This study aims to explore whether Albiziae Cortex-Tribuli Fructus can exert an anti-hepatic fibrosis effect by regulating the nuclear factor E2-related factor 2(Nrf2)/NOD-like receptor protein 3(NLRP3)/cysteine protease-1(caspase-1) pathway and analyze its potential mechanism. In the in vivo experiment, a mouse model of hepatic fibrosis was established by subcutaneous injection of carbon tetrachloride. The levels of alanine aminotransferase(ALT), aspartate aminotransferase(AST), collagen type Ⅳ(ColⅣ), laminin(LN), procollagen type Ⅲ(PCⅢ), and hyaluronic acid(HA) in the serum of mice were measured using a fully automated biochemical analyzer and ELISA. Hematoxylin and eosin(HE) and Masson staining were used to observe inflammation and collagen fiber deposition in the liver tissue. Western blot and RT-qPCR were employed to detect the protein and mRNA expression of collagen type Ⅰ(collagen Ⅰ), α-smooth muscle actin(α-SMA), Nrf2, NLRP3, gasdermin D(GSDMD), and caspase-1 in the hepatic tissue. In the in vitro experiment, human hepatic stellate cells(HSC-LX2) were pretreated with Nrf2 agonist or inhibitor, followed by the addition of blank serum, AngⅡ + blank serum, and AngⅡ + Albiziae Cortex-Tribuli Fructus-containing serum for intervention. Western blot was used to detect the protein expression of Nrf2, NLRP3, GSDMD, caspase-1, α-SMA, GSDMD-N, and apoptosis-associated speck-like protein(ASC) in cells. DCFH-DA fluorescence probe was used to detect the cellular ROS levels. The results from the in vivo experiment showed that, compared with the model group, Albiziae Cortex-Tribuli Fructus significantly reduced the serum levels of AST, ALT, ColⅣ, LN, PCⅢ, and HA, reduced the infiltration of inflammatory cells and collagen fiber deposition in the liver tissue, significantly upregulated the protein and mRNA expression of Nrf2 in the liver tissue, and significantly downregulated the protein and mRNA expression of collagen I, α-SMA, NLRP3, GSDMD, and caspase-1 in the liver tissue. The results from the in vitro experiment showed that Nrf2 activation decreased the protein expression of NLRP3, GSDMD, caspase-1, α-SMA, GSDMD-N, ASC, and ROS levels in HSC-LX2, while Nrf2 inhibition showed the opposite trend. Furthermore, Albiziae Cortex-Tribuli Fructus-containing serum directly decreased the expression of the above proteins and ROS levels. In conclusion, Albiziae Cortex-Tribuli Fructus can effectively improve hepatic fibrosis, and its mechanism of action may involve inhibiting pyroptosis through the regulation of the Nrf2/NLRP3/caspase-1 pathway.
Animals ; NF-E2-Related Factor 2/genetics* ; Liver Cirrhosis/genetics* ; Mice ; Drugs, Chinese Herbal/administration & dosage* ; Caspase 1/genetics* ; Male ; NLR Family, Pyrin Domain-Containing 3 Protein/genetics* ; Signal Transduction/drug effects* ; Humans ; Liver/metabolism* ; Mice, Inbred C57BL ; Plant Extracts ; Tribulus

Background Atherosclerotic cardiovascular disease (ASCVD) is a major contributor to the global burden of cardiovascular diseases. However, evidence from meta-analyses on the association between ambient ozone exposure and ASCVD risk remains relatively insufficient. Objective To explore the epidemiological association between ambient ozone exposure and ASCVD, providing scientific evidence for ASCVD prevention and control from the perspective of environmental risk factor management. Methods We systematically searched PubMed, Web of Science, Embase, the Cochrane Library, CNKI, Wanfang Database, CBM, and VIP for published epidemiological studies on the relationship between ambient ozone exposure and ASCVD from January 2007 to December 2023. We performed quality assessment and data extraction of the included studies, and utilized meta-analysis to evaluate the effects of short-term and long-term ozone exposure on different ASCVD outcomes, including mortality and incidence of ischemic heart disease (IHD) and ischemic stroke (IS). Results A total of 24 studies were included based on a set of predetermined eligibility criteria. The meta-analysis results indicated that short-term ozone exposure was associated with an increased risk of ASCVD mortality and incidence. Specifically, short-term ozone exposure was significantly associated with an elevated risk of IHD mortality (combined RR=1.011, 95%CI: 1.008, 1.015; P < 0.05). Additionally, short-term ozone exposure was significantly linked to increased IS mortality (combined RR=1.005, 95%CI: 1.003, 1.008; P < 0.05) and incidence (combined RR=1.015, 95%CI: 1.003, 1.027; P < 0.05). Conclusion Short-term exposure to ambient ozone significantly elevates acute cardiovascular disease risk. However, the epidemiological association between long-term ozone exposure and ASCVD remains inconclusive. Future high-quality cohort studies with refined exposure assessment methods are warranted to elucidate the chronic cardiovascular effects of ozone exposure.

Objective To establish a liquid chromatography method for the simultaneous determination of 13 aromatic amine compounds (AAs) in workplace air. Methods A total of 13 AAs in both vapor and aerosol phases were collected in workplace air using a new GDH-6 sampling tube. Samples were desorbed and eluted with methanol, separated using a Symmetry Shield™ RP₁₈ reversed-phase liquid chromatography column, and detected with a diode array detector. Quantification was performed using an external standard method. Results The linear range of the 13 AAs measured by this method was 0.02-373.60 μg/L with the correlation coefficients greater than 0.999 0. The minimum detection concentration was 0.09-14.37 μg/m³, and the minimum quantitative concentration was 0.31-47.90 μg/m³ (both calculated based on sampling 15.0 L of air and 3.0 mL of elution volume). The average desorption and elution efficiency ranged from 97.46% to 101.23%. The within-run relative standard deviation (RSD) was 0.10%-5.99%, and the between-run RSD was 0.17%-2.71%. Samples could be stably stored in sealed conditions at 2-8 ℃ for more than seven days. Conclusion This method is suitable for the simultaneous determination of 13 AAs in workplace air, including both vapor and aerosol phases.

Preeclampsia (PE) is a severe gestational disorder characterized by hypertension and proteinuria, with a subset of cases exhibiting an immune-driven phenotype marked by placental overexpression of proinflammatory cytokines and chronic inflammatory damage, profoundly impacting fetal development. To elucidate the pathophysiology of this PE subtype, we established an inflammation-driven PE mouse model via lipopolysaccharide (LPS) intraperitoneal injection, systematically evaluating histopathological changes in maternal heart, liver, lung, kidney, and placenta, and integrating transcriptomic profiling to uncover molecular mechanisms. LPS administration robustly induced maternal hypertension and proteinuria, hallmarks of PE, without significantly altering organ or fetal weights. Histological analyses revealed pronounced inflammatory damage in the maternal lung, kidney, and placenta, with the lung exhibiting the most severe pathology, characterized by inflammatory cell infiltration, alveolar wall thickening, and interstitial edema-challenging the conventional focus on placental and renal primacy in PE. Placental labyrinth and junctional zones displayed extensive structural disruption and necrosis, indicating functional impairment. Transcriptomic analysis identified 27 inflammation-related genes consistently upregulated across tissues, with protein-protein interaction networks pinpointing Il1β, Il6, Ccl5, Ccl2, Cxcl10, Tlr2, and Icam1 as hub genes. Quantitative PCR validation confirmed Tlr2 as a central regulator, evidenced by significant upregulation of Tlr2 in lung, kidney, and placenta of LPS-induced PE mice, while Cxcl10 exhibited placenta-specific upregulation, suggesting a synergistic inflammatory axis in placental pathology. These findings highlight the lung as a critical, yet underappreciated, target in inflammation-driven PE, reframe the multi-organ inflammatory landscape of the disease, and nominate Tlr2 and Cxcl10 as potential diagnostic biomarkers and therapeutic targets, offering new avenues for precision intervention in PE.
Animals ; Female ; Pregnancy ; Mice ; Pre-Eclampsia/genetics* ; Inflammation ; Lipopolysaccharides/adverse effects* ; Disease Models, Animal ; Transcriptome ; Placenta/pathology* ; Phenotype

Neuropathic pain, a debilitating condition caused by dysfunction of the somatosensory nervous system, remains difficult to treat due to limited understanding of its molecular mechanisms. Bioinformatics analysis identified cerebellin 2 (CBLN2) as highly enriched in human and murine proprioceptive and nociceptive neurons. We found that CBLN2 expression is persistently upregulated in dorsal root ganglia (DRG) following spinal nerve ligation (SNL) in mice. In addition, transcription factor SOX11 binds to 12 cis-regulatory elements within the Cbln2 promoter to enhance its transcription. SNL also induced SOX11 upregulation, with SOX11 and CBLN2 co-localized in nociceptive neurons. The siRNA-mediated knockdown of Sox11 or Cbln2 attenuated SNL-induced mechanical allodynia and thermal hyperalgesia. High-throughput sequencing of DRG following intrathecal injection of CBLN2 revealed widespread gene expression changes, including upregulation of numerous NF-κB downstream targets. Consistently, CBLN2 activated NF-κB signaling, and inhibition with pyrrolidine dithiocarbamate reduced CBLN2-induced pain hypersensitivity, proinflammatory cytokines and chemokines production, and neuronal hyperexcitability. Together, these findings identified the SOX11/CBLN2/NF-κB axis as a critical mediator of neuropathic pain and a promising target for therapeutic intervention.
Animals ; Neuralgia/metabolism* ; Ganglia, Spinal/metabolism* ; Up-Regulation ; Mice ; NF-kappa B/metabolism* ; SOXC Transcription Factors/genetics* ; Male ; Neuroinflammatory Diseases/metabolism* ; Mice, Inbred C57BL ; Nerve Tissue Proteins/genetics* ; Hyperalgesia/metabolism* ; Signal Transduction ; Spinal Nerves

Instrument separation is a critical complication during root canal therapy, impacting treatment success and long-term tooth preservation. The etiology of instrument separation is multifactorial, involving the intricate anatomy of the root canal system, instrument-related factors, and instrumentation techniques. Instrument separation can hinder thorough cleaning, shaping, and obturation of the root canal, posing challenges to successful treatment outcomes. Although retrieval of separated instrument is often feasible, it carries risks including perforation, excessive removal of tooth structure and root fractures. Effective management of separated instruments requires a comprehensive understanding of the contributing factors, meticulous preoperative assessment, and precise evaluation of the retrieval difficulty. The application of appropriate retrieval techniques is essential to minimize complications and optimize clinical outcomes. The current manuscript provides a framework for understanding the causes, risk factors, and clinical management principles of instrument separation. By integrating effective strategies, endodontists can enhance decision-making, improve endodontic treatment success and ensure the preservation of natural dentition.
Humans ; Root Canal Therapy/adverse effects* ; Consensus ; Root Canal Preparation/adverse effects*

ObjectiveTo understand the monitoring result of occupational hazard in the workplace of key industries in Guangdong Province from 2020 to 2023. Methods The data of occupational hazards in the workplace of 20 key industries in Guangdong Province from 2020 to 2023 were collected from the “Workplace Occupational Hazard Monitoring System” of the Chinese Disease Prevention and Control System subsystem. The monitoring result of occupational hazard factors, occupational health training, occupational health examination, occupational protection, detection of occupational hazardous agents such as dust, chemical substances and noise were analyzed. Results A total of 13 058 enterprises from key industries were recruited as the monitoring subjects in Guangdong Province. There were 290 large-, 1 342 medium-, 7 635 small-, and 3 791 micro-enterprises, with small and micro-enterprises accounting for 58.5% and 29.0% of the total, respectively. A total of 7 542 enterprises exceeded the national standard in the detection of occupational hazards, with a rate of 57.8%. A total of 1 942 517 workers from 13 058 enterprises were recruited, with 835 567 workers were exposed to occupational hazards, with a rate of 43.0%. The rate of occupational health training for enterprise leaders, occupational health management personnel, and workers was 71.9%, 73.8%, and 86.5%, respectively. The abnormal rate of occupational health examinations for workers exposed to noise, dust, and chemical agents was 2.0%, 0.6%, and 1.0%, respectively. The distribution rate of dust masks, anti-poisoning masks or face masks, and noise prevention earplugs or earmuffs was 83.3%, 71.3%, and 77.8%, respectively. The rate of installation of dust prevention facilities, anti-poisoning facilities, and noise prevention facilities was 85.6%, 81.2%, and 50.1%, respectively. The rate of exceeded the national standard of dust, noise in the worksites/types and workplaces showed a decreasing trend year by year (all P<0.01), while the rate of exceeded the national standard of chemical agents in worksites/types and workplaces showed an increasing trend year by year in various occupational hazards (all P<0.01). Conclusion Occupational hazards in the workplace of key industries in Guangdong Province are relatively common. The proportion of workers exposed to occupational hazards is relatively high. It is necessary to further improve the use of noise prevention facilities and protective equipment, strengthen occupational health training for enterprises throughout the province and regularly monitor occupational hazards to reduce the risk of occupational diseases.

ObjectiveTo establish a method for the determination of 1,1,1,2-tetrachloroethane (TeCA) and 1,1,2,2-TeCA in human urine using liquid-liquid extraction-gas chromatography. Methods The 5.0 mL urine sample was mixed with 2.0 g anhydrous sodium sulfate and 5.0 mL ethyl acetate, then vortexed mixing. The 1.0 mL extraction was separated by 100% dimethylpolysiloxane capillary gas chromatography column, detected by flame ionization detector, and quantified by an external standard method. Results The linear ranges of 1,1,1,2-TeCA and 1,1,2,2-TeCA were 0.250-50.750 mg/L, with both correlation coefficients of >0.999 9. The detection limit of 1,1,1,2-TeCA in urine was 0.020 mg/L, and the lower limit of quantification was 0.060 mg/L. The average recovery was 88.02%-101.32%, and the within-run and between-run relative standard deviations (RSDs) were 0.11%-0.47% and 0.39%-1.09%, respectively. The detection limit of 1,1,2,2-TeCA in urine was 0.050 mg/L, and the lower limit of quantification was 0.150 mg/L. The average recovery was 93.42%-101.32%, and the within-run and between-run RSDs were 0.28%-1.04% and 0.50%-1.03%, respectively. Both the 1,1,1,2-TeCA and 1,1,2,2-TeCA cannot be stored at room temperature. The 1,1,2,2-TeCA can be stored at 4 ℃ for at least three days. At -20 ℃, the 1,1,1,2-TeCA can only be stored for one day, while 1,1,2,2-TeCA can be stored for at least five days. Conclusion This method has high sensitivity, good specificity, simple sample pretreatment, and more intuitive and reliable results. It can be used to determine the level of 1,1,1,2-TeCA and 1,1,2,2-TeCA in urine of occupational population.

OBJECTIVE To explore the potential mechanism of Yishenqinglihuoxue Formula(YSQLF)in treating chronic kidney disease fibrosis in rats based on UHPLC-Q-TOF-MS technology and network pharmacology.METHODS UHPLC-Q-TOF-MS was used for qualitative analysis of Yishenqinglihuoxue Formula-containing serum.Targets of the plasma constituents and the disease were retrieved from SwissTargetPrediction,OMIM,GeneCards,and other databases.Then the protein-protein interaction(PPI)network was constructed and core targets were screened for GO term enrichment and KEGG pathway enrichment.Cytoscape software was em-ployed to construct the"drug-compound-core target-pathway"network and the targets and signaling pathways of Yishenqinglihuoxue Formula against fibrosis were predicted.A model of renal fibrosis was established to verify the core targets and pathway proteins.RE-SULTS A total of 56 constituents migrating to blood of Yishenqinglihuoxue Formula were identified.97 common targets of the constit-uents and the disease and 33 core targets were screened out.KEGG enrichment and PPI network analysis showed that Yishenqingli-huoxue Formula may play a role in the treatment of fibrosis through PI3K/Akt and other pathways.Furthermore,the results of animal experiments showed that Yishenqinglihuoxue Formula could reduce the levels of Scr and BUN,improve fibrosis areas,inhibit the acti-vation of the PI3K/Akt pathway,and reduce the protein expression of TNF-α.CONCLUSION Yishenqinglihuoxue Formula may play a role in the treatment of fibrosis by inhibiting PI3K/Akt signaling pathway and inhibiting TNF-α expression.

Background::Acute-on-chronic liver failure (ACLF) is a severe liver disease with complex pathogenesis. Clinical hypoglycemia is common in patients with ACLF and often predicts a worse prognosis. Accumulating evidence suggests that glucose metabolic disturbance, especially gluconeogenesis dysfunction, plays a critical role in the disease progression of ACLF. Lon protease-1 (LONP1) is a novel mediator of energy and glucose metabolism. However, whether gluconeogenesis is a potential mechanism through which LONP1 modulates ACLF remains unknown.Methods::In this study, we collected liver tissues from ACLF patients, established an ACLF mouse model with carbon tetrachloride (CCl 4), lipopolysaccharide (LPS), and D-galactose (D-gal), and constructed an in vitro hypoxia and hyperammonemia-triggered hepatocyte injury model. LONP1 overexpression and knockdown adenovirus were used to assess the protective effect of LONP1 on liver injury and gluconeogenesis regulation. Liver histopathology, biochemical index, mitochondrial morphology, cell viability and apoptosis, and the expression and activity of key gluconeogenic enzymes were detected to explore the underlying protective mechanisms of LONP1 in ACLF. Results::We found that LONP1 and the expressions of gluconeogenic enzymes were downregulated in clinical ACLF liver tissues. Furthermore, LONP1 overexpression remarkably attenuated liver injury, which was characterized by improved liver histopathological lesions and decreased serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) in ACLF mice. Moreover, mitochondrial morphology was improved upon overexpression of LONP1. Meanwhile, the expression and activity of the key gluconeogenic enzymes were restored by LONP1 overexpression. Similarly, the hepatoprotective effect was also observed in the hepatocyte injury model, as evidenced by improved cell viability, reduced cell apoptosis, and improved gluconeogenesis level and activity, while LONP1 knockdown worsened liver injury and gluconeogenesis disorders.Conclusion::We demonstrated that gluconeogenesis dysfunction exists in ACLF, and LONP1 could ameliorate liver injury and improve gluconeogenic dysfunction, which would provide a promising therapeutic target for patients with ACLF.