The systemic toxicity of different combinations of heavy metal mixtures (HMMs) was studied according to equivalent proportions of the eight most common detectable heavy metals found in fish consumption in the Ningbo area of China. The ion mass proportions of Zn, Cu, Mn, Cr, Ni, Cd, Pb, and Hg were 1070.0, 312.6, 173.1, 82.6, 30.0, 13.3, 6.6, and 1.0, respectively. In this study, 10 experimental groups were set as follows: M8 (Pb + Cd + Hg + Ni + Cu + Zn + Mn + Cr); M5 (Pb + Cd + Hg + Ni + Cr); M4A (Pb + Cd + Hg + Ni); M4B (Cu + Zn + Mn + Cr); M3 (Cu + Zn + Mn); Cr; Cu; Zn; Mn; and control. Sprague Dawley (SD) rats were orally treated with a single dose of each group every three days (10 times in total) for 34 days. After Morris water maze test, blood and tissue samples were collected to obtain biochemical, histopathological and western blot analysis. Results show abnormalities could be observed in different treatment groups, the M4B combination had the most significant change compared to all other groups. In conclusion, combination HMMs may have adverse effects on the hematologic, hepatic, renal and neurobehavioral function, and may also disturb electrolyte and lipid balance. Why M4B combination generated much higher toxic effects than any other combination mixtures or individual heavy metal needs to be further evaluated.

To investigate the association of the hygiene index values of live fresh aquatic products and food-borne diarrhea in the population of the Ningbo area in China. Volatile basic nitrogen (VBN), histamine (HIS), indole, tetrodotoxin (TTX), and paralytic, neurotoxic, amnesic and diarrhetic shellfish poisons (PSP, NSP, ASP, and DSP, respectively) in the samples of live fresh aquatic products and food-borne diarrhea cases in six studied districts were analyzed. Results indicate that the incidence rate of food-borne diarrhea is related to the hygiene index values. Aside from VBN, the main risk factors related to food-borne diarrhea in edible aquatic products include DSP (in marine fish, shrimp, and other shellfishes), NSP, and ASP (in marine shrimp and crab). Hygiene index values among different species were significantly different. No significant difference in the monitoring index values was found among the six different studied districts. The reported cases of food-borne diarrhea were positively associated with VBN and DSP in aquatic products in Haishu, Jiangbei, Zhenhai, and Beilun, as well as VBN and NSP in aquatic products in Jiangdong and Yinzhou. In conclusion, VBN, DSP, NSP, and ASP are important risk factors for the occurring of food-borne diarrhea in the population of the Ningbo area in China.

With the rapid economic development in recent years, China is facing a great challenge due to heavy metal pollution. The heavy metals may enter the human body through ingestion of aqua products to cause great health risks. In the present study, the inhibitory effects of luteolin on the combined toxicity of multi-heavy metals (including zinc, manganese, lead, copper, cadmium, mercury, chromium and nickel) were investigated in HL7702 hepatocyte cells. An MTT assay demonstrated that 20 µM luteolin significantly alleviated the multi-heavy metal mixture-induced cell death and morphological changes. Furthermore, 20 µM luteolin significantly inhibited multi-heavy metal mixture-induced reactive oxygen species (ROS) generation, lipid peroxidation (malondialdehyde content) and caused a decrease in adenosine triphosphate levels in HL7702 cells. A JC-1 staining assay indicated that 20 µM luteolin inhibited the mitochondrial membrane potential-reducing effect of the multi-heavy metal mixture. Apoptotic assays revealed that the multi-heavy metal mixture induced HL7702 cell apoptosis in a dose-dependent manner, which was significantly inhibited by 20 µM luteolin. Western blot analysis indicated that addition of luteolin to the multi‑heavy metal mixture significantly alleviated cytochrome c release from the mitochondria into the cytosol. In addition, 20 µM luteolin had a significant inhibitory effect on multi-heavy metal mixture-induced cleavage of caspase-9, caspase-3 and poly(adenosine diphosphate-ribose) polymerase-1 protein. Immunofluorescence staining demonstrated that addition of luteolin significantly alleviated caspase-3 cleavage induced by the multi-heavy metal mixture. The present results suggested luteolin exerts its inhibitory effects of on multi-heavy metal mixture induced cell apoptosis through downregulation of the ROS-activated mitochondrial pathway.

Background: Diabetic kidney disease, a severe diabetes microvascular complication affecting 30%~40% of diabetic patients, raises end‐stage renal disease and mortality risks. This study is aimed at developing and validate a novel index combining obesity measures and metabolic parameters to screen renal impairment in newly diagnosed T2DM patients. Methods: A total of 387 and 259 newly diagnosed T2DM patients were recruited for model development and validation, respectively. Renal impairment was defined as eGFR < 60 mL/min/1.73 m ² and/or urinary albumin‐to‐creatinine ratio (UACR) ≥ 30 mg/g. Obesity‐ or metabolism‐related indicators were collected. Significantly independent indicators were selected via bidirectional stepwise regression in the modeling patients to develop a comprehensive index termed InMOI. In the validation patients, restricted cubic spline analysis examined the dose‐response relationship between InMOI and renal impairment, whereas ROC curves assessed the screening performance. Results: The triglyceride‐glucose index (TyG) combined with various obesity measures showed significant associations with renal impairment. The InMOI, derived from TyG‐BMI and TyG‐waist to hip ratio (TyG‐WHR), demonstrated a linear dose‐response relationship with the odds ratio for renal impairment. InMOI achieved an AUC of 0.78 for identifying renal impairment. Optimizing the index by replacing WHR with the visceral‐to‐subcutaneous fat area ratio measured by DEXA, the modified InMOI (m‐InMOI) showed a better performance (AUC = 0.81). Conclusion: This study underscores the value of metabolism‐obesity indices in early detection of diabetic renal damage and highlights the pathogenic role of visceral obesity and metabolic dysregulation in diabetic kidney disease. The InMOI provides a practical tool for large‐scale screening and early prevention of diabetic kidney disease.