Wilson disease is a copper metabolism disorder caused by mutations in the ATP7B gene， which encodes a copper-transporting ATPase β， and can result in multisystem damage. The kidneys are the third most commonly affected organs after the liver and brain. In recent years， numerous diagnostic and treatment guidelines for Wilson disease have emerged. However， most of these focus primarily on hepatic and neurological manifestations and their management， with limited coverage of renal involvement. The high incidence， low awareness， and lack of clinical specificity of Wilson disease-related renal damage （WDRD） have made early detection and intervention particularly challenging in clinical practice. To further optimize the treatment of patients with WDRD， improve clinical diagnosis and management， and enhance patients' quality of life， the Neurology Committee of the Chinese Association of Integrative Medicine， in April 2024， initiated a revision of the first expert consensus on the integrated diagnosis， treatment， and management of WDRD. This effort brought together experts in hepatology， encephalopathy （neurology）， and nephrology from many tertiary-level grade A hospitals and research institutions across China. Through comprehensive literature review and integration of frontline clinical experience， the expert group jointly developed Chinese Expert Consensus on Integrated Chinese and Western Medicine Management of Wilson Disease-related Renal Damage （hereinafter referred to as the "Consensus"）. This article provides a detailed interpretation of the Consensus in terms of diagnostic criteria， traditional Chinese medicine （TCM） syndrome differentiation and treatment classification， and comprehensive disease management， aiming to better guide clinical application. Regarding diagnostic criteria， the Consensus integrates the latest standards in China and abroad， highlights the importance of biochemical diagnosis， and compensates for the limitations of genetic testing. In the area of TCM syndrome differentiation and treatment， the Consensus refines four major syndrome types， introduces a newly defined syndrome， i.e.， phlegm， blood stasis， and heat accumulation， and elaborates on treatment principles， prescriptions， and clinical modification rules for each syndrome. For comprehensive disease management， the Consensus emphasizes multi-dimensional intervention strategies， including diet， exercise， emotional regulation， medication， and medical care， with the goal of maximally controlling the progression of renal dysfunction and helping patients achieve a better quality of life.

With the rapid advancement of artificial intelligence technology, chatbots have shown great potential in the healthcare sector. From personalized health advice to chronic disease management and psychological support, chatbots have demonstrated significant advantages in improving the efficiency and quality of healthcare services. As the scope of their applications expands, the relationship between technological complexity and practical application scenarios has become increasingly intertwined, necessitating a more comprehensive evaluation of both aspects. This paper, from the perspective of he althcare applications, systematically reviews the technological pathways and development of chatbots in the medical field, providing an in-depth analysis of their performance across various medical scenarios. It thoroughly examines the advantages and limitations of chatbots, aiming to offer theoretical support for future research and propose feasible recommendations for the broader adoption of chatbot technologies in healthcare.

Objectives:To examine the feasibility of using foundation model in computer vision for echocardiographic left ventricular ejection fraction measurement. Methods:Based on the most extensive publicly accessible repository of echocardiographic loops,EchoNet-Dynamic,featuring 10024 recordings from individual patients,a foundation model in computer vision,VideoMAE V2,was fine-tuned,validated,tested using 7460,1288,and 1276 echocardiographic loops,respectively. Results:The mean absolute error between left ventricular ejection fraction measurements of VideoMAE V2 and expert's measurements was 3.94％ (95％CI:3.79％-4.11％).The Pearson's correlation coefficient was 0.91 (95％CI:0.89-0.92).Additionally,VideoMAE V2 demonstrated exceptional accuracy in identifying patients with a left ventricular ejection fraction below 50％,achieving an AUC of 0.96 (95％CI:0.95-0.97). Conclusions:This study validates the feasibility of using foundation model in computer vision for measuring left ventricular ejection fraction in echocardiographic loops and lays the foundation for the development of a generalized multimodal automated interpretation system for echocardiography.

Objective:To investigate the clinical efficacy of 595-nm pulsed dye laser (PDL) in the treatment of port-wine stains (PWS) in infants and toddlers.Methods:A retrospective analysis was conducted based on clinical data from 155 infants and toddlers with PWS treated with 595-nm PDL at West China Hospital of Sichuan University from January 2013 to October 2023, and the efficacy was evaluated according to pre- and post-treatment photographs. The children were grouped according to gender, age, lesion color, lesion area, lesion sites, and number of treatment sessions, separately, and the differences were analyzed between different groups. Further analysis was conducted to determine factors affecting efficacy of PDL for PWS. Adverse reactions after treatment were recorded. The Mann-Whitney U test and Kruskal-Wallis H test were used to analyze unidirectional ordered R × C contingency table data, the Bonferroni approach was used for multiple comparisons, and multivariate ordered logistic regression analysis was performed for multifactorial analysis. Results:After the treatment with 595-nm PDL, 135 infants and toddlers with PWS showed good response, with an overall response rate of 87.1%. Univariate analysis indicated that the efficacy was associated with the lesion area ( P = 0.016) and the number of treatment sessions ( P < 0.001), but not with age ( P = 0.340), gender ( P = 0.164), lesion color ( P = 0.530), or lesion sites ( P = 0.077), and the smaller the lesion area, the more the treatment sessions, the better the therapeutic effect. Multivariate ordered logistic regression analysis further confirmed the correlations of efficacy with lesion area ( P = 0.010) and number of treatment sessions ( P < 0.001). Adverse reactions occurred in 5 (3.2%) cases of PWS, including 2 (1.3%) of hypopigmentation, 2 (1.3%) of hyperpigmentation, and 1 (0.6%) of scar formation. Conclusion:The 595-nm PDL was safe and effective for the treatment of PWS in infants and toddlers with few adverse reactions, making it a reliable therapeutic option.

Abstract: Objective　To analyze the molecular serotyping and drug resistance of foodborne Listeria monocytogenes (LM)isolates from the food monitoring network of Liaoning Province, and to provide a reference for identifying and tracing the outbreaks of foodborne diseases. Methods　The Listeria monocytogenes isolates were identified, biochemical typing was conducted by VITEK biochemical identification and PCR amplification techniques were applied for molecular serotyping of 67 strains of Listeria monocytogenes detected from 2 797 food samples collected from 15 monitoring sites across the province during 2021-2022. Verification was performed according to the instructions of the serodiagnosis manual. The sensitivity of the strains to ampicillin, penicillin, meropenem, cotrimoxazole, and erythromycin was determined by broth dilution method. Results　In food from Liaoning Province, the molecular serotypes of Listeria monocytogenes carried were identified as 1/2a(3a), 1/2b(3b, 7), 1/2c(3c), and 4b (4d, 4e), with the predominant serotypes being 1/2a accounting for 62.7% (42/67), and 1/2b accounting for 28.4% (19/67). Among them, the 4b strain was isolated in 3 strains, representing 4.5%. The dominant strains of Listeria monocytogenes in 2021 and 2022 in Liaoning Province were 1/2a(3a) and 1/2b(3b, 7), with the most diverse types carried by meat and meat products. Double resistance to cotrimoxazole and erythromycin accounted for 11.9% (8/67), while resistance to only one cotrimoxazole accounted for 9.0% (6/67). Conclusions　The presence of pathogenic serotypes 1/2a(3a), 1/2b(3b, 7), 1/2c(3c), and 4b (4d, 4e) in food in Liaoning Province and the emergence of strains with one or more drug resistances indicate the existence of food safety issues caused by Listeria monocytogenes, posing a potential risk of listeriosis. There is a need to optimize source tracing methods and strengthen the confirmation of Listeria monocytogenes outbreaks.

Intracellular overexpression of cytoglobin (Cygb) has been shown to reduce extracellular matrix deposition and promote liver fibrosis recovery, but its mechanism is not yet clear. This study constructed and expressed a fusion protein (TAT-Cygb) of cell penetrating peptide TAT and Cygb, to investigate the effect of fusion protein TAT-Cygb on regulating hepatic stellate cells (HSCs) ferroptosis. Cultured human hepatic stellate cells line (LX2) were treated with TAT-Cygb and erastin in vitro, respectively. The effects of ferroptosis phenotype in LX2 cells induced by TAT-Cygb, including cell viability, cell morphology, iron ion (Fe²⁺) content, lipid peroxidation product levels, and antioxidant system indicators, were investigated using trypan blue staining, transmission electron microscopy, Prussian blue staining, and reagent kits detection. After co-treatment with TAT-Cygb and ferrostain-1, the levels of Fe²⁺, reactive oxygen species (ROS), malondialdehyde (MDA), 4-hydroxynonenal (4-HNE), nicotinamide adenine dinucleotide phosphate (NADPH) and glutathione (GSH) were measured by reagent kits. The protein expression levels of alpha smooth actin (α-SMA), collagen I and fibronectin were detected by Western blot, and the protein expression level of epidermal growth factor receptor (EGFR) and desmin relevant to fibrosis were observed by immunofluorescence. The results showed that TAT-Cygb could significantly reduce the viability of LX2 cells and trigger events relevant to ferroptosis, including promoting intracellular Fe²⁺ accumulation, and inducing mitochondrial morphological changes, and intensifying lipid peroxidation products accumulation, and decreasing the level of antioxidant indexes, which played a similar role as erastin; Fer-1 significantly weakened the increase in Fe²⁺, ROS, MDA, 4-HNE levels induced by TAT-Cygb, as well as the decrease in NADPH and GSH levels, while also weakening the TAT-Cygb-induced over-expression levels of α-SMA, collagen I and fibronectin, and TAT-Cygb-induced under-expression levels of EGFR and desmin. This cellular level study indicated that TAT-Cygb can induce ferroptosis of activated HSCs. This study revealed the potential mechanism of TAT-Cygb anti-liver fibrosis, and provided the experimental basis for further research on the molecular mechanism of TAT-Cygb realizing biological function by regulating the ferroptosis pathway.

OBJECTIVE To evaluate the effectiveness， safety， economy， innovation， suitability and accessibility of recombinant Mycobacterium tuberculosis fusion protein （EC）， and to provide evidence for selecting skin detection methods for tuberculosis infection diagnosis and auxiliary diagnosis of tuberculosis. METHODS The effectiveness and safety of EC compared with purified protein derivative of tuberculin （TB-PPD） were analyzed by the method of systematic review. Cost minimization analysis， cost-effectiveness analysis and cost-utility analysis were used to evaluate the short-term economy of EC compared with TB-PPD， and cost-utility analysis was used to evaluate the long-term economy. The evaluation dimensions of innovation， suitability and accessibility were determined by systematic review and improved Delphi expert consultation， and the comprehensive score of EC and TB-PPD in each dimension were calculated by the weight of each indicator. RESULTS The scores of effectiveness， safety， economy， innovation and suitability of EC were all higher than those of TB-PPD. The affordability scores of the two drugs were consistent， while the availability score of EC was lower than those of TB-PPD. After considering dimensions and index weight， the scores of effectiveness， safety， economy， innovation， suitability， accessibility and the comprehensive score of EC were all higher than those of TB-PPD. CONCLUSIONS Compared with TB-PPD， EC performs better in all dimensions of effectiveness， safety， economy， innovation， suitability and accessibility. However， it is worth noting that EC should further improve its availability in the dimension of accessibility.

Aim To investigate the effect of silencing circRNA ciRS-7 on cisplatin resistance of gastric cancer cells and its related mechanism. Methods Cisplatin-resistant gastric cancer cells HGC-27/DDP were constructed, ciRS-7 was silenced and HGC-27/DDP cells were treated with cisplatin. Real-time quantitative PCR (qRT-PCR) was used to detect the expression levels of ciRS-7 and microrNA-944 (miR-944). Cell counting kit-8 (CCK-8) was used to detect cell survival rate. Clone formation assay was used to detect the number of clones. Western blot was used to detect the protein expression levels of CyclinD1, proliferating cell nuclear antigen (PCNA), B-lymphocytoma-2-associated X protein (Bax), B-lymphocytoma-2 (Bcl-2) and cleaved aspartate-specific cysteine proteinase 3 (cleaved-caspase-3). Flow cytometry was used to detect cell apoptosis rate. In situ end labeling (TUNEL) was used to detect apoptosis index. Dual luciferase assay was used to verify the targeting relationship between ciRS-7 and miR-944. Results CiRS-7 was highly expressed in cisplatin-resistant gastric cancer tissues and cells, while miR-944 was low expressed in cisplatin-resistant gastric cancer tissues and cells. The survival rate, clonal formation number, protein expression levels of CyclinD1, PCNA and Bcl-2 in cisplatin-treated HGC-27/DDP cells were significantly reduced by silencing ciRS-7, while ciRS-7 expression level, apoptosis rate, apoptosis index, Bax, cleaved-caspase-3 protein expression levels of cisplatin-treated HGC-27/DDP cells were significantly raised. CiRS-7 targetedly inhibited the expression of miR-944. Conclusions Silencing ciRS-7 can reverse cisplatin resistance of gastric cancer cells, and the mechanism may be related to the promotion of miR-944 expression by silencing ciRS-7.

OBJECTIVE: To analyze the clinicopathological features, molecular changes and prognostic factors in angioimmunoblastic T-cell lymphoma (AITL). METHODS: Sixty-one cases AITL diagnosed by Department of Pathology of Peking University Cancer Hospital were collected with their clinical data. Morphologically, they were classified as typeⅠ[lymphoid tissue reactive hyperplasia (LRH) like]; typeⅡ[marginal zone lymphoma(MZL)like] and type Ⅲ [peripheral T-cell lymphoma, not specified (PTCL-NOS) like]. Immunohistochemical staining was used to evaluate the presence of follicular helper T-cell (TFH) phenotype, proliferation of extra germinal center (GC) follicular dendritic cells (FDCs), presence of Hodgkin and Reed-Sternberg (HRS)-like cells and large B transformation. The density of Epstein-Barr virus (EBV) + cells was counted with slides stained by Epstein-Barr virus encoded RNA (EBER) in situ hybridization on high power field (HPF). T-cell receptor / immunoglobulin gene (TCR/IG) clonality and targeted exome sequencing (TES) test were performed when necessary. SPSS 22.0 software was used for statistical analysis. RESULTS: Morphological subtype (%): 11.4% (7/61) cases were classified as type Ⅰ; 50.8% (31/61) as type Ⅱ; 37.8% (23/61) as type Ⅲ. 83.6% (51/61) cases showed classical TFH immunophenotype. With variable extra-GC FDC meshwork proliferation (median 20.0%); 23.0% (14/61) had HRS-like cells; 11.5% (7/61) with large B transformation. 42.6% (26/61) of cases with high counts of EBV. 57.9% (11/19) TCR⁺/IG^-, 26.3% (5/19) TCR⁺/IG⁺, 10.5% (2/19) were TCR^－/IG^－, and 5.3% (1/19) TCR^－/IG⁺. Mutation frequencies by TES were 66.7% (20/30) for RHOA, 23.3% (7/30) for IDH2 mutation, 80.0% (24/30) for TET2 mutation, and 33.3% (10/30) DNMT3A mutation. Integrated analysis divided into four groups: (1) IDH2 and RHOA co-mutation group (7 cases): 6 cases were type Ⅱ, 1 case was type Ⅲ; all with typical TFH phenotype; HRS-like cells and large B transformation were not found; (2) RHOA single mutation group (13 cases): 1 case was type Ⅰ, 6 cases were type Ⅱ, 6 cases were type Ⅲ; 5 cases without typical TFH phenotype; 6 cases had HRS-like cells, and 2 cases with large B transformation. Atypically, 1 case showed TCR^－/IG^－, 1 case with TCR^－/IG⁺, and 1 case with TCR⁺/IG⁺; (3) TET2 and/or DNMT3A mutation alone group (7 cases): 3 cases were type Ⅱ, 4 cases were type Ⅲ, all cases were found with typical TFH phenotype; 2 cases had HRS-like cells, 2 cases with large B transformation, and atypically; (4) non-mutation group (3 cases), all were type Ⅱ, with typical TFH phenotype, with significant extra-GC FDC proliferation, without HRS-like cells and large B transformation. Atypically, 1 case was TCR^－/IG^－. Univariate analysis confirmed that higher density of EBV positive cell was independent adverse prognostic factors for both overall survival (OS) and progression free survival(PFS), (P=0.017 and P=0.046). CONCLUSION Pathological diagnoses of ALTL cases with HRS-like cells, large B transformation or type Ⅰ are difficult. Although TCR/IG gene rearrangement test is helpful but still with limitation. TES involving RHOA, IDH2, TET2, DNMT3A can robustly assist in the differential diagnosis of those difficult cases. Higher density of EBV positive cells counts in tumor tissue might be an indicator for poor survival.
Humans ; Epstein-Barr Virus Infections/genetics* ; Herpesvirus 4, Human/genetics* ; T-Lymphocytes, Helper-Inducer/pathology* ; Immunoblastic Lymphadenopathy/pathology* ; Lymphoma, T-Cell, Peripheral/pathology* ; Receptors, Antigen, T-Cell

ObjectiveTo explore the mechanism of Huanglian Ejiaotang in intervening in insomnia based on 5-hydroxytryptamine （5-HT） system and gut microbiota. MethodFifty-five SPF-grade SD rats were randomly divided into normal group， model group， low-， medium-， and high-dose Huanglian Ejiaotang groups （1.925， 3.85， and 7.7 g·kg^-1）， and Estazolam group （0.1 mg·kg^-1）. Except for those in the normal group， the rats in the other five groups were subjected to sleep deprivation on a narrow platform for 12 hours daily for 21 consecutive days. After 14 days of drug intervention， the sleep， exploratory behavior， and depressive-like behavior of the rats were assessed using the pentobarbital sodium sleep synergistic test， the open field test， and the sugar preference test， respectively. Enzyme-linked immunosorbent assay （ELISA） was used to detect the levels of 5-HT， 5-hydroxyindoleacetic acid （5-HIAA）， tryptophan hydroxylase （TPH）， and monoamine oxidase-A （MAO-A）. Real-time polymerase chain reaction （Real-time PCR） was used to measure the mRNA expression of the 5-HT1A receptor （5-HT1AR） and 5-HT2A receptor （5-HT2AR）. Differences in gut microbiota among the groups were assessed using 16S rRNA sequencing， and the correlation between the 5-HT system and microbiota was revealed using redundancy analysis. ResultCompared with the normal group， the model group showed a prolonged sleep latency （P<0.05）， reduced sleep maintenance （P<0.01）， decreased central area activity time in the open field （P<0.01）， and reduced sugar preference rate （P<0.05）. Moreover， the model group also showed decreased levels of 5-HT， 5-HIAA， TPH， and MAO-A （P<0.01）， decreased 5-HIAA/5-HT ratio （P<0.01）， downregulated mRNA expression of 5-HT1AR （P<0.01）， and upregulated mRNA expression of 5-HT2AR （P<0.05）. The proportion of Firmicutes decreased， while that of Bacteroidetes increased， leading to a decreased Firmicutes/Bacteroidetes （F/B） ratio （P<0.05）. Compared with the model group， the high-dose Huanglian Ejiaotang group exhibited a shortened sleep latency （P<0.01）， and increased sleep maintenance （P<0.01）. The low-dose Huanglian Ejiaotang group showed increased central area activity time （P<0.01） and an increased sugar preference rate （P<0.05）. The high-dose Huanglian Ejiaotang group exhibited increased levels of 5-HT， 5-HIAA， TPH， and MAO-A （P<0.01）， increased 5-HIAA/5-HT ratio （P<0.05）， upregulated mRNA expression of 5-HT1AR （P<0.01）， and downregulated mRNA expression of 5-HT2AR （P<0.05）. The low-dose Huanglian Ejiaotang group displayed an increased proportion of Firmicutes and a decreased proportion of Bacteroidetes， resulting in an increased F/B ratio. At the phylum level， 5-HT， 5-HIAA， and MAO-A were positively correlated with Firmicutes and negatively correlated with Bacteroidetes. At the genus level， 5-HT， 5-HIAA， TPH， and MAO-A were negatively correlated with Prevotella and Lactobacillus and positively correlated with Blautia and Bacteroides. ConclusionHuanglian Ejiaotang can improve sleep deprivation-induced insomnia and depressive-like behavior by regulating the activity of the 5-HT system and the composition of gut microbiota.