While cranial radiotherapy effectively kills tumor cells and significantly prolongs patient survival, it often leads to progressive cognitive decline. To date, the specific mechanisms underlying radiation-induced cognitive decline have not been fully elucidated, which greatly limits the development of related therapeutic strategies. Therefore, this article provides a comprehensive analysis of post-radiation changes in neurogenesis, neuronal synaptic plasticity, myelin injury plasticity, and parenchymal cells such as microglia in the brain, systematically elucidates the potential mechanisms of radiation-induced cognitive decline, and summarizes feasible therapeutic approaches. These findings provide a solid foundation for developing novel strategies to mitigate radiation-induced cognitive decline.

Idiopathic pulmonary fibrosis （IPF） is a chronic and fibrotic lethal interstitial lung disease with poor prognosis. It is mainly treated by organ transplantation and administration of chemical drugs， which have poor efficacy and induce side effects， failing to meet the clinical needs. Therefore， it is urgent to develop more safe and effective drugs to treat IPF. Traditional Chinese medicine （TCM） has garnered increasing attention in recent years in the treatment of IPF due to its unique advantages. Increasing studies have shown that TCM has remarkable therapeutic effects on IPF and thus demonstrate broad application prospects. Modern medical research shows that the pathogenesis of IPF can be discussed from inflammation （macrophage polarization）， oxidative stress， epithelial-mesenchymal transition （EMT）， autophagy inhibition and other related signaling pathways， while few studies systematically explain the relationship between the signaling pathways and TCM theory. According to the theory of TCM， lung collateral obstruction is the basic pathogenesis of IPF. Therefore， according to the principle of dredging and replenishing lung collaterals， IPF can be treated with the methods of reinforcing healthy qi and eliminating pathogen， replenishing qi and activating blood， and detoxifying and dredging collaterals， which demonstrate definite curative effect and can effectively relieve clinical symptoms， restore the lung function and blood oxygen partial pressure， improve the quality of life of patients， and reduce adverse reactions. Experimental studies have found that dredging and replenishing lung collaterals have significant effects on IPF inflammation （macrophage polarization）， oxidative stress， EMT， autophagy inhibition and other signaling pathways. Therefore， from the perspective of impediment， this article reviews pathogenesis of IPF， the research progress in TCM treatment of IPF， and the treatment of IPF from active components， single herbs， and compound prescriptions of TCM， with the aim of revealing the scientific connotation of the treatment of IPF from impediment and providing a new theoretical basis for enriching the TCM methods of treating IPF.

Objective: To investigate the relationship between physical development indicators and the onset and progression of myopia among children and adolescents, so as to provide theoretical support for coordinated vision and physical health management. Methods: A prospective cohort study was conducted. In September 2022, 3 102 students from grade one in primary school to grade three in junior high school (five year primary school and four year junior high school) from six schools in Huantai County, Shandong Province, were selected using multistage cluster random sampling method to participate in an epidemiological survey on myopia, with follow up completed in September 2023. Follow up value minus baseline value( d ) was used to assess changes in physical development and vision indicators. Multivariate Logistic regression analysis was used to examine the relationship between physical development indicators and the incidence of myopia. Generalized linear models were established to analyze the relationship between physical development indicators and changes in d spherical equivalent (SE) and d axial length (AL) . Results: Multivariate Logistic regression analysis showed that, after adjusting for factors such as gender, age, and baseline body mass index, the third ( Q 3)and fourth ( Q 4)quartiles of d height showed increased risks of myopia onset within one year compared to the first quartile( Q 1) ( OR =1.85,95% CI =1.18-2.88; OR =1.74,95% CI =1.09-2.78,both P ＜0.05). Results from the generalized linear model indicated that, after adjusting for confounding factors such as gender, age, and baseline SE, d SE was negatively correlated with d height and d weight in children and adolescents ( β =-0.024, 95% CI =-0.031 to -0.018; β =-0.006, 95% CI =-0.011 to -0.001), d AL was positively correlated with d height and d weight in children and adolescents ( β =0.011, 95% CI =0.008-0.013; β =0.005, 95% CI =0.003-0.007) (all P ＜0.05). Conclusions Physical development indicators in children and adolescents were associated with the onset and progression of myopia. Dynamic monitoring and early intervention of myopia should be strengthened for children and adolescents with rapid height and weight gain to achieve coordinated management of myopia and physical development.

Objective: To investigate the distribution of pupil diameter and its association with myopia in school age children, providing ideas into the mechanisms of the role of pupil diameter in the onset and development of myopia. Methods: Adopting a combination of stratified cluster random sampling and convenience sampling method, 3 839 children from six schools in Shandong Province were included in September 2021. Pupil diameters distribution was analyzed by age, sex, and myopic status. Pearson correlation analysis was used to assess the relationship between pupil diameter and cycloplegic spherical equivalent (SE), as well as axial length (AL) and other variables. Propensity score matching (PSM) was applied to match myopic and non myopic children at a 1∶1 ratio based on age and sex. A generalized linear model (GLM) was constructed with pupil diameter as the dependent variable to identify independent factors influencing pupil size and its association with myopia. Results: The mean pupil diameter of school age children was (5.77±0.80)mm. Pupil diameter exhibited a significant increasing trend with age ( F =49.34， P trend ＜ 0.01). Myopic children had a significantly larger mean pupil diameter [(6.10±0.73)mm] compared to non myopic children [(5.62±0.79)mm] with a statistically significant difference( t=18.10, P <0.01). Multivariable GLM analysis, adjusted for age, amplitude of accommodation, and uncorrected visual acuity, revealed a negative correlation between pupil diameter and cycloplegic SE (before PSM: β =-0.089, after PSM: β =-0.063, both P ＜0.01). Conclusions Myopic school age children exhibite larger pupil diameters than their non myopic counterparts. Pupil diameter may serve as a potential indicator for monitoring myopia development in school age children.

This study aims to investigate the medication rules of patented traditional Chinese medi-cine(TCM)compound formulas and molecular mechanisms of core drugs for treating sepsis using data mining and network pharmacology approaches.In the present study,we first searched the PubMed database,Web of Science database,and the China National Knowledge Infrastructure(CNKI)since the establishment of the library to April 30,2024 for the relevant literature on the treatment of sepsis by traditional Chinese medicine.The prescriptions were then statistically ana-lyzed for drug frequency and association analysis to obtain the core drugs.Then we screened the ef-fective active ingredients of the core drugs by TCMSP and other database platforms,obtained sep-sis-related genes in GeneCards and other databases,and statistically intersected targets,and predic-ted the mechanism of action of the core TCMs by subjecting the intersected targets to PPI analy-sis,GO function and KEGG pathway enrichment analysis.Finally,the relationship between key tar-gets and herbal components was examined in reverse by molecular docking method.The results showed that 64 compound formulas were obtained,with a total of 150 Chinese medicines,which were mostly sweet in taste,cold in nature,and belonged to the spleen,stomach and intestinal me-ridians.According to the association rules,the core drugs were identified as"mirabilite-peach ker-nel-rheum officinale".There were 79 intersecting targets between the core drugs and sepsis,with core targets such as IL-1β,EGFR and SRC.MAPK,TNF,IL-17 and other signaling pathways are involved to mediate inflammatory responses,apoptosis and other biological processes to exert ther-apeutic effects on sepsis.The molecular docking results indicated that the docking activity of the key targets with the main components of the drug,and sennoside E_qt has the lowest binding ener-gy and the best docking activity with SRC.In conclusion,this study showed that the prescription of Chinese medicine for sepsis is mostly based on tonifying the spleen and clearing heat.The mecha-nism of action of the core drug"mirabilite-peach kernel-rheum officinale"in the treatment of sep-sis is multilevel and multifaceted,which provides a certain theoretical basis for the treatment of sepsis by traditional Chinese medicine.

To observe the effect of penthorum chinense pursh(PCP)on diarrhea in weaned pig-lets,and to explore its mechanism through network pharmacology and in vivo animal experiments.Animal experiment 1 A total of 160 1-day-old piglets were randomly divided into control group,low-dose prevention group(0.25％),medium-dose prevention group(0.50％)and high-dose pre-vention group(1.00％).Starting from the 14 th day,0.25％,0.50％and 1.00％PCP were added to the basal diet of the three prevention groups and weaned.PCP was stopped on the 29th day,and the diarrhea rate of piglets was recorded for 35 d.In animal experiment 2,35 4-week-old male Kunming mice were randomly divided into 5 groups(control group,LPS group,low-dose group,medium-dose group and high-dose group)for 8 d.The low-dose group,the medium-dose group and the high-dose group were intragastrically administered with 200,400 and 800 mg/kg PCP for 7 consecutive days,respectively.The control group and the LPS group were intragastrically administered with the same amount of sterile saline.On the 8th day of the experiment,except that the Control group was intraperitoneally injected with sterile normal saline,the other groups were intraperitoneally injec-ted with the same amount of LPS(15 mg/kg)to establish an intestinal injury model.HE staining was used for ileal histopathological observation,and fluorescence quantitative PCR was used to de-tect the expression levels of inflammatory factors and tight junction protein mRNA.The TCMSP database was used to screen the active components and targets of PCP,and the GeneCards database was used to obtain the targets of diarrhea.The targets of PCP and diarrhea were imported into Li-anchuan biological cloud platform,and the Venn diagram was obtained after intersection.The pro-tein-protein interaction(PPI)network was constructed by combining Cytoscape 3.7.1 and STRING database,and GO and KEGG enrichment analysis was performed by KOBAS-i platform.The results showed that compared with the control group,the diarrhea rate of weaned piglets in the low-dose prevention group(0.25％),the medium-dose prevention group(0.50％),and the high-dose prevention group(1.00％)was significantly reduced at 28-62 d(P＜0.05).According to the prediction of network pharmacology,there were 32 corresponding targets of 145 potential com-ponents of PCP,6 332 targets of diarrhea,and 118 intersection targets.The protective mechanism of PCP in the treatment of diarrhea may be related to NF-κB and PI3k-Akt signaling pathways.Further experiments confirmed that compared with the LPS group,PCP can significantly improve the pathological state of ileum in mice,the mRNA expression level of intestinal tight junction pro-tein Occludin(P＜0.05)was reversed.At the same time,PCP also significantly down-regulated the mRNA level of NF-κB.The results showed that PCP may alleviate diarrhea in piglets through multiple targets and multiple pathways.The main mechanism may be related to the inhibition of Akt-NF-κB signaling pathway.This study is conducive to providing a theoretical basis for the clini-cal application of PCP.

Objective:To evaluate the efficacy of shockwave therapy,acupuncture,hyperthermia,biofeedback therapy,elec-trical nerve stimulation,magnetotherapy and ultrasound therapy in the treatment of chronic prostatitis/chronic pelvic pain syndrome(CP/CPPS),and to provide evidence-based support for clinical decision-making.Methods:Two researchers independently searched PubMed,Web of Science,Embase,Cochrane Library,CNKI,Wanfang,VIP and Chinese Biomedical Literature databases for randomized controlled trials(RCTs)on the effects of different interventions on CP/CPPS from the establishment of the databases to August 2024.We evaluated the quality of the included literature and extracted the relevant data according to the Cochrane Handbook for Systematic Reviews of Interventions,followed by network meta-analysis using Revman 5.3,R 4.33 and Stata17 software.Results:A total of 25 RCTs involving 1 794 cases were included.The results of network meta-analysis showed that electrical nerve stimulation,shockwave therapy,biofeedback therapy,magnetotherapy,ultrasound therapy and acupuncture were significantly superior to conventional medication and placebo in the total NIH-CPSI scores(P＜0.05),and so were electrical nerve stimulation and shock-wave therapy to acupuncture and hyperthermia(P＜0.05),magnetic therapy to hyperthermia,and ultrasound therapy to placebo(P＜0.05).Shockwave therapy,biofeedback therapy,electrical nerve stimulation,magnetotherapy and ultrasound therapy achieved re-markably better clinical efficacy than conventional medication and placebo in the treatment of CP/CPPS,and so did shockwave therapy than electrical nerve stimulation,hyperthermia,ultrasonic therapy,magnetotherapy and acupuncture.Conclusion:For the treat-ment of CP/CPPS,electrical nerve stimulation is advantageous over the other interventions in improving total NIH-CPSI scores,and shockwave therapy is advantageous in relieving pain symptoms and clinical efficacy.This conclusion,however,needs to be further veri-fied by more high-quality clinical studies.

To observe the effect of penthorum chinense pursh(PCP)on diarrhea in weaned pig-lets,and to explore its mechanism through network pharmacology and in vivo animal experiments.Animal experiment 1 A total of 160 1-day-old piglets were randomly divided into control group,low-dose prevention group(0.25％),medium-dose prevention group(0.50％)and high-dose pre-vention group(1.00％).Starting from the 14 th day,0.25％,0.50％and 1.00％PCP were added to the basal diet of the three prevention groups and weaned.PCP was stopped on the 29th day,and the diarrhea rate of piglets was recorded for 35 d.In animal experiment 2,35 4-week-old male Kunming mice were randomly divided into 5 groups(control group,LPS group,low-dose group,medium-dose group and high-dose group)for 8 d.The low-dose group,the medium-dose group and the high-dose group were intragastrically administered with 200,400 and 800 mg/kg PCP for 7 consecutive days,respectively.The control group and the LPS group were intragastrically administered with the same amount of sterile saline.On the 8th day of the experiment,except that the Control group was intraperitoneally injected with sterile normal saline,the other groups were intraperitoneally injec-ted with the same amount of LPS(15 mg/kg)to establish an intestinal injury model.HE staining was used for ileal histopathological observation,and fluorescence quantitative PCR was used to de-tect the expression levels of inflammatory factors and tight junction protein mRNA.The TCMSP database was used to screen the active components and targets of PCP,and the GeneCards database was used to obtain the targets of diarrhea.The targets of PCP and diarrhea were imported into Li-anchuan biological cloud platform,and the Venn diagram was obtained after intersection.The pro-tein-protein interaction(PPI)network was constructed by combining Cytoscape 3.7.1 and STRING database,and GO and KEGG enrichment analysis was performed by KOBAS-i platform.The results showed that compared with the control group,the diarrhea rate of weaned piglets in the low-dose prevention group(0.25％),the medium-dose prevention group(0.50％),and the high-dose prevention group(1.00％)was significantly reduced at 28-62 d(P＜0.05).According to the prediction of network pharmacology,there were 32 corresponding targets of 145 potential com-ponents of PCP,6 332 targets of diarrhea,and 118 intersection targets.The protective mechanism of PCP in the treatment of diarrhea may be related to NF-κB and PI3k-Akt signaling pathways.Further experiments confirmed that compared with the LPS group,PCP can significantly improve the pathological state of ileum in mice,the mRNA expression level of intestinal tight junction pro-tein Occludin(P＜0.05)was reversed.At the same time,PCP also significantly down-regulated the mRNA level of NF-κB.The results showed that PCP may alleviate diarrhea in piglets through multiple targets and multiple pathways.The main mechanism may be related to the inhibition of Akt-NF-κB signaling pathway.This study is conducive to providing a theoretical basis for the clini-cal application of PCP.

Human naïve pluripotent stem cells (PSCs) hold great promise for embryonic development studies. Existing induction and culture strategies for these cells, heavily dependent on MEK inhibitors, lead to widespread DNA hypomethylation, aberrant imprinting loss, and genomic instability during extended culture. Here, employing high-content analysis alongside a bifluorescence reporter system indicative of human naïve pluripotency, we screened over 1,600 chemicals and identified seven promising candidates. From these, we developed four optimized media-LAY, LADY, LUDY, and LKPY-that effectively induce and sustain PSCs in the naïve state. Notably, cells reset or cultured in these media, especially in the LAY system, demonstrate improved genome-wide DNA methylation status closely resembling that of pre-implantation counterparts, with partially restored imprinting and significantly enhanced genomic stability. Overall, our study contributes advancements to naïve pluripotency induction and long-term maintenance, providing insights for further applications of naïve PSCs.
Humans ; DNA Methylation/drug effects* ; Genomic Instability ; Pluripotent Stem Cells/metabolism* ; Cell Culture Techniques/methods* ; Cells, Cultured

This study aimed to comprehensively examine the association of gallstones, cholecystectomy, and cancer risk. Multivariable logistic regressions were performed to estimate the observational associations of gallstones and cholecystectomy with cancer risk, using data from a nationwide cohort involving 239 799 participants. General and gender-specific two-sample Mendelian randomization (MR) analysis was further conducted to assess the causalities of the observed associations. Observationally, a history of gallstones without cholecystectomy was associated with a high risk of stomach cancer (adjusted odds ratio (aOR)=2.54, 95% confidence interval (CI) 1.50-4.28), liver and bile duct cancer (aOR=2.46, 95% CI 1.17-5.16), kidney cancer (aOR=2.04, 95% CI 1.05-3.94), and bladder cancer (aOR=2.23, 95% CI 1.01-5.13) in the general population, as well as cervical cancer (aOR=1.69, 95% CI 1.12-2.56) in women. Moreover, cholecystectomy was associated with high odds of stomach cancer (aOR=2.41, 95% CI 1.29-4.49), colorectal cancer (aOR=1.83, 95% CI 1.18-2.85), and cancer of liver and bile duct (aOR=2.58, 95% CI 1.11-6.02). MR analysis only supported the causal effect of gallstones on stomach, liver and bile duct, kidney, and bladder cancer. This study added evidence to the causal effect of gallstones on stomach, liver and bile duct, kidney, and bladder cancer, highlighting the importance of cancer screening in individuals with gallstones.
Humans ; Mendelian Randomization Analysis ; Gallstones/complications* ; Female ; Male ; Cholecystectomy/statistics & numerical data* ; Middle Aged ; Risk Factors ; Aged ; Adult ; Neoplasms/etiology* ; Stomach Neoplasms/epidemiology*