Hepatic fibrosis refers to excessive accumulation and abnormal proliferation of fibrous connective tissue in the liver triggered by multiple pathogenic factors， and it may progress to liver cirrhosis， portal hypertension， and liver cancer. The pathological mechanisms of hepatic fibrosis involve hepatocyte injury， inflammatory cell infiltration with the release of inflammatory mediators， hepatic stellate cell activation， and extracellular matrix deposition. Recent studies have focused on mitochondrial dysfunction in disease progression， including the molecular pathways for hepatic fibrosis driven by metabolic disorders， energy deficiency， oxidative stress， mitochondrial dynamic imbalance， and autophagic dysfunction， all of which can induce liver injury. This article reviews the latest advances in hepatic fibrosis， in order to provide new therapeutic strategies for clinical management.

Background Climate change poses a significant threat to public health. In China, relevant health intervention research is still in its early stages, and evidence for evaluating the effectiveness of regional climate change health adaptation strategies and measures is scarce. Objective To investigate the level of climate change-related health literacy among residents in Shenzhen, implement targeted health interventions, and assess the intervention effects as well as their influencing factors. Methods From July 2023 to January 2024, 4 communities were randomly selected in Shenzhen, and a total of 896 community residents were enrolled and divided into an intervention group (444 participants) and a control group (452 participants). Baseline and follow-up surveys on climate change-related health literacy were conducted among residents for both groups. During the period between the two surveys, the intervention group received targeted health interventions. Health literacy—comprising 3 dimensions: basic health knowledge and concepts, basic health skills, and healthy lifestyles—was defined as achieving ≥80% of the total score. A differences-in-differences model was adopted to analyze the impact of the intervention, and multiple linear regression was used to explore the factors influencing the intervention effect. Results The baseline survey showed that 240 out of the 896 surveyed residents (26.79%) possessed climate change health literacy. For the 3 dimensions, the number of residents and the proportions with corresponding literacy in descending order were: basic health skills (521, 58.15%), healthy lifestyles (345, 38.50%), and basic health knowledge and concepts (44, 4.91%). After the intervention, the intervention group showed a 3.19% increase in the total health literacy score, a 3.55% increase in basic health knowledge and concepts, and a 4.24% increase in basic health skills (t=2.79, 2.77, and 2.47 respectively) (P<0.05). No significant change was observed in healthy lifestyle scores (t=0.70, P>0.05). Further analysis showed that awareness of the “dual carbon goals” and occupation were significantly associated with the intervention effect on overall health literacy (P<0.05). For basic health knowledge and concepts, occupation, history of chronic diseases, and awareness of the “dual carbon goals” had statistically significant effects on the intervention outcomes (P<0.05). Regarding basic health skills, awareness of the “dual carbon goals” significantly influenced the intervention effect (P<0.001). In terms of healthy lifestyles, gender, educational level, occupation, and awareness of climate change were significantly associated with the intervention effect (P<0.05). Conclusion The climate change-related health literacy among community residents in Shenzhen is in urgent need of improvement. Health interventions can effectively enhance residents' basic health knowledge and concepts, basic health skills, and overall literacy level. In the future, it is necessary to strengthen the popularization of climate change health knowledge based on different population characteristics and further optimize intervention strategies, to comprehensively improve residents' health adaptation capacity to climate change.

Objective: To reveal the therapeutic effects of moxibustion in collagen-induced arthritis (CIA) rat models using the combined analysis of plasma and synovial membrane lipidomic profiling and to enhance the understanding of how moxibustion affects lipid metabolism in rheumatoid arthritis (RA). Methods: A total of 32 male Sprague-Dawley (SD) rats were randomly assigned to four groups: control, moxibustion control (MC), model, and moxibustion model (MM) groups, with 8 rats in each group. CIA was induced in SD rats by two immunizations. The paw volume was measured before the induction of CIA. Following induction, after assessing paw volume and arthritis index (AI) scores, the MC and MM groups received treatment at bilateral Shenshu (BL23) and Zusanli (ST36) acupoints for 10 min per acupoint. The intervention included three treatment courses, each spanning 6 d and followed by a 1-d interval. Paw volume and AI scores were assessed after each treatment course. After the completion of the three treatment courses, serum, plasma, synovial tissue, and ankle joint samples were collected. Enzyme-linked immunosorbent assay (ELISA) was employed to quantify the levels of interleukin (IL)-6 and tumor necrosis factor (TNF)-α in serum. Hematoxylin and eosin (HE) staining was performed for histopathological examination of the ankle joint tissues. Meanwhile, ultra-high-performance liquid chromatography coupled with Q-Exactive Orbitrap mass spectrometry (UHPLC-Q-Exactive Orbitrap MS) was utilized to analyze the plasma and synovial tissue samples. In addition, multivariate statistical analysis was performed to identify differential lipid metabolites, and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis was applied to explore metabolic pathways modulated by moxibustion therapy. Results: No significant difference in hind paw volume and AI scores was observed among the groups (P > 0.05). After CIA induction, model group showed increased hind paw volume and AI scores compared with control group (P < 0.05), which were significantly reduced after moxibustion treatment in MM group compared with model group (P < 0.05). The levels of IL-6 and TNF-α were significantly higher in model and MM groups compared with control group (P < 0.05), but were lower in MM group than those in model group (P < 0.05). Histopathological analysis showed improved cartilage and reduced inflammation in MM group. A total of 33 differential lipid metabolites in the plasma and 24 in the synovial membranes of CIA rat models were identified when compared with control group. Among these lipid metabolites, 31 in the plasma and all 24 in the synovial membranes were regulated by moxibustion treatment. Pathological analysis revealed upregulation of diacylglycerol (DG) and fatty acid (FA) levels, alongside downregulation of lysophosphatidylcholine (LPC), phosphatidylcholine (PC), and phosphatidylethanolamine (PE). Under physiological conditions, the treatment specifically reduced LPC and PC levels. Pathway enrichment analysis revealed that moxibustion predominantly affected α-linolenic acid, glycerophospholipid, and sphingolipid metabolism under pathological conditions. Under physiological conditions, the regulation was centered around α-linolenic acid and glycerophospholipid metabolism. Conclusion The RA rat models exhibited significant lipid metabolic disturbances. Moxibustion alleviated paw swelling, reduced AI scores, modulated inflammatory cytokine levels, and partially corrected the altered levels of multiple lipid metabolites. The potential metabolic pathways implicated in the regulation of lipid metabolism under both physiological and pathological conditions include α-linolenic acid, glycerophospholipid, and sphingolipid metabolism.

ObjectiveBased on transcriptomics， to explore the mechanism of Hei Xiaoyaosan regulating the phosphatidylinositol 3-kinase/protein kinase B （PI3K/Akt） signaling pathway to improve the learning and memory ability of insomnia rats with liver depression syndrome. MethodsSixty 8-week-old male SD rats were randomly divided into the blank group， model group， eszopiclone group （0.09 mg·kg^-1）， and low， medium， and high dose groups of Hei Xiaoyaosan （3.82， 7.65， 15.30 g·kg^-1）， with ten rats in each group. Except for the blank group， the other groups were induced insomnia rat model with liver depression by chronic restraint， tail clamping stimulation and intraperitoneal injection of p-chlorophenylalanine （PCPA）. Each treatment group received intragastric administration according to the specified dosage， once a day for 14 consecutive days. The pentobarbital sodium cooperative sleep test， open field test， and Morris water maze test were used to test the sleep quality， depressive-like behavior， and learning and memory abilities of rats. Additionally， enzyme-linked immunosorbent assay （ELISA） was used to detect the contents of 5-hydroxytryptamine （5-HT）， γ-aminobutyric acid （GABA）， brain-derived neurotrophic factor （BDNF）， glial cell line-derived neurotrophic factor （GDNF） and nitric oxide （NO） in hippocampus. Hematoxylin-eosin （HE） staining was performed to observe pathological changes of the hippocampal tissue， while terminal deoxynucleotidyl transferase deoxyuridine triphosphate （dUTP） nick end labeling （TUNEL） was used to evaluate apoptosis of hippocampal neurons. Transcriptomic sequencing technology was employed to identify differentially expressed genes in hippocampus between the model group and the blank group， as well as between the medium-dose group of Hei Xiaoyaosan and the model group. Gene Ontology （GO） and Kyoto Encyclopedia of Genes and Genomes （KEGG） enrichment analysis were performed on the intersecting genes. Subsequently， the enriched key genes and signaling pathways were analyzed and verified. Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR） was utilized to assess the mRNA expression levels of phosphatase and tensin homolog （PTEN）， B-cell lymphoma-2 （Bcl-2）-like protein 11 （BCL2L11）， and mitogen-activated protein kinase 1 （MAPK1） in hippocampus， and Western blot was employed to evaluate the protein expressions of PI3K， phosphorylation （p）-PI3K， Akt， p-Akt， Bcl-2， Bcl-2-associated X protein （Bax）， and cleaved Caspase-3 in the same tissue. ResultsCompared with the blank group， the model group exhibited a reduction in body weight， an increase in sleep latency， and a decrease in sleep duration （P<0.01）. Additionally， rats showed obvious depression-like behavior， and their learning and memory abilities decreased. Furthermore， the contents of 5-HT， GABA， NO， BDNF and GDNF in hippocampus decreased （P<0.01）. Histological examination revealed a disorganized cell arrangement in the CA1 region of the hippocampus， characterized by irregular cell shapes， a reduced cell count， deeply stained and pyknotic nuclei， increased vacuolar degeneration， and an elevated apoptosis rate （P<0.01）. Compared with the model group， the body weight of the high and medium dose groups of Hei Xiaoyaosan increased， the sleep latency shortened and the sleep time prolonged （P<0.05， P<0.01）. Additionally， depression-like behavior and learning and memory abilities of rats were significantly improved， the levels of 5-HT， GABA， NO， BDNF and GDNF in the hippocampus increased （P<0.05， P<0.01）. These interventions also ameliorated pathological damage in the hippocampal CA1 area and reduced the apoptosis of hippocampal neurons （P<0.01）. Transcriptomic sequencing results indicated that Hei Xiaoyaosan might exert a therapeutic effect by regulating PI3K/Akt pathway through key mRNAs such as PTEN， BCL2L11， and MAPK1. The roles of these key mRNAs and proteins within PI3K/Akt pathway were further validated. In comparison to the blank group， the expression levels of PTEN， BCL2L11 and MAPK1 mRNA in the hippocampus of rats in the model group were increased （P<0.01）， while the protein expression levels of p-PI3K， p-Akt and Bcl-2 were decreased （P<0.01）， and the protein expression levels of PTEN， Bax and cleaved Caspase-3 were increased （P<0.01）. Compared with the model group， the high-dose and medium-dose groups of Hei Xiaoyaosan could down-regulate the expressions of PTEN， BCL2L11 and MAPK1 mRNAs （P<0.01）， up-regulate the expressions of p-PI3K， p-Akt and Bcl-2 proteins （P<0.01）， and down-regulate the protein expressions of PTEN， Bax and cleaved Caspase-3 （P<0.05， P<0.01）. ConclusionHei Xiaoyaosan may regulate PI3K/Akt signaling pathway by down-regulating expressions of key genes such as PTEN， BCL2L11 and MAPK1， and thus improve the learning and memory abilities of insomnia rats with liver depression syndrome.

Objective To discuss the correlation between noninvasive hemodynamic parameters and major adverse cardiovascular events(MACE)in patients with acute anterior wall myocardial infarction after receiving percutaneous coronary intervention(PCI).Methods A total of 132 patients with acute anterior wall myocardial infarction,who received PCI at the Affiliated People's Hospital of Shandong First Medical University of China between October 2021 and February 2024,were collected.At 24 h and 7 d after surgery,the hemodynamic parameters,including mean arterial pressure(MAP),cardiac index(CI),cardiac output(CO),stroke volume(SV),peripheral vascular resistance index(SVRI),were recorded.Spearman correlation analysis was used to analyze the relationship between Killip grade of cardiac function and hemodynamic parameters.According to the presence or absence of MACE within 6 months after PCI,the patients were divided into MACE group and non-MACE group.The predictive value of hemodynamic parameters for MACE was analyzed by receiver operating characteristic(ROC)curves.Results The postoperative 7-day levels of CO,CI and SV were higher than their postoperative one-day levels,while the postoperative 7-day level of SVRI was lower than its postoperative one-day level(P＜0.05).Of the 132 patients,Killip classification of grade Ⅰ was seen in 39,grade Ⅱ in 62,grade Ⅲin 23 and grade Ⅳ in 8.The postoperative 7-day levels of CO,CI and SV in the patients with Killip gradeⅢ-Ⅳ were lower than those in the patients with Killip grade Ⅰ-Ⅱ,while the level of SVRI in the patients with Killip grade Ⅲ-Ⅳ was higher than that in the patients with Killip grade Ⅰ-Ⅱ(P＜0.05).The results of Spearman correlation analysis showed that Killip grade of cardiac function was negatively correlated with the postoperative 7-day levels of CO,CI and SV,while positively correlated with the postoperative 7-day level of SVRI after PCI(r=-0.518,r=-0.480,r=-0.416 and r=0.493 respectively,all P＜0.05).Six months after PCI,34 patients developed MACE.The levels of CO,CI and SV in MACE group were lower than those in the non-MACE group,while the level of SVRI in MACE group was higher than that in the non-MACE group(P＜0.05).The area under the ROC curve(AUC)of MAP,CO,CI,SV,SVRI and combination of the five indicators for predicting MACE was 0.620,0.687,0.676,0.649,0.710 and 0.860 respectively,and the AUC value of the combination of the five indicators was the greatest one.Conclusion In patients with acute anterior wall myocardial infarction after receiving PCI,the changes in the levels of MAP,CO,CI,SV and SVRI can reflect cardiac function level to a certain extent and can predict the occurrence of MACE events in the short term.

Objective To investigate the effect of interactions between hypoxia-inducing factor 1α(HIF-1α)and transforming growth faction-β2(TGF-β2)on the development of primary open-angle glaucoma(POAG)in high myopia(HM)and their early prediction value.Methods A prospective cohort study was conducted on 265 patients(421 eyes)with HM who were admitted to our hospital from February 2021 to June 2023.All patients underwent comprehensive oph-thalmological examinations,including optical coherence tomography to measure the total Bruch's membrane opening-disc edge minimum width(BMO)parameter,and the Humphrey field analyzer to measure the visual field index(VFI)and mean defect(MD)values.After a follow-up of 1 year(2 cases lost to follow up),the patients were divided into an occurrence group(51 cases,82 eyes)and a non-occurrence group(212 cases,337 eyes)according to whether POAG occurred.The clinical data[including age,gender,body mass index(BMI),central corneal thickness(CCT),axial length(AL),refrac-tive power,VFI,visual field MD,optic disc horizontal diameter,optic disc vertical diameter,elliptical index,optic disc ar-ea,optic cup area,disc rim area,cup-to-disc area ratio,and total BMO],tear HIF-1α and TGF-β2 were compared be-tween the two groups.The receiver operating characteristic(ROC)curves of tear HIF-1α and TGF-β2 for predicting HM with POAG were plotted to obtain the optimal cutoff value.The effects of tear HIF-1α,TGF-β2 and their interactions on the development of POAG in HM were analyzed.The Pearson method was used to analyze the correlation of tear HIF-1α and TGF-β2 with the optic disc structure of HM patients.The ROC analysis was used to evaluate the value of HIF-1α combined with TGF-β2 for predicting POAG.Results Compared with those in the non-occurrence group,the VFI and BMO were lower while the visual field MD,disc cup area,cup-to-disc area ratio,tear HIF-1α and TGF-β2 were higher in the occur-rence group(all P＜0.05).The interaction analysis showed that the interaction between tear HIF-1 α and TGF-β2 was a su-per-multiplication model,with a positive interaction effect on the occurrence of POAG in HM(P＜0.05).The Pearson analysis showed that tear HIF-1α and TGF-β2 were negatively correlated with VFI and total BMO,and positively correlated with their visual field MD,disc cup area,and cup-to-disc area ratio in patients with HM(all P＜0.05).The ROC curve analysis showed that the area under the ROC curve(AUC)of the effect of tear HIF-1α combined with TGF-β2 for predic-ting POAG in HM was 0.925(95％CI:0.896-0.949).The predictive value of tear HIF-1α combined with TGF-β2 was bet-ter than that of the two indicators alone.Conclusion HIF-1α and TGF-β2 are up-regulated in tears of HM patients com-plicated with POAG,and they interact positively during the occurrence of POAG.The combined detection of HIF-1α and TGF-β2 has predictive value for POAG.They can be used as an auxiliary clinical predictor of POAG,and can guide its clini-cal prevention and treatment.

Objective:To investigate the factors influencing sound localization in patients with unilateral sudden sensorineural hearing loss, so as to provide the reference for hearing rehabilitation of patients with unilateral sudden hearing loss.Methods:This study was a cross-sectional study that retrospectively analyzed the clinical data and audiological examination results of 228 patients with unilateral sudden sensorineural hearing loss(103 males and 125 females; aged from 18 to 80 years, with an average age of 46.2 years; 107 cases in the left ear and 121 cases in the right ear; 8 cases of low-frequency decline type, 42 cases of high-frequency decline type, 92 cases of flat decline type, and 86 cases of total deafness type)at the Eye and ENT Hospital of Fudan University from June 2023 to April 2024. The minimum audible angle (MAA) was calculated by the angle discrimination test of 1000 Hz and 4000 Hz warble tones, which were recorded as MAA 1 000 and MAA 4 000 according to the frequency of the given sound stimulus. The root mean square error (RMSE) was calculated by the angle recognition test with daily natural sounds as the stimulus sound. Using SPSS 27.0 statistical software, correlation and multiple regression analysis were used to research the clinical factors affecting the ability of sound localization in patients with unilateral sudden sensorineural hearing loss. Results:The mean MAA 1 000, MAA 4 000, RMSE of patients with unilateral sudden deafness were (53.97±29.14)°, (46.34±28.87)° and (30.06±13.64)°, respectively. Univariate analysis of variance revealed that there were significant differences between different classifications of sudden sensorineural hearing loss for sound localization tests (MAA 1 000: F=6.338, P<0.001,MAA 4 000: F=14.334, P<0.001,RMSE: F=49.918, P<0.001), post-hoc analysis observed that all significant contrasts were included the type of total deafness and low-frequency deafness. Correlation analysis showed the age of subjects in this study was weak positively correlated to the MAA 1 000 ( r=0.165, P=0.013), the duration of sudden sensorineural hearing loss was weak negatively related to RMSE ( r=-0.144, P=0.030), there were significant positive relationships between the threshold of PTA, PTA 1kHz, PTA 4kHz for the affected side, as well as the binaural PTA difference and sound localization test (MAA 1 000,MAA 4 000,RMSE) (all P<0.001). The multiple regression analysis showed the age and the binaural PTA difference for the affected side were the significant factors for the MAA 1 000 and MAA 4 000, the binaural PTA difference was the significant factors for the RMSE. The R 2 of multivariable linear regression model for MAA 1 000, MAA 4 000 and RMSE results in unilateral sudden deafness patients were 0.149, 0.207 and 0.553, respectively. Conclusion:Age, the hearing of the affected side, and binaural PTA difference are the significant factors for sound localization ability in patients with unilateral sudden sensorineural hearing loss, hearing compensation of the affected ear for these patients is hopeful to enhance the sound localization ability.

The global incidence of head and neck cancer (HNC) is rising, with over 60% of patients presenting at a locally advanced stage. Radiotherapy remains a cornerstone of HNC treatment, and advancements in modern techniques and concurrent chemotherapy have improved local control and survival rates of HNC patients. However, these benefits also bring challenges in the management of toxicities. Due to the proximity of salivary glands and tumors, especially the highly radiosensitive parotid and submandibular glands, this condition is among the most common adverse effects of radiotherapy. Radiation damages acinar cells and ducts, causing glandular atrophy, fibrosis, and reduced saliva secretion, thereby leading to xerostomia and related complications. The risk and severity of injury are associated with the radiation dose and volume affecting the glands. Prevention and management strategies emphasize precise radiotherapy planning, target optimization, and supportive care. Emerging multimodal imaging techniques offer potential for non-invasive prediction and early diagnosis and treatment of radiation-induced salivary gland injury. Future research in regenerative medicine, tissue engineering, and molecular biology aims to elucidate molecular mechanisms, such as signaling pathways and genomics, facilitating personalized strategies to mitigate radiotherapy-induced toxicities and enhance the quality of life of patients.

Osteoporosis is a prevalent skeletal condition characterized by reduced bone mass and strength, leading to increased fragility. Buqi-Tongluo (BQTL) decoction, a traditional Chinese medicine (TCM) prescription, has yet to be fully evaluated for its potential in treating bone diseases such as osteoporosis. To investigate the mechanism by which BQTL decoction inhibits osteoclast differentiation in vitro and validate these findings through in vivo experiments. We employed MTS assays to assess the potential proliferative or toxic effects of BQTL on bone marrow macrophages (BMMs) at various concentrations. TRAcP experiments were conducted to examine BQTL's impact on osteoclast differentiation. RT-PCR and Western blot analyses were utilized to evaluate the relative expression levels of osteoclast-specific genes and proteins under BQTL stimulation. Finally, in vivo experiments were performed using an osteoporosis model to further validate the in vitro findings. This study revealed that BQTL suppressed receptor activator of NF-κB ligand (RANKL)-induced osteoclastogenesis and osteoclast resorption activity in vitro in a dose-dependent manner without observable cytotoxicity. The inhibitory effects of BQTL on osteoclast formation and function were attributed to the downregulation of NFATc1 and c-fos activity, primarily through attenuation of the MAPK, NF-κB, and Calcineurin signaling pathways. BQTL's inhibitory capacity was further examined in vivo using an ovariectomized (OVX) rat model, demonstrating a strong protective effect against bone loss. BQTL may serve as an effective therapeutic TCM for the treatment of postmenopausal osteoporosis and the alleviation of bone loss induced by estrogen deficiency and related conditions.
Animals ; NFATC Transcription Factors/genetics* ; Drugs, Chinese Herbal/pharmacology* ; Ovariectomy ; Osteoclasts/metabolism* ; Female ; Osteogenesis/drug effects* ; Rats, Sprague-Dawley ; Rats ; NF-kappa B/genetics* ; Osteoporosis/genetics* ; Signal Transduction/drug effects* ; Bone Resorption/genetics* ; Cell Differentiation/drug effects* ; Humans ; RANK Ligand/metabolism* ; Mitogen-Activated Protein Kinases/genetics* ; Transcription Factors

Nine novel compounds, comprising seven tetrahydroanthraquinones (auxarthrolones A-G, 1-7), a γ-butenolide glycoside (malfilamentoside E, 26), and a γ-butenolide (auxarthrolide A, 27), together with eighteen known compounds (8-25) were isolated from rice-based solid culture of Auxarthron umbrinum (A. umbrinum) DSM3193 using the one strain many compounds (OSMAC) approach. The structural elucidation of these compounds was accomplished through nuclear magnetic resonance (NMR), mass spectrometry (MS), and NMR calculation combined with DP4+ analysis or MAEΔΔδ parameter, while the absolute configurations of new compounds were established through single-crystal X-ray diffraction, electronic circular dichroism (ECD) spectroscopic data analysis and/or chemical derivatization. Austrocortilutein (10) and auxarthrol H (14) demonstrated moderate cytotoxicity against U87 and U251 [half maximal inhibitory concentration (IC₅₀) 3.5-12.1 μmol·L^-1]. Additionally, auxarthrolone A (1), auxarthrol H (14), eupolyphagin B (15), and 7-hydroxy-2-(2-hydroxypropyl)-5-methylchromone (17) exhibited torsional effects on fibroblast proliferation challenges induced by oleic acid, thus demonstrating fibroblast proliferation-promoting activity.
4-Butyrolactone/pharmacology* ; Molecular Structure ; Anthraquinones/pharmacology* ; Humans ; Animals ; Mice ; Cell Line, Tumor ; Magnetic Resonance Spectroscopy