Hepatocellular carcinoma （HCC）， as the sixth most common malignant tumor worldwide， poses a serious threat to human health due to its insidious onset and high mortality rate. This article reviews the molecular mechanisms and intervention strategies of gut microbiota （GM） homeostasis in the development and progression of HCC， in order to provide new ideas for the intervention and treatment of HCC. Studies have shown that GM dysbiosis， intestinal leakage， microbial-associated molecular pattern， bacterial translocation， and metabolic products play key roles in the progression of HCC. GM imbalance may lead to immune escape， thereby promoting tumor cell proliferation and metastasis. This article elaborates on the association between GM and HCC， deeply analyzes the mechanism of action of GM in the development and progression of HCC， investigates the role of bile acid-related metabolites， short-chain fatty acid-related metabolites， and other metabolites in HCC， and explores the strategies for targeting GM in the treatment of HCC， including probiotics， prebiotics， antibiotics， Toll-like receptor 4 antagonists， and fecal microbiota transplantation. This article emphasizes that maintaining the integrity of the intestinal barrier and GM homeostasis is of great significance in the prevention and treatment of HCC， which provides a direction for developing new diagnosis and treatment strategies.

Liraglutide (Lira), a glucagon-like peptide-1 (GLP-1) receptor agonist approved for diabetes and obesity, has shown significant potential in treating metabolic dysfunction-associated steatotic liver disease (MASLD). However, its systematic molecular regulation and mechanisms remain underexplored. In this study, a mouse model of MASLD was developed using a high-fat diet (HFD), followed by Lira administration. Proteomics and glycoproteomics were analyzed using label-free liquid chromatography-tandem mass spectrometry (LC-MS/MS), while potential molecular target analysis was conducted via quantitative real-time polymerase chain reaction (qPCR) and Western blotting. Our results revealed that Lira treatment significantly reduced liver weight and serum markers, including alanine aminotransferase (ALT) and others, with glycosylation changes playing a more significant role than overall protein expression. The glycoproteome identified 255 independent glycosylation sites, emphasizing the impact of Lira on amino acid, carbohydrate metabolism, and ferroptosis. Simultaneously, proteomic analysis highlighted its effects on lipid metabolism and fibrosis pathways. 21 signature molecules, including 7 proteins and 14 N-glycosylation sites (N-glycosites), were identified as potential targets. A Lira hydrogel formulation (Lira@fibrin (Fib) Gel) was developed to extend drug dosing intervals, offering enhanced therapeutic efficacy in managing chronic metabolic diseases. Our study demonstrated the importance of glycosylation regulation in the therapeutic effects of Lira on MASLD, identifying potential molecular targets and advancing its clinical application for MASLD treatment.

OBJECTIVES: A stable, reliable, and easily implementable clinical diagnostic method for marginal velopharyngeal insufficiency (MVPI) was established on the basis of the subjective hearing judgement of hypernasality and objective examination of velopharyngeal closure to address the lack of unified diagnostic criteria for MVPI. METHODS: Nasopharyngeal fiberscopy and speech assessment results were collected from postoperative patients with cleft palate. These results were used to analyze the differences in the distribution of nasal resonance in patients with different velopharyngeal closure ratios and the correlation between velopharyngeal closure ratios and nasal resonance status. Mild-to-moderate hypernasality with its corresponding elopharyngeal closure ratio was employed to establish the diagnostic criteria of MVPI. The reproducibility of the criteria and whether the patients with MVPI diagnosed by using the criteria exhibited significantly different speech characteristics compared with other patients were verified. RESULTS: A strong correlation was found between velopharyngeal closure ratios and nasal resonance (P<0.001). Mild-to-moderate hypernasality mainly corresponded to velopharyngeal closure ratios ranging from 90% to 99%, and the combination of the two characteristics as the diagnostic criteria for MVPI demonstrated good consistency (Kappa value=0.789, P<0.001). Moreover, under the diagnostic criteria, significant differences in nasal resonance (P<0.001), nasal emission (P=0.007), and misarticulation (P<0.001) were found between patients with velopharyngeal insufficiency and those with MVPI. CONCLUSIONS Combining the subjective hearing judgement of mild-to-moderate hypernasality with velopharyngeal closure ratios over 90% under nasopharyngeal fiberscopy provides a reliable and effective clinical method for diagnosing MVPI.
Humans ; Velopharyngeal Insufficiency/physiopathology* ; Reproducibility of Results ; Cleft Palate/surgery* ; Male ; Female ; Child

ObjectiveTo investigate the syndrome evolution patterns， characteristics of the used herbal medicinals， and efficacy variations across different stages of rheumatoid arthritis （RA） progression. MethodsBased on the China Rheumatoid Arthritis Registry of Patients with Chinese Medicine （CERTAIN）， 2,506 RA patients were retrospectively enrolled and categorized into ＜6 months group （166 cases）， 6 months to ＜5 years group （1063 cases）， 5 to ＜20 years group （1067 cases）， and ≥20 years group （210 cases）. Syndromes were differentiated before and after traditional Chinese medicine （TCM） treatment， including damp-heat obstruction， wind-damp obstruction， cold-damp obstruction， blood stasis obstructed in the collaterals， phlegm-stasis obstruction， liver-kidney insufficiency， qi and blood deficiency， and qi-yin deficiency. The syndrome evolution rate was calculated for high-frequency syndromes before and after treatment. Analysis was conducted on top 20 frequently used Chinese herbs at the first diagnosis. Clinical efficacy of the 28-joint disease activity score based on erythrocyte sedimentation rate （DAS28-ESR） and 28-joint disease activity score based on C-reactive protein （DAS28-CRP） before and after treatment were assessed. A multivariate logistic regression analysis was performed to identify factors affecting the efficacy of TCM treatment. ResultsPatients with course of disease shorter than 6 months predominantly presented with cold-dampness obstruction syndrome （49/166， 29.5%）， wind-dampness obstruction syndrome （46/166， 27.7%）， and dampness-heat obstruction syndrome （43/166， 25.9%）. For patients with course of disease logner than 6 months and shorter than 5 years and those within 5 to 20 years， the dominant syndrome was dampness-heat obstruction syndrome （324/1063， 30.5% and 318/1067， 29.8%， respectively）. In patients with disease duration ≥20 years， liver-kidney insufficiency syndrome and dampness-heat obstruction syndrome both predominated， each accounting for 25.24% （53/210）. The syndromes with more than 100 cases before treatment and a syndrome evolution rate greater than 10% after treatment were dampness-heat obstruction （201/738， 27.2%）， liver-kidney insufficiency （119/367， 32.4%）， and phlegm-stasis obstruction syndromes （73/172， 42.4%）. These were classified as high-frequency syndromes. After treatment， damp-heat obstruction syndrome and liver-kidney insufficiency syndrome primarily evolved into wind-damp obstruction syndrome， while phlegm-stasis obstruction syndrome evolved into damp-heat obstruction and cold-damp obstruction syndrome. The top two commonly used Chinese herbs across all groups were Gancao （Radix et Rhizoma Glycyrrhizae） and Baishao （Radix Paeoniae Alba）. In the ＜6 months group and the 6 months to ＜5 years group， high-frequency herbs also included Fangfeng （Radix Saposhnikoviae）， Duhuo （Radix Angelicae Pubescentis）， Chuanxiong （Rhizoma Chuanxiong）， and Qianghuo （Radix et Rhizoma Notopterygii）. In the 5 to ＜20 years group and the ≥20 years group， the usage of Huangqi （Radix Astragali）， Fuling （Poria）， Niuxi （Radix Achyranthis Bidentatae）， and Danggui （Radix Angelicae Sinensis） increased， while the proportion of Fangfeng and Duhuo decreased. After treatment， the DAS28-ESR and DAS28-CRP scores in all groups significantly decreased （P＜0.05）. There were statistically significant differences in clinical efficacy based on DAS28-ESR and DAS28-CRP across all groups （P＜0.01）. Multivariate logistic regression revealed significantly reduced treatment efficacy in the 6 months-5 years group （OR=0.4）， 5~20 years group （OR=0.5）， and ≥20 years group （OR=0.4） compared to the ＜6 months group. ConclusionRA syndromes follow a progression pattern from excess to deficiency， with corresponding transition in herbal usage from pathogen-eliminating to healthy qi-reinforcing approaches. TCM intervention can significantly reduce disease activity of RA， with superior efficacy in patients with disease duration shorter than 6 months.

Liver macrophages are important immune cells in the liver,and they express proinflammatory factors and anti-inflammatory factors through polarization into M1 type and M2 type,respectively,thereby playing a role in regulating inflammatory damage response.The malignant transformation of hepatic progenitor cells is the core mechanism of the malignant progression of hepatic precancerous lesions,and its key factor is the continuous stimulation of inflammatory microenvironment,which is closely associated with M1/M2 macrophage polarization.This review mainly focuses on the association between macrophage polarization,chronic inflammation,and malignant transformation of hepatic progenitor cells,so as to provide a theoretical basis for the prevention and treatment of hepatic precancerous lesions.

Objective To evaluate the factors affecting urinary stone detection rate using virtual unenhanced(VUE)images obtained from triphasic dual-energy CT urography(DECTU)based on Logistic regression analysis.Methods For this study,150 patients who had suspected urinary stone and underwent triphasic DECTU were included.The true unenhanced(TUE)images were reconstructed as 120 kVp-like images,and VUE images at the portal venous phase[VUE(VP)]and excretory phase[VUE(EP)]were obtained using iodine removal technique from portal venous and excretory phase DECTU images,respectively.Two readers independently evaluated the above three types of images,and recorded the number of urinary stones,their anatomical locations,and whether there was residual iodine on the VUE images.Stone size and CT number were recorded only on the TUE images.Stone size,CT number,anatomical location,and iodine contrast agent were included in univariate and multivariate Logistic regression analyses to evaluate the factors affecting urinary stone detection rate using VUE images.Thresholds for detecting urinary stones on VUE images were determined using receiver operating characteristics(ROC)analysis.Results We detected 304 stones on TUE images,while the detection rates were 92.4％and 71.4％when using VUE(VP)and VUE(EP)images,respectively.Stone size and CT number were important factors influencing urinary stone detection rate using VUE(VP)and VUE(EP)images(P＜0.01).The area under curve(AUC)of using stone size and CT number for detecting stones using the VUE(VP)images was up to 0.96,and as threshold values,stones with size larger than 3.52 mm and CT number greater than 469 HU were found to have high accuracy.However,the AUC decreased to 0.88 when we combined stone size,CT number and anatomical location using the VUE(EP)images.In addition,different contrast agents did not affect the detection rate of stones on the VUE(EP)images(P=0.57).The stone detection rate in the kidney was significantly lower than those on the VUE(EP)images(P＜0.001).Conclusion VUE(VP)images provide better stone detection.Stone size and CT number have significant impacts on the stone detection rate using VUE images.The lower stone detection rate in the kidney on the VUE(EP)images is related to the residual iodine.

The universal health coverage agenda promotes population health and social equity and is a priority for the WHO and governments worldwide. This article outlines the basic concept, development, content, monitoring indicators, global progress, and challenges of the universal health coverage agenda. After over half a century of development, a global consensus has been reached on the definition and content of the universal health coverage agenda which emphasizes coverage proportion of the population, content of healthcare services, and economic protection measures. The implementation principle of the agenda for universal health coverage is to prioritize providing healthcare services of high health benefits and social value to the entire population under resource constraints. However, the healthcare service recommendations and evaluation frameworks proposed by the WHO and other international organizations tend to favor low-income countries, neglecting services related to injury prevention and mental health, and therefore may not be suitable for all countries. The development across various dimensions of the agenda for universal health coverage is uneven, with low-income countries lagging. Progress in the prevention and control of non-communicable diseases and injuries is delayed. Low-income groups and vulnerable populations are at a disadvantage in accessing services and economic protection. It is suggested that a globally applicable set of standards, methods, and processes be used to identify high-priority healthcare services. Countries should gradually expand the scope of healthcare services and population coverage based on their needs and capabilities. Additionally, efforts should be made to increase investment in healthcare system resources and international collaboration to promote the development and technological advancement of healthcare systems in low-income countries. Furthermore, it is also necessary to build a high-quality primary healthcare service system and strengthen protection for vulnerable groups.

Objective Flap division is the primary method for treating postoperative airway obstruction following pharyngeal flap surgery.However,a discussion on the treatment effectiveness and prognosis of this surgery is lacking.Therefore,this study aims to explore the effectiveness of flap division in improving airway obstruction and hyponasality after pharyngoplasty and to analyze the risk factors for postoperative complications.Methods A retrospective review was conducted on the data of all patients who underwent flap division following pharyngeal flap for airway obstruction at our institution.Pre-and post-operative assessments of ventilation,speech,and related factors were performed using the nasal obstruction symptom evaluation scale,speech evaluation scale,nasopharyngeal fiberscope,and lateral cephalo-metric radiographs.A nasopharyngeal fiberscope was uti-lized to observe the airway port of the patients,velopha-ryngeal closure,and the mobility of the lateral pharynge-al walls.Lateral cephalometric radiographs were employed to evaluate the patient's maxillomandibular relationship and adenoid dimensions.A logistic regression model incorporating univariate analysis and multivariate analyses was estab-lished to identify the prognostic factors influencing the occurrence of persistent postoperative airway obstruction and hy-pernasality.Results Among the 63 patients,56 patients(88.9％)experienced a reduction in the severity of airway ob-struction postoperatively but 20 patients(31.7％)still presented with moderate-to-severe airway obstruction.Age at sur-gery(P=0.023)and adenoid hypertrophy(P=0.003)were significantly associated with persistent postoperative airway ob-struction.All 39 individuals exhibiting preoperative hyponasality demonstrated effective resolution after flap division,and 11 patients(17.5％)experienced mild hypernasality postoperatively.Unilateral port obstruction(P=0.004)and BMI(P=0.027)were identified as potential independent factors influencing the development of postoperative hypernasality.Conclusion Flap division is an effective measure for improving postoperative airway obstruction and hyponasality fol-lowing pharyngeal flap,although some patients may continue to experience persistent airway obstruction and develop hy-pernasality after division.Age at surgery and adenoid hypertrophy are prognostic factors for persistent airway obstruction following flap division.Unilateral/bilateral nasal airway obstruction and BMI are related factors for post-operative hyper-nasality.

Objective To analyze the research hotspots and development trends in the pre-hospital emergency care field of stroke in China from 2014 to 2023 using bibliometric method.Methods Retrieve stroke pre-hospital emergency care research articles published in the China National Konwledge Infrastructure(CNKI),WanFang and CQVIP database from 2014 to 2023.Visualize and analyze authors,institutions,and keywords using CiteSpace 5.7.R5 software.Results We included 3,125 articles for analysis.The year 2021 marked the peak of publication activity with 500 articles.The top five authors with the highest number of publications were Guo Wei,Li Dou,Yu Longjuan,Peng Peng,and Zhang Lingjuan,respectively.The Beijing Emergency Center emerged as the institution with the most significant number of publications.Predominant research hotspots encompassed topics such as intravenous thrombolysis,therapeutic outcomes,nerve functions,pathways for emergency nursing care,and green Channel.Current trends are directed towards enhancing the quality of emergency services,optimizing interventional thrombectomy techniques,improving neurological outcomes,and prognostic assessments.Conclusion Over the last decade,there has been a progressive increase in the focus on pre-hospital emergency care research for stroke within China.Future research endeavors should aim at elevating the quality of emergency care,refining thrombectomy approaches,augmenting neurological functional recovery,and improving patient prognoses.

Kupffer cells(KC),an important subset of immune cells in the liver,are essential for maintaining tissue homeostasis and responding quickly to liver damage.The complement receptor of the immuno-globulin superfamily(CRIg)is a receptor protein on the KC membrane.CRIg can not only capture pathogens in the blood flowing through the liver by complement binding but also mediate immune responses by regulating im-mune cells in the liver.Recent studies have confirmed the role of CRIg in regulating liver immunity.This article reviews the main modes of action of CRIg and the research progress of CRIg in regulating liver immunity.