BACKGROUND:Acupuncture at Xinshu(BL 15)can significantly improve cardiac function and protect myocardial cells in acute myocardial ischemia,but the effect and mechanism of thread embedding treatment at Xinshu(BL 15)on cardiac function in acute myocardial ischemia are yet unclear.Nuclear factor κB activation often appears as an intranuclear translocation of the P65 isoform,and activation of the nuclear factor κB signaling pathway is marked by elevated P65 levels.OBJECTIVE:To explore the effects of thread embedding pretreatment at Xinshu(BL 15)on cardiac function and the expression levels of interleukin-10,tumor necrosis factor-α,P65 genes and proteins in rats with acute myocardial ischemia.METHODS:Thirty-two male Sprague-Dawley rats were randomly divided into a blank group,a model group,a Xinshu(BL 15)acupoint group,and a non-meridian/non-acupoint group using a random number table method,with eight rats in each group.Rat models of acute myocardial ischemia were established in the latter three groups.The Xinshu(BL 15)acupoint group had thread embedding at Xinshu(BL 15)for 14 days,followed by subcutaneous injection of isoproterenol hydrochloride into the back to establish an acute myocardial ischemia rat model.The non-meridian/non-acupoint group had local thread embedding for 14 days,and the rest procedures were the same as above.In the model group,Xinshu(BL 15)was only marked,and the rest procedures were the same as above.In the blank group,Xinshu(BL 15)was only marked,and then an equal amount of physiological saline was injected subcutaneously into the back.After 24 hours of modeling,electrocardiogram and cardiac ultrasound were performed.Abdominal aorta blood was extracted for detection of serum creatine kinase and creatine kinase isoenzyme levels using enzyme-linked immunosorbent assay.Subsequently,the rats were euthanized and samples were collected.Hematoxylin-eosin and TUNEL staining were used to observe the pathological changes of myocardial tissue and the apoptosis of myocardial cells.Real-time fluorescence quantitative PCR(RT-qPCR)and western blot were used to detect the mRNA and protein expression of tumor necrosis factor-α,interleukin-10,and P65 in myocardial tissue respectively.RESULTS AND CONCLUSION:(1)Electrocardiogram:Compared with the blank group,the model group,non-meridian/non-acupoint group,and Xinshu(BL 15)acupoint group had significantly elevated ST segment in lead Ⅱ of the electrocardiogram.(2)Cardiac ultrasound:Compared with the model group,the Left ventricular end-systolic dimension in the Xinshu(BL 15)acupoint group were significantly reduced(P＜0.05),while left ventricular ejection fraction and left ventricular fractional shortening rate were significantly increased(P＜0.05).(4)Serum creatine kinase and creatine kinase isoenzyme:Compared with the model group,the Xinshu(BL 15)acupoint group showed a significant decrease in serum creatine kinase and creatine kinase isoenzyme levels(P＜0.05).(4)Hematoxylin-eosin staining:Compared with the model group,the arrangement of myocardial fibers in the Xinshu(BL 15)acupoint group was basically neat,with less edema and a small amount of inflammatory cell infiltration.(5)TUNEL staining:Compared with the model group,the fluorescence intensity of myocardial cell apoptosis in the Xinshu(BL 15)acupoint group was significantly reduced,and its apoptosis rate was significantly reduced(P＜0.05).(6)RT-qPCR and western blot:Compared with the model group,the myocardial tissue interleukin-10 level in the Xinshu(BL 15)acupoint group was significantly increased(P＜0.05),while tumor necrosis factor-α and P65 levels were significantly decreased(P＜0.05).These findings indicate that thread embedding pretreatment at Xinshu(BL 15)can improve cardiac function in rats with acute myocardial ischemia,and its mechanism of action may be related to the inhibition of the activation of the nuclear factor-κB signaling pathway.

BACKGROUND:Acupuncture at Xinshu(BL 15)can significantly improve cardiac function and protect myocardial cells in acute myocardial ischemia,but the effect and mechanism of thread embedding treatment at Xinshu(BL 15)on cardiac function in acute myocardial ischemia are yet unclear.Nuclear factor κB activation often appears as an intranuclear translocation of the P65 isoform,and activation of the nuclear factor κB signaling pathway is marked by elevated P65 levels.OBJECTIVE:To explore the effects of thread embedding pretreatment at Xinshu(BL 15)on cardiac function and the expression levels of interleukin-10,tumor necrosis factor-α,P65 genes and proteins in rats with acute myocardial ischemia.METHODS:Thirty-two male Sprague-Dawley rats were randomly divided into a blank group,a model group,a Xinshu(BL 15)acupoint group,and a non-meridian/non-acupoint group using a random number table method,with eight rats in each group.Rat models of acute myocardial ischemia were established in the latter three groups.The Xinshu(BL 15)acupoint group had thread embedding at Xinshu(BL 15)for 14 days,followed by subcutaneous injection of isoproterenol hydrochloride into the back to establish an acute myocardial ischemia rat model.The non-meridian/non-acupoint group had local thread embedding for 14 days,and the rest procedures were the same as above.In the model group,Xinshu(BL 15)was only marked,and the rest procedures were the same as above.In the blank group,Xinshu(BL 15)was only marked,and then an equal amount of physiological saline was injected subcutaneously into the back.After 24 hours of modeling,electrocardiogram and cardiac ultrasound were performed.Abdominal aorta blood was extracted for detection of serum creatine kinase and creatine kinase isoenzyme levels using enzyme-linked immunosorbent assay.Subsequently,the rats were euthanized and samples were collected.Hematoxylin-eosin and TUNEL staining were used to observe the pathological changes of myocardial tissue and the apoptosis of myocardial cells.Real-time fluorescence quantitative PCR(RT-qPCR)and western blot were used to detect the mRNA and protein expression of tumor necrosis factor-α,interleukin-10,and P65 in myocardial tissue respectively.RESULTS AND CONCLUSION:(1)Electrocardiogram:Compared with the blank group,the model group,non-meridian/non-acupoint group,and Xinshu(BL 15)acupoint group had significantly elevated ST segment in lead Ⅱ of the electrocardiogram.(2)Cardiac ultrasound:Compared with the model group,the Left ventricular end-systolic dimension in the Xinshu(BL 15)acupoint group were significantly reduced(P＜0.05),while left ventricular ejection fraction and left ventricular fractional shortening rate were significantly increased(P＜0.05).(4)Serum creatine kinase and creatine kinase isoenzyme:Compared with the model group,the Xinshu(BL 15)acupoint group showed a significant decrease in serum creatine kinase and creatine kinase isoenzyme levels(P＜0.05).(4)Hematoxylin-eosin staining:Compared with the model group,the arrangement of myocardial fibers in the Xinshu(BL 15)acupoint group was basically neat,with less edema and a small amount of inflammatory cell infiltration.(5)TUNEL staining:Compared with the model group,the fluorescence intensity of myocardial cell apoptosis in the Xinshu(BL 15)acupoint group was significantly reduced,and its apoptosis rate was significantly reduced(P＜0.05).(6)RT-qPCR and western blot:Compared with the model group,the myocardial tissue interleukin-10 level in the Xinshu(BL 15)acupoint group was significantly increased(P＜0.05),while tumor necrosis factor-α and P65 levels were significantly decreased(P＜0.05).These findings indicate that thread embedding pretreatment at Xinshu(BL 15)can improve cardiac function in rats with acute myocardial ischemia,and its mechanism of action may be related to the inhibition of the activation of the nuclear factor-κB signaling pathway.

Objective: To investigate the current status of screening myopia and anxiety symptoms and associated factors among junior and senior high school students in Beijing, so as to provide evidence for myopia prevention and control and the improvement of mental health among adolescents. Methods: From September to November 2024, a total of 17 245 junior high schools, general senior high schools and vocational high schools from 16 districts in Beijing were enrolled by stratified cluster sampling method. Questionnaire surveys and vision screening were conducted to collect data on anxiety symptom and screening diagnosed myopia. The Chi square test was used to analyze the co-occurrence of myopia and anxiety symptoms, and binary Logistic regression analysis was adopted to explore the related factors of the co-occurrence. Results: The overall detection rate of cooccurrence screening myopia and anxiety symptoms among Beijing junior and senior high school students was 6.00%. The detection rate was higher in females ( 7.15 %) than in males (4.90%), higher in urban areas (6.65%) than in suburban areas (5.41%), and higher in general senior high school students (7.61%) than in vocational high school students (6.46%) and junior high school students (4.65%). All differences were statistically significant ( χ 2=38.49, 11.66, 54.88, all P <0.01). Binary Logistic regression analysis showed that female gender ( OR =1.43), general senior high school ( OR =1.60), vocational high school ( OR =1.59), daily sugar sweetened beverage intake ( OR =1.66), participation in academic extracurricular classes in preschool ( OR =1.30), electronic screen use for more than 2 hours per day ( OR =1.21), and insufficient sleep ( OR =2.41) were associated with an increased risk of co-occurring screening diagnosed myopia and anxiety symptoms (all P <0.05). Conclusions The co-occurrence of screening diagnosed of myopia and anxiety symptoms among junior and senior high school students in Beijing is common. Female gender, senior high school students, and unhealthy lifestyle behaviors are all risk factors for the co-occurrence of myopia and anxiety symptom. Comprehensive intervention measures can be adopted to simultaneously promote vision protection and mental health among junior and senior high school students.

Objective: To explore the association between CDKAL1 rs35261542, FAIM2 rs 3205718, and VGLL4 rs 2574704 polymorphisms with childhood obesity and related metabolic phenotypes to provide evidence for personalized prevention and management strategies. Methods: Based on the 2023 Long term Nutritional Health Effects of Early Childhood Nutrition Package Intervention project, the study enrolled 1 078 children aged 5-7 years from four counties in Henan (Songxian and Ruyang countries) and Guizhou (Guiding and Fuquan countries) provinces. Using BMI Z scores, 87 overweight and obese(OVOB) children were selected and matched by sex, age, and BMI Z score with 117 normal weight controls. Participants were further stratified into four metabolic phenotype groups: metabolically healthy normal weight (MHNW, n =51), metabolically unhealthy normal weight (MUNW, n =66), metabolically healthy obesity (MHO, n =31) and metabolically unhealthy obesity (MUO, n =56) based on four conventional cardiometabolic risk factor (CR) criteria. Data were collected through questionnaires, anthropometric measurements, serum biochemical tests, and KASP genotyping. The distribution of three genetic polymorphisms ( CDKAL1 rs35261542, FAIM2 rs3205718, VGLL4 rs 2574704) across metabolic subgroups was analyzed. Multivariate Logistic regression models assessed associations between these polymorphisms and obesity/metabolic phenotypes. Results: Multivariate Logistic regression analysis showed that Homozygous mutant AA genotype of CDKAL1 rs 35261542 was positively associated with OVOB( OR =3.63), MHO ( OR =11.04), MUO ( OR = 4.88 ) ( P <0.05). Homozygous TT genotype of FAIM2 rs 3205718 increased OVOB risk ( OR =4.44, P <0.05) but showed no association with metabolic phenotypes ( P >0.05). Homozygous mutant TT of VGLL4 rs 2574704 reduced the risks of MHO and MUO ( OR = 0.30, 0.24， P <0.05). Cumulative genetic effects analysis demonstrated carriers of 1 or 2 risk genotypes of rs 35261542 and rs 3205718 had progressively higher OVOB risk ( OR =2.53, 20.79), and the combination of rs 35261542 and rs 2574704 increased risks for both MHO ( OR =8.50) and MUO ( OR =5.00) ( P <0.05). Conclusions The AA genotype of rs 35261542 ( CDKAL1 ) positively correlates with childhood obesity and metabolic abnormalities. The TT genotype of rs 3205718 ( FAIM 2) increases obesity risk but not metabolic phenotypes. The TT genotype of rs 2574704 ( VGLL 4) shows protective effects against metabolic dysfunction. Risk genotypes exhibit dosedependent cumulative effects on obesity and metabolic outcomes.

BACKGROUND: Treatment with chimeric antigen receptor-T (CAR-T) cells has shown promising effectiveness in patients with relapsed/refractory B-cell acute lymphoblastic leukemia (R/R B-ALL), although the process of preparing for this therapy usually takes a long time. We have recently created CD19 Fast-CAR-T (F-CAR-T) cells, which can be produced within a single day. The objective of this study was to evaluate and contrast the effectiveness and safety of CD19 F-CAR-T cells with those of CD19 conventional CAR-T cells in the management of R/R B-ALL. METHODS: A multicenter, retrospective analysis of the clinical data of 44 patients with R/R B-ALL was conducted. Overall, 23 patients were administered with innovative CD19 F-CAR-T cells (F-CAR-T group), whereas 21 patients were given CD19 conventional CAR-T cells (C-CAR-T group). We compared the rates of complete remission (CR), minimal residual disease (MRD)-negative CR, leukemia-free survival (LFS), overall survival (OS), and the incidence of cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS) between the two groups. RESULTS: Compared with the C-CAR-T group, the F-CAR-T group had significantly higher CR and MRD-negative rates (95.7% and 91.3%, respectively; 71.4% and 66.7%, respectively; P = 0.036 and P = 0.044). No significant differences were observed in the 1-year or 2-year LFS or OS rates between the two groups: the 1-year and 2-year LFS for the F-CAR-T group vs.C-CAR-T group were 47.8% and 43.5% vs. 38.1% and 23.8% (P = 0.384 and P = 0.216), while the 1-year and 2-year OS rates were 65.2% and 56.5% vs. 52.4% and 47.6% (P = 0.395 and P = 0.540). Additionally, among CR patients who underwent allogeneic hematopoietic stem cell transplantation (allo-HSCT) following CAR-T-cell therapy, there were no significant differences in the 1-year or 2-year LFS or OS rates: 57.1% and 50.0% vs. 47.8% and 34.8% (P = 0.506 and P = 0.356), 64.3% and 57.1% vs. 65.2% and 56.5% (P = 0.985 and P = 0.883), respectively. The incidence of CRS was greater in the F-CAR-T group (91.3%) than in the C-CAR-T group (66.7%) (P = 0.044). The incidence of ICANS was also greater in the F-CAR-T group (30.4%) than in the C-CAR-T group (9.5%) (P = 0.085), but no treatment-related deaths occurred in the two groups. CONCLUSION Compared with C-CAR-T-cell therapy, F-CAR-T-cell therapy has a superior remission rate but also leads to a tolerably increased incidence of CRS/ICANS. Further research is needed to explore the function of allo-HSCT as an intermediary therapy after CAR-T-cell therapy.

This study aims to comprehensively analyze the material basis of toad visceral oil(hereafter referred to as toad oil), and explore the pharmacological effect of toad oil on atopic dermatitis(AD). Ultra-high performance liquid chromatography-linear ion trap/orbitrap high-resolution mass spectrometry(UHPLC-LTQ-Orbitrap-MS) and gas chromatography-mass spectrometry(GC-MS) were employed to comprehensively identify the chemical components in toad oil. The animal model of AD was prepared by the hapten stimulation method. The modeled animals were respectively administrated with positive drug(0.1% hydrocortisone butyrate cream) and low-and high-doses(1%, 10%) of toad oil by gavage. The effect of toad oil on AD was evaluated with the AD score, ear swelling rate, spleen index, and pathological section results as indicators. A total of 99 components were identified by UHPLC-LTQ-Orbitrap-MS, including 14 bufadienolides, 7 fatty acids, 6 alkaloids, 10 ketones, 18 amides, and other compounds. After methylation of toad oil samples, a total of 20 compounds were identified by GC-MS. Compared with the model group, the low-and high-dose toad oil groups showed declined AD score, ear swelling rate, and spleen index, alleviated skin lesions, and reduced infiltrating mast cells. This study comprehensively analyzes the chemical composition and clarifies the material basis of toad oil. Meanwhile, this study proves that toad oil has a good therapeutic effect on AD and is a reserve resource of traditional Chinese medicine for external use in the treatment of AD.
Animals ; Dermatitis, Atopic/immunology* ; Disease Models, Animal ; Mice ; Male ; Gas Chromatography-Mass Spectrometry ; Humans ; Bufonidae ; Oils/administration & dosage* ; Chromatography, High Pressure Liquid ; Female ; Mice, Inbred BALB C

This study delves into the mechanism of total flavone of Abelmoschus manihot(TFA) in treating ulcerative colitis(UC) and depression via inhibiting M1 polarization of macrophages and reshaping intestinal flora and glycerolphospholipid metabolism. The study established a mouse model of UC and depression induced by chronic restraint stress(CRS) and dextran sulfate sodium(DSS). The fecal microbiota transplantation(FMT) experiment after TFA intervention was conducted. Mice in the FMT donor group were modeled and treated, and fecal samples were taken to prepare the bacterial solution. Mice in the FMT receptor group were treated with antibiotic intervention, and then administered bacterial solution by gavage from mice in the donor group, followed by UC depression modeling. After the experiment, behavioral tests were conducted to evaluate depressive-like behaviors by measuring the levels of 5-hydroxytryptamine(5-HT) and brain-derived neurotrophic factor(BDNF) in the hippocampus of mice. The levels of tumor necrosis factor-α(TNF-α),interleukin-6(IL-6),and interleukin-1β(IL-1β)in the brain and colon tissue of mice were also measured, and the polarization status of macrophages was evaluated by measuring the mRNA levels of CD86 and CD206. 16S ribosomal RNA(16S rRNA) sequencing technology was used to analyze changes in the intestinal flora of mice. Wide target lipidomics was used to detect serum lipid metabolite levels in mice after FMT,and correlation analysis was conducted between lipids and differential intestinal flora significantly regulated by TFA. In vitro experiments, representative glycerophospholipid metabolites and glycerophospholipid inhibitors were used to intervene in Raw264.7 macrophages, and the mRNA levels of TNF-α,IL-6,IL-1β,CD86,and CD206 were detected. The results showed that TFA and FMT after intervention could significantly improve depressive-like behavior and intestinal inflammation in mice with UC and depression, significantly downregulate pro-inflammatory cytokines and CD86 mRNA expression in brain and colon tissue, inhibiting M1 polarization of macrophages, and significantly upregulate CD206 mRNA expression, promoting M2 polarization of macrophages. In addition, the high-dose group had a more significant effect. After TFA intervention, FMT significantly corrected the metabolic disorder of glycerophospholipids in mice with UC and depression, and there was a significant correlation between differential intestinal flora and glycerophospholipids. In vitro experiments showed that glycerophospholipid metabolites, especially lysophosphatidylcholine(LPC),significantly upregulated pro-inflammatory cytokines and CD86 mRNA expression, promote M1 polarization of macrophages, while glycerophospholipid inhibitors had the opposite effect. The results indicate that TFA effectively treats depression and UC by correcting intestinal flora dysbiosis and reshaping glycerophospholipid metabolism, thereby inhibiting M1 polarization of macrophages.
Animals ; Mice ; Gastrointestinal Microbiome/drug effects* ; Abelmoschus/chemistry* ; Macrophages/metabolism* ; Colitis, Ulcerative/immunology* ; Flavones/administration & dosage* ; Male ; Depression/genetics* ; Glycerophospholipids/metabolism* ; Humans ; Drugs, Chinese Herbal/administration & dosage* ; Mice, Inbred C57BL

Traditional Chinese medicine(TCM) resources are the essential material foundation for the development of TCM. The national survey of TCM resources serves as a periodic summary of these resources, ensuring the continuity, prosperity, and development of TCM in China. Since 1949, four national surveys of TCM resources have been conducted. The fourth survey incorporated an investigation into traditional knowledge related to TCM resources, including the traditional medicinal knowledge of Chinese ethnic minorities, with the goal of systematically exploring, preserving, and inheriting this knowledge. This manuscript provides an overview of the basic findings from the first three national surveys of TCM resources, while also clarifying the concepts, categories, forms, carriers, and acquisition pathways of traditional knowledge related to TCM resources. A preliminary summary of the findings from traditional knowledge investigations reported in current literature is also presented. Based on the fourth survey, this manuscript emphasizes the urgency of developing public medical knowledge through empirically-based investigations, the excavation, and compilation of traditional knowledge. It also outlines the potential for conducting "precise" investigations based on first-hand data obtained from the survey, as well as facilitating the discovery and evaluation of new medicines using traditional knowledge related to ethnic minority medicinal practices. This manuscript is expected to provide valuable insights for promoting the health and industrial development of ethnic minority populations in the post-"survey" phase.
Humans ; Medicine, Chinese Traditional ; China/ethnology* ; Minority Groups ; Ethnicity ; Drugs, Chinese Herbal/therapeutic use* ; Health Knowledge, Attitudes, Practice/ethnology* ; Surveys and Questionnaires

The quality of drugs is a crucial premise for ensuring the safety and effectiveness of clinical medication, while quality control during the pharmaceutical process directly affects the quality and consistency of the final product formulation. However, there is a lack of a comprehensive and scientific system for assessing and optimizing the quality control level during the manufacturing process in the field of drug quality control. Therefore, this study proposed the concept of "pharmaceutical process omics", clarified its advantages in guiding drug production, and explored in depth the research approaches, diverse analytical techniques, and broad range of applications in drug quality control. In addition, this study anticipated the broad application prospects of pharmaceutical process omics in the field of drug quality control, aiming to provide a scientific basis for the development of pharmaceutical process quality control standards.
Quality Control ; Humans ; Drugs, Chinese Herbal/chemistry*

This study aimed to explore the mechanisms and molecular targets of total flavones of Abelmoschus manihot(TFA) plus empagliflozin(EM) in attenuating diabetic tubulopathy(DT) by targeting mitochondrial homeostasis and pyroptosis-apoptosis-necroptosis(PANoptosis). In the in vivo study, the authors established the DT rat models through a combination of uninephrectomy, administration of streptozotocin via intraperitoneal injections, and exposure to a high-fat diet. Following modeling successfully, the DT rat models received either TFA, EM, TFA+EM, or saline(as a vehicle) by gavage for eight weeks, respectively. In the in vitro study, the authors subjected the NRK52E cells with or without knock-down Z-DNA binding protein 1(ZBP1) to a high-glucose(HG) environment and various treatments including TFA, EM, and TFA+EM. In the in vivo and in vitro studies, The authors investigated the relative characteristics of renal tubular injury and renal tubular epithelial cells damage induced by reactive oxygen species(ROS), analyzed the relative characteristics of renal tubular PANoptosis and ZBP1-mediatted PANoptosis in renal tubular epithelial cells, and compared the relative characteristics of the protein expression levels of marked molecules of mitochondrial fission in the kidneys and mitochondrial homeostasis in renal tubular epithelial cells, respectively. Furthermore, in the network pharmacology study, the authors predicted and screened targets of TFA and EM using HERB and SwissTargetPrediction databases; The screened chemical constituents and targets of TFA and EM were constructed the relative network using Cytoscape 3.7.2 network graphics software; The relative targets of DT were integrated using OMIM and GeneCards databases; The intersecting targets of TFA, EM, and DT were enriched and analyzed signaling pathways by Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG) software using DAVID database. In vivo study results showed that TFA+EM could improve renal tubular injury, the protein expression levels and characteristics of key signaling molecules in PANoptosis pathway in the kidneys, and the protein expression levels of marked molecules of mitochondrial fission in the kidneys. And that, the ameliorative effects in vivo of TFA+EM were both superior to TFA or EM. Network pharmacology study results showed that TFA+EM treated DT by regulating the PANoptosis signaling pathway. In vitro study results showed that TFA+EM could improve ROS-induced cell injury, ZBP1-mediatted PANoptosis, and mitochondrial homeostasis in renal tubular epithelial cells under a state of HG, including the protein expression levels of marked molecules of mitochondrial fission, mitochondrial ultrastructure, and membrane potential level. And that, the ameliorative effects in vitro of TFA+EM were both superior to TFA or EM. More importantly, using the NRK52E cells with knock-down ZBP1, the authors found that, indeed, ZBP1 was mediated PANoptosis in renal tubular epithelial cells as an upstream factor. In addition, TFA+EM could regulate the protein expression levels of marked signaling molecules of PANoptosis by targeting ZBP1. In summary, this study clarified that TFA+EM, different from TFA or EM, could attenuate DT with multiple targets by ameliorating mitochondrial homeostasis and inhibiting ZBP1-mediated PANoptosis. These findings provide the clear pharmacological evidence for the clinical treatment of DT with a novel strategy of TFA+EM, which is named "coordinated traditional Chinese and western medicine".
Animals ; Rats ; Mitochondria/metabolism* ; Benzhydryl Compounds/administration & dosage* ; Glucosides/administration & dosage* ; Abelmoschus/chemistry* ; Male ; Homeostasis/drug effects* ; Flavones/administration & dosage* ; Rats, Sprague-Dawley ; Diabetic Nephropathies/physiopathology* ; Drugs, Chinese Herbal/administration & dosage* ; DNA-Binding Proteins/genetics* ; Humans ; Apoptosis/drug effects*