Background/Aims: Dysregulated cholesterol metabolism is a hallmark of hepatocellular carcinoma (HCC) that drives tumor initiation and progression. However, clinical targeting of cholesterol metabolism has yielded limited benefits due to stringent feedback in tumor cells. Identifying a central mediator capable of restoring cholesterol homeostasis within the cell’s intrinsically fine-tuned regulatory framework is urgently needed. Methods: We integrated a proteomic dataset from patients with cholesterol-dysregulated HCC into a global cholesterol metabolic regulatory network to identify potential therapeutic targets for disrupted cholesterol homeostasis. The prognostic significance of the candidate targets was further validated in an independent cohort through immunohistochemistry. Functional and mechanistic studies were conducted in vitro using HCC cell lines and in vivo using mouse models. The pharmacological efficacy of the candidate agent was evaluated in both subcutaneous and orthotopic HCC mouse models. Results: ER lipid raft-associated 1 (ERLIN1), a pivotal regulator of cholesterol metabolism reprogramming, was identified as an independent favorable prognostic indicator in HCC. ERLIN1 constrains HCC progression both in vitro and in vivo by stabilizing the INSIG1–SCAP–SREBP2 axis and maintaining the metabolic balance of intracellular cholesterol. Under hypoxia, impaired factor-inhibiting hypoxia-1-dependent hydroxylation of ASB11 at asparagine residues 90 and 92 enhances ASB11-mediated ERLIN1 degradation. Pharmacological targeting of this axis using zoledronic acid (ZoA) attenuated HCC progression by weakening the ASB11–ERLIN1 interaction and restoring cholesterol homeostasis. Conclusions ERLIN1 represents a druggable metabolic vulnerability in cholesterol-dysregulated HCC. Targeting the ASB11–ERLIN1 axis with the clinically approved ZoA reestablishes cholesterol homeostasis and offers a promising therapeutic strategy to overcome the current limitations of cholesterol-targeted HCC therapies.

Malignant gastrointestinal tumors （GT） mainly include laryngeal cancer， esophageal cancer， gastric cancer， pancreatic cancer， hepatocellular carcinoma， bile duct cancer， and colorectal cancer. At present， the morbidity and mortality of GT are high. Tumor immune escape is one of the key reasons for cancer development and treatment failure， and it is also the main direction of current tumor immunotherapy research. Traditional Chinese medicine （TCM） plays a role in treating GT and alleviating systemic symptoms， especially showing potential advantages in regulating the immune escape mechanism. This article elaborates on the immune escape mechanism of GT and systematically reviews that TCM active components or compound prescriptions act on key immune checkpoints such as programmed cell death protein-1 （PD-1） and programmed cell death ligand-1 （PD-L1） to reduce the proportion of marrow-derived suppressor cells （MDSCs）， promote the polarization of M1 macrophages， activate effector immune cells， enhance CD8⁺ T cell recruitment and interferon （IFN）-γ secretion， enhance the killing activity of natural killers （NKs）， and reduce foxhead box protein P3（FoxP3⁺）-positive regulatory T （Treg） cell infiltration. TCM active components or compound prescriptions can remodel the tumor microenvironment （TME）， such as improving immunosuppressive factors， promoting vascular normalization， and regulating intestinal microbiota. Through the regulation of TME， enhancement of antigen presentation， inhibition of immune checkpoint molecules， regulation of cellular network factors and metabolites， etc.， TCM active components or compound prescriptions enhance the immune function， thereby inhibiting the immune escape of GT. This paper summarizes and reflects on the research results of TCM in regulating immune escape to treat GT in recent years， aiming to help transform TCM from empirical medication to precision treatment based on immune regulation， reduce drug resistance and enhance treatment effect.

ObjectiveTo establish an objective evaluation system based on the quality characteristics of Gardeniae Fructus without relying on the origin label according to the theory of excellent shape， high quality， and superior effect of authentic medicinal materials， thus providing a scientific basis for the standardization of Gardeniae Fructus. MethodsDifferent batches of Gardeniae Fructus samples were collected from different producing areas. Through herbal textual research and a review of modern literature， fruit length， maximum fruit diameter， and chroma were selected as quantitative indicators to characterize the traditional appearance traits of Gardeniae Fructus. The above indicators were measured by a vernier caliper and a spectrophotometer. Through classical famous prescription data and literature analysis， total iridoid glycosides， total crocus glycosides， and total flavonoids were selected as the core component indicators related to efficacy， and their content was determined. Finally， through cluster analysis， the threshold ranges of the quantitative indicators of excellent shape and high quality were determined， and the applicability of the established evaluation system was verified by the determination of the indicators for each batch of medicinal materials. ResultsThe excellent shape indicators of Gardeniae Fructus were the fruit length-to-maximum fruit diameter ratio ≤1.86， 0°≤h≤45°， and L^*≥ 37.32. The content of total iridoid glycosides， total crocus glycosides， and total flavonoids should be no less than 2.2%， 0.44%， and 0.028%， respectively. The measurement results of different batches of Gardeniae Fructus showed that the evaluation system could effectively distinguish the Gardeniae Fructus samples in line with the traditional cognition of excellent shape and high quality. ConclusionThis study preliminarily constructs an excellent shape and high quality-based quality evaluation system for Gardeniae Fructus， which links appearance traits with chemical indicators and provides a methodological basis for the quality control and scientific grading of this herbal medicine.

Objective: To evaluate the suitability of the existing hemolysis rate standards for locally processed red blood cell components by retrospectively analyzing 5-year hemolysis rate data at the end of storage. Methods: A total of 720 blood samples of three types of red blood cell components from our blood station from January 2019 to December 2023 were collected. Parameters included hemoglobin concentration (Hb), hematocrit (Hct), and free hemoglobin concentration (fHb). Hemolysis rate were taken as the control standard of 0.8% in accordance with the national standard. The hemolysis rates were compared against the national standard threshold of 0.8% (GB18469-2012), and annual trends of the detection parameters were observed. Results: The hemolysis rates (x-+s,%) of leukocyte-depleted whole blood at the end of storage were (0.038±0.023 8) in 2019, (0.049±0.039 5) in 2020, (0.043±0.040 7) in 2021, (0.049±0.030 7) in 2022, and (0.058±0.054 8) in 2023, respectively; The hemolysis rates (x-+s" />,%) of leukocyte-depleted suspended red blood cells at the end of storage were (0.093±0.050 2) in 2019, (0.086±0.049 5) in 2020, (0.123±0.072 3) in 2021, (0.122±0.052 1) in 2022, and (0.106±0.058 6) in 2023, respectively; The hemolysis rates (x-+s,%) of washed red blood cells at the end of storage were (0.127±0.038 2) in 2019, (0.150±0.066 5) in 2020, (0.121±0.052 2) in 2021, (0.124±0.038 9) in 2022, and (0.128±0.044 3) in 2023, respectively. Conclusion: Hemolysis rates at the end of blood storage of three red blood cell components were significantly lower than the limits specified in Quality Requirements for Whole Blood and Components (GB18469-2012), as well as standards from the EU, AABB and the United States. The results demonstrate excellent product quality control. A regional internal control standard of <0.2% is proposed for hemolysis rates at the end of storage.

Local anesthetics (LAs), such as articaine (AT), exhibit limited efficacy in inflammatory environments, which constitutes a significant limitation in their clinical application within oral medicine. In our prior research, we developed AT-17, which demonstrated effective properties in chronic inflammatory conditions and appears to function as a novel oral LA that could address this challenge. In the present study, we further elucidated the beneficial effects of AT-17 in acute inflammation, particularly in oral acute inflammation, where mitochondrial-related apoptosis played a crucial role. Our findings indicated that AT-17 effectively inhibited lipopolysaccharide (LPS)-induced nerve cell apoptosis by ameliorating mitochondrial dysfunction in vitro. This process involved the inhibition of mitochondrial reactive oxygen species (mtROS) production and the subsequent activation of the NRF2 pathway. Most notably, improvements in mitochondria-related apoptosis were key contributors to AT-17's inhibition of voltage-gated sodium channels. Additionally, AT-17 was shown to reduce mtROS production in nerve cells through the Na⁺/NCLX/ETC signaling axis. In conclusion, we have developed a novel local anesthetic that exhibits pronounced anesthetic functionality under inflammatory conditions by enhancing mitochondria-related apoptosis. This advancement holds considerable promise for future drug development and deepening our understanding of the underlying mechanisms of action.

This study aims to explore the pharmacodynamic material basis of Jinbei Oral Liquid(JBOL) against idiopathic pulmonary fibrosis(IPF) based on serum pharmacochemistry and network pharmacology. The ultra-high performance liquid chromatography-quadrupole time-of-flight tandem mass spectrometry(UHPLC-Q-TOF-MS/MS) technology was employed to analyze and identify the components absorbed into rat blood after oral administration of JBOL. Combined with network pharmacology, the study explored the pharmacodynamic material basis and potential mechanism of JBOL against IPF through protein-protein interaction(PPI) network construction, "component-target-pathway" analysis, Gene Ontology(GO) functional enrichment, and Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment analysis. First, a total of 114 compounds were rapidly identified in JBOL extract according to the exact relative molecular mass, fragment ions, and other information of the compounds with the use of reference substances and a self-built compound database. Second, on this basis, 70 prototype components in blood were recognized by comparing blank serum with drug-containing serum samples, including 28 flavonoids, 25 organic acids, 4 saponins, 4 alkaloids, and 9 others. Finally, using these components absorbed into blood as candidates, the study obtained 212 potential targets of JBOL against IPF. The anti-IPF mechanism might involve the action of active ingredients such as glycyrrhetinic acid, cryptotanshinone, salvianolic acid B, and forsythoside A on core targets like AKT1, TNF, and ALB and thereby the regulation of multiple signaling pathways including PI3K/AKT, HIF-1, and TNF. In conclusion, JBOL exerts the anti-IPF effect through multiple components, targets, and pathways. The results would provide a reference for further study on pharmacodynamic material basis and pharmacological mechanism of JBOL.
Drugs, Chinese Herbal/pharmacokinetics* ; Animals ; Tandem Mass Spectrometry ; Network Pharmacology ; Rats ; Chromatography, High Pressure Liquid ; Rats, Sprague-Dawley ; Male ; Idiopathic Pulmonary Fibrosis/metabolism* ; Humans ; Administration, Oral ; Protein Interaction Maps/drug effects* ; Signal Transduction/drug effects*

Panax ginseng as a perennial herb of Araliaceae, exhibits pharmacological effects such as central nervous system stimulation, anti-tumor properties, and cardiovascular and cerebrovascular protection. The B3 gene family plays a crucial role in growth and development, antioxidant activity, stress resistance, and secondary metabolism regulation of plants and has been extensively studied in various plants. However, the identification and analysis of the B3 gene family in P. ginseng have not been reported. In this study, a total of 145 B3 genes(PgB3s) with complete open reading frames(ORF) were identified from P. ginseng and classified into five subfamilies based on domain types. Through correlation analysis with ginsenoside content, SNP/InDels analysis, and interaction analysis with key enzyme genes, 15 PgB3 transcripts were found to be significantly correlated with ginsenoside content and exhibited a close interaction network with key enzyme genes involved in ginsenoside biosynthesis, which indicated that these genes may participate in the regulation of ginsenoside biosynthesis. Additionally, this study found that PgB3 genes exhibited induced expression in response to methyl jasmonate(MeJA) stress, which aligned with the presence of abundant stress response elements in their promoters, confirming the important role of the B3 gene family in P. ginseng in stress resistance. The results of this study revealed the potential functions of PgB3 genes in ginsenoside biosynthesis and stress response, providing a significant theoretical basis for further research on the functions of PgB3 genes and their regulatory mechanisms.
Panax/metabolism* ; Gene Expression Regulation, Plant ; Plant Proteins/metabolism* ; Ginsenosides/biosynthesis* ; Multigene Family ; Phylogeny

OBJECTIVES: To study the clinical and genetic characteristics of children with congenital adrenal hyperplasia (CAH). METHODS: Clinical data, laboratory findings, and genetic test results of 63 children diagnosed with CAH at Henan Children's Hospital from January 2017 to December 2024 were retrospectively reviewed. RESULTS: Of the 63 patients, the mean age at the first visit was (21 ± 14) days; 29 (46%) were of male sex and 34 (54%) were of female sex. The predominant clinical manifestations were poor weight gain or weight loss (92%, 58/63), poor feeding (84%, 53/63), skin hyperpigmentation (83%, 52/63), and female external genital anomalies (100%, 34/34). Laboratory abnormalities included hyponatremia (87%, 55/63), hyperkalemia (68%, 43/63), metabolic acidosis (68%, 43/63), and markedly elevated 17-hydroxyprogesterone (92%, 58/63), testosterone (89%, 56/63), and adrenocorticotropic hormone (81%, 51/63). Among 49 patients who underwent genetic testing, CYP21A2 variants were identified in 90% (44/49), with c.293-13A/C>G (33%, 30/91) and large deletions/gene conversions (29%, 26/91) being the most frequent; STAR (8%, 4/49) and HSD3B2 (2%, 1/49) variants were also detected. Following hormone replacement therapy, electrolyte disturbances were corrected in 57 cases, with significant reductions in 17-hydroxyprogesterone, adrenocorticotropic hormone, and testosterone levels (P<0.001). CONCLUSIONS CAH presenting in neonates or young infants is characterized by electrolyte imbalance, external genital anomalies, and abnormal hormone levels. Genetic testing enables definitive subtype classification; in CYP21A2-related CAH, c.293-13A/C>G is a hotspot variant. These findings underscore the clinical value of genetic testing for early diagnosis and genetic counseling in CAH. Citation:Chinese Journal of Contemporary Pediatrics, 2025, 27(11): 1367-1372.
Humans ; Adrenal Hyperplasia, Congenital/diagnosis* ; Male ; Female ; Retrospective Studies ; Infant ; Infant, Newborn

AIM To evaluate the quality of Gegen Formula Granules.METHODS Linear calibration with two reference substances(LCTRS)was adopted in the predicting of retention time with puerarin and daidzein as internal standards.UPLC characteristic chromatograms were established.The contents of 3'-hydroxy puerarin,puerarin(internal standard),3'-methoxy puerarin,puerarin 6"-O-xyloside,puerarin apioside and daidzin were determined by quantitative determination analysis multi-components by a single marker(QAMS),after which their transfer rates were calculated.RESULTS Compared with relative retention time method,LCTRS demonstrated higher positional accuracy for characteristic peaks and wider application range for columns.There were 9 characteristic peaks in the characteristic chromatograms for 14 batches of formula granules and 15 batches of standard decoctions with the similarities of more than 0.95.The contents and transfer rates of various constituents in formula granules and standard decoctions were basically consistent.CONCLUSION The chemical constituents in formula granules and their standard decoctions of Puerariae lobatae Radix display good consistency,reliable preparation process is observable in the former.

Vertebral refracture following percutaneous vertebral augmentation (PVA) is commonly seen in elderly patients with osteoporotic thoracolumbar compression fractures (OTLCF). It can lead to recurrent pain, loss of vertebral height, progression of kyphosis, and even neurological dysfunction, significantly impairing patients′ quality of life. Current diagnosis and treatment face multiple challenges, including high misdiagnosis rate, difficulty in choosing between surgical and non-surgical treatment options, lack of standardized surgical protocols, interference from intralesional bone cement during procedures, inadequate stability of internal fixation in osteoporotic bone, and suboptimal compliance of anti-osteoporotic therapy. Establishing a standardized diagnostic and therapeutic framework is urgently needed. To standardize the management process and improve outcomes for vertebral refractures after PVA in elderly OTLCF patients, Spinal Trauma Group of the Orthopedic Branch of Chinese Medical Doctor Association organized experts in the field to develop Guideline for the diagnosis and treatment of vertebral refracture after percutaneous vertebral augmentation in elderly patients with osteoporotic thoracolumbar compression fractures ( version 2025), based on current literature and clinical experience, and adhering to principles of scientific rigor and clinical applicability. A total of 11 recommendations were proposed, encompassing diagnosis, treatment, and rehabilitation of vertebral refracture after PVA in elderly patients with OTLCF, aiming to provide a foundation for a standardized management.