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*

"Weibing" is a fundamental concept in traditional Chinese medicine (TCM), representing a transitional state characterized by diminished self-regulatory abilities without overt physiological or social dysfunction. This perspective delves into the biological foundations and quantifiable markers of Weibing, aiming to establish a research framework for early disease intervention. Here, we propose the "Health Quadrant Classification" system, which divides the state of human body into health, sub-health, disease-susceptible state, and disease. We suggest the disease-susceptible stage emerges as a pivotal point for TCM interventions. To understand the intrinsic dynamics of this state, we propose laboratory and clinical studies utilizing time-series experiments and stress-induced disease susceptibility models. At the molecular level, bio-omics technologies and bioinformatics approaches are highlighted for uncovering intricate changes during disease progression. Furthermore, we discuss the application of mathematical models and artificial intelligence in developing early warning systems to anticipate and avert the transition from health to disease. This approach resonates with TCM's preventive philosophy, emphasizing proactive health maintenance and disease prevention. Ultimately, our perspective underscores the significance of integrating modern scientific methodologies with TCM principles to propel Weibing research and early intervention strategies forward.

Flavonoid 3-O-glucosyltransferase (3GT) is a key enzyme in the glucosidation of anthocyanins. To investigate the 3GT gene in rhododendron, we cloned an open reading frame (ORF) of 3GT gene (named Rh3GT) from Rhododendron hybridum Hort (Red cultivar) and then characterized this gene and the deduced protein in terms of the biochemical characteristics, expression level, and enzymatic function. The results showed that Rh3GT had a full length of 993 bp and encoded 330 amino acid residues. The deduced protein was hydrophilic, stable, weak acid, belonging to the glycosyltransferase family (GT-B type), with glutamine (Q) at position 44 in the PSPG box. The phylogenetic analysis showed that Rh3GT was most closely related to Vc3GT from Vaccinium corymbosum and Vm3GT from Vaccinium myrtillus. Rh3GT was expressed in the stems, leaves, and flowers and almost not expressed in the roots, with the highest expression level in petals during full blooming stage. Introduction of pCAMBIAL1302-Rh3GT into petals significantly up-regulated the expression level of Rh3GT and increased the total anthocyanin accumulation. Rh3GT was successfully expressed in Escherichia coli BL21 in the form of inclusion bodies with a size of about 36 kDa. The results of HPLC showed that the recombinant Rh3GT after denaturation, purification, and dilution could catalyze the synthesis of cyanidin and UDP-glucose to synthesize cyanidin 3-O-glucoside, indicating that the expressed protein had 3GT activity. This study provides basic data for further studying the molecular regulation mechanism of anthocyanin biosynthesis and theoretical support for molecular breeding of rhododendron.
Rhododendron/classification* ; Glucosyltransferases/metabolism* ; Cloning, Molecular ; Escherichia coli/metabolism* ; Recombinant Proteins/biosynthesis* ; Anthocyanins/biosynthesis* ; Phylogeny ; Plant Proteins/metabolism* ; Amino Acid Sequence

Objective To investigate the expression of miR-6768-5p in lung cancer tissue and its effect on the proliferation and invasion of lung cancer cells through targeted regulation of carboxypeptidase A4(CPA4).Methods The expression of miR-6768-5p in lung cancer tissues and adjacent tissues was analyzed u-sing the TCGA database.Quantitative real-time PCR(qPCR)was used to detect the expression of miR-6768-5p in human lung cancer cell lines(HCC1588,H1650,H1299,A549,HCC827)and normal alveolar epithelial cells(HPAEpiC cells).Lung cancer cells were transfected with NC mimics and miR-6768-5p mimics,respec-tively,and divided into NC group and miR-6768-5p group.The MTS assay and Matrigel invasion assay were used to detect the cell proliferation and invasion ability of each group,respectively.The putative binding sites of miR-6768-5p and CPA4 were verified using RNAhybrid software and dual-luciferase reporter gene experi-ment.The expression of CPA4 mRNA in each group of cells was detected by qPCR.The expression of AKT/c-MYC signaling pathway proteins in the cells of each group was analyzed by Western blot.Results Com-pared with the adjacent tissues,the relative expression level of miR-6768-5p in lung cancer tissues was signifi-cantly decreased,and the difference was statistically significant(P＜0.05).Compared with HPAEpiC cells,the relative expression level of miR-6768-5p was significantly decreased in lung cancer cell lines,and the differ-ence was statistically significant(P＜0.05).Compared with the NC group,the cell proliferation rate of miR-6768-5p group was significantly decreased(P＜0.05).The number of invasive cells in NC group and miR-6768-5p group was(131.30±12.55)and(37.45±7.77),respectively,and the number of invasive cells in miR-6768-5p group was significantly lower than that in NC group(P＜0.05).The relative expression level of CPA4 mRNA in H1299 cells of miR-6768-5p group was significantly lower than that in NC group(t=4.93,P＜0.05).Compared with the NC group,the expressions of AKT/c-myC signaling pathway proteins p-AKT,p-mTORC1,XIAP,MDM2 and C-myC proteins in miR-6768-5p group were significantly decreased.Conclusion The expression of miR-6768-5p is decreased in lung cancer tissues,and miR-6768-5p may inhibit the activation of AKT/c-MYC signaling pathway by targeting CPA4,and reduce the proliferation and invasion ability of lung cancer H1299 cells.

Objective:To study the biological traits and mutations of the influenza A (H3N2) virus in order to produce a vaccine and offer references for controlling and preventing influenza epidemics.Methods:Four strains of the influenza A(H3N2) virus were chosen from the Huai′an surveillance network laboratory. Nucleic acid extraction, library building, and sequencing (CridION x5 MKI Nanopore) were used to produce the whole-genome sequences. Using homologous alignments of whole-genome sequences, phylogenetic tree construction, and amino acid variant screening, bioinformatics analysis was carried out.Results:The nucleotide identity between 8 gene segments ranged from 97.1% to 100.0%. The gene that differed the most from the reference sequences was HA (97.1%-99.9%), and the gene that differed the least was MP (98.6%-99.9%). The HA gene (3.06%) and MP gene (1.43%) were the regions with the greatest and lowest frequencies of nucleotide site change, respectively. The rates of nucleotide change varied significantly between the genes ( χ2=14.293, P=0.046). Four influenza A(H3N2) virus strains′ whole-genome phylogenies from each of the eight gene segments maintained a roughly consistent topological structure. One strain was linked to the 3C.2a1b.1b clade, which was lost at the 142NWT, 149NGT(HA1), and 436NLS(NA). Three strains were linked to the 3C.2a1b.2a.1a clade lineage. Amantadine and NA inhibitors were effective against all Huai′an strains. Conclusions:The antigenicity of one strain of Huai'an strain changed and its matching with the vaccine strain of that year was low. It is suggested that the genetic surveillance of H3N2 influenza virus should be continuously strengthened to provide scientific basis for influenza prevention and control and influenza vaccine screening.

Objective: To determine the current prevalence of health risk behaviors among college students in Henan Province, and to conduct an in depth analysis of the impact of cumulative ecological risks on health risk behaviors, so as to provide scientific basis for promoting healthy development of adolescents. Methods: Using a multi stage stratified cluster sampling method, 9 743 college students from six universities in Henan Province were included as the research subjects from April to June 2023. A questionnaire survey was conducted using the College Student Cumulative Ecological Risk Scale and the China Urban Adolescent Health Related Behavior Survey Questionnaire (University Version). Data were analyzed by descriptive statistical analysis, Chi square test and binary Logistic regression. Results: The reporting rates of unhealthy eating behavior, unhealthy weight loss behaviors, lack of physical activity, daily risk behaviors, negative emotions, current smoking behavior current drinking behaviors, Internet addiction emotions and dangerous sexual behaviors among college students in Henan Province were 40.2%, 39.5%, 76.0%, 13.7%, 28.1%, 11.3%, 12.7%, 5.9% and 2.2%, respectively. The reporting rates of negative emotions, current smoking behaviors, current drinking behaviors, dangerous sexual behaviors and daily risk behaviors of college students were higher in boys than in girls ( χ 2=44.00, 995.20, 902.49, 121.95, 103.09, P <0.05). In terms of reporting rates of unhealthy diet, unhealthy weight loss and lack of exercise behavior, girls were higher than boys ( χ 2=107.59, 13.01, 145.83, P <0.05). Cumulative ecological risk was positively correlated with overall health risk behaviors. For every unit increase in the cumulative ecological risk index, the risk of health risk behaviors among college students increased by 48%. Conclusions The prevalence of health risk behaviors among college students is relatively common. It should adrocate for a healthy lifestyle, reduce the cumulative ecological risk and the occurrence of health risk behaviors to promote the healthy development of adolescents.

Objective:To investigate the effect of lncRNA AC132217.4 on the proliferation and invasion of liver cancer MHCC97-H cells and its molecular mechanism.Methods:The TCGA database was used to analyze the differential expression of AC132217.4 in liver cancer tissue and adjacent tissue, and to analyze the relationship between the expression level of AC132217.4 and the overall survival of liver cancer patients. Transfection of pcDNA-AC132217.4 plasmid into MHCC97-H cells was defined as AC132217.4 group, transfection of pcDNA plasmid into MHCC97-H cells was defined as negative control (NC) group, respectively. The proliferation and invasion ability of MHCC97-H cells were detected by MTT method and Matrigel invasion assay. The binding site between AC132217.4 and miR-18a-5p was analyzed by starBase v2.0 software and dual luciferase reporter gene assay. Real-time quantitative PCR (RT-qPCR) detected the differential expression of miR-18a-5p in the two groups of MHCC97-H cells. The expression of epithelial-mesenchymal transition protein was detected by Western-blotting. Measurement data with normal distribution were expressed as mean±standard deviation ( ± s), and t-test was used for comparison between the two groups. Results:Compared with adjacent tissues, the expression of AC132217.4 was down-regulated in liver cancer tissues ( P<0.01). Compared with liver cancer patients with low expression of AC132217.4, the overall survival of liver cancer patients with high AC132217.4 expression was longer ( P<0.05). The pcDNA-AC132217.4 plasmid significantly inhibited the proliferation of MHCC97-H cells ( P<0.05). The number of invasive cells in the NC group and AC132217.4 group were (131.30±12.55) and (37.45±7.77), respectively. The pcDNA-AC132217.4 plasmid significantly inhibited the invasive ability of MHCC97-H cells ( t=6.36, P<0.01). AC132217.4 directly complemented miR-18a-5p ( P<0.01). The expression of miR-18a-5p in MHCC97-H cells in AC132217.4 group (1.04±0.30) was significantly lower than that in NC group (6.13±0.75) ( t=6.27, P<0.01). Compared with the NC group, the expressions of epithelial phenotype proteins Cytokeratin and Claudin-1 in MHCC97-H cells in AC132217.4 group were up-regulated, while the expressions of mesenchymal phenotype proteins Vimentin, Slug and Snail were down-regulated. Conclusions:The expression of AC132217.4 is low in liver cancer tissue, and it is related to the overall survival of liver cancer patients. AC132217.4 might inhibit the proliferation and invasion of liver cancer MHCC97-H cells by sponge miR-18a-5p.

Objective:To explore the feasibility of using multivariate statistical analysis to evaluate the quality of Astmgali radix from different habitats. Methods:The contents of Astragaloside saponinⅠ, Astragalus saponin Ⅱ, Astragaloside Ⅲ and Astragaloside A were determined by UPLC-ELSD. The components of astragalus saponins from different habitats were analyzed by TOPSIS and cluster thermogram.Results:TOPSIS analysis showed that the comprehensive quality of Astmgali radix samples from Shanxi, Gansu and Inner Mongolia was related(were 0.297 3, 0.346 0, 0.322 5), and the whole quality of S13 and S14 from Shanxi and N5 from Inner Mongolia were higher than others. Cluster thermogram showed that Astmgali radix was grouped into three groups according to region, and the quality difference of Astmgali radix was mainly reflected on Astragaloside saponinⅠand Astragalus saponin Ⅱ. Conclusions:The theory of multivariate statistical analysis is perfect, objective and reliable. It can be used as a reference for comprehensive quality evaluation of Traditional Chinese Medicine (TCM), selection of excellent germplasm resources and traceability of origin of TCM.

Grape (Vitis vinifera L.) in production is frequently exposed to inadequate light, which significantly affects its agronomic traits via inhibiting their physiological, metabolic and developmental processes. To explore the mechanism how the grape plants respond to the weak light stress, we used 'Yinhong' grape and examined their physiology-biochemistry characteristics and transcriptional profile under different levels of weak light stress. The results showed that grape seedlings upon low intensity shading treatments were not significantly affected. As the shading stress intensity was strengthened, the epidermis cells, palisade tissue, and spongy tissue in the leaves were thinner, the intercellular space between the palisade tissue and spongy tissue was larger compared with that of the control, and the activities of superoxide dismutase, catalase and peroxidase were decreased gradually. Additionally, the soluble protein content increased and the free proline content decreased gradually. Compared with the control, significant changes in plant photosynthetic characteristics and physiology-biochemistry characteristics were observed under high intensity of shading (80%). RNA-seq data showed that the differentially expressed genes between CK and T2, CK and T4, T2 and T4 were 13 913, 13 293 and 14 943, respectively. Most of the enrichment pathways were closely related with the plant's response to stress. Several signaling pathways in response to stress-resistance, e.g. JA/MYC2 pathway and MAPK signal pathway, were activated under weak light stress. The expression level of a variety of genes related to antioxidation (such as polyphenol oxidase and thioredoxin), photosynthesis (such as phytochrome) was altered under weak light stress, indicating that 'Yinhong' grape may activate the antioxidation related pathways to cope with reactive oxygen species (ROS). In addition, it may activate the expression of photosynthetic pigment and light reaction structural protein to maintain the photosynthesis activity. This research may help better understand the relevant physiological response mechanism and facilitate cultivation of grape seedlings under weak light.
Vitis/metabolism* ; Gene Expression Regulation, Plant ; Photosynthesis/genetics* ; Plant Leaves ; Light ; Seedlings/metabolism*

Objective To analyze the chemical compounds of Shenqi Dihuang decoction by the ultraperformance liquid chromatography coupled with linear quadrupole ion trap-orbitrap mass spectrometry (UPLC-LTQ-Orbitrap-MS). Methods Warters ACQUITY UPLC HSS T3 (2.1 mm ×100 mm, 1.8 μm) was used as chromatographic column with mobile phase: 0.1% formic acid water (A)-0.1% formic acid acetonitrile (B) with gradient elution, and flow rate was 0.3 ml/min. Electrospray ion source (ESI) and an electrostatic field orbital ion trap mass analyzer were adopted, which was used to collect mass spectrometry fragment information with positive and negative ion modes, by comparing with the relative retention time of the reference substance. In addition, the fragment information of the mass spectrum was used to identify the compounds. The accurate identification of the chemical components in Shenqi Dihuang decoction was confirmed with literature. Results The study found that UPLC-LTQ-Orbitrap-MS technology could be used to identify 62 chemical components, including 13 aromatic acids, 9 flavonoids, 8 saponins, and 5 aromatic amines, 3 keto acids, 2 phenols, 1 aromatic quinone and other ingredients in Shenqi Dihuang decoction. Conclusion The identification analysis method in this study was efficient and accurate, which could be applied to the identification and analysis of chemical components in Shenqi Dihuang decoction and provided the important experimental data for the research on the material basis and mechanism.