In recent years, the incidence of dry eye disease(DED)is increasing, positioning it as one of the most prevalent diseases affecting the ocular surface. Inflammatory response is the pathological basis of DED, involving various inflammatory mediators and inflammatory signaling pathways. Consequently, anti-inflammatory treatment emerges as a fundamental strategy for preventing and managing DED. This review summarizes the classic inflammatory factors involved in the development and progression of DED, including interleukins, tumor necrosis factor, matrix metalloproteinases, chemokines, and cell adhesion molecules. It also discusses the relevant inflammatory signaling pathways: the MAPKs pathway, NF-κB pathway, Wnt pathway and TLR pathway. Additionally, this review addresses the mechanisms of action and alterations in relevant biomarkers associated with current first-line recommended anti-inflammatory therapies, including corticosteroids, immunosuppressants, nonsteroidal anti-inflammatory drugs, and traditional Chinese medicine approaches to inflammation management. This comprehensive overview aims to enhance understanding of the inflammatory mechanisms underlying DED while exploring future therapeutic prospects.

In recent years, the incidence of dry eye disease(DED)is increasing, positioning it as one of the most prevalent diseases affecting the ocular surface. Inflammatory response is the pathological basis of DED, involving various inflammatory mediators and inflammatory signaling pathways. Consequently, anti-inflammatory treatment emerges as a fundamental strategy for preventing and managing DED. This review summarizes the classic inflammatory factors involved in the development and progression of DED, including interleukins, tumor necrosis factor, matrix metalloproteinases, chemokines, and cell adhesion molecules. It also discusses the relevant inflammatory signaling pathways: the MAPKs pathway, NF-κB pathway, Wnt pathway and TLR pathway. Additionally, this review addresses the mechanisms of action and alterations in relevant biomarkers associated with current first-line recommended anti-inflammatory therapies, including corticosteroids, immunosuppressants, nonsteroidal anti-inflammatory drugs, and traditional Chinese medicine approaches to inflammation management. This comprehensive overview aims to enhance understanding of the inflammatory mechanisms underlying DED while exploring future therapeutic prospects.

AIM: To investigate the effectiveness and safety of defocus incorporated multiple segments(DIMS)on myopia in adolescents, and provide a theoretical basis for clinical application.METHODS:Retrospective study. A total of 560 myopic children(560 eyes)aged 8-13 years who were admitted to our hospital from January 2019 to January 2022 were selected as research subjects, of whom 180 cases(180 eyes)were enrolled in the DIMS group. The orthokeratology(OK lens)group consisted of 182 patients(182 eyes), and the single vision(SV)group consisted of 198 patients(198 eyes). The changes of the spherical equivalent and axial length in the three groups were observed after 1 and 2 a respectively. The myopia degree(group A: spherical equivalent ≥-3.00 D and group B: -6.00 D≤ spherical equivalent <-3.00 D), and age(group Ⅰ: 8-10 years old and group Ⅱ: 11-13 years old)were grouped to further analyze the effect of myopia degree and age on treatment effect.RESULTS: At 1 and 2 a after wearing lenses, the spherical equivalent in the DIMS and SV groups was statistically significant(all P<0.05); there was statistical significance in the axial length among the DIMS, OK and SV groups(F=21.791, 3.576, all P<0.05). At 1 and 2 a after wearing lenses, there was statistical significance in the changes of spherical equivalent in both the DIMS and SV groups of the groups A and B(all P<0.05); and there was statistical significance in axial length growth of the DIMS, OK and SV groups(all P<0.05). At 1 and 2 a after wearing lenses, there was statistical significance in the changes of spherical equivalent in the DIMS and SV groups of the groups Ⅰ and Ⅱ(all P<0.01); in the group Ⅰ, there was statistical significance in the comparison of axial length growth in the DIMS, OK and SV groups(all P<0.05); in the group Ⅱ, there was no statistical significance in the changes of axial length in the DIMS and OK groups. The efficacy of DIMS and OK in the prevention and treatment of myopia was comparable, and the myopia progression was delayed, and the efficacy was enhanced in those older adolescents wearing DIMS.CONCLUSION: Compared with SV lens, DIMS and OK lenses effectively slow down the myopia progression in adolescents. The overall myopia control effect of DIMS is slightly inferior to that of OK lens. However, with the increase of age and the degree of refractive error, the delaying effect of DIMS on myopia progression is enhanced.

Myelin formation is considered the last true "invention" in the evolution of vertebrate nervous system cell structure. The rapid jumping pulse propagation achieved by myelin enables the high conduction speed that is the basis of human movement, sensation, and cognitive function. As a key structure in the brain, white matter is the gathering place of myelin. However, with age, white matter-associated functions become abnormal and a large number of myelin sheaths undergo degenerative changes, causing serious neurological and cognitive disorders. Despite the extensive time and effort invested in exploring myelination and its functions, numerous unresolved issues and challenges persist. In-depth exploration of the functional role of myelin may bring new inspiration for the treatment of central nervous system (CNS) diseases and even mental illnesses. In this study, we conducted a comprehensive examination of the structure and key molecules of the myelin in the CNS, delving into its formation process. Specifically, we propose a new hypothesis regarding the source of power for myelin expansion in which membrane compaction may serve as a driving force for myelin extension. The implications of this hypothesis could provide valuable insights into the pathophysiology of diseases involving myelin malfunction and open new avenues for therapeutic intervention in myelin-related disorders.
Myelin Sheath/metabolism* ; Humans ; Central Nervous System/metabolism* ; Animals

Objective:To construct an artificial intelligence (AI)-assisted system based on deep learning for corneal in vivo confocal microscopy (IVCM) image recognition and to evaluate its value in clinical applications. Methods:A diagnostic study was conducted.A total of 18 860 corneal images were collected from 331 subjects who underwent IVCM examination at Renmin Hospital of Wuhan University and Zhongnan Hospital of Wuhan University from May 2021 to September 2022.The collected images were used for model training and testing after being reviewed and classified by corneal experts.The model design included a low-quality image filtering model, a corneal image diagnosis model, and a 4-layer identification model for corneal epithelium, Bowman membrane, stroma, and endothelium, to initially determine normal and abnormal corneal images and corresponding corneal layers.A human-machine competition was conducted with another 360 database-independent IVCM images to compare the accuracy and time spent on image recognition by three senior ophthalmologists and the AI system.In addition, 8 trainees without IVCM training and with less than three years of clinical experience were selected to recognize the same 360 images without and with model assistance to analyze the effectiveness of model assistance.This study adhered to the Declaration of Helsinki.The study protocol was approved by the Ethics Committee of Renmin Hospital of Wuhan University (No.WDRY2021-K148).Results:The accuracy of this diagnostic model in screening high-quality images was 0.954.Its overall accuracy in identifying normal/abnormal corneal images was 0.916 and 0.896 in the internal and external test sets, respectively.Its accuracy reached 0.983, 0.925 in the internal test sets and 0.988, 0.929 in the external test sets in identifying corneal layers of normal and abnormal images, respectively.In the human-machine competition, the overall recognition accuracy of the model was 0.878, which was similar to the average accuracy of the three senior physicians and was approximately 300 times faster than the experts in recognition speed.Trainees assisted by the system achieved an accuracy of 0.816±0.043 in identifying corneal layers of normal and abnormal images, which was significantly higher than 0.669±0.061 without model assistance ( t=6.304, P<0.001). Conclusions:A deep learning-based assistant system for corneal IVCM image recognition is successfully constructed.This system can discriminate normal/abnormal corneal images and diagnose the corresponding corneal layer of the images, which can improve the efficiency of clinical diagnosis and assist doctors in training and learning.

【Objective】 To explore the effects of breastfeeding on the immune response of CD4⁺T lymphocytes in infants in non-inflammatory state, and to analyze the immunomodulatory significance of the whole composition of breast milk. 【Methods】 A retrospective cohort study was conducted. From January to September 2022, six-month-old infants who took physical examination in the Child Healthcare Department of Changzhou Children′s Hospital Affiliated to Nantong University, were selected based on inclusion criteria, and were divided into breastfeeding group (n=33) and formula feeding group (n=27) based on their feeding patterns. Flow cytometry was used to detect the percentage of CD4⁺ T cells, including helper T cell (Th) 1, Th2, Th17, regulatory T cell (Treg), and the levels of related cytokines interleukin (IL)-2, IL-4, IL-6, IL-10, tumor necrosis factor (TNF)-α, interferon (IFN)-γ, IL-17 in peripheral blood. The differences in these indicators between the two groups were compared. 【Results】 Compared with the formula feeding group, the breastfeeding group showed significantly higher percentages of Th1(t=3.038), Treg (t=2.088). The ratio of Th1 to Th2(Z=2.756), IL-10(Z=2.297) and IFN-γ (Z=2.076) in the peripheral blood of the breastfeeding group were also significantly higher. Conversely, the breastfeeding group had significantly lower percentage of Th17(Z=2.704) and IL-17A (t=2.187) (P<0.05). There was no significant difference the percentage of Th2, as well as in the levels of IL-2, IL-4, IL-6 and TNF-α between the two groups (P>0.05). 【Conclusions】 Breastfeeding has a regulatory effect on the immune response of infant CD4⁺ T lymphocytes. It promotes the development of Th1/Th2 towards Th1 and the immunomodulatory effect of Treg. Moreover, it inhibits the Th17 type immune response. These findings suggest that the complete composition of breast milk contributes to the development and maturation of infant immune system, enhancing immune defense and immune tolerance.

Uncontrolled hypertension in the perioperative period may affect the hemodynamic stability of patients during surgery and thus affect the prognosis of patients.This increases the risk of other complications and death.For hypertensive patients undergoing surgery,it is necessary to weigh the pros and cons,and choose appropriate antihypertensive drugs to reduce the incidence of perioperative adverse events.There is no unified conclusion on perioperative blood pressure management in China.This paper systematically reviewed the perioperative blood pressure control objectives and drug use programs,including non-cardiac surgery,cardiac surgery,pregnancy,and pheochromocytoma.It provided a reference for the perioperative management of hypertensive patients.

Polymyxins are the first-line drugs used in multidrug resistance(MDR)Gram-negative infections.Polymyxin-induced nephrotoxicity is the major dose-limiting factor hindering its clinical use.It has been suggested that the mechanism of polymyxin-associated nephrotoxicity is related to its accumulation in the kidney upon extensive reabsorption from renal proximal tubular cells,and one or more renal transporters may mediate the process that polymyxins enter the renal tubular cells across cytomembrane.This review aimed to describe the roles of renal transporters in polymyxins reabsorption into the renal tubular cells and provide reference for reducing the nephrotoxicity of polymyxin.

17q12 deletion syndrome is a rare autosomal dominant disorder affecting multiple organ systems caused by the deletion of DNA fragments approximately 1.4～1.8 Mb in band 2 of region 1,the long arm of chromosome 17,including hepatocyte nuclear factor 1B.The clinical manifestation of the disease ismaturity-onset diabetes of youth type 5,abnormalities in renalstructure or function,as well as in neurodevelopment or psychiatric systems.

Objective:To investigate the inhibitory effect of miR-497 on the corneal epithelial healing in diabetic mice and its possible mechanism.Methods:Forty healthy clean-grade wild-type C57BL/J6 mice were randomly divided into a blank control group and a model control group, with 20 mice in each group.Another 20 CRISPR/Cas9-mediated miR-497 knockout mice and miR-497 overexpression mice were taken as miR-497 knockout and miR-497 overexpression groups, respectively.The diabetes model was constructed by continuous intraperitoneal injection of streptozotocin (STZ) to the mice in model control, miR-497 knockout and miR-497 overexpression groups, and the mice in blank control group were injected with an equal amount of citrate buffer, followed by 8-week normal feeding.After the establishment of diabetes model, the corneal epithelial injury model was further constructed by scraping off part of the corneal epithelium with a central diameter of 2 mm.The corneal epithelial defect area of mice in 0, 12, 24 and 36 hours after corneal epithelial injury was observed by corneal fluorescein sodium staining.The expression of Wnt3a and β-catenin proteins in mice corneal tissues was detected by Western blot.The expression of miR-497 as well as the mRNA expression levels of cell proliferation-associated factor genes CyclinD1, c-Myc, and Ki-67 mRNA was detected by real-time quantitative fluorescence PCR.The targeting relationship between miR-497 and wnt3a was detected by a dual luciferase reporter gene assay.Human corneal epithelial cells (HCEC) were cultured in vitro and transfected with miR-497 mimics, miR-497 mimics negative control, miR-497 inhibitor, and miR-497 inhibitor negative control by Lipo8000 as miR-497 mimics group, mimics negative control group, miR-497 inhibitor group, andmiR-497 inhibitor negative control group, respectively, all of which were cultured in high glucose medium containing 25% glucose.Another two groups of HCEC were taken and cultured in medium containing 5% and 25% glucose as control and high glucose groups, respectively.The cell proliferation viability was determined by CCK8 method.The use and care of animals complied ith the ARVO statement.The study protocol was approved by the Ethics Committee of Renmin Hospital of Wuhan University (2019K-K010). Results:Eight weeks after STZ injection, the blood glucose of mice was significantly higher and the weight was significantly lower in each diabetic model group than those of blank control group (all at P<0.05). At 12, 24 and 36 hours after the corneal epithelial injury, the percentages of corneal epithelial defect area observed by slit-lamp microscopy in model control group were significantly higher than those in blank control group and miR-497 knockout group and lower than those in miR-497 overexpression group, and the differences were statistically significant (all at P<0.05). The relative expressions of wnt3a and β-catenin proteins in the corneal tissues of model control group were significantly lower than those of blank control group and miR-497 knockout group, but higher than those of miR-497 overexpression group, and the differences were statistically significant (all at P<0.05). The relative expressions of CyclinD1, c-Myc and Ki-67 mRNA in model control group were lower than those in miR-497 knockout group, but higher than those in miR-497 overexpression group, and the differences were statistically significant (all at P<0.05). The relative expression of miR-497 in model control group, miR-497 knockout group and miR-497 overexpression group was 1.00±0.02, 0.63±0.06 and 1.48±0.03, respectively, with a statistically significant difference ( F=19.62, P<0.01). The luciferase activity of miR-497-5p mimics group in wild-type wnt3a transfected cells was lower than that of miR-497-5p negative control group and empty vector group, and the differences were statistically significant (all at P<0.05). In the mutant wnt3a transfected cells, there was no significant difference in the luciferase activity among various groups ( F=0.73, P=0.59). The cell proliferation A value of high glucose group was 0.59±0.03, which was significantly lower than 0.59±0.03 of normal control group and 0.88±0.08 of miR-497 inhibitor group, but significantly higher than 0.48±0.11 of miR-497 mimics group (all at P<0.05). Conclusions:The silencing of miR-497 may promote the repair of diabetic corneal epithelial defects by targeting wnt/β-catenin pathway.