Objective: To analyze the epidemiological characteristics of pulmonary tuberculosis (PTB) among college students in Yangzhou from 2020 to 2024, so as to provide a scientific basis for developing prevention and control strategies. Methods: An epidemiological investigation was conducted among 162 college students with PTB, and 7 134 of their contacts were screened. Data were obtained from the tuberculosis information management system and on campus screening records. Using descriptive epidemiological methods, trends in incidence, seasonal distribution, and bacteriological characteristics were analyzed. Results: From 2020 to 2024, the annual average incidence of pulmonary tuberculosis among college students in Yangzhou was 29.42 per 100 000, showing an overall fluctuating downward trend ( χ 2=12.36, P <0.01). Cases were mainly concentrated in summer and autumn, with the highest proportion in autumn (41.36%, 67/162), followed by summer (23.46%, 38/162). The proportion of etiologically positive cases increased from 37.21% in 2020 to 71.43% in 2024; among positive cases, the proportion of latent tuberculosis infection (LTBI) decreased from 66.67% (10/15) to 26.67% (4/15). The etiological positive rate was higher in females than in males ( χ 2= 11.76 , P <0.01). Comparison of screening methods showed that among index cases, the LTBI detection rate of the recombinant Mycobacterium tuberculosis fusion protein skin test (C-TST) was higher than that of the tuberculin skin test (TST), but the difference was not statistically significant ( χ 2=0.65, P =0.42); among close contacts, the detection rate of TST was higher than that of C-TST (15.1%,10.1%; χ 2=5.23, P <0.05). Conclusion From 2020 to 2024, the annual average incidence of pulmonary tuberculosis among college students in Yangzhou showed an overall fluctuating downward trend, with differences in TB infection screening methods and gender.

The interaction between m⁶A-methylated RNA and chromatin modification remains largely unknown. We found that targeted inhibition of bromodomain-containing protein 4 (BRD4) by siRNA or its inhibitor (JQ1) significantly decreases mRNA m⁶A levels and suppresses the malignancy of breast cancer (BC) cells via increased expression of demethylase AlkB homolog 5 (ALKBH5). Mechanistically, inhibition of BRD4 increases the mRNA stability of ALKBH5 via enhanced binding between its 3' untranslated regions (3'UTRs) with RNA-binding protein RALY. Further, BRD4 serves as a scaffold for ubiquitin enzymes tripartite motif containing-21 (TRIM21) and ALKBH5, resulting in the ubiquitination and degradation of ALKBH5 protein. JQ1-increased ALKBH5 then demethylates mRNA of extra spindle pole bodies like 1 (ESPL1) and reduces binding between ESPL1 mRNA and m⁶A reader insulin like growth factor 2 mRNA binding protein 3 (IGF2BP3), leading to decay of ESPL1 mRNA. Animal and clinical studies confirm a critical role of BRD4/ALKBH5/ESPL1 pathway in BC progression. Further, our study sheds light on the crosstalks between histone modification and RNA methylation.

Coronavirus-related diseases pose a significant challenge to the global health system. Given the diversity of coronaviruses and the unpredictable nature of disease outbreaks, the traditional "one bug, one drug" paradigm struggles to address the growing number of emerging crises. Therefore, there is an urgent need for therapeutic agents with broad-spectrum anti-coronavirus activity. Here, we provide evidence that ATV006, an anti-SARS-CoV-2 nucleoside analog targeting RNA-dependent RNA polymerase (RdRp), has broad antiviral activity against human and animal coronaviruses. Using mouse hepatitis virus (MHV) and human coronavirus NL63 (HCoV-NL63) as a model, we show that ATV006 has potent prophylactic and therapeutic activity against murine coronavirus infection in vivo. Remarkably, ATV006 successfully inhibits viral replication in mice even when administered 96 h after infection. Due to its oral bioavailability and potency against multiple coronaviruses, ATV006 has the potential to become a useful antiviral agent against SARS-CoV-2 and other circulating and emerging coronaviruses in humans and animals.

Retinopathy of prematurity (ROP) is a proliferative retinal vascular disease that threatens the vision of premature infants. Various novel drugs have demonstrated therapeutic potential for ROP by targeting signaling pathways associated with vascular endothelial growth factor (VEGF) [such as PI3K/AKT, hypoxia-inducible factor (HIF)-1α/VEGF], oxidative stress, tumor necrosis factor (TNF)-α, and Notch pathways. Propranolol, insulin-like growth factor-1, and celecoxib attenuate pathological neovascularization via the PI3K/Akt signaling pathway. Tripterine and melatonin inhibit retinal neovascularization by modulating the HIF-1α/VEGF signaling axis. Adiponectin mitigates the damage caused by oxidative stress and preserves endothelial function by enhancing endothelial nitric oxide synthase activity. Omega-3 polyunsaturated fatty acids suppress TNF-α-mediated inflammatory responses, modulate retinal development and angiogenesis, and reduce retinal neovascular lesions. DAPT, a γ-secretase inhibitor, blocks Notch signaling to suppress abnormal vascular proliferation. These agents exhibit synergistic multi-pathway anti-angiogenic effects in preclinical models and early-phase clinical trials, offering critical insights for advancing drug development and clinical translation in ROP management.
Retinopathy of Prematurity/metabolism* ; Humans ; Signal Transduction/drug effects* ; Infant, Newborn ; Vascular Endothelial Growth Factor A/metabolism* ; Hypoxia-Inducible Factor 1, alpha Subunit/metabolism* ; Tumor Necrosis Factor-alpha/metabolism* ; Oxidative Stress/drug effects* ; Fatty Acids, Omega-3/therapeutic use* ; Phosphatidylinositol 3-Kinases/metabolism* ; Proto-Oncogene Proteins c-akt/metabolism* ; Receptors, Notch/metabolism* ; Angiogenesis Inhibitors/therapeutic use* ; Insulin-Like Growth Factor I/therapeutic use*

Objective:To construct a symptom network for type 2 diabetes mellitus (T2DM) patients, identify bridging symptoms and core symptoms, and explore influencing factors, providing references for precise and efficient symptom management.Methods:A convenience sampling method was used to select 340 T2DM patients hospitalized in the Endocrinology Department of Affiliated Hospital of North Sichuan Medical College from December 2023 to February 2024. A general information survey and the Chinese version of Diabetes Symptom Checklist-Revised were used to collect data. Multiple linear regression analysis was performed to explore the influencing factors of T2DM patients' lack of vitality. Network analysis was used to identify core symptoms and bridging symptoms among symptom clusters. A total of 340 questionnaires were distributed, and 336 valid questionnaires were returned, resulting in a valid response rate of 98.8% (336/340) .Results:The most common symptoms in T2DM patients included thirst and dry mouth, foamy urine, and overall fatigue. The most troublesome symptoms were overall fatigue, lack of vitality, and thirst and dry mouth. In the symptom network, lack of vitality had the highest intensity ( rs=7.980) and closeness centrality ( rc=0.014), followed by overall fatigue ( rs=7.940) and feeling down ( rs=7.200). Overall fatigue ( rbs=7.190, rbc=0.380) was identified as the strongest bridging symptom in the network. Univariate analysis showed that age, education level, diabetes duration, diabetes complications, and regular blood glucose monitoring were significant factors affecting lack of vitality in T2DM patients ( P<0.05). Multiple linear regression analysis indicated that education level, regular blood glucose monitoring, and diabetes complications were significant factors affecting lack of vitality ( P<0.05) . Conclusions:Lack of vitality is the core symptom in T2DM patients, and overall fatigue is the bridging symptom connecting different symptom clusters. The lack of vitality is influenced by factors such as education level, regular blood glucose monitoring, and diabetes complications. Healthcare providers should use symptom network analysis to timely identify core symptoms, bridging symptoms, and their influencing factors, and develop precise and efficient interventions to improve symptom management and reduce the symptom burden in T2DM patients.

Objective:To construct a symptom network for type 2 diabetes mellitus (T2DM) patients, identify bridging symptoms and core symptoms, and explore influencing factors, providing references for precise and efficient symptom management.Methods:A convenience sampling method was used to select 340 T2DM patients hospitalized in the Endocrinology Department of Affiliated Hospital of North Sichuan Medical College from December 2023 to February 2024. A general information survey and the Chinese version of Diabetes Symptom Checklist-Revised were used to collect data. Multiple linear regression analysis was performed to explore the influencing factors of T2DM patients' lack of vitality. Network analysis was used to identify core symptoms and bridging symptoms among symptom clusters. A total of 340 questionnaires were distributed, and 336 valid questionnaires were returned, resulting in a valid response rate of 98.8% (336/340) .Results:The most common symptoms in T2DM patients included thirst and dry mouth, foamy urine, and overall fatigue. The most troublesome symptoms were overall fatigue, lack of vitality, and thirst and dry mouth. In the symptom network, lack of vitality had the highest intensity ( rs=7.980) and closeness centrality ( rc=0.014), followed by overall fatigue ( rs=7.940) and feeling down ( rs=7.200). Overall fatigue ( rbs=7.190, rbc=0.380) was identified as the strongest bridging symptom in the network. Univariate analysis showed that age, education level, diabetes duration, diabetes complications, and regular blood glucose monitoring were significant factors affecting lack of vitality in T2DM patients ( P<0.05). Multiple linear regression analysis indicated that education level, regular blood glucose monitoring, and diabetes complications were significant factors affecting lack of vitality ( P<0.05) . Conclusions:Lack of vitality is the core symptom in T2DM patients, and overall fatigue is the bridging symptom connecting different symptom clusters. The lack of vitality is influenced by factors such as education level, regular blood glucose monitoring, and diabetes complications. Healthcare providers should use symptom network analysis to timely identify core symptoms, bridging symptoms, and their influencing factors, and develop precise and efficient interventions to improve symptom management and reduce the symptom burden in T2DM patients.

Endothelial-mesenchymal transition (EndMT) disrupts vascular endothelial integrity and induces atherosclerosis. Active integrin β1 plays a pivotal role in promoting EndMT by facilitating TGFβ/Smad signaling in endothelial cells. Here, we report a novel anthraquinone compound, Kanglexin (KLX), which prevented EndMT and atherosclerosis by activating MAP4K4 and suppressing integrin β1/TGFβ signaling. First, KLX effectively counteracted the EndMT phenotype and mitigated the dysregulation of endothelial and mesenchymal markers induced by TGFβ1. Second, KLX suppressed TGFβ/Smad signaling by inactivating integrin β1 and inhibiting the polymerization of TGFβR1/2. The underlying mechanism involved the activation of FGFR1 by KLX, resulting in the phosphorylation of MAP4K4 and Moesin, which led to integrin β1 inactivation by displacing Talin from its β-tail. Oral administration of KLX effectively stimulated endothelial FGFR1 and inhibited integrin β1, thereby preventing vascular EndMT and attenuating plaque formation and progression in the aorta of atherosclerotic Apoe^-/- mice. Notably, KLX (20 mg/kg) exhibited superior efficacy compared with atorvastatin, a clinically approved lipid-regulating drug. In conclusion, KLX exhibited potential in ameliorating EndMT and retarding the formation and progression of atherosclerosis through direct activation of FGFR1. Therefore, KLX is a promising candidate for the treatment of atherosclerosis to mitigate vascular endothelial injury.
Animals ; Atherosclerosis/prevention & control* ; Mice ; Receptor, Fibroblast Growth Factor, Type 1/metabolism* ; Signal Transduction/drug effects* ; Anthraquinones/pharmacology* ; Humans ; Integrin beta1/metabolism* ; Epithelial-Mesenchymal Transition/drug effects* ; Male ; Transforming Growth Factor beta/metabolism* ; Disease Models, Animal ; Mice, Inbred C57BL ; Human Umbilical Vein Endothelial Cells/drug effects*

Objective To investigate and analyze the current status and challenges of infant and toddler nutritional services in urban and rural medical facilities in Sichuan Province.Methods In 2022,a questionnaire survey was conducted to collect data on infant and toddler nutritional services,including feeding guidance,physical growth assessment,and micronutrient deficiency screening,as well as information on personnel and tools in medical facilities throughout Sichuan Province.The provision of nutritional services was analyzed and the urban-rural disparities were assessed.Results A total of 2206 medical facilities(29.1%from urban areas and 70.9%from rural areas)were investigated.Only 35.8%of medical facilities provided all three types of nutritional services.Specifically,the overall service provision rates were high for feeding guidance(94.6%)and physical growth assessment(85.0%),but lower for micronutrient deficiency screening(37.4%).Rural facilities exhibited significantly lower rates than their urban counterparts for both physical growth assessment and micronutrient deficiency screening(P＜0.05).The provision rates of feeding guidance ranged from 70.6%to 93.2%,with responsive feeding guidance being the least implemented(70.6%),particularly in rural areas compared to urban areas(P＜0.05).Rates for physical growth assessment and micronutrient deficiency screening ranged from 75.3%to 81.8%and 23.6%to 30.8%,respectively,both showing lower rates in rural settings compared to urban ones(P＜0.05).Nutrition service providers were predominantly nurses(52.3%)and clinical practitioners(43.4%).The availability of dietary assessment tools ranged from 7.7%to 15.9%,significantly lower in rural areas compared to urban areas(P＜0.001),while physical measurement tools were widely available at rates of 94.6%to 98.5%.Conclusion At present,the infant and toddler nutritional service provisions of medical facilities in Sichuan Province are incomplete,particularly so in the implementation of feeding guidance,physical growth assessment,and micronutrient deficiency screening.There is a notable shortage of personnel and necessary tools,with rural areas facing more significant challenges.Enhancing the overall capacity of infant and toddler nutritional services in Sichuan Province is essential,with specific attention needed for rural healthcare settings.

Objective:To explore the current situation of hypoglycemia fear of elderly patients with type 2 diabetes mellitus (T2DM) in the community, identify different types of hypoglycemia fear among elderly T2DM patients in the community by latent profile analysis, and analyze its influencing factors, so as to provide reference for formulating intervention measures.Methods:From February to April 2023, convenience sampling was used to select 300 elderly T2DM patients from three community health service centers in Shunqing District, Nanchong City, Sichuan Province as the research subject. The self-designed General Information Questionnaire, the Chinese Version Hypoglycemia Fear Survey-Ⅱ (CHFS-Ⅱ), and the Summary Diabetes Self Care Activities (SDSCA) were used to investigate the patients, and the latent profile of hypoglycemia fear was analyzed. Binary Logistic regression was used to analyze the influencing factors of different latent categories of hypoglycemic fear in elderly T2DM patients in the community.Results:A total of 300 questionnaires were distributed, and 290 valid questionnaires were collected, with an effective response rate of 96.7% (290/300). Among 290 elderly T2DM patients in the community, the hypoglycemia fear could be divided into two latent categories, including the "moderate worry-normal coping" group ( n=134) and the "high fear-cautious behavior" group ( n=156). The binary Logistic regression showed that marital status, whether there were complications of diabetes, treatment plan and self-management were the factors influencing the latent categories of elderly T2DM patients in the community, and the difference was statistically significant ( P<0.05) . Conclusions:There are classification characteristics of hypoglycemic fear levels in elderly T2DM patients in the community. Community medical and nursing staff should early identify patients in the "high fear-cautious behavior" group, regularly carry out targeted hypoglycemic health education and psychological intervention, reduce their hypoglycemic fear, and improve their quality of life.

Objective:To investigate the role of long non-coding RNA nuclear paraspeckle assembly transcript 1 (Neat1) in pyroptosis of ultraviolet B (UVB)-induced human lens epithelial cells (LECs) and to explore the possible mechanism.Methods:The human lens epithelial cell line HLE-B3 was cultured in vitro, and cells at log phase were exposed to ultraviolet B for 0, 2, 4 and 8 hours, respectively.The expression of cysteine aspartic acid-specific protease-1 (caspase-1), a protein related to pyroptosis, was detected by Western blot.The relative expression level of Neat1 in cells after different irradiation durations was determined by real-time quantitative PCR.Cell viability was determined by the cell counting kit-8 (CCK-8) method to screen the optimal irradiation duration for UVB-induced LECs pyroptosis, which was finally determined to be 4 hours.HLE-B3 cells were divided into negative siRNA transfection group, siRNA Neat1 transfection group, negative siRNA transfection+ irradiation group and siRNA Neat1 transfection+ irradiation group, and were transfected with corresponding reagents for 24 hours.The negative siRNA transfection+ irradiation group and siRNA Neat1 transfection+ irradiation group were irradiated with UVB for 4 hours after transfection.The cell viability was detected by the CCK-8 method.The pyroptosis rate was detected by flow cytometry.The expression levels of caspase-1, gasdermin D (GSDMD) and nod-like receptor protein 3 (NLRP3) proteins were detected by Western blot.The concentration of interleukin (IL)-1β was detected by enzyme-linked immunosorbent assay (ELISA). Ultrastructural changes in HLE-B3 cells were observed under a transmission electron microscope. Results:The grayscale of caspase-1 protein bands increased with the extension of irradiation duration.The relative expression levels of caspase-1 protein at 0, 2, 4 and 8 hours of irradiation were 0.05±0.01, 0.25±0.07, 0.51±0.04 and 0.74±0.02, respectively, with a statistically significant overall difference ( F=168.223, P<0.001), and significant differences were found in paired comparisons (all at P<0.05). With prolonged irradiation, the relative expression level of Neat1 mRNA increased and the cell viability decreased, with statistically significant differences in paired comparisons (all at P<0.05). Compared with negative siRNA transfection group, the cell viability was increased in siRNA Neat1 transfection group and decreased in negative siRNA transfection+ irradiation group, with statistically significant differences (both at P<0.01). Compared with negative siRNA transfection+ irradiation group, the cell viability was increased in siRNA Neat1 transfection+ irradiation group, showing a statistically significant difference ( P<0.05). The pyroptosis rate was significantly lower in negative siRNA transfection group and siRNA Neat1 transfection+ irradiation group than in negative siRNA transfection+ irradiation group, and the differences were statistically significant (both at P<0.01). The relative expression levels of caspase-1, NLRP3 and GSDMD proteins in negative siRNA transfection+ irradiation group were higher than those in negative siRNA transfection group and siRNA Neat1 transfection+ irradiation group and the differences were statistically significant (all at P<0.01). The concentration of IL-1β was significantly higher in negative siRNA transfection+ irradiation group than in negative siRNA transfection group and siRNA Neat1 transfection+ irradiation group, and the differences were statistically significant (all at P<0.05). Cell swelling, formed cell membrane pores, vacuolated cells and fuzzy mitochondrial cristae were seen in negative siRNA transfection+ irradiation group and siRNA Neat1 transfection+ irradiation group by transmission electron microscopy.Compared with negative siRNA transfection+ irradiation group, slighter cell swelling, fewer cell membrane pores and lighter mitochondrial swelling were seen in siRNA Neat1 transfection+ irradiation group. Conclusions:Neat1 is involved in human LECs pyroptosis induced by UVB through the classic pyroptosis pathway mediated by caspase-1.Knockdown of Neat1 can inhibit the pyroptosis of human LECs.