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

ObjectivePhotoacoustic tomography (PAT) holds significant potential for high-resolution deep-tissue imaging. In preclinical research, custom-designed concave arc-shaped ultrasound transducer arrays are often used to maximize the detection aperture. However, manufacturing limitations and assembly tolerances frequently cause the actual physical positions of array elements to deviate from their theoretical design. Additionally, concave arrays are typically covered with an acoustic lens, which introduces a mismatch in the speed of sound between the coupling medium and the lens material. The combination of these geometric and acoustic-phase errors leads to severe image artifacts, reduced contrast, and degraded resolution. This study proposes a systematic two-step calibration strategy to address these issues and substantially improve image quality. MethodsFirst, a high-intensity isotropic photoacoustic point source was constructed using a multi-mode optical fiber coated with carbon nanotubes (CNTs) to acquire high signal-to-noise ratio calibration data. The Akaike information criterion (AIC) was employed to accurately determine the time of arrival (ToA) of photoacoustic signals. Subsequently, a geometric calibration algorithm based on nonlinear least-squares (NLS) estimation was developed. This algorithm iteratively solves for the true spatial coordinates of each array element by minimizing the residual between theoretical and measured acoustic path lengths. To further address sound-speed inhomogeneity caused by the acoustic lens, a phase compensation algorithm based on bilinear interpolation was proposed. This algorithm computes a pixel-specific phase delay map across the imaging region and performs point-by-point signal correction during delay-and-sum (DAS) reconstruction. The proposed methods were validated using a custom 96-channel concave arc-shaped array (center frequency: 12  MHz) through both phantom imaging and in vivo mouse tumor models. ResultsPhantom experiments showed that at an imaging depth of14 mm, the reconstruction position deviation of the point source in the uncalibrated system reached up to 1  mm. After applying the combined calibration, the lateral resolution (full width at half maximum, FWHM) at the focal point of the arc array reached 95  μm—representing a 85% reduction compared to the uncalibrated state and a 79% reduction compared to geometric calibration alone without phase compensation. In vivo experiments demonstrated that the calibrated system clearly resolved the microvascular network of subcutaneous tumors in mice. Photoacoustic signals were strictly confined within tumor boundaries delineated by ultrasound imaging (USI), eliminating the vascular spillover artifacts commonly observed in uncalibrated images. Furthermore, after intravenous injection of indocyanine green (ICG), the system successfully detected weak photoacoustic signals at a depth of 5 mm, performing significantly better than the uncalibrated system. ConclusionThe proposed calibration method, which integrates nonlinear least-squares estimation with phase compensation, significantly improves image fidelity and spatial resolution consistency across a wide field of view by correcting systemic geometric errors and acoustic phase aberrations. This approach demonstrates high robustness and provides a reliable technical foundation for the clinical translation of photoacoustic probes with non-standard geometries.

Sepsis is a life-threatening organ dysfunction caused by a dysregulated host response to infection. Septic shock is the primary cause of mortality in sepsis, with its core pathophysiological mechanism being severe ischemia and hypoxia in critical units—composed of microcirculation and the mitochondria of functional cells—resulting from disruptions in blood flow and oxygen flow following a dysregulated host response. Due to the systemically convergent yet clinically heterogeneous nature of the host response, current understanding and management strategies for hemodynamics remain inconsistent, often leading to inadequate resuscitation or overtreatment. To improve the quality of care, based on a systematic review of the "blood flow-oxygen flow" theory, an expert panel emphasizes reevaluating septic shock from an integrated perspective of blood flow and oxygen flow, and has formulated the Expert Consensus on Blood Flow and Oxygen Delivery Phenotyping and Clinical Management of Septic Shock (2025). The consensus proposes that clinical typing of blood flow-oxygen flow should comprehensively consider cardiac function, vascular tone, oxygen flow utilization status in critical units, and disease trajectory, while optimizing subtype identification by integrating host response phenotypes and artificial intelligence technologies. It advocates establishing a continuous assessment system through multi-site oxygen flow monitoring for organ perfusion, peripheral perfusion monitoring, and critical care ultrasound. Under the framework of the "critical care triangle", the consensus promotes the implementation of individualized, bundled management strategies, providing guidance for multiple management points to restore blood flow-oxygen flow matching, reduce the risk of organ failure, and decrease patient mortality.

ObjectiveTo investigate the effects of zinc finger E-box binding homeobox 1 （ZEB1） on the proliferation， migration， and invasion of lung adenocarcinoma H322 cells， as well as its underlying molecular mechanisms. MethodsThe gene expression characteristics of the transcription factor ZEB1 in lung adenocarcinoma were analyzed using data from the GEO and TCGA public databases. RT-qPCR and Western blot were employed to measure mRNA and protein expression levels of ZEB1 in lung adenocarcinoma cell lines （H322， A549， 95-D） and normal human bronchial epithelial cells （BEAS-2B）. Lentiviral transduction was utilized to establish stable ZEB1-overexpressing （Oe-ZEB1） and vector control （Oe-NC） H322 cell lines. Cell proliferation was assessed using CCK-8， colony formation， and EdU assays， while apoptosis was evaluated by Hoechst33258/PI double staining. Wound healing and Transwell assays were performed to examine cell migration and invasion capabilities. Cell cycle distribution was determined by flow cytometry， and Western blot was used to analyze protein expression changes in relevant signaling pathways. ResultsThe findings from GEO and TCGA indicated that ZEB1 expression in lung adenocarcinoma varied with tumor malignancy grade. RT-qPCR and Western blot analyses revealed significantly higher ZEB1 expression in lung adenocarcinoma cell lines compared to BEAS-2B cells （P0.05）. Results from the CCK-8， colony formation， EdU， wound healing， and Transwell assays demonstrated that， compared with the un-transfected control （Control） group， Oe-ZEB1 H322 cells exhibited enhanced proliferation， migration， and invasion capabilities （P0.05）. Hoechst33258/PI double staining and flow cytometry analyses showed that， relative to the Control group， apoptosis was reduced in Oe-ZEB1 H322 cells （P0.05）. Additionally， a decreased proportion of cells in the G₁ phase and an increased proportion in the S phase were observed in Oe-ZEB1 cells， indicating accelerated cell cycle progression. Western blot analysis further revealed that， compared with the Control group， Oe-ZEB1 H322 cells exhibited upregulated expression of N-cadherin， mutant p53 （mutp53）， and Cyclin D1 （P0.05）， while expression levels of E-cadherin， murine double minute 2 （MDM2）， and p21 were downregulated （P0.05）. ConclusionOverexpression of ZEB1 promotes the proliferation， migration， and invasion of lung adenocarcinoma H322 cells and may facilitate cell cycle progression by modulating the MDM2/mutp53/p21 signaling pathway， thereby promoting the transition of cells from the G₀/G₁ phase to the S phase.

ObjectiveTo investigate the effects of Trpc6 knockout on chronic lipopolysaccharide （LPS）-induced myocardial inflammation and fibrosis in mice and its potential mechanisms. MethodsMale C57BL/6 wild-type （WT） mice and Trpc6 knockout （Trpc6^-/-） mice of the same background were randomly divided into four groups： WT control， WT+LPS （200 μg/kg）， Trpc6^-/- control， and Trpc6^-/-+LPS （200 μg/kg）. Group with LPS received intraperitoneal LPS injections for 21 consecutive days to induce chronic myocardial inflammatory injury. Cardiac ultrasound assessed changes in left ventricular ejection fraction （EF）， left ventricular shortening fraction （FS）， and cardiac output （CO）. Hematoxylin and eosin （HE） staining and periodic acid-Schiff （PAS） staining were used to examine morphological alterations in myocardial tissue. Masson’s trichrome staining was used to assess myocardial fiber alterations； Western blot analysis was used to measure myocardial tissue expression of transient receptor potential calcium channel 6 （TRPC6）， NOD-like receptor family pyrin domain-containing 3 inflammasome （NLRP3），absent in melanoma 2 inflammasome （AIM2）， Caspase-1， interleukin （IL）-6， and IL-1β in mouse myocardial tissue. ResultsCompared with the WT control group， the WT+LPS group exhibited decreased cardiac EF （P<0.01）， FS （P<0.01）， and CO （P<0.05）， along with significantly increased myocardial tissue damage， glycoprotein deposition， and fibrosis （P<0.01）. Further analysis revealed that compared with the WT control group， the WT+LPS group exhibited markedly increased myocardial tissue expression of TRPC6， NLRP3， AIM2， Caspase-1， IL-6， and IL-1β （P<0.01）. Compared with the WT+LPS group， mice in the Trpc6^-/- +LPS group exhibited elevated EF （P<0.01） and FS （P<0.05）， along with reduced myocardial tissue injury， glycoprotein deposition， and fibrosis （P<0.05）. ConclusionChronic LPS treatment can activate NLRP3/AIM2 inflammasomes through the up-regulation of TRPC6 expression， and then lead to chronic myocardial inflammatory injury and fibrosis， while Trpc6 knockdown can reduce myocardial inflammatory injury and fibrosis， and the mechanism is related to inhibiting the activation of NLRP3/AIM2 inflammasomes.

ObjectiveTo investigate the mechanism by which Jianpi Xiao'ai prescription （JPXAP） inhibits colorectal cancer progression by regulating the inducible nitric oxide synthase-arginase 1 （iNOS-ARG1） metabolic axis and inducing mitochondrial reactive oxygen species （mito-ROS）-mediated mitochondrial structural and functional impairment. MethodsAn arginine metabolism disorder model of human colorectal cancer HCT116 cells was established by combined treatment with recombinant human interferon-γ （IFN-γ， 10 μg·L^-1） and N（ω）-hydroxy-L-arginine （Nor-NOHA， 200 μmol·L^-1） for 24 h， followed by intervention with 5%， 10%， or 20% JPXAP-containing serum. Cell proliferation was assessed using cell counting kit-8 （CCK-8）， 5-ethynyl-2′-deoxyuridine （EdU） staining， and colony formation assays. Cell invasion and migration were evaluated using Transwell chamber and wound healing assays. Mitochondrial membrane potential （MMP） and ROS levels were assessed by JC-1 and MitoSOX staining， respectively. Mitochondrial ultrastructure was observed by transmission electron microscopy （TEM）. The expression of iNOS， ARG1， and mitochondrial dynamics-related proteins， including mitofusin 2 （MFN2） and dynamin-related protein 1 （DRP1）， was analyzed by Western blot and immunofluorescence. The levels of L-arginine， citrulline， and urea were determined by colorimetric methods and enzyme-linked immunosorbent assay （ELISA）. ResultsCompared with the blank group， the model group exhibited significantly upregulated iNOS expression， downregulated ARG1 expression， a decreased ARG1/iNOS ratio， reduced L-arginine and urea levels， and increased citrulline levels （P<0.05）. Meanwhile， mito-ROS accumulation was significantly increased， the JC-1 red/green fluorescence ratio was decreased， and mitochondria showed swelling and cristae disruption， indicating that metabolic disorder induced mitochondrial injury. Compared with the model group， all JPXAP-treated groups further decreased the ARG1/iNOS ratio， enhanced nitric oxide （NO） and reactive nitrogen species accumulation， further reduced L-arginine and urea levels， and increased citrulline levels （P<0.01）. EdU-positive rate， colony formation rate， wound healing rate， and Transwell invasion number all decreased significantly with increasing serum concentration （P<0.01）. Mito-ROS levels were further elevated， and the JC-1 red/green ratio further decreased. TEM revealed aggravated mitochondrial swelling and vacuolization. MFN2 expression was downregulated and DRP1 expression was upregulated （P<0.01），in a dose-dependent manner. ConclusionJPXAP further activates NO-mediated oxidative/nitrosative stress under arginine metabolism imbalance， inducing mito-ROS accumulation， MMP collapse， and mitochondrial dynamics imbalance， thereby inhibiting colorectal cancer cell proliferation and migration. These findings reveal an antitumor mechanism of JPXAP based on coordinated targeting of the "metabolism-mitochondria" axis.

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.

OBJECTIVE To discuss the impact of Wenyang lishui formula on ventricular remodeling in rats with pulmonary hypertension-induced right heart failure （RHF） based on the Hippo/Yes-associated protein （YAP） signaling pathway. METHODS Ten rats were randomly selected as the control group. The remaining 63 rats were given a single intraperitoneal injection of monocrotaline to establish the pulmonary hypertension-induced RHF model. The 50 rats that successfully underwent the model establishment were randomly divided into the RHF group， low-dose group of Wenyang lishui formula （4.25 g/kg）， high-dose group of the Wenyang lishui formula （17.00 g/kg）， furosemide group （20 mg/kg）， and high-dose group of Wenyang lishui formula+ Hippo/YAP signaling pathway activator group （17.00 g/kg of Δ Wenyang lishui formula+16 mg/kg of PY-60）， with 10 rats in each group. The rats in each group were given the corresponding drug solution or normal saline by gavage or/andtail vein injection， once a day， for 4 consecutive weeks. During the experiment， the general conditions of the rats in each group were observed； after the last administration， the right ventricular diameter， right atrial diameter， end-diastolic volume， pulmonary artery blood flow acceleration time （PAAT） and its ratio to ejection time （ET） （PAAT/ET）， pulmonary artery pressure and its ratio to pulmonary arterial flow velocity （pulmonary artery pressure/velocity） were measured. The plasma levels of brain natriuretic peptide and angiotensin Ⅱ （Ang Ⅱ） were detected. The pathological changes of the right ventricular tissue were observed， and the collagen volume fraction， the phosphorylation levels of the large tumor suppressor 1/2 （LATS1/2） and YAP， and the protein expression of the transcriptional coactivator of PDZ-binding motif （TAZ） were also detected. RESULTS Compared with the RHF group， the rats in Wenyang lishui formula low-dose and high-dose groups showed improved hair color， movement， diet， and mental state. The atrophy of right ventricular myocardial cells， the increase of inflammatory cells， collagen deposition， and hypertrophy of myocardial fibers were significantly alleviated. The right ventricular internal diameter， right atrial internal diameter， end-diastolic volume， pulmonary artery pressure， pulmonary artery pressure/velocity， the plasma levels of brain natriuretic peptide and AngⅡ ， collagen volume fraction， the phosphorylation level of YAP and protein expression of TAZ were significantly decreased， while the PAAT， PAAT/ET and the phosphorylation level of LATS1/2 were significantly increased （P＜0.05）. PY-60 could significantly reverse the improvement effects of high-dose Wenyang lishui formula on the above quantitative indicators （P＜ 0.05）. CONCLUSIONS Wenyang lishui formula can restore the right heart function of pulmonary hypertension-induced RHF rats， reduce their pulmonary artery pressure， alleviate the pathological changes in their cardiac tissues， and the above effects may be related to the activation of Hippo expression and the inhibition of YAP phosphorylation.

BACKGROUND: The role of inflammation in the development of gestational diabetes mellitus (GDM) has recently become a focus of research. The systemic immune-inflammation index (SII) and systemic inflammation response index (SIRI), novel indices, reflect the body's chronic immune-inflammatory state. This study aimed to investigate the associations between the SII or SIRI and GDM. METHODS: A prospective birth cohort study was conducted at Beijing Obstetrics and Gynecology Hospital from February 2018 to December 2020, recruiting participants in their first trimester of pregnancy. Baseline SII and SIRI values were derived from routine clinical blood results, calculated as follows: SII = neutrophil (Neut) count × platelet (PLT) count/lymphocyte (Lymph) count, SIRI = Neut count × monocyte (Mono) count/Lymph count, with participants being grouped by quartiles of their SII or SIRI values. Participants were followed up for GDM with a 75-g, 2-h oral glucose tolerance test (OGTT) at 24-28 weeks of gestation using the glucose thresholds of the International Association of Diabetes and Pregnancy Study Groups (IADPSG). Logistic regression was used to analyze the odds ratios (ORs) (95% confidence intervals [CIs]) for the the associations between SII, SIRI, and the risk of GDM. RESULTS: Among the 28,124 women included in the study, the average age was 31.8 ± 3.8 years, and 15.76% (4432/28,124) developed GDM. Higher SII and SIRI quartiles were correlated with increased GDM rates, with rates ranging from 12.26% (862/7031) in the lowest quartile to 20.10% (1413/7031) in the highest quartile for the SII ( Ptrend <0.001) and 11.92-19.31% for the SIRI ( Ptrend <0.001). The ORs (95% CIs) of the second, third, and fourth SII quartiles were 1.09 (0.98-1.21), 1.21 (1.09-1.34), and 1.39 (1.26-1.54), respectively. The SIRI findings paralleled the SII outcomes. For the second through fourth quartiles, the ORs (95% CIs) were 1.24 (1.12-1.38), 1.41 (1.27-1.57), and 1.64 (1.48-1.82), respectively. These associations were maintained in subgroup and sensitivity analyses. CONCLUSION The SII and SIRI are potential independent risk factors contributing to the onset of GDM.
Humans ; Female ; Pregnancy ; Diabetes, Gestational/immunology* ; Prospective Studies ; Adult ; Inflammation/immunology* ; Glucose Tolerance Test ; Birth Cohort