Objective To investigate the effects of dapagliflozin on inflammatory factors and prognosis in patients with type 2 diabetes mellitus (T2DM) and acute myocardial infarction (AMI). Methods In a randomized, double-blind trial, 146 patients with T2DM and AMI (within 7 days of onset) were divided into dapagliflozin (dapagliflozin 10 mg/d combining AMI standard therapy) and control (AMI standard therapy) groups, and were followed up for 12 months. Serum levels of interleukin-1β (IL-1β), IL-6, high-sensitivity C reactive protein (hs-CRP) at baseline, 1, 3, 6, and 12 months, and left ventricular ejection fraction (LVEF), brain natriuretic peptide (BNP), and major adverse cardiovascular events (MACE) rate at 12 months were compared between the two groups. Kaplan-Meier curves were used to analyze the cumulative incidences of MACE in the two groups. Results Three patients were withdrawn or dropped out. At 12 months, IL-1β, IL-6, and hs-CRP levels were significantly lower in dapagliflozin group (n＝71) than those in control group (n＝72, P＜0.01), approaching normal levels. Compared with the control group, LVEF was higher (P＜0.01), BNP was lower (P＜0.01), MACE incidence was lower (P＝0.047) in dapagliflozin group at 12 months. Generalized linear mixed models showed significant group-time interactions in IL-1β, IL-6, and hs-CRP (P＜0.001), and these factors declined faster in the dapagliflozin group. Kaplan-Meier curve showed the cumulative incidences of MACE and heart failure were lower in dapagliflozin group than those in non-dapagliflozin group (P＜0.05). Conclusions For patients with T2DM patients and AMI, dapagliflozin has good anti-inflammatory and cardioprotective effects.

Perimenopausal women are more susceptible to fire pathogen disturbances,often resulting in the restlessness of the mind owing to the deficiency and decline of the thoroughfare and conception vessels,as well as the insufficiency of the essence and blood of the viscera.CHENG Zhongling's theory of thief and child fire in Medical Insights proposes that thief fire primarily arises from exogenous pathogen invasion and improper diet,leading to syndromes such as food retention in the stomach or phlegm-fire stagnation.In contrast,child fire is generated endogenously,often owing to liver and kidney deficiency,resulting in an imbalance of water and fire and liver dysfunction,leading to excessive fire transformation.This theory provides a novel perspective for understanding the pathogenesis of perimenopausal insomnia.An in-depth exploration of the role of thief fire and child fire in perimenopausal insomnia is presented,along with a detailed discussion of corresponding treatment strategies.For the invasion of thief fire,therapeutic approaches include ascending and dispersing stagnant fire,clearing and moistening to remove interior heat,purging the heat accumulation to unblock the bowels,and subduing the fire and nourishing yin to eliminate depression.When child fire disturbs the spirit,treatment methods involve smoothing and relieving the liver qi to clear the stagnant heat,nourishing the true yin to restrain the yang,warming and nurturing the primordial qi and harmonizing the nutrient and defensive qi,and guiding and reducing the deficient heat to remove the floating fire.Clinical practice necessitates precise identification of thief and child fire,thorough investigation of exogenous pathogens and internal damage,and careful differentiation between deficiency and excess,as well as the superficial and internal aspects.Strict adherence to the treatment principle of"nourishing the child fire can drive out the thief fire,but driving out the thief fire should not harm the child fire"ensures a balanced approach.By harmonizing the yin and yang of the viscera and allowing the mind to be at ease,this strategy effectively alleviates perimenopausal insomnia.The application of these principles provides a practical and feasible theoretical foundation and practical guidance for the treatment of perimenopausal insomnia using traditional Chinese medicine.

The exploration of pathogenic single nucleotide polymorphisms in the genome plays a pivotal role in the study of human disease-associated genetic mutations. However, there remains a lack of suitable high-throughput screening platforms to investigate the impact of point mutations on genomic structure and function. CRISPR/Cas9-mediated base editors has enabled large-scale annotation of the human genome and phenotypic characterization of monogenic genetic disorders. Base editors, a precise gene-editing technology capable of achieving targeted base substitutions, can be employed to induce mutations at specific functional sites, thereby observing their effects on gene expression, protein function, and cellular phenotypes. Furthermore, integrating base editors with high-throughput screening technologies allows for the large-scale evaluation of multiple candidate sites, accelerating the identification of functional loci and providing a powerful tool for disease research and therapeutic target discovery. This article aims to introduce the working principles of various base editors, including cytosine base editors, adenine base editors, and prime editors, and summarize recent advances in high-throughput screening of functional genomic sites using base-editing techniques.

Objective To determine the material basis of the antioxidant activity of Mori Folium by examining the spec-trum-effect relationship.Methods High-performance liquid chromatography(HPLC)was utilized to establish the fingerprints of Mori Folium.The antioxidant activity of Mori Folium was assessed using the 1,1-diphenyl-2-picrylhydrazyl(DPPH)radical scavenging assay and other related indicators.The spectrum-effect relationship of antioxidation was analyzed using gray relational analysis,bivariate correlation analysis,and partial least squares regression analysis.Molecular docking techniques were employed to predict potential interaction targets.Results HPLC fingerprints for 13 batches of Mori Folium were established,and thirteen common peaks were marked,with similarities ranging from 0.932 to 0.998.Nine common peaks were identified by comparing them to reference substances.Differences in antioxidant activity were observed among the different batches of Mori Folium.Based on the analysis of the spectrum-effect relationship,chemical components such as chlorogenic acid,cryptochlorogenic acid,rutin,and iso-chlorogenic acid B were found to contribute significantly to the antioxidant activity.These components may exert their effects by binding to several antioxidant protein targets,such as XOD,NO-1,and PPAR-α.This implies that Mori Folium might exert its an-tioxidant action via multiple components and targets.Conclusions By integrating the fingerprint and antioxidant activity of Mori Folium,the contributions of individual components to its antioxidant activity were determined.This study provides an experi-mental basis for elucidating the substances responsible for the antioxidant activity of Mori Folium and for establishing quality con-trol methods.

This report described a fetus with prenatal ultrasound findings of microcephaly, lateral ventriculomegaly, and shallow lateral Sylvian fissures, ultimately diagnosed with complex cortical dysplasia with other brain malformations 4 through family-based whole-exome sequencing. At 25 weeks of gestation, prenatal ultrasound revealed fetal microcephaly, mild ventriculomegaly, and shallow Sylvian fissures. Neither chromosomal karyotyping nor chromosomal microarray analysis detected abnormalities. Family-based whole-exome sequencing identified a de novo heterozygous missense variant in TUBG1 gene [c.511G>C (p.Val171Leu)], leading to a diagnosis of complex cortical dysplasia with other brain malformations 4. Following genetic counseling, the pregnancy was terminated.

The exploration of pathogenic single nucleotide polymorphisms in the genome plays a pivotal role in the study of human disease-associated genetic mutations. However, there remains a lack of suitable high-throughput screening platforms to investigate the impact of point mutations on genomic structure and function. CRISPR/Cas9-mediated base editors has enabled large-scale annotation of the human genome and phenotypic characterization of monogenic disorders. Base editors, a precise gene-editing technique capable of achieving targeted base substitutions, can be employed to induce mutations at specific functional sites, thereby observing their effects on gene expression, protein function, and cellular phenotypes. Furthermore, integrating base editors with high-throughput screening technologies allows for large-scale evaluation of multiple candidate sites, accelerating the identification of functional loci and providing a powerful tool for disease research and therapeutic target discovery. This article aims to introduce the working principles of various base editors, including cytosine base editors, adenine base editors, and prime editors, and summarize recent advances in high-throughput screening of functional genomic sites using base-editing techniques.
Humans ; Gene Editing/methods* ; CRISPR-Cas Systems/genetics* ; Genome, Human ; Polymorphism, Single Nucleotide

Hepatolenticular degeneration, also known as Wilson's disease, is a type of autosomal recessive genetic disorder of copper metabolism. The causative gene, ATP7B, is located on the long arm of chromosome 13 and encodes a P-type ATPase that is involved in copper transport. Pathogenic mutations in the ATP7B gene sequence lead to the diminished or lost function of the ATP7B protein, resulting in pathological copper deposition in organs such as the liver, brain, kidneys, and cornea. Currently, the treatment of Wilson's disease primarily involves oral medications to promote copper excretion or reduce copper absorption so as to alleviate the state of illness. However, pharmacological treatment has objective limitations, including the need for lifelong therapy and varying degrees of adverse drug reactions in some patients. Gene therapy can fully correct the genetic defect, restore ATP7B protein function, achieve a curative effect, and improve the patient's quality of life.

Perimenopausal women are more susceptible to fire pathogen disturbances,often resulting in the restlessness of the mind owing to the deficiency and decline of the thoroughfare and conception vessels,as well as the insufficiency of the essence and blood of the viscera.CHENG Zhongling's theory of thief and child fire in Medical Insights proposes that thief fire primarily arises from exogenous pathogen invasion and improper diet,leading to syndromes such as food retention in the stomach or phlegm-fire stagnation.In contrast,child fire is generated endogenously,often owing to liver and kidney deficiency,resulting in an imbalance of water and fire and liver dysfunction,leading to excessive fire transformation.This theory provides a novel perspective for understanding the pathogenesis of perimenopausal insomnia.An in-depth exploration of the role of thief fire and child fire in perimenopausal insomnia is presented,along with a detailed discussion of corresponding treatment strategies.For the invasion of thief fire,therapeutic approaches include ascending and dispersing stagnant fire,clearing and moistening to remove interior heat,purging the heat accumulation to unblock the bowels,and subduing the fire and nourishing yin to eliminate depression.When child fire disturbs the spirit,treatment methods involve smoothing and relieving the liver qi to clear the stagnant heat,nourishing the true yin to restrain the yang,warming and nurturing the primordial qi and harmonizing the nutrient and defensive qi,and guiding and reducing the deficient heat to remove the floating fire.Clinical practice necessitates precise identification of thief and child fire,thorough investigation of exogenous pathogens and internal damage,and careful differentiation between deficiency and excess,as well as the superficial and internal aspects.Strict adherence to the treatment principle of"nourishing the child fire can drive out the thief fire,but driving out the thief fire should not harm the child fire"ensures a balanced approach.By harmonizing the yin and yang of the viscera and allowing the mind to be at ease,this strategy effectively alleviates perimenopausal insomnia.The application of these principles provides a practical and feasible theoretical foundation and practical guidance for the treatment of perimenopausal insomnia using traditional Chinese medicine.

Objective To determine the material basis of the antioxidant activity of Mori Folium by examining the spec-trum-effect relationship.Methods High-performance liquid chromatography(HPLC)was utilized to establish the fingerprints of Mori Folium.The antioxidant activity of Mori Folium was assessed using the 1,1-diphenyl-2-picrylhydrazyl(DPPH)radical scavenging assay and other related indicators.The spectrum-effect relationship of antioxidation was analyzed using gray relational analysis,bivariate correlation analysis,and partial least squares regression analysis.Molecular docking techniques were employed to predict potential interaction targets.Results HPLC fingerprints for 13 batches of Mori Folium were established,and thirteen common peaks were marked,with similarities ranging from 0.932 to 0.998.Nine common peaks were identified by comparing them to reference substances.Differences in antioxidant activity were observed among the different batches of Mori Folium.Based on the analysis of the spectrum-effect relationship,chemical components such as chlorogenic acid,cryptochlorogenic acid,rutin,and iso-chlorogenic acid B were found to contribute significantly to the antioxidant activity.These components may exert their effects by binding to several antioxidant protein targets,such as XOD,NO-1,and PPAR-α.This implies that Mori Folium might exert its an-tioxidant action via multiple components and targets.Conclusions By integrating the fingerprint and antioxidant activity of Mori Folium,the contributions of individual components to its antioxidant activity were determined.This study provides an experi-mental basis for elucidating the substances responsible for the antioxidant activity of Mori Folium and for establishing quality con-trol methods.

The exploration of pathogenic single nucleotide polymorphisms in the genome plays a pivotal role in the study of human disease-associated genetic mutations. However, there remains a lack of suitable high-throughput screening platforms to investigate the impact of point mutations on genomic structure and function. CRISPR/Cas9-mediated base editors has enabled large-scale annotation of the human genome and phenotypic characterization of monogenic genetic disorders. Base editors, a precise gene-editing technology capable of achieving targeted base substitutions, can be employed to induce mutations at specific functional sites, thereby observing their effects on gene expression, protein function, and cellular phenotypes. Furthermore, integrating base editors with high-throughput screening technologies allows for the large-scale evaluation of multiple candidate sites, accelerating the identification of functional loci and providing a powerful tool for disease research and therapeutic target discovery. This article aims to introduce the working principles of various base editors, including cytosine base editors, adenine base editors, and prime editors, and summarize recent advances in high-throughput screening of functional genomic sites using base-editing techniques.