AIM: To investigate the risk factors of myopia, and provide evidence for the prevention and treatment of myopia in preschool children.METHODS:This is a retrospective case-control study. A total of 168 preschool-aged children(168 eyes)were enrolled from the ophthalmology department at Affiliated Hospital of Qingdao University between September 2021 and September 2023, selecting the eye with poorer vision for inclusion; the right eye was selected when both eyes had equal vision. Grouping criteria: Children with spherical equivalent(SE)>0 D and age-appropriate normal visual acuity(≥0.5 for ages 3-5; ≥0.7 for ages 6-7)were directly assigned to the non-myopia group. Children with SE <0 D underwent cycloplegic refraction after 3 days of 1% atropine sulfate gel application(three times daily). Those with SE ≤-0.50 D and failure to achieve age-normal visual acuity(<0.5 for ages 3-5; <0.7 for ages 6-7)were assigned to the myopia group, with 84 children(84 eyes)in each group. All participants underwent measurements of visual acuity, intraocular pressure, refraction, and ocular biometric parameters. Parents or guardians completed risk factor questionnaires during the visit, covering daily outdoor activity duration, daily electronic device usage/reading time, parental myopia status, maternal delivery mode, and full-term birth status.RESULTS:Significant differences were observed in uncorrected visual acuity, spherical power, SE, and axial length between the two groups of children(all P<0.05). No statistically significant differences were found in daily sleep duration, daily reading/homework time, maternal myopia status, mode of delivery, or full-term delivery status(all P>0.05). However, significant differences existed in daily outdoor activity time, daily electronic device usage duration, maternal myopia degree, paternal myopia degree, maternal age of myopia onset, and paternal age of myopia onset(all P<0.05). Logistic regression analysis identified the following risk factors for myopia in preschool children: daily outdoor activity under 2 h, daily electronic device use exceeding 60 min, maternal myopia degree, maternal early-onset myopia, paternal high myopia, and paternal early-onset myopia. Analysis of interaction effects children gender and myopia-related factors on SE revealed significant interactions of children gender with paternal myopia degree, maternal and paternal age of myopia onset(P<0.05). Simple effects analysis further demonstrated that girls exhibited higher degree of myopia than boys in families with paternal early-onset myopia, maternal early-onset myopia, or paternal high myopia(P<0.05).CONCLUSION:Insufficient daily outdoor activity time(under 1 h), daily electronic device use exceeding 60 min, and parental myopia are significant risk factors for myopia development in preschool children. Among these children, girls' refractive status was particularly associated with parental refractive status.

Alzheimer’s disease (AD) is a central neurodegenerative disease characterized by progressive cognitive decline and memory impairment in clinical. Currently, there are no effective treatments for AD. In recent years, a variety of therapeutic approaches from different perspectives have been explored to treat AD. Although the drug therapies targeted at the clearance of amyloid β-protein (Aβ) had made a breakthrough in clinical trials, there were associated with adverse events. Neuroinflammation plays a crucial role in the onset and progression of AD. Continuous neuroinflammatory was considered to be the third major pathological feature of AD, which could promote the formation of extracellular amyloid plaques and intracellular neurofibrillary tangles. At the same time, these toxic substances could accelerate the development of neuroinflammation, form a vicious cycle, and exacerbate disease progression. Reducing neuroinflammation could break the feedback loop pattern between neuroinflammation, Aβ plaque deposition and Tau tangles, which might be an effective therapeutic strategy for treating AD. Traditional Chinese herbs such as Polygonum multiflorum and Curcuma were utilized in the treatment of AD due to their ability to mitigate neuroinflammation. Non-steroidal anti-inflammatory drugs such as ibuprofen and indomethacin had been shown to reduce the level of inflammasomes in the body, and taking these drugs was associated with a low incidence of AD. Biosynthetic nanomaterials loaded with oxytocin were demonstrated to have the capability to anti-inflammatory and penetrate the blood-brain barrier effectively, and they played an anti-inflammatory role via sustained-releasing oxytocin in the brain. Transplantation of mesenchymal stem cells could reduce neuroinflammation and inhibit the activation of microglia. The secretion of mesenchymal stem cells could not only improve neuroinflammation, but also exert a multi-target comprehensive therapeutic effect, making it potentially more suitable for the treatment of AD. Enhancing the level of TREM2 in microglial cells using gene editing technologies, or application of TREM2 antibodies such as Ab-T1, hT2AB could improve microglial cell function and reduce the level of neuroinflammation, which might be a potential treatment for AD. Probiotic therapy, fecal flora transplantation, antibiotic therapy, and dietary intervention could reshape the composition of the gut microbiota and alleviate neuroinflammation through the gut-brain axis. However, the drugs of sodium oligomannose remain controversial. Both exercise intervention and electromagnetic intervention had the potential to attenuate neuroinflammation, thereby delaying AD process. This article focuses on the role of drug therapy, gene therapy, stem cell therapy, gut microbiota therapy, exercise intervention, and brain stimulation in improving neuroinflammation in recent years, aiming to provide a novel insight for the treatment of AD by intervening neuroinflammation in the future.

Immobilized enzyme-based enzyme electrode biosensors, characterized by high sensitivity and efficiency, strong specificity, and compact size, demonstrate broad application prospects in life science research, disease diagnosis and monitoring, etc. Immobilization of enzyme is a critical step in determining the performance (stability, sensitivity, and reproducibility) of the biosensors. Random immobilization (physical adsorption, covalent cross-linking, etc.) can easily bring about problems, such as decreased enzyme activity and relatively unstable immobilization. Whereas, directional immobilization utilizing amino acid residue mutation, affinity peptide fusion, or nucleotide-specific binding to restrict the orientation of the enzymes provides new possibilities to solve the problems caused by random immobilization. In this paper, the principles, advantages and disadvantages and the application progress of enzyme electrode biosensors of different directional immobilization strategies for enzyme molecular sensing elements by specific amino acids (lysine, histidine, cysteine, unnatural amino acid) with functional groups introduced based on site-specific mutation, affinity peptides (gold binding peptides, carbon binding peptides, carbohydrate binding domains) fused through genetic engineering, and specific binding between nucleotides and target enzymes (proteins) were reviewed, and the application fields, advantages and limitations of various immobilized enzyme interface characterization techniques were discussed, hoping to provide theoretical and technical guidance for the creation of high-performance enzyme sensing elements and the manufacture of enzyme electrode sensors.

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.

Objective To develop dynamic prediction models based on multiple postnatal time points to support early diagnosis and individualized intervention for bronchopulmonary dysplasia(BPD)in preterm infants with gestational age<32 weeks.Methods Clinical data of 472 preterm infants with gestational age<32 weeks admitted to the Second Xiangya Hospital of Central South University between January 2016 and November 2020 were retrospectively analyzed.Multivariable logistic regression was applied to develop five independent prediction models at postnatal days 1,7,14,21,and 28.The performance of the models was assessed using the area under the receiver operating characteristic curve(AUC)and the Hosmer-Lemeshow test.Results Baseline characteristics such as gestational age and birth weight differed significantly between the BPD group(n=147)and the non-BPD group(n=325)(P<0.05).Predictors of BPD evolved across time points:on day 1,key predictors included gestational age,birth weight,Score for Neonatal Acute Physiology II(SNAP-II),invasive mechanical ventilation,and fraction of inspired oxygen>30%;by day 7,additional variables emerged,including fasting duration>2 days,mean feeding advancement rate<8.5 mL/(kg·d),neonatal respiratory distress syndrome,apnea of prematurity,and positive sputum culture;from day 14 onward,nutrition-and treatment-related indicators were incorporated additionally.The models demonstrated good discrimination at postnatal days 1,7,14,21,and 28,with AUCs of 0.917,0.927,0.939,0.944,and 0.968,respectively,and good calibration(Hosmer-Lemeshow P>0.05).Internal validation showed AUCs ranging from 0.899 to 0.958,indicating robust performance.Conclusions Dynamic postnatal prediction models incorporating indicators spanning perinatal factors,respiratory support,nutritional management,and therapeutic interventions demonstrate high predictive performance and facilitate dynamic risk assessment for BPD in preterm infants with gestational age<32 weeks.

Advances in genomics,biochemistry,and genetics have deepened our understanding of epigenetic mechanisms.These mechanisms play a crucial role in life,heredity,and evo-lution.Their growing significance is driving biomedical research toward personalized and precise medicine.Renal diseases,par-ticularly chronic kidney disease and acute kidney injury,require new treatment strategies.Their subtle clinical symptoms and challenges in early diagnosis limit current therapeutic options.Research on epigenetic modifications in renal diseases is expan-ding rapidly.This field is emerging as a promising approach for kidney disease treatment.The transition from basic mechanistic studies to clinical applications is underway.Epigenetic modifica-tions hold great potential for improving early diagnosis,enabling personalized treatment,and advancing precision medicine in re-nal diseases.

Aim To investigate the effects of the fangchinoline derivative LYY-32 on the biological prop-erties of the BLM642-1290 DNA helicase,in order to lay a foundation for further research on its antitumor activity.Methods Fluorescence polarization assay,malachite green-phosphate and ammonium molybdate colorime-try,and fluorescein-labeled DNA gel electrophoresis experiments were conducted to study the effects of fangchinoline derivative LYY-32 on the DNA binding activity,ATPase activity,and DNA unwinding activity of BLM642-1290 DNA helicase.The effects of LYY-32 on the DNA unwinding activity of DNA helicase in cells were studied using fluorescent techniques and time-lapse microscopy.Ultraviolet spectral scanning was used to investigate the effects of LYY-32 on the confor-mation of the BLM642-1290 DNA helicase.Results At a concentration of 10 μmol·L-1,the inhibition rate of LYY-32 on BLM642-1290 DNA helicase binding to dsDNA was 53.17％.At a concentration of 5 μmol·L-1,the inhibition rate of LYY-32 on BLM642-1290 DNA helicase binding to ssDNA was 88.49％.The inhibition rate of LYY-32 on the ATPase activity of BLM642-1290 DNA he-licase was 89.3％at a concentration of 50 μmol·L-1.When the concentration of LYY-32 exceeded 5μmol·L-1,its inhibition rate on the DNA unwinding activity of BLM642-1290 DNA helicase was 100％.LYY-32 also significantly inhibited the DNA unwinding ac-tivity of DNA helicase in cells.However,LYY-32 had no effect on the conformation of BLM642-1290 DNA heli-case.Conclusion The DNA binding activity,AT-Pase activity,and DNA unwinding activity of BLM642-1290 DNA helicase could be significantly inhibi-ted by the fangchinoline derivative LYY-32.

Objective:To construct a clinical early warning model for bladder spasm occurred after transurethral resection of the prostate(TURP)in patients with benign prostatic hyperplasia(BPH)based on LASSO regression.Methods:The clinical data of 139 patients with BPH who underwent TURP treatment in Yellow River Sanmenxia Hospital from January 2022 to June 2024 were prospectively selected,and they were divided into spasm group(39 cases)and non-spasm group(100 cases)according to whether bladder spasm occurred after surgery.The characteristics of bladder spasm occurred after TURP in patients with BPH were statistically analyzed,and the general data between the two groups were compared.LASSO regression was used to screen the characteristic variables related to bladder spasm occurred after TURP,multivariate logistic regression was used to analyze the influencing factors of bladder spasm after TURP.The prediction model of bladder spasm after TURP was constructed,and the receiver operating characteristic(ROC)curve was drawn to evaluate the efficacy of the prediction model.Results:The incidence of bladder spasm after TURP was 28.06％.There were significant differences in age,history of diabetes,operation time,temperature of irrigating fluid,traction tension of urinary catheter,prostate volume and postoperative hospital stay between non-spasm group and spasm group(P＜0.05).LASSO regression showed that operation time,age,traction tension of urinary catheter,temperature of irrigating fluid,history of diabetes were important characteristics of bladder spasm occurred after TURP.Multivariate logistic regression analysis showed that old age,history of diabetes and long operation time were independent risk factors of bladder spasm occurred after TURP(P＜0.05).ROC curve showed that the area under the curve(AUC)of the risk prediction model for bladder spasm occurred after TURP was 0.885(95％CI:0.752-0.921).Conclusions:Old age,history of diabetes and long operation time are independent risk factors of bladder spasm occurred after TURP,the clinical warning model based on LASSO regression has a certain value in predicting the risk for bladder spasm occurred after TURP,which helps to identify high-risk patients early.

Abnormal expression of CMTM4 protein is closely related to tumour occurrence,development and prognosis.Although the important role of CMTM4 in tumours has been gradually manifested,its spe-cific mechanism of action in cervical cancer remains unclear.The aim of this study was to investigate the relationship between CMTM4 expression and clinicopathological features in cervical cancer and study its mechanism.Immunohistochemistry and Western blot were used to detect the expression level of CMTM4 in cancer tissues and paracancerous tissues,and it was found that CMTM4 was significantly under-ex-pressed in cervical cancer tissues(P＜0.001).The chi-square test analysed the relationship between high and low CMTM4 expression and the clinical and pathological characteristics of cervical cancer pa-tients and results found that CMTM4 expression was correlated with the number of births,HPV infection status,pathological type,FIGO stage and lymph node metastasis.Data from Western blot and RT-qPCR found that CMTM4 protein and mRNA levels in HaCaT cells were significantly higher than that of C-33A cells,HeLa cells,U14 cells,and HT-3 cells.Among them,the most significant change in CMTM4 ex-pression was observed in C-33A cells,so the C-33A cell line was selected for subsequent overexpression experiments.CCK-8 analysis found that the proliferation ability of C-33A cervical cancer cells in the pcDNA-CMTM4 group was significantly lower than that in the pcDNA-NC group(P＜0.001).Flow cy-tometry and Western blot results indicated that CMTM4 overexpression promoted apoptosis(P＜0.001),significantly increased Bax(P＜0.001)and cleaved caspase 3(P＜0.05)protein levels,and significant-ly decreased Bcl-2 protein level(P＜0.01).Western blot results further found that CMTM4 overexpres-sion significantly reduced the protein levels of p-PI3K(P＜0.001)and p-AKT(P＜0.01),but did not affect the protein levels of PI3K and AKT(P＞0.05).The above findings indicated that CMTM4 gene expression was down-regulated in cervical cancer,and CMTM4 overexpression inhibited cervical cancer cell proliferation and induced apoptosis by inhibiting the PI3K/AKT pathway.Therefore,CMTM4 may be used as a biological marker for screening cervical cancer.

Objective:To analyze the predictive role of WT1 expression levels pre-and early post-transplantation on relapse and overall survival(OS)in patients with acute myeloid leukemia(AML)undergoing allogeneic hematopoietic stem cell transplantation(allo-HSCT)during their first complete remission(CR1).Methods:A retrospective analysis was conducted on the clinical data of 107 adult AML patients who underwent allo-HSCT during their CR1 at our center between May 2012 and December 2021.The predictive role of bone marrow WT1 expression levels before transplantation and at 3 and 6 months post-transplantation on relapse and OS was explored in combination with relevant clinical factors.Results:The median follow-up time for the 107 patients was 70(range:11-117)months.Among the patients,15 cases died.Kaplan-Meier survial analysis showed that the 3-year overall survival(OS)rate was 85.0％.20 patients experienced relapse,with a median time to relapse of 8(range:0.5-44)months and a l-year cumulative relapse rate of 13.1％.The overall median value of WT1 before transplantation,3 months after transplantation,and 6 months after transplantation was 0.26％(range:0％-23.64％),with an upper quartile value of 0.74％.No statistically significant differences in WT1 expression levels were observed among the pre-transplantation,3-month post-transplantation,and 6-month post-transplantation time points(P=0.227).Univariate analysis showed that patients with WT1 levels＞0.74％at 3 months post-transplantation had a higher 1-year relapse rate(P=0.029)and lower 3-year OS rate(P＜0.001)compared to patients with WT1 levels ≤0.74％.Other significant factors affecting 1-year relapse included stem cell source(P=0.041)and chronic graft-versus-host disease(cGVHD)(P=0.013).For 3-year OS,additional influencing factors were genetic high risk(P=0.048)and stem cell source(P=0.016).Multivariate analysis revealed that WT1 level＞0.74％at 3 months post-transplantation had a trend to affect 1-year relapse rate(HR=3.309,95％CI:0.958-11.431,P=0.058),while the absence of cGVHD was an independent risk factor for 1-year relapse(HR=3.473,95％CI:0.749-16.100,P=0.037).Only WT1 level＞0.74％at 3 months post-transplantation was an independent risk factor for 3-year OS(HR=6.886,95％CI:2.402-19.738,P＜0.001).Conclusion:High WT1 expression level at 3 months post-transplantation in AML patients undergoing allo-HSCT during CR1 affects the 1-year relapse rate and 3-year OS,and is an independent risk factor affecting 3-year OS.These findings suggest that dynamic monitoring of WT1 expression levels has certain value in prognostic assessment of AML patients who received allo-HSCT during CR1.