ObjectiveTo investigate the anti-Alzheimer's disease （AD） effect of Dipsacus asper（DA） in the Caenorhabditis elegans model， and decipher the underlying mechanism via the peroxisome proliferator-activated receptor α （PPARα）/transcription factor EB （TFEB） pathway. MethodsFirst， transgenic AD C. elegans individuals were assigned into the blank control， model， positive control （WY14643， 20 µmol·L^-1）， and low-， medium-， and high-dose （100， 200， and 400 mg·L^-1， respectively） DA groups. The amyloid β-42 （Aβ₄₂） formation in the muscle cells， the paralysis time， and the deposition of amyloid β-protein （Aβ） in the head were detected. The lysosomal autophagy in the BV2 cell model was examined by Rluc-LC3wt/G120A. The expression levels of lysosomal autophagy-related proteins LC3Ⅱ， LC3I， LAMP2， and TFEB were detected by Western blot. Real-time quantitative polymerase chain reaction （Real-time PCR） was employed to determine the mRNA levels of autophagy-related genes beclin1 and Atg5 and lysosome-related genes LAMP2 and CLN2 downstream of PPARα/TFEB. A reporter gene assay was used to detect the transcriptional activities of PPARα and TFEB. Immunofluorescence was used to detect the fluorescence intensity of PPARα， and the active components of the ethanol extract of DA were identified by UPLC-MS. RCSB PDB， Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform （TCMSP）， and Autodock were used to analyze the binding between the active components and PPARα-ligand-binding domain （LBD）. ResultsCompared with the model group， the positive control group and 200 and 400 mg·L^-1 DA groups showed prolonged paralysis time （P<0.05）， and all the treatment groups showed decreased Aβ deposition in the head （P<0.01）. DA within the concentration range of 50-500 mg·L^-1 did not affect the viability of BV2 cells. In addition， DA enhanced the autophagy flux （P<0.05）， up-regulated the mRNA levels of beclin1， Atg5， LAMP2， and CLN2 （P<0.05， P<0.01）， promoted the nuclear translocation of TFEB （P<0.05）， increased LAMP2 expression and autophagy flux （P<0.05， P<0.01）， and enhanced the transcriptional activities of PPARα and TFEB （P<0.01）. The positive control group and 200 and 400 mg·L^-1 DA groups showed enhanced fluorescence intensity of PPARα in the BV2 nucleus （P<0.01）. UPLC-MS detected nine known compounds of DA， from which 8 active components of DA were screened out. The docking results suggested that a variety of components in DA could bind to PPARα-LBD and form stable hydrogen bonds. ConclusionDA may reduce the pathological changes in AD by regulating the PPARα-TFEB pathway.

Rabies is an acute infectious disease caused by rabies virus with a high fatality rate. Post-exposure human rabies vaccination is an important measure to reduce the risk of rabies. Rabies vaccine is mainly used for post-exposure immunization with safety and tolerance. However, adverse reactions may occur in some recipients, mainly including local reactions such as pain, redness and swelling, and systemic reactions such as fever and headache. Usually, the symptoms are mild and self-limited, but severe adverse reactions in allergic patients may be life-threatening. The occurrence of adverse reactions to rabies vaccine for human use is closely related to individual differences, vaccine production process, and vaccination factors. The articles on adverse reaction of rabies vaccine for human use published in CNKI and PubMed database from 2006 to 2024 were retrieved. The incidence, causes and countermeasures of adverse reaction of rabies vaccine for human use were reviewed, so as to provide reference for reducing adverse reactions of rabies vaccine.

Objective:Inflammation has been confirmed to play an important role in the occurrence and development of sudden sensorineural hearing loss（SSNHL）, and the neutrophil-to-lymphocyte ratio（NLR） is a biomarker positively correlated with the degree of inflammation. This study aims to identify the difference in serum NLR between patients with SSNHL and normal population, and to evaluate the predictive efficacy of NLR for the occurrence and prognosis of SSNHL, thereby guiding the clinical diagnosis and treatment of SSNHL. Methods:In this study, 96 patients diagnosed with SSNHL admitted to our department from January 2023 to March 2024 and 96 patients diagnosed with vocal cord polyps admitted to our department during the same period were recruited as a control group. Multivariate Logistic regression was used to evaluate independent related factors, and a nomogram was constructed to predict the probability of SSNHL. The receiver operating characteristic（ROC） curve and calibration curve were used to evaluate the accuracy of prediction. Results:Multivariate logistic regression analysis showed that a high level NLR（OR2.215; 95%CI1.597-3.073; P<0.001） were independently associated with the presence of SSNHL. High age（OR1.036; 95%CI1.009-1.067; P=0.012）, high FIB（OR2.35; 95%CI1.176-4.960; P=0.019） were the risk factor for SSNHL. Incorporating these 3 factors, a forest plot and a nomogram were generated. The ROC curve, nomogram and calibration curve showed that the model had good clinical practicability. A low NLR（OR0.598; 95%CI0.439-0.816; P<0.001） was significantly associated with a favorable prognosis of SSNHL. Conclusion:Elevated NLR can serve as an promising biomarker for assessing the risk of SSNHL. The nomograms calculation model may be utilized as a tool to estimate the probability of SSNHL. Low level NLR is significantly associated with a good prognosis of SSNHL.
Humans ; Neutrophils ; Female ; Male ; Lymphocytes ; Hearing Loss, Sensorineural/blood* ; Hearing Loss, Sudden/diagnosis* ; Middle Aged ; Prognosis ; Nomograms ; ROC Curve ; Adult ; Logistic Models ; Biomarkers/blood* ; Lymphocyte Count ; Inflammation/blood* ; Clinical Relevance

[This corrects the article DOI: 10.1016/j.apsb.2019.01.013.].

Objective Melatonin has been shown to have neuroprotective effects.This study is aimed at observing the effects of copper deposition on cognitive function in a toxic milk(TX)mouse model of Wilson disease(WD),and investigating the effects and mechanisms of action of Gandou Bushen Decoction(GDBSD)on melatonin synthesis and pineal function in the WD model mice.Methods A total of 30 homozygous TX mice were randomly assigned to 3 groups(n=10 in each group),including a WD group,a GDBSD group,and a dimercaptosuccinic acid(DMSA)group.A total of 10 DL mice were included in the normal control(NC)group.The structure and copper content of pineal gland tissues,oxidative stress and apoptosis-related markers,and serum melatonin levels were evaluated using hematoxylin-eosin(HE)staining,enzyme-linked immunosorbent assay(ELISA),flow cytometry,and Western blot.Results Compared with the NC group,the WD group exhibited decreased learning and cognitive abilities(P＜0.05),damaged pineal gland structure,increased copper content,reactive oxygen species(ROS)levels,and mitochondrial damage rate in the pineal gland(P＜0.01),altered levels of melatonin and oxidative stress-related markers(P＜0.05),upregulated expression levels of pro-apoptotic proteins Bax and Caspase-3,and decreased expression of the anti-apoptotic protein Bcl-2(P＜0.01).After treatment with GDBSD and DMSA,the SIRT3/FOXO3α signaling pathway was activated,the copper content in the pineal gland was reduced,and oxidative stress and apoptosis-related damages were improved,leading to an improvement in learning and memory abilities(P＜0.05).Conclusion GDBSD can alleviate cognitive impairments in WD mice caused by pineal gland copper deposition by inhibiting oxidative stress and apoptosis in the pineal gland.The underlying molecular mechanism is associated with the regulation of the SIRT3/FOXO3α signaling pathway.

Objective To explore the value of neutrophil extracellular trapping nets(neutrophil extracellular traps,NETs)in the diagnosis and monitoring of acute ischemic stroke(acute ischemic stroke,AIS).Methods From June 2023 to February 2024,63 patients newly diagnosed with AIS at the Ganmei Hospital Affiliated with Kunming Medical University were selected as the experimental group,and 58 non-AIS individuals matched in gender,age,and other characteristics were selected as the control group.The NETs levels of patients in the experimental group were detected before and 7-10 days after treatment,and general clinical data and related laboratory results were statistically analyzed.Results The experimental group showed significantly higher levels of NEUT,LYMPH,MONO,EO,FDP,D-dimer,and NETs compared to the control group(P<0.05).The NETs levels before treatment were significantly higher than those at 7～10 days after treatment and in the control group(P<0.05).The NETs levels 7～10 days after treatment were significantly higher than those in the control group(P<0.05).NEUT,MONO,FDP,D-dimer,and NIHSS scores were positively correlated with the pre-treatment NETs levels(P<0.05).Elevated serum NETs levels were associated with AIS risk factors(P<0.05).The combined diagnostic value of NEUT,D-dimer,and NETs for AIS was superior to other indicators.Conclusion NETs are highly expressed in the serum of patients with acute ischemic stroke,and serum NETs have certain value in the auxiliary diagnosis and monitoring of acute ischemic stroke.

The pathogenesis of urolithiasis is not yet clear， and there are obvious limitations in the prevention and treatment of urolithiasis by either Chinese or western medicine. The microscopic pathological changes of the kidney from anatomical perspective have a certain internal connection with viewpoint of “kidney storing insufficiency， and kidney deficiency as the root” in the traditional Chinese medicine （TCM） zang-fu （脏腑） theory. Accordingly， the prevention and treatment of urolithiasis by integrated traditional Chinese and western medicine based on “shen-kidney” theory has been proposed. It is believed that the prevention and treatment of urolithiasis can be divided into two stages， that is expelling stones and preventing stones. In terms of preventing stones from kideny， it is recommended to focus on the early pathological changes of the kidney； for preventing stones from shen， it is advised to prevent and treat urolithiasis from kidney deficiency. The treatment should be time-based and stage by stage. Adhering to the principle of “prevention before disease occurs， prevention is more important than treatment” aims to advance the intervention targets for the prevention and treatment of urolithiasis. Emphasizing on the simultaneous treatment of kidney disease and urolithiasis， it is critical to put focus on the development of calcium-containing crystalline nephropathy in the early stage of stone formation， as well as the fundamental pathogenesis of kidney deficiency in TCM. Shen-kidney theory aims to further promote the integration of traditional Chinese and western medicine in the prevention and treatment of urolithiasis， which may provide certain reference for solving the current dilemma of urolithiasis prevention and treatment.