Background and aims:Primary sclerosing cholangitis(PSC)is an autoimmune liver disease characterized by complex pathogenesis and limited available therapeutic options.The mechanisms underlying the development and progression of PSCs remain unclear.Liver X receptor beta(LXR-β)is recognized to modulate lipid metabolism and immune response,but its specific involvement in the PSC has not been elucidated.Here,we explored the role and mechanism of LXR-β in PSC induced by 3,5-diethoxycarbonyl-1,4-dihydro-2,4,6-collidine(DDC).Methods:CRISPR-Cas9 technology was applied to generate Abcb4(coding MDR2,next named as Mdr2),Nr1h2(coding LXR-β,next named as Lxrβ),and Rag2(coding RAG2)knockout mice.DDC was used to induce PSC.Hematoxylin and eosin and Sirius red staining were used to assess the extent of hepatic injury and fibrosis.Flow cytometry was used to observe immune cell subsets.Results:We observed a declining trend in hepatic Lxrβ in the PSC model.Unexpectedly,Lxrβ knockout failed to modulate DDC-induced PSC pathogenesis.Concomitantly,assessment of the influence of Rag2 deficiency on PSC progression revealed the absence of aggravated or alleviated hepatic injury or fibrosis in the Rag2-/-DDC mice.However,Lxrβ depletion intensified DDC-induced PSC in the Rag2-/-mice,with more abundant infiltrative inflammatory cells and more severe liver fibrosis.Compared with Rag2-/-DDC mice,Lxrβ-/-Rag2-/-DDC mice had higher serum ALT and AST levels and mRNA expression of proinflammatory and profibrotic genes.Flow cytometry showed that LXR-β deficiency resulted in a diminished population of hepatic innate immune cells.Conclusion:This study indicated innate immune cell LXR-β deficiency can exacerbate hepatic injury and fibrosis in murine models of PSC suggesting that LXR-β may regulate the function of innate immunity in the fibrotic advancement of PSC.

OBJECTIVES: To study the impact of SURF4 expression level on long-term prognosis of gastric cancer (GC) and biological behaviors of GC cells. METHODS: SURF4 expression level in GC and its association with long-term patient prognosis were analyzed using publicly available databases and in 155 GC patients with low and high SURF4 expressions detected immunohistochemically. The Cox proportional hazard model and Kaplan-Meier survival curves were used to analyze independent prognostic predictors of GC and the 5-year survival rate of the patients with different SURF4 expression levels. Informatics analyses were conducted to explore the correlation of SURF4 expression level with immune cell infiltration in GC, SURF4-related differential genes and their associated pathways. In cultured GC cell line HGC-27, the effects of SURF4 knockdown and overexpression on proliferation, migration, invasion and epithelial-mesenchymal transition (EMT) were investigated. RESULTS: Analysis of GEPIA dataset and immunohistochemical results suggested significant SURF4 overexpression in GC (P<0.05), which was associated with shortened 5-year survival time of the patients (χ²=38.749, P<0.001). The prognosis of GC was closely related to tumor stage T3-4, N2-3, CEA≥5 μg/L and CA19-9≥37 kU/L (P<0.05). SURF4 expression level was negatively correlated with activated B cells, NK cells and CD8⁺ effector memory T cells (P<0.05) and positively correlated with CD4⁺ T cells (P<0.05). GO and KEGG enrichment analysis suggested that SUFR4 may participate in GC carcinogenesis by promoting EMT through the tight junction pathway. In HGC-27 cells, SURF4 overexpression significantly decreased E-cadherin expression, increased N-cadherin expression, inhibited ZO-1 and claudin-1 expressions, and promoted cell proliferation, migration and invasion. CONCLUSIONS SURF4 is highly expressed in GC, and its overexpression is associated with a shortened 5-year survival of the patients possibly by enhancing tumor cell proliferation, migration and invasion via inhibiting tight junction proteins and promoting EMT.
Humans ; Stomach Neoplasms/metabolism* ; Cell Proliferation ; Cell Movement ; Epithelial-Mesenchymal Transition ; Cell Line, Tumor ; Neoplasm Invasiveness ; Prognosis ; Tight Junction Proteins/metabolism* ; Membrane Proteins/metabolism* ; Female ; Male

To rapidly and accurately detect Mycobacterium avium subsp.paratuberculosis(MAP),this study designed and screened primers and probes using its specific gene F57 as the detection target,established a recombinant enzyme-mediated isothermal amplification(RAA)fluorescence detection method,and applied this method to detect 116 clinical samples from cattle and sheep.The results showed that using the primer and probe combination B12F/B2R(0.4 μmol/L)+Probe B(0.12 μmol/L),MAP could be detected at a constant temperature of 42 ℃ within 20 min;this de-tection method had no cross-reaction with 11 common pathogens such as Escherichia coli,Clos-tridium,and bovine viral diarrhea in sheep and cattle;the lowest detection limit was 1.0×102 cop-ies/μL;the coefficient of variation was 3.77％—5.29％;24 clinical samples were positive,with a co-incidence rate of 88.89％with GBT27637-2011.In summary,this study established a fluorescent RAA detection method for MAP,which is simple,rapid,highly specific,sensitive,reproducible,and has a high coincidence rate with national standards,making it suitable for clinical detection and epi-demiological studies.

The integration of multi-source data and the establishment of early warning indicator systems constitute pivotal elements for advancing surveillance and early warning capacities in respiratory infectious diseases. Given the multifaceted transmission mechanisms and complex contributing factors inherent in respiratory infectious diseases, surveillance datasets and associated early warning indicators demonstrate notable heterogeneity and sophisticated interrelationships. Furthermore, as surveillance and early warning requirements significantly vary across diverse epidemiological scenarios, accurate assessment of the value and applicability of distinct data types and indicators is imperative. This paper systematically reviews and synthesizes recent advancements in surveillance data and early warning indicators for respiratory infectious diseases, drawing on both domestic and international research. Particular attention is dedicated to analyzing the applicability and efficacy of various data types and indicators within multiple practical contexts, aiming to provide robust theoretical frameworks and methodological guidance to facilitate the development of resilient and efficient surveillance and early warning systems for respiratory infectious diseases.

BACKGROUND: The American Heart Association recently released a new cardiovascular health (CVH) metric, Life's Essential 8 (LE8), for health promotion. However, the association between LE8 scores and the risk of chronic kidney disease (CKD) remains uncertain. We aimed to explore the association of LE8 scores with new-onset CKD and examine whether socioeconomic deprivation and genetic risk modify this association. METHODS: A total of 286,908 participants from UK Biobank and without prior CKD were included between 2006 and 2010. CVH was categorized using LE8 scores: low (LE8 scores <50), moderate (LE8 scores ≥50 but <80), and high (LE8 scores ≥80). The study outcome was new-onset CKD, ascertained by data linkage with primary care, hospital inpatient, and death data. Cox proportional hazard regression models were used to investigate the association between CVH categories and new-onset CKD. RESULTS: During a median follow-up of 12.5 years, 8857 (3.1%) participants developed new-onset CKD. Compared to the low CVH group, the moderate (adjusted hazards ratio [HR], 0.50; 95% confidence interval [CI]: 0.47-0.53) and high CVH (adjusted HR, 0.31; 95% CI: 0.27-0.34) groups had a significantly lower risk of developing new-onset CKD. The population-attributable risk associated with high vs. intermediate or low CVH scores was 40.3%. Participants who were least deprived ( vs.  most deprived; adjusted HR, 0.75; 95% CI: 0.71-0.79) and with low genetic risk of CKD ( vs.  high genetic risk; adjusted HR, 0.89; 95% CI: 0.85-0.94) had a significantly lower risk of developing new-onset CKD. However, socioeconomic deprivation and genetic risks of CKD did not significantly modify the relationship between LE8 scores and new-onset CKD (both P -interaction >0.05). CONCLUSION Achieving a higher LE8 score was associated with a lower risk of developing new-onset CKD, regardless of socioeconomic deprivation and genetic risks of CKD.
Humans ; Renal Insufficiency, Chronic/epidemiology* ; Male ; Female ; Middle Aged ; Genetic Predisposition to Disease/genetics* ; Aged ; Risk Factors ; Adult ; Proportional Hazards Models ; Socioeconomic Factors

Objective:To investigate the potential causes of the rising epidemic of severe fever with thrombocytopenia syndrome (SFTS) in Weifang, Shandong province.Methods:The temporal trend of SFTS epidemic was segmented using Joinpoint regression analysis. Changes in epidemiological characteristics across different periods were compared, and correlation analysis was conducted to identify meteorological factors influencing the epidemic trend.Results:Joinpoint regression revealed two distinct periods for SFTS epidemic in Weifang: 2015-2021 and 2022-2024. No significant trend was observed during 2015-2021 ( P=0.634), while a sharp annual increase of 46.69% occurred from 2022 to 2024 ( P=0.006). Spatial autocorrelation analysis demonstrated a global Moran’s I of 0.42 ( Z=8.55, P<0.001) for 2015-2021, with 15 high-high clustering areas identified. For 2022-2024, the global Moran’s I decreased to 0.37 ( Z=7.31, P<0.001), with 13 high-high clusters, including newly emerging hotspots in Anqiu and Zhucheng in the southeastern region. High-risk populations remained individuals aged ≥50 in mountainous and hilly areas, with a marked rise in incidence in these groups. The male-to-female ratio of cases was higher in plain areas than in mountainous/hilly regions. Autumn (September-November) temperatures from the preceding year showed a positive correlation with annual case numbers ( P=0.004, r=0.82). The linear regression expression is y=40.61x-580.78 (y is the annual incidence, and x is the average daily temperature of last autumn). Conclusions:The SFTS epidemic in Weifang is showing a rising trend. There is a linear correlation between the temperature of the previous autumn and the scale of SFTS epidemic in the following year. This correlation allows for predicting the subsequent year′s epidemic, thereby enabling early warning of SFTS.

Objective:To investigate the efficacy and treatment adherence of digital cognitive behavioral therapy for insomnia (dCBT-I) in patients with insomnia disorder accompanied by anxiety and depressive symptoms, and to provide empirical evidence for its clinical application.Methods:From December 2023 to December 2024, 102 patients with insomnia disorder accompanied by anxiety and depressive symptoms were recruited from the outpatient department of Inner Mongolia Brain Hospital and randomly assigned to either the dCBT-I group ( n=56) or the digital sleep hygiene education (dSHE) group ( n=46). The dCBT-I group received a 4-week intervention comprising 5 core modules, while the dSHE group received 4 weeks of digital sleep hygiene education. Both groups received weekly guidance from clinical psychologists. Subjective sleep quality (Insomnia Severity Index, ISI), anxiety (Hamilton Anxiety Scale, HAMA), and depressive symptoms (17-item Hamilton Depression Scale, HAMD 17) were assessed at baseline, week 4, week 8, and week 12. Objective sleep parameters (polysomnography, PSG) and cognitive function (Repeatable Battery for the Assessment of Neuropsychological Status, RBANS) were evaluated at baseline and week 4. Linear mixed-effects model was used to analyze the effects of group, timepoint, and their interaction on outcome measures, after controlling medication history, age, sex, education level, ethnicity, and marital status as covariates. Results:A total of 76 patients (dCBT-I: n=42; dSHE: n=34) completed the 4-week intervention, yielding a treatment adherence rate of 74.5%(76/102). At weeks 4, 8, and 12, the dCBT-I group demonstrated significantly lower scores on the ISI, HAMA, and HAMD 17 scales compared to the dSHE group (β=-1.70--0.66, t=-15.38--6.21, all P<0.05), along with higher rates of medication reduction (χ 2=16.40, 9.22, 6.66, all P<0.05). No significant differences were observed in PSG parameters between the two groups. However, the dCBT-I group demonstrated significant improvements in RBANS subdomains, including immediate memory, language function, and delayed memory (β=0.45, 0.86, 1.43, t=3.09, 2.67, 4.36, all P<0.05). Conclusion:dCBT-I is an effective and well-adhered intervention for patients with insomnia disorder accompanied by anxiety and depressive symptoms, warranting broader clinical implementation.

The integration of multi-source data and the establishment of early warning indicator systems constitute pivotal elements for advancing surveillance and early warning capacities in respiratory infectious diseases. Given the multifaceted transmission mechanisms and complex contributing factors inherent in respiratory infectious diseases, surveillance datasets and associated early warning indicators demonstrate notable heterogeneity and sophisticated interrelationships. Furthermore, as surveillance and early warning requirements significantly vary across diverse epidemiological scenarios, accurate assessment of the value and applicability of distinct data types and indicators is imperative. This paper systematically reviews and synthesizes recent advancements in surveillance data and early warning indicators for respiratory infectious diseases, drawing on both domestic and international research. Particular attention is dedicated to analyzing the applicability and efficacy of various data types and indicators within multiple practical contexts, aiming to provide robust theoretical frameworks and methodological guidance to facilitate the development of resilient and efficient surveillance and early warning systems for respiratory infectious diseases.

To rapidly and accurately detect Mycobacterium avium subsp.paratuberculosis(MAP),this study designed and screened primers and probes using its specific gene F57 as the detection target,established a recombinant enzyme-mediated isothermal amplification(RAA)fluorescence detection method,and applied this method to detect 116 clinical samples from cattle and sheep.The results showed that using the primer and probe combination B12F/B2R(0.4 μmol/L)+Probe B(0.12 μmol/L),MAP could be detected at a constant temperature of 42 ℃ within 20 min;this de-tection method had no cross-reaction with 11 common pathogens such as Escherichia coli,Clos-tridium,and bovine viral diarrhea in sheep and cattle;the lowest detection limit was 1.0×102 cop-ies/μL;the coefficient of variation was 3.77％—5.29％;24 clinical samples were positive,with a co-incidence rate of 88.89％with GBT27637-2011.In summary,this study established a fluorescent RAA detection method for MAP,which is simple,rapid,highly specific,sensitive,reproducible,and has a high coincidence rate with national standards,making it suitable for clinical detection and epi-demiological studies.

Objective:To investigate the potential causes of the rising epidemic of severe fever with thrombocytopenia syndrome (SFTS) in Weifang, Shandong province.Methods:The temporal trend of SFTS epidemic was segmented using Joinpoint regression analysis. Changes in epidemiological characteristics across different periods were compared, and correlation analysis was conducted to identify meteorological factors influencing the epidemic trend.Results:Joinpoint regression revealed two distinct periods for SFTS epidemic in Weifang: 2015-2021 and 2022-2024. No significant trend was observed during 2015-2021 ( P=0.634), while a sharp annual increase of 46.69% occurred from 2022 to 2024 ( P=0.006). Spatial autocorrelation analysis demonstrated a global Moran’s I of 0.42 ( Z=8.55, P<0.001) for 2015-2021, with 15 high-high clustering areas identified. For 2022-2024, the global Moran’s I decreased to 0.37 ( Z=7.31, P<0.001), with 13 high-high clusters, including newly emerging hotspots in Anqiu and Zhucheng in the southeastern region. High-risk populations remained individuals aged ≥50 in mountainous and hilly areas, with a marked rise in incidence in these groups. The male-to-female ratio of cases was higher in plain areas than in mountainous/hilly regions. Autumn (September-November) temperatures from the preceding year showed a positive correlation with annual case numbers ( P=0.004, r=0.82). The linear regression expression is y=40.61x-580.78 (y is the annual incidence, and x is the average daily temperature of last autumn). Conclusions:The SFTS epidemic in Weifang is showing a rising trend. There is a linear correlation between the temperature of the previous autumn and the scale of SFTS epidemic in the following year. This correlation allows for predicting the subsequent year′s epidemic, thereby enabling early warning of SFTS.