Non-alcoholic fatty liver disease （NAFLD） is a chronic liver disease closely related to metabolism， which is mainly characterized by abnormal lipid deposition in hepatocytes. In recent years， with the increasing prevalence of obesity and metabolic syndrome， NAFLD has become one of the most common chronic diseases in the world. The pathogenesis of NAFLD is complex and varied， involving the cross-regulation of multiple signaling pathways such as glucose-lipid metabolism， oxidative stress， and inflammation. The TLR4 signaling pathway plays a key role in the development and progression of NAFLD， and abnormal activation of this pathway accelerates the deterioration of NAFLD by promoting the release of pro-inflammatory cytokines， inducing oxidative stress， and exacerbating insulin resistance. Studies have shown that traditional Chinese medicine （TCM） can regulate the TLR4 signaling pathway to alleviate the symptoms and pathological features of NAFLD. The present review summarizes the experimental research progress in the TCM regulation of the TLR4 signaling pathway in treating NAFLD in the past 5 years， covering a wide range of TCM active ingredients （such as polysaccharides， terpenoids， alkaloids， flavonoids） and compound prescriptions. The active ingredients and compound prescriptions of TCM can effectively ameliorate lipid metabolism disorders， reduce insulin resistance， regulate intestinal flora， and inhibit inflammation and oxidative stress by regulating the TLR4 signaling pathway via multiple targets and pathways， thus slowing down the progression of NAFLD. Through in-depth analysis of the pathological mechanisms of NAFLD and exploration of the potential of TLR4 signaling pathway as a therapeutic target， we can provide theoretical support for the application of TCM in the treatment of NAFLD， as well as new perspectives and directions for future clinical research and new drug development， thereby promoting the innovation and development of therapeutic strategies for NAFLD.

Objective: To analyze the temporal variation patterns of sickness absenteeism among primary and secondary school students in Shanghai, so as to explore models suitable for predicting peaks and intensity of absenteeism rates. Methods: The seasonal and trend decomposition using loess (STL) method was used to analyze the seasonal and long term trend changes in sickness absenteeism among primary and secondary school students from September 1 in 2010 to June 30 in 2018, in Shanghai. A hierarchical clustering method based on Dynamic Time Warping (DTW) was employed to classify absenteeism symptoms with similar temporal patterns. Based on historical data, the study constructed and evaluated different time series algorithms and machine learning models to optimize the accuracy of predicting the trend of sickness absenteeism. Results: During the research period, the average new absenteeism rate due to illness was 16.86 per 10 000 person day for every academic year, and the trend of sickness absenteeism exhibited both seasonality and a long term upward trend, reaching its highest point in the 2017 academic year (22.47 per 10 000 person day). The symptoms of absenteeism were divided into three categories: high incidence in winter and spring (respiratory symptoms, fever and general discomfort, etc.), high incidence in summer (eye symptoms, nosebleeds, etc.) and those without obvious seasonality (skin symptoms, accidental injuries, etc.).The constructed time series models effectively predicted the trend of absenteeism due to illness, although the accuracy of predicting peak intensity was relatively low. Among them, the multi layer perceptron (MLP) model performed the best, with an root mean squared error (RMSE) of 8.96 and an mean absolute error (MAE) of 4.37, reducing 36.51% and 39.02% compared to the baseline model. Conclusion Time series models and machine learning algorithms could effectively predict the trend of sickness absenteeism, and corresponding prevention and control measures can be taken for absenteeism caused by different symptoms during peak periods.

BACKGROUND: The potential impact of pre-existing coronary artery stenosis (CAS) on right ventricular (RV) function during acute pulmonary embolism (PE) episodes remains underexplored. This study aimed to investigate the association between pre-existing CAS and RV dysfunction in patients with acute PE. METHODS: In this multicenter, case-control study, 89 cases and 176 controls matched for age were enrolled at three study centers (Peking Union Medical College Hospital, Fuwai Hospital, and the Second Affiliated Hospital of Harbin Medical University) from January 2016 to December 2020. The cases were patients with acute PE with CAS, and the controls were patients with acute PE without CAS. Coronary artery assessment was performed using coronary computed tomographic angiography. CAS was defined as ≥50% stenosis of the lumen diameter in any coronary vessel >2.0 mm in diameter. Conditional logistic regression analysis was used to evaluate the association between CAS and RV dysfunction. RESULTS: The percentages of RV dysfunction (19.1% [17/89] vs. 44.6% [78/176], P <0.001) and elevated systolic pulmonary artery pressure (sPAP) (19.3% [17/89] vs. 39.5% [68/176], P = 0.001) were significantly lower in the case group than those in the control group. In the multivariable logistic regression model, CAS was independently and negatively associated with RV dysfunction (adjusted odds ratio [OR]: 0.367; 95% confidence interval [CI]: 0.185-0.728; P = 0.004), and elevated sPAP (OR: 0.490; 95% CI: 0.252-0.980; P = 0.035), respectively. CONCLUSIONS Pre-existing CAS was significantly and negatively associated with RV dysfunction and elevated sPAP in patients with acute PE. This finding provides new insights into RV dysfunction in patients with acute PE with pre-existing CAS.
Humans ; Pulmonary Embolism/complications* ; Case-Control Studies ; Male ; Ventricular Dysfunction, Right/physiopathology* ; Female ; Middle Aged ; Aged ; Coronary Stenosis/complications* ; Logistic Models ; Adult

Objective:To explore the feasibility and preliminary efficacy of domestic single-port robotic surgical system in the surgical treatment of thyroid cancer. Methods:Thyroid cancer patients who underwent domestic single-port robotic surgery in the Department of Head and Neck Surgery of Sichuan Cancer Hospital from June 2024 to January 2025 were prospectively included. Clinical data, oncological characteristics, and perioperative indicators were systematically collected. Results:A total of 7 patients were included, including 3 males and 4 females, with an age of （34.57±10.26） years. All procedures were successfully completed without conversion to open surgery. Operative time was（180.00±30.41） minutes. Blood loss was（5.00[15.00 ]）mL. Postoperative drainage volume was （167.86±130.95） mL. The postoperative pathological results were all thyroid papillary carcinoma. There were no system failures, no device-related complications and adverse events were observed during the operation and perioperative period. No tumor recurrence or metastasis was observed during the follow-up period. Conclusion:Preliminary data indicate that the domestic single-port robotic surgical system is safe and feasible for the surgical treatment of thyroid cancer, providing a practical basis for subsequent multi-disease, multi-center, and large-sample studies.
Humans ; Thyroid Neoplasms/surgery* ; Robotic Surgical Procedures/instrumentation* ; Male ; Female ; Adult ; Thyroidectomy/methods* ; Operative Time ; Middle Aged ; Prospective Studies

Most cancers are currently incurable, partly due to abnormal post-translational modifications (PTMs). In this study, we initially used multiple myeloma (MM) as a working model and found that SUMOylation activating enzyme subunit 1 (SAE1) promotes the malignancy of MM. Through proteome microarray analysis, SAE1 was identified as a potential target for bioactive colcemid or its derivative colchicine. Elevated levels of SAE1 were associated with poor clinical survival and increased MM proliferation in vitro and in vivo. Additionally, SAE1 directly SUMOylated and upregulated the total protein expression of p27, leading to LLPS-mediated nuclear export of p27. Our study also demonstrated the involvement of SAE1 in other types of cancer cells, and provided the first monomer crystal structure of SAE1 and its key binding model with colchicine. Colchicine also showed promising results in the Patient-Derived Tumor Xenograft (PDX) model. Furthermore, a controlled clinical trial with 56 MM patients demonstrated the clinical efficacy of colchicine. Our findings reveal a novel mechanism by which tumor cells evade p27-induced cellular growth arrest through p27 SUMOylation-mediated nuclear export. SAE1 may serve as a promising therapeutic target, and colchicine may be a potential treatment option for multiple types of cancer in clinical settings.

In this study, we employed a combination of genome mining and heteronuclear single quantum coherence (HSQC)-based small molecule accurate recognition technology (SMART) technology to search for fernane-type triterpenoids. Initially, potential endophytic fungi were identified through genome mining. Subsequently, fine fractions containing various fernane-type triterpenoids were selected using HSQC data collection and SMART prediction. These triterpenoids were then obtained through targeted isolation and identification. Finally, their antifungal activity was evaluated. As a result, three fernane-type triterpenoids, including two novel compounds, along with two new sesquiterpenes and four known compounds were isolated from one potential strain, Diaporthe discoidispora. Their structures were elucidated through analysis of high-resolution electrospray ionization mass spectrometry (HR-ESI-MS) and nuclear magnetic resonance (NMR) spectroscopic data. The absolute configurations were determined using single-crystal X-ray diffraction analysis and electron capture detector (ECD) analysis. Compound 3 exhibited moderate antifungal activity against Candida albicans CMCC 98001 and Aspergillus niger.
Triterpenes/isolation & purification* ; Antifungal Agents/isolation & purification* ; Molecular Structure ; Candida albicans/drug effects* ; Ascomycota/genetics* ; Magnetic Resonance Spectroscopy ; Aspergillus niger/drug effects* ; Genome, Fungal ; Microbial Sensitivity Tests

Bacillus velezensis DJ1 exhibits broad-spectrum antagonistic activity against diverse phytopathogenic fungi, while its biocontrol mechanisms against Fusarium graminearum, the causal agent of maize stalk rot, remain poorly characterized. In this study, we integrated genomics and transcriptomics to elucidate the antifungal mechanisms of strain DJ1. The results demonstrated that DJ1 inhibited F. graminearum with the efficacy of 64.4%, while its polyketide crude extract achieved the control efficacy of 55% in pot experiments against this disease. Whole-genome sequencing revealed a single circular chromosome (3 929 792 bp, GC content of 47%) harboring 12 biosynthetic gene clusters for secondary metabolites, six of which encoded known antimicrobial compounds (macrolactin H, bacillaene, difficidin, surfactin, fengycin, and bacilysin). Transcriptomic analysis identified 243 differentially expressed genes (152 upregulated and 91 downregulated, P < 0.05), which were potentially associated with the antagonistic activity against F. graminearum. KEGG enrichment analysis highlighted activation (P < 0.05) of cysteine/methionine metabolism, pentose phosphate pathway, and polyketide biosynthesis pathways, indicating that DJ1 employed synergistic strategies involving antimicrobial compound synthesis, energy metabolism enhancement, and nutrient competition to suppress pathogens. This study provides a theoretical foundation for developing novel microbial resources and application technologies to combat phytopathogenic fungi.
Fusarium/drug effects* ; Bacillus/metabolism* ; Plant Diseases/prevention & control* ; Antifungal Agents/pharmacology* ; Genomics ; Zea mays/microbiology* ; Transcriptome ; Gene Expression Profiling ; Antibiosis ; Multigene Family ; Multiomics

Objective: To explore the current status and associated factors of bullying behavior among middle school students in Shanghai, so as to provide a reference basis for carrying out bullying intervention work. Methods: From May to June 2021, a stratified cluster sampling method was used to select 19 000 middle school students from 63 schools in 16 districts of Shanghai, and the Shanghai Youth Health Risk Behavior Survey Questionnaire was used to conduct an anonymous questionnaire survey of enrolled students. Chi square test and binary Logistic regression analysis were employed to investigate the associated factors of bullying among middle school students. Results: The prevalence of bullying behaviors in Shanghai was 15.5%, with males and junior high school students exhibiting the higher reporting rate(19.5%,17.2%). And malicious teasing or name calling had the highest reported rate at 9.4%. The results of binary Logistic regression analysis showed that fighting ( OR =5.02), attempting to smoke ( OR =3.22), having a feeling of sadness and hopelessness ( OR =2.50) and getting drunk( OR =1.72) were positively associated with bullying behavior among middle school students. Fighting ( OR =3.83-8.97), attempting to smoke ( OR =2.92-5.52), having a feeling of sadness and hopelessness ( OR =2.40-4.34), and getting drunk ( OR =1.66-2.34) were positively correlated with 6 forms of bullying (malicious teasing or name calling, intentionally damaging someone else s belongings, deliberately excluding someone from activities or isolating someone, threatening or intimidating others, hitting, kicking, or pushing someone, and verbally harassing or attacking someone online) ( P <0.05). Conclusions Bullying behavior of middle school students in Shanghai primarily presents as verbal harassment. In the future, greater attention should be directed towards bullies, and it should recognize potential hazards promptly and implement precise intervention measures.

Objective To explore the mechanism of electroacupuncture pretreatment(EP)for relieving post-stroke spasticity in rats.Methods Eighteen rats were randomized equally into sham-operated group,middle cerebral artery occlusion(MCAO)group,and MCAO+EP group.In MCAO+EP group,the rats received electroacupuncture at the acupoints Qubin and Baihui for 3 consecutive days prior to MCAO.Neurological deficits and cognitive function of the rats were evaluated,and pathologies in the hippocampus were examined using HE,Nissl,and TUNEL staining.The expressions of IL-4,IL-6,TNF-α,and TMAO in the brain tissues were detected with ELISA,and the mRNA and protein expression levels of NF-κB p65,NLRP3,caspase-3,and caspase-9 were determined with qRT-PCR,Western blotting,and immunohistochemistry.Results The rats receiving MCAO had significantly increased neurological deficit scores and showed increased muscle tension,number of apoptotic neurons,and expressions of IL-6,TNF-α,NF-κB p65,NLRP3,caspase-3 and caspase-9 in the hippocampus and significantly reduced length of time for new object recognition.Microscopically,the cells in the hippocampus of the MCAO rats showed uneven and loosened arrangement and unclear cell boundaries.In contrast,the rats in I/R+EP group showed significantly lowered neurological deficit scores and dystonia rating scores,reduced cell apoptosis,lowered hippocampal expressions of IL-6,TNF-α,caspase-3,caspase-9,and NF-κB p65,increased time for new object recognition,tightly arranged and uniformly stained hippocampal cells with clear boundaries,with also an increased number of active neurons and enhanced expression of IL-4 in the hippocampus.Conclusion EP alleviates post-stroke spasticity in rats by inhibiting inflammatory responses and hippocampal neuronal apoptosis mediated by the NF-κB/NLRP3 signaling pathway.

Objective To explore the mechanism of electroacupuncture pretreatment(EP)for relieving post-stroke spasticity in rats.Methods Eighteen rats were randomized equally into sham-operated group,middle cerebral artery occlusion(MCAO)group,and MCAO+EP group.In MCAO+EP group,the rats received electroacupuncture at the acupoints Qubin and Baihui for 3 consecutive days prior to MCAO.Neurological deficits and cognitive function of the rats were evaluated,and pathologies in the hippocampus were examined using HE,Nissl,and TUNEL staining.The expressions of IL-4,IL-6,TNF-α,and TMAO in the brain tissues were detected with ELISA,and the mRNA and protein expression levels of NF-κB p65,NLRP3,caspase-3,and caspase-9 were determined with qRT-PCR,Western blotting,and immunohistochemistry.Results The rats receiving MCAO had significantly increased neurological deficit scores and showed increased muscle tension,number of apoptotic neurons,and expressions of IL-6,TNF-α,NF-κB p65,NLRP3,caspase-3 and caspase-9 in the hippocampus and significantly reduced length of time for new object recognition.Microscopically,the cells in the hippocampus of the MCAO rats showed uneven and loosened arrangement and unclear cell boundaries.In contrast,the rats in I/R+EP group showed significantly lowered neurological deficit scores and dystonia rating scores,reduced cell apoptosis,lowered hippocampal expressions of IL-6,TNF-α,caspase-3,caspase-9,and NF-κB p65,increased time for new object recognition,tightly arranged and uniformly stained hippocampal cells with clear boundaries,with also an increased number of active neurons and enhanced expression of IL-4 in the hippocampus.Conclusion EP alleviates post-stroke spasticity in rats by inhibiting inflammatory responses and hippocampal neuronal apoptosis mediated by the NF-κB/NLRP3 signaling pathway.