Dry eye disease(DED)is a common ocular surface disorder worldwide, primarily characterized by a loss of homeostasis of the tear film, and frequently associated with meibomian gland dysfunction(MGD), decreased tear film stability, ocular discomfort, and visual impairment. In recent years, factors such as the widespread use of digital devices,the aging population, and environmental changes have contributed to a significant increase in its global prevalence, making it a major public health concern. Red light therapy(RLT), also known as low-level laser therapy(LLLT)or photobiomodulation(PBM), is a non-invasive treatment that utilizes low-energy red or near-infrared light to irradiate tissues. It exerts photobiomodulatory effects to promote cellular repair and functional recovery. This therapy has demonstrated considerable potential in treating various ocular conditions. Its broader clinical application could improve therapeutic outcomes, alleviate patient discomfort and financial burden, and reduce the consumption of healthcare resources, thereby yielding significant socio-economic benefits. This paper systematically reviews the multifaceted mechanisms and application prospects of RLT in managing DED, including its anti-inflammatory effects, improvement of meibomian gland function, promotion of conjunctival goblet cell repair, and alleviation of visual fatigue, aiming to provide a theoretical foundation and practical reference for its clinical adoption.

Corynebacterium pseudotuberculosis(C.pseudotuberculosis)is a group of intracellular Gram-positive bacteria that can cause zoonotic diseases.This study investigated the mechanisms of inflammatory mediator secretion and the phagocytic and bactericidal functions of mouse peritoneal macrophages following C.pseudotuberculosis infection.Initially,transcriptomic sequencing was em-ployed to identify genes critical for C.pseudotuberculosis infection in macrophages.Subsequently,gene knockout mice were utilized to assess the impact of these key genes on inflammatory media-tor secretion,activation of inflammatory signaling pathways,and the phagocytic and bactericidal functions of macrophages infected with C.pseudotuberculosis.Techniques such as ELISA,Western blot,and immunofluorescence were employed in this analysis.Further,transcriptomic sequencing was conducted to identify key downstream genes.Following C.pseudotuberculosis infection,GO enrichment analysis was performed,and TLR2 was identified as the focal point of the study.Perito-neal macrophages from C57BL/6J and TLR2 knockout(TLR2-/-)mice were infected with C.pseudotuberculosis.ELISA results revealed that the levels of TNF-α,IL-1β,and IL-10 were signifi-cantly downregulated in TLR2-/-macrophages compared to C57BL/6J macrophages post-infec-tion.Western blot demonstrated that the absence of TLR2 led to a marked decrease in M APK(p38 and ERK)signaling pathway phosphorylation following C.pseudotuberculosis infection.Immuno-fluorescence results indicated that the phagocytic rate of TLR2-/-macrophages was significantly higher than that of C57BL/6J macrophages after infection.Subsequently,transcriptomic analysis of C57BL/6J and TLR2-/-macrophages infected with C.pseudotuberculosis was performed,followed by GO enrichment analysis of differential genes.IL-36a,Cx3cr1,TLR1,and TLR2 were identified as key differential genes.TLR2 plays a crucial role in the inflammatory response induced by C.pseudotuberculosis infection in mice,influencing the progression of the inflammatory response and host outcomes through the secretion of inflammatory mediators,activation of signaling pathways,and modulation of phagocytic and bactericidal functions.IL-36a and Cx3cr1 were identified as key downstream factors in this process.

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.

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

Objective To investigate the clinical efficacy and mechanism of Weiwei Decoction in treating patients with precancerous lesions of gastric cancer(PLGC)differentiated as deficiency-stasis-turbidity syndrome.Methods From August 2021 to August 2023,a clinical observation was performed on 60 patients diagnosed as chronic atrophic gastritis accompanied by mild to moderate dysplasia and differentiated as deficiency-stasis-turbidity syndrome through traditional Chinese medicine(TCM)syndrome differentiation,electronic gastroscopy,and histopathological examination at the Department of Gastroenterology,Guangdong Second Traditional Chinese Medicine Hospital.The patients were randomly divided into a treatment group and a control group using a random number table,with 30 patients in each group.The control group was treated with oral use of Weifuchun Tablets,while the treatment group was given modified Weiwei Decoction according to syndrome differentiation.The treatment course lasted 24 weeks.Before and after treatment,the changes in TCM syndrome scores,gastroscopy and histopathological grading,and expression levels of markers of cancer-associated fibroblasts(CAFs)in gastric mucosal tissues of the two groups were observed.After treatment,the efficacy of TCM syndromes and medication safety were evaluated in both groups.Results(1)After 24 weeks of treatment,the total effective rate in the treatment group was 93.33%(28/30),and that in the control group was 63.33%(19/30).The TCM syndrome efficacy in the treatment group was significantly superior to that in the control group(P＜0.05).(2)After treatment,the TCM syndrome scores in both groups were significantly decreased compared to those before treatment(P＜0.01),and the decrease in the treatment group was significantly superior to that in the control group(P＜0.05).(3)After treatment,the histopathological grading of gastric mucosal atrophy,intestinal metaplasia,and dysplasia in the treatment group was significantly improved compared to that before treatment(P＜0.05),while no significant improvement was presented in the control group(P＞0.05).The improvement in histopathological grading of gastric mucosal atrophy,intestinal metaplasia,and dysplasia in the treatment group was significantly superior to that in the control group(P＜0.05 or P＜0.01).(4)After treatment,the expression levels of CAFs markers of fibroblast activation protein(FAP)and α-smooth muscle actin(α-SMA)in the treatment group were significantly decreased(P＜0.05),while the expression levels of FAP and α-SMA in the control group were significantly increased(P＜0.05)compared to those before treatment.The decrease in FAP and α-SMA expression levels of the treatment group was significantly greater than that of the control group(P＜0.01).(5)During the treatment period,no adverse drug events occurred in either group,indicating high safety.Conclusion Weiwei Decoction has significant therapeutic effect on PLGC patients with deficiency-stasis-turbidity syndrome.Its mechanism may be related to the down-regulation of FAP and α-SMA levels and inhibition of the expression of CAFs.

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.

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.

Hypertension is one of the important causes of premature death worldwide,and the prevention and treatment of hypertension is of great significance in reducing the incidence and mortality rate of cardiovascular disease.Antihypertensive drugs and food homologous traditional Chinese medicine have the advantages of easy access,high safety,and minimal side effects.Based on the list of 101 traditional Chinese medicinal materials that are both medicinal and food substances released by the National Health Commission,a search was conducted on 101 Chinese medicinal materials related to hypertension using the China National Knowledge Infrastructure(CNKI).The screening criteria are single drug,extract,or monomer therapy for hypertension,and the number of literature is≥2,resulting in 14 medicinal and food homologous traditional Chinese medicines with antihypertensive effects.Search for 14 Chinese medicine names and hypertension keywords on PubMed,Web of Science,and Google Scholar to collect reports on the treatment of hypertension with medicinal and food homologous traditional Chinese medicine.Based on the search results of China National Knowledge Infrastructure,summarize their classification,drug properties,efficacy,antihypertensive effects,and mechanism of action,in order to provide inspiration for new prescriptions,drug development,and functional foods for treating hypertension.Most of the antihypertensive traditional Chinese medicines with the same origin as medicine and food belong to the categories of clearing heat and tonifying deficiency;Most drugs have a sweet and spicy taste,which belongs to the liver,spleen,and kidney meridians.The efficacy is mostly to clear the liver and brighten the eyes,tonify the liver and kidneys,promote qi circulation,dispel blood stasis,and disperse nodules.It mainly inhibits ACE activity;Reduce REN and AngⅡ levels;Upregulate SOD levels and reduce MDA expression;Improve the expression level of NO/NOS;Enhance antioxidant effects;Improve endothelial function;Relieve inflammatory reactions;Various methods such as reducing target organ damage can play a role in treating hypertension.

Objective To systematically investigate the impact of music intervention on neuroplasticity in patients with Alzheimer's disease(AD).Methods PubMed,EBSCOhost,Web of Science,Embase,CNKI,Wanfang data and VIP were searched for studies pub-lished up to February,2025.They were analysed using GingerALE 3.0.2 for meta-analysis.Results Five fMRI studies were included,involving 134 participants(99 with AD).A total of 49 activation coordinates were extracted.The main activation regions in the healthy group were concentrated in the left precuneus,the right inferior frontal gyrus and the right superior temporal gyrus,while the primary activated regions in AD group shifted to the right operculum and adjacent right insula,left superior frontal gyrus,right medial frontal gyrus,and left superior temporal gyrus,indicating that during music processing,neural activation patterns in AD patients shifted from higher-order associative cortices to subcortical structures,accompanied by compensatory changes in frontal lobe activation and a loss of activation in the parietal lobe,particularly in the precuneus.Conclusion Music intervention can activate the relatively preserved subcortical-limbic system in patients with AD and promote compensatory reorganization of the frontal lobes.