OBJECTIVE: To analyze the clinical characteristics, treatment, and prognosis of seven pediatric patients with Acute myeloid leukemia (AML) positive for the t(16;21)(p11;q22) FUS::ERG fusion gene. METHODS: A retrospective analysis was carried out on the clinical data, treatment, and prognosis of seven AML patients with t(16;21)(p11;q22) FUS::ERG fusion gene admitted to Henan Children's Hospital between June 2015 and November 2024. Relevant literature was also reviewed. This study was approved by the Medical Ethics Committee of the Hospital (Ethics No.: 2024-102-001). RESULTS: Among 297 pediatric patients with AML, 7 cases (2.36%) were positive for the t(16;21)(p11;q22) FUS::ERG fusion gene, including 3 males and 4 females, with a median age of 11 years (range: 3 ~ 12 years). According to the FAB classification, these included 1 case of M2, 3 cases of M5, and 3 cases of AML-not otherwise specified (non-M3). All 7 patients were found to harbor the t(16;21)(p11;q22) translocation, with 3 cases showing additional chromosomal abnormalities. Immunophenotyping revealed universal expression of CD13, CD33, CD34, and CD117, with partial expression of CD56, CD4, CD64, CD123, CD15, CD38, CD11b, HLA-DR, cMPO, and CD16. One patient achieved complete remission (CR) after the first course of DAE (cytarabine + daunorubicin + etoposide) induction chemotherapy but relapsed and discontinued the treatment. Six patients received DAH (cytarabine + daunorubicin + homoharringtonine) induction therapy, of whom 2 achieved CR after two courses and underwent allogeneic hematopoietic stem cell transplantation (allo-HSCT), resulting in an overall CR rate of 42.86%. Five children did not receive allo-HSCT and had a median overall survival of 9 months (range: 6 ~ 18 months). Two children who underwent transplantation achieved bone marrow morphological and molecular biological relapse at 6 and 9 months post-transplantation, respectively. After receiving combined chemotherapy and donor lymphocyte infusion, one child failed to achieve remission and died at 22 months post-transplantation, while the other has been followed up to date with positive fusion gene status. Their overall survival was 25 months and 30 months, respectively. CONCLUSION The t(16;21)(p11;q22) FUS::ERG fusion gene is rare in pediatric AML and associated with poor prognosis. Allo-HSCT may mitigate the adverse prognostic impact of the FUS::ERG fusion gene and contribute to prolonged survival.
Humans ; Male ; Child ; Female ; Leukemia, Myeloid, Acute/drug therapy* ; Oncogene Proteins, Fusion/genetics* ; Translocation, Genetic ; Retrospective Studies ; RNA-Binding Protein FUS/genetics* ; Chromosomes, Human, Pair 16/genetics* ; Adolescent ; Child, Preschool ; Chromosomes, Human, Pair 21/genetics* ; Prognosis ; Treatment Outcome

Health economics evidence plays an important role in linking clinical value evidence with health resource allocation decisions in the development of clinical practice guidelines. It can not only effectively balance clinical effectiveness and economic feasibility but also avoid forming "idealized" recommendations that are detached from the affordability of the healthcare system or the burden-bearing capacity of patients. To promote guideline developers to use health economics evidence more standardizedly and fully, this paper conducts an in-depth analysis of the current application status, existing challenges, access channels, and application processes of health economics evidence in current guidelines, and on this basis, puts forward considerations and suggestions for strengthening and standardizing the application of health economics evidence in China's clinical practice guidelines.

Membrane proteins are integral components of cellular membranes, accounting for approximately 30% of the mammalian proteome and serving as targets for 60% of FDA-approved drugs. They are critical to both physiological functions and disease mechanisms. Their functional protein-protein interactions form the basis for many physiological processes, such as signal transduction, material transport, and cell communication. Membrane protein interactions are characterized by membrane environment dependence, spatial asymmetry, weak interaction strength, high dynamics, and a variety of interaction sites. Therefore, in situ analysis is essential for revealing the structural basis and kinetics of these proteins. This paper introduces currently available in situ analytical techniques for studying membrane protein interactions and evaluates the characteristics of each. These techniques are divided into two categories: label-based techniques (e.g., co-immunoprecipitation, proximity ligation assay, bimolecular fluorescence complementation, resonance energy transfer, and proximity labeling) and label-free techniques (e.g., cryo-electron tomography, in situ cross-linking mass spectrometry, Raman spectroscopy, electron paramagnetic resonance, nuclear magnetic resonance, and structure prediction tools). Each technique is critically assessed in terms of its historical development, strengths, and limitations. Based on the authors’ relevant research, the paper further discusses the key issues and trends in the application of these techniques, providing valuable references for the field of membrane protein research. Label-based techniques rely on molecular tags or antibodies to detect proximity or interactions, offering high specificity and adaptability for dynamic studies. For instance, proximity ligation assay combines the specificity of antibodies with the sensitivity of PCR amplification, while proximity labeling enables spatial mapping of interactomes. Conversely, label-free techniques, such as cryo-electron tomography, provide near-native structural insights, and Raman spectroscopy directly probes molecular interactions without perturbing the membrane environment. Despite advancements, these methods face several universal challenges: (1) indirect detection, relying on proximity or tagged proxies rather than direct interaction measurement; (2) limited capacity for continuous dynamic monitoring in live cells; and (3) potential artificial influences introduced by labeling or sample preparation, which may alter native conformations. Emerging trends emphasize the multimodal integration of complementary techniques to overcome individual limitations. For example, combining in situ cross-linking mass spectrometry with proximity labeling enhances both spatial resolution and interaction coverage, enabling high-throughput subcellular interactome mapping. Similarly, coupling fluorescence resonance energy transfer with nuclear magnetic resonance and artificial intelligence (AI) simulations integrates dynamic structural data, atomic-level details, and predictive modeling for holistic insights. Advances in AI, exemplified by AlphaFold’s ability to predict interaction interfaces, further augment experimental data, accelerating structure-function analyses. Future developments in cryo-electron microscopy, super-resolution imaging, and machine learning are poised to refine spatiotemporal resolution and scalability. In conclusion, in situ analysis of membrane protein interactions remains indispensable for deciphering their roles in health and disease. While current technologies have significantly advanced our understanding, persistent gaps highlight the need for innovative, integrative approaches. By synergizing experimental and computational tools, researchers can achieve multiscale, real-time, and perturbation-free analyses, ultimately unraveling the dynamic complexity of membrane protein networks and driving therapeutic discovery.

Forensic medicine has been designated as a first-level discipline,presenting new opportunities and challenges for the development of forensic medicine.Since the 1980s,the establishment of foren-sic medicine discipline and the cultivation of high-level forensic talents have become hot topics in the development of forensic medicine in China.Since the 13th Five-Year Plan,the forensic team of Shanxi Medical University has been aiming at the forefront,proposing the development goals of"Five First-class"and the discipline development path"Six Major Achievements".It has selected benchmark disci-plines,identified gaps in disciplinary development,unified thoughts,formulated completion timelines,concentrated superior resources,assigned tasks to individuals,and created an"Organized Fill-in-the-Blank Format"forensic medicine discipline construction model with the characteristics of the new era.The construction model of forensic medicine has achieved good results in the goals,discipline frame-work,scientific research,talent cultivation,discipline team and platform construction,forming a rela-tively complete discipline construction and management system,and accumulating valuable experience for the construction of first-level discipline and high-level talent cultivation of forensic medicine.

Combined with elastic network model (ENM), the perturbation response scanning (PRS) has emerged as a robust technique for pinpointing allosteric interactions within proteins. Here, we proposed the PRS analysis of drug-target networks (DTNs), which could provide a promising avenue in network medicine. We demonstrated the utility of the method by introducing a deep learning and network perturbation-based framework, for drug repurposing of multiple sclerosis (MS). First, the MS comorbidity network was constructed by performing a random walk with restart algorithm based on shared genes between MS and other diseases as seed nodes. Then, based on topological analysis and functional annotation, the neurotransmission module was identified as the "therapeutic module" of MS. Further, perturbation scores of drugs on the module were calculated by constructing the DTN and introducing the PRS analysis, giving a list of repurposable drugs for MS. Mechanism of action analysis both at pathway and structural levels screened dihydroergocristine as a candidate drug of MS by targeting a serotonin receptor of serotonin 2B receptor (HTR2B). Finally, we established a cuprizone-induced chronic mouse model to evaluate the alteration of HTR2B in mouse brain regions and observed that HTR2B was significantly reduced in the cuprizone-induced mouse cortex. These findings proved that the network perturbation modeling is a promising avenue for drug repurposing of MS. As a useful systematic method, our approach can also be used to discover the new molecular mechanism and provide effective candidate drugs for other complex diseases.

Objective:To investigate the impacts of Glaucocalyxin A on myocardial inflammation and immune function in dia-betes rats by regulating cyclic guanosine monophosphate-adenosine monophosphate synthase(cGAS)/stimulator of interferon genes(STING)pathway.Methods:STZ was injected intraperitoneally to model diabetes in rats,after successful modeling,the rats were divided into model group,low-dose Glaucocalyxin A group[10 mg/(kg·d)],high-dose Glaucocalyxin A group[20 mg/(kg·d)]and H-151(750 nmol/d)group,control group was also set up,with 10 rats in each group,the model group and control group were given the same volume of physiological saline for 4 weeks.The fully automated biochemical analyzer was applied to detect TG,TC,HDL-C and LDL-C levels;flow cytometry was applied to detect the levels of CD4+T,CD8+T,CD4+T/CD8+T in the serum of rats in each group;ELISA was applied to detect the levels of TNF-α,IL-6 and IL-1β in myocardial tissue;HE staining was applied to observe pathologi-cal changes in rat myocardium;TUNEL staining was applied to observe the apoptosis of myocardial cells;Western blot was applied to detect the levels of Bcl-2,Bax,cGAS and STING pathway proteins.Results:The myocardial cells of rats in the control group were ar-ranged neatly and structurally intact;compared with the control group,the myocardial cells of rats in the model group were arranged in a disordered manner,with unclear nuclear structure and infiltration of inflammatory cells,the levels of serum TG,TC,CD8+T,myo-cardial tissue TNF-α,IL-6 and IL-1β,myocardial cell apoptosis rate,and the protein expression levels of Bax,cGAS and STING in rats were obviously increased,the levels of HDL-C,CD4+T,CD4+T/CD8+T,and the protein expression level of Bcl-2 were obviously reduced(P<0.05);compared with the model group,the pathological damage status of myocardial cells in the low and high doses Glau-cocalyxin A groups and H-151 group was obviously reduced,the levels of serum TG,TC,CD8+T,myocardial tissue TNF-α,IL-6 and IL-1β,myocardial cell apoptosis rate,and the protein expression levels of Bax,cGAS,and STING in rats were obviously reduced,the levels of HDL-C,CD4+T,CD4+T/CD8+T,and the protein expression level of Bcl-2 were obviously increased(P<0.05);compared with the high-dose Glaucocalyxin A group,there was no statistically obvious difference in all detection indicators in the H-151 group(P>0.05).Conclusion:Glaucocalyxin A may reduce myocardial inflammation and improve immune function in diabetes rats by inhi-biting cGAS-STING signaling pathway.

Objective To explore the effects of Shenyuan Yiqi Huoxue Capsules on cardiopulmonary exercise function and quality of life in patients with ischemic cardiomyopathy.Methods Totally 66 patients with ischemic cardiomyopathy were divided into treatment group and control group using random number table method,with 33 cases in each group.Both groups received standardized Western medicine treatment,and the treatment group was additionally given Shenyuan Yiqi Huoxue Capsules,the control group was given Shenyuan Yiqi Huoxue Capsules simulator,three capsules per time,three times a day,orally.The observation period was 30 days.To evaluate the efficacy of TCM syndrome in two groups.The observation indicators included baseline data,TCM syndrome scores,cardiopulmonary exercise test detection indicators,MLHFQ score,SF-36 score,echocardiographic indicators,N-terminal pro-B-type natriuretic peptide(NT-pro BNP)and safety indicators.Results The total effective rate of the treatment group was 93.94%(31/33),while that of the control group was 78.79%(26/33).The treatment group was significantly better than the control group(P<0.05).Compared with before treatment,the TCM syndrome scores of the two groups of patients decreased(P<0.05),and after treatment,the TCM syndrome score of the treatment group was lower than that of the control group(P<0.05).Compared with before treatment,the peak oxygen uptake(peak VO2),anaerobic threshold(AT)and peak oxygen pulse(peak O2 pulse)of both groups of patients increased,while the carbon dioxide ventilation equivalent slope(VE/VCO2 slope)decreased(P<0.05).After treatment,the treatment group had higher peak VO2,AT and peak O2 pulse than the control group,while the VE/VCO2 slope was lower than the control group(P<0.05).Compared with before treatment,both groups of patients showed a decrease in MLHFQ score and an increase in SF-36 score(P<0.05);after treatment,the MLHFQ score in the treatment group was lower than that in the control group,and the SF-36 score was higher than that in the control group(P<0.05).Compared with before treatment,both groups of patients showed a decrease in left ventricular end systolic diameter,left ventricular end diastolic diameter and NT-pro BNP levels,while myocardial motion index and left ventricular ejection fraction increased(P<0.05);after treatment,the treatment group showed a decrease in left ventricular end systolic diameter,left ventricular end diastolic diameter and NT-pro BNP levels,while myocardial motion index and left ventricular ejection fraction increased(P<0.05).During the treatment period,no adverse reactions such as dizziness,nausea,vomiting or diarrhea were found in both groups of patients.Conclusion Shenyuan Yiqi Huoxue Capsules can significantly improve the clinical efficacy of ischemic cardiomyopathy patients,alleviate TCM symptoms,improve their cardiorespiratory function and quality of life.

Objectives:This study aims to evaluate the causal relationship between plasma proteins and myocardial infarction(MI)using two-sample bidirectional Mendelian randomization(MR)analysis,identify key biomarkers,and validate their expression.Methods:The study utilized publicly available genome-wide association study(GWAS)data of 4 907 plasma proteins as the exposure factor,with single nucleotide polymorphisms(SNPs)as instrumental variables,and four MI datasets as outcomes.Two-sample MR analysis was performed using the inverse variance weighted(IVW)method,complemented by simple model,weighted model,weighted median estimator(WME),and MR-Egger regression methods to assess the causal relationship between exposure factors and outcomes.Venn diagrams and word clouds were used to screen proteins associated with MI as candidate biomarkers.Reverse MR analysis was conducted to evaluate reverse causality.Sensitivity analysis was performed to assess the robustness of the results.Immunohistochemistry(IHC)was used to validate the expression of proteasome activator subunit 1(PSME1)and vacuolar protein sorting 29(VPS29)in the aorta of mice,and enzyme-linked immunosorbent assay(ELISA)was used to verify the expression of PSME1 and VPS29 in plasma from patients with acute myocardial infarction(AMI).Results:The two-sample MR analysis indicated that PSME1 was significantly negatively associated with myocardial infarction in all four datasets,with OR(95%CI)of 0.684(0.557-0.839),0.990(0.987-0.993),0.579(0.448-0.748),and 0.993(0.990-0.996),respectively,with all P<0.001.Similarly,VPS29 also showed a significant negative association with MI in all four datasets,with OR(95%CI)of 0.902(0.862-0.945),0.998(0.997-0.999),0.866(0.808-0.929),and 0.998(0.997-0.999),respectively,with all P<0.001.Reverse MR analysis did not detect reverse causality,and sensitivity analysis confirmed the robustness of the results.IHC results showed significantly reduced expression of PSME1 and VPS29 in the aortas of AMI mice with an atherosclerotic background compared to control mice(both P<0.05).ELISA results indicated significantly lower plasma levels of PSME1 and VPS29 in AMI patients compared to healthy controls(both P<0.05).Conclusions:Higher levels of PSME1 and VPS29 are negatively associated with the risk of MI,suggesting that PSME1 and VPS29 may serve as protective biomarkers for cardiovascular diseases.

Objective:To describe the prevalence of non-alcoholic fatty liver disease (NAFLD) in people living with HIV in Taizhou, Zhejiang Province, and identify the factors associated with NAFLD in this population.Methods:A cross-sectional survey was conducted from 2021 to 2023. Based on the routine follow-up management of people living with HIV, liver ultrasound examination, physical examination and laboratory test were conducted to collect the information about the diagnosis of NAFLD and biochemical indicators in this population. Logistic regression model was used to identify the factors associated with the prevalence of NAFLD.Results:In the 2 550 study participants, the prevalence of NAFLD was 21.5% (548/2 550), abnormal liver function was found in 23.7% (604/2 550) of the study participants, and liver fibrosis was found in 45.2% (1 152/2 550) of the study participants. Multivariable logistic regression analyses showed that being women (a OR=0.55, 95% CI: 0.42-0.73), being overweight or obese (a OR=3.22, 95% CI: 2.59-4.01), having diabetes (a OR=3.37, 95% CI: 2.15-5.29), having dyslipidemia (a OR=2.96, 95% CI: 2.25-3.89), CD4 + T lymphocyte (CD4) counts <200 cells/μl (a OR=0.61, 95% CI: 0.42-0.88), and receiving Efavirenz (EFV) + Lamivudine (3TC) + Zidovudine (AZT) for antiretroviral therapy (ART)(a OR=1.52, 95% CI: 1.17-1.98) were associated with NAFLD. NAFLD was positively associated with abnormal liver function (a OR=2.01, 95% CI: 1.60-2.52) and inversely associated with liver fibrosis (a OR=0.76, 95% CI: 0.59-0.98). The 45-59 age group (a OR=7.05, 95% CI: 5.65-8.80), CD4 counts <200 cells/μl (a OR=1.45, 95% CI: 1.06-1.97) and receiving Nevirapine (NVP)+3TC+AZT of ART (a OR=1.87,95% CI: 1.44-2.43) were the main factors associated with liver fibrosis. Conclusions:The prevalence of NAFLD in people living with HIV Taizhou was more than 20.0%, with a significant proportion of them having abnormal liver function and liver fibrosis. Being overweight or obese, suffering from diabetes, having dyslipidemia, low CD4 counts, and receiving specific ART were associated with NAFLD. NAFLD, CD4 counts and specific ART were the main factors associated with abnormal liver function and liver fibrosis.

Objective:To explore the independent association between handgrip strength and chronic kidney disease (CKD) in adult residents in Anhui Province using data from the China Adult Chronic Disease and Risk Factor Surveillance (2023).Methods:A multi-stage stratified cluster random sampling method was used to select residents aged ≥18 years for surveys, physical measurements, and laboratory tests. Relevant covariates were adjusted, and a multivariable logistic regression model was established to infer the association between handgrip strength and CKD, followed by subgroup analysis.Results:A total of 7 295 participants were included in the study, with age of (61.5±13.2) years, and 55.6% of the study participants were women. The results of the multivariate logistic regression analysis showed that with each 1.0 kg increase in handgrip strength, the risk for CKD decreased by 1.3% ( OR=0.987, 95% CI: 0.978-0.997). Compared with those with low handgrip strength, the people with moderate hasdgrip strength ( OR=0.818, 95% CI: 0.694-0.964) and high handgrip strength ( OR=0.729, 95% CI: 0.598-0.989) had lower risk for CKD. In the subgroup analysis, the association between handgrip strength and risk for CKD remained unchanged regardless age, sex, smoking status, and alcohol consumption statuys, and the prevalence of hypertension and hyperlipidemia (interaction P>0.05), except BMI and diabetes. Conclusion:The decline in handgrip strength is associated with an increased risk for CKD in adult residents in Anhui.