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ObjectiveTo explore the cytotoxicity of four wild mushrooms involved in a case of Yunnan sudden unexplained death （YNSUD）, to provide the experimental basis for prevention and treatment of YNSUD.MethodsFour kinds of wild mushrooms that were eaten by family members in this YNSUD incident were collected and identified by expert identification and gene sequencing. Raw extracts from four wild mushrooms were extracted by ultrasonic extraction to intervene HEK293 cells, and the mushrooms with obvious cytotoxicity were screened by Cell Counting Kit-8 （CCK-8）. The selected wild mushrooms were prepared into three kinds of extracts, which were raw, boiled, and boiled followed by enzymolysis. HEK293 cells were intervened with these three extracts at different concentrations. The cytotoxicity was detected by CCK-8 combined with lactate dehydrogenase （LDH） Assay Kit, and the morphological changes of HEK293 cells were observed under an inverted phase contrast microscope.ResultsSpecies identification indicated that the four wild mushrooms were Butyriboletus roseoflavus, Boletus edulis, Russula virescens and Amanita manginiana. Cytotoxicity was found only in Amanita manginiana. The raw extracts showed cytotoxicity at the mass concentration of 0.1 mg/mL, while the boiled extracts and the boiled followed by enzymolysis extracts showed obvious cytotoxicity at the mass concentration of 0.4 mg/mL and 0.7 mg/mL, respectively. In addition to the obvious decrease in the number of HEK293 cells, the number of synapses increased and the refraction of HEK293 cells was poor after the intervention of Amanita manginiana extracts.ConclusionThe extracts of Amanita manginiana involved in this YNSUD case has obvious cytotoxicity, and some of its toxicity can be reduced by boiled and enzymolysis, but cannot be completely detoxicated. Therefore, the consumption of Amanita manginiana is potentially dangerous, and it may be one of the causes of the YNSUD.

To improve the accuracy of computer aided diagnosis (CAD) based on dynamic contrast enhanced magnetic resonance imaging (DCE-MRI) in the differentiation of benign and malignant breast lesions, this study proposed a convolutional neural network model (AC_Ulsam_CNN) that is based on multi-modal feature fusion and the combination of asymmetric convolution (AC) and ultra-lightweight subspace attention module (Ulsam). Firstly, the transfer learning method was used to pre-train the model to screen out the most effective DCE-MRI time phase scan for differentiating benign and malignant breast lesions. Then, a network model based on AC_Ulsam_CNN was constructed based on the optimal time phase scan images to enhance the feature expression ability and robustness of the classification model. Finally, multimodal information such as breast imaging reporting and data system (BI-RADS) classification, apparent diffusion coefficient (ADC) and time-signal intensity curve (TIC) type were incorporated for feature fusion, to further improve the distinguishing performance of benign and malignant breast lesions. The performance of the model was verified by 5-fold cross-validation method, and the accuracy (ACC) of the proposed method was 0.826 and the area under the curve (AUC) was 0.877. The experimental results show that the proposed algorithm performs well in the classification of benign and malignant breast lesions with small sample size, and the fusion model based on multimodal data further enriches the feature information, thus this study improves the detection accuracy of lesions, and provides a new method for automatic differential diagnosis of benign and malignant breast lesions.

Background: Iron deficiency is prevalent in patients with chronic kidney disease (CKD), even in those without anemia. However, the effects of iron deficiency on CKD progression and all-cause mortality in non-dialysis-dependent CKD (NDD-CKD) patients without anemia remain incompletely understood. Methods: This multicenter retrospective nationwide cohort study included adult patients with non-anemia NDD-CKD from 24 hospitals across China. The study investigated the associations between serum ferritin or transferrin saturation (TSAT) levels and the risks of CKD progression and all-cause mortality. Results: Among 18,878 patients with NDD-CKD, 9,989 patients were included in the kidney outcome analysis, and 18,481 patients in the all-cause mortality analysis. Of the patients with the measurement, 2,450 (27.2%) had ferritin levels ≤ 100ng/mL and 2,440 (13.1%) had a TSAT level ≤ 20%. Compared with patients with TSAT level of > 20%, those with TSAT level of ≤ 20% had significantly higher risks of CKD progression (adjusted hazard ratio [aHR]: 1.66, 95% confidence intervals [CI]: 1.16–2.37; P = 0.005) and all-cause mortality (aHR: 2.21, 95% CI: 1.36–3.57; P = 0.001). The robustness of results was supported by subgroup analyses. However, there was no significant association found between ferritin levels and the risk of CKD progression or all-cause mortality (P > 0.05). Conclusion: Iron deficiency was prevalent in NDD-CKD patients without anemia, and TSAT could be a modifiable risk factor of CKD progression and all-cause mortality. The screening of iron biomarkers, especially TSAT, in the early stage of NDD-CKD is important to assess and improve prognosis. [ABSTRACT FROM AUTHOR]

Background: The effects of acute kidney injury (AKI) on liver-related outcomes in patients with hepatitis B virus (HBV) infection remain unclear. The study aimed to evaluate the association between AKI with liver-related mortality and complications in patients with HBV infection. Methods: The multicenter, retrospective cohort study included Chinese adults with HBV infection from 24 regional central hospitals between January 2000 and December 2022. AKI was defined as a ≥ 26.5 μmol/l increase in serum creatinine concentration within 48 h, or a ≥ 50% increase over the baseline within 7 days. The primary outcome was post-discharge liver-related mortality, while the secondary outcome was a composite of new-onset liver cirrhosis and hepatocellular carcinoma. Cox proportional hazard model was employed for analyses. Results: Of the 86,204 inpatients with HBV infection and without liver cancer or cirrhosis at baseline, 4407(5.1%) patients experienced AKI. During a mean follow-up of 4.6 ± 2.4 years, 334 (0.4%) patients died of liver-related events. After adjustment, AKI during hospitalization was significantly associated with a higher risk of liver-related mortality after discharge (adjusted hazard ratio (HR), 1.78; 95% confidence intervals (CI), 1.26–2.51, P = 0.001), especially in those with severe AKI. Similarly, AKI was associated with a higher risk of cirrhosis or new-onset hepatocellular carcinoma (adjusted HR, 1.33; 95%CI, 1.10–1.60, P = 0.004). The association between AKI and liver-related outcomes remained consistent across different subgroups. Conclusions: AKI during hospitalization was associated with substantial increased risk of liver-related mortality and incident liver-related complication. Our findings highlight the importance of monitoring AKI in patients with HBV infection for tailoring personalized treatments. [ABSTRACT FROM AUTHOR]

Background: Diabetic kidney disease (DKD) is a significant contributor to the development of end-stage renal disease and cardiovascular disease (CVD), with inflammation being a critical factor in its pathogenesis. The aim of this study is to examine the relationship between the neutrophil-to-lymphocyte ratio (NLR), a new inflammatory marker, and mortality from all causes and CVD in patients with DKD. Methods: This multicenter, retrospective cohort study utilized data from the China Renal Data System (CRDS) on patients with DKD hospitalized between January 1, 2000, and February 28, 2023. The patients' demographic information, along with their initial clinical and laboratory results, were collected and recorded. Follow-up continued until July 1, 2023, and patients were categorized into two groups based on the median baseline NLR. The Cox proportional hazards regression, Restricted cubic spline (RCS) curves, The Kaplan–Meier curve, Fine–Gray competing risk model, Time-dependent ROC and subgroup analysis were used to analyze the association between all-cause mortality and CVD mortality in patients having DKD with varying NLR. Results: This study included 11,427 patients who had been clinically diagnosed with DKD. Baseline NLR was associated with C-reactive protein, procalcitonin, high-sensitivity C-reactive protein, plasma D-dimer, cystatin C, creatinine, urea nitrogen, brain natriuretic peptide, and eGFR. We selected the demographic characteristics, differential factors from univariate analysis, and clinically DKD-related laboratory indicators as covariates for Cox analysis. Results indicated that NLR was an independent risk factor for both all-cause and CVD mortality after adjusting for the relevant variables. The risk of all-cause death and CVD death in the high NLR group was 4.688 and 2.141 times higher, respectively, compared to the low NLR group (HR = 4.688, 95% CI 1.153– 19.061, P = 0.031; HR = 2.141, 95% CI 1.257– 3.644, P = 0.005). However, potential confounding factors and biases, such as unmeasured variables and the influence of treatment interventions, could not be fully accounted for. Conclusion: NLR can independently predict the risk of all-cause and CVD mortality in patients with DKD. Identifying individuals with a high NLR and providing further intervention could be crucial measures to reduce both all-cause and CVD mortality. However, the results should be interpreted with caution due to the study's limitations. [ABSTRACT FROM AUTHOR]

Rosuvastatin and atorvastatin are the most widely prescribed moderate- to high-intensity statins, but evidence on their efficacy and safety during actual use is limited. This study compared the real-world effectiveness and safety of rosuvastatin and atorvastatin among adults with data in the China Renal Data System and UK Biobank databases. Visual Abstract. Comparative Effectiveness and Safety of Atorvastatin Versus Rosuvastatin: Rosuvastatin and atorvastatin are the most widely prescribed moderate- to high-intensity statins, but evidence on their efficacy and safety during actual use is limited. This study compared the real-world effectiveness and safety of rosuvastatin and atorvastatin among adults with data in the China Renal Data System and UK Biobank databases. Background: Rosuvastatin and atorvastatin are the most widely prescribed moderate- to high-intensity statins. However, evidence on their efficacy and safety during actual use is limited. Objective: To compare the real-world effectiveness and safety of rosuvastatin and atorvastatin. Design: Active comparator cohort study using target trial emulation. Setting: The China Renal Data System (CRDS) and UK Biobank (UKB) databases. Participants: Adults newly prescribed rosuvastatin or atorvastatin. Measurements: The primary outcome was all-cause mortality. Cox proportional hazards regressions were used after 1:1 multilevel propensity score matching. Results: Among the 285 680 eligible participants in both databases, 6-year all-cause mortality was lower for rosuvastatin than for atorvastatin (2.57 vs. 2.83 per 100 person-years in the CRDS database and 0.66 vs. 0.90 per 100 person-years in the UKB database), with differences in cumulative incidence of −1.03% (95% CI, −1.44% to −0.46%) in the CRDS database and −1.38% (CI, −2.50% to −0.21%) in the UKB database. For secondary outcomes in both databases, rosuvastatin conferred lower risks for major adverse cardiovascular events and major adverse liver outcomes. In the UKB database, the risk for development of type 2 diabetes mellitus was higher with rosuvastatin, and the 2 medications carried similar risks for development of chronic kidney disease and other statin-related adverse effects. Limitation: Possible residual confounding. Conclusion: This study found differences in risks for some important outcomes associated with rosuvastatin and atorvastatin. The differences were relatively small, and many did not meet traditional standards for statistical significance. Further research is needed to understand whether these findings can be used with confidence in clinical practice. Primary Funding Source: National Key R&D Program of China and National Natural Science Foundation of China. [ABSTRACT FROM AUTHOR]