Increasing evidence shows that the early lesions of Parkinson's disease (PD) originate from gut, and correction of microbiota dysbiosis is a promising therapy for PD. FLZ is a neuroprotective agent on PD, which has been validated capable of alleviating microbiota dysbiosis in PD mice. However, the detailed mechanisms still need elucidated. Through metabolomics and 16S rRNA analysis, we identified glycoursodeoxycholic acid (GUDCA) was the most affected differential microbial metabolite by FLZ treatment, which was specially and negatively regulated by Clostridium innocuum, a differential microbiota with the strongest correlation to GUDCA production, through inhibiting bile salt hydrolase (BSH) enzyme. The protection of GUDCA on colon and brain were also clarified in PD models, showing that it could activate Nrf2 pathway, further validating that FLZ protected dopaminergic neurons through promoting GUDCA production. Our study uncovered that FLZ improved PD through microbiota-gut-brain axis, and also gave insights into modulation of microbial metabolites may serve as an important strategy for treating PD.

Although enteric glial cell (EGC) abnormal activation is reported to be involved in the pathogenesis of Parkinson's disease (PD), and inhibition of EGC gliosis alleviated gut and dopaminergic neuronal dysfunction was verified in our previous study, the potential role of gut microbiota on EGC function in PD still need to be addressed. In the present study, fecal microbiota transplantation revealed that EGC function was regulated by gut microbiota. By employing 16S rRNA and metabolomic analysis, we identified that 3-indolepropionic acid (IPA) was the most affected differential microbial metabolite that regulated EGC gliosis. The protective effects of IPA on PD were validated in rotenone-stimulated EGCs and rotenone (30 mg/kg i.g. for 4 weeks)-induced PD mice, as indicated by decreased inflammation, improved intestinal and brain barrier as well as dopaminergic neuronal function. Mechanistic study showed that IPA targeted pregnane X receptor (PXR) in EGCs, and inhibition of IL-13Rα1 involved cytokine-cytokine receptor interaction pathway, leading to inactivation of downstream JAK1-STAT6 pathway. Our data not only provided evidence that EGC gliosis was critical in spreading intestinal damage to brain, but also highlighted the potential role of microbial metabolite IPA in alleviating PD pathological damages through gut-brain axis.

[This corrects the article DOI: 10.1016/j.apsb.2025.02.029.].

Objective:To analyze the viscosity characteristics of liver tumors and investigate the clinical value of shear wave dispersion (SWD) in the differentiation of benign and malignant liver tumors.Methods:A total of 103 patients with focal liver lesions were prospectively collected in Zhongshan Hospital Affiliated to Fudan University from October 2020 to July 2021, including 80 cases with single lesion and 23 cases with multiple lesions, and only the largest lesion was observed in patients with multiple lesions. SWD values were measured within the tumor and in the liver parenchyma 2 cm away from the tumor, and were compared between benign tumor group and maligant tumor group. The ROC curves of SWD value, SWD ratio and their combination in differentiating benign and malignant liver tumors were plotted respectively, and the optimal diagnostic threshold, the sensitivity, specificity and accuracy of different diagnostic methods were analyzed.Results:Among the 103 patients, 35 were benign and 68 were malignant. The SWD value of liver benign tumor group was lower than that of liver malignant tumor group [(16.38±3.58)m·s -1·kHz -1 vs (18.59±3.12)m·s -1·kHz -1], the SWD value of liver parenchyma background in liver benign tumor group was lower than that in liver malignant tumor group [(10.88±3.37)m·s -1·kHz -1 vs (14.31±3.34)m·s -1·kHz -1], and the differences were statistically significant (all P<0.05). The SWD ratio of benign tumor to surrounding liver parenchyma was higher than that of malignant tumor group [1.57(1.25, 2.00) vs 1.27(1.06, 1.57)], and the difference was statistically significant ( P<0.05). When the SWD value >15.60 m·s -1·kHz -1 was used as the cut-off value, the area under ROC curve (AUC) was 0.72, the sensitivity was 88.2%, the specificity was 51.4%, and the accuracy was 75.7%. The sensitivity, specificity, accuracy and AUC were 58.8%, 74.2%, 63.1%, and 0.68, respectively, when the ratio of SWD value<1.32 was used as the cut-off value. SWD value combined with SWD ratio for the diagnosis of liver malignant tumor, the AUC was 0.88, the sensitivity was 82.3%, the specificity was 83.0%, and accuracy was 81.6%. The diagnostic efficacy of the two in combination for liver malignant tumor was superior to SWD value ( Z=2.678, P=0.007 4) and SWD value ratio ( Z=3.822, P=0.000 1). Conclusions:SWD imaging can reflect the viscosity information of liver tumors and surrounding liver parenchyma, and has potential clinical application value in the differentiation of benign and malignant tumors.

Objective:To explore the diagnostic performance of ultrasound attenuation imaging (ATI) in grading the degree of hepatic steatosis in metabolic dysfunction-associated fatty liver disease (MAFLD).Methods:The liver gray-scale ultrasound and ATI examinations were performed on 212 subjects who were treated in Zhongshan Hospital Affiliated to Fudan University from August 2020 to March 2021. The attenuation coefficient(AC) values among different degrees of hepatic steatosis were analyzed and the diagnostic performance of ATI was evaluated. Relationships between AC values and clinical characteristics were assessed by Pearson′s correlation analysis.Results:The AC values for normal liver, mild, moderate and severe fatty liver were (0.56±0.05)dB·cm -1·MHz -1, (0.68±0.09)dB·cm -1·MHz -1, (0.82±0.09)dB·cm -1·MHz -1, (0.94±0.09)dB·cm -1·MHz -1, respectively. There were significant differences in AC values among different hepatic steatosis divisions( P<0.008). There was highly significant correlation between AC values and the degree of hepatic steatosis( r=0.860, P<0.01), moderate correlation between AC values and BMI( r=0.425, P<0.01), weak correlation between AC values and HDL-C( r=-0.237, P=0.029), no correlations between AC values and age, TC, TG, LDL-C ( r=0.083, 0.055, 0.133, -0.039, all P>0.05) .The areas under the receiver operating characteristics curve of ATI for mild fatty liver and above, moderate fatty liver and above, severe fatty liver and above were 0.958, 0.962, 0.918; the sensitivity were 90.1%, 95.8%, 94.9%, the specificity were 96.1%, 87.1%, 73.9%, and the cut-off values were 0.666 dB·cm -1·MHz -1, 0.719 dB·cm -1·MHz -1, 0.803 dB·cm -1·MHz -1, respectively. Conclusions:ATI is a reliable and convenient method for evaluating the degree of hepatic steatosis in MAFLD.

Parkinson's disease (PD) is the second most common neurodegenerative disease, but none of the current treatments for PD can halt the progress of the disease due to the limited understanding of the pathogenesis. In PD development, the communication between the brain and the gastrointestinal system influenced by gut microbiota is known as microbiota-gut-brain axis. However, the explicit mechanisms of microbiota dysbiosis in PD development have not been well elucidated yet. FLZ, a novel squamosamide derivative, has been proved to be effective in many PD models and is undergoing the phase I clinical trial to treat PD in China. Moreover, our previous pharmacokinetic study revealed that gut microbiota could regulate the absorption of FLZ

Objective To improve the orotracheal intubation verifying technique and reduce the complication of backflow in rat experiment.Methods A new position evaluation of anti-backflow device was designed and made of safety IV catheter and closed IV catheter system.60 adult male Sprague Dawley rats 216±20 g were randomly assigned to two groups: group A (n=40) for verifying placement, group B (n=20) for anti-backflow test.Group A was further divided into group A1 using self-designed positioning device, group A2 using aerosol, group A3 taking cotton fiber for positioning judgment.The group B was divided into two subgroups, B1 and B2, counting escaped bubbles as a means of positioning observation, the difference is that group B1 using frustum of a cone shape anti-backflow device, while the group B2 using common airway tube.Routine endotracheal intubation was performed to observe and record the time of positioning, the location of exhalation phase, and the length of inspiratory phase countercurrent water column.The group A1 further performed tracheotomy under direct vision clearly to confirm the anatomic positioning status.Results During the exhalation cycle,three or more bubbles were observed to escape continuously, indicating that the intubation tube was properly placed and open in the airway.Positioning time: It took 1.75±1.02 respiratory cycles in group A1,3.30±0.95 respiratory cycles in group A2 and 4.10±0.99 respiratory cycles in group A3 to complete the assessment the positioning status.There was no statistically significant difference between groups A2 and A3 (P> 0.05).The time needed for group A1 was significantly shorter than that of groups A2 and A3 (P < 0.01).The longest countercurrent water column length in group B1 was 3.23±0.53 cm, and 8.48±1.01 cm in the group B2.Conclusions The new designed anti-backflow positioning evaluation device is a simple and convenient appliance to evaluate the location of orotracheal intubation in rat experiment.It can effectively improve the positioning efficiency and has practical application value.

BACKGROUND: Earthworms are one of the most important constituents in the ecosystem and become an environmental information carrier between terrestrial organisms and soil ecosystem. They were known as important non-target terrestrial soil organisms for assessing the general impact of pollution on the soil community. Protein content and growth rate in response to organic and heavy metal contaminants in soil are often used to assess the soil ecotoxicity.OBJECTIVES: To investigate the effects of 1, 8-dihydroxyanthraquinone,one representative of hydroxyanthraquinones, on the earthworm eisenia foetide under laboratory conditions of the growth rate and protein content.DESIGN: Experimental study based on the experimental animals.SETTING: Eco-toxicological laboratory and genetic laboratory in a university.MATERIALS: The experiment was conducted in the Eco-toxicological Laboratory and the Genetic Laboratory, Dalian University of Technology from February to July 2004. Eisenia foetide, a kind of international standard earthworm, were maintained in a soil mixture before experiments. Earthworms used in this study were healthy adults with 1 -2 month old and 200 - 300 mg mass and the number of the earthworms in each analytical experiment was 10.METHODS: The earthworms were removed from the soil 12 hours before use and stored in Petri dishes on damp filter paper to void gut contents.Then, these earthworms were exposed for various durations to soils contaminated. The earthworm weight and protein content were determined respectively at every 7 days interval.MAIN OUTCOME MEASURES: Effects of 1, 8-dihydroxyanthraquinone on growth rate and protein content of earthworms.RESULTS: No lethal effect of 1, 8-dihydroxyanthraquinone was observed even at the highest concentration(1.0 g/kg soil) of exposure. The sub-lethal effect, however, was evident at all the concentration scale. 1,8-dihydroxyanthraquinone caused a significant reduction in the growth rate (maximum -22. 5% ) at the dosage of 1.0 g/kg and 28 days contact time.Additionally a reduction in total soluble protein was observed in all treated worms(maximum- 39.6% ) at the dosage of 0. 8 g/kg and 7 days contact time.CONCLUSION: 1, 8-dihydroxyanthraquinone was potentially dangerous to the soil ecosystem and more ecological risk assessment of this chemical material should be thoroughly carried out.