OBJECTIVE: To investigate the common mechanisms among collagen-induced arthritis (CIA), bleomycin (BLM)-induced pulmonary fibrosis, and CIA+BLM to evaluate the therapeutic effect of triptolide (TP) on CIA+BLM. METHODS: Thirty-six male Sprague-Dawley rats were randomly assigned to 6 groups according to a random number table (n=6 per group): normal control (NC), CIA, BLM, combined CIA+BLM model, TP low-dose (TP-L, 0.0931 mg/kg), and TP high-dose (TP-H, 0.1862 mg/kg) groups. The CIA model was induced by intradermal injection at the base of the tail with emulsion of bovine type II collagen and incomplete Freund's adjuvant (1:1), with 200 µL administered on day 0 and a booster of 100 µL on day 7. Pulmonary fibrosis was induced via a single intratracheal injection of BLM (5 mg/kg). The CIA+BLM model combined both protocols, and TP was administered orally from day 14 to 35. After successful modeling, arthritis scores were recorded every 3 days, and pulmonary function was assessed once at the end of the treatment period. Lung tissues were collected for histological analysis (hematoxylin eosin and Masson staining), immunohistochemistry, measurement of hydroxyproline (HYP) content, and calculation of lung coefficient. In addition, HE staining was performed on the ankle joint. Total RNA was extracted from lung tissues for transcriptomic analysis. Differentially expressed genes (DEGs) were compared with those from the RA-associated interstitial lung diseases patient dataset GSE199152 to identify overlapping genes, which were then used to construct a protein-protein interaction network. Hub genes were identified using multiple topological algorithms. RESULTS: The successfully established CIA+BLM rat model exhibited significantly increased arthritis scores and severe pulmonary fibrosis (P<0.01). By intersecting the DEGs obtained from transcriptomic analysis of lung tissues in CIA, BLM, and CIA+BLM rats with DEGs from rheumatoid arthritis-interstitial lung disease patients (GSE199152 dataset), 50 upregulated and 44 downregulated genes were identified. Through integrated PPI network analysis using multiple topological algorithms, IGF1 was identified as a central hub gene. TP intervention significantly improved pulmonary function by increasing peak inspiratory flow (P<0.01), and reduced lung index and HYP content (P<0.01). Histopathological analysis showed that TP alleviated alveolar collapse, interstitial thickening, and collagen deposition in the lung tissues (P<0.01). Moreover, TP treatment reduced the expression of collagen type I and α-SMA and increased E-cadherin levels (P<0.01). TP also significantly reduced arthritis scores and ameliorated synovial inflammation (P<0.05). Both transcriptomic and immunohistochemical analyses confirmed that IGF1 expression was elevated in the CIA+BLM group and downregulated following TP treatment (P<0.05). CONCLUSION TP exerts protective effects in the CIA+BLM model by alleviating arthritis and pulmonary fibrosis through the inhibition of IGF1-mediated EMT.
Animals ; Pulmonary Fibrosis/complications* ; Bleomycin/adverse effects* ; Phenanthrenes/pharmacology* ; Male ; Rats, Sprague-Dawley ; Diterpenes/pharmacology* ; Epoxy Compounds/therapeutic use* ; Arthritis, Experimental/complications* ; Insulin-Like Growth Factor I/metabolism* ; Rats ; Lung/physiopathology*

OBJECTIVE: To explore the functional roles and underlying mechanisms of neferine in the context of angiotensin II (Ang II)-induced hypertension and vascular dysfunction. METHODS: Male mice were infused with Ang II to induce hypertension and randomly divided into treatment groups receiving neferine or a control vehicle based on baseline blood pressure using a random number table method. The hypertensive mouse model was constructed by infusing Ang II via a micro-osmotic pump (500 ng/kg per minute), and neferine (0.1, 1, or 10 mg/kg), valsartan (10 mg/kg), or double distilled water was administered intragastrically once daily for 6 weeks. A non-invasive blood pressure system, ultrasound, and hematoxylin and eosin staining were performed to assess blood pressure and vascular changes. RNA sequencing and network pharmacology were employed to identify differentially expressed transcripts (DETs) and pathways. Vascular ring tension assay was used to test vascular function. A7R5 cells were incubated with neferine for 24 h and then treated with Ang II to record the real-time Ca²⁺ concentration by confocal microscope. Immunohistochemistry (IHC) and Western blot were used to evaluate vasorelaxation, calcium, and the extracellular signal-regulated kinase (ERK)1/2 pathway. RESULTS: Neferine treatment effectively mitigated the elevation in blood pressure, pulse wave velocity, aortic thickening in the abdominal aorta of Ang II-infused mice (P<0.05). RNA sequencing and network pharmacology analysis identified 355 DETs that were significantly reversed by neferine treatment, along with 25 potential target genes, which were further enriched in multiple pathways and biological processes, such as ERK1 and ERK2 cascade regulation, calcium pathway, and vascular smooth muscle contraction. Further investigation revealed that neferine treatment enhanced vasorelaxation and reduced Ca²⁺-dependent contraction of abdominal aortic rings, independent of endothelium function (P<0.05). The underlying mechanisms were mediated, at least in part, via suppression of receptor-operated channels, store-operated channels, or voltage-operated calcium channels. Neferine pre-treatment demonstrated a reduction in intracellular Ca²⁺ release in Ang II stimulated A7R5 cells. IHC staining and Western blot confirmed that neferine treatment effectively attenuated the upregulation of p-ERK1/2 both in vivo and in vitro, which was similar with treatment of ERK1/2 inhibitor PD98059 (P<0.05). CONCLUSIONS Neferine remarkably alleviates Ang II-induced elevation of blood pressure, vascular dysfunction, and pathological changes in the abdominal aorta. This beneficial effect is mediated by the modulation of multiple pathways, including calcium and ERK1/2 pathways.
Animals ; Angiotensin II ; Male ; Benzylisoquinolines/therapeutic use* ; Network Pharmacology ; Blood Pressure/drug effects* ; Sequence Analysis, RNA ; Mice ; Hypertension/chemically induced* ; Mice, Inbred C57BL ; Calcium/metabolism*

Objective To investigate the effect of tritiated water on the immune system of zebrafish and its potential molecular mechanism. Methods Zebrafish embryos (2.5 to 3 hours post-fertilization [hpf]) were exposed to 3.7 × 10⁴ Bq/mL tritiated water (tritiated water group), and those exposed to E3 culture medium were used as the control group. The mortality rate, hatching rate, deformity rate, heart rate, body length, yolk sac area, neutrophil count in the tail, immune-related gene expression, and immune-related protein expression of zebrafish in the two groups were determined. Then transcriptome technology was used to further analyze the possible mechanism of tritiated water affecting the immune system of zebrafish. Results Compared with the control group, zebrafish at 72 hpf in the tritiated water group had no significant changes in the mortality rate, hatching rate, deformity rate, body length, and yolk sac area((t = 0.9045, 0.5000, 1.0000, 0.7238, 0.0337, P = 0.4169, 0.6433, 0.3739, 0.4785, 0.9735), but had significantly increased heart rate(t = 4.575，P = 0.002). At 4 days post-fertilization (dpf), the neutrophil count in the tail of zebrafish in the tritiated water group was significantly increased(t = 2.563，P = 0.0196), the mRNA expression of TNF-α was significantly decreased(t = 2.891, P = 0.045), the protein expression of nuclear factor-kappa B (NF-κB) was significantly increased(t = 3.848, P = 0.018), and the protein expression of NLRP3 was significantly decreased(t = 14.98, P = 0.001). At 7 dpf, the neutrophil count in the tail and the protein expression levels of NF-κB, NLRP3, and interleukin-1β were significantly decreased(t = 3.772, 7.048, 15.620, 4.423, P = 0.014, 0.002, 0.0001, 0.012). Transcriptome sequencing revealed that differentially expressed genes were mainly enriched in the “neutrophil activation” and “platelet activation pathways” at 4 dpf and in the “neutrophil apoptosis”, “ferroptosis”, and “necroptosis” pathways at 7 dpf. Conclusion Tritiated water exposure induces a temporally dynamic immune response in zebrafish, potentially affecting immune homeostasis by regulating neutrophil activation and apoptosis, as well as the expression of NF-κB and NLRP3.

OBJECTIVE: Asthma imposes a significant global health burden. This study examines changes in the asthma-related disease burden from 1990 to 2021 and projects future burdens for 2050 under different scenarios. METHODS: Using data from the Global Burden of Disease 2021 study, we analyzed asthma incidence, prevalence, mortality, and disability-adjusted life years (DALYs) from 1990 to 2021. We projected the disease burden for 2050 based on current trends and hypothetical scenarios in which all risk factors are controlled. Temporal trends in age-standardized incidence, prevalence, mortality, and DALY rates were explored using Annual Percent Change. RESULTS: In 2021, the age-standardized rates for asthma incidence, prevalence, mortality, and DALYs in China were 364.17 per 100,000 (95% uncertainty interval [ UI]: 283.22-494.10), 1,956.49 per 100,000 (95% UI: 1,566.68-2,491.87), 1.47 per 100,000 (95% UI: 1.15-1.79), and 103.76 per 100,000 (95% UI: 72.50-145.46), respectively. A higher disease burden was observed among Chinese men and individuals aged 70 years or older. Compared to the current trend, a combined scenario involving improvements in environmental factors, behavioral and metabolic health, child nutrition, and vaccination resulted in a greater reduction in the disease burden caused by asthma. CONCLUSION Addressing modifiable risk factors is essential for further reducing the asthma-related disease burden.
Humans ; Asthma/mortality* ; China/epidemiology* ; Male ; Female ; Adult ; Middle Aged ; Aged ; Child ; Adolescent ; Global Burden of Disease/trends* ; Child, Preschool ; Young Adult ; Infant ; Cost of Illness ; Disability-Adjusted Life Years ; Prevalence ; Incidence ; Infant, Newborn ; Aged, 80 and over ; Risk Factors

OBJECTIVE: This study aims to analyze the burden of lower respiratory infections in Chinese elderly people aged 70 and above. METHODS: This study utilized Global Burden of Disease (GBD) 1990-2050 prediction data to analyze changes in mortality rates and disability-adjusted life year (DALY) rates for lower respiratory infections in the elderly population (aged 70 and above) in China from 1990 to 2050. It also discusses future trends in the burden of lower respiratory infections (LRI) in China under different scenarios. RESULTS: According to GBD predictions, the burden of lower respiratory infections in the elderly aged 70 years and above in China is lower than the global average. The burden has been decreasing from 1990 to 2020, but is projected to increase from 2020 to 2050. Scenario-based predictions suggest that, under scenarios involving improvements in nutrition and vaccination, the burden of lower respiratory infections in the elderly in China is expected to be the lowest in 2050. CONCLUSION This study indicates that the burden of lower respiratory infections in elderly people aged 70 years and above in China remains a significant public health issue and may worsen. The government should consider strengthening the preventive measures and management strategies for respiratory infections in the elderly population.
Humans ; China/epidemiology* ; Aged ; Respiratory Tract Infections/mortality* ; Aged, 80 and over ; Male ; Female ; Forecasting ; Disability-Adjusted Life Years ; Global Burden of Disease ; Cost of Illness

Objective:To analyze the epidemiological characteristics and trend of acute hemorrhagic conjunctivitis (AHC) in China from 2015 to 2022, and to provide evidence for the adjustment of prevention and control strategies and measures for AHC.Methods:The case data of AHC reported by national notifiable disease information system from 2015 to 2022 were collected, and descriptive analysis method were used to analyze the population distribution characteristics, temporal epidemiological trends and spatial clusters of AHC in China.Results:From 2015 to 2022, the incidence of AHC in China ranged from 1.85/100 000 to 2.97/100 000, with a fluctuating downward trend. The average annual percent change (AAPC) was -4.91 (95% CI: -7.74 to -2.00, P<0.05), with an annual percent change (APC) of 2.73 (95% CI: -2.34 to 8.06, P=0.189) for 2015—2019 and an APC of -14.23 (95% CI: -21.78 to -5.94, P<0.05). The age-specific incidence rate was highest in children aged 0-4 years (fluctuating between 4.69 and 5.67/100 000 from 2015 to 2019; It decreased significantly during 2020—2022, fluctuating between 1.93 and 2.72 per 100 000).The proportion of cases in children at 0-4 years of age showed a fluctuating downward trend from 8.68% in 2015 to 3.76% in 2020, with an increase in 2021—2022 to 5.74%. After 2020, the proportion of the population aged 60 years and above has increased, reaching 33.59% in 2022. Cases were mainly farmers, with a fluctuating upward trend of around 50% per year, with the highest percentage of 60.96% in 2020. The peak seasonal incidence of AHC was obvious from May to September from 2015 to 2019, but it was not obvious in 2020—2022. The cases were mainly distributed in Guangxi, Hainan and other provinces in the southwestern part of China. The high incidence counties were concentrated in Leye County of Guangxi, Maojian District of Hubei, Fuchuan Yao Autonomous County of Guangxi, Funing County of Yunnan, and Pulan County of Tibet every year. Conclusions:The overall epidemic rate of AHC in China showed a fluctuating downward trend from 2015 to 2022, with a pronounced decline observed between 2020 and 2022, potentially linked to non-pharmaceutical interventions during the COVID-19 pandemic. Increased attention needs to be given to farmers and people above 60 years of age to reduce the risk of morbidity. Moreover, prevention and control efforts should be strengthened in high-risk areas of southwestern China, and comprehensive measures should be implemented in counties with high incidence, including enhanced health education campaigns and improved allocation of sanitary facilities, to reduce the risk of AHC infection. This study is the first to highlight the potential impact of public health policies on AHC epidemiology, thereby offering a scientific foundation for population- and region-specific precision prevention strategies, particularly guiding the refinement of control measures in high-burden areas.

Establishing a one-stop diagnosis and treatment mode centered on patients and linked by diseases is of great significance for optimizing the medical process and improving the medical experience. In March 2024, a tertiary hospital integrated pediatric outpatient and emergency resources, established a pediatric diagnosis and treatment island through reasonable department settings, strengthened talent team construction, optimized diagnosis and treatment processes, and established supporting guarantee mechanisms. It was officially put into use in June of the same year, providing one-stop diagnosis and treatment services for children and achieving the goal of " not leaving the island for minor illnesses and not leaving the hospital for major illnesses". Before the operation of island (January May 2024), the complaint rate and waiting time for pediatric outpatient and emergency department were 39 cases per 100 000 patients and 15 to 30 minutes, respectively; After operation (June August 2024), the complaint rate and waiting time decreased to 17 cases per 100 000 people and 10 to 20 minutes respectively; The average monthly comprehensive income of outpatient and emergency departments increased by 33%. The pediatric diagnosis and treatment island mode could assist in the sustainable high-quality development of pediatrics in hospital, and provide references for optimizing outpatient and emergency department management in other tertiary public hospitals. In the future, we should further enrich the service content of the island and strengthen information technology construction.

Objective:To analyze the clinical characteristics, RAN-binding protein 2 ( RANBP2) gene variations, and prognosis in Chinese acute necrotizing encephalopathy (ANE) patients. Methods:A retrospective analysis of ANE cases registered in the Peking Union Medical College Hospital Encephalitis Registry System from 2022 to 2024, involving patients from Peking Union Medical College Hospital and other hospitals, was conducted. A descriptive study was performed on the clinical characteristics, treatments and prognosis, cerebrospinal fluid examination results, and imaging findings of these patients based on adjusted ANE diagnostic criteria. Whole-exome sequencing technology was used to detect gene mutations in these patients.Results:A total of 18 ANE cases were included, ranged in age from 2 to 72 [20(5, 43)] years. The male-to-female ratio was 4∶5. All patients were found with precipitating infections including COVID-19, influenza A virus and Mycoplasma pneumoniae infections. All patients presented with fever, with varying degrees of consciousness disturbance observed in 16 cases, and seizures in 10 cases. All patients underwent lumbar puncture, with normal or mildly elevated white cell counts [3(2, 13)×10 6/L] and mildly to moderately elevated protein levels [1.90(0.92, 4.65) g/L]. A total of 6 patients were found with extremely elevated interleukin-6 level [950(164, 2 000) pg/ml] in cerebrospinal fluid. Bilateral symmetric thalamic lesions were typical imaging features of ANE, while involvement of other areas such as cortical and subcortical white matter, brainstem, and cerebellum was also observed. A total of 14 patients performed genetic tests while 4 patients were identified with RANBP2 gene mutations (c.1754C>T in 3 cases, c.1966A>G in 1 case). All patients received immunotherapy, and 7 patients died at discharge while other patients presented with neurological sequelae of varying degrees. Conclusions:ANE is a rare and severe parainfectious encephalopathy that can occur in both children and adults. Clinically, it is characterized by rapidly progressing encephalopathy following systematic infection, with bilateral symmetric thalamic lesions. The detection of RANBP2 gene mutations could help make the diagnosis.

Objective:To explore the expressions and significance of nucleotide binding oligomerization domain-like receptor protein 3 (NLRP3), cysteinyl aspartate specific proteinase-1 (Caspase-1) and interleukin-1β (IL-1β) in patients with hemorrhagic stroke.Methods:One hundred and three patients with hemorrhagic stroke who visited the Department of Neurosurgery of the Second Affiliated Hospital of Zhengzhou University from January 2022 to January 2024 were selected as the hemorrhage group.Another 90 healthy individuals who underwent physical examinations were selected as the control group.The differences in the levels of NLRP3, Caspase-1 and IL-1β in peripheral blood between the two groups were compared. The National Institutes of Health neurological deficiency score (NHISS) was used to evaluate the degree of neurological deficits of patients in the hemorrhage group. All patients were followed up for 3 months. The prognosis of patients was evaluated by modified Rankin scale (mRS). The statistical analysis was performed using SPSS 20.0 software. The relationship between peripheral blood indexes and blood loss, severity of neurological impairment was analyzed by Spearman correlation analysis. The predictive value of peripheral blood indexes for prognosis was evaluated by receiver operating characteristic (ROC) curves.Results:The expression levels of NLRP3 mRNA (2.67±0.42, 1.04±0.28), Caspase-1 mRNA (1.24±0.26, 0.75±0.14) and IL-1β protein ((24.92±4.97) pg/mL, (13.39±2.35) pg/mL) in the hemorrhage group were higher than those in the control group ( t=31.243, 15.967, 20.126, all P<0.05). When comparing the levels of NLRP3 mRNA, Caspase-1 mRNA and IL-1β in the peripheral blood of patients with different amounts of bleeding, those with massive bleeding were higher than those with moderate bleeding, and those with moderate bleeding were higher than those with mild bleeding (all P<0.05).The Spearman correlation analysis showed that the levels of NLRP3 mRNA, Caspase-1 mRNA and IL-1β in peripheral blood were positively correlated with the amount of bleeding in patients with hemorrhagic stroke ( r=0.646, 0.585, 0.604, all P<0.05). The levels of NLRP3 mRNA, Caspase-1 mRNA and IL-1β in patients with severe neurological deficits were higher than those in patients with moderate and mild neurological deficits, and those in patients with moderate neurological deficits were higher than those in patients with mild neurological deficits (all P<0.05). The results of Spearman correlation analysis showed that the levels of NLRP3 mRNA, Caspase-1 mRNA and IL-1β in peripheral blood were positively correlated with the degree of neurological deficits in patients with hemorrhagic stroke ( r=0.607, 0.522, 0.546, all P<0.05). The expression levels of NLRP3 mRNA, Caspase-1 mRNA and IL-1β in peripheral blood in the poor prognosis group were higher than those in the good prognosis group (all P<0.05). The prediction results indicated that bleeding into the cerebral ventricles, large amount of bleeding, and high expression of NLRP3, Caspase-1 and IL-1β in peripheral blood were independent risk factors for poor prognosis in patients with hemorrhagic stroke (all P<0.05). The area under the ROC curve for the combined assessment of poor prognosis in hemorrhagic stroke by the levels of NLRP3 mRNA, Caspase-1 mRNA and IL-1β was 0.856, which was larger than the areas under the curves of the three indicators detected separately (0.720, 0.703, 0.715, P<0.05). Conclusion:The expressions of peripheral blood NLRP3, Caspase-1 and IL-1β are up-regulated in patients with hemorrhagic stroke, and their high expressions are related to blood loss and the severity of neurological deficit, which also indicate poor prognosis of patients.

China has become the country with the highest global burden of heart failure(HF).Despite the widespread use of prognostic-improving medications today,the mortality rate of HF remains high,reaching 13.7％at one year-particularly among patients with heart failure with reduced ejection fraction(HFrEF).HF interventional device therapy(structural intervention)targets the structural factors underlying HF,including atrial pressure,ventricular remodeling,and valvular intervention.It leverages the heart's intrinsic physiological properties and pathological progression mechanisms to deliver treatments through interventions without external active forces,achieving anatomical or functional repair.This field has emerged as a rapidly growing area and plays an increasingly critical role in HF management.This article provides a comprehensive review and summary of the latest advancements in HF and cardiomyopathy interventional therapy over the past year.It covers various novel technologies and products currently in the research phase,aiming to provide an in-depth analysis of the current status and future directions of HF interventional therapy,and further advance the development of this discipline.