Retinopathy of prematurity(ROP)is a leading cause of childhood blindness, with extremely preterm and very-low-birth-weight infants now constituting the main high-risk group. ROP progresses in two stages: early retinal microvascular degeneration and progressive vascular arrest, followed by abnormal neovascularization in the avascular area. Early oxidative and nitrosative stress—amplified by oxygen fluctuations and immature antioxidant defenses—drives the two-phase pathogenesis via hypoxia-inducible factor/vascular endothelial growth factor(HIF/VEGF), NOX/STAT3, and nuclear factor erythroid 2 related factor 2(Nrf2)-antioxidant response element(ARE)pathways, mediating apoptosis of endothelial cells, damage to barrier and pathological angiogenesis. This review systematically analyzes different oxygen-induced retinopathy(OIR)models, elucidates key signaling pathways including Notch, Wnt in physiological and pathological vascularization, with particular emphasis on the biphasic effects of Nrf2 and the differential roles of NOX signaling between phases. We also discuss the limitations of anti-VEGF therapy and oxygen management principles. Reactive oxygen species(ROS)play context-dependent roles across vaso-obliteration and neovascularization phases. Based on mechanistic insights, we propose future directions including combined/sequential interventions, ferroptosis and lipid peroxidation targeting, nano-delivery systems for enhanced bioavailability, and perinatal safety assessment strategies, aiming to provide translatable mechanistic basis for reducing pathological neovascularization while promoting physiological vascular development.

Chronic obstructive pulmonary disease (COPD) is the most common chronic respiratory disease around the world, and pharmacotherapy is the foremost treatment method currently. In recent decades, with the rapid development of bronchoscopic interventional therapy, endoscopic physical ablation technology presents a therapeutic effect in treating COPD, with few treatment-related side effects, showing excellent application prospects in treating COPD. Since ablation techniques in this field are emerging technologies with low patient acceptance, they are not widely used in the clinical treatment of COPD. This article reviews the development process of physical ablation techniques. Moreover, their current application status and the prospects in the field of COPD treatment are also summarized and analyzed. We hope to promote the application of physical ablation in the clinical treatment of COPD and provide practical references and a theoretical basis for the clinical treatment of COPD.

[This corrects the article DOI: 10.1016/j.apsb.2025.02.029.].

OBJECTIVES: To investigate the effects of dihydroartemisinin (DHA) combined with doxorubicin (DOX) on proliferation and apoptosis of triple-negative breast cancer cells and explore the underlying molecular mechanism. METHODS: MDA-MB-231 cells were treated with 50, 100 or 150 μmol/L DHA, 0.5 μmol/L DOX, or with 50 μmol/L DHA combined with 0.5 μmol/L DOX. The changes in proliferation and survival of the treated cells were examined with MTT assay and colony-forming assay, and cell apoptosis was analyzed with flow cytometry. Western blotting was performed to detect the changes in protein expression levels of PCNA, cleaved PARP, Bcl-2, Bax, STAT3, p-STAT3, HIF-1α and survivin. RESULTS: The IC₅₀ of DHA was 131.37±29.87 μmol/L in MDA-MB-231 cells. The cells with the combined treatment with DHA and DOX showed significant suppression of cell proliferation. Treatment with DHA alone induced apoptosis of MDA-MB-231 cells in a dose-dependent manner, but the combined treatment produced a much stronger apoptosis-inducing effect than both DHA and DOX alone. DHA at 150 μmol/L significantly inhibited clone formation of MDA-MB-231 cells, markedly reduced cellular expression levels of PCNA, p-STAT3, HIF-1α and survivin proteins, and obviously increased the expression level of cleaved PARP protein and the Bax/Bcl-2 ratio, and the combined treatment further reduced the expression level of p-STAT3 protein and increased the Bax/Bcl-2 ratio. CONCLUSIONS DHA combined with DOX produces significantly enhanced effects for inhibiting cell proliferation and inducing apoptosis in MDA-MB-231 cells possibly as result of DHA-mediated negative regulation of the STAT3/HIF-1α pathway.
Humans ; STAT3 Transcription Factor/metabolism* ; Apoptosis/drug effects* ; Hypoxia-Inducible Factor 1, alpha Subunit/metabolism* ; Doxorubicin/pharmacology* ; Triple Negative Breast Neoplasms/metabolism* ; Cell Line, Tumor ; Artemisinins/pharmacology* ; Female ; Cell Proliferation/drug effects* ; Signal Transduction/drug effects* ; Survivin

OBJECTIVE: To investigate the effect of aquaporin 5 (AQP5) on Toll-like receptor 4 (TLR4)/myeloid differentiation factor 88 (MyD88)/nuclear factor κB (NF-κB) signaling pathway in Sjögren syndrome (SS) rats. METHODS: The SS gene expression data sets GSE406611 and GSE84844 were extracted from the Gene Expression Omnibus (GEO), and the AQP5 mRNA expression was analyzed by R software. The rat SS model was constructed. The successfully modeled rats were divided into SS group, SS+NC group, and SS+pc group, 10 rats in each group; and 10 rats were set as Normal group. The rats in the SS+NC group were injected with 10 μg of rno-pcDNA3.1-AQP5-NC at the submandibular gland, subcutaneously every day for 28 days. The rats in the SS+pc group were injected with 10 μg of rno-pcDNA3.1-AQP5 at the submandibular gland, subcutaneously every day for 28 days. The enzyme-linked immunosorbent assay (ELISA) kit was used to detect the content of tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) in the serum. High-throughput sequencing was used to identify the target genes. Quantitative real-time PCR (qPCR) and Western blot were used to detect the mRNA and protein expressions of AQP5, TLR4, MyD88, and NF-κB in the rat submandibular gland tissue. RESULTS: In the SS dataset GSE406611 and GSE84844, the mRNA expression of AQP5 in SS was significantly reduced. Compared with the Normal group, the content of TNF-α and IL-1β in the serum, the mRNA and protein expressions of TLR4, MyD88, and NF-κB in the SS group were significantly increased, the mRNA and protein expressions of AQP5 were significantly decreased. After overexpression of AQP5, the content of TNF-α and IL-1β in the serum, the mRNA and protein expressions of TLR4, MyD88, and NF-κB in the SS+pc group were significantly decreased, the mRNA and protein expressions of AQP5 were significantly increased. The differences were statistically significant (all P < 0.05). CONCLUSION The expression of AQP5 is involved in the progression of SS. Increasing the expression of AQP5 can significantly inhibit inflammatory stress and reduce the pathological damage of submandibular gland tissue. This may be related to the inhibition of TLR4/MyD88/NF-κB conduction.
Animals ; Toll-Like Receptor 4/genetics* ; Myeloid Differentiation Factor 88/genetics* ; Aquaporin 5/metabolism* ; Sjogren's Syndrome/genetics* ; Signal Transduction ; NF-kappa B/metabolism* ; Rats ; Rats, Sprague-Dawley ; Interleukin-1beta/metabolism* ; Female

To ensure the quality of care for inpatients in ophthalmic hospitals, address the complex and variable conditions of postoperative patients, and conduct more comprehensive, accurate and real-time monitoring of patients, an intelligent monitoring system based on computer vision and artificial intelligence has been designed. This system is employed for real-time monitoring of patient health conditions and intelligent care, with primary applications in medical monitoring, rehabilitation therapy, and inpatient care. It comprises intelligent data acquisition devices, smart cameras, continuous physiological data analysis algorithms, AI algorithms, and software. Given the complex and variable conditions of postoperative patients in ophthalmic hospitals, a comprehensive, accurate, and real-time monitoring of patients is required. Therefore, it is necessary to explore a monitoring technology that imposes low physiological and psychological burdens. The intelligent monitoring system can continuously collect patients' physiological parameter indicators and transmit the monitoring data to doctors' workstations or nurse stations after analysis using intelligent algorithms, providing new tools for patient monitoring, disease assessment, risk warning, and more. Furthermore, through the application of computer vision and artificial intelligence technologies, the system can analyze facial expressions, body postures, and other data to identify patients' emotional states and bedridden postures, enabling the timely detection of abnormal situations and implementation corresponding measures. This helps improving the daily work of medical staff, enhance the nursing safety in single-patient rooms in wards, and potentially find applications in the care of critically ill patients and elderly patients, thereby improving nursing efficiency and quality.
Artificial Intelligence ; Humans ; Monitoring, Physiologic/methods* ; Algorithms

Increasing evidence shows that the early lesions of Parkinson's disease (PD) originate from gut, and correction of microbiota dysbiosis is a promising therapy for PD. FLZ is a neuroprotective agent on PD, which has been validated capable of alleviating microbiota dysbiosis in PD mice. However, the detailed mechanisms still need elucidated. Through metabolomics and 16S rRNA analysis, we identified glycoursodeoxycholic acid (GUDCA) was the most affected differential microbial metabolite by FLZ treatment, which was specially and negatively regulated by Clostridium innocuum, a differential microbiota with the strongest correlation to GUDCA production, through inhibiting bile salt hydrolase (BSH) enzyme. The protection of GUDCA on colon and brain were also clarified in PD models, showing that it could activate Nrf2 pathway, further validating that FLZ protected dopaminergic neurons through promoting GUDCA production. Our study uncovered that FLZ improved PD through microbiota-gut-brain axis, and also gave insights into modulation of microbial metabolites may serve as an important strategy for treating PD.

Although enteric glial cell (EGC) abnormal activation is reported to be involved in the pathogenesis of Parkinson's disease (PD), and inhibition of EGC gliosis alleviated gut and dopaminergic neuronal dysfunction was verified in our previous study, the potential role of gut microbiota on EGC function in PD still need to be addressed. In the present study, fecal microbiota transplantation revealed that EGC function was regulated by gut microbiota. By employing 16S rRNA and metabolomic analysis, we identified that 3-indolepropionic acid (IPA) was the most affected differential microbial metabolite that regulated EGC gliosis. The protective effects of IPA on PD were validated in rotenone-stimulated EGCs and rotenone (30 mg/kg i.g. for 4 weeks)-induced PD mice, as indicated by decreased inflammation, improved intestinal and brain barrier as well as dopaminergic neuronal function. Mechanistic study showed that IPA targeted pregnane X receptor (PXR) in EGCs, and inhibition of IL-13Rα1 involved cytokine-cytokine receptor interaction pathway, leading to inactivation of downstream JAK1-STAT6 pathway. Our data not only provided evidence that EGC gliosis was critical in spreading intestinal damage to brain, but also highlighted the potential role of microbial metabolite IPA in alleviating PD pathological damages through gut-brain axis.

Objective A data mining method was used to analyse and summarize Professor Zheng Wenlong's ideas and prescription and medication rules for the treatment of cirrhosis,taking the case of cirrhosis of the liver in Ren-yin year(2022)as an example.Methods A collection of traditional Chinese medicine prescriptions for liver cirrhosis patients who received treatment at the clinic of chief traditional Chinese medicine physician Zheng Wenlong at Hangzhou Traditional Chinese Medicine Hospital of Zhejiang Chinese Medical University from January 20,2022 to January 19,2023,and who met the inclusion and exclusion criteria.An excel database was created to standardize the data,followed by frequency statistical analyzes of prescriptions,medications and the characteristics of herbal remedies.Association rule analysis was carried out using SPSS Modeler 18,which facilitated the creation of complex network diagrams,subsequently enhanced through visualization in software Cytoscape.Clustering analysis was executed utilizing SPSS 25.0.Results A total of 176 prescriptions were selected,and the top 3 most frequently used prescriptions were Lingzhu decoction,Shengming decoction and Beihua decoction,with the frequency of 10.13%(23/227),10.13%(23/227)and 9.69%(22/227).A diverse array of 155 herbal medicines were employed,and the top 3 most frequently used drugs were Glycyrrhiza,Poria and Zingiberis Rhizoma Recens,with the frequency of 4.75%(127/2 676),4.26%(114/2 676)and 3.21%(86/2 676).The predominant medicinal properties of these herbs were classified as either cold or warm,while the primary tastes identified were bitter,sweet and spicy,with channel tropism were liver,lung,stomach and spleen.According to the descending order of improvement percentage,the results showed that the strongly correlated pairs of herbs were Chaenomelis Fructus-Aconiti Lateralis Radix Praeparata and Citri Reticulatae Pericarpium Viride-Pericarpium Citri Reticulatae,with improvement degrees of 2.74%and 2.55%respectively;the strongly correlated 3-herb combinations(Jiao Yao)included Aconiti Lateralis Radix Praeparata-Poria-Chaenomelis Fructus and Aconiti Lateralis Radix Praeparata-Rhizoma Atractylodis Macrocephalae-Chaenomelis Fructus,with improvement degrees of 3.24%and 3.23%respectively.The clustering analysis categorized the high-frequency herbs into 3 distinct groups:C1:Citri Reticulatae Pericarpium Viride,Pericarpium Citri Reticulatae,Jujubae Fructus,Pinelliae Rhizoma Praeparatumcum Zingibere Et Alumine,and Zingiberis Rhizoma Recens;C2:Rhizoma Atractylodis Macrocephalae,Aconiti Lateralis Radix Praeparata,Artemisiae Scopariae Herba,and Paeoniae Radix Alba;C3:Schisandra Chinensis,Rhizoma Alismatis,Radix Glycyrrhizae,Poria,Zingiberis Rhizoma and Ramulus Cinnamomi.These correspond to the formulas of Erchen decoction,Yinchenshufu decoction and Wuling powder.Conclusions The underlying pathogenesis of cirrhosis is linked to dysfunctions of the Jueyin and Yangming meridians,as well as disturbances in the Shaoyang axis.The primary therapeutic approach of Professor Zheng Wenlong involves a comprehensive evaluate all of the patient's clinical presentation to identify the shared pathogenesis underlying various symptoms,integrating the patient's personal constitution with the annual cycle of the Five Phases(Wuyun)and Six Qi(Liuqi)as described in traditional Chinese medicine,and formulate prescriptions based on the interactions of the Five Phases(Wuxing)and guided by the yin-yang theory of"Opening-Closing-Pivot"(Kai-He-Shu).The focus of prescriptions is rehabilitation and the final goal is reach the state of"Tian Ren He Yi".