OBJECTIVE To investigate the effects and mechanisms of Lycium ruthenicum Murr. in improving sleep. METHODS Network pharmacology was employed to identify the active components of L. ruthenicum and their associated disease targets， followed by enrichment analysis. A caffeine‑induced zebrafish model of sleep deprivation was established ， and the zebrafish were treated with L. ruthenicum Murr. extract （LRME） at concentrations of 0.1， 0.2 and 0.4 mg/mL， respectively； 24 h later， behavioral changes of zebrafish and pathological alterations in brain neurons were subsequently observed. The levels of inflammatory factors [interleukin-6 （IL-6）， IL-1β， IL-10， tumor necrosis factor-α （TNF-α）]， oxidative stress markers [superoxide dismutase （SOD）， malondialdehyde （MDA）， glutathione peroxidase （GSH-Px）， catalase （CAT）]， and neurotransmitters [5- hydroxytryptamine （5-HT）， γ-aminobutyric acid （GABA）， glutamic acid （Glu）， dopamine （DA）， and norepinephrine （NE）] were measured. The protein expression levels of protein kinase B1 （AKT1）， phosphorylated AKT1 （p-AKT1）， epidermal growth factor receptor （EGFR）， B-cell lymphoma 2 （Bcl-2）， sarcoma proto-oncogene，non-receptor tyrosine kinase （SRC）， and heat shock protein 90α family class A member 1 （HSP90AA1） in the zebrafish were also determined. RESULTS A total of 12 active components and 176 intersecting disease targets were identified through network pharmacology analysis. Among these， apigenin， naringenin and others were recognized as core active compounds， while AKT1， EGFR and others served as key targets； EGFR tyrosine kinase inhibitor resistance signaling pathway was identified as the critical pathway. The sleep improvement rates in zebrafish of LRME low-， medium-， and high-dose groups were 54.60%， 69.03% and 77.97%， 开发。E-mail：hjp_yft@163.com respectively， while the inhibition ratios of locomotor distance were 0.57， 0.83 and 0.95， respectively. Compared with the model group， the number of resting counts， resting time and resting distance were significantly increased/extended in LRME medium- and high-dose groups （P＜0.05）. Neuronal damage in the brain was alleviated. Additionally， the levels of IL-6， IL-1β， TNF-α， MDA， Glu， DA and NE， as well as the protein expression levels of AKT1， p-AKT1， EGFR， SRC and HSP90AA1， were markedly reduced （P＜0.05）， while the levels of IL-10， SOD， GSH-Px， CAT， 5-HT and GABA， as well as Bcl-2 protein expression， were significantly elevated （P＜0.05）. CONCLUSIONS L. ruthenicum Murr. demonstrates sleep-improving effects， and its specific mechanism may be related to the regulation of inflammatory responses， oxidative stress， neurotransmitter balance， and the EGFR tyrosine kinase inhibitor resistance signaling pathway.

Bronchiolar adenoma (BA) is a rare type of lung tumor characterized by bilayered epithelial cells having a continuous basal layer and a luminal layer. It resembles mucinous adenocarcinoma (MA) on frozen section, with difficulty in distinguishing the basal layer. Immunohistochemistry is the best choice for verifying the diagnosis. This study aimed to comprehensively characterize three cases of BA-combined carcinoma using clinical, histopathological, and genetic features. BA and carcinoma sections were subjected to next-generation sequencing, respectively. It was hypothesized that while different mutation forms matched different regions, BA and lung adenocarcinoma shared the same gene mutation when they co-occurred in the same location. BA with extensive carcinoma is extremely rare and presents diagnostic challenges due to its overlap with conditions such as MA. Because of its distinctive morphological characteristics, BA may be regarded as a low-grade malignancy, particularly during a confusing evaluation. A multifaceted examination of clinical, radiological, immunohistochemical, and genetic data is necessary for an accurate diagnosis.

Objectives: . The prognostic value of the pretreatment albumin-to-alkaline phosphatase ratio (AAPR) in head and neck cancer (HNC) remains uncertain. This meta-analysis aimed to evaluate the predictive role of AAPR for survival outcomes in patients with HNC. Methods: . A comprehensive search of the Cochrane Library, PubMed, and Embase databases was conducted to identify relevant studies published up to July 30, 2024. We included studies on AAPR and survival outcomes in HNC patients. Results: . Eight studies comprising 1,737 HNC patients were analyzed using random-effects models. Lower AAPR values were significantly correlated with worse overall survival (hazard ratio [HR], 2.08), progression-free survival (HR, 2.00), and disease-free survival (HR, 2.18). Sensitivity analyses confirmed the robustness of these results, with no significant publication bias detected. Conclusion . Our findings suggest that pretreatment AAPR could serve as a valuable and cost-effective prognostic indicator in HNC, potentially aiding clinicians in risk stratification and treatment decision-making. However, additional validation studies are warranted to confirm its clinical applicability.

Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoen-cephalopathy (CADASIL) is caused by NOTCH3 gene variants and is predominantly characterized by cerebral small vessel disease. Previous studies have suggested that CADASIL may also involve the macrovascular system. This study aimed to explore the association between rare NOTCH3 variants and macrovascular lesions.

ObjectiveTo systematically identify the main chemical components of Linggui Zhugan granules （LGZGG）， and to explore the pharmacodynamic substance basis for the treatment of metabolic dysfunction-associated steatohepatitis （MASH）. MethodsThe chemical components of LGZGG were systematically analyzed by ultra-performance liquid chromatography-quadrupole-time-of-flight tandem mass spectrometry （UPLC-Q-TOF-MS/MS）. The protein-protein interaction （PPI） network and "compound prescription-disease-component-target" network were constructed by network target analysis to predict the potential pharmacodynamic substances and core targets of LGZGG in the treatment of MASH. The potential pharmacodynamic substances were enriched by macroporous adsorption resin， and the chemical composition of the LGZGG-50% ethanol elution fraction （LGZGG-50） was analyzed by UPLC-Q-TOF-MS/MS. The mouse model of MASH was established by feeding a high-fat， high-cholesterol， and high-fructose diet for 12 weeks. Mice were randomly allocated into normal， model， positive drug （MGL-3196， 1 mg·kg^-1）， LGZGG （crude drug， 34 g·kg^-1·d^-1）， LGZGG-50 （crude drug， 34 g·kg^-1·d^-1） groups. The levels of aspartate aminotransferase （AST）， alanine aminotransferase （ALT）， total cholesterol （TC）， triglyceride （TG）， low-density lipoprotein cholesterol （LDL-C）， and high-density lipoprotein cholesterol （HDL-C） in the serum were measured， and the pathological changes in the liver tissue were observed by hematoxylin-eosin （HE） and Sirius red staining. The in vivo efficacy of LGZGG and LGZGG-50 in the treatment of MASH was evaluated on the basis of the findings. The expression levels of adenosine monophosphate-activated protein kinase （AMPK）， phosphorylated AMPK （p-AMPK）， silent information regulator 2-related enzyme 1 （SIRT1）， peroxisome proliferator-activated receptor α （PPARα）， and carnitine palmitoyltransferase 1A （CPT1A） in the liver tissue were determined by Western blot to verify the regulatory effects of core targets. ResultsA total of 83 chemical components were identified from LGZGG， including 20 flavonoids， 13 terpenoids， 17 organic acids， 7 amino acids， 11 glycosides， 3 nucleosides， 3 aromatics， 3 alkaloids， 2 phenylpropanoids， 2 sugars， 1 nucleic acid， and 1 steroid. A total of 134 common targets were obtained by network target analysis. The core targets included SIRT1， PPARα， nuclear factor-kappa B subunit 1 （NF-κB1）， and interleukin-6 （IL-6）. Kyoto Encyclopedia of Genes and Genomes （KEGG） enrichment analysis revealed that the targets were mainly enriched in the AMPK， PPAR and other signaling pathways. The topological analysis of the "compound prescription-disease-component-target" network showed that the potential pharmacodynamic substances of LGZGG against MASH were flavonoids and terpenoids. The relative content of flavonoids and terpenes in LGZGG-50 were 74.00% and 62.41% in positive and negative ion modes， respectively， indicating that LGZGG-50 effectively enriched total flavonoids and total terpenoids. The results of in vivo efficacy showed that compared with the model group， LGZGG and LGZGG-50 reducef the body weight， liver weight， serum TG， GLU， and ALT levels of MASH mice （P<0.05，P<0.01）， and LGZGG additionally increased the HDL-C level （P<0.01）. Both groups alleviated the pathological damage in the liver tissue. The results of Western blot showed that compared with the model group， the protein levels of p-AMPK/AMPK， SIRT1， PPARα， and CPT1A were up-regulated in the LGZGG group （P<0.05，P<0.01）， and those of p-AMPK/AMPK and CPT1A were up-regulated in the LGZGG-50 group （P<0.01）. ConclusionLGZGG ameliorates MASH， with the main pharmacodynamic substances being flavonoids and terpenoids. The mechanism may be related to the regulation of AMPK/SIRT1/PPARα signaling pathway， improvement of lipid metabolism， and alleviation of pathological damage in the liver tissue.

Sanhuang Xiexintang （SHXXT）， originating from the Synopsis of the Golden Chamber （Jin Gui Yao Lue）， comprises three medicinal herbs： Rhei Radix et Rhizoma， Coptidis Rhizoma， and Scutellariae Radix. Renowned for its effects of purging fire， detoxifying， drying dampness， and draining heat， SHXXT primarily treats syndromes characterized by internal excess heat， dampness-heat stagnation， and reckless blood movement due to heat. Because of the concise formulation and remarkable efficacy of this formula， modern research has extensively explored the chemical composition， clinical applications， and pharmacological mechanisms of SHXXT， yielding significant advancements. As a modern derivative of SHXXT， Yiqing granules exemplify the transformation of classical formulas into convenient and precise applications， embodying the paradigm of modern development of classical formulas. This systematic review synthesizes recent research progress in SHXXT. Chemical analyses reveal that the active components—anthraquinones， alkaloids， and flavonoids—of SHXXT exert holistic therapeutic effects through multi-component synergy. Clinical studies demonstrate broad utility of this formula in managing digestive disorders， endocrine diseases， urinary tract infections， dermatological conditions， and systemic inflammatory diseases， highlighting its multi-system regulatory potential. Mechanism investigations elucidate its multi-target mechanism of action， including antimicrobial， anti-inflammatory， metabolic-regulatory， hepatoprotective， and gastrointestinal-modulating effects， reflecting an integrated multi-component， multi-target， multi-pathway mode of action. This review systematically summarizes the modern research progress in SHXXT， providing a theoretical foundation for deciphering the scientific essence of classical formulas and advancing their precision application in clinical practice.

OBJECTIVE: Hepatocellular carcinoma (HCC) is sensitive to ferroptosis, a new form of programmed cell death that occurs in most tumor types. However, the mechanism through which ferroptosis modulates HCC remains unclear. This study aimed to investigate the oncogenic role and prognostic value of FANCD2 and provide novel insights into the prognostic assessment and prediction of immunotherapy. METHODS: Using clinicopathological parameters and bioinformatic techniques, we comprehensively examined the expression of FANCD2 macroscopically and microcosmically. We conducted univariate and multivariate Cox regression analyses to identify the prognostic value of FANCD2 in HCC and elucidated the detailed molecular mechanisms underlying the involvement of FANCD2 in oncogenesis by promoting iron-related death. RESULTS: FANCD2 was significantly upregulated in digestive system cancers with abundant immune infiltration. As an independent risk factor for HCC, a high FANCD2 expression level was associated with poor clinical outcomes and response to immune checkpoint blockade. Gene set enrichment analysis revealed that FANCD2 was mainly involved in the cell cycle and CYP450 metabolism. CONCLUSION To the best of our knowledge, this is the first study to comprehensively elucidate the oncogenic role of FANCD2. FANCD2 has a tumor-promoting aspect in the digestive system and acts as an independent risk factor in HCC; hence, it has recognized value for predicting tumor aggressiveness and prognosis and may be a potential biomarker for poor responsiveness to immunotherapy.
Humans ; Carcinoma, Hepatocellular/diagnosis* ; Liver Neoplasms/diagnosis* ; Immunotherapy ; Fanconi Anemia Complementation Group D2 Protein/metabolism* ; Prognosis ; Male ; Female ; Middle Aged ; Biomarkers, Tumor/metabolism*

OBJECTIVE: To investigate chronic hepatitis C virus (HCV) infection's effect on gestational liver function, pregnancy and delivery complications, and neonatal development. METHODS: A total of 157 HCV antibody-positive (anti-HCV[+]) and HCV RNA(+) patients (Group C) and 121 anti-HCV(+) and HCV RNA(-) patients (Group B) were included as study participants, while 142 anti-HCV(-) and HCV RNA(-) patients (Group A) were the control group. Data on biochemical indices during pregnancy, pregnancy complications, delivery-related information, and neonatal complications were also collected. RESULTS: Elevated alanine aminotransferase (ALT) rates in Group C during early, middle, and late pregnancy were 59.87%, 43.95%, and 42.04%, respectively-significantly higher than Groups B (26.45%, 15.70%, 10.74%) and A (23.94%, 19.01%, 6.34%) ( P < 0.05). Median ALT levels in Group C were significantly higher than in Groups A and B at all pregnancy stages ( P < 0.05). No significant differences were found in neonatal malformation rates across groups ( P > 0.05). However, neonatal jaundice incidence was significantly greater in Group C (75.16%) compared to Groups A (42.25%) and B (57.02%) ( χ ² = 33.552, P < 0.001). HCV RNA positivity during pregnancy was an independent risk factor for neonatal jaundice ( OR = 2.111, 95% CI 1.242-3.588, P = 0.006). CONCLUSIONS Chronic HCV infection can affect the liver function of pregnant women, but does not increase the pregnancy or delivery complication risks. HCV RNA(+) is an independent risk factor for neonatal jaundice.
Humans ; Female ; Pregnancy ; Adult ; Pregnancy Complications, Infectious/epidemiology* ; Retrospective Studies ; Pregnancy Outcome ; Infant, Newborn ; Viremia/virology* ; Hepatitis C ; Hepacivirus/physiology* ; Hepatitis C, Chronic/virology* ; Young Adult ; Alanine Transaminase/blood*

OBJECTIVE: Lipid oxidation is involved in the pathogenesis of atherosclerosis and may be contribute to the development of Ischemic stroke (IS). However, the lipid profiles associated with IS have been poorly studied. We conducted a pilot study to identify potential IS-related lipid molecules and pathways using lipidomic profiling. METHODS: Serum lipidomic profiling was performed using LC-MS in 20 patients with IS and 20 age- and sex-matched healthy controls. Univariate and multivariate analyses were simultaneously performed to identify the differential lipids. Multiple testing was controlled for using a false discovery rate (FDR) approach. Enrichment analysis was performed using MetaboAnalyst software. RESULTS: Based on the 294 lipids assayed, principal component analysis (PCA) and orthogonal partial least squares discriminant analysis (OPLS-DA) models were used to distinguish patients with IS from healthy controls. Fifty-six differential lipids were identified with an FDR-adjusted P less than 0.05 and variable influences in projection (VIP) greater than 1.0. These lipids were significantly enriched in glycerophospholipid metabolism (FDR-adjusted P = 0.009, impact score = 0.216). CONCLUSIONS Serum lipid profiles differed significantly between patients with IS and healthy controls. Thus, glycerophospholipid metabolism may be involved in the development of IS. These results provide initial evidence that lipid molecules and their related metabolites may serve as new biomarkers and potential therapeutic targets for IS.
Humans ; Pilot Projects ; Lipidomics ; Male ; Female ; Biomarkers/blood* ; Middle Aged ; Ischemic Stroke/blood* ; Aged ; China ; Lipids/blood* ; Adult ; Case-Control Studies ; East Asian People

OBJECTIVE: Recombination events are common and serve as the primary driving force of diverse human adenovirus (HAdV), particularly in children with acute respiratory tract infections (ARIs). Therefore, continual monitoring of these events is essential for effective viral surveillance and control. METHODS: Respiratory specimens were collected from children with ARIs between January 2022 and December 2023. The penton base, hexon, and fiber genes were amplified from HAdV-positive specimens and sequenced to determine the virus type. In cases with inconsistent typing results, genes were cloned into the pGEM-T vector to detect recombination events. Metagenomic next-generation sequencing (mNGS) was performed to characterize the recombinant HAdV genomes. RESULTS: Among 6,771 specimens, 277 (4.09%, 277/6,771) were positvie for HAdV, of which 157 (56.68%, 157/277) were successfully typed, with HAdV-B3 being the dominant type (91.08%, 143/157), and 14 (5.05%, 14/277) exhibited inconsistent typing results, six of which belonged to species B. The penton base genes of these six specimens were classified as HAdV-B7, whereas their hexon and fiber genes were classified as HAdV-B3, resulting in a recombinant genotype designated P7H3F3, which closely resembled HAdV-B114. Additionally, a partial gene encoding L1 52/55 kD was identified, which originated from HAdV-B16. CONCLUSION A novel recombinant, P7H3F3, was identified, containing sequences derived from HAdV-B3 and HAdV-B7, which is similar to HAdV-B114, along with additional sequences from HAdV-B16.
Humans ; Adenoviruses, Human/isolation & purification* ; Respiratory Tract Infections/epidemiology* ; Child, Preschool ; Child ; Recombination, Genetic ; Male ; Beijing/epidemiology* ; Infant ; Female ; Phylogeny ; Adenovirus Infections, Human/epidemiology* ; Acute Disease ; Genome, Viral