Objective:To investigate ferroptosis-related genes in pterygium tissue by using bioinformatic analysis.Methods:The pterygium gene expression profile dataset GSE2513 was downloaded from the Gene Expression Omnibus Database to identify differentially expressed genes (DEGs) related to ferroptosis.Functional annotation and enrichment analysis of the DEGs were performed using Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG).Hub genes were identified from the DEGs using LASSO logistic regression analysis and a support vector machine recursive feature elimination (SVM-REF).Single-gene GSEA analysis was performed on hub genes and a competitive endogenous RNA interaction network was constructed to determine the RNA regulatory relationships of the hub genes.Pterygium tissue samples from 9 patients (9 eyes) undergoing pterygium surgery and conjunctival tissue samples from 9 patients (9 eyes) undergoing strabismus surgery who visited the First Affiliated Hospital of Zhengzhou University were collected from 2022 to 2023 during surgery, and the expression of hub genes and ferroptosis-related marker genes was detected by fluorescence quantitative PCR.This study followed the Declaration of Helsinki, and the study protocol was reviewed and approved by the Ethics Committee of the First Affiliated Hospital of Zhengzhou University (No.2022-KY-0006-001).Results:In the dataset, there were 37 ferroptosis-related genes with significant expression differences, including 16 upregulated genes and 21 downregulated genes.GO analysis revealed significant enrichment in responses to external stimuli, responses to nutritional levels, responses to extracellular stimuli, responses to oxidative stress and starvation, transcription regulatory complexes, and RNA polymerase Ⅱ transcription regulatory complexes, RNA polymerase Ⅱ-specific transcription, and DNA-binding transcription.KEGG analysis showed that the DEGs were primarily enriched in ferroptosis and NOD-like receptor signaling pathways.LASSO regression analysis identified DUOX2, ATF3, NDRG1, EGR1, and ALDH3A2 as hub genes, and SVM-REF analysis identified NDRG1, NF2, IDH2, DUOX2, CHP1, ATF3, and SREBF1 as hub genes. DUOX2, ATF3, and NDRG1 were identified as the intersection hub genes.Single-gene GSEA analysis revealed that DUOX2 was enriched in the cell adhesion molecule CAMs pathway, the heparan sulfate glycosaminoglycan biosynthesis pathway, and the glycosaminoglycan biosynthesis ganglioside series pathway. ATF3 and NDRG1 were enriched in the PPAR signaling pathway and other pathways.Compared with normal conjunctival tissue, the relative expression levels of the ferroptosis markers PTGS2 and TFRC mRNA were increased in pterygium tissue, while the relative expression levels of FTH1, GPX4, SLC40A1, HSPB1, and NFE2L2 mRNA were decreased, with statistically significant differences ( t=12.220, 16.580, 5.664, 6.455, 8.691, 9.883, 17.590; all P<0.01). Conclusions:Ferroptosis may play an important role in the pathogenesis of pterygium. DUOX2, ATF3, and NDRG1 may be the hub genes affecting this complicated process.

Objective: To observe the effect of Xipayimaizibizi oral liquid (XP) in an overactive bladder (OAB) experimental rat model and to explore its pharmacological mechanisms. Methods: Network pharmacology was used to explore the potential mechanisms of action of XP. The rats underwent bladder outlet obstruction surgery and were administered the corresponding drug concentrations by gavage for 4 weeks. The study observed the body weight, water intake, bladder and kidney indices (to evaluate their general status), urination behavior pattern (to observe frequency and urgency), and urodynamics (to measure bladder parameters). Hematoxylin and eosin and Masson's trichome staining were used to observe changes in the bladder structure. Enzyme-linked immunosorbent assay was used to measure the levels of nerve growth factor, brain-derived neurotrophic factor, and acetylcholine in the urine. The key targets involved in these mechanisms were validated using reverse transcription-quantitative polymerase chain reaction, immunohistochemistry, and western blot in vivo/vitro experiments. Result: Network pharmacological analysis predicted that XP may alleviate OAB by affecting the cholinergic synapse and calcium signaling pathways. XP treatment significantly reduced the bladder index, improved urine behavior and urodynamic parameters, decreased the neurotransmitters in urine, and reduced the thickness of the bladder wall and collagen ratio. These results indicate that XP can alleviate OAB symptoms and improve the bladder structure. In vivo/vitro experiments further demonstrated that XP can inhibit targets, such as muscarinic acetylcholine receptor 2, and participate in cholinergic synapses to further regulate the parasympathetic nervous system. It can also reduce the overexpression of Ca2+ caused by agonists, inhibit targets such as transient receptor potential vanilloid type 1, and participate in calcium signaling pathways to maintain Ca2+ homeostasis. Conclusion These results suggest that XP inhibited bladder overactivity by maintaining Ca2+ homeostasis and regulating the parasympathetic nervous system.

To target the pivotal BCR/ABL oncoprotein in chronic myeloid leukemia (CML) cells, tyrosine kinase inhibitors (TKIs) are utilized as landmark achievements in CML therapy. However, TKI resistance and intolerance remain principal obstacles in the treatment of CML patients. In recent years, drug repositioning provided alternative and promising perspectives apart from the classical cancer therapies, and promoted anthelmintic mebendazole (MBZ) as an effective anti-cancer drug in various cancers. Here, we investigated the role of MBZ in CML treatment including imatinib-resistant CML cells. Our results proved that MBZ inhibited the proliferation and induced apoptosis in CML cells. We found that MBZ effectively suppressed BCR/ABL kinase activity and MEK/ERK signaling pathway by reducing p-BCR/ABL and p-ERK levels with ABL1 targeting ability. Meanwhile, MBZ directly targeted the colchicine-binding site of β-tubulin protein, hampered microtubule polymerization and induced mitosis arrest and mitotic catastrophe. In addition, MBZ increased DNA damage levels and hampered the accumulation of ataxia-telangiectasia mutated and DNA-dependent protein kinase into the nucleus. This work discovered that anthelmintic MBZ exerts remarkable anticancer effects in both imatinib-sensitive and imatinib-resistant CML cells in vitro and revealed mechanisms underlying. From the perspective of drug repositioning and multi‐target therapeutic strategy, this study provides a promising option for CML treatment, especially in TKI-resistant or intolerant individuals.

To target the pivotal BCR/ABL oncoprotein in chronic myeloid leukemia (CML) cells, tyrosine kinase inhibitors (TKIs) are utilized as landmark achievements in CML therapy. However, TKI resistance and intolerance remain principal obstacles in the treatment of CML patients. In recent years, drug repositioning provided alternative and promising perspectives apart from the classical cancer therapies, and promoted anthelmintic mebendazole (MBZ) as an effective anti-cancer drug in various cancers. Here, we investigated the role of MBZ in CML treatment including imatinib-resistant CML cells. Our results proved that MBZ inhibited the proliferation and induced apoptosis in CML cells. We found that MBZ effectively suppressed BCR/ABL kinase activity and MEK/ERK signaling pathway by reducing p-BCR/ABL and p-ERK levels with ABL1 targeting ability. Meanwhile, MBZ directly targeted the colchicine-binding site of β-tubulin protein, hampered microtubule polymerization and induced mitosis arrest and mitotic catastrophe. In addition, MBZ increased DNA damage levels and hampered the accumulation of ataxia-telangiectasia mutated and DNA-dependent protein kinase into the nucleus. This work discovered that anthelmintic MBZ exerts remarkable anticancer effects in both imatinib-sensitive and imatinib-resistant CML cells in vitro and revealed mechanisms underlying. From the perspective of drug repositioning and multi‐target therapeutic strategy, this study provides a promising option for CML treatment, especially in TKI-resistant or intolerant individuals.

To target the pivotal BCR/ABL oncoprotein in chronic myeloid leukemia (CML) cells, tyrosine kinase inhibitors (TKIs) are utilized as landmark achievements in CML therapy. However, TKI resistance and intolerance remain principal obstacles in the treatment of CML patients. In recent years, drug repositioning provided alternative and promising perspectives apart from the classical cancer therapies, and promoted anthelmintic mebendazole (MBZ) as an effective anti-cancer drug in various cancers. Here, we investigated the role of MBZ in CML treatment including imatinib-resistant CML cells. Our results proved that MBZ inhibited the proliferation and induced apoptosis in CML cells. We found that MBZ effectively suppressed BCR/ABL kinase activity and MEK/ERK signaling pathway by reducing p-BCR/ABL and p-ERK levels with ABL1 targeting ability. Meanwhile, MBZ directly targeted the colchicine-binding site of β-tubulin protein, hampered microtubule polymerization and induced mitosis arrest and mitotic catastrophe. In addition, MBZ increased DNA damage levels and hampered the accumulation of ataxia-telangiectasia mutated and DNA-dependent protein kinase into the nucleus. This work discovered that anthelmintic MBZ exerts remarkable anticancer effects in both imatinib-sensitive and imatinib-resistant CML cells in vitro and revealed mechanisms underlying. From the perspective of drug repositioning and multi‐target therapeutic strategy, this study provides a promising option for CML treatment, especially in TKI-resistant or intolerant individuals.

To target the pivotal BCR/ABL oncoprotein in chronic myeloid leukemia (CML) cells, tyrosine kinase inhibitors (TKIs) are utilized as landmark achievements in CML therapy. However, TKI resistance and intolerance remain principal obstacles in the treatment of CML patients. In recent years, drug repositioning provided alternative and promising perspectives apart from the classical cancer therapies, and promoted anthelmintic mebendazole (MBZ) as an effective anti-cancer drug in various cancers. Here, we investigated the role of MBZ in CML treatment including imatinib-resistant CML cells. Our results proved that MBZ inhibited the proliferation and induced apoptosis in CML cells. We found that MBZ effectively suppressed BCR/ABL kinase activity and MEK/ERK signaling pathway by reducing p-BCR/ABL and p-ERK levels with ABL1 targeting ability. Meanwhile, MBZ directly targeted the colchicine-binding site of β-tubulin protein, hampered microtubule polymerization and induced mitosis arrest and mitotic catastrophe. In addition, MBZ increased DNA damage levels and hampered the accumulation of ataxia-telangiectasia mutated and DNA-dependent protein kinase into the nucleus. This work discovered that anthelmintic MBZ exerts remarkable anticancer effects in both imatinib-sensitive and imatinib-resistant CML cells in vitro and revealed mechanisms underlying. From the perspective of drug repositioning and multi‐target therapeutic strategy, this study provides a promising option for CML treatment, especially in TKI-resistant or intolerant individuals.

To target the pivotal BCR/ABL oncoprotein in chronic myeloid leukemia (CML) cells, tyrosine kinase inhibitors (TKIs) are utilized as landmark achievements in CML therapy. However, TKI resistance and intolerance remain principal obstacles in the treatment of CML patients. In recent years, drug repositioning provided alternative and promising perspectives apart from the classical cancer therapies, and promoted anthelmintic mebendazole (MBZ) as an effective anti-cancer drug in various cancers. Here, we investigated the role of MBZ in CML treatment including imatinib-resistant CML cells. Our results proved that MBZ inhibited the proliferation and induced apoptosis in CML cells. We found that MBZ effectively suppressed BCR/ABL kinase activity and MEK/ERK signaling pathway by reducing p-BCR/ABL and p-ERK levels with ABL1 targeting ability. Meanwhile, MBZ directly targeted the colchicine-binding site of β-tubulin protein, hampered microtubule polymerization and induced mitosis arrest and mitotic catastrophe. In addition, MBZ increased DNA damage levels and hampered the accumulation of ataxia-telangiectasia mutated and DNA-dependent protein kinase into the nucleus. This work discovered that anthelmintic MBZ exerts remarkable anticancer effects in both imatinib-sensitive and imatinib-resistant CML cells in vitro and revealed mechanisms underlying. From the perspective of drug repositioning and multi‐target therapeutic strategy, this study provides a promising option for CML treatment, especially in TKI-resistant or intolerant individuals.

Objective:To investigate ferroptosis-related genes in pterygium tissue by using bioinformatic analysis.Methods:The pterygium gene expression profile dataset GSE2513 was downloaded from the Gene Expression Omnibus Database to identify differentially expressed genes (DEGs) related to ferroptosis.Functional annotation and enrichment analysis of the DEGs were performed using Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG).Hub genes were identified from the DEGs using LASSO logistic regression analysis and a support vector machine recursive feature elimination (SVM-REF).Single-gene GSEA analysis was performed on hub genes and a competitive endogenous RNA interaction network was constructed to determine the RNA regulatory relationships of the hub genes.Pterygium tissue samples from 9 patients (9 eyes) undergoing pterygium surgery and conjunctival tissue samples from 9 patients (9 eyes) undergoing strabismus surgery who visited the First Affiliated Hospital of Zhengzhou University were collected from 2022 to 2023 during surgery, and the expression of hub genes and ferroptosis-related marker genes was detected by fluorescence quantitative PCR.This study followed the Declaration of Helsinki, and the study protocol was reviewed and approved by the Ethics Committee of the First Affiliated Hospital of Zhengzhou University (No.2022-KY-0006-001).Results:In the dataset, there were 37 ferroptosis-related genes with significant expression differences, including 16 upregulated genes and 21 downregulated genes.GO analysis revealed significant enrichment in responses to external stimuli, responses to nutritional levels, responses to extracellular stimuli, responses to oxidative stress and starvation, transcription regulatory complexes, and RNA polymerase Ⅱ transcription regulatory complexes, RNA polymerase Ⅱ-specific transcription, and DNA-binding transcription.KEGG analysis showed that the DEGs were primarily enriched in ferroptosis and NOD-like receptor signaling pathways.LASSO regression analysis identified DUOX2, ATF3, NDRG1, EGR1, and ALDH3A2 as hub genes, and SVM-REF analysis identified NDRG1, NF2, IDH2, DUOX2, CHP1, ATF3, and SREBF1 as hub genes. DUOX2, ATF3, and NDRG1 were identified as the intersection hub genes.Single-gene GSEA analysis revealed that DUOX2 was enriched in the cell adhesion molecule CAMs pathway, the heparan sulfate glycosaminoglycan biosynthesis pathway, and the glycosaminoglycan biosynthesis ganglioside series pathway. ATF3 and NDRG1 were enriched in the PPAR signaling pathway and other pathways.Compared with normal conjunctival tissue, the relative expression levels of the ferroptosis markers PTGS2 and TFRC mRNA were increased in pterygium tissue, while the relative expression levels of FTH1, GPX4, SLC40A1, HSPB1, and NFE2L2 mRNA were decreased, with statistically significant differences ( t=12.220, 16.580, 5.664, 6.455, 8.691, 9.883, 17.590; all P<0.01). Conclusions:Ferroptosis may play an important role in the pathogenesis of pterygium. DUOX2, ATF3, and NDRG1 may be the hub genes affecting this complicated process.

AIM: To determine the patient-related risk factors for pain during phacoemulsification.METHODS: Retrospective case-control study. A total of 62 patients(62 eyes)diagnosed as cataract in the First Affiliated Hospital of Zhengzhou University from December 2023 to January 2024 were included. The numeric rating scale was used to assess the pain level within 5 min postoperatively. The highest pain value was used as the primary outcome during the procedure. Based on pain values, patients were divided into pain group(n=25)and pain-free group(n=37). Subsequently, patients in the pain group were further divided into mild(n=16), moderate(n=7), and severe groups(n=2). Spearman correlation and Logistic regression analysis were conducted to determine risk factors for pain during the phacoemulsification.RESULTS: Binary Logistic regression showed preoperative sleep durations and times of operations were important risk factors for intraoperative pain(all P<0.05). Spearman analysis showed that intraoperative pain was negatively correlated with sleep duration(rs=-0.386, P=0.002), and positively correlated with times of operations(rs=0.421, P<0.001). The results of the ordinal Logistic regression analysis showed that for every additional hour of sleep, the likelihood of experiencing one higher level of intraoperative pain decreased by 37.60%(OR=0.376, P=0.014). In contrast, the times of operations did not show a statistically significant difference(P=0.083). Receiver operating characteristic curve showed a joint prediction model of sleep duration and operative times with an area under the curve of 0.809, 84% sensitivity, and 73% specificity.CONCLUSION: The intraoperative pain during phacoemulsification is negatively correlated with sleep duration and positively correlated with times of operations.

Background::In East Asia, Helicobacter pylori ( H. pylori) infection and related diseases are common, primarily during childhood and adolescence. The rates of primary antibiotic resistance in H. pylori among East Asian children and adolescents have not been extensively explored; few relevant systematic reviews or meta-analyses have been conducted. We evaluated the rates of antibiotic resistance in H. pylori among East Asian children and adolescents, with the goal of facilitating individualized treatment recommendations. Methods::We searched PubMed, Embase, and the Cochrane Library for studies in any language published up to February 2023 that explored antibiotic resistance in H. pylori among East Asian children and adolescents. We used MeSH and non-MeSH terms related to the topic, including terms related to children, adolescents, antibiotic resistance, H. pylori, and nations or regions. Additionally, we reviewed the reference lists of relevant articles. Studies that matched our strict predefined eligibility criteria were included in the screening process. Using established assessment methods, we evaluated the quality of the included studies. Results::We identified 15 observational studies involving 4831 H. pylori isolates, all published between 2001 and 2022. There was substantial primary antibiotic resistance in H. pylori isolates from East Asian children and adolescents. The rates of primary resistance were 51% (95% confidence interval [CI]: 40–62%) for metronidazole; 37% (95% CI: 20–53%) for clarithromycin; 19% (95% CI: 11–28%) for levofloxacin; and less than 3% each for amoxicillin, tetracycline, and furazolidone. Subgroup analysis revealed a prominent increase in metronidazole resistance over time. Clarithromycin and levofloxacin resistance rates fluctuated between 2005 and 2015, then remained stable; other antibiotic resistance rates were generally stable. Metronidazole, clarithromycin, and levofloxacin resistance rates were significantly higher in the Chinese mainland than in other East Asian regions. The rates of dual and multiple antibiotic resistance were 28% (95% CI: 21–36%) and 10% (95% CI: 7–14%), highlighting the potential for diverse resistance patterns. Conclusions::H. pylori isolates from East Asian children and adolescents exhibit high levels of metronidazole and clarithromycin resistance, particularly in the Chinese mainland. The non-negligible rates of dual and multiple resistance highlight the complexity of this problem. Registration::PROSPERO, No. CRD42023402510.