with these indicators.The results show that both calorie restriction and the time-restricted feeding intervention can improve the weight and glucose metabolism of mice,and both intervention modes caused the remodeling of the gut microbiota,which helped to improve the metabolic disorders.

In the face of constantly changing environments, the central nervous system (CNS) rapidly and accurately calculates the body's needs, regulates feeding behavior, and maintains energy homeostasis. The arcuate nucleus of the hypothalamus (ARC) plays a key role in this process, serving as a critical brain region for detecting nutrition-related hormones and regulating appetite and energy homeostasis. Agouti-related protein (AgRP)/neuropeptide Y (NPY) neurons in the ARC are core elements that interact with other brain regions through a complex appetite-regulating network to comprehensively control energy homeostasis. In this review, we explore the discovery and research progress of AgRP neurons in regulating feeding and energy metabolism. In addition, recent advances in terms of feeding behavior and energy homeostasis, along with the redundant neural mechanisms involved in energy metabolism, are discussed. Finally, the challenges and opportunities in the field of neural regulation of feeding and energy metabolism are briefly discussed.
Energy Metabolism/physiology* ; Animals ; Humans ; Hypothalamus/metabolism* ; Neurons/metabolism* ; Feeding Behavior/physiology* ; Brain Stem/metabolism* ; Agouti-Related Protein/metabolism* ; Homeostasis/physiology* ; Neuropeptide Y/metabolism*

Objective: To evaluate the application of blood conservation measures in obstetric patients with different red blood cell transfusion volumes and to assess the impact of different transfusion volumes on postpartum outcomes. Methods: A retrospective investigation was conducted on 448 obstetric patients who received blood transfusions at the Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine from January 2016 to December 2022. Patients were divided into four groups (1-2 units group, 3-4 units group, 5-6 units group, and >6 units group) based on the volumes of red blood cells (RBCs) transfused during and within 7 days after delivery. The maternal physiological indicators, pre- and postpartum laboratory test indicators, obstetric complications, application of blood conservation measures, use of blood products, and postpartum outcomes were reviewed. The clinical characteristics, application of blood conservation measures, and their impact on postpartum outcomes were compared among different transfusion groups. Results: There were statistically significant differences in the multivariate logistic analysis of history of previous cesarean section (OR=1.781), eclampsia/pre-eclampsia/(OR=1.972) and postpartum blood loss>1 000 mL（OR=1.699）(P<0.05) among different transfusion groups. In terms of blood conservation measures, the more RBCs transfused, the higher the rate of mothers receiving blood conservation measures such as balloon occlusion, arterial ligation, autologous blood transfusion with a cell saver, and hysterectomy. With the increase in the volume of RBCs transfusion, the demand for fresh frozen plasma（FFP）, cryoprecipitate, and platelet transfusions also increased. The hospitalization days for the four groups of parturients were 6.0 (4.0-9.0), 7.5 (5.0-14.8), 7.0 (4.5-13.0) and 11.0 (9.0-20.5), respectively (P<0.05) and the rates of ICU transfer were 2.0% (5/250), 9.4% (12/128),18.2% (6/33) and 51.4% (19/37), respectively (P<0.05). Both increased significantly with the increase in the volume of RBCs transfusion, and the differences between groups were statistically significant. Conclusion: Parturients who received higher volume of RBCs had multiple risks factors for bleeding before childbirth, had higher postpartum blood loss, and had a higher rate of application of various blood conservation measures. In addition, an increase in the volume of RBCs transfusion may have adverse effects on postpartum recovery.

Background: Aristolochic acid II (AAII), a major nephrotoxic and carcinogenic component of aristolochic acids (AAs), has been less studied compared with its well-characterized analog, aristolochic acid I (AAI). Although AAs are known to induce carcinogenesis via DNA adduct formation, the toxicity mechanisms, environmental prevalence, and long-term health impacts of AAII remain poorly understood. Objective: This study aimed to systematically evaluate AAII’s acute and chronic toxicity, carcinogenic mechanisms, and environmental exposure patterns using integrated murine models and phytochemical analyses to clarify its toxicological profile and associated health risks. Methods: C57BL/6J mice were used in the following experiments: (1) determination of AAII content in 3 commonly used Aristolochia medicinal materials via liquid chromatography-mass spectrometry/mass spectrometry; (2) acute toxicity testing with single doses of 10, 20, or 40 mg/kg; and (3) chronic exposure with 1 or 10 mg/kg administered every other day for 24 weeks, followed by 21 to 40 weeks of postexposure monitoring. Histopathological examination, whole-exome sequencing, biochemical assays, and micronucleus tests were performed to assess multi-organ damage, tumorigenesis, genomic mutation signatures, and direct clastogenicity. Phytochemical analyses were used to evaluate environmental distribution. Results: (1) A single 40 mg/kg dose of AAII induced dose-dependent renal tubular degeneration without hepatotoxicity; (2) the 10 mg/kg group showed significant mortality (20%), tumor incidence (33.3%, primarily forestomach and bladder transitional cell carcinomas), persistent renal interstitial fibrosis, and subclinical hepatic injury. Chronic exposure to 1 mg/kg still induced 13.3% mortality and 15.5% tumor incidence over a 64-week period; (3) whole-exome sequencing revealed a predominance of C>T mutations and pathway enrichment in chemical carcinogenesis and cytochrome P450-mediated metabolism, indicating reactive metabolite-driven mechanisms distinct from classical AA-DNA adducts; and (4) no histopathological changes were observed in nontarget organs (brain, heart, and testes), and micronucleus assays confirmed the absence of direct clastogenicity. Conclusion: This study highlights the delayed carcinogenic risks of low-dose chronic AAII exposure and emphasizes the need to update regulatory frameworks to ensure the safe use of aristolochiaceae-containing herbal products.

Ferroptosis, an iron-dependent form of regulated cell death driven by lipid peroxidation, has been recently identified as a key role in Parkinson's disease (PD) pathogenesis. In particular, lipid peroxidation-mediated ferroptosis is considered a key event leading to the death of dopaminergic neurons. This article reviews the role of lipid peroxidation-mediated ferroptosis in PD and its involved key signaling pathways, and explores the related targeted therapeutic strategies, with the aim of providing new ideas for targeted treatment of PD.

BACKGROUND:Both calorie restriction and time-restricted feeding,as two common dietary patterns,have been shown to improve health by regulating metabolism.However,the difference between these dietary patterns,metabolic indices,as well as the gut microbiota still requires further attention.OBJECTIVE:To explore the differences of calorie restriction and time-restricted feeding on the metabolic indices and gut microbiota of mice.METHODS:The C57BL/6J mice were randomly divided into three groups of ad libitum,calorie restriction,and time-restricted feeding(n=6 per group)for 28 weeks of dietary intervention.Various parameters such as body weight,food intake,glucose tolerance,serum fasting insulin,Homeostasis Model Assessment of Insulin Resistance,and leptin were measured.The impact of different interventions on the gut microbiota structure in mice was explored using 16S rRNA sequence analysis.Key operational taxonomic units responsive to dietary interventions were identified through LEfSe analysis.RESULTS AND CONCLUSION:(1)Compared with the ad libitum group,the body weight,food intake,area under the glucose tolerance curve of the calorie restriction and time-restricted feeding groups were decreased(P＜0.01),and the serum leptin was decreased(P＜0.05).The fasting insulin level and serum leptin level of the calorie restriction group were decreased(P＜0.05)and were significantly lower than those of the time-restricted feeding group(P＜0.05);homeostasis model assessment of insulin resistance decreased in the calorie restriction group(P＜0.01).(2)Compared with the ad libitum group,the αdiversity of gut microbiota in the calorie restriction group and the time-restricted feeding group was decreased(P＜0.05),but the diversity of the time-restricted feeding group was slightly lower than that in the calorie restriction group.(3)There were 15 key operational taxonomic units related to calorie restriction and the time-restricted feeding intervention,of which 8 were positively correlated with metabolic phenotypes and their abundance decreased,and 3 were negatively correlated with metabolic phenotypes and their abundance increased(P＜0.05).OTU819 Lachnospiraceae_UCG-006 was positively correlated with body weight,area under the glucose tolerance curve,homeostasis model assessment of insulin resistance,and fasting insulin,while OTU1397 Muribaculaceae was negatively correlated with these indicators.The results show that both calorie restriction and the time-restricted feeding intervention can improve the weight and glucose metabolism of mice,and both intervention modes caused the remodeling of the gut microbiota,which helped to improve the metabolic disorders.

Objective To investigate the clinical and MRI imaging features of ovarian endometrioid adenofibroma and to analyze its pathological features in order to promote the diagnostic and differential diagnostic ability.Methods The clinical and MRI imaging features of 5 cases of ovarian endometrioid adenofibroma confirmed by pathology were analyzed retrospectively.Results Among the 5 patients,2 were diagnosed with postmenopausal vaginal bleeding,while the other 3 cases were incidental findings with no obvious clinical discomfort.One patient had elevated estrogen level,but the remaining patients showed no obvious abnormalities in laboratory examinations.All the lesions in 5 patients were cystic-solid masses,MRI showed mixed iso-and hypointensity on T1 WI,and slightly hyperintensity and hypointensity of solid components on T2WI.The solid components showed scattered cystic foci with smooth cyst walls and partial septa.The signal in the capsule was homogeneous.Diffusion weighted imaging(DWI)showed slightly hyperintensity and hypointensity.Contrast-enhanced scans showed gradual enhancement in the solid part of the massed with no enhancement in the cystic areas.Conclusion The clinical manifestations of ovarian endometrioid adenofibroma are non-specific,but MRI manifestations are specific to some extent.The final diagnosis depends on pathological diagnosis.

Objective To investigate the clinical and MRI imaging features of ovarian endometrioid adenofibroma and to analyze its pathological features in order to promote the diagnostic and differential diagnostic ability.Methods The clinical and MRI imaging features of 5 cases of ovarian endometrioid adenofibroma confirmed by pathology were analyzed retrospectively.Results Among the 5 patients,2 were diagnosed with postmenopausal vaginal bleeding,while the other 3 cases were incidental findings with no obvious clinical discomfort.One patient had elevated estrogen level,but the remaining patients showed no obvious abnormalities in laboratory examinations.All the lesions in 5 patients were cystic-solid masses,MRI showed mixed iso-and hypointensity on T1 WI,and slightly hyperintensity and hypointensity of solid components on T2WI.The solid components showed scattered cystic foci with smooth cyst walls and partial septa.The signal in the capsule was homogeneous.Diffusion weighted imaging(DWI)showed slightly hyperintensity and hypointensity.Contrast-enhanced scans showed gradual enhancement in the solid part of the massed with no enhancement in the cystic areas.Conclusion The clinical manifestations of ovarian endometrioid adenofibroma are non-specific,but MRI manifestations are specific to some extent.The final diagnosis depends on pathological diagnosis.

Ferroptosis, an iron-dependent form of regulated cell death driven by lipid peroxidation, has been recently identified as a key role in Parkinson's disease (PD) pathogenesis. In particular, lipid peroxidation-mediated ferroptosis is considered a key event leading to the death of dopaminergic neurons. This article reviews the role of lipid peroxidation-mediated ferroptosis in PD and its involved key signaling pathways, and explores the related targeted therapeutic strategies, with the aim of providing new ideas for targeted treatment of PD.

BACKGROUND:In recent years,the incidence of hyperuricemia caused by purine metabolism disorders has been increasing,which can induce inflammatory responses and lead to renal injury. OBJECTIVE:To explore the role and mechanism of solute carrier family 2 member 12(SLC2A12)in hyperuricemia-related renal injury. METHODS:Renal tubular cells(HK2 cells)were divided into five groups:HK2 group,HK2+uric acid group,HK2+uric acid+NC group,HK2+uric acid+siSLC2A12 group,and HK2+uric acid+siSLC2A12+MK-2206 group.HK2 cells were treated with uric acid and transfected with siRNA SLC2A12,followed by MK-2206 treatment to inhibit AKT expression.Cell proliferation was detected by CCK-8 assay.Apoptosis was detected by TUNEL assay.qRT-PCR and western blot assay were used to detect fibrogenic factors as well as activation of the AKT/FOXO3a pathway.The concentrations of inflammatory cytokines were measured by enzyme-linked immunosorbent assay. RESULTS AND CONCLUSION:(1)Uric acid treatment inhibited cell proliferation and promoted cell apoptosis in the HK2+uric acid group compared with the HK2 group.The proliferative ability of cells in the HK2+uric acid+siSLC2A12 group was further decreased and apoptotic cells were further increased compared with the HK2 group.Compared with the HK2+uric acid+siSLC2A12 group,the HK2+uric acid+siSLC2A12+MK-2206 group showed an increase in cell proliferation and a decrease in apoptotic cells.(2)Compared with the HK2 group,the connective tissue growth factor(CTGF),α-smooth muscle actin(α-SMA)and transforming growth factor beta(TGF-β)expressions increased in the HK2+uric acid group;CTGF,α-SMA and TGF-β expression further increased in the HK2+uric acid+siSLC2A12 group.Compared with the HK2+uric acid+siSLC2A12 group,the CTGF,α-SMA and TGF-β expressions decreased.(3)Compared with the HK2 group,the expression of p-AKT,FOXO3a,and p-FOXO3a elevated in the HK2+uric acid group;the expression of p-AKT further increased,while the expression of FOXO3a and p-FOXO3a decreased in the HK2+uric acid+siSLC2A12 group.Compared with the HK2+uric acid+siSLC2A12 group,p-AKT expression decreased;FOXO3a and p-FOXO3a expression increased in the HK2+uric acid+siSLC2A12+MK-2206 group.(4)Compared with the HK2 group,interleukin-6,interleukin-1 β,and tumor necrosis factor α levels increased in the HK2+uric acid group;interleukin-6,interleukin-1 β,and tumor necrosis factor α levels further increased in the HK2+uric acid+siSLC2A12 group.Compared with the HK2+uric acid+siSLC2A12 group,interleukin-6,interleukin-1 β,and tumor necrosis factor α levels diminished in the HK2+uric acid+siSLC2A12+MK-2206 group.(5)These findings indicate that SLC2A12 may protect against hyperuricemia-induced renal injury by counteracting uric acid-induced tubular fibrosis and inflammation through activation of the FOXO3a pathway.