N,N-Dimethylglycine (DMG) is a glycine derivative, and its sodium salt (DMG-Na) has been demonstrated to possess various biological activities, including immunomodulation, free radical scavenging, and antioxidation, collectively contributing to the stability of tissue and cellular functions. However, its direct effects and underlying mechanisms in wound healing remain unclear. In this study, a full-thickness excisional wound model was established on the dorsal skin of mice, and wounds were treated locally with DMG-Na. Wound healing progression was assessed by calculating wound closure rates. Histopathological analysis was conducted using hematoxylin-eosin (HE) staining, and keratinocyte proliferation, migration, and differentiation were evaluated using CCK-8 assays, scratch wound assays, and quantitative reverse transcription PCR (qRT-PCR). Inflammation-related cytokine expression in keratinocytes was analyzed via ELISA and qRT-PCR. Results revealed that DMG-Na treatment significantly accelerated wound healing in mice and improved overall wound closure quality. The wound healing rates on days 3, 6, and 9 were 49.18%, 68.87%, and 90.55%, respectively, with statistically significant differences compared to the control group ( P<0.05). DMG-Na treatment downregulated the mRNA levels of keratinocyte differentiation markers while enhancing cell proliferation and migration ( P<0.05). Furthermore, DMG-Na decreased the secretion of LPS-induced keratinocyte inflammatory cytokines, including IL-1β, IL-6, IL-8, TNF-α, and CXCL10 ( P<0.05). These findings indicate that DMG-Na regulates inflammatory responses and promotes keratinocyte proliferation and migration, thereby facilitating the healing of skin wounds.
Animals ; Wound Healing/drug effects* ; Mice ; Cell Proliferation/drug effects* ; Keratinocytes/drug effects* ; Cell Movement/drug effects* ; Cell Differentiation/drug effects* ; Glycine/pharmacology* ; Skin/injuries* ; Male

OBJECTIVE: To detect the expression of methyltransferase-like 7B ( METTL7B) in bone marrow specimens of patients with acute myeloid leukemia (AML), and to analyze its influence and significance on clinical diagnosis, treatment, and prognosis of AML patients. METHODS: Bone marrow specimens from 60 newly diagnosed AML patients were collected as the observation group, and bone marrow specimens from 20 iron-deficiency anemia (IDA) patients were collected as the control group. Clinical and pathological data of AML patients were also collected. Real-time fluorescent quantitative PCR (qRT-PCR) was used to detect the expression of METTL7B in AML patients and IDA patients. Statistical analyses were performed to investigate the relationship between the expression level of METTL7B and clinical-pathological characteristics in AML patients, as well as the impact of METTL7B expression level on efficacy. Kaplan-Meier method was used to analyze the effect of METTL7B expression level on the overall survival time (OS) in AML patients. Meanwhile, a Cox proportional hazards regression model was constructed to identify the factors potentially affecting the prognosis of AML patients. RESULTS: Compared with the control group, the expression level of METTL7B was significantly upregulated in AML patients (P < 0.05). Compared with the low-expression group of METTL7B, the high-expression group had a higher proportion of patients with high white blood cell (WBC) count, poor prognosis, and ineffective treatment, and the differences were statistically significant (P < 0.05). The OS of patients in the high-expression group of METTL7B was significantly shorter than that in the low-expression group (P < 0.05). Multivariate Cox regression analysis showed that high WBC count, poor prognosis in prognosis stratification, and high expression of METTL7B were independent risk factors for the prognosis of AML patients (P < 0.05). CONCLUSION METTL7B is highly expressed in AML patients, and patients with high METTL7B expression exhibit shorter survival and poor prognosis. METTL7B is expected to serve as a new indicator for evaluating the prognosis of AML patients and may develop into a potential target for targeted treatment of AML in the future.
Humans ; Leukemia, Myeloid, Acute/metabolism* ; Prognosis ; Methyltransferases/metabolism* ; Male ; Female ; Middle Aged ; Adult ; Proportional Hazards Models

Direct electrical stimulation of the human cortex can produce subjective visual sensations, yet these sensations are unstable. The underlying mechanisms may stem from differences in electrophysiological activity within the distributed network outside the stimulated site. To address this problem, we recruited 69 patients who experienced visual sensations during invasive electrical stimulation while intracranial electroencephalography (iEEG) data were recorded. We found significantly flattened power spectral slopes in distributed regions involving different brain networks and decreased integrated information during elicited visual sensations compared with the non-sensation condition. Further analysis based on minimum information partitions revealed that the reconfigured network interactions primarily involved the inferior frontal cortex, posterior superior temporal sulcus, and temporoparietal junction. The flattened power spectral slope in the inferior frontal gyrus was also correlated with integrated information. Taken together, this study indicates that the altered electrophysiological signatures provide insights into the neural mechanisms underlying subjective visual sensations.
Humans ; Male ; Female ; Adult ; Visual Perception/physiology* ; Electric Stimulation ; Middle Aged ; Young Adult ; Electrocorticography ; Electroencephalography ; Brain Mapping

Objective To observe the clinical efficacy of"triple-posture positive bone-setting"chiropractic manipulation combined with Tongluo Huoxue Formula for the treatment of lumbar spinal stenosis(LSS)with qi deficiency and blood stasis syndrome.Methods Sixty patients with LSS of qi deficiency and blood stasis type were randomly divided into trial group and control group,with 30 cases in each group.The trial group was treated with"triple-posture positive bone-setting"chiropractic manipulation(a chiropractic manipulation performed under the positive cooperation of the patients at three postures)combined with Tongluo Huoxue Formula,while the control group was treated with"triple-posture positive bone-setting"chiropractic manipulation combined with conventional western medicine.The course of treatment for the two groups covered 4 weeks.Before and after treatment,the patients of the two groups were observed in the changes of pain visual analogue scale(VAS)score,Japanese Orthopedic Association(JOA)score of lumbar function,Oswestry Disability Index(ODI)score,straight-leg raising test results and serum interleukin 6(IL-6)and C-reactive protein(CRP)levels.After treatment,the clinical efficacy and safety of the two groups were evaluated.Results(1)After 4 weeks of treatment,the total effective rate of the trial group was 96.67％(29/30)and that of the control group was 63.33％(19/30).The intergroup comparison(tested by Fisher's exact test)showed that the clinical efficacy of the trial group was significantly superior to that of the control group(P＜0.05).(2)After treatment,the lumbar function indicators of pain VAS scores and ODI scores in the trial group were significantly lower(P＜0.05),and the JOA scores were significantly higher than those before treatment(P＜0.05),while in the control group,only the ODI scores were significantly lower than those before treatment(P＜0.05).The intergroup comparison showed that the decrease of VAS and ODI scores and the increase of JOA scores in the trial group were significantly superior to those in the control group(P＜0.05 or P＜0.01).(3)After treatment,the Laseque s sign of the trial group was significantly improved compared with that before treatment(P＜0.05),while no significant improvement was presented in the control group(P＞0.05).The intergroup comparison showed that the improvement of Laseque's sign in the trial group was significantly superior to that in the control group(P＜0.01).(4)After treatment,the levels of serum inflammatory factors of IL-6 and CRP in the two groups were lower than those before treatment(P＜0.05),and the decrease of serum IL-6 level in the trial group was significantly superior to that in the control group(P＜0.05),but CRP level in the two groups after treatment did not differ from that before treatment,no statistically significant difference was shown between the two groups after treatment,either(P＞0.05).(5)The incidence of adverse reactions in the trial group was 6.67％(2/30)and that in the control group was 13.33％(4/30),and the intergroup comparison(by Fisher's exact test)showed that there was no significant difference between the two groups(P＞0.05).Conclusion The therapeutic effect of"triple-posture positive bone-setting"chiropractic manipulation combined with Tongluo Huoxue Formula exert certain effect for the treatment of LSS patients with qi deficiency and blood stasis syndrome,and it has more obvious advantages in improving the lumbar function,promoting the rehabilitation of the patients,and lowering the level of serum inflammatory factors than"triple-posture positive bone-setting"chiropractic manipulation combined with conventional western medication.

ObjectiveTo systematically compare the chemical compositional differences between Puerariae Thomsonii stem base（PTSB） and Puerariae Thomsonii Radix（PTR）， and to explore the potential hepatoprotective effects of PTSB by liver metabolomics. MethodUltra performance liquid chromatography-quadrupole-time-of-flight mass spectrometry（UPLC-Q-TOF-MS/MS） was used to analyze the chemical compositions of PTSB and PTR. Twenty Kunming mice aged 6-8 weeks， half male and half female， were randomly divided into the blank group（sterile water） and PTSB group（1.95 g·kg^-1）， with 10 mice in each group， and the drug was administered by gavage for 14 d， and the body mass was weighed once a day. After the last administration， mice were anesthetized， organs such as heart， liver， spleen， lungs and kidneys were collected， and the organ index was calculated. Enzyme-linked immunosorbent assay（ELISA） was used to measure the levels of aspartate aminotransferase（AST）， alanine aminotransferase（ALT）， total cholesterol（TC） and triglyceride（TG） in the serum of mice from each group， the morphological changes of heart， liver， spleen， lung and kidney tissues were observed by hematoxylin-eosin（HE） staining， and the regulation of PTSB for the hepatic metabolic profiles of mice was analyzed by UPLC-Q-TOF-MS/MS， then the differential metabolites between the blank group and PTSB group were designated， and the metabolic pathways was enriched by Kyoto Encyclopedia of Genes and Genomes（KEGG）. ResultA total of 19 common chemical constituents were identified from PTSB and PTR， all of which were the main pharmacodynamic substances of PTR. The pharmacodynamic results showed that PTSB could control the growth of body mass of mice and reduce the contents of TC， TG， ALT and AST in serum of mice. HE staining observations and organ indexes showed that there was no significant effect of PTSB on all major organs at the highest clinically equivalent dose. A total of 38 differential metabolites were identified by metabolomics， of which 35 were up-regulated and 3 were down-regulated. These differential metabolites were mainly compounds such as amino acids， fatty acids， vitamins， steroids， nucleosides， pyrimidines and alkaloids. Three key metabolic pathways， including tyrosine metabolism， vitamin B₆ metabolism and tryptophan metabolism， were screened by metabolic pathway analysis. ConclusionPTSB has a similar chemical composition to that of PTR， and it may regulate the metabolism of amino acids and vitamins through the flavonoids and isoflavonoids， thus exerting a potential hepatoprotective effect. This study provides an experimental reference for the clinical application and product development of PTSB.

Objective:To investigate the clinical features and characteristics of gene mutation of patients with Hereditary spherocytosis(HS) and report novel mutations found in this work.Method:We reviewed the literatures for the clinical and genetic features of the 35 patients (24 boys and 11 girls, median age 7.8 years) with HS admitted to Wuhan Children′s Hospital from June 2017 to January 2023. Analyze clinical manifestations the blood routine, and biochemical laboratory results, and use Next-generation sequencing (NGS) to detect pathogenic mutation. Mann-Whitney U testing method was used to analyze the hematological parameters between different genotypes. Results:All of the patients showed clinical manifestations of anemia; 33 children had jaundice, 28 children had splenomegaly, and 11 children had gallstones. Gene mutations were detected in all 35 patients. 17 patients carried ANK1 variants, 14 patients harbored SPTB variants, 1 patient carried SPTA1variants, 1 patient carried SLC4A1 variants, and 2 patients harbored both ANK1 and SPTB variants. A total of 39 heterozygous mutations were found, among which 27 were pathogenic, 6 was likely pathogenic and 6 were of unknown significance according to the ACMG guideline; Among 39 mutations identified, 31 were novel. There were no significant differences in peripheral blood cell parameters and hemolysis indicators between the ANK1 mutant group and the SPTB group (all P>0.05). Conclusion:SPTB and ANK1 mutations are the most common mutations in HS pathogenic genes among patients in Hubei, China, and there was no significant difference in phenotype between ANK1 and SPTB genotype. We found 31 unreported novel variants and expanded the spectrum of variation in this type of disease .

Objective To investigate the effects and mechanisms of modified Taohong Siwu Decoction on myocardial ischemia-reperfusion injury in rats based on transcriptome sequencing.Methods Totally 15 SPF rats were randomly divided into sham-operation group,model group and modified Taohong Siwu Decoction group,with 5 rats in each group.The modified Taohong Siwu Decoction group was pre-administered with modified Taohong Siwu Decoction by gavage for 5 days,while the sham-operation group and model group were given equal volume of distilled water by gavage,myocardial ischemia-reperfusion injury rat model was established.The cardiac function of the rats was assessed using echocardiography,serum oxidative stress and inflammatory factor contents were detected using reagent kits,TUNEL staining was used to detect myocardial cell apoptosis,transcriptome sequencing was performed on myocardial tissue,and differential expression genes were analyzed using Venn diagram and heatmap.GO and KEGG pathway enrichment analysis were performed on common differentially expressed genes.RT-qPCR was used to validate differentially expressed genes PTX3 and EGR2.Results Compared with the sham-operation group,the EF and FS of the model group rats significantly decreased(P<0.01),the cells apoptosis rate of myocardial tissue and serum LDH,TNF-α,IL-1β and IL-6 contents significantly increased(P<0.01),and SOD activity and IL-10 content significantly decreased(P<0.01).Compared with the model group,the modified Taohong Siwu Decoction group showed a significant increase in EF and FS(P<0.05),while the cell apoptosis rate of myocardial tissue and serum CK-MB,LDH,TNF-α,IL-1β and IL-6 contents significantly decreased(P<0.01),and SOD activity and IL-10 content significantly increased(P<0.01).Transcriptome sequencing revealed 4 227 differentially expressed genes(2 259 upregulated and 1 968 downregulated)between the sham-operation group and the model group,1 933 differentially expressed genes(1 301 upregulated and 632 downregulated)between the sham-operation group and the modified Taohong Siwu Decoction group,and 94 differentially expressed genes(46 upregulated and 48 downregulated)between the model group and the modified Taohong Siwu Decoction group.There were 35 common differential genes in the three groups,and the differential genes were mainly enriched in signaling pathways such as fluid shear stress and atherosclerosis,ubiquitin mediated proteolysis,C-type lectin receptor signaling pathway,sphingolipid signaling pathway,cell cycle,chemokine signaling pathway,lipid and atherosclerosis.RT-qPCR showed that gene expressions of PTX3 and EGR2 in myocardial tissue of the model group were significantly increased than that of the sham-operation group,and the gene expressions of PTX2 and EGR2 of modified Taohong Siwu Decoction group were significantly decreased than that of the model group(P<0.01).Conclusion Modified Taohong Siwu Decoction exhibits a certain protective effect against myocardial ischemia-reperfusion injury in rats,characterized by improvements in rat cardiac function,reduction in cell apoptosis and inflammatory cytokine release,as well as alleviation of oxidative stress levels.The mechanism may be related to the regulation of PTX3 and EGR2 gene expression.

Chromodomain-helicase-DNA-binding protein 1 (CHD1) deletion is among the most common mutations in prostate cancer (PCa), but its role remains unclear. In this study, RNA sequencing was conducted in PCa cells after clustered regularly interspaced palindromic repeat (CRISPR)/CRISPR-associated protein 9 (Cas9)-based CHD1 knockout. Gene set enrichment analysis (GSEA) indicated upregulation of hypoxia-related pathways. A subsequent study confirmed that CHD1 deletion significantly upregulated hypoxia-inducible factor 1α (HIF1α) expression. Mechanistic investigation revealed that CHD1 deletion upregulated HIF1α by transcriptionally downregulating prolyl hydroxylase domain protein 2 (PHD2), a prolyl hydroxylase catalyzing the hydroxylation of HIF1α and thus promoting its degradation by the E3 ligase von Hippel-Lindau tumor suppressor (VHL). Functional analysis showed that CHD1 deletion promoted angiogenesis and glycolysis, possibly through HIF1α target genes. Taken together, these findings indicate that CHD1 deletion enhances HIF1α expression through PHD2 downregulation and therefore promotes angiogenesis and metabolic reprogramming in PCa.
Male ; Humans ; Von Hippel-Lindau Tumor Suppressor Protein/metabolism* ; DNA-Binding Proteins/metabolism* ; Prolyl Hydroxylases/metabolism* ; Hypoxia ; Prostatic Neoplasms/pathology* ; Glycolysis ; Hypoxia-Inducible Factor 1, alpha Subunit/metabolism* ; Cell Line, Tumor ; DNA Helicases/metabolism*

Objective:To investigate the mechanism of Candida albicans Int1 in regulating septin organization. Methods:A series of full-length and truncated fragments of Int1 were constructed and fused with green fluorescent protein (GFP). The intracellular localization of the fusion proteins was observed under a fluorescence microscope. The region in Int1 that was required for bud neck localization was identified. Full-length and fragments of Int1 were overexpressed in the yeast Saccharomyces cerevisiae and the changes in cell growth, cell morphology and septin organization were investigated to determine the functional region in Int1 that mediated the interaction with septin. Moreover, the co-localization of the region and septin was analyzed. Results:The full-length Int1 consisted of 1 661 amino acid residues. A middle region of 209 amino acid residues, Int1-M4 (739-947 aa), that could be localized at the bud neck during both small and large bud periods was identified. Overexpression of Int1-M4 led to significant growth defects, elongated bud and disorganized septin. In the cells with elongated bud, Int1-M4 and septin with abnormal structures could be co-localized.Conclusions:Int1-M4 (739-947 aa), the middle region of Int1 containing 209 amino acid residues, mediated the bud neck localization and the interaction with septin, playing an important role in regulating septin organization.