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.

BACKGROUND:Coptis chinensis can clear heat,dry dampness,relieve fire,and detoxify.Coptis chinensis and its components have a significant protective effect on cerebral ischemia.The action mechanism of anti-cerebral ischemia of Coptidis Rhizoma Alkaloids was explored based on network pharmacology and transcriptome sequencing. OBJECTIVE:Based on the study of the protective effects of Coptidis Rhizoma Alkaloids on cerebral ischemia of rats,the action mechanism of Coptidis Rhizoma Alkaloids intervention in cerebral ischemia was investigated by using network pharmacology and transcriptome sequencing technology. METHODS:The SD rats were randomly divided into sham operation group,ischemia/reperfusion group,positive drug group,and Coptidis Rhizoma Alkaloids group.The ischemia/reperfusion model of middle cerebral artery occlusion was prepared by modified thread method in the latter three groups.No thread was inserted and the other operations were the same in the sham operation group.TTC staining,Longa 5 neurological deficient score,hematoxylin and eosin staining,and Nissl staining were used to evaluate the protective effect of Coptidis Rhizoma Alkaloids on ischemia/reperfusion model rats.Transcriptome sequencing was performed on the brain tissues of rats in sham operation group,ischemia/reperfusion group,and Coptidis Rhizoma Alkaloids group.Differentially expressed genes,gene Ontology analysis,Kyoto encyclopedia of genes and genomes analysis,and Correlation Analysis of Transcriptomics and Network Pharmacology were used to elucidate the effect of Coptidis Rhizoma Alkaloids on cerebral ischemia.Finally,ELISA and immunofluorescence staining were used to verify the key targets of Coptidis Rhizoma Alkaloids in the intervention of cerebral ischemia. RESULTS AND CONCLUSION:(1)Coptidis Rhizoma Alkaloids treatment decreased the Longa 5 neurological deficit scores and cerebral infarction area of ischemia/reperfusion model rats,increased the number of neurons and Nissl bodies.(2)Differentially expressed gene after Coptidis Rhizoma Alkaloids treatment analyzed by functional enrichment analysis of gene ontology includes biological processes such as inflammatory reaction and positive regulation of mitogen-activated protein kinase cascade.The enrichment analysis of Kyoto gene and genome encyclopedia analysis pathway mainly involves interleukin-17 signaling pathway,neuroactive ligand-receptor interaction,cyclic adenosine-3′,5′-mconophosphate signaling pathway and so on.(3)Analysis of transcriptomics showed that the main genes regulated by Coptidis Rhizoma Alkaloids were prostaglandin endoperoxide synthase 2,brain derived neurotrophic factor,and transient receptor potential A1.(4)Network pharmacology analysis revealed that nine components in Coptidis Rhizoma Alkaloids may exert their effects by associating with 87 targets related to prostaglandin endoperoxide synthase 2,brain derived neurotrophic factor,and transient receptor potential A1.(5)ELISA and immunofluorescence staining results further confirmed that Coptidis Rhizoma Alkaloids regulated the expression of prostaglandin endoperoxide synthase 2,brain derived neurotrophic factor,and transient receptor potential A1.(6)It is concluded that Coptidis Rhizoma Alkaloids treatment can significantly improve the injury in ischemia/reperfusion model rats,possibly by regulating prostaglandin endoperoxide synthase 2,brain derived neurotrophic factor,and transient receptor potential A1.

Background The adverse effects of long working hours, shift rotation, and job stress on the physical and mental health of occupational populations require urgent attention. Objective To investigate and compare the positive rates of WMSDs between different industries, analyze the exposure status of long working hours, shift rotation, and job stress among key occupational groups, and evaluate the impacts of these factors on WMSDs in the manufacturing and service industries. Methods The study subjects were derived from key occupational populations in Yunnan Province, recruited by the Chinese National Occupational Health Literacy Monitoring Survey in 2022. A cross-sectional design was used for this survey. The key occupational populations were recruited from the secondary industry (manufacturing industry, metal mining and beneficiation industry, and non-metal mining and beneficiation industry) by stratified random sampling and from the tertiary industry (medical and healthcare industry, education industry, environmental sanitation industry, transportation industry, and express/takeaway delivery industry) by proportional probability sampling, and 12014 front-line workers were finally included as survey participants. General information, work-related factors (shift rotation, weekly working hours, job stress, etc.) and WMSDs assessment results were obtained through a web-based self-reported questionnaire, and the associations of long working hours, shift rotation, and job stress with WMSDs were analyzed using χ² test and logistic regression. Results The average positive rate of WMSDs among the key occupational groups in Yunnan Province was 77.2%. The positive rate of WMSDs in the secondary industry group was 69.4%, while it was 81.6% in the tertiary industry group, with a statistically significant difference (P<0.001). Among the eight surveyed sectors, the education sector had the highest positive rate of WMSDs (94.2%). The single-site WMSDs mainly involved the neck, shoulders, and low back. In the secondary industry, WMSDs was reported in 1−2 body parts, while in the tertiary industry, WMSDs was mainly reported in multiple (≥5) body parts. Long working hours (OR: 1.119, 1.165, 1.163, respectively), shift rotation (OR: 1.094, 1.199, 1.230, respectively), and job stress (OR: 1.795, 1.854, 2.006, respectively) were risk factors for WMSDs in the neck, shoulder, or low back, and all three were also risk factors for multi-site WMSDs. Moreover, as the number of involved body parts increased, the effects of long working hours and job stress became more pronounced. For 1-2, 3-4, and 5 or more body parts compared to no pain reported, their OR values were 0.971 (95%CI: 0.871, 1.082), 1.133 (95%CI: 1.004, 1.279), and 1.285 (95%CI: 1.155, 1.429) for long working hours, respectively, and the OR values were 1.009 (95%CI: 0.878, 1.160), 1.360 (95%CI: 1.174, 1.575), and 2.797 (95%CI: 2.471, 3.166) for job stress, respectively. Conclusion The positive rate of WMSDs is higher in the tertiary industry than that in the secondary industry among the key occupational groups in Yunnan Province. Long working hours, rotating shift work, and job stress could significantly increase the risk of WMSDs.

Serving as cerebral macrophages， microglial cells are meticulously regulated by the microenvironment of the central nervous system.In response to various environmental and cellular stresses， microglial cells are rapidly activated and exhibit either pro-inflammatory or anti-inflammatory phenotypes to maintain brain tissue homeostasis， and during this process， significant changes are observed in glucose metabolism of microglial cells. Aerobic glycolysis is the primary energy source for pro-inflammatory microglial cells， while oxidative phosphorylation is the energy source for anti-inflammatory microglial cells.This article systematically elaborates on glucose metabolism and glucose metabolic reprogramming pathways in microglial cells， as well as their role in central nervous system diseases. In addition， this article also discusses the potential of targeting glucose metabolic reprogramming in microglial cells for the treatment of related diseases.

Radiopharmaceuticals operate by combining radionuclides with carriers. The radiation energy emitted by radionuclides is utilized to selectively irradiate diseased tissues while minimizing damage to healthy tissues. In comparison to external beam radiation therapy, radionuclide drugs demonstrate research potential due to their biological targeting capabilities and reduced normal tissue toxicity. This article reviews the applications and research progress of radiopharmaceuticals in cancer treatment. Several key radionuclides are examined, including ²²³Ra, ⁹⁰Y, Lutetium-177 (¹⁷⁷Lu), ²¹²Pb, and Actinium-225 (²²⁵Ac). It also explores the current development trends of radiopharmaceuticals, encompassing the introduction of novel radionuclides, advancements in imaging technologies, integrated diagnosis and treatment approaches, and equipment-medication combinations. We review the progress in the development of new treatments, such as neutron capture therapy, proton therapy, and heavy ion therapy. Furthermore, we examine the challenges and breakthroughs associated with the clinical translation of radiopharmaceuticals and provide recommendations for the research and development of novel radionuclide drugs.
Humans ; Radiopharmaceuticals/therapeutic use* ; Neoplasms/radiotherapy* ; Radioisotopes/therapeutic use* ; Animals

AIM: To explore the dynamic expression of high mobility group box 1(HMGB1)in scar tissues after glaucoma drainage valve implantation, and to further reveal the role and possible mechanism of HMGB1 in scarring after glaucoma surgery.METHODS: A total of 60 New Zealand white rabbits were randomly divided into control group(n=20), model group(n=20, silicone implantation under conjunctival sac)and model with drug administration group(n=20, silicone implantation under conjunctival sac combined with 5-fluorouracil injection). The conjunctival tissues were collected at 4 and 8 wk after surgery. HE staining and Masson staining were used to detect the proliferation and distribution of fibroblasts and collagen fibers in conjunctival tissues. Immunohistochemistry was utilized to detect the distribution and changes of HMGB1, transforming growth factor(TGF)-β1, Smad3 and α-smooth muscle actin(SMA)in conjunctival tissues. RT-PCR and Western blot were adopted to detect the mRNA and protein expression of HMGB1, TGF-β1, Smad3 and α-SMA in conjunctival tissues.RESULTS: HE staining and Masson staining showed that the proliferation of inflammatory cells, fibroblasts and collagen fibers in the model group was significantly higher than that in the control group at both 4 and 8 wk. Meanwhile, the proliferation of fibroblasts and collagen fibers in the model with drug administration group was significantly lower than that in the model group. Immunohistochemical staining showed that the expression of HMGB1, TGF-β1, Smad3 and α-SMA protein was observed in the conjunctival tissues of the model group both 4 and 8 wk, with brown and significantly deeper staining of the model group at 8 wk. Meanwhile, the positive staining in the model with drug administration group at both 4 and 8 wk was significantly lower than that in the model group. There was positive correlations between the number of fibroblasts stained with HE and the expression of HMGB1 in the conjunctival tissue of the model group at both 4 and 8 wk(r=0.602, 0.703, all P<0.05). RT-PCR and Western blot revealed that the mRNA and protein expression levels of HMGB1, TGF-β1, Smad3 and α-SMA in the model group were significantly higher than those in the control group at both 4 and 8 wk(all P<0.05). Meanwhile, the mRNA and protein expression levels of HMGB1, TGF-β1, Smad3 and α-SMA in the model with drug administration group were significantly lower than those in the model group(all P<0.05). There was positive correlations between mRNA expressions of HMGB1 and TGF-β1, Smad3 in the model group and the model with drug administration group(all P<0.05).CONCLUSION: The expression of HMGB1 increased at a time-dependent manner after glaucoma valve implantation. HMGB1 acts an indispensable role in the initiation and progression of scar formation after glaucoma surgery, which may be involved in the regulation of TGF-β/Smad signaling pathway.

Objective:To observe the effect of bone forming protein 4 (BMP4) on the proliferation and migration of human retinal pigment epithelium (RPE) cells under oxidative stress, and to preliminarily explore its effect on epithelial-mesenchymal transition (EMT) of RPE cells.Methods:Human RPE cells cultured in vitro were divided into normal group, pure 4-hydroxynonenal (HNE) group (4-HNE group), 4-HNE+NC group and 4-HNE+ small interfering BMP (siBMP4) group. The effect of 4-HNE on the proliferation of RPE cells was detected by thiazole blue colorimetry. The effects of 4-HNE and BMP4 on cell migration were determined by cell scratch test. The expression of BMP4 was detected by immunofluorescence staining, Western blot and real-time quantitative polymerase chain reaction. The transfection efficiency of siBMP4 was observed by fluorescence microscopy. Mitochondrial reactive oxygen species (MitoSOX) were detected by flow cytometry. The expression of EMT markers E-cadherin and Fibronection were detected by immunofluorescence assay. t-test was used for comparison between the two groups, and one-way analysis of variance was used for comparison between the three groups. Results:Compared with normal group, cell proliferation and migration ability of 4-HNE group were significantly enhanced, with statistical significance ( t=21.619, 24.469; P<0.05). The expression of BMP4 in cells was significantly increased, and the difference was statistically significant ( t=19.441, P<0.05). The relative expression levels of BMP4 mRNA and protein were also significantly increased, with statistical significance ( t=26.163, 37.163; P<0.05). After transfection with siBMP4 for 24 h, the transfection efficiency of BMP4 in RPE cells was>90%. Compared with 4-HNE group and 4-HNE+NC group, the relative expression levels of BMP4 protein ( F=27.241), mRNA ( F=36.943), cell mobility ( F=46.723) and MitoSOX expression levels ( F=39.721) in normal group and 4-HNE+siBMP4 group were significantly decreased. The differences were statistically significant ( P<0.05). The epithelial marker E-cadherin increased significantly, while the mesenchymal marker Fibronection decreased significantly, with statistical significance ( F= 51.722, 45.153; P<0.05). Conclusions:BMP4 inhibits RPE proliferation and migration under oxidative stress. BMP4 is involved in inducing EMT in RPE cells.

Objective:To observe the effects of NDRG1 on proliferation, migration and lumen formation of retinal vascular endothelial cells (RF/6A cells) in monkeys under high glucose condition. Methods:RF/6A cells were divided into normal group, mannitol group, high glucose group, small interfering RNA (siRNA) negative control group without target gene (siRNA group), 30 nmol/L siRNA down-regulated NDRG1 genome (siNDRG1 group) and 50 nmol/L siNDRG1 group. Normal group cells were cultured conventionally. The mannitol group was added with 25 mmol/L mannitol, and the high-glucose group was added with 25 mmol/L glucose. In the siRNA group, 25 mmol/L glucose was added, and then blank siRNA was added for induction. The 30 and 50 nmol/L siNDRG1 groups were added with 25 mmol/L glucose and induced with 30 and 50 nmol/L siRNDRG1, respectively. All cells were incubated for 24 h for follow-up experiments. Cell proliferation was observed by 4', 6-diaminidine 2-phenylindole staining. Cell counting kit-8 staining was used to detect cell activity. The expression level of NDRG1 mRNA and protein was detected by Western blot and real-time quantitative polymerase chain reaction. Cell migration was observed by cell scratch assay. Cell lumen formation assay was used to detect lumen formation. The two-tailed Student t test was used to compare the two groups. One-way analysis of variance was used to compare groups. Results:There were significant differences in cell proliferation rate ( t=36.659, 57.645) mobility rate ( t=24.745, 33.638) and lumen formation number ( t=41.276, 22.867) between high glucose group and normal group and mannitol group ( P <0.01). Compared with normal group and mannitol group, the relative expression levels of NDRG1 gene mRNA and protein in high glucose group were significantly decreased, with statistical significance ( t=46.145, 21.541, 36.738, 32.976; P<0.001). Compared with the siRNA negative group, the relative expression levels of NDRG1 gene mRNA and protein in 30 nmol/L siNDRG1 group and 50 nmol/L siNDRG1 group were significantly decreased, and the differences were statistically significant ( t=44.275, 40.7577, 57.167, 25.877; P<0.01). Compared with normal group and siRNA group, cell mobility in 30 nmol/LsiNDRG1 group was increased, and the difference was statistically significant ( t=57.562, 49.522; P<0.01). Compared with normal group and siRNA group, the number of cell lumen formation in 30 nmol/LsiNDRG1 group was significantly increased in the same field of vision, and the difference was statistically significant ( t=63.446, 42.742; P<0.01). Conclusion:Down-regulation of NDRG1 gene can improve the activity, migration and lumen formation of RF/6A cells under hyperglycemia.

Aim To explore the mechanism of oxidized lipoprotein(a)(oxLp(a))inducing pyroptosis of vascu-lar endothelial cells.Methods After incubating human umbilical vein endothelial cells(HUVEC)with 100 mg/L ox-Lp(a)for 24 hours,Western blot and RT-qPCR was used to detect pyroptosis related proteins,pro-inflammatory cytokines,mitochondrial related proteins NRF1,NRF2,PGC-1α and mitochondrial gene cytochrome b(CYTB),ELISA was used to detect the levels of inflammatory factors,scanning electron microscopy was used to detect cell membrane rup-ture,transmission electron microscopy was used to detect mitochondrial morphology,Hoechst33342/PI staining was used to detect cell apoptosis,MitoSOX probe was used to detect mitochondrial reactive oxygen species(mtROS),Flu-4AM probe was used to detect calcium ions,JC-1 probe was used to detect mitochondrial membrane potential(MMP),and Calcein AM staining was used to detect mitochondrial permeability transition pore(mPTP).Transfecting HUVEC with CYTB overexpressing lentivirus and analyzing its effects on oxLp(a)induced pyroptosis and mitochondrial function.Results After treatment with oxLp(a),the expression of NLRP3,pro-Caspase-1,Caspase-1,GSDMD and GSDMD-N proteins re-lated to pyroptosis were significantly increased(P＜0.05);the protein and mRNA levels of CYTB and pro-inflammatory cy-tokine IL-1β,IL-18 were significantly increased(P＜0.05).Small pores appeared on the cell membrane,the percentage of PI stained positive cells significantly increased(P＜0.05).OxLp(a)significantly inhibited the expression of mito-chondrial related proteins NRF1,NRF2 and PGC-1α,and the expression of mitochondrial gene CYTB,promoted an in-crease in mtROS generation,Ca2+overload,a decrease in ATP levels,a decrease in MMP,an increase in mPTP values,and abnormal mitochondrial morphology.After transfection with pHelper 2.0 lentivirus vector overexpressing CYTB,it was found that oxLp(a)induced HUVEC pyroptosis and mitochondrial morphological and functional abnormalities were par-tially reversed by overexpression of CYTB.Conclusion oxLp(a)promotes mitochondrial morphological and functional abnormalities and induces HUVEC pyroptosis by downregulating CYTB.

Purpose To assess the right atrial and right ventricular strain and right ventricular-pulmonary artery(RV-PA)coupling in rheumatoid arthritis(RA)via two-dimensional speckle tracking.Materials and Methods Sixty patients with RA in the General Hospital of Ningxia Medical University from June 2020 to June 2022 were prospectively selected,and all RA patients were divided into three groups according to pulmonary artery systolic pressure(PASP),including group A(n=20 cases)with PASP<33 mmHg,group B(n=20 cases)with PASP 33-39 mmHg as mild ePH,and group C(n=20 cases)PASP≥40 mmHg,twenty healthy individuals were selected as the control group.All subjects underwent transthoracic echocardiography,and right atrial and right ventricular systolic function was assessed by two-dimensional speckle tracking technique,and RV-PA coupling was assessed noninvasively by right ventricular free wall strain/pulmonary artery systolic pressure(RV FWS/PASP),pulmonary function was analyzed by pulmonary function instruments.Spearman's analysis was used to analyze the correlation between right heart function and RV-PA coupling to pulmonary diffusion function.Results There were statistical differences in right ventricular base diameter,right atrium diameter,tricuspid annular plane systolic excursion,inferior vena cava diameter,PASP,right ventricular global strain,RV FWS,right atrium strain-reservoi,right atrium strain-conduit(S-CD),RV FWS/PASP among the four groups(F/H=2.369-74.880,all P<0.05).Right atrium strain-reservoi[(36.0±7.9)%vs.(30.9±7.8)%],right atrium S-CD[(19.9±6.9)%vs.(15.3±4.7)%]and RV FWS/PASP(0.96±0.19 vs.0.56±0.13)in group B were significantly lower than those of group A(t=2.040,2.262,7.704,all P<0.05).There was a good correlation between diffusing capacity of the lung for carbon monoxide single-breathmethod and right ventricular global strain,RV FWS,right atrium S-CD and RV FWS/PASP in RA patients(r=0.392,0.472,0.431,0.572,all P<0.05).Conclusion The more increases of pulmonary artery pressures,the more decreases of right heart function in RA patients,and the more uncoupling in RV-PA.Right heart dysfunction and right ventricle-pulmonary artery uncoupling have developed in RA patients with PASP 33-39 mmHg,with association of pulmonary diffusion dysfunction.