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

OBJECTIVE: To identify the CDYL-interacting proteins in murine testis and investigate the mechanism of CDYL involved in spermatogenesis. METHODS: CDYL-interacting partners in testis were identified using co-immunoprecipitation coupled with liquid chromatography-tandem mass spectrometry (LC-MS/MS). Expression pattern of CDYL-interacting protein MYH9 was analyzed through immunohistochemistry (IHC), confocal immunofluorescence (IF) and Western blot (WB) in mouse testicular cells. The effect of the Cdyl conditional knockout (CdylcKO) in spermatogenic cell on Myh9 expression was quantified via RT-qPCR, WB and IF imaging in both spermatids and spermatozoa from cauda epididymides. RESULTS: Direct interaction between MYH9 and CDYL was confirmed in murine testis. During spermiogenesis, MYH9 exhibited co-localization with CDYL at the manchette structure, and binding to F-ACTIN, the component of manchette. In cauda epididymal spermatozoa, MYH9 signal concentrated on acrosomal region and continuously distributed along the tail length. Conditional deletion of Cdyl in spermatogenic cell resulted in the transcriptional downregulation of Myh9. In spermatids, CdylcKO led to reduced but retained MYH9 localization to the disorganized manchette structure. In spermatozoa from CdylcKO mice, abnormalities of MYH9 localization were observed, including attenuation of acrosomal signal and/or partial vanishment/enhancement of tail signal. CONCLUSION In murine spermatids, MYH9 protein is localized to the manchette structure, with its expression and subcellular distribution is affected by CDYL protein. CDYL-MYH9 interaction is essential for the spermiogenesis.
Animals ; Male ; Mice ; Testis/metabolism* ; Myosin Heavy Chains/metabolism* ; Spermatogenesis ; Mice, Knockout

Myocardial infarction (MI) is the leading cause of cardiovascular disease-related death worldwide. Nonetheless, existing therapeutic approaches for MI are hampered by issues such as reliance on pharmacological agents and suboptimal patient adherence. Caffeic acid (CA) is a bioactive polyphenolic compound with important anti-inflammatory, anti-bacterial and anti-oxidant functions. Still, its specific role and mechanism in treating cardiovascular disease remain to be further studied. In recent years, a large number of studies have shown that the kelch-like ECH-associated protein 1/nuclear factor erythroid 2 related factor 2 (Keap1/Nrf2) pathway is a key factor in the occurrence and development of cardiovascular diseases. In this study, H₂O₂-induced oxidative stress model of H9c2 cells and left anterior descending branch (LAD) conjunctival induced acute myocardial infarction reperfusion (AMI/R) model were used to evaluate the protective effect of CA on the heart. The interaction between CA and Keap1 was analyzed by CA-labeled fluorescence probe, target fishing, isothermal titration calorimetry (ITC), protein crystallography and surface plasmon resonance (SPR). Our results suggested that CA binds Keap1 and degrades Keap1 in a p62-dependent manner, further promoting nuclear transcription of Nrf2 and thus effectively reducing oxidative stress. In addition, based on the three-dimensional eutectic structure, it was confirmed that CA directly targets Keap1 protein by interacting with residues M550 and N532, inducing conformation changes in Keap1 protein. We also found that the CA analog chlorogenic acid (GCA) can bind Keap1. In conclusion, this study elucidates a novel molecular mechanism and structural basis for the protective effects of CA against oxidative damage via the Keap1-Nrf2 pathway.

Objective: To screen and identify the key active molecules, signaling pathways, and therapeutic targets of Shuxuening (SXN) injection for treating liver cirrhosis (LC) and to evaluate its therapeutic potential using a mouse model. Methods: Target genes of SXN and LC were retrieved from public databases, and enrichment analysis was performed. A protein–protein interaction (PPI) network was constructed using the Search Tool for the Retrieval of Interacting Genes/Proteins (STRING), and hub genes were identified using Molecular Complex Detection (MCODE). LC was induced in rats and mice via intraperitoneal injections of diethylnitrosamine and carbon tetrachloride (CCl4) for 12 weeks. Starting at week 7, SXN was administered intraperitoneally to the mice in the treatment group. Serum and liver tissues of the mice were collected for the detection of indicators, pathological staining, and expression analysis of hub targets using quantitative real-time polymerase chain reaction (qRT-PCR). Results: We identified 368 overlapping genes (OLGs) between SXN and LC targets. These OLGs were subsequently used to build a PPI network and to screen for hub genes. Enrichment analysis showed that these genes were associated with cancer-related pathways, including phosphoinositide-3-kinase/Akt and mitogen-activated protein kinase signaling and various cellular processes, such as responses to chemicals and metabolic regulation. In vivo experiments demonstrated that SXN treatment significantly improved liver function and pathology in CCl4-induced LC mice by reducing inflammation and collagen deposition. Furthermore, qRT-PCR demonstrated that SXN regulated the expression of MAPK8, AR and CASP3 in the livers of LC mice. Conclusion This study highlighted the therapeutic effects of SXN in alleviating LC using both bioinformatics and experimental methods. The observed effect was associated with modulation of hub gene expression, particularly MAPK8, and CASP3.

RNA editing, an essential post-transcriptional reaction occurring in double-stranded RNA (dsRNA), generates informational diversity in the transcriptome and proteome. In mammals, the main type of RNA editing is the conversion of adenosine to inosine (A-to-I), processed by adenosine deaminases acting on the RNAs (ADARs) family, and interpreted as guanosine during nucleotide base-pairing. It has been reported that millions of nucleotide sites in human transcriptome undergo A-to-I editing events, catalyzed by the primarily responsible enzyme, ADAR1. In hematological malignancies including myeloid/lymphocytic leukemia and multiple myeloma, dysregulation of ADAR1 directly impacts the A-to-I editing states occurring in coding regions, non-coding regions, and immature miRNA precursors. Subsequently, aberrant A-to-I editing states result in altered molecular events, such as protein-coding sequence changes, intron retention, alternative splicing, and miRNA biogenesis inhibition. As a vital factor of the generation and stemness maintenance in leukemia stem cells (LSCs), disordered RNA editing drives the chaos of molecular regulatory network and ultimately promotes the cell proliferation, apoptosis inhibition and drug resistance. At present, novel drugs designed to target RNA editing(e.g., rebecsinib) are under development and have achieved outstanding results in animal experiments. Compared with traditional antitumor drugs, epigenetic antitumor drugs are expected to overcome the shackle of drug resistance and recurrence in hematological malignancies, and provide new treatment options for patients. This review summarized the recent advances in the regulation mechanism of ADAR1-mediated RNA editing events in hematologic malignancies, and further discussed the medical potential and clinical application of ADAR1.

BACKGROUND:With a gradually aging population,improving the ability to screen for the risk of death after arthroplasty and implementing timely personalized intervention programs for the increasing number of elderly patients with femoral neck fractures is key to improving the postoperative status of patients and prolonging survival expectations. OBJECTIVE:To investigate the risk factors for postoperative mortality in elderly patients with femoral neck fractures and to construct a nomogram predictive model to predict their mortality risk. METHODS:The study was conducted on 155 elderly patients(≥65 years old)who underwent arthroplasty for femoral neck fracture from January 2016 to January 2021,and 147 patients who met the inclusion criteria were analyzed to collect clinical data that may affect the patients'postoperative mortality.Single-factor and multi-factor Cox regression analyses were successively used to screen independent risk factors associated with postoperative mortality.The column line graph model was constructed and validated using Rstudio software. RESULTS AND CONCLUSION:(1)Age,frailty(age-adjusted Charlson comorbidities score),preoperative activity status,osteoporosis,and postoperative serum albumin level were five independent risk factors for postoperative mortality in elderly patients with femoral neck fractures(P<0.05).(2)The nomogram predictive model was constructed based on the results of multifactorial analysis,with a consistency index of 0.819(95%CI:0.771-0.868).Receiver operating characteristic curve analysis showed that the area under curve for 1-year and 3-year survival prediction was 0.8543 and 0.7263,respectively,indicating that the nomogram predictive model has good discriminatory and predictive power;calibration curve and decision curve analysis also showed good model discriminative power and clinical utility value.(3)The constructed nomogram predictive model has good diagnostic efficacy and accuracy,and can effectively assess the risk of postoperative death of patients.

This study investigated the epidemiological and genotypic characteristics of group A rotavirus(RVA)in children under 5 years of age with diarrhea at a viral diarrhea surveillance sentinel hospital in Guangdong Province from 2021 to 2022,to provide a basis for RVA prevention and control.A total of 1 858 fecal samples from children under 5 years of age with diarrhea in 2021-2022 were collected.Rotavirus antigen was detected with ELISA,and positive samples were further sequenced and categorized.Among the 1 858 samples,156 were RVA positive.The positivity rates in boys and girls were 8.76％and 7.87％,respectively.Significant differences were observed in the detection rates of RVA infection among age groups.The rate of RVA infection increased gradually from December to April of the following year.In 2021,the main endemic strains of RVA in the Guangdong region were of the G9P[8]subtype,and the rare G8P[8]subtype increased in China.In 2022,the G8P[8]subtype surpassed the G9P[8]subtype for the first time.In cases of diarrhea in infants younger than 5 years in Guangdong Province from 2021 to 2022,the RVA genotypes were diverse,the G9P[8]genotype significantly decreased,and the G8P[8]subtype became a dominant genotype.Continuous RVA genotype monitoring remains necessary to assess the risk of RVA-related disea-ses.

Objective:To explore the efficacy and safety of haploidentical hematopoietic stem cell transplantation combined with umbilical cord blood infusion for the treatment of aplastic anaemia in children.Methods:Nine cases of children with aplastic anaemia treated with umbilical cord blood combined with haploidentical hematopoietic stem cell transplantation at the People's Hospital of Henan University of Chinese Medicine from January 1,2021 to September 15,2023 with a median age of 11(2-13)years and a median follow up of 18(7.5-21)months were included,and the clinical data were retrospectively analyzed.Hematopoiesis reconstitution,the incidence of graft-versus-host disease(GVHD),infections and survival of the patients were analyzed.Results:All 9 children were successfully implanted.The median time to neutrophil and platelet implantation was 11.11±1.27 d and 12.44±3.36 d,respectively.One case developed acute gastrointestinal GVHD of degree I,which was improved after treatment,and the patient developed superficial gastritis and chronic gastrointestinal GVHD at a later stage,which is currently under clinical follow-up.Acute GVHD of Ⅱ-Ⅳ degree was 0％.Hemorrhagic cystitis in 3 cases,CMV infection in 5 cases and bacterial and fungal infections in 5 cases improved with symptomatic treatment.All 9 children demonstrated complete donor chimerism within 1 month after transplantation,at two years of follow-up,all nine children survived without recurrence or development of grade Ⅱ-Ⅳ GVHD,and there were no children with transplant-related deaths.Conclusion:Haploidentical hematopoietic stem cell transplantation combined with umbilical cord blood transfusion for aplastic anaemia in children has a low incidence and mild degree of GVHD,with significant efficacy,and can be used as a therapeutic option for children without an HLA full donor chimeric match.

[Objective]To investigate the effect of esketamine pretreatment on early negative postoperative behavioural occurrence after pediatric concealed penis correction.[Methods]A total of 88 children,aged 4-10 years old,of American Society of Anesthesiologists physical status Ⅰ-Ⅱ,undergoing pediatric cryptorchid penis correction operation within 1 hour,were randomly divided into the esketamine group(Group E,n=44)and the control group(Group C,n=44)according to the computer-generated random numeral order.Esketamine was infused intravenously at a dose of 0.5 mg/kg 20 minutes before entering the operating room in Group E,while equal volume of normal saline was given instead of esketamine in group C.General anesthesia with laryngeal mask and inhalation anesthesia was used in both groups.The anxiety level of children was evaluated by modified Yale Preoperative Anxiety Scale(m-YPAS)on the day before surgery and before entering operating room on the day of the operation.The induction compliance level of children was evaluated by the Induction Compliance Checklist(ICC).Heart rate(HR)and mean arterial pressure(MAP)were recorded before the induction of anesthesia(T0),immediately after the induction(T1),the beginning of the operation(T2),the time of admission to the PACU(T3),10 min after the PACU(T4),and before discharge from PACU(T5).Paediatric Anaesthesia Awakening Delirium Scale(PAED)and Pain Behavioural Assessment Scale(FLACC)scores were performed during awakening.A volume of 3 mL of peripheral venous blood was collected on the first preoperative day as well as the first postoperative day,and the levels of monocyte chemotactic protein 1(MCP-1),cortisol and epinephrine were measured.The Postoperative Behavioural Questionnaire(PHBQ)questionnaire was recorded on postoperative days 3 and 7 for all children.[Results]The incidence of NPOBCs on postoperative days 3 and 7 was significantly lower in Group E compared with that of Group C(31.8%vs.63.6%,P<0.05;18.2%vs.40.9%,P<0.05).The incidence of separation anxiety,sleep anxiety,and eating disorders in the PHBQ on postoperative day 3 was significantly lower in Group E than in Group C.The difference was statistically significant(P<0.05);there was no statistically significant difference between the two groups when comparing the incidence of overall anxiety,aggression,and apathetic withdrawal(P>0.05).On postoperative day 7,the incidence of all indicators in the PHBQ was not statistically different between the 2 groups(P>0.05).Compared with Group C,postoperative MCP-1 was significantly lower in Group E,and the difference was statistically significant(P<0.05);whereas for epinephrine and cortisol levels,there was no statistically significant difference between the 2 groups(P>0.05).Multivariable logistic regression analysis suggested that the possible risk factors for NPOBCs after pediatric concealed penis correction included the m-YPAS score[OR=1.152,95%CI(1.083,1.226);P=0.000],and the use of esketamine[OR=0.223,95%CI(0.062,0.803);P=0.022].The AUC under the ROC curve of m-YPAS and the use of esketamine as two predictors of the occurrence of NPOBCs were 0.918[P＜0.001,95%CI(0.849,0.988)]and 0.659[P=0.010,95%CI(0.544,0.774)],respectively.There was no statistically significant difference in PAED scores and FLACC scores between the two groups in the PACU(P>0.05).[Conclusion]Esketamine pretreatment can reduce the incidence of NPOBCs in children undergoing concealed penis correction,which may be associated with a reduction in postoperative MCP-1,without an increase in perioperative adverse events and with a high safety profile.