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.

Objective To compare the mid- and long-term clinical results of mitral valve plasty (MVP) and mitral valve replacement (MVR) in the treatment of functional mitral regurgitation (FMR). Methods Patients with FMR who underwent surgical treatment in the Department of Cardiovascular Surgery of the General Hospital of Northern Theater Command from 2012 to 2021 were collected. The patients who underwent MVP were divided into a MVP group, and those who underwent MVR into a MVR group. The clinical data and mid-term follow-up efficacy of two groups were compared. Results Finally 236 patients were included. There were 100 patients in the MVP group, including 53 males and 47 females, with an average age of (61.80±8.03) years. There were 136 patients in the MVR group, including 72 males and 64 females, with an average age of (61.29±8.97) years. There was no statistical difference in baseline data between the two groups (P＞0.05). There was no statistical difference between the two groups in the extracorporeal circulation time, aortic occlusion time, postoperative hospital and ICU stay, intraoperative blood loss, or hospitalization death (P＞0.05), but the time of mechanical ventilation in the MVP group was significantly shorter than that in the MVR group (P=0.022). The total follow-up rate was 100.0%, the longest follow-up was 10 years, and the average follow-up time was (3.60±2.55) years. There were statistical differences in the left atrial diameter, left ventricular end-diastolic diameter, left ventricular end-systolic diameter and cardiac function between the two groups compared with those before surgery (P<0.05). The postoperative left ventricular ejection fraction in the MVP group was statistically higher than that before surgery (P=0.002), but there was no statistical difference in the MVR group before and after surgery (P=0.658). The left atrial diameter in the MVP group was reduced compared with the MVR group (P=0.026). The recurrence rate of mitral regurgitation in the MVP group was higher than that in the MVR group, and the difference was statistically significant (10.0% vs. 1.5%, P=0.003). There were 14 deaths in the MVP group and 19 in the MVR group. The cumulative survival rate (P=0.605) and cardiovascular events-free survival rate (P=0.875) were not statistically significant between the two groups by Kaplan-Meier survival analysis. Conclusion The safety, and mid- and long-term clinical efficacy of MVP in the treatment of FMR patients are better than MVR, and the left atrial and left ventricular diameters are statistically reduced, and cardiac function is statistically improved. However, the surgeon needs to be well aware of the indications for the MVP procedure to reduce the rate of mitral regurgitation recurrence.

Refined operational management is crucial to enhance hospital operational efficiency and achieve sustainable and high-quality development.A large tertiary comprehensive hospital,selected as an observation subject in this study,has har-nessed the value inherent in its extensive operational data,thereby constructing a data-driven operational management framework.Through measures such as developing an operational management system,setting up an operational data hub,and optimizing re-source allocation based on data modeling,this hospital has conducted comprehensive operational analysis at the hospital,depart-ment,and project levels,established a performance management system grounded in data,and enhanced risk prevention and con-trol capabilities,investigating the refined operational management.These efforts have led to incremental improvements in hospital quality,continuous enhancements in operational efficiency,and significant increases in patient and employee satisfaction.

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.

Objective To observe the effects of Bushen Huoxue Prescription on the pathway related to necroptosis of nucleus pulposus cells in a model rabbit of intervertebral disc degeneration;To explore its mechanisms in delaying intervertebral disc degeneration.Methods A intervertebral disc degeneration rabbit model was established using the spinal instability method.Totally 40 model rabbits were randomly divided into model group,ibuprofen group and Bushen Huoxue Prescription low-,medium-and high-dosage groups.Additionally,a normal control group and a sham-operation group were set up,with 8 rabbits in each group.Each treatment groups received the corresponding drugs via gavage for two consecutive weeks.HE staining was used to observe morphology of nucleus pulposus tissue,transmission electron microscopy was used to observe ultrastructure in nucleus pulposus cells,immunohistochemical staining was used to assess the expressions of Aggrecan and Collagen Ⅱ in nucleus pulposus tissue,Western blot was used to detect the expressions of p-RIPK1,p-RIPK3 and p-MLKL protein in nucleus pulposus tissue.Results Compared with the sham-operation group,the model group showed a significant decrease in nucleus pulposus cells,disordered cell arrangement,reduced extracellular matrix,interrupted cell membrane continuity under transmission electron microscopy,organelle swelling,nuclear membrane disruption,partial chromatin loss,and positive expression of Aggrecan and Collagen Ⅱ in nucleus pulposus tissue decreased(P<0.01),while the expressions of p-RIPK1,p-RIPK3 and p-MLKL protein significantly increased(P<0.01).Compared with the model group,the treatment groups showed an increased number of nucleus pulposus cells with orderly arrangement and more extracellular matrix,the ultrastructural damage of the cell membrane,organelle and nucleus in nucleus pulposus cells was partially restored under transmission electron microscopy,the positive expressions of Aggrecan and Collagen Ⅱ significantly increased in Bushen Huoxue Prescription medium-and high-dosage groups and the ibuprofen group(P<0.05,P<0.01),while the expressions of p-RIPK1,p-RIPK3 and p-MLKL protein significantly decreased(P<0.05,P<0.01).Conclusion Bushen Huoxue Prescription may delay intervertebral disc degeneration of the model rabbit by inhibiting the expressions of p-RIPK1,p-RIPK3 and p-MLKL protein in nucleus pulposus cells,and promoting the generation of extracellular matrix components Aggrecan and Collagen Ⅱ.

Objective To observe the effects of Bushen Huoxue Prescription on pressure-induced necroptosis in human nucleus pulposus cells and the expressions of RIPK1/RIPK3/MLKL pathway;To explore its potential mechanism in delaying intervertebral disc degeneration.Methods Human primary nucleus pulposus cells were cultured in vitro,and a model of nucleus pulposus cell degeneration was established using continuous load pressure method.After modeling,the nucleus pulposus cells were divided into model group,Bushen Huoxue Prescription group and inhibitor group,blank serum,Bushen Huoxue Prescription containing serum and necroptotic apoptosis inhibitor(Nec-1)intervention were administered,respectively.Normal group nucleus pulposus cells were cultured routinely.AO/EB fluorescence dual staining method was used for detecting cell apoptosis,flow cytometry was used to detect the necroptosis rate of nucleus pulposus cells,Western blot was used to detect the protein expressions of p-receptor interacting protein kinase(RIPK)1,p-RIPK3 and p-mixed lineage kinase domain like protein(MLKL),RT-qPCR was used to detect the mRNA expressions of RIPK1,RIPK3 and MLKL.Results Compared with the normal group,the model group showed more red fluorescence under AO/EB staining of nucleus pulposus cells,which were round and condensed,the necroptosis rate of nucleus pulposus cells increased(P<0.05),the protein expressions of p-RIPK1,p-RIPK3 and p-MLKL increased(P<0.05,P<0.01),while there was no significant difference in RIPK1 mRNA expression(P>0.05),and RIPK3 and MLKL mRNA expression increased(P<0.01).Compared with the model group,Bushen Huoxue Prescription group and the inhibitor group had less red condensed chromatin in the nucleus pulposus cells,Bushen Huoxue Prescription group had a lower rate of necroptosis(P<0.05),while the inhibitor group showed a decreasing trend in necroptosis rate(P>0.05),the protein expressions of p-RIPK1,p-RIPK3 and p-MLKL decreased in Bushen Huoxue Prescription group and the inhibitor group(P<0.05,P<0.01),while there was no significant difference in RIPK1 mRNA expression(P>0.05),and RIPK3 and MLKL mRNA expressions decreased(P<0.01).Conclusion Bushen Huoxue Prescription can alleviate pressure-induced damage to nucleus pulposus cells and inhibit necroptosis,thereby slowing the progression of intervertebral disc degeneration.Its mechanism may be related to the RIPK1/RIPK3/MLKL pathway mediated necroptosis.

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*