Developing and identifying effective medications and targets for treating hepatic fibrosis is an urgent priority. Our previous research demonstrated the efficacy of artesunate (ART) in alleviating liver fibrosis by eliminating activated hepatic stellate cells (HSCs). However, the underlying mechanism remains unclear despite these findings. Notably, endocytic adaptor protein (NUMB) has significant implications for treating hepatic diseases, but current research primarily focuses on liver regeneration and hepatocellular carcinoma. The precise function of NUMB in liver fibrosis, particularly its ability to regulate HSCs, requires further investigation. This study aims to elucidate the role of NUMB in the anti-hepatic fibrosis action of ART in HSCs. We observed that the expression level of NUMB significantly decreased in activated HSCs compared to quiescent HSCs, exhibiting a negative correlation with the progression of liver fibrosis. Additionally, ART induced senescence in activated HSCs through the NUMB/P53 tumor suppressor (P53) axis. We identified NUMB as a crucial regulator of senescence in activated HSCs and as a mediator of ART in determining cell fate. This research examines the specific target of ART in eliminating activated HSCs, providing both theoretical and experimental evidence for the treatment of liver fibrosis.
Hepatic Stellate Cells/cytology* ; Liver Cirrhosis/genetics* ; Artesunate/pharmacology* ; Cellular Senescence/drug effects* ; Membrane Proteins/genetics* ; Animals ; Humans ; Nerve Tissue Proteins/genetics* ; Tumor Suppressor Protein p53/genetics* ; Male ; Mice

Objective By establishing a clinical decision reminder information system for the prevention of venous thromboembolism in hospitals,the aim is to improve the standardized prevention rate of VTE in hospitalized patients,thereby re-ducing the incidence of VTE in hospitals,reducing potential unexpected and perioperative deaths,improving medical quality,and ensuring patient safety.Methods Select high-risk patients with venous VTE and no bleeding who were hospitalized in a certain hospital in June 2023 and October 2023 as the control group and observation group,respectively.The observation group uses the hospital's venous VTE prevention clinical decision reminder system,which reminds physicians through information warning,clin-ical decision assistance,and standardized medical order sets,Integrate information technology between the risk assessment level of VTE for patients by nursing staff and the standardized prevention measures that physicians should provide,and compare the quality indicators of VTE prevention between the two groups through training,education,and other methods.Results By estab-lishing a clinical decision reminder system for the prevention of venous VTE in hospitals,the drug prevention execution rate in-creased from 18.01％to 56.10％,and the hospital related VTE incidence rate decreased from 2.42％to 1.75％,with statisti-cally significant differences.Conclusion The establishment of a clinical decision reminder system for the prevention of venous thromboembolism in hospitals can effectively improve the standardized prevention rate of VTE in hospitals and promote the im-provement of medical quality and safety management.

Aim To investigate the effects of Gubu decoction combined with intraluminal reconstruction on bi-pedal vibration sensation threshold and microcirculation in patients with lower extremity arteriosclerotic occlusive disease(LEAOD).Methods A total of 152 patients who came to Lishui Gentral Hospital for LEAOD treatment from April 2021 to April 2023 were divided into the observation group(intraluminal reconstruction+Gubu decoction,76 cases)and the control group(intraluminal reconstruction,76 cases)by random number table method,and the traditional Chinese medicine(TCM)syndrome scores,clinical efficacy,microcirculation indicators and bifoot vibration sensation threshold of the two groups were compared.Results After treatment,the scores of TCM syndromes such as limb pain,limb numbness,intermittent claudication,and limb fear of cold decreased after treatment in both groups,and the decrease of ob-servation group was more obvious(P＜0.05).The clinical effect of observation group(96.05％)was significantly higher than that of control group(84.21％)(P＜0.05).After treatment,the flow state integral,tube loop integral and periloop integral decreased,and the apical vessel diameter increased in both groups,and the changes of various indexes in the ob-servation group were more significant(P＜0.05).After treatment,the threshold of sensation in both groups decreased,and the observation group was significantly lower(P＜0.05).Conclusion Gubu decoction combined with intraluminal reconstruction can effectively reduce the foot sensation threshold and improve the microcirculation of affected limbs in LEAOD patients.

Brain signals refer to electrical signals or metabolic changes that occur as a consequence of brain cell activity.Among the various non-invasive measurement methods,electroencephalogram(EEG)stands out as a widely employed technique,providing valuable insights into brain patterns.The deviations observed in EEG reading serve as indicators of abnormal brain activity,which is associated with neurological diseases.Brain?computer interface(BCI)systems enable the direct extraction and transmission of information from the human brain,facilitating interaction with external devices.Notably,the emergence of artificial intelligence(AI)has had a profound impact on the enhancement of precision and accuracy in BCI technology,thereby broadening the scope of research in this field.AI techniques,encompassing machine learning(ML)and deep learning(DL)models,have demonstrated remarkable success in classifying and predicting various brain diseases.This comprehensive review investigates the application of AI in EEG-based brain disease diagnosis,highlighting advancements in AI algorithms.

Background Perfluorinated alkyl substances (PFAS) are a class of synthetic organic fluorides, which have adverse health effects on brain function, and limited research has been conducted on their effects on depression. Objective To assess potential correlation between serum PFAS and depression. Methods Using the 2015—2016 and 2017—2018 National Health and Nutrition Examination Survey (NHANES) datasets, 2626 subjects with complete relevant information in people ≥20 years old were selected. Logistic regression and restricted cubic splines were used to analyze the association and dose-response relationship between serum PFAS concentration and depression. Subgroup analysis was performed on sex, age, race, education level, marital status, family income to poverty ratio, moderate exercise, body mass index, and drinking status. Results Among the 2626 subjects, there were 666 patients (25.4%) with mild or above depression. After adjusting for race, education level, marital status, body mass index, moderate exercise, drinking history, cotinine, and other types of PFAS, serum perfluorooctane sulfonate (PFOS) was positively associated with the risk of depression (OR=1.85, 95%CI: 1.14, 3.02), and showed a nonlinear dose-response relationship (χ²=6.37, P_nonlinear=0.012). Perfluorononanoic acid (PFNA) was inversely associated with the risk of depression (OR=0.23, 95%CI: 0.14, 0.39), and showed a linear dose-response relationship (P_trend<0.001, χ²=35.13, P_overall<0.001). After subgroup analysis, it was found that males, 20-39 year-olds and 40-64 year-olds were more sensitive to PFNA exposure (OR=0.15, 95%CI: 0.06, 0.37; OR=0.16, 95%CI: 0.06, 0.40; OR=0.18, 95%CI: 0.08, 0.39). PFOS only showed a statistically significant health effect in people aged 20-39 years (OR=3.00, 95%CI: 1.14, 7.94). In addition, among subgroups of non-Hispanic blacks, cohabitants, current drinkers, high school graduates, and obese patients, exposure to PFAS was significantly associated with the risk of depression. Conclusion PFOS exposure may be associated with increased levels of depression, whereas PFNA exposure may be protective.

气味是评价食品新鲜度最重要的参数之一。当气味以其自然浓度存在时，会在嗅觉系统中引发不同的神经活动模式。本研究提出了一种通过检测食物气味进行食物检测与评价的在体生物传感系统。我们通过将多通道微电极植入在清醒大鼠嗅球的僧帽/丛状细胞层上，进而对神经信号进行实时检测。结果表明，不同的气味可以引起不同的神经振荡活动，每个僧帽/丛状细胞会表现出特定气味的锋电位发放模式。单个大鼠的少量细胞携带足够的信息，可以根据锋电位发放频率变化率的极坐标图来区分不同储存天数的食物。此外，研究表明气味刺激后，β振荡比γ振荡表现出更特异的气味响应模式，这表明β振荡在气味识别中起着更重要的作用。综上，本研究提出的在体神经接口为评估食品新鲜度提供了一种可行性方法。
Olfactory Bulb ; Odorants ; Smell

Objective: To observe the effect of acupuncture on the intestinal flora in Parkinson disease (PD) model mice and explore the mechanism of acupuncture in improving the locomotor function in PD. Methods: Thirty-two C57BL/6 mice were randomly divided into a control group, a 1-methyl-4-phenyl-1,2,3,6- tetrahydropyridine (MPTP) group, a MPTP + acupuncture group (MPTP+A), and a MPTP + madopar group (MPTP+M), with 8 mice in each group. Except for the control group, the other groups were intraperitoneally injected [25 mg/(kg·bw)] with MPTP to establish PD mouse models. After successful modeling, the MPTP group received no intervention, the MPTP+A received acupuncture at Tianshu (ST25), Guanyuan (CV4), and Zusanli (ST36), and the MPTP+M was given madopar [125 mg/(kg·bw)] by intragastric gavage. After consecutive 10-day interventions, the intestinal function and behaviors of the mice were detected. The 16S rRNA gene sequence was used to analyze the composition of fecal intestinal flora in each group. Real-time fluorescence quantitative polymerase chain reaction (RT-qPCR) and enzyme-linked immunosorbent assay were used to detect the expression levels of inflammatory cytokines in the brain and serum. The expression levels of tyrosine hydroxylase (TH) and α-synuclein in the substantia nigra (SN) were detected by immunohistochemical staining. Toll-like receptor (TLR) 2 and lipopolysaccharide receptor CD14 (CD14) in the SN were determined by RT-qPCR. Myeloid differentiation factor (MyD) 88, nuclear factor kappa-B (NF-κB) and Akt1 in the SN were detected by Western blotting. Results: After the intervention, compared with the control group, the intestinal motility, fecal water content, and the expression of TH in the SN were significantly decreased in the MPTP group (P<0.05), along with an increased α-synuclein expression (P<0.05). Additionally, the results of the fecal microflora test showed that the alpha diversity of the MPTP decreased, and the levels of inflammatory cytokines [tumor necrosis factor (TNF)-α, inducible nitric oxide synthase (iNOS), interleukin (IL)-1β, and IL-6] in the serum and SN, and the expression of NF-κB in the SN were significantly increased (P<0.05). Compared with the MPTP group, acupuncture intervention significantly enhanced the autonomous horizontal movement and coordination ability of PD mice (P<0.05); acupuncture and madopar interventions significantly reduced the levels of α-synuclein, inflammatory cytokines (TNF-α, iNOS, IL-1β, and IL-6) in the serum and SN, and the NF-κB expression in the SN, along with significantly increased alpha diversity richness index (P<0.05). In addition, the relative abundance of Bacteroides increased significantly in the MPTP+A (P<0.05), while the relative abundance of Firmicutes and Cyanobacteria decreased significantly (P<0.05). Conclusion: Acupuncture intervention can improve locomotor function, reduce α-synuclein aggregation and inflammatory factors expression, and increase the Akt signaling pathway in PD mice. In addition, acupuncture intervention can benignly regulate the intestinal flora of PD mice. Therefore, it suggests that acupuncture intervention can protect PD model mice probably by regulating intestinal flora and activating Akt signaling pathway.

BACKGROUND: Parkinson's disease is a neurodegenerative disorder, and recent studies suggested that oxidative stress contributes to the degeneration of dopamine cell in Parkinson's disease. Glutamine also has a positive role in reducing oxidative stress damage. In this study, we hypothesized that glutamine offers protection against oxidative stress injury in 1-methyl-4-phenylpyridinium (MPP)-induced Parkinson's disease cell model. METHODS: MPP was used to induce PD models in PC12 cells and classified into control, M0 (MPP), G0 (glutamine), and M0+G0 groups. CCK-8 and AO/EB staining assays were used to examine cell proliferation and apoptosis, respectively. Western blotting was applied to examine the protein expression of PI3K, P-Akt, Akt, P-mTOR, and mTOR. RESULTS: We showed that glutamine suppressed cytotoxicity induced by MPP in PC12 cells. MPP decreased the superoxide dismutase and glutathione peroxidase activity and increased the malondialdehyde content, which were restored by glutamine. Moreover, MPP increased the expression of PI3K, P-Akt, Akt, P-mTOR, and mTOR, which were inhibited by glutamine. And the antioxidant capacity of glutamine on PC12 cells could be improved by LY294002 and inhibited by IGF-1. CONCLUSION These results suggest that glutamine strengthens the antioxidant capacity in PC12 cells induced by MPP through inhibiting the activation of the PI3K/Akt signaling pathway. The effects of glutamine should be investigated and the protective mechanism of glutamine in PD must be explored in future studies.
1-Methyl-4-phenylpyridinium ; administration & dosage ; Analysis of Variance ; Animals ; Cell Culture Techniques ; Disease Models, Animal ; Glutamine ; pharmacology ; Oxidative Stress ; drug effects ; Parkinson Disease ; Phosphatidylinositol 3-Kinases ; metabolism ; Protective Agents ; pharmacology ; Proto-Oncogene Proteins c-akt ; metabolism ; Rats

Objective To investigate the prevalence of mcr-1 gene,a plasmid-mediated polymyxin resistance gene,in Escherichia coli(E.coli) strains isolated in Dongyang of Zhejiang Province and to under-stand the epidemiological characteristics of E.coli strains carrying mcr-1 gene in order to provide local clini-cians with a theoretical basis for prevention and control of the spread of mcr-1-bearing E.coli strains. Meth-ods A total of 315 E.coli strains were collected in the People′s Hospital of Dongyang, Zhejiang Province from January to December 2016. All strains were isolated from specimens of blood,urine,respiratory tract, etc. PCR was performed to detect the genes confering resistance to polymyxin (mcr-1 gene), β-lactamase and carbapenem. Minimal inhibitory concentrations (MIC) of antibiotics against mcr-1-positive strains were determined by micro-broth dilution method. Conjugation test was performed to confirm whether the mcr-1 gene was located on the transferable plasmid. Multilocus sequence typing (MLST) was used for molecular typing of mcr-1-positive strains. Results Five mcr-1-positive strains were identified from 315 E.coli strains with a positive rate of 1.6%. Two out of the five mcr-1-positive E.coli strains contained β-lactamase resist-ance genes,blaTEM-1and blaCTX-M-14. Both of them were resistant to the first, second and third generation of cephalosporins and one was also resistant to cefepime. All of the five mcr-1-positive E.coli strains were sen-sitive to ciprofloxacin and levofloxacin,but resistant to ticarcillin/clavulanic acid. No carbapenem resistance genes were detected. One transconjugant was successfully obtained by transconjugation assay. MLST analysis showed that a total of four sequence types were identified, including ST131 (two strains), ST43 (one strain),ST69 (one strain) and ST349(one strain). Conclusion Only 1.6% of all E.coli strains isolated in Dongyang area of Zhejiang Province carry mcr-1 gene,indicating that there is no epidemic of mcr-1 gene-positive E.coli infection. The coexistence of mcr-1 gene and β-lactamase resistance genes in E.coli strains isolated in Dongyang suggests that local clinicians should avoid antibiotic abuse to prevent the spread of drug-resistant E.coli.