ObjectiveTo understand the epidemiological distribution and gene evolutionary variation of influenza A (H3N2) viruses in Fengxian District, Shanghai, in the surveillance year of 2023, and to provide a reference basis for influenza prevention and control. MethodsThe prevalence of influenza virus in Fengxian District in the 2023 influenza surveillance year (April 2023‒March 2024) was analyzed. The hemagglutinin (HA) gene, neuraminidase (NA) gene, and amino acid sequences of 75 strains of H3N2 influenza viruses were compared with the vaccine reference strain for similarity matching and phylogenetic evolutionary analysis, in addition to an analysis of gene characterization and variation. ResultsIn Fengxian District, there was a mixed epidemic of H3N2 and H1N1 in the spring of 2023, with H3N2 being the predominant subtype in the second half of the year, and Victoria B becoming the predominant subtype in the spring of 2024. A total of 75 influenza strains of H3N2 with HA and NA genes were distributed in the 3C.2a1b.2a.2a.2a.3a.1 and B.4 branches, with overall similarity to the reference strain of the 2024 vaccine higher than that of the reference strain of the 2022 and 2023 vaccine. Compared with the 2023 vaccine reference strain, three antigenic sites and one receptor binding site were changed in HA, with three glycosylation sites reduced and two glycosylation sites added; where as in NA seven antigenic sites and the 222nd resistance site changed with two glycosylation sites reduced. ConclusionThe risk of antigenic variation and drug resistance of H3N2 in this region is high, and it is necessary to strengthen the publicity and education on the 2024 influenza vaccine and long-term monitoring of influenza virus prevalence and variation levels.

ObjectiveTo investigate the pathogenic spectrum and epidemiological characteristics of diarrheal disease in Fengxian District of Shanghai, and to provide scientific basis for the prevention and control of diarrheal diseases. MethodsBasic information of the initial adult cases visited diarrheal disease surveillance sentinel hospital in Fengxian District, Shanghai, was collected from August 2013 to 2023, and fecal samples were collected at 1∶5 sampling intervals to isolate and identify 5 kinds of diarrheagenic Escherichia coli (DEC), Salmonella (SAL), Vibrio parahaemolyticus, Campylobacter, Vibrio cholerae, Shigella and Yersinia enterocolitica (YE). Simultaneously, nucleic acid detection was performed for 3 kinds of rotavirus, 2 kinds of norovirus, intestinal adenovirus, astrovirus and sapovirus. ResultsA total of 1 861 cases of newly diagnosed diarrheal disease were reported, with the peak in July to August. Additionally, 704 surveillance samples were detected, with a total positive detection rate of 50.57%. The detection rates of bacterial, viral and mixed infection were 25.14%, 21.02% and 4.40%, respectively. Among the pathogens detected, DEC accounted for the highest (17.61%, 124/704), followed by norovirus (16.48%, 116/704), rotavirus (6.39%, 45/704), SAL (5.97%, 42/704) and Campylobacter (3.84%, 27/704). DEC detected were mainly enteroaggregative Escherichia coli and enterotoxigenic Escherichia coli, with no detection of Vibrio cholerae, Shigella and YE. The highest total pathogen detection rate was observed from June to September, and the detection peaks of norovirus were from March to June and from October to December, whereas that of DEC was from June to October. The detection rate of rotavirus peaked from January to February, but which was not detected between 2020‒2023. The SAL positive rate peak was in September, whereas that of Campylobacter was from July to September. ConclusionThe main pathogens detected in Fengxian District from 2013‒2019 are DEC, norovirus, rotavirus, SAL and Campylobacter. Different pathogens have different detection peaks, with bacteria predominating in summer and viruses in winter and spring. Prevention and control measures should be carried out according to the epidemiological characteristics of different seasons.

Objective　To analyze the current situation and influencing factors of health-care seeking delay of tuberculosis patients registered in Changsha from 2019 to 2023, and to understand the current status of health-care seeking delay after the transformation of the tuberculosis prevention and treatment service model in Changsha, so as to provide reference bases for improving the patient discovery strategy and optimizing tuberculosis control and prevention measures. Methods　The case data of 23 371 tuberculosis patients registered in Changsha City from 2019 to 2023 were collected, and the time of health-care seeking delay and the rate of health-care seeking delay were calculated. Comparison of differences between groups with different characteristics using rank sum test and chi-square test, and the Cochran-Armitage method was used to analyze the trend of health-care seeking delay rate, and multifactorial analysis was carried out with the help of logistic regression model. Results　The median health-care seeking time of tuberculosis patients in Changsha City from 2019-2023 was 16 (5, 44) days, and the overall health-care seeking delay rate was 53.5%, with an overall increasing trend (Z=-7.256, P<0.001). Between-group comparisons revealed differences in health-care seeking delay time and health-care seeking delay rate between groups of patients with different gender, age group, occupation, current address, types of household registration, medical history, complication, diagnostic triage, pathogenic results and geographic accessibility (P<0.05). The results of multifactorial analysis showed that compared to the<25 years age group, the 25-<65 years age group (OR=1.579, 95%CI: 1.490-1.669) and the ≥65 years age group (OR=2.016，95%CI: 1.918-2.113) had a higher risk of health-care seeking delay, presence of complication (OR=1.213，95%CI:1.141-1.285), positive pathology (OR=1.503, 95%CI: 1.449-1.556), and average geographic accessibility of healthcare services (OR=1.073, 95%CI:1.017-1.129) were risk factors for health-care seeking delay, and the risk was relatively lower in the migrating population (OR=0.920, 95%CI: 0.815-0.989). Conclusion　The rate of delayed health-care seeking for tuberculosis patients in Changsha City in 2019-2023 is at a moderate level in the surrounding areas, and the overall trend is increasing. It suggests that proactive screening strategies for key populations should be optimized to improve the accessibility of healthcare services and reduce the rate of health-care seeking delay.

In order to accurately capture the respiratory muscle movement and extract the synchronization signals corresponding to the breathing phases, a comprehensive signal sensing system for sensing the movement of the respiratory muscle was developed with applying the thin-film varistor FSR402 IMS-C07A in this paper. The system integrated a sensor, a signal processing circuit, and an application program to collect, amplify and denoise electronic signals. Based on the respiratory muscle movement sensor and a STM32F107 development board, an experimental platform was designed to conduct experiments. The respiratory muscle movement data and respiratory airflow data were collected from 3 healthy adults for comparative analysis. In this paper, the results demonstrated that the method for determining respiratory phase based on the sensing the respiratory muscle movement exhibited strong real-time performance. Compared to traditional airflow-based respiratory phase detection, the proposed method showed a lead times ranging from 33 to 210 ms [(88.3 ± 47.9) ms] for expiration switched into inspiration and 17 to 222 ms [(92.9 ± 63.8) ms] for inspiration switched into expiration, respectively. When this system is applied to trigger the output of the ventilator, it will effectively improve the patient-ventilator synchrony and facilitate the ventilation treatment for patients with respiratory diseases.
Humans ; Respiratory Muscles/physiology* ; Signal Processing, Computer-Assisted ; Movement/physiology* ; Respiration ; Monitoring, Physiologic/methods* ; Adult

Psoriasis is an incurable chronic inflammatory disease that requires new interventions. Here, we found that fibroblasts exacerbate psoriasis progression by promoting macrophage recruitment via CCL2 secretion by single-cell multi-omics analysis. The natural small molecule celastrol was screened to interfere with the secretion of CCL2 by fibroblasts and improve the psoriasis-like symptoms in both murine and cynomolgus monkey models. Mechanistically, celastrol directly bound to the low-density lipoprotein receptor-related protein 1 (LRP1) β-chain and abolished its binding to the transcription factor c-Jun in the nucleus, which in turn inhibited CCL2 production by skin fibroblasts, blocked fibroblast-macrophage crosstalk, and ameliorated psoriasis progression. Notably, fibroblast-specific LRP1 knockout mice exhibited a significant reduction in psoriasis like inflammation. Taken together, from clinical samples and combined with various mouse models, we revealed the pathogenesis of psoriasis from the perspective of fibroblast-macrophage crosstalk, and provided a foundation for LRP1 as a novel potential target for psoriasis treatment.

Objective Airway resistance(R)and lung compliance(C)under non-invasive positive pressure ventilation(NPPV)conditions were measured using a brief pressure release at the end of expiration,and the measurement accuracy was also evaluated.Methods An NPPV respirator was developed by programming a method for calculating R and C.An experimental platform based on the active servo lung ASL5000 was designed.By simulating a healthy adult(R=5 cmH2 O and C=50 mL/cmH2 O,1 cmH2 O=0.098 kPa),an adult patient with acute respiratory distress syndrome(R=10 cmH2 O and C=30 mL/cmH2 O),and an adult patient with chronic obstructive pulmonary disease(R=20 cmH2 O and C=50 mL/cmH2 O),a series of experiments for calculating the R and C were conducted.Results The maximum relative error of R was-12.67%,which occurred in calculating the R of an average adult.The maximum relative error of C was 17.37%,which occurred when calculating the C values of patients with acute respiratory distress syndrome.Each group of data was analyzed using a paired t-test,which showed statistically significant differences(P>0.05).Conclusions The calculation method for R and C at the end of expiration during NPPV is feasible,and its realization and application will be beneficial for achieving precise and personalized respiratory ventilation.

Background::Thoracic aortic aneurysm (TAA) is a fatal cardiovascular disease, the pathogenesis of which has not yet been clarified. This study aimed to identify and validate the diagnostic markers of TAA to provide a strong theoretical basis for developing new methods to prevent and treat this disease.Methods::Gene expression profiles of the GSE9106, GSE26155, and GSE155468 datasets were acquired from the Gene Expression Omnibus (GEO) database. Differentially expressed genes (DEGs) were identified using the "limma" package in R. Least absolute shrinkage and selection operator (LASSO), support vector machine-recursive feature elimination (SVM-RFE), random forest, and binary logistic regression analyses were used to screen the diagnostic marker genes. Single-sample gene set enrichment analysis (ssGSEA) was used to estimate immune cell infiltration in TAA.Results::A total of 16 DEGs were identified. The enrichment and functional correlation analyses showed that DEGs were mainly associated with inflammatory response pathways and collagen-related diseases. Collagen type I alpha 1 chain ( COL1A1) and synaptotagmin like 2 ( SYTL2) were identified as diagnostic marker genes with a high diagnostic value for TAA. The expression of COL1A1 and SYTL2 was considerably higher in TAA vascular wall tissues than in the corresponding normal tissues, and there were significant differences in the infiltration of immune cells between TAA and normal vascular wall tissues. Additionally, COL1A1 and SYTL2 expression were associated with the infiltration of immune cells in the vascular wall tissue. Single-cell analysis showed that COL1A1 in TAA was mainly derived from fibroblasts and SYTL2 mainly from cluster of differentiation (CD)8 + T cells. In addition, single-cell analysis indicated that fibroblasts and CD8 + T cells in TAA were significantly higher than those in normal arterial wall tissue. Conclusions::COL1A1 and SYTL2 may serve as diagnostic marker genes for TAA. The upregulation of SYTL2 and COL1A1 may be involved in the inflammatory infiltration of the vessel wall and poor extracellular matrix remodeling, promoting the progression of TAA.

Objective To explore novel methods for efficient respiratory viral infection of organoids by microinjection and polarity inversion techniques.Methods Lung tissue samples were obtained from 8-week-old male C57BL/6 mouse,and respiratory epithelial cells were extracted to establish a transwell organoid culture model.The green fluorescent protein(GFP)labeled influenza virus PR8(GFP-PR8)was quantitatively injected into organoids by improving the traditional microinjection platform,and morphologic changes in organoids and the immunofluorescence staining characteristics of tight junction proteins and microtubule proteins were observed.Polarity inversion apical-out(AO)was induced by suspension culture,and the morphological characteristics of polarity inversion was determined by HE staining.Normal and inverted organoids were infected with PR8,and the infection efficiency and expression differences of key pathway genes under different virus concentrations were observed.Results Ordinary organoids showed a significant increase in volume after microinjection.Following PR8 injection,the efficiency of infection was significantly higher in the apical region of organoids,accompanied by noticeable damage,as evidenced by significant down-regulation of tight junction proteins and microtubule protein expression.After suspension culture of the organoids,the polarity of ciliated cells gradually inverted outward over time,and the proportion of AO organoids stabilized on the 6th day.The efficiency of viral infection significantly increased in the inverted organoids,accompanied by significant cellular damage.After PR8 infection at 0.01 MOI,AO organoids showed significant changes in the inflammatory pathway and differentiation-related genes,with the opposite trend observed after higher concentration of PR8 infection.Conclusion Both polarity inversion and microinjection techniques significantly enhance the efficiency of influenza virus infection in organoids,thereby facilitating organoid widespread application in the field of respiratory tract infections.