Dry eye disease is a chronic ocular surface disorder of multifactorial origin, characterized by a loss of tear film homeostasis and associated with a range of ocular discomfort symptoms. Growing evidence underscores a significant bidirectional relationship between dry eye and depression: individuals with dry eye disease exhibit a higher prevalence of depressive disorders, and conversely, those diagnosed with depression demonstrate an increased susceptibility to developing dry eye. This interplay is mediated through several pathophysiological pathways, such as chronic inflammation, cerebral functional alterations, gut microbiome dysregulation, and sleep disturbances, which may collectively sustain a vicious cycle. The use of antidepressant therapy introduces further complexity, exerting heterogeneous effects on dry eye—some agents may offer symptomatic relief, whereas others can aggravate ocular surface impairment. The mechanisms responsible for these differential outcomes remain incompletely elucidated and merit further investigation. This review systematically consolidates epidemiological data on the dry eye-depression link, examines potential shared pathological mechanisms, and evaluates current therapeutic options. We propose an integrated management approach that combines conventional dry eye treatments, such as traditional Chinese medicine, electroacupuncture, physical activity and antidepressants—a multimodal strategy that may yield synergistic benefits in alleviating both ocular and affective symptoms, thereby improving overall quality of life. Moving forward, research should focus on deciphering the underlying mechanistic pathways and facilitating the translation of these insights into clinical practice to inform targeted, combined treatment regimens for patients with dry eye and depression.

Objective: To investigate the efficacy of magnesium-strontium co-doped hydroxyapatite mineralized collagen (MSHA/Col) in improving the bone repair microenvironment and enhancing bone regeneration capacity, providing a strategy to address the insufficient biomimetic composition and limited bioactivity of traditional hydroxyapatite mineralized collagen (HA/Col) scaffolds. Methods: A high-molecular-weight polyacrylic acid-stabilized amorphous calcium magnesium strontium phosphate precursor (HPAA/ACMSP) was prepared. Its morphology and elemental distribution were characterized by high-resolution transmission electron microscopy (TEM) and energy-dispersive spectroscopy. Recombinant collagen sponge blocks were immersed in the HPAA/ACMSP mineralization solution. Magnesium-strontium co-doped hydroxyapatite was induced to deposit within collagen fibers (experimental group: MSHA/Col; control group: HA/Col). The morphological characteristics of MSHA/Col were observed using scanning electron microscopy (SEM). Its crystal structure and chemical composition were analyzed by X-ray diffraction and Fourier transform infrared spectroscopy, respectively. The mineral phase content was evaluated by thermogravimetric analysis. The scaffold's porosity, ion release, and in vitro degradation performance were also determined. For cytological experiments, CCK-8 assay, live/dead cell staining, alkaline phosphatase staining, alizarin red S staining, RT-qPCR, and western blotting were used to evaluate the effects of the MSHA/Col scaffold on the proliferation, viability, early osteogenic differentiation activity, late mineralization capacity, and gene and protein expression levels of key osteogenic markers [runt-related transcription factor 2 (Runx2), collagen type Ⅰ (Col-Ⅰ), osteopontin (Opn), and osteocalcin (Ocn)] in mouse embryonic osteoblast precursor cells (MC3T3-E1). Results: HPAA/ACMSP appeared as amorphous spherical nanoparticles under TEM, with energy spectrum analysis showing uniform distribution of carbon, oxygen, calcium, phosphorus, magnesium, and strontium elements. SEM results of MSHA/Col indicated successful complete intrafibrillar mineralization. Elemental analysis showed the mass fractions of magnesium and strontium were 0.72% (matching the magnesium content in natural bone) and 2.89%, respectively. X-ray diffraction revealed characteristic peaks of hydroxyapatite crystals (25.86°, 31°-34°). Infrared spectroscopy results showed characteristic absorption peaks for both collagen and hydroxyapatite. Thermogravimetric analysis indicated a mineral phase content of 78.29% in the material. The scaffold porosity was 91.6% ± 1.1%, close to the level of natural bone tissue. Ion release curves demonstrated sustained release behavior for both magnesium and strontium ions. The in vitro degradation rate matched the ingrowth rate of new bone tissue. Cytological experiments showed that MSHA/Col significantly promoted MC3T3-E1 cell proliferation (130% increase in activity at 72 h, P < 0.001). MSHA/Col exhibited excellent efficacy in promoting osteogenic differentiation, significantly upregulating the expression of osteogenesis-related genes and proteins (Runx2, Col-Ⅰ, Opn, Ocn) (P < 0.01). Conclusion The MSHA/Col scaffold achieves dual biomimicry of natural bone in both composition and structure, and effectively promotes osteogenic differentiation at the genetic and protein levels, breaking through the functional limitations of pure hydroxyapatite mineralized collagen. This provides a new strategy for the development of functional bone repair materials

Alzheimer’s disease (AD) is a prevalent neurodegenerative condition characterized by progressive cognitive decline and memory loss. As the incidence of AD continues to rise annually, researchers have shown keen interest in the active components found in natural plants and their neuroprotective effects against AD. Quercetin, a flavonol widely present in fruits and vegetables, has multiple biological effects including anticancer, anti-inflammatory, and antioxidant. Oxidative stress plays a central role in the pathogenesis of AD, and the antioxidant properties of quercetin are essential for its neuroprotective function. Quercetin can modulate multiple signaling pathways related to AD, such as Nrf2-ARE, JNK, p38 MAPK, PON2, PI3K/Akt, and PKC, all of which are closely related to oxidative stress. Furthermore, quercetin is capable of inhibiting the aggregation of β‑amyloid protein (Aβ) and the phosphorylation of tau protein, as well as the activity of β‑secretase 1 and acetylcholinesterase, thus slowing down the progression of the disease.The review also provides insights into the pharmacokinetic properties of quercetin, including its absorption, metabolism, and excretion, as well as its bioavailability challenges and clinical applications. To improve the bioavailability and enhance the targeting of quercetin, the potential of quercetin nanomedicine delivery systems in the treatment of AD is also discussed. In summary, the multifaceted mechanisms of quercetin against AD provide a new perspective for drug development. However, translating these findings into clinical practice requires overcoming current limitations and ongoing research. In this way, its therapeutic potential in the treatment of AD can be fully utilized.

ObjectiveTo investigate the influencing factors for recompensation in patients with decompensated hepatitis C cirrhosis， and to establish a predictive model. MethodsA total of 217 patients who were diagnosed with decompensated hepatitis C cirrhosis and were admitted to The Third People’s Hospital of Kunming l from January， 2019 to December， 2022 were enrolled， among whom 63 patients who were readmitted within at least 1 year and had no portal hypertension-related complications were enrolled as recompensation group， and 154 patients without recompensation were enrolled as control group. Related clinical data were collected， and univariate and multivariate analyses were performed for the factors that may affect the occurrence of recompensation. The independent-samples t test was used for comparison of normally distributed measurement data between two groups， and the Mann-Whitney U test was used for comparison of non-normally distributed measurement data between two groups； the chi-square test or the Fisher’s exact test was used for comparison of categorical data between two groups. A binary Logistic regression analysis was used to investigate the influencing factors for recompensation in patients with decompensated hepatitis C cirrhosis， and the receiver operating characteristic （ROC） curve was used to assess the predictive performance of the model. ResultsAmong the 217 patients with decompensated hepatitis C cirrhosis， 63 （29.03%） had recompensation. There were significant differences between the recompensation group and the control group in HIV history （χ²=4.566， P=0.034）， history of partial splenic embolism （χ²=6.687， P=0.014）， Child-Pugh classification （χ²=11.978， P=0.003）， grade of ascites （χ²=14.229， P<0.001）， albumin （t=4.063， P<0.001）， prealbumin （Z=-3.077， P=0.002）， high-density lipoprotein （t=2.854， P=0.011）， high-sensitivity C-reactive protein （Z=-2.447， P=0.014）， prothrombin time （Z=-2.441， P=0.015）， carcinoembryonic antigen （Z=-2.113， P=0.035）， alpha-fetoprotein （AFP） （Z=-2.063， P=0.039）， CA125 （Z=-2.270， P=0.023）， TT3 （Z=-3.304， P<0.001）， TT4 （Z=-2.221， P=0.026）， CD45⁺ （Z=-2.278， P=0.023）， interleukin-5 （Z=-2.845， P=0.004）， tumor necrosis factor-α （Z=-2.176， P=0.030）， and portal vein width （Z=-5.283， P=0.005）. The multivariate analysis showed that history of partial splenic embolism （odds ratio ［OR］=3.064， P=0.049）， HIV history （OR=0.195， P=0.027）， a small amount of ascites （OR=3.390， P=0.017）， AFP （OR=1.003， P=0.004）， and portal vein width （OR=0.600， P<0.001） were independent influencing factors for the occurrence of recompensation in patients with decompensated hepatitis C cirrhosis. The ROC curve analysis showed that HIV history， grade of ascites， history of partial splenic embolism， AFP， portal vein width， and the combined predictive model of these indices had an area under the ROC curve of 0.556， 0.641， 0.560， 0.589， 0.745， and 0.817， respectively. ConclusionFor patients with decompensated hepatitis C cirrhosis， those with a history of partial splenic embolism， a small amount of ascites， and an increase in AFP level are more likely to experience recompensation， while those with a history of HIV and an increase in portal vein width are less likely to experience recompensation.

AIM: To assess the stability of the tear film and the characteristics of corneal nerves in patients with Parkinson's disease(PD).METHODS: This cross-sectional observational study included 72 PD patients and 50 healthy controls. Disease severity was determined using the Hoehn-Yahr(H-Y)scale, dividing patients into mild and moderate PD groups. Dry eye symptoms were evaluated via the ocular surface disease index(OSDI)questionnaire, while tear secretion was quantified using the Schirmer I test. Ocular surface damage was assessed through staining scores, and comprehensive ocular examinations were performed utilizing the LipiView ocular surface interferometer and an ocular surface analyzer. Corneal nerve parameters were examined using corneal confocal microscopy in conjunction with automated analysis software ACCMetrics, with correlations drawn between these parameters, PD course, and severity.RESULTS: PD patients exhibited significantly elevated OSDI scores, indicative of more pronounced dry eye symptoms compared to the control group(F=70.290, P<0.01). Tear film stability was markedly compromised, with significantly shorter tear film breakup time and increased corneal fluorescein staining, both showing statistically significant differences relative to controls(all P<0.01). Tear secretion indices, including Schirmer I test results and tear meniscus height, were significantly reduced in PD patients(all P<0.01), whereas lipid secretion indices, such as lipid layer thickness and meibomian gland dropout score, did not show significant variation. Corneal nerve analysis revealed significant reductions in corneal nerve fiber density, nerve branch density, fiber length, and total branch density in PD patients compared to controls(all P<0.01). Furthermore, blink frequency was markedly prolonged(F=62.353, P<0.01). Correlation analysis demonstrated a significant relationship between alterations in tear film stability and both disease duration and H-Y scores.CONCLUSION: PD patients have obvious dry eye manifestations in the early stage of the disease, including the reduction of tear film stability and corneal nerve fiber density, and gradually aggravate with the progress of the disease. Neurodegenerative disease-related dry eye needs to be diagnosed early and actively treated.

The innate immune system can be boosted in response to subsequent triggers by pre-exposure to microbes or microbial products, known as “trained immunity”. Compared to classical immune memory, innate trained immunity has several different features. Firstly, the molecules involved in trained immunity differ from those involved in classical immune memory. Innate trained immunity mainly involves innate immune cells (e.g., myeloid immune cells, natural killer cells, innate lymphoid cells) and their effector molecules (e.g., pattern recognition receptor (PRR), various cytokines), as well as some kinds of non-immune cells (e.g., microglial cells). Secondly, the increased responsiveness to secondary stimuli during innate trained immunity is not specific to a particular pathogen, but influences epigenetic reprogramming in the cell through signaling pathways, leading to the sustained changes in genes transcriptional process, which ultimately affects cellular physiology without permanent genetic changes (e.g., mutations or recombination). Finally, innate trained immunity relies on an altered functional state of innate immune cells that could persist for weeks to months after initial stimulus removal. An appropriate inducer could induce trained immunity in innate lymphocytes, such as exogenous stimulants (including vaccines) and endogenous stimulants, which was firstly discovered in bone marrow derived immune cells. However, mature bone marrow derived immune cells are short-lived cells, that may not be able to transmit memory phenotypes to their offspring and provide long-term protection. Therefore, trained immunity is more likely to be relied on long-lived cells, such as epithelial stem cells, mesenchymal stromal cells and non-immune cells such as fibroblasts. Epigenetic reprogramming is one of the key molecular mechanisms that induces trained immunity, including DNA modifications, non-coding RNAs, histone modifications and chromatin remodeling. In addition to epigenetic reprogramming, different cellular metabolic pathways are involved in the regulation of innate trained immunity, including aerobic glycolysis, glutamine catabolism, cholesterol metabolism and fatty acid synthesis, through a series of intracellular cascade responses triggered by the recognition of PRR specific ligands. In the view of evolutionary, trained immunity is beneficial in enhancing protection against secondary infections with an induction in the evolutionary protective process against infections. Therefore, innate trained immunity plays an important role in therapy against diseases such as tumors and infections, which has signature therapeutic effects in these diseases. In organ transplantation, trained immunity has been associated with acute rejection, which prolongs the survival of allografts. However, trained immunity is not always protective but pathological in some cases, and dysregulated trained immunity contributes to the development of inflammatory and autoimmune diseases. Trained immunity provides a novel form of immune memory, but when inappropriately activated, may lead to an attack on tissues, causing autoinflammation. In autoimmune diseases such as rheumatoid arthritis and atherosclerosis, trained immunity may lead to enhance inflammation and tissue lesion in diseased regions. In Alzheimer’s disease and Parkinson’s disease, trained immunity may lead to over-activation of microglial cells, triggering neuroinflammation even nerve injury. This paper summarizes the basis and mechanisms of innate trained immunity, including the different cell types involved, the impacts on diseases and the effects as a therapeutic strategy to provide novel ideas for different diseases.

Natural arabinogalactan， an important polysaccharide， has a wide range of sources， a complex structure， various biological activities， and great application potential. Natural arabinogalactan is mainly rich in plants and microorganisms， and its structure varies due to different sources， including types Ⅰ， type Ⅱ， type Ⅱ-related types， and new configurations. Natural arabinogalactan has shown a variety of biological activities， such as anti-tumor， anti-oxidation， anti-coagulation， anti-aging， blood glucose-lowering， intestinal health-maintaining， anti-inflammatory， and immunomodulatory activities. In addition， natural arabinogalactan shows good biocompatibility and low toxicity， serving as a potential material in the biomedical field. Natural arabinogalactan has been designed as a carrier in the drug delivery system to effectively improve drug stability and targeting. Natural arabinogalactan is often added to skin care products to help delay skin aging and enhance skin barrier function because of their moisturizing and antioxidant properties. Additionally， natural arabinogalactan acts as a thickener， stabilizer， and emulsifier to improve the texture and taste while enhancing the nutritional value of food products. The review of latest research reports is helpful to further understand the relationship between the structure， biological activity， and functional application of natural arabinogalactan and provides an important reference for future research and development.

BACKGROUND:Osteoarthritis is now considered a metabolic disease.Previous studies have shown that glycolysis plays an important role in the occurrence and development of osteoarthritis.Compound 3k,as a novel small molecule inhibitor of glycolysis,has anti-inflammatory and anti-tumor effects.Therefore,it can target glycolysis and is expected to provide new ideas for the treatment of osteoarthritis. OBJECTIVE:To explore the role of Compound 3k in osteoarthritis caused by glycolytic overactivity based on the hypoxia-inducible factor 1 alpha(HIF-1α)/reactive oxygen species(ROS)pathway. METHODS:ATDC5 chondroblasts at logarithmic growth phase were taken to induce osteoarthritis in an in vitro cellular model by the action of 10 ng/mL interleukin-1β for 24 hours.The cytotoxicity of Compound 3k at different concentrations(0.25,0.5,1,2.5,5,10,15 &mu;mol/L)was detected by cell counting kit-8 assay,and the appropriate concentrations were selected for the subsequent experiments.The chondrocytes were randomly divided into control,model and treatment groups.The model group was induced with 10 ng/mL interleukin 1β,and the treatment group was pre-stimulated with Compound 3k for 2 hours and then co-cultured with interleukin 1β.The proliferation of the cells in each group was detected by the cell counting kit-8 assay;the inflammatory level of the cells in each group was detected by the ELISA kit;the ROS,extracellular lactate and glucose contents were detected using the kit;qRT-PCR and western blot were used to detect the levels of related inflammatory factors,interleukin-6 and tumor necrosis factor-α,glycolysis-related genes glucose transporter protein-1,glyceraldehyde 3-phosphate dehydrogenase,monocarboxylate transporter protein-1 and HIF-1α. RESULTS AND CONCLUSION:Compared with the control group,the model group showed a decrease in cell proliferative activity,active glycolysis level,manifested by an increase in extracellular lactate content(P<0.001)and a decrease in glucose content(P<0.001),interleukin-6(P<0.000 1)and tumor necrosis factor-α(P<0.001).The expression levels of glycolysis-related genes glucose transporter protein-1(P<0.001),glyceraldehyde 3-phosphate dehydrogenase(P<0.001),monocarboxylic acid transporter protein-1(P<0.001)and HIF-1α(P<0.001)in the model group were all up-regulated,accompanied by oxidative stress and overproduction of ROS.Compared with the model group,Compound 3k treatment effectively increased cell proliferation activity and inhibited the level of overactive glycolysis(P<0.001),while suppressing the expression of genes related to inflammation(P<0.001)and glycolysis in osteoarthritic chondrocytes,inhibiting oxidative stress,downregulating the expression level of HIF-1α(P<0.000 1)and decreasing the content of ROS.To conclude,Compound 3k inhibits interleukin-1β induced chondrocyte inflammation,and its mechanism may be related to glycolysis and HIF-1α/ROS mediated oxidative stress.

BACKGROUND:During healing process of chronic wounds,excessive production of reactive oxygen species can impair the function of L929 fibroblasts,thereby delaying wound repair.Therefore,protecting fibroblasts from oxidative stress is important to promote wound healing. OBJECTIVE:To assess the protective effects of carboxymethyl chitosan-oxidized chondroitin sulfate/platelet-rich plasma(CMC-OCS/PRP)hydrogel on L929 cells under H2O2 stimulation. METHODS:CMC-OCS/PRP hydrogels were prepared,and the micromorphology,degradation performance,scavenging ability of H2O2 and hydroxyl radical and biocompatibility of the hydrogels were characterized.L929 cells with good growth state were taken and cultured in five groups.The control group was cultured conventionally.H2O2 was added to the H2O2 group.Carboxymethyl chitosan-oxidized chondroitin sulfate hydrogel extract+H2O2 was added to the CMC-OCS group.Platelet-rich plasma gel extract+H2O2 was added to the PRP group.The CMC-OCS/PRP group was treated with carboxymethyl chitosan-oxidized chondroitin sulfate/platelet-rich plasma hydrogel extract+H2O2.Each group was treated with hydrogel extract for 6 hours,and then H2O2 for 24 hours.After culture,the levels of active oxygen and malondialdehyde,apoptosis and expression of collagen fiber I protein were detected.In the presence of H2O2,the above hydrogel extracts were directly or indirectly co-cultured with L929 fibroblasts for 36 hours,respectively.Migration ability of the cells was detected by scratch test and Transwell chamber test. RESULTS AND CONCLUSION:(1)CMC-OCS/PRP hydrogels had uniform and interrelated porous structure and good degradation ability,could effectively remove H2O2 and hydroxyl radicals in vitro,and had good biocompatibility.(2)Compared with the control group,the apoptosis rate,reactive oxygen species,and malondialdehyde levels were increased(P<0.05);the spread area of cells was decreased(P<0.05),and the expression of collagen fiber I protein had no significant changes(P>0.05)in the H2O2 group.Compared with the H2O2 group,reactive oxygen species level was decreased in the CMC-OCS group(P<0.05),malondialdehyde level was decreased(P<0.05),and cell spread area was increased(P<0.05)in the PRP group,CMC-OCS group,and CMC-OCS/PRP group;apoptosis rate was decreased in the CMC-OCS/PRP group(P<0.05),and collagen fiber I protein expression was increased in the PRP group,CMC-OCS group,and CMC-OCS/PRP group(P<0.05).(3)Compared with the control group,the number of cell migration was decreased(P<0.05),and the migration area had no significant change(P>0.05)in the H2O2 group.Compared with the H2O2 group,the number and area of cell migration were increased in the PRP group,CMC-OCS group,and CMC-OCS/PRP group(P<0.05),and the increase was most significant in the CMC-OCS/PRP group.(4)Under oxidative stress,CMC-OCS/PRP hydrogel can improve the migration ability of fibroblasts,resist cell apoptosis,and preserve cell extension function.

BACKGROUND:Lijin manipulation can promote skeletal muscle repair and treat skeletal muscle injury.However,the formation of fibrosis and scar tissue hyperplasia are closely related to the quality of skeletal muscle repair.To study the regulatory effect of Lijin manipulation on the formation of fibrosis and scar tissue hyperplasia is helpful to explain the related mechanism of Lijin manipulation to improve the repair quality of skeletal muscle injury. OBJECTIVE:To explore the mechanism of Lijin manipulation to improve the repair quality of skeletal muscle injury in rabbits,thereby providing a scientific basis for clinical treatment. METHODS:Forty-five healthy adult Japanese large-ear white rabbits were randomly divided into blank group,model group and Lijin group,with 15 rats in each group.Gastrocnemius strike modeling was performed in both model group and Lijin group.The Lijin group began to intervene with tendon manipulation on the 3rd day after modeling,once a day,and 15 minutes at a time.Five animals in each group were killed on the 7th,14th and 21st days after modeling.The morphology and inflammatory cell count of gastrocnemius were observed by hematoxylin-eosin staining,the collagen fiber amount was observed by Masson staining,the expression of interleukin-6 and interleukin-10 in gastrocnemius was detected by ELISA.The protein and mRNA expressions of paired cassette gene 7,myogenic differentiation factor,myoblastogenin,alpha-actin,transforming growth factor beta 1,and type Ⅰ collagen were detected by western blot and RT-PCR,respectively,and the expression of type Ⅰ collagen protein was detected by immunohistochemistry. RESULTS AND CONCLUSION:Hematoxylin-eosin staining and Masson staining showed that compared with the model group,inflammatory cell infiltration and collagen fiber content decreased in the Lijin group(P<0.01),and the muscle fibers gradually healed.ELISA results showed that compared with the model group,the expression of interleukin-6 in the Lijin group continued to decrease(P<0.05),and the expression of interleukin-10 increased on the 7th day after modeling(P<0.05)and then showed a decreasing trend(P<0.05).Western blot and RT-PCR results showed that compared with the model group,the protein and mRNA expressions of paired cassette gene 7,myogenic differentiation factor,myoblastogenin in the Lijin group were significantly increased on the 14th day after modeling(P<0.05),but decreased on the 21st day(P<0.05);the protein and mRNA expressions of alpha-actin,transforming growth factor beta 1,and type Ⅰ collagen in the Lijin group were significantly decreased compared with those in the model group(P<0.05).Immunohistochemical results showed that the expression of type Ⅰ collagen in the Lijin group was significantly lower than that in the model group(P<0.05).To conclude,Lijin manipulation could improve the repair quality of skeletal muscle injury by inhibiting inflammation,promoting the proliferation and differentiation of muscle satellite cells,and reducing fibrosis.