Idiopathic pulmonary fibrosis （IPF） is a chronic and fibrotic lethal interstitial lung disease with poor prognosis. It is mainly treated by organ transplantation and administration of chemical drugs， which have poor efficacy and induce side effects， failing to meet the clinical needs. Therefore， it is urgent to develop more safe and effective drugs to treat IPF. Traditional Chinese medicine （TCM） has garnered increasing attention in recent years in the treatment of IPF due to its unique advantages. Increasing studies have shown that TCM has remarkable therapeutic effects on IPF and thus demonstrate broad application prospects. Modern medical research shows that the pathogenesis of IPF can be discussed from inflammation （macrophage polarization）， oxidative stress， epithelial-mesenchymal transition （EMT）， autophagy inhibition and other related signaling pathways， while few studies systematically explain the relationship between the signaling pathways and TCM theory. According to the theory of TCM， lung collateral obstruction is the basic pathogenesis of IPF. Therefore， according to the principle of dredging and replenishing lung collaterals， IPF can be treated with the methods of reinforcing healthy qi and eliminating pathogen， replenishing qi and activating blood， and detoxifying and dredging collaterals， which demonstrate definite curative effect and can effectively relieve clinical symptoms， restore the lung function and blood oxygen partial pressure， improve the quality of life of patients， and reduce adverse reactions. Experimental studies have found that dredging and replenishing lung collaterals have significant effects on IPF inflammation （macrophage polarization）， oxidative stress， EMT， autophagy inhibition and other signaling pathways. Therefore， from the perspective of impediment， this article reviews pathogenesis of IPF， the research progress in TCM treatment of IPF， and the treatment of IPF from active components， single herbs， and compound prescriptions of TCM， with the aim of revealing the scientific connotation of the treatment of IPF from impediment and providing a new theoretical basis for enriching the TCM methods of treating IPF.

Background: s/Aims: Sarcomatoid hepatocellular carcinoma (HCC) is a rare histological subtype of HCC characterized by extremely poor prognosis; however, its molecular characterization has not been elucidated. Methods: In this study, we conducted an integrated multiomics study of whole-exome sequencing, RNA-seq, spatial transcriptome, and immunohistochemical analyses of 28 paired sarcomatoid tumor components and conventional HCC components from 10 patients with sarcomatoid HCC, in order to identify frequently altered genes, infer the tumor subclonal architectures, track the genomic evolution, and delineate the transcriptional characteristics of sarcomatoid HCCs. Results: Our results showed that the sarcomatoid HCCs had poor prognosis. The sarcomatoid tumor components and the conventional HCC components were derived from common ancestors, mostly accessing similar mutational processes. Clonal phylogenies demonstrated branched tumor evolution during sarcomatoid HCC development and progression. TP53 mutation commonly occurred at tumor initiation, whereas ARID2 mutation often occurred later. Transcriptome analyses revealed the epithelial–mesenchymal transition (EMT) and hypoxic phenotype in sarcomatoid tumor components, which were confirmed by immunohistochemical staining. Moreover, we identified ARID2 mutations in 70% (7/10) of patients with sarcomatoid HCC but only 1–5% of patients with non-sarcomatoid HCC. Biofunctional investigations revealed that inactivating mutation of ARID2 contributes to HCC growth and metastasis and induces EMT in a hypoxic microenvironment. Conclusions We offer a comprehensive description of the molecular basis for sarcomatoid HCC, and identify genomic alteration (ARID2 mutation) together with the tumor microenvironment (hypoxic microenvironment), that may contribute to the formation of the sarcomatoid tumor component through EMT, leading to sarcomatoid HCC development and progression.

Purpose: There is still insufficient evidence for predicting stroke risk in patients with mild carotid atherosclerotic stenosis. This study aimed to explore the association between carotid intraplaque neovascularization (IPN) in mild stenosis and ischemic stroke, using contrast-enhanced ultrasound (CEUS) imaging. Methods: This retrospective observational study included 369 patients from July 2021 to March 2022. These patients were categorized as symptomatic or asymptomatic based on their recent history of ipsilateral ischemic stroke. Initial parameters of carotid plaques, such as IPN grading and contrast enhancement index, were assessed using B-mode ultrasonography and CEUS. The follow-up period lasted 12 months or until a newly-developed ischemic stroke occurred. Logistic regression models and Cox proportional-hazards regression models were employed to explore the associations between ultrasonic parameters and the incidence of recent and future ischemic strokes. Results: In patients with mild stenosis, both increasing age and grade 2 carotid IPN were significant predictors of recent primary ischemic stroke. Furthermore, grade 2 carotid IPN independently predicted future ischemic strokes in both symptomatic and asymptomatic patients. Conclusion This study demonstrated that carotid IPN as detected by CEUS imaging holds potential as a useful non-invasive biomarker for predicting recent and future ischemic strokes in patients with mild carotid stenosis.

Oral solid dosage forms require processes such as disintegration and dissolution to release the drug before it can be absorbed and utilized by the body. In this manuscript, imaging technology was used to continuously visualize and characterize the in vitro static drug release process of gliclazide modified release tablets from 15 manufacturers, combined with the traditional method of in vitro dissolution testing, to determine the release profile of gliclazide modified release tablets, to evaluate the similarity of the release profiles by using the similarity factor (f₂) method and based on the analysis of the release profiles fitted with a variety of mathematical models. The results indicate that the gliclazide modified release tablets produced by 14 companies are hydrophilic gel matrix tablets. Compared to the reference listed drug, the release profiles of formulations from 11 companies show high similarity (f₂ > 50) to the reference. Among these, formulations with visual characteristics similar to the reference exhibit similar release curves. This study provides an alternative method for the in vitro consistency evaluation of gliclazide modified release tablets, aiming to assess the in vitro release behaviour of generic formulations more accurately and comprehensively.

OBJECTIVE To investigate the improvement effects and potential mechanism of ulinastatin （UTI） on cisplatin （CP）-induced myocardial injury. METHODS Rabbits were used as study subjects and randomly divided into blank group （normal saline 2 mL/d， for consecutive 7 d）， CP group （150 mg/m2， on the 1st and 4th day）， UTI low-dose/high-dose group （UTIL/UTIH group， UTL 25 000 or 50 000 IU/kg， once a day， for consecutive 7 d）， c-Jun N-terminal kinase （JNK） inhibitor group （JNKi group， SP600125 15 mg/kg， on the 1st and 4th day+CP 150 mg/m2， on the 1st and 4th day+normal saline 2 mL/d， on the other 5 days）. Except for the blank group， rabbits in the other groups were injected with relevant medicine and/or normal saline via a marginal ear vein on one side. The serum level of cardiac troponin Ⅰ （cTnⅠ） in rabbits on the 1st and 8th days of the detection experiment， as well as the levels of superoxide dismutase （SOD）， glutathione （GSH） and malondialdehyde （MDA） in myocardial tissue on the 8th day of the experiment， were all measured in each group. The pathological changes and myocardial cell apoptosis in myocardial tissue were observed， and the protein expressions of B-cell lymphoma-2 （Bcl-2）， Bcl-2 associated X protein （Bax）， JNK， phosphorylated JNK （P-JNK）， mitochondrial fission factor （Mff）， and dynamin-related protein 1 （Drp1） in myocardial tissue were all determined. RESULTS Compared with the blank group， the CP group showed significant myocardial injury. The cell apoptotic rate， the levels of cTnⅠ in serum and MDA in myocardial tissue， as well as protein expressions of Bax， JNK， p-JNK， Mff， and Drp1， were all significantly increased or up-regulated， SOD level and protein expression of Bcl-2 significantly reduced or down+regulated（P＜0.05）. Compared with the CP group， the myocardial injury in rabbits from each drug treatment group showed improvement. The cell apoptosis index， the levels of cTnⅠ in serum and MDA in myocardial tissue， as well as protein expressions of Bax， JNK， p-JNK， Mff （except for UTIL group）， and Drp1， were all significantly reduced or down-regulated， while SOD， GSH level and protein expression of Bcl-2 significantly increased or up-regulated （P＜0.05）； moreover， the improvement in some indicators was significantly better in the UTIH group and the JNKi group compared to the UTIL group （P＜0.05）. CONCLUSIONS UTI may ameliorate CP-induced myocardial injury， the potential mechanism of which may be associated with antagonizing oxidative stress and inhibiting the JNK/Mff signaling pathway.

[Objective] To investigate the factors associated with alanine aminotransferase (ALT) abnormalities in multi-ethnic blood donors across five Zang autonomous prefectures in the plateau regions of Qinghai Province, and to provide evidence for ensuring blood safety and formulating screening strategies. [Methods] A retrospective analysis was performed on the ALT abnormal test results of blood donors in the Zang autonomous prefectures of Qinghai from 2022 to 2024. The correlations between ALT levels and factors including gender, age, altitude, and infectious markers were investigated. [Results] The overall ALT unqualified rate among blood donors in this region was 9.01%. Significant differences in ALT levels were observed across genders and age groups (P<0.05). Variations in ALT abnormality rates were also noted among different plateau regions (P<0.05). Overall, ALT values exhibited an increasing trend with rising altitude. The average ALT unqualified rates were 11.19% in Zang donors, 7.96% in Han donors, and 4.79% in donors from other ethnic groups (P<0.05). No statistically significant association was observed between ALT abnormality and the presence of HBV/HCV infectious markers (P>0.05). [Conclusion] In the plateau areas of Qinghai, multi-ethnic blood donors have a relatively high ALT levels and ALT unqualified rates, showing distinct regional characteristics. ALT elevation in voluntary blood donors is related to non-pathological factors such as gender, age, and dietary habits, but not to infectious indicators.

ObjectiveBola-like short peptides exhibit novel self-assembly properties due to the formation of peptide dimers via hydrogen bonding interactions between their C-terminals. In this configuration, hydrophilic amino acids are distributed at both terminals, making these peptides behave similarly to Bola peptides. The electrostatic repulsive interactions arising from the hydrophilic amino acids at each terminal can be neutralized, thereby greatly promoting the lateral association of β-sheets. Consequently, assemblies with significantly larger widths are typically the dominant nanostructures for Bola-like peptides. To investigate the effect of hydrophilic amino acids on the self-assembly behavior of Bola-like peptides, the peptides Ac-RI₃-CONH₂ and Ac-HI₃-CONH₂ were designed and synthesized using the Bola-like peptide Ac-KI₃-CONH₂ as a template. Their self-assembly behavior was systematically examined. MethodsAtomic force microscopy (AFM) and transmission electron microscopy (TEM) were employed to characterize the morphology and size of the assemblies. The secondary structures of the assemblies were analyzed using circular dichroism (CD) and Fourier transform infrared (FTIR) spectroscopy. Small-angle neutron scattering (SANS) was used to obtain detailed structural information at a short-length scale. Based on these experimental results, the effects of hydrophilic amino acids on the self-assembly behavior of Bola-like short peptides were systematically analyzed, and the underlying formation mechanism was explored. ResultsThe aggregation process primarily involved three steps. First, peptide dimers were formed through hydrogen bonding interactions between their C-terminals. Within these dimers, the hydrophilic amino acids K, R, and H were positioned at both terminals, enabling the peptides to self-assemble in a manner similar to Bola peptides. Next, β-sheets were formed via hydrogen bonding interactions along the peptide backbone. Finally, self-assemblies were generated through the lateral association of β-sheets. The results demonstrated that both Ac-KI₃-CONH₂ and Ac-RI₃-CONH₂ could self-assemble into double-layer nanotubes with diameters of approximately 200 nm. These nanotubes were formed by the edge fusion of helical ribbons, which initially emerged from twisted ribbons. Notably, the primary assemblies of these peptides exhibited opposite chirality: nanofibers formed by Ac-KI₃-CONH₂ displayed left-handed chirality, whereas those formed by Ac-RI₃-CONH₂ exhibited right-handed chirality. This reversal in torsional direction was primarily attributed to the different abilities of K and R to form hydrogen bonds with water. In contrast, Ac-HI₃-CONH₂ formed narrower twisted ribbons with a significantly reduced width of approximately 30 nm, which was attributed to the strong steric hindrance caused by the imidazole rings. The multilayer height of these ribbons was mainly due to the unique structure of the imidazole rings, which can function as both hydrogen bond donors and acceptors, thereby promoting aggregate growth in the vertical direction. ConclusionThe final morphology of the self-assemblies resulted from a delicate balance of various non-covalent interactions. By altering the types of hydrophilic amino acid residues in Bola-like short peptides, the relative strength of non-covalent interactions that drive assembly formation can be effectively regulated, allowing precise control over the morphology and chirality of the assemblies. This study provides a simple and effective approach for constructing diverse self-assemblies and lays a theoretical foundation for the development of functional biomaterials.

To investigate body composition and associated factors in adolescents undergoing long-term regular sports training.

Purpose: There is still insufficient evidence for predicting stroke risk in patients with mild carotid atherosclerotic stenosis. This study aimed to explore the association between carotid intraplaque neovascularization (IPN) in mild stenosis and ischemic stroke, using contrast-enhanced ultrasound (CEUS) imaging. Methods: This retrospective observational study included 369 patients from July 2021 to March 2022. These patients were categorized as symptomatic or asymptomatic based on their recent history of ipsilateral ischemic stroke. Initial parameters of carotid plaques, such as IPN grading and contrast enhancement index, were assessed using B-mode ultrasonography and CEUS. The follow-up period lasted 12 months or until a newly-developed ischemic stroke occurred. Logistic regression models and Cox proportional-hazards regression models were employed to explore the associations between ultrasonic parameters and the incidence of recent and future ischemic strokes. Results: In patients with mild stenosis, both increasing age and grade 2 carotid IPN were significant predictors of recent primary ischemic stroke. Furthermore, grade 2 carotid IPN independently predicted future ischemic strokes in both symptomatic and asymptomatic patients. Conclusion This study demonstrated that carotid IPN as detected by CEUS imaging holds potential as a useful non-invasive biomarker for predicting recent and future ischemic strokes in patients with mild carotid stenosis.