OBJECTIVE To investigate the effects and potential mechanism of Yiqi wenyang huwei decoction （YQWY） in improving airway inflammation and remodeling in rats with bronchial asthma （BA） based on the Toll-like receptor 4 （TLR4）/myeloid differentiation primary response protein 88 （MyD88）/nuclear factor-κB （NF-κB） signaling pathway. METHODS Male SD rats were randomly divided into the normal group， the model group， the dexamethasone group （positive control， 0.5 mg/kg）， and YQWY low-， medium- and high-dose groups （5， 10， 20 g/kg， calculated by the crude drug）， with 8 rats in each group. Except for the normal group， rats in all other groups were sensitized twice with ovalbumin combined with aerosol challenge to establish a BA model. From day 14 to day 34 of the experiment， the rats in each group were administered the corresponding drug solution or normal saline intragastrically， once a day， 1 hour before aerosol challenge. At 24 hours after the final aerosol challenge， asthma symptom scores were assessed， serum levels of immunoglobulin E （IgE） were measured， and the levels of inflammatory cytokines （interleukin-4， interleukin-5， interleukin-13 and tumor necrosis factor-α） and the numbers of inflammatory cells （white blood cell， eosinophil， neutrophil， lymphocyte， monocyte and basophil） in bronchoalveolar lavage fluid were determined. Pathological changes in lung tissue were observed. The mRNA expressions of TLR4， MyD88 and NF-κB， as well as the protein expressions of TLR4， MyD88， NF-κB p65 and phosphorylated NF-κB p65 in lung tissue， were detected. RESULTS Compared with the model group， the pathological changes， such as inflammatory cell infiltration， abnormal deposition of collagen fibers， and goblet cell hyperplasia in the lung tissue of rats in each drug group， were alleviated to varying degrees. The asthma symptom scores （except for the YQWY low-dose group）， the levels of IgE and inflammatory cytokines （except for interleukin-5 in the YQWY medium-dose group）， the number of inflammatory cells （except for monocyte and basophil in the YQWY low-dose group）， the mRNA expression of TLR4， MyD88 and NF-κB， as well as the protein expressions of TLR4， MyD88， NF-κB p65 and phosphorylated NF-κB p65 （except for MyD88 and NF-κB p65 proteins in the YQWY low-dose group as detected by Western blo t） were all significantly reduced or down-regulated （ P ＜0.05 or P ＜0.01）. CONCLUSIONS YQWY can alleviate asthma-like manifestations in BA rats and improve their airway inflammation and remodeling； these effects may be related to the formula’s inhibition of the abnormal activation of the TLR4/MyD88/NF-κB signaling pathway.

Epilepsy affects over 50 million people worldwide. Drug-resistant epilepsy (DRE) accounts for up to a third of these cases, and neuro-inflammation is thought to play a role in such cases. Despite being a long-debated issue in the field of DRE, the mechanisms underlying neuroinflammation have yet to be fully elucidated. The pro-inflammatory microenvironment within the brain tissue of people with DRE has been probed using single-cell multimodal transcriptomics. Evidence suggests that inflammatory cells and pro-inflammatory cytokines in the nervous system can lead to extensive biochemical changes, such as connexin hemichannel excitability and disruption of neurotransmitter homeostasis. The presence of inflammation may give rise to neuronal network abnormalities that suppress endogenous antiepileptic systems. We focus on the role of neuroinflammation and brain network anomalies in DRE from multiple perspectives to identify critical points for clinical application. We hope to provide an insightful overview to advance the quest for better DRE treatments.
Humans ; Drug Resistant Epilepsy/metabolism* ; Neuroinflammatory Diseases/immunology* ; Animals ; Brain/pathology* ; Nerve Net/pathology*

Objective To investigate the predictive value of serum vasoactive intestinal peptide(VIP)and 5-hydroxytryptamine(5-HT)levels on the outcome of spinal cord electrical stimulation(SCS)in patients with postherpetic neuralgia(PHN).Methods A total of 96 PHN patients who received SCS treatment in Ziy-ang Central Hospital from January 2022 to December 2023 were selected.According to the disease outcomes of all PHN patients after 6 months of treatment,a good group(n=71)and a poor group(n=25)were set up.The clinical data of the two groups were collected and the serum VIP and 5-HT levels were detected in all pa-tients before treatment.The predictive value of serum VIP and 5-HT on disease outcome after SCS treatment in PHN patients was evaluated by receiver operating characteristic(ROC)curve,and the influencing factors of disease outcome after SCS treatment in PHN patients was explored by multivariate Logistic steppe gression a-nalysis.Results The levels of serum VIP and 5-HT in poor group were higher than those in good group(P＜0.05).The area under the curve(AUC)of serum VIP and 5-HT for predicting the disease outcome of PHN patients after SCS treatment were 0.829(95％CI:0.779-0.874)and 0.743(95％CI:0.693-0.793),respec-tively,and the AUC of combined prediction was 0.941(0.891-0.986).There were no significant differences in age,gender,body moss index,education,location of onset,hypertension and drinking history between the two groups(P＞0.05).The time of initial hospital admission in the poor group was longer than that in the good group,skin rash area in the poor group was larger than that in the good group,and diabetes mellitus and smoking history in the poor group were higher than those in the good group(P＜0.05).The time of admis-sion for initial treatment＞3 d(OR=2.188,95％CI:1.383-3.461),skin rash area＞10 cm2(OR=2.018,95％CI:1.283-3.173),diabetes mellitus(OR=2.264,95％CI:1.379-3.717),serum VIP level ≥41.78 ng/L(OR=3.022,95％CI:1.685-5.420),serum 5-HT level ≥99.27 ng/mL(OR=3.579,95％CI:1.885-6.793)were the influencing factors of disease outcome after SCS treatment in PHN patients(P＜0.05).Con-clusion The elevated levels of serum VIP and 5-HT before treatment are associated with poor outcomes after SCS in patients with PHN,and could be used as potential markers to predict the outcomes of SCS in patients with PHN.

Objective To construct a database for molecular mass spectra of toxins and drugs in order to facilitate the management and retrieval of mass spectra for nerve agents,metabolites and other small molecules.Methods Requirement analysis and functional design were performed using software engineering methods.The Spec2Vec algorithm was used for vector representation of mass spectra,while SMILES molecular structures were vectorized using the extended connectivity fingerprint(ECFP).A data storage model integrating structured information and vector representations was established using the Milvus database.Similarity search of mass spectra and molecular structures was conducted via vector similarity comparison and the FlashEntropySearch algorithm.Results The constructed database of mass spectra encompassed over 400,000 entries from such sources as OCAD,NIST,MASSBANK,metabolic products,and natural products of TCM,which was capable of searching for similarities in mass spectra and molecular structures.On a standard server,similarity search of mass spectra took no more than 5 seconds,while that of molecular structures took no more than 1 second.Conclusion The system enables efficient management of complex mass spectra and provides rapid retrieval and comparison of mass spectra-related information through advanced vector indexing technology,offering robust data support and research tools for toxicology and pharmacology.

Objective:Primary bladder chondroma is extremely rare in clinical practice.We report a case of primary bladder chondroma. The patient presented with urinary frequency and urgency for over one month, and a hypoechoic nodule on the anterior bladder wall was detected via urinary tract ultrasound. Preoperative evaluation suggested a benign bladder lesion, and transurethral resection of the bladder tumor was performed. Postoperative histopathology confirmed the diagnosis of bladder chondroma. Regular follow-up for over one year revealed no signs of recurrence or metastasis.

Objective:Primary bladder chondroma is extremely rare in clinical practice.We report a case of primary bladder chondroma. The patient presented with urinary frequency and urgency for over one month, and a hypoechoic nodule on the anterior bladder wall was detected via urinary tract ultrasound. Preoperative evaluation suggested a benign bladder lesion, and transurethral resection of the bladder tumor was performed. Postoperative histopathology confirmed the diagnosis of bladder chondroma. Regular follow-up for over one year revealed no signs of recurrence or metastasis.

Human beings are inevitably exposed to toxic substances as a result of influences of potential contamination factors in the environment,food and medicines,which poses a threat to human health.In order to effectively screen and prevent the exposure or intake of such substances,it is neces-sary to develop in vitro assays for the detection and toxicity evaluation of toxic substances.High content screening(HCS)has been recognized as an important tool for toxicity testing and risk assessment of compounds due to its high throughput and automation advantages,and has been widely used in in vitro toxicology research.In this review,we described the system components of HCS and its workflow in toxicity screening and toxicity evaluation by focusing on cases of their application in toxicity detection and evaluation studies,including the cytotoxicity,hepatotoxicity,nephrotoxicity,genotoxicity,neurotox-icity,cardiotoxicity,and developmental toxicity.In addition,the applications and developments of machine learning in HCS were explored,especially to the advantages of supervised and unsupervised machine learning strategies for high throughput image screening and data analysis.Finally,the future applications of HCS in toxicity screening and evaluation are outlined,especially in terms of binding new models and gene editing technology.

Objective:To investigate the risk factors and prognostic value of the textbook outcome (TO) in patients with advanced gastric cancer (AGC) who underwent neoadjuvant chemotherapy followed by surgical resection.Methods:This is a retrospective cohort study. A total of 253 patients with AGC who underwent neoadjuvant chemotherapy combined with gastrectomy and D2 lymphadenectomy in the Department of Gastric Surgery, Fujian Medical University Union Hospital from January 2010 to December 2019 were retrospectively included. There were 195 males and 58 females, aged (60.3±10.0) years (range: 27 to 75 years). The patients were then divided into the TO group ( n=168) and the non-TO group ( n=85). Multivariate Logistic regression was used to analyze the independent predictors of TO. Univariate and multivariate Cox analysis were used to analyze independent prognosis factors for overall survival (OS) and disease-free survival (DFS). Propensity score matching was performed to balance the TO and non-TO groups, and the Kaplan-Meier method was used to calculate survival rates and draw survival curves. Results:Among the 253 patients, 168 patients (66.4%) achieved TO. The Eastern Cooperative Oncology Group score ( OR=0.488, 95% CI: 0.278 to 0.856, P=0.012) and ypN stage ( OR=0.626, 95% CI:0.488 to 0.805, P<0.01) were independently predictive of TO. Multivariate analysis revealed that TO was an independent risk factor for both OS ( HR=0.662, 95% CI: 0.457 to 0.959, P=0.029) and DFS ( HR=0.687, 95% CI: 0.483 to 0.976, P=0.036). After matching, the 5-year OS rate (42.2% vs. 27.8%) and the 5-year DFS rate (37.5% vs. 27.8%) were significantly higher in the TO group than in the non-TO group (both P<0.05). Furthermore, patients in the non-TO group benefited significantly from postoperative chemotherapy (both P<0.05), but those in the TO group did not (both P>0.05). Conclusion:TO is an independent prognosis factor in patients undergoing neoadjuvant chemotherapy and surgery for AGC and is associated with postoperative chemotherapy benefits.

Objective:To investigate and explore the clinical significance of the expression levels and differences of autophagy related genes ATG3, ATG5, ATG12, ATG16, LC3 and Beclin-1 in peripheral blood mononuclear cells of patients with refractory moderate-to-severe rheumatoid arthritis (RA), who were treated with abatacept.Methods:Peripheral blood samples of 30 patients admitted to the affiliated hospital of North Sichuan Medical College from June 2020 to June 2022 were collected before and after abatacept treatment. Autophagy associated genes were detected by RT-qPCR and, autophagy associated proteins were detected by Western Blot. Correlation analysis with clinical parameters was performed. SPSS26.0 and GraphPad Prism 9.0 were used for statistical analysis, Independent sample t-test was used for comparison between groups, and non-normal distribution data were expressed as M ( Q1, Q3), Spearman correlation analysis was used to analyze the correlation between variables, and P<0.05 was considered statistically significant. Results:①Compared with the mRNA expression levels of ATG12(0.007 6±0.005 9), ATG16(0.003 1±0.002 2) and LC3(0.038 2±0.017 1) before treatment, after 24 weeks treatment with abatacept, the mRNA expression levels of ATG12 (0.011 4±0.003 1) and ATG16 (0.004 2±0.000 7) increased ( t=-2.49, P=0.042; t=-2.15, P=0.038), and the mRNA expression level of LC3 (0.022 6±0.008 3) was decreased ( t=3.28, P=0.003) after 24 weeks of abatacept treatment.②After 24 weeks, the expression level of ATG16 mRNA in the remission group (0.004 8±0.000 8) was higher than that in the non-remission group (0.003 8±0.000 3) ( t=-3.41, P=0.003). The expression level of LC3 mRNA in remission group (0.027 3±0.007 3) was lower than that in non-remission group (0.017 9±0.006 5) ( t=3.69, P=0.017). ③ATG5 mRNA expression level was positively correlated with TJC, ESR and anti-CCP antibody ( r=0.75, P=0.049; r=0.43, P=0.044; r=0.97, P=0.011). The expression level of ATG12 mRNA was negatively correlated with DAS28, ESR and hsCRP ( r=-0.46, P=0.025; r=-0.51, P=0.026; r=-0.41, P=0.031). The expression level of ATG16 mRNA was positively correlated with ESR and hsCRP ( r=0.50, P=0.030; r=0.40, P=0.024). The expression level of Beclin-1 mRNA was significantly higher than TJC, RF-IgG and anti-CCP antibody were negatively correlated ( r=-0.51, P=0.025; r=-0.42, P=0.035; r=-0.81, P=0.043). The expression level of LC-3 mRNA was positively correlated with ESR and hsCRP ( r=0.55, P=0.028; r=0.56, P=0.024). ④Compared with the protein expression level before the treatment, of ATG12 (0.675 3±0.036 3), which (1.547 7±0.080 5) increased after 24 weeks of treatment ( t=-7.80, P=0.001). Compared with the protein expression levels of ATG16 (0.817 1±0.089 0), LC3Ⅱ (0.807 1±0.072 1) and IL-1β (1.129 7±0.118 9) before treatment, 24 weeks after, the protein expression levels of ATG16 (0.424 6±0.103 5), LC3Ⅱ (0.353 7±0.056 9) and IL-1β (0.346 7±0.050 8) decreased ( t=2.62, P=0.042; t=2.88, P=0.045; t=2.25, P=0.038) 24 weeks after treatment. Conclusion:Autophagy related genes is associated with several clinical presentations and disease activity. The results of this study suggest that autophageius are involved in the pathogenesis of RA. Abatacept may be a potential autophage modulator by regulating autophagy related genes including ATG12、ATG16 and LC3.

Objective To explore the feasibility of the multiplexed sensitivity encoding diffusion weighted imaging(MUSE-DWI)sequence in neck MRI,and to compare with traditional single-shot echo-planar imaging diffusion weighted imaging(SS-EPI-DWI)sequence.Methods Thirty healthy volunteers underwent MUSE-DWI and SS-EPI-DWI sequences scanning in neck.Two groups of images were independently scored by two radiologists for magnetic sensitivity artifact,chemical shift artifact,geometric distortion and overall image quality.The noise,signal-to-noise ratio(SNR)and contrast-to-noise ratio(CNR)of the regions of interest(ROI)of the two groups of images were measured and compared on the nasopharyngeal fossa layer,parotid gland layer,glottic layer and thyroid layer.Results Qualitative analysis showed that the image quality scores of MUSE-DWI sequence were significantly better than those of SS-EPI-DWI sequence in terms of magnetic sensitivity artifact,chemical shift artifact,geometric distortion and overall image quality(P<0.001).Quantitative analysis showed that the noise values of ROIs of MUSE-DWI sequence were significantly lower than those of SS-EPI-DWI sequence(P<0.001).The SNR and CNR of ROIs of MUSE-DWI sequence were higher than those of SS-EPI-DWI sequence(P<0.001).Conclusion MUSE-DWI sequence can significantly reduce geometric distortion,magnetic sensitivity artifact and chemical shift artifact,and SNR and CNR of images are significantly increased compared with SS-EPI-DWI sequence,which is more suitable for neck MRI scanning.