Abstract The prevention and control of myopia in Chinese children and adolescents has become a major public health issue. While maintaining increased outdoor activity as a cornerstone intervention, there is an urgent need to explore new complementary approaches that can be effectively implemented in both indoor and outdoor settings. In recent years, environmental spatial frequency has gained increasing attention as one of the key environmental factors influencing the development and progression of myopia. Both animal studies and human research have confirmed that indoor environments lacking mid to high spatial frequency components, often characterized as "visually impoverished", can promote axial elongation and myopia through mechanisms such as disruption of retinal neural signaling, impaired accommodative function, and altered expression of related molecules. Based on the scientific consensus, it is recommended that "enriching of environmental spatial frequency" should be integrated into the myopia prevention and control framework. Following the principles of schoolled organization, family cooperation, community involvement, and student participation, specific measures are put forward in three areas：optimizing school visual settings, improving home spatial environments, and promoting healthy visual behavior. The aim is to create "visually friendly" indoor environments as an important supplement to outdoor activity, thereby providing a novel perspective and strategy for comprehensively advancing myopia prevention and control among children and adolescents.

ObjectiveTo investigate the therapeutic effect of Astragali Radix-mediated changes in gut microbiota on treating type 2 diabetes （T2DM）. MethodsA 12-week randomized， placebo-controlled clinical trial enrolled eighty patients with newly diagnosed type 2 diabetes and poor glycemic control in the Qi deficiency type. All patients received insulin therapy. The observation group （40 cases） was administered with Astragali Radix Granules， while the control group （40 cases） received a placebo. Both treamtents were taken orally twice daily. Changes in gut microbiota were assessed by 16s rDNA sequencing. Serum glucagon-like peptide-1 （GLP-1） levels were measured using enzyme-linked immunosorbent assay （ELISA）. Glucose metabolism indicators including fasting blood glucose （FPG）， 2-hour postprandial blood glucose （2 h PG），glycated albumin（GA）， and glycated hemoglobin （HbA1c） were evaluated. Pancreatic function was evaluated using fasting C-peptide （FCP）， 2-hour postprandial C-peptide （2 h CP）， and C-peptide area under the curve （AUC_cp）. Traditional Chinese medicine （TCM） syndrome scores， clinical efficacy， and safety indicators were also observed. ResultsIn terms of glucose metabolism indicators， compared with the baseline， both groups exhibited significantly lower FPG， 2 h PG， GA and HbA1C （P<0.01），while FCP， 2 h CP and AUC_cp were significantly higher （P<0.01）. Compared with the control group after the treatment， the observation group showed significantly lower FPG， 2 h PG， GA and HbA1C（P<0.05， P<0.01），and significantly higher FCP， 2 h CP and AUC_cp （P<0.05， P<0.01）， indicating that Astragali Radix can improve glucose metabolism. In terms of the diversity of gut microbiota， no significant differences were detected in the Chao1， Shannon and Simpson indexes of the two groups compared with their respective baselines. However， compared with the post-treatment control group， the observation group demonstrated significant increases in the Chao1， Shannon and Simpson indexes （P<0.05， P<0.01）. The β-diversity analysis showed significant separation in gut microbiota composition before and after treatment in both groups， indicating that Astragali Radix can significantly alter the structure and improve the diversity of gut microbiota. At the phylum level， compared with the baseline， both groups showed a significant increase in the relative abundance of Bacteroidota（P<0.01）. The relative abundance of the potentially harmful phylum Proteobacteria was significantly lower in the observation Group after treatment （P<0.01）. Compared with the post-treatment control group， the observation group had a significantly higher relative abundance of Bacteroidota（P<0.01）. No significant difference was found in Firmicutes/Bacteroidota （F/B） ratio between the two groups after treatment， and other phyla showed no significant differences. At the genus level， compared with the baseline， the observation group exhibited a significant increase in Bacteroides （P<0.01） and a significant decrease in Escherichia-Shigella （P<0.01）， whereas no significant difference was seen in the control group . Compared with the control group after treatment， the observation group after treatment had a significantly higher relative abundance of Bacteroides （P<0.01）. No significant differences were seen in other genera. Linear discriminant analysis （LDA） identified potential characteristics taxa： in the observation group， Bacteroidota at the phylum level and Bacteroides and Dubosiella at the genus level， in the control group， Proteobacteria at the phylum level as well as Barnesiella and Staphylococcus at the genus level. Correlation analysis based on a heatmap revealed that GLP-1 levels were positively correlated with Firmicutes， F/B ratio and Fusobacterium， and negatively correlated with Bacteroidota， Proteobacteria， Bacteroides and Escherichia-Shigella. In terms of clinical efficacy， compared with the control group， the total effective rate of the observation group was significantly higher （P<0.05）. Compared with the baseline， the scores for shortness of breath， fatigue， weakness， spontaneous sweating and reluctance to speak significantly decreased in both groups （P<0.01）. Compared with the control group after treatment， the score for weakness was significantly lower in the observation group （P<0.01），indicating that Astragali Radix could improve clinical symptoms and alleviate weakness symptoms. In terms of safety， compared with the baseline， alanine aminotransferase （ALT） levels significantly decreased in both groups （P<0.05，P<0.01），indicating that Astragali Radix did not induce any significant abnormalities in liver and kidney functions. ConclusionAstragali Radix demonstrates the potential to significantly improve the gut microbiota environment in patients of newly diagnosed type 2 diabetes with Qi deficiency. The therapeutic effect may contribute to glycemic control， possibly mediated by an elevation in GLP-1 level. These findings may support its further clinical investigations and potential applications.

Osteonecrosis of femoral head （ONFH） is a disease that causes osteocyte death due to interruption of blood supply of the femoral head， which may cause symptoms such as joint movement disorders， pain， and even femoral head collapse. Currently， the commonly used methods for treating ONFH in clinical practice are accompanied by problems such as long-term side effects， inaccurate efficacy， technical limitations， and complication risks. Traditional Chinese medicine （TCM） has shown unique advantages of holistic regulation， mild side effects， and symptom alleviation. A review of the related literature shows that Salviae Miltiorrhizae Radix et Rhizoma， as a representative Chinese herbal medicine for activating blood and resolving stasis， has the effects of activating blood， resolving stasis， dredging meridians， and relieving pain. Its active ingredients （such as salvianolic acid B， tanshinone Ⅱ_A， and tanshinone Ⅰ） interfere with bone metabolism balance， osteogenesis and differentiation， and improve bone microcirculation and bone microstructure. Salviae Miltiorrhizae Radix et Rhizoma is often combined with the herbal medicines with the effects of tonifying the liver and spleen or activing blood to form herb pairs （such as Salviae Miltiorrhizae Radix et Rhizoma-Angelicae Sinensis Radix， Salviae Miltiorrhizae Radix et Rhizoma-Chuanxiong Rhizoma， and Salviae Miltiorrhizae Radix et Rhizoma-Drynariae Rhizoma）， which enhances the efficacy through synergistic effects. In the application of TCM compound formulas， Bushen Huoxue prescription， Bushen Huoxue capsules， Gubi Tongxiao granules， and Shenggu Zaizao pills can regulate signaling pathways such as Wnt/β-catenin， Hedgehog， Notch， transforming growth factor（TGF）-β₁/Smads， and mitogen-activated protein kinase （MAPK） through multiple targets to significantly improve bone metabolism and hip joint function， playing an important role in preventing and treating ONFH. Through a review of available studies， this paper systematically explains the outstanding advantages of the active ingredients， herb pairs， and compound formulas of Salviae miltiorrhizae Radix et Rhizoma in the prevention and treatment of ONFH. The mechanisms may be related to factors such as promoting osteoblast generation and inhibiting osteoclast formation， increasing osteogenic differentiation， promoting angiogenesis， increasing bone density， inhibiting inflammatory response， and regulating signaling pathways. In the future， modern technology can be employed to optimize dosage forms， and high-quality clinical research should be conducted to further clarify its mechanism of action and promote the precise application of TCM. This review aims to provide more thinking directions for the application of Salviae miltiorrhizae Radix et Rhizoma in preventing and treating ONFH.

BACKGROUND: In the interim analysis of MONARCH plus, adding abemaciclib to endocrine therapy (ET) improved progression-free survival (PFS) and objective response rate (ORR) in predominantly Chinese postmenopausal women with HR+/HER2- advanced breast cancer (ABC). This study presents the final pre-planned PFS analysis. METHODS: In the phase III MONARCH plus study, postmenopausal women in China, India, Brazil, and South Africa with HR+/HER2- ABC without prior systemic therapy in an advanced setting (cohort A) or progression on prior ET (cohort B) were randomized (2:1) to abemaciclib (150 mg twice daily [BID]) or placebo plus: anastrozole (1.0 mg/day) or letrozole (2.5 mg/day) (cohort A) or fulvestrant (500 mg on days 1 and 15 of cycle 1 and then on day 1 of each subsequent cycle) (cohort B). The primary endpoint was PFS of cohort A. Secondary endpoints included cohort B PFS (key secondary endpoint), ORR, overall survival (OS), safety, and health-related quality of life (HRQoL). RESULTS: In cohort A (abemaciclib: n  = 207; placebo: n  = 99), abemaciclib plus a non-steroidal aromatase inhibitor improved median PFS vs . placebo (28.27 months vs . 14.73 months, hazard ratio [HR]: 0.476; 95% confidence interval [95% CI]: 0.348-0.649). In cohort B (abemaciclib: n  = 104; placebo: n  = 53), abemaciclib plus fulvestrant improved median PFS vs . placebo (11.41 months vs . 5.59 months, HR: 0.480; 95% CI: 0.322-0.715). Abemaciclib numerically improved ORR. Although immature, a trend toward OS benefit with abemaciclib was observed (cohort A: HR: 0.893, 95% CI: 0.553-1.443; cohort B: HR: 0.512, 95% CI: 0.281-0.931). The most frequent grade ≥3 adverse events in the abemaciclib arms were neutropenia, leukopenia, anemia (both cohorts), and lymphocytopenia (cohort B). Abemaciclib did not cause clinically meaningful changes in patient-reported global health, functioning, or most symptoms vs . placebo. CONCLUSIONS: Abemaciclib plus ET led to improvements in PFS and ORR, a manageable safety profile, and sustained HRQoL, providing clinical benefit without a high toxicity burden or reduced quality of life. TRIAL REGISTRATION ClinicalTrials.gov (NCT02763566).
Humans ; Female ; Fulvestrant/therapeutic use* ; Breast Neoplasms/metabolism* ; Aminopyridines/therapeutic use* ; Benzimidazoles/therapeutic use* ; Middle Aged ; Aromatase Inhibitors/therapeutic use* ; Aged ; Receptor, ErbB-2/metabolism* ; Adult ; Letrozole/therapeutic use* ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use* ; Anastrozole/therapeutic use*

High-performance liquid chromatography(HPLC) was used to determine the content of three major components in Citri Reticulatae Semen(CRS), including limonin, nomilin, and obacunone. The chromaticity of the CRS sample during salt processing and stir-frying was measured using a color difference meter. Next, the relationship between the color and content of the salt-processed CRS sample was investigated through correlation analysis. By integrating the oil bath technique for processing simulation with HPLC, the changes in the relative content of nomilin and its transformation products were analyzed, with its structural transformation pattern during processing identified. Additionally, RAW264.7 cells were induced with lipopolysaccharides(LPSs) to establish an inflammatory model, and the anti-inflammatory activity of nomilin and its transformation product, namely obacunone was evaluated. The results indicated that as processing progressed, E~*ab and L~* values showed a downward trend; a~* values exhibited a slow increase over a certain period, followed by no significant changes, and b~* values remained stable with no significant changes over a certain period and then started to decrease. The limonin content remained barely unchanged; the nomilin content decreased, and the obacunone increased significantly. The changing trends in content and color parameters during salt-processing and stir-frying were basically consistent. The content of nomilin and obacunone was significantly correlated with the colorimetric values(L~*, a~*, b~*, and E~*ab), while limonin content showed no significant correlation with these values. By analyzing HPLC patterns of nomylin at different heating temperatures and time, it was found that under conditions of 200-250 ℃ for heating of 5-60 min, the content of nomilin significantly decreased, while the obacunone content increased pronouncedly. The in vitro anti-inflammatory activity results indicated that compared to the model group, the group with a high concentration of nomilin and the groups with varying concentrations of obacunone showed significantly reduced release of nitric oxide(NO)(P<0.01). When both were at the same concentration, obacunone showed better performance in inhibiting NO release. In this study, the obvious correlation between the color and content of major components during the processing of CRS samples was identified, and the dynamic patterns of quality change in CRS samples during processing were revealed. Additionally, the study revealed and confirmed the transformation of nomilin into obacunone during processing, with the in vitro anti-inflammatory activity of obacunone significantly greater than that of nomilin. These findings provided a scientific basis for CRS processing optimization, tablet quality control, and its clinical application.
Mice ; Animals ; Drugs, Chinese Herbal/pharmacology* ; RAW 264.7 Cells ; Limonins/chemistry* ; Chromatography, High Pressure Liquid ; Citrus/chemistry* ; Color ; Benzoxepins/chemistry* ; Anti-Inflammatory Agents/chemistry*

Atrial fibrillation (AF) is the most common arrhythmia in clinical practice. It has a high prevalence and poor prognosis. The application of antiarrhythmic drugs and even surgery cannot completely treat the disease, and there are many sequelae. AF can be classified into the category of "palpitation" in Chinese medicine according to its symptoms. Acupuncture has a significant effect on AF. The authors find that an important mechanism of acupuncture in AF treatment is to regulate the cardiac vagus nerve. Therefore, this article intends to review the distribution and function of vagus nerve in the heart, the application and the regulatroy effect for the treatment of AF.
Atrial Fibrillation/physiopathology* ; Humans ; Acupuncture Therapy ; Vagus Nerve/physiology* ; Animals

Objective To investigate the effects of meropenem and amikacin on gut microbiota diversity and composition in a neonatal rat model of necrotizing enterocolitis(NEC).Methods Neonatal SD rats(1～2 d,weighing 5～10 g,both sexes)were subjected to establish a NEC model through artificial formula feeding,hypoxic-cold stress,and lipopolysaccharide(LPS)gavage.The rats were randomly divided into normal control group(Group C,n=12),NEC group(Group N,n=20),meropenem intervention group(Group M,n=20),and amikacin intervention group(Group A,n=20).Following modeling,Group M and Group A received intraperitoneal injections of meropenem(125 mg/kg)or amikacin(468 mg/kg),twice daily for 3 consecutive days.Groups C and N were administered an equal volume of normal saline.At the end of the intervention,colonic contents or fecal samples were collected.The gut microbiota structure was analyzed using 16S rDNA high-throughput sequencing.Bioinformatics analysis was performed using the QIIME2 platform.Alpha diversity was evaluated using Chao1,Shannon,and Simpson indices.Beta diversity was assessed based on Bray-Curtis distance through principal coordinate analysis(PCoA)and non-metric multidimensional scaling(NMDS).Venn and UpSet plots were generated to visualize the composition and overlap of operational taxonomic units(OTUs).Linear discriminant analysis effect size(LEfSe)was applied to identify differentially abundant taxa across groups.Results High-throughput 16S rDNA sequencing showed that the N group had significantly lower 3 indices of α diversity than the C group(P<0.01),that is,a Chao1 index from 230 to 40,a Shannon index from 1.65 to 0.85,and a Simpson index from 0.65 to 0.42.After antibiotic intervention,both the M group and A group obtained obvious increases in the Chao1 index than the N group(P<0.001),with a greater increase observed in the M group than in the A group(P<0.05).However,neither antibiotic group exhibited notable improvements in the Shannon index or Simpson index compared with the N group(P>0.05).Venn and UpSet analyses revealed that the M group had the highest number of unique OTUs(283),while the A group shared the most OTUs(63)with the C group.PCoA and NMDS analyses indicated that the microbial structure of the A group was closer to that of the C group,with better clustering.Taxonomic composition and LEfSe analysis demonstrated that the N group was enriched with potentially pathogenic taxa such as Escherichia coli B2 and Klebsiella under the phylum Proteobacteria,while beneficial bacteria including Lactobacillaceae and Bifidobacteriaceae(phylum Firmicutes)were significantly reduced,indicating severe dysbiosis.In contrast,the A group exhibited a significant increase in beneficial bacteria and a structural tendency toward ecological recovery.The M group,however,was enriched with various conditionally pathogenic and environmentally associated genera,displaying a microbial configuration notably deviating from a healthy state.Conclusion Meropenem and amikacin exhibit differential regulatory effects on the intestinal microbiota in the context of NEC.Amikacin demonstrates superior efficacy in restoring microbial stability and levels of beneficial bacteria,whereas meropenem,although effective for early infection control,warrants caution due to its potential long-term impact on the gut microbiome.

A method for determination and targeted screening of diflorasone components in health products using ultra performance liquid chromatography-quadrupole time of flight mass spectrometry(UPLC-Q-TOF/MS)was established.Four representative diflorasone and esters(diflorasone,diflorasone diacetate,diflorasone-17-propionate,and diflorasone-21-propionate)were selected to optimize the pretreatment conditions,and 10 mL of extraction solvent dosage,15 min of extraction time and 5 g of salting-out agent as the optimal conditions were selected by response surface methodology.The results showed that the four analytes exhibited good linearity within the concentration range of 2.0?100 μg/L with the chromatographic peak area,and the correlation coefficients(R2)were all greater than 0.9990,while the results of recovery and relative standard deviation could satisfy the requirements of determination.The common characteristic ions of diflorasone and esters werem/z121 andm/z335,and their specific structures were obtained by analyzing the cleavage pathway based on the optimized determination conditions.A targeted screening method for other esters of diflorasone based on characteristic ions guidance strategy was established.This method had many advantages such as high efficiency,high sensitivity and good reproducibility,and could be used for targeted screening of diflorasone and esters in health products.The developed characteristic ion guided strategy could be employed to construct mass spectral databases for various glucocorticoids,enabling comprehensive targeted screening across a broad range of compounds.

Metal-organic frameworks(MOFs)are a class of organic-inorganic hybrid materials formed by the self-assembly of metal ions or metal clusters with organic ligands through coordination,and possess high specific surface area,tunable pore size and diverse structures.In recent years,MOFs and their composites have shown great application potential in the field of drug detection,especially in selective recognition,enhancing detection sensitivity and on-site rapid detection.This paper summarized the structural characteristics,synthesis methods and detection principles of MOFs and their composites,and reviewed the latest research progresses in detection of various drugs such as opioids,amphetamines,cannabinoids,cathinones,cocaine,ketamine,fentanyls and psychotropic drugs.The advantages and challenges of MOFs materials in the pretreatment of complex biological samples,sensor construction and on-site rapid detection were discussed,and the prospects for future development were analyzed,with the aim of providing theoretical support and technical references for promoting the applications of MOFs in anti-drug practice.

Forced oscillation technique (FOT) enables early diagnosis of chronic obstructive pulmonary disease (COPD) by quantifying the impedance of COPD patients during normal breathing and reflecting the airway obstruction and distribution of the patients. The flow sensors using in FOT for diagnosis of COPD mainly include differential pressure flow sensors, ultrasonic flow sensors, hot wire gas flow sensors, fiber-optic flow sensors and flow sensors based on friction nanoelectricity technology. In this review, the principles, characteristics, and current application status of these five types of flow sensors were summarized, and their future development prospects were prospected.