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 Results Three patients were withdrawn or dropped out.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.

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

Various therapeuti modailities have been engineered for lung cancer treatment, but their clinic application is severely impeded by the poor therapy efficiency and immunosuppressive microenvironment. Herein, we fabricated a library of small molecule redox-labile nanoparticles (NPs) (i.e., diPTX-2C NPs, diPTX-2S NPs, and diPTX-2Se NPs) by the self-assembly of dimer paclitaxel (PTX) prodrug, and then utilized these NPs with the traditional Chinese medicine (TCM) Qi-Yu-San-Long-Fang (Q) for effective chemoimmunotherapy on Lewis lung carcinoma (LLC)-bearing mice models. Under the high concentration of glutathione (GSH) and H₂O₂, diPTX-2Se NPs could specifically release PTX in cancer cells and exert a higher selectivity and toxicity than normal cells. In LLC tumor-bearing mice, oral administration of Q not only effectively downregulated programmed death ligand-1 (PD-L1) expression, but also remodeled the immunosuppressive tumor immune microenvironment via the increase of CD4⁺ T and CD8⁺ T cell proportion and the repolarization of M2 into M1 macrophages in tumor tissues, collectively achieving superior synergistic treatment outcomes in combination with intravenous PTX prodrug NPs. Besides, we found that the combination regimen also demonstrated excellent chemoimmunotherapeutic performances on low-dose small established tumor and high-dose large established tumor models. This study may shed light on the potent utilization of Chinese and Western-integrative strategy for efficient tumor chemoimmunotherapy.

The phrase"wood element characterized by spreading harmony"from the Huangdi Neijing five-phase theory summarizes the fundamental nature and functions of the wood element,emphasizing the crucial significance of the harmonious virtue of wood in promoting the generation and transformation of all things.In human physiology,"wood element characterized by spreading harmony"corresponds to the harmonious spreading of liver-gallbladder qi,ensuring smooth liver qi regulation and proper functioning of the ascending-descending movement mechanisms.Bipolar disorder,categorized in traditional Chinese medicine as"depression"or"manic depressive psychosis,"primarily arises from hepatic wood dysfunction.Insufficient wood qi dispersion typically manifests as a depressive phase,whereas excessive dispersion leads to a manic phase,with alternating manic-depressive phase indicating qi movement disorder.By integrating wood qi characteristics,disease pathogenesis of bipolar disorder,and our team's clinical experience in treating emotional disorders,this study developed an integrated acupuncture and moxibustion diagnosis and treatment approach for bipolar disorder,focusing on soothing the liver and regulating spirit,structured as"acupuncture-moxibustion-consolidation."Based on the physiological characteristics of"wood element characterized by spreading harmony,"from liver failing to controll conveyance and dispersion:depressive phase should apply warm-nourishing growth method,manic phase should suppress hyperactive liver for tranquillizing mind method,and alternating manic-depressive phase should apply harmonized rigidity-flexibility method.These methods aim to regulate the spirit of the heart and brain,harmonize the qi movement of the spleen and stomach,and replenish the essence and blood of the liver and kidney.Clinical application through syndrome differentiation has demonstrated satisfactory therapeutic outcomes.

The phrase"wood element characterized by spreading harmony"from the Huangdi Neijing five-phase theory summarizes the fundamental nature and functions of the wood element,emphasizing the crucial significance of the harmonious virtue of wood in promoting the generation and transformation of all things.In human physiology,"wood element characterized by spreading harmony"corresponds to the harmonious spreading of liver-gallbladder qi,ensuring smooth liver qi regulation and proper functioning of the ascending-descending movement mechanisms.Bipolar disorder,categorized in traditional Chinese medicine as"depression"or"manic depressive psychosis,"primarily arises from hepatic wood dysfunction.Insufficient wood qi dispersion typically manifests as a depressive phase,whereas excessive dispersion leads to a manic phase,with alternating manic-depressive phase indicating qi movement disorder.By integrating wood qi characteristics,disease pathogenesis of bipolar disorder,and our team's clinical experience in treating emotional disorders,this study developed an integrated acupuncture and moxibustion diagnosis and treatment approach for bipolar disorder,focusing on soothing the liver and regulating spirit,structured as"acupuncture-moxibustion-consolidation."Based on the physiological characteristics of"wood element characterized by spreading harmony,"from liver failing to controll conveyance and dispersion:depressive phase should apply warm-nourishing growth method,manic phase should suppress hyperactive liver for tranquillizing mind method,and alternating manic-depressive phase should apply harmonized rigidity-flexibility method.These methods aim to regulate the spirit of the heart and brain,harmonize the qi movement of the spleen and stomach,and replenish the essence and blood of the liver and kidney.Clinical application through syndrome differentiation has demonstrated satisfactory therapeutic outcomes.

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.

In order to understand the characteristics of avian leukosis virus(ALV)infection and the polymorphisms of receptor genes Tva,Tvb and NHE1 sequences in different Qingyuan Ma chick-en breeding farms,the isolation and identification of exogenous ALV virus,receptor gene amplifi-cation and sequencing analysis were carried out in five Qingyuan Ma chicken breeding farms.The results of virus isolation and subtype identification showed that the positive rate of exogenous ALV virus isolation in farms A,B and C was less than 5％,among which there was ALV-J infection alone in farm A,mixed infection with ALV-J and ALV-K in farm B,ALV-K infection a-lone in farm C,and no exogenous ALV infection was detected in farm D and E.Polymorphism anal-ysis of recipient genes showed that there were different frequencies of Tvar3,Tvar4 and Tvbr3 re-sistance alleles in A-E farms,and the distribution frequency of Tvar3 was 0.2-0.6,the distribution frequency of Tvar4 was 0.3-0.7,and the distribution frequency of Tvbr3 was 0.1-0.7.In addition,there were Tvar5 resistance alleles in both B and D farms,with a distribution frequency of 0.2.A to-tal of 18 SNP mutations occurred in the NHE1 receptor gene sequence,and further analysis showed that positions 1 279,1 361,1 369,1 406,1 442,and 1 912 were non-synonymous mutations,which could cause changes in amino acids.The study suggested that there were differences in the exogenous ALV and its subtypes among the five Qingyuan Ma chicken breeders,and each farm should have a more targeted and unique purification strategy.The distribution of Tva and Tvb re-sistance alleles at different frequencies,along with the occurrence of 6 non-synonymous mutations in the NHE1 gene,indicate that Qingyuan Ma chicken have the potential of genetic resistance breeding.