Metabolic associated fatty liver disease (MAFLD) is fundamentally driven by an imbalance in hepatic fatty-acid flux: the influx of fatty acids exceeds the liver’s capacity for disposal, resulting in excessive hepatic lipid accumulation, predominantly in the form of triglycerides (TGs). The occurrence and progression of MAFLD depend on disordered regulation across multiple metabolic steps, including fatty-acid uptake, de novo lipogenesis (DNL), fatty-acid oxidation (FAO), and very low-density lipoprotein (VLDL) export. Forkhead box protein O1 (FOXO1) is a key transcriptional regulator within the hepatic network coordinating glucose and lipid metabolism. Under metabolic stress and insulin resistance (IR), FOXO1 expression is frequently increased, whereas its inhibitory phosphorylation is reduced. These changes enhance FOXO1 nuclear localization and transcriptional activity, thereby reprogramming the expression of genes related to metabolism in the liver. Because hepatic lipid deposition is the central pathological feature of MAFLD, the functional status of FOXO1 directly influences hepatic lipid homeostasis. Growing evidence suggests that FOXO1 can exert bidirectional, environment-dependent effects on hepatic lipid accumulation; however, the molecular basis for this functional switch remains incompletely understood. This review systematically summarizes the biological functions and regulatory mechanisms of FOXO1 and its roles in hepatic lipid metabolism, with a particular focus on its crosstalk with insulin signaling. FOXO1 expression is shaped by RNA modifications and epigenetic regulation mediated by non-coding RNAs. Its transcriptional output is precisely governed by post-translational modifications—such as phosphorylation and acetylation—as well as by coordinated nucleocytoplasmic shuttling. Notably, these regulatory patterns vary markedly across nutritional states, degrees of insulin resistance, and stages of disease. In the fed state, insulin/IGF-1 signaling activates the PI3K-AKT pathway, promoting the inhibitory phosphorylation of FOXO1 and facilitating additional modifications, including acetylation, methylation, and ubiquitination. Together, these events drive FOXO1 export from the nucleus and dampen its transcriptional activity, suppressing gluconeogenesis and constraining lipogenic programs. Conversely, during fasting or when insulin signaling is weakened, FOXO1 inhibition is relieved. FOXO1 accumulates in the nucleus, binds to DNA, and regulates the transcription of downstream target genes. Mechanistically, FOXO1 can aggravate hepatic lipid accumulation by activating genes involved in TG synthesis while repressing FAO-related pathways, thereby favoring storage over oxidation. However, under specific conditions, FOXO1 may also alleviate the hepatic lipid burden by promoting TG hydrolysis and enhancing VLDL secretion, thereby reducing the net hepatic lipid load. In addition, lipotoxic signals mediated by ceramides and diacylglycerols (Cer/DAG) activate atypical protein kinase C (aPKC), further exacerbating the disruption of the AKT-FOXO1 axis. This vicious cycle ultimately produces a metabolic paradox in which increased hepatic glucose output coexists with persistent, insulin-independent lipogenesis, accelerating MAFLD progression. Importantly, FOXO1 regulation is not uniform: during early metabolic overload, insulin-mediated suppression may remain effective, whereas in advanced insulin resistance, the loss of AKT control permits sustained FOXO1 activity. Such stage-dependent dynamics may help explain why FOXO1 can either promote steatosis or, in certain contexts, support programs that facilitate lipid turnover. Accordingly, interventions should be liver-specific and tuned to the disease stage, aiming to curb maladaptive FOXO1 signaling while preserving its capacity to promote triglyceride hydrolysis and VLDL secretion when advantageous. Overall, this review offers an important perspective on MAFLD pathogenesis, emphasizing FOXO1 as a potential therapeutic target and providing a theoretical basis for developing liver-specific, disease-course-dependent precision interventions.

The development of traditional Chinese medicine (TCM) diagnosis and treatment has undergone multiple paradigms, evolving from sporadic experiential practices to systematic approaches in syndrome differentiation and treatment and further integration of disease and syndrome frameworks. TCM is a vital component of the medical system, valued alongside Western medicine. Treatment based on syndrome differentiation embodies both personalized treatment and holistic approaches; however, the inconsistency and lack of stability in syndrome differentiation limit clinical efficacy. The existing integration of diseases and syndromes primarily relies on patchwork and embedded systems, where the full advantages of synergy between Chinese and Western medicine are not fully realized. Recently, driven by the development of diagnosis and treatment concepts and advances in analytical technology, Western medicine has been rapidly transforming from a traditional biological model to a precision medicine model. TCM faces a similar need to progress beyond traditional syndrome differentiation and disease-syndrome integration toward a more precise diagnosis and treatment paradigm. Unlike the micro-level precision trend of Western medicine, precision diagnosis and treatment in TCM is primarily reflected in data-driven applications that incorporate information at various levels, including precise syndrome differentiation, medication, disease management, and efficacy evaluation. The current priority is to accelerate the development of TCM precision diagnosis and treatment technology platforms and advance discipline construction in this area.

Objective To investigate the effects and mechanisms of ubiquitin-associated domain-containing protein 2(UBAC2)mediated by m6A methylation modification on the invasion and migration abilities of colorectal cancer cells.Methods The GEPIA2.0 database was utilized to analyze the expression differences of UBAC2 mRNA between colorectal cancer tissues and adjacent normal tissues,as well as its expression in colorectal cancer tissues at different stages.The correlation between Wilms tumor 1-associated protein(WTAP)and UBAC2 expression was analyzed.The Kaplan-Meier plotter online tool was applied to analyze the correlation between UBAC2 and the overall survival rate of colorectal cancer patients.The RMVar and SRAMP databases were employed to predict potential m6A methylation modification sites in the UBAC2 gene.Quantitative real-time PCR(qRT-PCR)and Western blotting were performed to detect the expression levels of UBAC2 mRNA and protein in colorectal cancer cell lines.For UBAC2 knockdown experiments,SW480 cells were divided into control group(no treatment),sh-NC group(transfected with sh-NC negative control plasmid),and sh-UBAC2 group(transfected with sh-UBAC2 plasmid).For WTAP knockdown experiments,groups included control group(no treatment),si-NC group(transfected with negative control siRNA),and si-WTAP group(transfected with WTAP-targeting siRNA).For UBAC2 overexpression experiments,groups were control group(no treatment),si-WTAP group(transfected with pcDNA3.1 empty plasmid),and si-WTAP+OE-UBAC2 group(transfected with UBAC2 overexpression plasmid pcDNA3.1-UBAC2).Western blotting was used to detect the protein expression levels of UBAC2,WTAP,E-cadherin,N-cadherin,and Vimentin;qRT-PCR was applied to detect the expression level of UBAC2 mRNA;Transwell assays were conducted to assess cell invasion and migration abilities.MeRIP-qPCR was employed to detect the m6A methylation modification of UBAC2 mRNA;RIP-qPCR experiments were conducted to verify the binding of WTAP to UBAC2 mRNA.In nude mouse colorectal cancer lung metastasis experiments,groups included LV-sh-NC group(tail vein injection of SW480 cells stably infected with LV-sh-NC)and LV-sh-UBAC2 group(tail vein injection of SW480 cells stably infected with LV-sh-UBAC2).After 42 d of tumor-implantation in nude mice,lung tissues were harvested:the number of lung nodules observed by hematoxylin/eosin(HE)staining,and the expression level of Luc2 mRNA detected by qRT-PCR.Results GEPIA2.0 database analysis revealed that the expression level of UBAC2 mRNA in colorectal cancer tissues was significantly higher than that in adjacent normal tissues,and it gradually increased with the progression of tumor stage(P<0.05).The expression levels of UBAC2 mRNA and protein in multiple colorectal cancer cell lines were significantly higher than those in normal colonic epithelial cells(P<0.05).Compared with sh-NC group,sh-UBAC2 group showed significantly increased E-cadherin protein expression,significantly decreased N-cadherin and Vimentin protein expression,and significantly reduced number of invaded and migrated SW480 cells(P<0.05).GEPIA2.0 database analysis results indicated a positive correlation between WTAP and UBAC2 expression(r=0.24,P<0.001).Compared with si-NC group,si-WTAP group showed significantly decreased expression levels of WTAP and UBAC2 mRNA and protein in SW480 cells(P<0.05).MeRIP-qPCR results demonstrated that the m6A modification level of UBAC2 mRNA in si-WTAP group was significantly lower than that in si-NC group(P<0.05).RIP-qPCR further confirmed that WTAP could bind to UBAC2 mRNA.Compared with control group,si-WTAP group showed significantly increased E-cadherin protein expression and significantly decreased N-cadherin and Vimentin protein expression in SW480 cells(P<0.05);compared with si-WTAP group,si-WTAP+OE-UBAC2 group showed significantly decreased E-cadherin protein expression and significantly increased N-cadherin and Vimentin protein expression in SW480 cells(P<0.05).The number of lung nodules in LV-sh-UBAC2 group was significantly fewer than that in LV-sh-NC group,and the expression level of Luc2 mRNA in lung tissues was significantly lower than that in LV-sh-NC group(P<0.05).Conclusion UBAC2 mediated by m6A methylation modification can regulate the epithelial-mesenchymal transition(EMT)process in colorectal cancer cells,thereby affecting the invasion and migration abilities of colorectal cancer cells.

Shock and death resulting from traumatic massive hemorrhage have become the leading cause of trauma-related mortality,accounting for over 70%of deaths within 24 hours.Therefore,achieving rapid hemostasis to reduce multiple organ failure caused by excessive blood loss and then improving survival rates has become a critical challenge in trauma care.Common local hemostatic materials for trauma can be categorized by their properties into organic and inorganic materials,or by their mechanism of action into three types:physical adsorbents,biologically active agents,and adhesive sealants.This review summarizes the characteristics and drawbacks of typical representatives from these three categories.It then focuses on discussing the application of zeolite materials in hemostasis,specifically three forms:zeolite particles,zeolite-polymer composites,and bio-based zeolite materials.Furthermore,the latest research progress in the fundamental theory and practical applications of zeolite-based hemostatic materials are reviewed,aiming to provide new insights for future research on zeolite in hemostasis.

Objective To explore the effectiveness of"near peer learning"(NPL)in the electromyo-graphy(EMG)teaching module for neurology residents.Methods The Department of Neurology,Peking Union Medical College Hospital implemented an NPL instructional design for a course on EMG for residents from November 2020 to March 2024.This teaching session was held annually,in which senior residents in-structed juniors who were 1 or 2 years earlier in their training.The residents participated in the pre-course/post-course tests and completed a feedback survey at the end of the session.This evaluation method was used to un-derstand the effectiveness of the NPL intervention in EMG teaching.Results Over four years,a total of 83 residents participated.Among them,there were 24 postdoctoral students,52 postgraduates and 7 junior resi-dents.The results showed that the post-course test scores were significantly improved compared with pre-course test scores(74.33±2.43 vs.70.11±2.49,P=0.005),with the most remarkable improvements seen for"tu-tees"(73.84±20.53 vs.70.29±21.46,P=0.020),postgraduates(74.04±22.51 vs.68.97±21.40,P=0.009),first-year residents(70.19±4.02 vs.63.59±3.59,P=0.040)and first-time participating resi-dents(65.23±3.24 vs.60.97±3.21,P=0.030).The post-program feedback showed that both tutors and tu-tees thought highly of NPL,believing that it enabled them to gain knowledge and helped them to improve teaching skills.Conclusions The NPL intervention is suitable for the teaching of EMG,because of its contri-bution to knowledge acquisition and basic clinical skills improvement.The NPL is worth replicating in other teaching and learning programs.

OBJECTIVE: To explore the incidence, clinical features, genetic variant characteristics and prognosis of Glutaric acidemia type I (GA1) among neonates from Henan Province. METHODS: A total of 814 625 neonates undergoing screening for inherited metabolic diseases by tandem mass spectrometry (MS/MS) at the Third Affiliated Hospital of Zhengzhou University from January 2016 to December 2022 were selected as the study subjects. A retrospective method was adopted to collect the clinical data of the patients. Whole exome sequencing was carried out to detect GCDH gene variants in individuals with positive results by GA1 newborn screening, and Sanger sequencing was used to verify the candidate variants. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), the pathogenicity of candidate variants was rated. This study was approved by the Medical Ethics Committee of the Hospital (Ethics Number: 2019 Medical Ethics Review No. 67). RESULTS: Eight cases of GA1 were diagnosed among the 814 625 neonates. Blood glutaryl carnitine (C5DC) and urine glutaric acid (GA) levels of the 8 children were higher than the normal reference values. In total 12 variants were detected, all of which were missense variants. c.1064G>A (p.Arg355His) was the most common one, accounting for 21.4% (3/14). Three GCDH gene variants, including 1297G>C (p.Ala433Pro), c.467G>A (p.Gly156Asp) and c.1125T>G (p.Cys375Trp), were previously unreported. REVEL software analysis predicted that all of the three variants were harmful. 3D protein structure modeling indicated that the three variants may cause amino acid residue alterations, and c.1297G>C (p.Ala433Pro) and c.1125T>G (p.Cys375Trp) may result in increase in hydrogen bonds and affect the function of GCDH protein. By December 2023, one of the eight children had deceased, and another child had severe clinical symptoms with poor prognosis. Six children had a good prognosis, of which two had mild motor development delay and four had normal development without clinical symptoms. CONCLUSION The incidence of GA1 in newborns screened by MS/MS in Henan Province is 1/101 828, and the carrier rate of pathogenic GCDH variants is 1/160. The c.1064G>A (p.Arg355His) may be the hotspot variant of the GCDH gene among children with GA1 in Henan. Discovery of the three novel variants has enriched the mutational spectrum of the GCDH gene and provide a basis for the early diagnosis, treatment, prognosis and genetic counseling of this disease.
Humans ; Amino Acid Metabolism, Inborn Errors/epidemiology* ; Glutaryl-CoA Dehydrogenase/chemistry* ; Infant, Newborn ; Female ; Neonatal Screening/methods* ; Male ; Brain Diseases, Metabolic/epidemiology* ; China/epidemiology* ; Retrospective Studies ; Mutation ; Genetic Variation ; Glutarates

OBJECTIVE: To explore the impact of age on the genetic variant spectrum and prognosis of patients with previously untreated Diffuse large B-cell lymphoma (DLBCL). METHODS: A retrospective analysis was conducted on the clinical data and follow-up information of 254 previously untreated DLBCL patients from 14 hospitals in the Jiangsu Cooperative Lymphoma Group (JCLG) enrolled from July 2018 and July 2023. Following extraction of DNA from tumor tissue samples, next-generation sequencing (NGS) technique was employed to analyze the genetic variant spectrum of the DLBCL patients, with an evaluation of the relationship between age and genetic variants as well as prognosis. This study was approved by the Medical Ethics Committee of the Affiliated Hospital of Nantong University (Ethics No.: 2023-K048-01). RESULTS: The median age of the 254 DLBCL patients was 62 years old, with 55% of patients aged 60 years or above. Clinical evaluation showed that younger (< 60 years) patients had higher complete response (CR) (70% vs. 59%), and objective response rate (ORR) (88% vs. 79%) than older patients, though the difference between the two groups was not statistically. Survival analysis indicated that both the five-year overall survival (OS) (82.7% vs. 71.7%, P = 0.006) and progression-free survival (PFS) (70.6% vs. 50.2%, P < 0.05) rates were significantly higher in younger patients. NGS showed that 99.6% of the patients harbored genetic variants, with PIM1, KMT2D, TP53, MYD88, and CD79B being the most common genes. Age significantly affected the variant frequency of certain genes, with MYC variants serving an adverse prognostic factor for OS in younger patients (P = 0.002), while TP53 (P = 0.024) and BCL2 (P = 0.002) variants significantly impacted OS in older patients. Prognostic analysis identified age ≥ 60 years (HR = 3.439, 95%CI: 1.318~9.874), presence of B symptoms (HR = 2.871, 95%CI = 1.133~7.307), and elevated lactate dehydrogenase (HR = 3.528, 95%CI = 1.231~10.66) as independent adverse prognostic factors. CONCLUSION Age, genetic variants, and clinical factors may significantly affect the prognosis of the DLBCL patients. Younger patients have better survival compared to older patients. Variants of the MYC, BCL2, and TP53 genes are closely associated with poor prognosis.
Humans ; Lymphoma, Large B-Cell, Diffuse/diagnosis* ; Middle Aged ; Female ; Male ; Retrospective Studies ; Aged ; Prognosis ; Adult ; Aged, 80 and over ; High-Throughput Nucleotide Sequencing ; Young Adult ; Adolescent ; Genetic Variation

OBJECTIVE: To analyze the ABO serological and molecular characteristics of a Chinese pedigree carrying an ABO*cisAB.01 allele for the blood subgroup. METHODS: A proband undergoing blood preparation for a surgery due to an open rupture of the extensor hallucis longus tendon in the left thumb on September 5, 2024 at Weihai Central Hospital and his family members were selected as study subjects. ABO serological type of six individuals from three generations was determined by serological methods. PCR was carried out to amplify exons 6 and 7 of the ABO gene, and the amplified products were directly sequenced. Samples of the proband and his mother, son, and daughter were subjected to clone sequencing analysis. This study was approved by the Medical Ethics Committee of Weihai Central Hospital (Ethics No.: LL-2024-269-01). RESULTS: Serological testing showed that the proband and his mother were of the AB subtype, whilst his daughter was A subtype B, his father was of O, his wife was AB, and his son was A. Direct sequencing showed that the proband's genotype was ABO*cisAB.01/O.01.02, and his mother, son, and daughter had all carried an ABO*cisAB.01 allele. There were significant differences in allelic competition when the A, B and O genes were co-dominant with the cisAB.01 allele, respectively. CONCLUSION There is allelic competition between the cisAB.01 allele and different ABO alleles. Blood type serological tests combined with molecular methods and family investigations can help ascertain and interpret the ABO blood type phenotypes.
Humans ; ABO Blood-Group System/genetics* ; Male ; Female ; Phenotype ; Pedigree ; Alleles ; Genotype ; Adult ; Asian People/genetics*

Objective:To compare the clinical outcomes of immediate breast reconstruction using latissimus dorsi flap with implant versus mesh with implant based on BREAST-Q evaluation.Methods:From the clinical database of the First Affiliated Hospital of Nanjing Medical University, the patients who underwent immediate breast reconstruction after total mastectomy from January 2020 to December 2023 were selected as the research subjects. All breast reconstruction surgeries were performed by the same surgeon. Patients were divided into two groups according to surgical methods: the latissimus dorsi muscle flap combined with implant immediate breast reconstruction group (LD group) and the mesh combined with implant immediate breast reconstruction group (mesh group). Patients were followed up in outpatient clinics or by telephone one year after surgery. The BREAST-Q was used to evaluate the surgical outcomes of both groups from four dimensions: psychosocial well-being, sexual well-being, chest-physical well-being, and breast satisfaction. The score range for each dimension was 0-100, with higher scores indicating greater patient satisfaction with quality of life and surgical outcomes. Statistical analysis was performed using SPSS 22.0 software. Normally distributed measurement data were expressed as Mean ± SD, and comparisons between the two groups were performed using independent sample t-test. Count data were expressed as number of cases and percentages, and comparisons between groups were performed using chi-square test or Fisher’s exact test. P<0.05 was considered statistically significant. Results:A total of 123 patients were included, with 59 patients in the LD group and 64 patients in the mesh group. In the LD group, the mean age was (37.7±7.0) years, body mass index (BMI) was (22.6±2.6) kg/m 2, and clinical tumor staging showed 2, 22, 30, and 5 cases for stages 0, Ⅰ, Ⅱ, and Ⅲ, respectively. In the mesh group, the mean age was (39.1±7.0) years, BMI was (22.6±2.8) kg/m 2, and clinical tumor staging showed 1, 25, 38, and 0 cases for stages 0, Ⅰ, Ⅱ, and Ⅲ, respectively. There were no statistically significant differences between the two groups in baseline characteristics including age, BMI, and clinical tumor staging (all P>0.05). One year after surgery, the BREAST-Q result showed no statistically significant differences between the LD group and mesh group in psychosocial well-being [(83.0±19.8) points vs. (80.8±19.3) points] and sexual well-being [(62.1±30.4) points vs. (65.8±25.6) points] (all P>0.05). However, the LD group had lower chest-physical well-being scores than the mesh group [(40.6±9.7) points vs. (45.1±9.6) points, P<0.05], while breast satisfaction scores were higher in the LD group than in the mesh group [(68.0±17.8) points vs. (59.8±12.6) points, P<0.01]. Conclusion:Immediate breast reconstruction by both latissimus dorsi flap with implant and mesh with implant can improve patients’ psychosocial and sexual well-being by enhancing breast appearance. However, LD technique provides better breast satisfaction, while the mesh technique offers advantages in physical well-being of the chest wall and upper body. Surgeons should select the most appropriate breast reconstruction technique based on patients’ anatomical conditions, treatment history, and individual needs to optimize postoperative quality of life and satisfaction.

[Objective]To explore the origin and evolution of the unnamed prescriptions in Handbook of Prescriptions for Emergency in order to clarify the development context of the unnamed prescriptions in this book and provide some ideas for exploring the origins of other unnamed prescriptions in medical formulary.[Methods]By using methods of cataloging,bibliology and historical research,this article briefly describes the version of the Handbook of Prescriptions for Emergency and its unnamed prescriptions.Besides,it compares and analyzes the unnamed prescriptions in the Handbook of Prescriptions for Emergency with those in related medical books to investigate the origin and evolution of the unnamed prescriptions in this book.[Results]Apart from the accompanying prescriptions,Handbook of Prescriptions for Emergency contains a total of 1 130 unnamed prescriptions.There are 14 unnamed prescriptions in Handbook of Prescriptions for Emergency that can be traced back to the medical prescriptions on the wooden slips unearthed in Liye and Zhoujiatai,and the Formulas for Fifty-two Diseases written on silk from the Mawangdui Han Tomb,were particularly closely related to the latter formulas.Besides,there are 22 unnamed prescriptions in Handbook of Prescriptions for Emergency derived from Treatise on Febrile Diseases and Synopsis of the Golden Chamber.Although there are 26 unnamed prescriptions for treating sudden death and poisoning caused by drugs and food,which are similar to the content of"miscellaneous treatment prescriptions""taboos for poultry,animals,fish,insects"and"taboos for fruits,vegetables and grains"in the current edition of Synopsis of the Golden Chamber,they are suspected to be written by GE Hong and were confused by Song officials and added to Synopsis of the Golden Chamber.In addition,there are 255 unnamed prescriptions in Handbook of Prescriptions for Emergency that gradually evolved into named prescriptions in later generations,were mainly recorded in five books including Important Formulas Worth a Thousand Gold Pieces for Emergency,Arcane Essentials from the Imperial Library,Taiping Royal Prescriptions,Comprehensive Recording of Divine Assistance and Formulas for Universal Relief.Finally,it is speculated that Huanglian Jiedu Decoction in Cuishi Fang and Xiaodingzhi Pill in Sanyin Jiyi Bingzheng Fanglun are all originated from unnamed prescriptions in Handbook of Prescriptions for Emergency.[Conclusion]The emergence of prescriptions is not static,which has gone through a process from simple to complex,from unnamed prescriptions to named prescriptions.Taking the famous prescription book Handbook of Prescriptions for Emergency from the Jin Dynasty as an example,the unnamed prescriptions recorded in the book can be dated back to the medical records inscribed wooden slips of the Qin and Han Dynasties,and have inspired later famous prescriptions,revealing to some extent the laws of the origin and evolution of prescriptions.