ObjectiveTo investigate the mechanisms by which Mahuang Lianqiao Chixiaodoutang （MLC） improves obesity-type polycystic ovary syndrome （PCOS） through the phosphatidylinositol 3-kinase （PI3K）/protein kinase B （Akt） signaling pathway. MethodsThirty-six female Sprague-Dawley （SD） rats were randomly divided into a blank control group （Con） and an obesity-type PCOS model preparation group. The model was induced by gavage with letrozole （1 mg·kg^-1） combined with a high-fat diet （HFD）. After model establishment， the obesity-type PCOS model preparation group was further divided into the model group （Mod， normal saline）， metformin group （Met， 0.3 g·kg^-1）， low-dose MLC group （MLC-L， 4.3 g·kg^-1）， medium-dose MLC group （MLC-M， 8.6 g·kg^-1）， and high-dose MLC group （MLC-H， 17.2 g·kg^-1）. Active components of MLC and targets of obesity-type PCOS were screened from databases， a protein-protein interaction （PPI） network was constructed， and gene ontology（GO）and Kyoto Encyclopedia of Genes and Genomes （KEGG） pathway enrichment analysis was performed. The gut microbiota structure was analyzed based on 16S rRNA sequencing and correlated with network pharmacology pathways. Body weight and estrous cycle were dynamically monitored. Ovarian morphology was observed by hematoxylin-eosin （HE） staining. Cell apoptosis was detected by terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling （TUNEL）. Enzyme-linked immunosorbent assay （ELISA） was used to detect levels of follicle-stimulating hormone （FSH）， luteinizing hormone （LH）， anti-Müllerian hormone （AMH）， testosterone （T）， and estradiol （E₂）. Western blot was used to detect the protein expression levels of phosphorylated PI3K/PI3K （p-PI3K/PI3K）， phosphorylated Akt/Akt （p-Akt/Akt）， B-cell lymphoma-2 （Bcl-2）， and Bcl-2-associated X protein （Bax）. ResultsNetwork pharmacology screening identified 124 active components of MLC and 408 overlapping targets between the herbal formula and the disease. Core targets such as Akt1 and Bcl-2 were revealed. As indicated by 16S rRNA sequencing， the abundances of Lachnospiraceae， Lachnoclostridium， and Dorea were increased in the MLC groups （P<0.05）， while the abundance of Veillonella was decreased （P<0.05）. KEGG correlation analysis integrating network pharmacology and gut microbiota data showed significant enrichment of the PI3K/Akt signaling pathway. Animal experiments showed that， compared with the Mod group， body weight decreased to normal levels in the Met， MLC-M， and MLC-H groups. The estrous cycle became regular. The number of corpora lutea increased and cystic follicles decreased. Serum levels of T， FSH， and LH/FSH were reduced （P<0.05， P<0.01）， while the E₂ level was increased （P<0.01）. Ovarian cell apoptosis was reduced （P<0.01）， and the protein expression levels of p-PI3K/PI3K， p-Akt/Akt， and Bcl-2 in ovarian tissue were significantly increased， whereas Bax protein expression was significantly decreased （P<0.05， P<0.01）. ConclusionMLC can regulate gut microbiota structure， effectively improve ovarian pathology in rats with obesity-type PCOS， and inhibit ovarian granulosa cell apoptosis. The mechanism may be associated with upregulation of the PI3K/Akt signaling pathway.

ObjectiveTo investigate the mechanisms by which Mahuang Lianqiao Chixiaodoutang （MLC） improves obesity-type polycystic ovary syndrome （PCOS） through the phosphatidylinositol 3-kinase （PI3K）/protein kinase B （Akt） signaling pathway. MethodsThirty-six female Sprague-Dawley （SD） rats were randomly divided into a blank control group （Con） and an obesity-type PCOS model preparation group. The model was induced by gavage with letrozole （1 mg·kg^-1） combined with a high-fat diet （HFD）. After model establishment， the obesity-type PCOS model preparation group was further divided into the model group （Mod， normal saline）， metformin group （Met， 0.3 g·kg^-1）， low-dose MLC group （MLC-L， 4.3 g·kg^-1）， medium-dose MLC group （MLC-M， 8.6 g·kg^-1）， and high-dose MLC group （MLC-H， 17.2 g·kg^-1）. Active components of MLC and targets of obesity-type PCOS were screened from databases， a protein-protein interaction （PPI） network was constructed， and gene ontology（GO）and Kyoto Encyclopedia of Genes and Genomes （KEGG） pathway enrichment analysis was performed. The gut microbiota structure was analyzed based on 16S rRNA sequencing and correlated with network pharmacology pathways. Body weight and estrous cycle were dynamically monitored. Ovarian morphology was observed by hematoxylin-eosin （HE） staining. Cell apoptosis was detected by terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling （TUNEL）. Enzyme-linked immunosorbent assay （ELISA） was used to detect levels of follicle-stimulating hormone （FSH）， luteinizing hormone （LH）， anti-Müllerian hormone （AMH）， testosterone （T）， and estradiol （E₂）. Western blot was used to detect the protein expression levels of phosphorylated PI3K/PI3K （p-PI3K/PI3K）， phosphorylated Akt/Akt （p-Akt/Akt）， B-cell lymphoma-2 （Bcl-2）， and Bcl-2-associated X protein （Bax）. ResultsNetwork pharmacology screening identified 124 active components of MLC and 408 overlapping targets between the herbal formula and the disease. Core targets such as Akt1 and Bcl-2 were revealed. As indicated by 16S rRNA sequencing， the abundances of Lachnospiraceae， Lachnoclostridium， and Dorea were increased in the MLC groups （P<0.05）， while the abundance of Veillonella was decreased （P<0.05）. KEGG correlation analysis integrating network pharmacology and gut microbiota data showed significant enrichment of the PI3K/Akt signaling pathway. Animal experiments showed that， compared with the Mod group， body weight decreased to normal levels in the Met， MLC-M， and MLC-H groups. The estrous cycle became regular. The number of corpora lutea increased and cystic follicles decreased. Serum levels of T， FSH， and LH/FSH were reduced （P<0.05， P<0.01）， while the E₂ level was increased （P<0.01）. Ovarian cell apoptosis was reduced （P<0.01）， and the protein expression levels of p-PI3K/PI3K， p-Akt/Akt， and Bcl-2 in ovarian tissue were significantly increased， whereas Bax protein expression was significantly decreased （P<0.05， P<0.01）. ConclusionMLC can regulate gut microbiota structure， effectively improve ovarian pathology in rats with obesity-type PCOS， and inhibit ovarian granulosa cell apoptosis. The mechanism may be associated with upregulation of the PI3K/Akt signaling pathway.

Background/Aims: Liver transplantation (LT) following total hepatectomy is a life-saving treatment for hepatocellular carcinoma (HCC). The HCC recurrence after LT hinders the effectiveness of the procedure. The objective of this study is to develop a pre-operative risk stratification model based on a liquid biopsy. Methods: We conducted a comprehensive multi-omics study of 260 HCC patients from three centers, including clinical data, low-coverage whole-genome sequencing of cell-free DNA (cfDNA) from plasma, as well as whole-exome, single-nucleus RNA, and spatial transcriptomics from matched tumor and non-tumor tissues. Results: We identified cfDNA-derived copy number alteration (CNA) signatures associated with post-transplant recurrence. By integrating cfDNA-derived CNA profiles with single-cell transcriptomic data, we traced recurrence-associated cfDNA to a distinct subpopulation of malignant cells within the primary tumor. These cells were embedded in a pro-metastatic microenvironment of specialized endothelial subtypes and cancer-associated fibroblasts. Notably, most recurrence-associated lesions were detectable in cfDNA prior to liver transplantation (LT). Building on these insights, we developed the ZJU Criteria based on CNA fragments and tumor markers, a pre-LT risk prediction tool that integrates conventional clinical factors with cfDNA-derived CNA signatures, and validated it using internal and independent external cohorts. Conclusion Our findings suggest that post-transplant recurrence commonly originates from advanced subclones that emerge late during tumor evolution. The ZJU Criteria provides an accurate, non-invasive strategy that significantly improves pre-LT risk stratification and clinical decision-making for patients with HCC.

ObjectiveTo reveal the effects of overexpression and knockdown of CDH18 gene on cervical cancer proliferation and migration levels through the Wnt/β-catenin signaling pathway in cervical cancer cells. MethodsA comprehensive analysis of CDH18-interacting molecules was performed via the bioinformatics STRING database （http：//cn.string-db.org）. Molecular docking between Wnt/β-catenin inhibitor XAV939 and β-catenin was performed using the bioinformatics tool AutoDock （http：//autodock.scripps.edu）. The effect of CDH18 on β-catenin subcellular distribution was detected by laser confocal microscopy. EdU assay， wound healing assay and Transwell assay were used to detect the effects of CDH18 gene overexpression， CDH18 gene knockdown and the XAV939 on cell proliferation and migration. Western blot was performed to measure the expression levels of Wnt/β-catenin pathway-related molecules， including β-catenin， transcription factor 4 （TCF4）， and cellular myelocytomatosis oncogene （c-Myc）， following CDH18 gene overexpression， CDH18 gene knockdown， or XAV939 treatment. ResultsIn SiHa and HeLa cells， CDH18 gene overexpression significantly increased the protein expression levels of β-catenin， TCF4 and c-Myc， decreased the protein expression of GSK-3β， and enhanced cell proliferation and migration， with statistically significant differences （P<0.05）. Conversely， CDH18 gene knockdown significantly reduced the protein expression of β-catenin， TCF4 and c-Myc， elevated GSK-3β expression， and suppressed cell proliferation and migration （P<0.05）.Treatment with XAV939 in SiHa and HeLa cells downregulated β-catenin， TCF4 and c-Myc， upregulated GSK-3β， and inhibited cell proliferation and migration， with significant differences （P<0.05）. ConclusionCDH18 promotes the proliferation and migration of cervical cancer cells via the Wnt/β-catenin signaling pathway.

Abstract: To explore the relationship between the replication-associated bromodomain protein 4 ( BRD4)and human papillomavirus (HPV) 16(HPV16) viral load in cervical squamous cell carcinoma and CIN Ⅰ tissues , confirm the effects of BRD4 degradation agent MZ1 on viral load . Methods : Thirty HPV16-positive cervi- cal cancer specimens and 30 non-cervical cancer specimens were collected , and the viral load of the samples was detected by real-time fluorescence quantitative PCR , and the expression of BRD4 was analyzed by immunohisto- chemistry and Western blot. Results : The viral load was higher in the samples of cervical cancer group than in the samples of non-cancer group , the difference is statistically significant ( P < 0. 01) . Immunohistochemistry results showed that the expression of BRD4 were significantly higher in cervical cancer specimens than in noncancerous specimens , the difference is statistically significant (P < 0. 05) . BRD4 expression was significantly and positively correlated with high viral loads , the difference is statistically significant (P < 0. 001) . the BRD4 degradation agent MZ1 significantly reduced the viral load , the difference is statistically significant (P < 0. 01) . Conclusion BRD4 may be involved in the replication of HPV16 virus , and BRD4 degradation agent MZ1 can inhibit the replication of HPV16 virus .

The European Association for Cardio-Thoracic Surgery (EACTS) has recently updated and published the "2024 EACTS guidelines on perioperative medication in adult cardiac surgery". Based on the latest evidence, the guidelines have been updated in multiple aspects including underlying disease management, antithrombotic medication, arrhythmia treatment and other supportive care, etc. This paper aims to summarize and interpret the guidelines, in order to promote clinicians’ understanding and optimize perioperative medical treatment in adult cardiac surgery.

Objective To systematically evaluate the economic burden of echinococcosis patients in western China using meta-analysis, so as to provide insights into formulation of effective echinococcosis control strategies and optimization of medical resource allocation. Methods Articles pertaining to the economic burden of echinococcosis patients in western China were retrieved in international and Chinese databases, including PubMed, Web of Science, CNKI, Wanfang Data, and VIP Chinese Science and Technology Periodicals Full-Text Database. Studies were screened according to inclusion and exclusion criteria, and the basic characteristics of included articles, characteristics of included studies, and echinococcosis patients’ economic burden were extracted. A meta-analysis was performed using the software R package. The pooled effect size and heterogeneity were examined using a random effects model, and subgroup analyses were conducted. Results A total of 13 articles were enrolled, including 12 Chinese publications and one English publication, and all were retrospective studies. Included studies covered 4 western provinces (autonomous regions) of China, including Ningxia Hui Autonomous Region, Xinjiang Uygur Autonomous Region, Sichuan Province, and Qinghai Province, which involved 11 282 echinococcosis patients, and the study period spanned from 2006 to 2023. Meta-analysis showed that the pooled direct medical costs of echinococcosis patients were 24 730 [95% confidence interval (CI): (13 040, 36 430)] Yuan in endemic areas of western China, appearing a significant heterogeneity (I² = 79.95%, P < 0.01). Subgroup analyses showed the pooled direct medical costs of 9 090 [95% CI: (-4 970, 23 150)] Yuan for echinococcosis patients in Ningxia Hui Autonomous Region and 18 140 [95% CI: (8 440, 27 840)] Yuan in Xinjiang Uygur Autonomous Region, and pooled direct medical costs of 9 470 [95% CI: (-1 850, 20 790)] Yuan for cystic echinococcosis patients prior to 2007 and 15 270 [95% CI: (560, 24 030)] Yuan after 2007, respectively. There were high heterogeneities in the pooled direct medical costs for echinococcosis patients in terms of date of publication (I² = 82.05%, P < 0.001), treatment modality (I² = 83.28%, P < 0.001) and type of echinococcosis (I² = 72.63%, P < 0.001). In addition, the pooled indirect medical costs and direct non-medical costs were 5 670 Yuan and 4 000 Yuan for echinococcosis patients in western regions of China, respectively. Conclusions Echinococcosis patients suffer from a high economic burden in endemic areas of western China, and there are disparities in the direct medical costs for echinococcosis patients depending on disease type, study areas and study period.

Liquid biopsy,as an emerging minimally invasive early detection method for tumors,has shown great potential;however,several challenges limit its application in tumor diagnosis.Tetrahedral framework nucleic acids(tFNAs)have garnered significant attention in the biomedical field due to their structural stabili-ty,programmability,and superior intracellular endocytosis and tissue penetration capabilities.These properties make tFNAs an ideal candidate for constructing advanced biosensing platforms for liquid biopsy applications.tFNAs significantly enhance the binding efficiency of circulating tumor cells(CTCs),circulating tumor DNA(ctDNA),and extracellular vesicles(EVs),thereby improving the sensitivity and detection capability of the liquid biopsy biosensing platform.This review provides a comprehensive overview of tFNAs-based biosensors in the liquid biopsy field.It elaborates on the synthesis,characteristics,and applications of tFNAs in detecting CTCs,ctDNA,and EVs.Additionally,it discusses the diverse strategies and advantages of tFNAs in biosens-ing applications,highlighting how these features significantly enhance the performance and reliability of bio-sensors.Finally,this review addresses the current challenges faced by tFNAs in liquid biopsy and explores their future prospects,aiming to facilitate early screening,precise diagnosis,and integrated diagnostic-treat-ment approaches for tumors.

Objective:To investigate the efficacy of combined sufentanil and remifentanil in pediatric ear, nose, and throat surgeries.Methods:This study used a prospective study design. A total of 110 pediatric children who underwent elective ear, nose, and throat surgery at Xi'an Children's Hospital from January 2022 to December 2023 were included in this study. The patients were randomly divided into a control group ( n = 55) and an observation group ( n = 55) using a random number table method. In the control group, only sufentanil was used for general anesthesia, while the observation group received both sufentanil and remifentanil during the anesthesia process. The changes in average arterial pressure and heart rate were compared between the two groups at five time points: T1 (before anesthesia induction), T2 (during tracheal intubation), T3 (at the start of surgery), T4 (5 min after the start of surgery), and T5 (immediately after surgery). Additionally, the recovery time for spontaneous breathing, the time to open eyes, extubation time, and adverse reactions were compared between the two groups. Ramsay sedation scores were compared between the two groups at three time points: T6 (5 min after extubation), T7 (15 min after extubation), and T8 (30 min after extubation). Pain Visual Analog Score was compared between the two groups at T8 (30 min after extubation), T9 (60 min after extubation), and T10 (90 min after extubation). Results:The differences in average arterial pressure and heart rate between the two groups at time points T1-T5, as well as Ramsay sedation scores at T6-T8 and Visual Analog Score scores at T8-T10, were all statistically significant ( F = 152.93, 2 718.29, 2 347.47, 751.77, all P < 0.05). In the observation group, the recovery time for spontaneous breathing [(5.37 ± 2.18) min vs. (6.74 ± 2.42) min], the time to open eyes [(9.03 ± 2.02) min vs. (10.84 ± 3.11) min], and extubation time [(13.22 ± 4.22) min vs. (16.47 ± 5.14) min] were significantly shorter in the observation group than in the control group ( t = 3.11, 3.62, 3.62, all P < 0.001). The incidence of adverse reactions was significantly lower in the observation group than in the control group [3.64% (2/55) vs. 16.36% (9/55), χ2 = 4.94, P < 0.05]. Conclusions:Both sufentanil alone and in combination with remifentanil yield effective anesthesia outcomes in pediatric ear, nose, and throat surgeries. However, the combination of sufentanil and remifentanil significantly shortens the recovery time for spontaneous breathing, the time to open eyes, and extubation time. This combined approach also lowers the incidence of adverse reactions, improves surgical outcomes, and promotes postoperative recovery of children.

Objective·To fabricate a 3D-printed dental crown and bridge resin slurry using digital light processing(DLP)technology,investigate the influence of different printing parameters on its mechanical properties,determine the optimal printing parameters,and optimize the composition ratio of DLP-printed crown and bridge resin.Methods·Based on the viscosity characteristics of the mixture,the optimal ratio of urethane dimethacrylate(UDMA)to poly(propylene glycol)dimethacrylate(PPGDMA)was explored.After silanizing silicon dioxide(SiO2),it was mixed with UDMA,PPGDMA,and 2,4,6-trimethylbenzoyl bis(p-tolyl)phosphine oxide(TMO)to prepare DLP-printed dental crown and bridge resin slurries with different solid contents,and their rheological properties were tested.The Beer-Lambert equation was used to calculate the light penetration depth and critical exposure energy of the printing slurry.Based on these values,different exposure intensities,exposure times,post-curing times,and layer thicknesses were set respectively to carry out a series of printing experiments.By comparing and analyzing the flexural strength of the products under different printing parameters,the optimal printing parameter combination was screened out.Results·Viscosity tests showed that the optimal UDMA-to-PPGDMA ratio was 6∶4.The rheological behavior of printing slurries with different solid contents was tested,and the results showed that the DLP-printed dental crown and bridge resin with a solid content of 22%exhibited the best printing performance.According to the Beer-Lambert analysis,the light penetration depth Dp of the printing slurry was 119.79 μm,and the critical exposure energy Ec was 25.54 mJ/cm2.When the exposure intensity was 20 mW/cm2,the flexural strength reached a maximum of(132.39±8.92)MPa,and the difference was statistically significant(P<0.05).The flexural results of different exposure times showed that the flexural strength could reach(131.73±9.43)MPa when the single-layer exposure time was 3.0 s,and there was no significant difference when the exposure time was further increased.The flexural results of different post-curing times showed that when the post-curing time reached 30 min,there was no significant relationship between the flexural strength value and the increase in post-curing time.Regarding the influence of different layer thicknesses on the flexural performance,the test results showed that when the layer thickness was 50 μm,the result was the best,and the difference was statistically significant(P<0.001).Conclusion·Based on viscosity and rheological tests,a DLP-printable crown and bridge resin slurry was successfully developed.The optimal printing parameters were determined through statistical analysis of flexural strength:exposure intensity of 20 mW/cm2,exposure time of 3.0 s,post-curing time of 30 min,and a layer thickness of 50 μm.