OBJECTIVE: To observe the efficacy and safety of eye transcutaneous electrical acupoint stimulation (Eye-TEAS) on preventing the progression of pre-myopic to myopia in children aged 6-12 years. METHODS: A total of 170 pre-myopic children aged 6-12 years were randomly divided into an Eye-TEAS group (85 cases, 3 cases dropped out, 2 cases were eliminated) and a placebo Eye-TEAS group (85 cases, 3 cases dropped out, 2 cases were eliminated). The Eye-TEAS group received Eye-TEAS intervention at bilateral Cuanzhu (BL2), Yuyao (EX-HN4), Sizhukong (TE23), Taiyang (EX-HN5), Sibai (ST2), and Jingming (BL1), with continuous wave at a frequency of 4 Hz and a current of 1-2 mA for 30 min per session. The placebo Eye-TEAS group received sham intervention with the same equipment and procedure, but no electrical stimulation. Both groups received intervention once every other day, at least 3 times a week, for a duration of 20 weeks. After intervention and during the 28-week follow-up period after the intervention completion, the changes in axial length (AL), spherical equivalent refraction (SER), and the incidence of myopia were compared between the two groups. Adherence and safety during the intervention period were also evaluated. RESULTS: Compared before intervention, both groups showed an increase in AL after the intervention and during the follow-up (P<0.01). The AL during follow-up was higher than that after the intervention in the two groups (P<0.01). The Eye-TEAS group exhibited a smaller change in AL than the placebo Eye-TEAS group after the intervention and during follow-up (P<0.01, P<0.05). Compared before intervention, both groups showed a decrease in SER after the intervention and during follow-up (P<0.01). The SER during follow-up was lower than that after the intervention in the two groups (P<0.01). The Eye-TEAS group had a higher SER than the placebo Eye-TEAS group after the intervention (P<0.05). The Eye-TEAS group exhibited a smaller change in SER than the placebo Eye-TEAS group after the intervention and during follow-up (P<0.01). The incidence of myopia in the Eye-TEAS group was lower than that in the placebo group during follow-up (20.0% [14/70] vs 34.7% [25/72], P<0.05). Both groups had good adherence, with no adverse events related to the intervention. CONCLUSION Eye-TEAS can delay the progression of pre-myopic to myopia in children, and has a high safety profile.
Humans ; Child ; Male ; Female ; Acupuncture Points ; Myopia/prevention & control* ; Transcutaneous Electric Nerve Stimulation ; Treatment Outcome ; Disease Progression

The circadian clock plays a critical role in regulating various physiological processes, including gene expression, metabolic regulation, immune response, and the sleep-wake cycle in living organisms. Post-translational modifications (PTMs) are crucial regulatory mechanisms to maintain the precise oscillation of the circadian clock. By modulating the stability, activity, cell localization and protein-protein interactions of core clock proteins, PTMs enable these proteins to respond dynamically to environmental and intracellular changes, thereby sustaining the periodic oscillations of the circadian clock. Different types of PTMs exert their effects through distincting molecular mechanisms, collectively ensuring the proper function of the circadian system. This review systematically summarized several major types of PTMs, including phosphorylation, acetylation, ubiquitination, SUMOylation and oxidative modification, and overviewed their roles in regulating the core clock proteins and the associated pathways, with the goals of providing a theoretical foundation for the deeper understanding of clock mechanisms and the treatment of diseases associated with circadian disruption.
Protein Processing, Post-Translational/physiology* ; Circadian Rhythm/physiology* ; Humans ; Animals ; CLOCK Proteins/physiology* ; Circadian Clocks/physiology* ; Phosphorylation ; Acetylation ; Ubiquitination ; Sumoylation

OBJECTIVE: To assess the efficacy of Qingda Granule (QDG) in ameliorating hypertension-induced cardiac damage and investigate the underlying mechanisms involved. METHODS: Twenty spontaneously hypertensive rats (SHRs) were used to develope a hypertension-induced cardiac damage model. Another 10 Wistar Kyoto (WKY) rats were used as normotension group. Rats were administrated intragastrically QDG [0.9 g/(kg•d)] or an equivalent volume of pure water for 8 weeks. Blood pressure, histopathological changes, cardiac function, levels of oxidative stress and inflammatory response markers were measured. Furthermore, to gain insights into the potential mechanisms underlying the protective effects of QDG against hypertension-induced cardiac injury, a network pharmacology study was conducted. Predicted results were validated by Western blot, radioimmunoassay immunohistochemistry and quantitative polymerase chain reaction, respectively. RESULTS: The administration of QDG resulted in a significant decrease in blood pressure levels in SHRs (P<0.01). Histological examinations, including hematoxylin-eosin staining and Masson trichrome staining revealed that QDG effectively attenuated hypertension-induced cardiac damage. Furthermore, echocardiography demonstrated that QDG improved hypertension-associated cardiac dysfunction. Enzyme-linked immunosorbent assay and colorimetric method indicated that QDG significantly reduced oxidative stress and inflammatory response levels in both myocardial tissue and serum (P<0.01). CONCLUSIONS Both network pharmacology and experimental investigations confirmed that QDG exerted its beneficial effects in decreasing hypertension-induced cardiac damage by regulating the angiotensin converting enzyme (ACE)/angiotensin II (Ang II)/Ang II receptor type 1 axis and ACE/Ang II/Ang II receptor type 2 axis.
Animals ; Drugs, Chinese Herbal/therapeutic use* ; Hypertension/pathology* ; Renin-Angiotensin System/drug effects* ; Rats, Inbred SHR ; Oxidative Stress/drug effects* ; Male ; Rats, Inbred WKY ; Blood Pressure/drug effects* ; Myocardium/pathology* ; Rats ; Inflammation/pathology*

Long-term hypertension causes excessive vascular remodeling and leads to adverse cardiovascular events. Balance of ubiquitination and deubiquitination has been linked to several chronic conditions, including pathological vascular remodeling. In this study, we discovered that the expression of ubiquitin-specific protease 25 (USP25) is significantly up-regulated in angiotensin II (Ang II)-challenged mouse aorta. Knockout of Usp25 augments Ang II-induced vascular injury such as fibrosis and endothelial to mesenchymal transition (EndMT). Mechanistically, we found that USP25 interacts directly with Forkhead box O3 (FOXO3) and removes the K63-linked ubiquitin chain on the K258 site of FOXO3. We also showed that this USP25-mediated deubiquitination of FOXO3 increases its binding to light chain 3 beta isoform and autophagosomic-lysosomal degradation of FOXO3. In addition, we further validated the biological function of USP25 by overexpressing USP25 in the mouse aorta with AAV9 vectors. Our studies identified FOXO3 as a new substrate of USP25 and showed that USP25 may be a potential therapeutic target for excessive vascular remodeling-associated diseases.

ObjectiveA rapid method for identification of chemical constituents in Baoyuantang reference sample was established in order to clarify the material basis of this formula. MethodBased on ultra-performance liquid chromatography-quadrupole-time-of-flight mass spectrometry（UPLC-Q-TOF-MS/MS） and self-established database information， the chemical components in Baoyuantang were systematically characterized and identified. The chromatography was performed on a Waters ACQUITY UPLC HSS T3 column（2.1 mm×100 mm， 1.8 μm） with mobile phase of 0.1% formic acid aqueous solution（A）-0.1% formic acid acetonitrile solution（B） for gradient elution（0-3 min， 2%-19%B； 3-8 min， 19%B； 8-8.1 min， 19%-22%B； 8.1-14 min， 22%-29%B； 14-16 min， 29%B； 16-32 min， 29%-45%B； 32-32.1 min， 45%-90%B； 32.1-35 min， 90%-95%B； 35-36 min， 95%-98%B； 36-37 min， 98%-2%B； 37-40 min， 2%B）. Based on electrospray ionization（ESI）， continuum data format was collected in both positive and negative ion modes with a scanning range of m/z 50-1 500. Chemical constituents in the decoction of Baoyuantang were systematically analyzed by UNIFI 1.9.4 software matching， control comparison， The Encyclopedia of Traditional Chinese Medicine（ETCM） database search and literature reports. ResultA total of 229 components were identified under negative ion mode and 181 under positive ion mode， with a total of 322 components after removing duplicates， including 116 triterpene saponins， 66 flavonoids， 19 organic acids， 6 gingerphenols， 6 gingerols， 5 gingerones， 10 amino acids， 7 saccharides， 5 coumarins and 82 other components. Among them， 83， 141， 39， 35 and 38 components were attributed to Ginseng Radix et Rhizoma， Glycyrrhizae Radix et Rhizoma， Astragali Radix， Cinnamomi Cortex and Zingiberis Rhizoma Recens， respectively. ConclusionIn this study， the rapid characterization and identification of multi-class components in Baoyuantang was realized， and it was confirmed that the material basis of this formula was mainly triterpenoid saponins， flavonoids， gingerols and organic acids， and the chemical composition was attributed and analyzed， which provided a reference for the subsequent quality control research.

Cation exchange chromatography, as a commonly used separation and purification technique in biopharmaceutical manufacturing, is often employed for downstream processes to separate target monoclonal antibodies from their charge variants. For samples with complex and poorly resolved charge variant profiles, the collection solely based on ultraviolet detection does not provide specific compositional information for individual charge variants, making it challenging to determine the range of pooled fractions directly. Subsequent laborious fractionation analysis is then required to guide collection according to production requirements. A mechanistic model for the cation exchange chromatography process of the target monoclonal antibody's critical components was established, and it was employed to assist in product collection. The model accurately predicted the elution peak shapes of the modeled variants, with a root mean square error between predicted and actual values below 0.009. In comparison to the online ultraviolet-based collection method, the model-assisted collection method not only visualized the chromatographic process but also increased the relative productivity by fourfold while ensuring compliance rate.

Aim To analyze the differences in plasma biomarkers and metabolic pathways between Atractylodes chinensis and Atractylodes coreana after intervention in spleen deficiency rats, and discuss the spleen strengthening mechanism of the two from a non targeted metabolomics perspective. Methods A spleen deficiency model was established in SD rats using a composite factor method of improper diet, excessive fatigue, and bitter cold diarrhea. To determine the content of gastrointestinal and immunological indicators, UHPLC-QE-MS technology was used, combined with principal component analysis (PC A) and orthogonal projections to latent structures-discriminant analysis (OPLS-DA) methods to search for biomarkers in plasma of spleen deficiency rats, and metabolic pathways were induced using the Pathway database. Results After administration of Atractylodes chinensis and Atractylodes coreana, various indicators in plasma of spleen deficiency rats showed varying degrees of regression. Metabolomics analysis showed that Atractylodes chinensis and Atractylodes coreana respectively recalled 70 and 82 plasma differential metabolites. Atractylodes chinensis mainly regulated two metabolic pathways : "Glycine, serine, and threonine metabolism, and "Thiamine metabolism". Atractylodes coreana mainly regulated five metabolic pathways, "Glycine, serine, and threonine metabolism", "Thiamine metabolism, "Pyrimidine metabolism", "Butanoate metabolism", and "Riboflavin metabolism". Conclusions Both Atractylodes chinensis and Atractylodes coreana have certain regulatory effects on spleen deficiency rats, and their mechanism of action may be related to regulating metabolic pathways such as "Glycine, serine, and threonine metabolism, and "Thiamine metabolism"in spleen deficiency.

Objective To explore the magnetic resonance imaging(MRI)manifestations of acute cerebral infarction(ACI)and the correlation between lipoprotein-associated phospholipase A2(Lp-PLA2),cystatin C(Cys C)and short-term prognosis.Methods A total of 110 ACI patients admitted to the department of neurology in our hospital from January 1,2022 to January 1,2023 were selected as the study objects.The clinical data and multimodal MRI were collected,and the serum Lp-PLA2 and Cys C levels of patients were detected.The patients were divided into the good prognosis group and the poor prognosis group according to the modified Rankin scale(mRS)score 90 days after onset.The predictive value of MRI manifestations and Lp-PLA2 and Cys C levels for short-term poor prognosis was analyzed.Results There were statistically significant differences in the time from onset to admission,National Institute of Health Stroke Scale(NIHSS)score on admission,hypertension or diabetes,coronary heart disease or atrial fibrillation of patients between the good prognosis group and the poor prognosis group(P<0.05).The proportions of patients with ischemic penumbra,HV positive,cortical-subcortical infarction,large perforating branch infarction,small perforating branch infarction,bilateral anterior circulation infarction,posterior circulation infarction,anterior-posterior circulation infarction,middle cerebral artery(MCA)stenosis or occlusion,both internal carotid artery(ICA)and MCA stenosis or occlusion,posterior cerebral artery(PCA)or vertebral artery(VA)stenosis or occlusion and hemorrhage transformation in the poor prognosis group were significantly higher than those in the good prognosis group(P<0.05).The Lp-PLA2 and Cys C levels of patients in the poor prognosis group were significantly higher than those in the good prognosis group(P<0.05).Small penetrating branch infarction,posterior circulation infarction,anterior-posterior circulation infarction,MCA stenosis or occlusion,both ICA and MCA stenosis or occlusion,hemorrhage transformation,serum Lp-PLA2 and Cys C had certain predictive value for patients with short-term poor prognosis(P<0.05).Conclusion MRI manifestations(ischemic penumbra,HV positivity,different types of cerebral infarction,and vascular stenosis)and serum Lp-PLA2 and Cys C levels can predict the short-term prognosis of ACI patients and provide important reference for the formulation of clinical treatment plans.