ObjectiveTo examine the influences of Shenfu injection on the endogenous metabolic byproducts in the myocardium of the rat model exhibiting chronic heart failure， thus deciphering the therapeutic mechanism of the Qi-reinforcing and Yang-warming method. MethodsSD rats were randomly allocated into a control group and a modeling group. Chronic heart failure with heart-Yang deficiency syndrome in rats was modeled by multi-point subcutaneous injection of isoproterenol， and the rats were fed for 14 days after modeling. The successfully modeled rats were randomized into model， Shenfu injection （6.0 mL·kg^-1）， and trimetazidine （10 mg·kg^-1） groups and treated with corresponding agents for 15 days. The control group and the model group were injected with equal doses of normal saline， and the samples were collected after the intervention was completed. Cardiac color ultrasound was performed. Hematoxylin-eosin （HE） staining was used to observe histopathological morphology， and the serum level of N-terminal pro-brain natriuretic peptide （NT-proBNP） was assessed by enzyme-linked immunosorbent assay （ELISA）. The mitochondrial morphological and structural changes of cardiomyocytes were observed by transmission electron microscopy， and the metabolic profiling was carried out by ultra high performance liquid chromatography-quantitative exactive-mass spectrometry （UHPLC-QE-MS）. Differential metabolites were screened and identified by orthogonal partial least squares-discriminant analysis （OPLS-DA） and other methods， and then the MetaboAnalyst database was used for further screening. The relevant biological pathways were obtained through pathway enrichment analysis. The receiver operating characteristic （ROC） curve was established to evaluate the diagnostic value of each potential biomarker for myocardial injury and the evaluation value for drug efficacy. ResultsThe results of color ultrasound showed that Shenfu Injection improved the cardiac function indexes of model rats （P<0.05）. The results of HE staining showed that Shenfu injection effectively alleviated the pathological phenomena such as myocardial tissue structure disorder and inflammatory cell infiltration in model rats. The results of ELISA showed that Shenfu injection effectively regulated the serum NT-proBNP level in the model rats. Transmission electron microscopy （TEM） showed that Shenfu injection effectively restored the mitochondrial morphological structure. The results of metabolomics showed that the metabolic phenotypes of myocardial samples presented markedly differences between groups. Nine differential metabolites could be significantly reversed in the Shenfu injection group， involving three metabolic pathways： pyruvate metabolism， histidine metabolism， and citric acid cycle （TCA cycle）. The results of ROC analysis showed that the area under the curve （AUC） values of all metabolites were between 0.75 and 1.0， indicating that the differential metabolites had high diagnostic accuracy for myocardial injury， and the changes in their expression levels could be used as potential markers for efficacy evaluation. ConclusionShenfu injection significantly alleviated the damage of cardiac function， myocardium， and mitochondrial structure in the rat model of chronic heart failure with heart-Yang deficiency syndrome by ameliorating energy metabolism remodeling. Reinforcing Qi and warming Yang is a key method for treating chronic heart failure with heart-Yang deficiency syndrome.

ObjectiveTo explore the effect and mechanism of Jianpi Xiaoai prescription （JPXA） in ameliorating the 5-fluorouracil （5-FU） resistance of colon cancer. MethodsA HCT116/5-FU resistant cell line was established. Different concentrations （10%， 15%， 20%） of JPXA-containing serum and drug-free serum were used for intervention， and 10% fetal bovine serum （10% FBS）， fibroblast growth factor receptor （FGFR） inhibitor （AZD4547）， and recombinant fibroblast growth factor 2 （FGF2） were set as the control groups. Sensitive HCT116 cells were used in the FGF2 group， while HCT116/5-FU cells were used in other groups. Drug resistance， the level of FGF2 in the cell culture medium， the mRNA level of FGF2 in cells， and the protein levels of FGF2/FGFR and phosphatidylinositol 3-kinase/protein kinase B （PI3K/Akt） were determined. The drug-resistant cells were transplanted into the axilla of nude mice to establish a tumor model. The modeled mice were allocated into model， JPXA （15 g·kg^-1）， 5-FU （0.02 g·kg^-1）， JPXA+5-FU （15 g·kg^-1+0.02 g·kg^-1）， AZD4547 （0.012 5 g·kg^-1）， and AZD4547+5-FU （0.012 5 g·kg^-1+0.02 g·kg^-1） groups. The tumor growth and the protein levels of FGF/FGFR and PI3K/Akt in each group were observed. ResultsThe survival rate of HCT116/5-FU cells decreased in all the JPXA groups with different concentrations. The cell survival rate was decreased most obviously in the 20% JPXA group. The level of FGF2 in the cell culture medium and the mRNA level of FGF2 in cells of each JXPA group decreased， and the decrease was the most significant in the 20% group （P<0.01）. HCT116/5-FU cells showed up-regulated protein levels of FGF2 and phosphorylated fibroblast growth factor receptor 1 （p-FGFR1）， but down-regulated protein level of FGFR1 （P<0.01）. JPXA down-regulated the expression of FGF2 and p-FGFR1 and up-regulated the expression of FGFR1 （P<0.05）. In addition， JPXA down-regulated the expression levels of phosphorylated protein kinase B （p-Akt） and phosphorylated mammalian target of rapamycin （p-mTOR）， while up-regulating the expression levels of Akt and Bcl-2-asociated death promoter （Bad） （P<0.05）. Animal experiments showed that the JPXA combined with 5-FU significantly inhibited the growth of drug-resistant tumors， reduced the protein levels of FGF2， p-FGFR1， phosphorylated phosphatidylinositol-3-kinase （p-PI3K）， p-Akt， and p-mTOR， and increased the expression of Bad. It indicated that JPXA can inhibit the FGF2/FGFR1 signaling in colon cancer and regulate PI3K/Akt and downstream signaling pathways. ConclusionJPXA can ameliorate the chemotherapy resistance of colon cancer through down-regulating FGF2 expression and inhibiting the activation of the PI3K/Akt signaling pathway.

Hereditary fibrosing poikiloderma with tendon contractures, myopathy, and pulmonary fibrosis (POIKTMP) is a rare autosomal dominant genetic disorder. It may also involve many other organ systems, leading to complications such as exocrine pancreatic insufficiency, liver dysfunction, lymphedema, and developmental delay. The FAM111B has been determined as the pathogenic gene associated with POIKTMP syndrome, whose protein product plays a critical role in regulating essential cellular processes including DNA repair and replication, cell cycle progression, apoptosis, nuclear transport, and telomere length maintenance. This article has provided a comprehensive review for the genetic basis of POIKTMP syndrome and its correlation with various phenotypes, which may offer insights for basic research and clinical diagnosis of this disease.
Humans ; Pulmonary Fibrosis/genetics* ; Skin Diseases, Genetic/genetics*

Objective: To systematically evaluate the therapeutic efficacy and maintenance effects of digital psychological therapies on depressive symptoms among adolescents, so as to provide a reference for clinical practice. Methods: Randomized controlled trial(RCT) investigating digital psychological therapies to improve depressive symptoms among adolescents were searched across databases, including PubMed, Embase, Cochrane Library, Web of Science, China National Knowledge Infrastructure (CNKI), Wanfang database, VIP database, and SinoMed, from database inception to November 20, 2025. Following literature screening, quality assessment, and data extraction, a Meta analysis was performed using Stata 18.0 software. Results: A total of 20 studies involving 2 042 adolescents aged 11-19 were included. The Meta analysis revealed that digital psychological therapies significantly alleviated depressive symptoms in adolescents ( SMD =-0.59, 95% CI =-0.85 to -0.32, P <0.01). The therapeutic effect was sustained at long term follow up ( SMD =-0.21, 95% CI =-0.34 to -0.09, P <0.01). Furthermore, depression scores in the intervention group showed a continued decrease from post intervention to long term follow up ( SMD =-0.28, 95% CI =-0.41 to -0.14, P <0.01). Egger s linear regression test indicated possible publication bias (Kendall s tall=0.28, P <0.01). Conclusions Digital psychological therapies can effectively improve depressive symptoms among adolescents, with stable long term efficacy. However, current evidence remains limited and exhibits substantial heterogeneity. Therefore, further large sample, high quality RCTs are warranted to validate the effectiveness of this intervention.

Circular RNAs (circRNAs) represent a distinct group of RNA molecules produced through back-splicing of precursor mRNAs. Their covalently closed structure, which lacks both a 5′ cap and a poly(A) tail, renders them highly resistant to exonucleolytic degradation and contributes to their remarkable intracellular stability. Although circRNAs were historically viewed as noncoding transcripts, accumulating evidence indicates that certain circRNAs can undergo translation under appropriate molecular contexts. Two major modes of noncanonical translation have been described so far: initiation mediated by internal ribosome entry sites (IRESs) and translation triggered by N6-methyladenosine (m6A) modification. Recent studies have revealed that, beyond their canonical classification as non-coding RNAs, circRNAs can give rise to functional peptides through cap-independent translational mechanisms. Accumulating evidence indicates that circRNA-encoded peptides participate in key biological processes during tumor initiation and progression by modulating tumor-associated signaling pathways and protein-protein interaction networks. Functionally, these peptides may promote tumor cell proliferation, migration, invasion, and epithelial-mesenchymal transition, while others exert tumor-suppressive effects by inhibiting oncogenic signaling pathways or interfering with critical protein interactions. Their dual and context-dependent functions highlight the complexity of circRNA-mediated regulation and suggest that these translation products participate in multiple layers of tumor initiation and progression. In this review, we synthesize current knowledge regarding the molecular mechanisms that enable circRNAs to be translated, with particular attention to IRES-driven initiation, m6A-dependent regulation, ribosome accessibility, and the structural determinants required for translation competence. We further summarize well-characterized circRNA-encoded peptides and discuss how they influence tumor-associated signaling networks. In addition, we examine the potential translational applications of these peptides, including their value as diagnostic indicators, prognostic markers, or therapeutic entry points. Their inherent sequence stability, relative expression specificity, and detectability in clinical specimens make circRNA-derived peptides promising candidates for future biomarker and therapeutic development. Overall, circRNA translation research is reshaping our understanding of RNA function and offers new perspectives for studying tumor biology. We propose that expanding investigations into circRNA-encoded peptides will not only improve the mechanistic resolution of cancer research but may also pave the way for innovative strategies in precision oncology, including RNA-based therapeutics and peptide-targeting interventions.

Circular RNAs (circRNAs) represent a distinct group of RNA molecules produced through back-splicing of precursor mRNAs. Their covalently closed structure, which lacks both a 5′ cap and a poly(A) tail, renders them highly resistant to exonucleolytic degradation and contributes to their remarkable intracellular stability. Although circRNAs were historically viewed as noncoding transcripts, accumulating evidence indicates that certain circRNAs can undergo translation under appropriate molecular contexts. Two major modes of noncanonical translation have been described so far: initiation mediated by internal ribosome entry sites (IRESs) and translation triggered by N6-methyladenosine (m6A) modification. Recent studies have revealed that, beyond their canonical classification as non-coding RNAs, circRNAs can give rise to functional peptides through cap-independent translational mechanisms. Accumulating evidence indicates that circRNA-encoded peptides participate in key biological processes during tumor initiation and progression by modulating tumor-associated signaling pathways and protein-protein interaction networks. Functionally, these peptides may promote tumor cell proliferation, migration, invasion, and epithelial-mesenchymal transition, while others exert tumor-suppressive effects by inhibiting oncogenic signaling pathways or interfering with critical protein interactions. Their dual and context-dependent functions highlight the complexity of circRNA-mediated regulation and suggest that these translation products participate in multiple layers of tumor initiation and progression. In this review, we synthesize current knowledge regarding the molecular mechanisms that enable circRNAs to be translated, with particular attention to IRES-driven initiation, m6A-dependent regulation, ribosome accessibility, and the structural determinants required for translation competence. We further summarize well-characterized circRNA-encoded peptides and discuss how they influence tumor-associated signaling networks. In addition, we examine the potential translational applications of these peptides, including their value as diagnostic indicators, prognostic markers, or therapeutic entry points. Their inherent sequence stability, relative expression specificity, and detectability in clinical specimens make circRNA-derived peptides promising candidates for future biomarker and therapeutic development. Overall, circRNA translation research is reshaping our understanding of RNA function and offers new perspectives for studying tumor biology. We propose that expanding investigations into circRNA-encoded peptides will not only improve the mechanistic resolution of cancer research but may also pave the way for innovative strategies in precision oncology, including RNA-based therapeutics and peptide-targeting interventions.

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.

ObjectiveTo investigate the material basis of the pathogenesis of cerebral ischemic injury with blood stasis and toxin syndrome and to explore the protective effects of Huayu Jiedu prescription （HYJDP） on neutrophil extracellular trap-related cell death （NETosis） in cerebral ischemic injury following acute cerebral infarction. MethodsSeventy-two Sprague-Dawley （SD） rats were randomly divided into six groups （n=12 per group）： sham operation （Sham） group， blood stasis and toxin model （Model） group， low-， medium-， and high-dose HYJDP groups （HYJDP-L， HYJDP-M， and HYJDP-H； 9， 18， and 36 g·kg^-1， respectively）， and butylphthalide （NBP） group （0.06 g·kg^-1）. Except for the Sham group， rats in all other groups were subjected to carrageenan/dry yeast combined with a modified intraluminal filament method to establish a focal cerebral ischemia model of the middle cerebral artery with blood stasis and toxin syndrome. Neurological function was evaluated at 24 h after modeling using the Zea-Longa neurological deficit score. Cerebral infarction rate was assessed by 2，3，5-triphenyltetrazolium chloride （TTC） staining. Pathological morphology of brain tissue was observed using hematoxylin-eosin （HE） staining. Enzyme-linked immunosorbent assay （ELISA） was used to determine serum levels of interleukin-8 （IL-8）， myeloperoxidase-DNA complexes （MPO-DNA）， and citrullinated histone H3 （CitH3）. Protein expression of phosphorylated phosphatidylinositol 3-kinase （p-PI3K）， protein kinase B （p-Akt）， mammalian target of rapamycin （p-mTOR）， sequestosome 1 （p62）， and CitH3 in brain tissue was detected by Western blot. Immunofluorescence （IF） was used to detect the expression of neutrophil-specific marker Ly6G， CitH3， and neuron-specific nuclear protein （NeuN） in brain tissue. ResultsCompared with the Sham group， neurological deficit scores and cerebral infarction rates in the model group were significantly increased （P<0.01 for both）. HE staining showed varying degrees of neuronal degeneration and necrosis， characterized by blurred neuronal structures， nuclear pyknosis and fragmentation， cytoplasmic dissolution into a vacuolated reticular pattern， and mild glial cell proliferation. ELISA results showed that serum levels of IL-8， MPO-DNA， and CitH3 were significantly increased （P<0.01）. Western blot analysis demonstrated decreased expression of p-PI3K， p-Akt， p-mTOR， and p62， while CitH3 expression was significantly increased （P<0.01）. IF results showed an increased number of NETs⁺ cells and a significant decrease in NeuN⁺ cells （P<0.01）. Compared with the Model group， neurological deficit scores in the HYJDP-H group were significantly decreased （P<0.05）， and cerebral infarction rates in the HYJDP-H and NBP groups were significantly reduced （P<0.01）. HE staining showed that brain tissue damage was markedly alleviated in the HYJDP-H group. ELISA results showed that levels of IL-8， MPO-DNA， and CitH3 were significantly decreased in the HYJDP-M， HYJDP-H， and NBP groups （P<0.01）. Western blot analysis showed that expression of p-PI3K， p-Akt， p-mTOR， and p62 was significantly increased in the HYJDP-H and NBP groups， while CitH3 expression was significantly reduced in all drug intervention groups （P<0.01）. IF results showed that the number of NETs⁺ cells was significantly decreased and the number of NeuN⁺ cells was significantly increased in all drug intervention groups （P<0.01）. ConclusionNETs may be the material basis of the pathogenesis of cerebral ischemic injury characterized by blood stasis and toxin. HYJDP can regulate the PI3K/Akt/mTOR signaling pathway， reduce the release of pro-inflammatory mediators and NETosis-related products， alleviate cerebral ischemic injury caused by autophagy-dependent NETosis， and thereby exert a neuroprotective effect.

This paper systematically expounds the core challenges and development vision facing transfusion medicine and discipline construction in China under the strategic goals of achieving "Chinese modernization" and "Healthy China". This article puts forward for the first time the "blood transfusion view" of Chinese blood transfusion practitioners and elaborates on key challenges in the field, including the disciplinary system, talent pool, service balance, technical bottlenecks and standardization in emerging fields. To address the challenges, it is urgently necessary to establish the disciplinary status of transfusion medicine, improve talent cultivation, enhance the integration of scientific research and technology, optimize transfusion assessment, promote autologous blood transfusion, advance the localization of evidence-based medicine, and expand the management functions of biological therapy. The ultimate goal is to build a modern blood transfusion system led by science and technology and with Chinese characteristics to safeguard people's health.

Transfusion and Anemia Expertise Initiative-Control/Avoidance of Bleeding developed a strategy for platelet and plasma infusion management in critically ill children based on systematic reviews and consensus meetings of international multidisciplinary experts. One good practice statement and six expert consensus statements were proposed for plasma and platelet transfusions in critically ill children following severe trauma, traumatic brain injury, and/or intracranial hemorrhage. This article introduces the specific methods and basis for the formation of recommendations in this part of the guide.