OBJECTIVE To investigate the ameliorative effect and mechanism of Euphorbia hirta L.-derived exosome-like nanovesicles（Eh-ENVs） on acetaminophen （APAP）-induced liver injury based on the nuclear factor erythroid 2 related factor 2 （Nrf2）/heme oxygenase-1 （HO-1）/NAD（P）H：quinone oxidoreductase 1 （NQO1） pathway. METHODS The safety of Eh-ENVs was evaluated by examining their effects on the viability of RAW264.7 and AML12 cells， as well as serum liver and kidney function indicators and histopathology of liver， lung， and other tissues in normal mice. A lipopolysaccharide （1 μg/mL）-induced RAW264.7 cell inflammation model was constructed to investigate the effects of 10 and 20 μg/mL Eh-ENVs on the mRNA expression of inflammatory factors and reactive oxygen species （ROS） level in model cells， and the uptake efficiency of Eh-ENVs by RAW264.7 cells was also examined. An APAP-induced liver injury mouse model was established to investigate the effects of 4 mg/kg Eh-ENVs on serum liver function indicators， liver histopathology， mRNA expression of inflammatory factors， malondialdehyde （MDA） level， superoxide dismutase （SOD） level， and mRNA and protein expressions related to the Nrf2/HO-1/NQO1 pathway in liver tissue of model mice. RESULTS In vitro results showed that Eh-ENVs had no inhibitory effect on the proliferation of RAW264.7 and AML12 cells；Eh-ENVs could be efficiently taken up by RAW264.7 cells and significantly reduced the mRNA expression of interleukin-1β （IL-1β）， tumor necrosis factor-α （TNF-α）， and ROS level in cells （ P ＜0.05）. In vivo results showed that 4 mg/kg Eh-ENVs had no obvious toxic side effects on normal mice，could significantly decrease the serum alanine transaminase （ALT） and aspartate transaminase （AST） levels in model mice （ P ＜0.05），upregulated/increased the mRNA expressions of IL-10， as well as the mRNA and protein expressions of Nrf2， HO-1， and NQO1， and SOD level in liver tissue （ P ＜0.05）， and down-regulated/decreased the mRNA expression of TNF-α， IL-1β and MDA level in liver tissue （ P ＜0.05）. CONCLUSIONS Eh-ENVs may activate the Nrf2/HO-1/NQO1 pathway to inhibit inflammatory response and alleviate oxidative stress， thereby improving APAP-induced liver injury.

Objective To investigate the therapeutic effect and underlying mechanism of piceatannol against hepatic ischemia-reperfusion injury (HIRI) in fatty liver. Methods A mouse model of fatty liver combined with HIRI was established, and experimental animals were assigned into four groups: sham operation group, fatty liver HIRI group, fatty liver HIRI + piceatannol group, and fatty liver HIRI + piceatannol + ML385 group (n=5). Serum levels of alanine transaminase (ALT), aspartate transaminase (AST) and lactate dehydrogenase (LDH) were detected in each group. Hepatic tissue injury was evaluated by hematoxylin-eosin staining. Biochemical assays were performed to measure the contents of malondialdehyde (MDA), glutathione (GSH) and superoxide dismutase (SOD). Reactive oxygen species (ROS) were quantified using the DHE fluorescent probe method, while the expression of 4-hydroxynonenal (4-HNE) was determined via immunohistochemical staining. Western blot was adopted to detect the protein expression of glutathione peroxidase 4 (GPX4), acyl-CoA synthetase long-chain family member 4 (ACSL4), heme oxygenase-1 (HO-1) and nuclear factor E2-related factor 2 (Nrf2). Primary mouse hepatocytes were isolated and cultured in vitro. After treatment with palmitic acid, an hypoxia/reoxygenation (H/R) model was established. Cellular experiments were divided into control group, steatosis H/R group, steatosis H/R + piceatannol group, and steatosis H/R + piceatannol + ML385 group. Calcein-AM/PI dual staining was used to observe cell viability, C11 BODIPY staining was used to determin lipid peroxidation levels, and DCFH-DA fluorescent probe was utilized to test intracellular ROS levels. Western blot was used to detect the protein abundances of GPX4, ACSL4, HO-1 and Nrf2, and real-time fluorescence quantitative polymerase chain reaction was applied to quantify their corresponding messenger RNA (mRNA) expression levels. Results Compared with the sham operation group, the levels of ALT, AST and LDH, liver injury score, DHE positive rate, MDA level and 4-HNE level increased, the levels of GSH and SOD decreased, the relative expression level of ACSL4 protein increased, and the relative expression levels of GPX4, Nrf2 and HO-1 proteins decreased in the fatty liver HIRI group; compared with the fatty liver HIRI group, the levels of ALT, AST and LDH, liver injury score, DHE positive rate, MDA level and 4-HNE level decreased, the levels of GSH and SOD increased, the relative expression level of ACSL4 protein decreased, and the relative expression levels of GPX4, Nrf2 and HO-1 proteins increased in the fatty liver HIRI + piceatannol group; compared with the fatty liver HIRI + piceatannol group, the levels of ALT, AST and LDH, liver injury score, DHE positive rate, MDA level and 4-HNE level increased, the levels of GSH and SOD decreased, the relative expression level of ACSL4 protein increased, and the relative expression levels of Nrf2 and HO-1 proteins decreased in the fatty liver HIRI + piceatannol + ML385 group (all P<0.05). Compared with the control group, the mean fluorescence intensity of DCFH-DA and MDA level increased, the levels of GSH and SOD decreased, the proportion of oxidized lipids increased, the protein and mRNA expression levels of ACSL4 increased, and the protein and mRNA expression levels of GPX4, HO-1 and Nrf2 decreased in the steatosis H/R group; compared with the steatosis H/R group, the mean fluorescence intensity of DCFH-DA and MDA level decreased, the levels of GSH and SOD increased, the proportion of oxidized lipids decreased, the relative protein and mRNA expression levels of ACSL4 decreased, and the relative protein and mRNA expression levels of GPX4, HO-1 and Nrf2 increased in the steatosis H/R + piceatannol group; compared with the steatosis H/R + piceatannol group, the mean fluorescence intensity of DCFH-DA and MDA level increased, the levels of GSH and SOD decreased, the proportion of oxidized lipids increased, the relative protein and mRNA expression levels of ACSL4 increased, and the relative protein and mRNA expression levels of GPX4, HO-1 and Nrf2 decreased in the steatosis H/R + piceatannol + ML385 group (all P<0.05). Conclusions Piceatannol relieves HIRI in fatty liver by activating the Nrf2/HO-1 signaling pathway to suppress ferroptosis in hepatocytes.

ObjectiveTo describe the characteristics of cardiorespiratory fitness levels in the baseline population of the South China Cohort， and to identify the potential contributing factors. MethodsFace-to-face surveys and physical examinations were conducted to collect information on demographic characteristics， medical histories， medications， lifestyles， and physical activity conditions. After excluding individuals with missing cardiorespiratory fitness-related data and covariates including physical activity and dietary information， a total of 77 024 participants aged 25 to 85 were included. Cardiorespiratory fitness levels were evaluated using a non-exercise algorithm， and low cardiorespiratory fitness level was defined as below the lower tertile of the population distribution. Logistic regression analysis was used to examine the distribution of low cardiorespiratory fitness level， and log-binomial regression and ordered logistic regression analyses were used to analyze the associations of cardiorespiratory fitness with demographic characteristics， socioeconomic factors， lifestyle factors （including alcohol consumption and dietary diversity）， and chronic diseases conditions （including diabetes， hypertension， pulmonary diseases， and cardiovascular diseases）. ResultsCardiorespiratory fitness levels showed a sufficiently normal distribution in both male and female group. We found that the proportion of low cardiorespiratory fitness level was higher among Han ethnicity， those with an educational level below 9th grade， households with an annual income of more than 100 000 Yuan， as well as those who drank alcohol at least one time per week and who exhibited low dietary diversity （all P＜0.001）. Ethnicity， socioeconomic status， lifestyle factors， and chronic diseases were found to be statistically associated with cardiorespiratory fitness levels in the South China population （all P＜0.001）. ConclusionCardiorespiratory fitness levels varied across different population groups in South China， with ethnicity， socioeconomic status， lifestyle factors， and chronic diseases serving as key determinants. Therefore， it is recommended that the public pay attention to cardiorespiratory fitness， as strengthening population-level monitoring and interventions for cardiorespiratory fitness carries significant public health implications.

ObjectiveTo characterize the features of etomidate-related criminal cases in Guangxi after its formal scheduling as a controlled substance in China. MethodsWe collected judicial documents of etomidate-related criminal cases in Guangxi， published on China Judgments Online from October 2023 to July 2025. Demographic， criminological， and forensic toxicological characteristics were extracted. We analyzed the differences in demographic characteristics between the offenders and the baseline of the general population in Guangxi， and examined the associations of age， educational attainment， prior criminal conviction， and employment status with offense types. ResultsA total of 51 adjudicated cases were included， involving 174 individuals. The offenders were predominantly male， young adults， with low educational attainment， prior criminal convictions， and unemployed status. Statistically significant differences were observed between the offenders and the baseline of the general population in Guangxi across four dimensions： gender， age， educational attainment， and employment status （all P values＜0.01）. The primary offense types were the crime of providing shelter for others to use drugs and drug trafficking offenses. The majority of cases involved joint offenses committed by multiple perpetrators， with e-cigarettes and related products as the main drug delivery vehicles. Forensic toxicological testing confirmed concurrent polydrug use of etomidate and ketamine among the involved individuals. Prior criminal conviction status was statistically associated with the choice of offense type （Fisher's P = 0.006）. Offenders with prior convictions predominantly committed single-type offenses， while those without prior convictions accounted for a significantly higher proportion of multiple concurrent offenses relative to the former group. ConclusionAfter the scheduling of etomidate， the offender population in etomidate-related criminal cases in Guangxi is characterized by low educational attainment， low employment rate， and high prevalence of prior criminal convictions. The offenses exhibited covert modus operandi， group-based offending patterns， and a growing trend of polydrug use. We recommend strengthening the monitoring of high-risk populations and upgrading the technical system of forensic toxicological testing to address the challenges posed by emerging illicit drugs.

Objective : To reveal the role of periodontal ligament stem cell-derived exosomes (PDLSC-Exos) in orthodontic bone remodeling, in order to provide new therapeutic strategies for orthodontic tooth movement (OTM). Methods : This study has been reviewed and approved by the Ethics Committee. Healthy periodontal ligament tissues from clinical orthodontic reduction extractions were collected, and periodontal ligament stem cells (PDLSCs) were isolated and cultured. When cultured to the third generation, their self-renewal ability and multidirectional differentiation potential were detected. PDLSC-Exos were isolated and purified by gradient centrifugation and identified by transmission electron microscopy, immunofluorescence, ZetaView, and nanoflow cytometry. The co-culture of 10 μg/mL PDLSC-Exos and PDLSCs (PDLSCs+Exos) induced osteogenic differentiation to evaluate the effect of osteogenesis. Bone marrow-mononuclear cells (BMMs), promoted by osteoclast differentiation [30 ng/mL macrophage colony stimulating factor (M-CSF) + 50 ng/mL receptor activator of nuclear factor-κ B ligand (RANKL)], and then were treated with 10 μg/mL PDLSC-Exos to assess the effect on osteoclasts. We established a rat model of OTM, and 50 μg/mL PDLSC-Exos was injected locally into the periodontal ligament before we established the model (OTM + Exos), every 2 days for 14 days. Alveolar bone remodeling was analyzed by micro-CT, and alveolar bone osteoclasts were analyzed by immunohistochemistry and immunofluorescence. Results: The isolated and purified PDLSCs met the basic characteristics of mesenchymal stem cells, and PDLSC-Exos had typical characteristics of extracellular vesicles. PDLSCs-Exos significantly promoted the osteogenic differentiation of PDLSCs, and promoted the osteoclast differentiation and bone resorption activity of BMMs (P < 0.05). The rate of alveolar bone remodeling in rats with local periodontal injection of PDLSC-Exos was significantly accelerated, and the tooth movement distance was significantly increased (P < 0.05); immunohistochemistry results showed that PDLSC-Exos promoted the differentiation of osteoclasts (P < 0.05). In addition, immunofluorescence showed that PDLSC-Exos co-localized with osteoclasts, indicating that PDLSC-Exos may promote osteoclast differentiation in vivo. Conclusion PDLSC-Exos accelerate the rate of orthodontic bone remodeling by promoting osteogenic differentiation of PDLSCs and osteoclast differentiation of BMMs, thereby accelerating OTM.

Objective To understand the situation of dental cone beam computed tomography (CBCT) quality control testing phantoms in radiation health technical service institutions in Guangdong province, analyze the differences among different phantoms, and provide a reference for dental CBCT quality control testing. Methods The testing phantoms of 49 radiation health technical service institutions were used as the research objects. The designated CBCT equipment was used for scanning and imaging. The Z-score method was used to evaluate the high-contrast resolution, low-contrast resolution, and distance measurement deviation of each phantom. Results The satisfaction rates of various items for the phantoms in 49 institutions ranged from 85.7% to 100%. The distance measurement deviations of four institutions were “suspicious”, and the high-contrast resolution of four institutions and the distance measurement deviation of one institution were “unsatisfactory”. Conclusion The overall performance of dental CBCT quality control testing phantoms in radiological health technical service institutions in Guangdong province is satisfactory. However, there are still some phantoms with poor results in items such as distance measurement deviation and high-contrast resolution. The structural design, material selection, and manufacturing process of the phantom may all affect the results of quality control testing. Therefore, appropriate phantoms, optimized exposure conditions, and suitable reconstruction algorithms should be used in CBCT quality control testing to ensure accurate and reliable measurements.

ObjectiveTo investigate whether co-activated mesenchymal stem cells（MSCs） exert therapeutic effects against schistosomiasis by modulating macrophage polarization. MethodsTwenty adult male Balb/c mice were randomly divided into four groups： uninfected， infected， MSC-treated， and MSC^TLR4+IFN-γ-treated groups. The Schistosoma japonicum infection model was established via abdominal patch method with cercariae. At week 5 post-infection， praziquantel was administered orally for antiparasitic treatment. At week 6， mice received either MSCs treatments （with or without pre-activation） or no treatment. Body weight changes were monitored weekly. Hepatic pathological alterations were evaluated via HE and Masson staining. RT-qPCR was used to assess α-SMA and collagen （Col-I， Col-Ⅲ） mRNA levels to quantify fibrosis. The mRNA levels of hepatic inflammatory cytokines and matrix metalloproteinases（MMP） were analyzed to explore fibrotic mechanisms. The expressions of i-Nos and Arg-1 in liver tissues were detected by RT-qPCR， and the ratio of M1 or M2 macrophages was detected by immunofluorescence staining， aiming to analyze the correlation between MSCs treatment and macrophage polarization. An in vitro co-culture system validated direct MSC-macrophage interactions. ResultsCompared with the infected group， the MSC^TLR4+IFN-γ group exhibited increased body weight gain （P< 0.01）， reduced hepatic granulomatous lesion area （P< 0.001）， and decreased α-SMA， Col-I， and Col-Ⅲ mRNA levels （P< 0.01）. Additionally， the MSC^TLR4+IFN-γ group showed reduced TNF-α and IL-1β expression （P< 0.05）， as well as elevated MMP2， Mmp9， and MMP13 levels （P< 0.01）. The MSC^TLR4+IFN-γ group showed higher expression of M2 marker Arg-1 mRNA compared with the infection group （P < 0.001） ， while the expression of M1 marker i-Nos decreased （P< 0.05）. Immunofluorescence confirmed a lower i-Nos+ cell ratio （P< 0.05） and higher F4/80⁺CD206⁺ cell ratio （P< 0.000 1） in the MSC^TLR4+IFN-γ group compared with the infection group. In vitro co-culture experiments further demonstrated that MSC^TLR4+IFN-γ promoted Arg-1 expression， suppressed pro-inflammatory cytokine i-Nos and TNF-α levels， consistent with ELISA results. ConclusionsThis study reveals that TLR4 and IFN-γ co-activated MSCs alleviate Schistosoma japonicum-induced hepatic fibrosis， potentially through modulating macrophage polarization toward the M2 phenotype. This mechanism may suppress inflammation and enhance extracellular matrix degradation， providing a therapeutic strategy for schistosomiasis-associated liver fibrosis.