Sleep fragmentation， characterized by disrupted nocturnal sleep，is a core manifestation of chronic insomnia and exhibits a close and complex bidirectional relationship with Alzheimer disease （AD）. On the one hand， sleep fragmentation impairs glymphatic system function， reducing the clearance efficiency of toxic metabolites such as amyloid-beta （Aβ） and tau proteins in the brain interstitial fluid， thereby acting as a promoting factor for AD. Concurrently， sleep disturbances directly dysregulate pathogenic protein dynamics，and chronic sleep deprivation exacerbates neuroinflammation and oxidative stress， worsening the AD pathological environment.On the other hand， inherent AD pathological changes further aggravate sleep fragmentation. Damage to brain regions associated with AD leads to circadian rhythm disruption and reduced non-rapid eye movement （NREM） sleep.Additionally，imbalances in neurotransmitters such as orexin and melatonin during AD progression contribute to the disintegration of the sleep-wake cycle. This review aims to explore the mutual interactions between sleep fragmentation and AD， identify current research gaps， and provide new directions for future studies.

ObjectiveThis paper aims to clarify the material basis of Gualou Niubangtang and establish a quantitative analysis method for its main constituents， providing a reference for the overall quality control of this preparation. MethodsThe constituents in the formula were systematically characterized based on ultra-performance liquid chromatography-quadrupole time-of-flight tandem mass spectrometry （UPLC-Q-TOF-MS/MS）. Identification was performed by matching with the UNIFI 9.6 software and utilizing database platforms such as PubChem， ChemicalBook， and ChemSpider， combined with relevant literature reports. A quantitative analysis method for the seven main constituents in Gualou Niubangtang was established by using high performance liquid chromatography （HPLC）. ResultsUPLC-Q-TOF-MS/MS analysis identified 155 constituents， including 69 flavonoids， 36 terpenoids， 23 phenylpropanoids， 8 phenylethanoid glycosides， and 19 other types of constituents. In the established quantitative analysis method， the seven main constituents showed good linearity within their respective linear ranges. The precision， repeatability， stability， and spike recovery all met the required standards. The results showed that the content ranges of geniposide， liquiritin， hesperidin， arctiin， baicalin， oroxylin A-7-O-β-D-glucuronide， and wogonoside in 15 batches of Gualou Niubangtang were 13.67-21.25， 1.20-7.64， 5.45-7.45， 22.97-33.51， 29.95-39.07， 2.58-4.80， and 6.56-9.31 mg·g^-1， respectively. ConclusionThis study successfully characterizes and attributes multi-category constituents in Gualou Niubangtang， clarifying that its material basis is primarily composed of flavonoids， terpenoids， phenylethanoid glycosides， and phenylpropanoids. Furthermore， it enables the quantification of seven constituents within the formula. This work lays a foundation for research on the quality control， action mechanism， and clinical application of this formula.

Childhood simple obesity has become a significant public health issue in China. Modern medicine primarily relies on lifestyle interventions and often suffers from poor long-term compliance， while pharmacological options are limited and associated with potential adverse effects. Traditional Chinese Medicine （TCM） has a long history in the prevention and management of this condition， demonstrating eight distinct advantages， including systematic theoretical foundation， diversified therapeutic approaches， definite therapeutic efficacy， high safety profile， good patient compliance， comprehensive intervention strategies， emphasis on prevention， and stepwise treatment protocols. Additionally， TCM is characterized by six distinctive features： the use of natural medicinal substances， non-invasive external therapies， integration of medicinal dietetics， simple exercise regimens， precise syndrome differentiation， and diverse dosage forms. By combining internal and external treatments， TCM facilitates individualized regimen adjustment and holistic regulation， demonstrating remarkable effects in improving obesity-related metabolic indicators， regulating constitutional imbalance， and promoting healthy behaviors. However， challenges remain， such as inconsistent operational standards， insufficient high-quality clinical evidence， and a gap between basic research and clinical application. Future efforts should focus on accelerating the standardization of TCM diagnosis and treatment， conducting multicenter randomized controlled trials， and fostering interdisciplinary integration， so as to enhance the scientific validity and international recognition of TCM in the prevention and treatment of childhood obesity.

Myasthenia gravis is an autoimmune disorder characterized by impaired neuromuscular transmission. Thymectomy is one of the therapeutic options for acetylcholine receptor antibody-positive myasthenia gravis patients. The quality of perioperative care is directly associated with surgical safety and patient outcomes. However, there is currently a lack of specialized nursing consensus or guidelines specifically addressing the care of these patients domestically or internationally. To promote the standardization and normalization of perioperative nursing care for myasthenia gravis patients undergoing thymectomy and to ensure treatment efficacy, a panel of 57 experts from relevant fields was convened. Based on evidence-based medicine and clinical practice experience, discussions were held on various aspects including condition assessment, nutritional support, medication management, and airway care, resulting in a consensus with 18 final recommendations by using the Delphi method through two rounds of expert consultation. This consensus aims to provide a scientific reference for the perioperative nursing care of myasthenia gravis patients undergoing thymectomy.

Ecoflex is a commercial designation for elastomers developed based on the principles of environmental sustainability and flexibility. Various manufacturers offer different types of Ecoflex products with distinct compositions and functions. Among these, the platinum-catalyzed silicone rubber Ecoflex series has demonstrated considerable applicability in various fields of oral medicine due to its excellent flexibility, biocompatibility, stability across a wide temperature range, and tunable mechanical properties. In tissue engineering, it can simulate the mechanical behavior of oral mucosa, and is used in cleft lip surgical training models and preoperative evaluation for temporal bone defect reconstruction. In the field of wearable devices, leveraging its encapsulation protection and flexible characteristics, highly sensitive sensors constructed from Ecoflex can monitor signals such as oral bite force and masticatory muscle activity, thereby aiding in the diagnosis of temporomandibular joint disorders and postoperative evaluation of cleft lip and palate. Moreover, when combined with bio-waste materials, it promotes the functionalization and sustainability of oral wearable devices.In drug delivery systems, its conformability and controlled-release capability address challenges in localized oral drug administration. Designs such as flexible microneedles and temperature-responsive composite systems provide precise solutions for treating periodontitis and oral ulcers. In minimally invasive surgical instruments, its softness enables the development of soft robots and magnetically controlled microfluidic valves, enhancing surgical safety and precision. In the field of oral rehabilitation, Ecoflex soft liner materials, inspired by the suction cup structure of octopus tentacles, improve denture retention. Their low modulus reduces mucosal irritation, ensuring both comfort and durability. Although Ecoflex shows great potential in biomedical applications, it still faces certain challenges, particularly regarding long-term stability after implantation, mechanical fatigue resistance, and microbial colonization, which require further investigation. In the future, with advancements in 3D printing technology, Ecoflex is expected to achieve more precise clinical translation across multiple fields and drive innovation in intelligent biomaterials.

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.

Sonodynamic therapy （SDT） applies low-frequency ultrasound to activate sonosensitizers that have accumulated in tumor location， which induces cavitation effects and leads to the in-situ generation of reactive oxygen species （ROS）， thereby achieving precise and efficient tumor treatment. Owing to its advantages such as deep tissue penetration and controllable treatment range， SDT has attracted significant attention and has been widely used in the research on the treatment of various tumors. While conventional treatment modalities have achieved significant efficacy in the treatment of hepatocellular carcinoma （HCC）， there are still certain limitations. In this context， nanomedicine-based SDT leverages the targeting capabilities of nano-agents to realize specific killing of HCC cells， and furthermore， it can synergize with photodynamic therapy， chemotherapy， and immunotherapy to provide new opportunities for developing novel treatment modalities for HCC. This article reviews the mechanism of action of SDT and the advances in the research and application of SDT in the treatment of HCC， analyzes the shortcomings of existing studies， and proposes the directions for future development， in order to provide a theoretical foundation and scientific guidance for related research on HCC.

Objective:Human papilloma virus(HPV)E6/E7mRNA in situ hybridization detection technology was used to explore whether high-grade squamous intraepithelial lesion(HSIL)of cervix with negative high-risk human papilloma virus(HR-HPV)typing test was caused by HPV infection,so as to provide new insights for the accurate diagnosis and treatment of cervical HSIL.Methods:305 tissue samples were collected from patients with HSIL who underwent cervical biopsy or surgical treatment in the Department of Gynecology,Affiliated Hospital of Shandong Second Medical University,from January 2020 to October2022.Patients with negative HR-HPV genoty-ping results(15 cases)were assigned to the study group,while those with positive results(290 cases)served as the control group.RNAscope in situ hybridization was used to detect the expression of HPV E6/E7 mRNA in the two groups,and the expression of HPV E6/E7 mRNA was analyzed by semi-quantitative scoring of staining inten-sity.Immunohistochemistry(IHC)was used to detect the expression of p16 and Ki-67.Results:①Among 305 pa-tients with HSIL,15 patients had negative HR-HPV typing test,with an incidence of 4.9％(15/305).②73.3％(11/15)of the study group showed positive expression of HPV E6/E7 mRNA,which was statistically significant compared with 100.0％(290/290)of the control group(P＜0.001).③The positive expression rate of p16 in the study group was significantly lower than that in the control group(93.3％vs.100.0％,P=0.049),while there was no significant difference in the positive expression rate of Ki-67 between the two groups(100.0％vs.100.0％).④In the samples with histopathological type cervical intraepithelial neoplasia(CIN)2,the overall score of HPV E6/E7 mRNA in the study group was significantly lower than that in the control group,which was statistically significant(P=0.004).In CIN3 samples,although the overall score of HPV E6/E7 mRNA in the study group was lower than that in the control group,there was no statistically significant difference(P=0.158).Conclusions:4.9％of pa-tients with HSIL in cervical cancer screening may be missed or misdiagnosed due to negative HR-HPV typing test.HPV E6/E7 mRNA in situ hybridization detection technology was helpful to reduce the false negative rate of HR-HPV typing test in HSIL,and it may assist in predicting the progression of cervical lesions,so as to provide a new idea for individualized precise treatment.

Objective Based on multi-dimensional bioinformatics technology,the molecular pathological mechanism of acute hypotension is systematically analyzed.Methods Integrate the gene expression profile of the Gene Expression Omnibus database(GSE2401),use limma package(R software)to screen differential genes,and optimize targets through data dimensionality reduction(log2(FC)＞1,P＜0.05);Further combine Gene Ontology,Kyoto Encyclopedia of Genes and Genomes and gene set enrichment analysis pathway enrichment and STRING-Cytoscape(MCODE,CytoHubba plug-in)to build a protein-protein interaction(PPI)network to mine core genes;realize the full-chain analysis of"differential gene-functional pathway-PPI network".Results 676 differential genes(304 upregulated,372 downregulated),ribosome structural components(Rps8,Rps27,Rpl35,etc.)and multiple pathways such as forkhead box protein and cyclic adenosine monophosphate were found to coordinate the regulation of acute hypotension.Conclusion This study uses a low-cost and efficient bioinformatics analysis framework to reveal the association between ribosomal dysfunction,changes in insulin signal efficacy and blood pressure regulation,providing new ideas for targeted therapy.

Purpose To investigate the relationship between SERPINA4 expression and clinicopathological fea-tures and prognosis in metastatic colorectal cancer(CRC).Methods EnVision two-step immunohistochemical method was used to detect the expression of SERPINA4 protein in 104 cases of primary and metastatic tumor paraffin tissues of metastatic colorectal cancer and adjacent intestinal normal mucosa,and its relationship with clinicopathological features of patients was analyzed.qRT-PCR was used to detect the expression of SERPINA4 mRNA in 11 pairs of metastatic CRC metastases and paired primary tumor paraffin-embedded tissue samples.The survival of patients was followed up,and the relationship between SERPINA4 expression and patient prognosis was analyzed by Kaplan-Meier method.Re-sults Immunohistochemical results showed that the strong positive expression rate of SERPINA4 was 97.10％in nor-mal mucosa,71.20％in primary lesions,and 39.40％in metastatic lesions.The difference between the three groups was statistically significant(P＜0.001).qRT-PCR results showed that SERPINA4 mRNA was lowly expressed in me-tastatic lesions of metastatic CRC(P＜0.05).The expression of SERPINA4 in metastatic lesions was significantly cor-related with histological grade,N stage and M stage of the tumor(P＜0.05),but not significantly correlated with age,gender,tumor location and T stage of patients(P＞0.05).The survival time of patients with metastatic colorectal cancer with high expression of SERPINA4 was longer than that of patients with low expression.Conclusion The ex-pression of SERPINA4 is of great significance in the survival and prognosis of patients with metastatic CRC.