Stress-Induced Metabolic Disorder in Peripheral CD4+ T Cells Leads to Anxiety-like Behavior.

Physical or mental stress leads to neuroplasticity in the brain and increases the risk of depression and anxiety. Stress exposure causes the dysfunction of peripheral T lymphocytes. However, the pathological role and underlying regulatory mechanism of peripheral T lymphocytes in mood disorders have not been well established. Here, we show that the lack of CD4+ T cells protects mice from stress-induced anxiety-like behavior. Physical stress-induced leukotriene B4 triggers severe mitochondrial fission in CD4+ T cells, which further leads to a variety of behavioral abnormalities including anxiety, depression, and social disorders. Metabolomic profiles and single-cell transcriptome reveal that CD4+ T cell-derived xanthine acts on oligodendrocytes in the left amygdala via adenosine receptor A1. Mitochondrial fission promotes the de novo synthesis of purine via interferon regulatory factor 1 accumulation in CD4+ T cells. Our study implicates a critical link between a purine metabolic disorder in CD4+ T cells and stress-driven anxiety-like behavior.

Clinical Characteristics, Treatment, and Prognosis of Osteoarticular Brucellosis: A Retrospective Real-World Study in Shenyang, China, 2014-2019.

This study aimed to assess the clinical characteristics, treatment, and prognosis of osteoarticular brucellosis. We conducted a retrospective study enrolling brucellosis patients from the Sixth People's Hospital of Shenyang between September 2014 and June 2019. A total of 1917 participants were admitted during this period. After applying propensity score matching, we retrospectively analyzed 429 patients with osteoarthritis and 429 patients without osteoarthritis. The primary outcome was treatment completion. The secondary outcome was symptom disappearance and seroconversion. Brucellosis patients with osteoarthritis had longer treatment course (160 [134.3-185.7] vs. 120 [102.3-137.7] d, p = 0.008) than those without osteoarthritis. The most common involved site was lumbar vertebrae (290 [67.6%]) in brucellosis patients with osteoarthritis. Longer symptom duration (90 [83.0-97.0] vs. 42 [40.2-43.8], p < 0.001) along with no significant difference in seroconversion (180 [178.8-181.2] vs. 180 [135.1-224.9], p = 0.212) was observed in osteoarthritis patients with treatment course >90 d. Peripheral joint involvement (adjusted hazard ratio [95% confidence interval] 1.485 [1.103-1.999]; p = 0.009) had a shorter symptom duration compared with shaft joint involvement. No significant differences were observed in treatment therapy between doxycycline plus rifampin (DR) or plus cephalosporins (DRC) in treatment course (p = 0.190), symptom persistence (p = 0.294), and seroconversion (p = 0.086). Lumbar vertebra was the most commonly involved site. Even if all symptoms disappeared, Serum agglutination test potentially remained positive in some patients. Compared with peripheral arthritis, shaft arthritis was the high-risk factor for longer symptom duration. The therapeutic effects were similar between DR and DRC. In summary, our study provided important insights into the clinical characteristics, treatment, and outcomes of osteoarticular brucellosis. Clinical Trial Registration number: NCT04020536.

[Role and mechanism of cysteine and glycine-rich protein 2 in the malignant progression of neuroblastoma].

OBJECTIVE: To investigate the function and underlying mechanism of cysteine and glycine-rich protein 2 (CSRP2) in neuroblastoma (NB). METHODS: The correlation between the expression level of CSRP2 mRNA and the prognosis of NB children in NB clinical samples was analyzed in R2 Genomics Analysis and Visualization Platform. The small interfering RNA (siRNA) targeting CSRP2 or CSRP2 plasmid were transfected to NB cell lines SK-N-BE(2) and SH-SY5Y. Cell proliferation was observed by crystal violet staining and real-time cellular analysis. The ability of colony formation of NB cells was observed by colony-forming unit assay. Immunofluorescence assay was used to detect the expression of the proliferation marker Ki-67. Flow cytometry analysis for cell cycle proportion was used with cells stained by propidium iodide (PI). Annexin V/7AAD was used to stain cells and analyze the percentage of cell apoptosis. The ability of cell migration was determined by cell wound-healing assay. The level of protein and mRNA expression of CSRP2 in NB primary tumor and NB cell lines were detected by Western blot and quantitative real-time PCR (RT-qPCR). RESULTS: By analyzing the NB clinical sample databases, it was found that the expression levels of CSRP2 in high-risk NB with 3/4 stages in international neuroblastoma staging system (INSS) were significantly higher than that in low-risk NB with 1/2 INSS stages. The NB patients with high expression levels of CSRP2 were shown lower overall survival rate than those with low expression levels of CSRP2. We detected the protein levels of CSRP2 in the NB samples by Western blot, and found that the protein level of CSRP2 in 3/4 INSS stages was significantly higher than that in 1/2 INSS stages. Knockdown of CSRP2 inhibited cell viability and proliferation of NB cells. Overexpression of CSRP2 increased the proliferation of NB cells. Flow cytometry showed that the proportion of sub-G1, G0/G1 and S phase cells and Annexin V positive cells were increased after CSRP2 deficiency. In the cell wound-healing assay, the healing rate of NB cells was significantly attenuated after knockdown of CSRP2. Further mechanism studies showed that the proportion of the proliferation marker Ki-67 and the phosphorylation levels of extracellular signal-regulated kinases 1/2 (ERK1/2) were significantly decreased after CSRP2 knockdown. CONCLUSION: CSRP2 is highly expressed in high-risk NB with 3/4 INSS stages, and the expression levels of CSRP2 are negatively correlated with the overall survival of NB patients. CSRP2 significantly increased the proliferation and cell migration of NB cells and inhibited cell apoptosis via the activation of ERK1/2. All these results indicate that CSRP2 promotes the progression of NB by activating ERK1/2, and this study will provide a potential target for high-risk NB therapy.

Contour Information-Guided Multi-Scale Feature Detection Method for Visible-Infrared Pedestrian Detection.

Infrared pedestrian target detection is affected by factors such as the low resolution and contrast of infrared pedestrian images, as well as the complexity of the background and the presence of multiple targets occluding each other, resulting in indistinct target features. To address these issues, this paper proposes a method to enhance the accuracy of pedestrian target detection by employing contour information to guide multi-scale feature detection. This involves analyzing the shapes and edges of the targets in infrared images at different scales to more accurately identify and differentiate them from the background and other targets. First, we propose a preprocessing method to suppress background interference and extract color information from visible images. Second, we propose an information fusion residual block combining a U-shaped structure and residual connection to form a feature extraction network. Then, we propose an attention mechanism based on a contour information-guided approach to guide the network to extract the depth features of pedestrian targets. Finally, we use the clustering method of mIoU to generate anchor frame sizes applicable to the KAIST pedestrian dataset and propose a hybrid loss function to enhance the network's adaptability to pedestrian targets. The extensive experimental results show that the method proposed in this paper outperforms other comparative algorithms in pedestrian detection, proving its superiority.

Early identification and severity prediction of acute respiratory infection (ESAR): a study protocol for a randomized controlled trial.

BACKGROUND: The outbreak of SARS-CoV-2 at the end of 2019 sounded the alarm for early inspection on acute respiratory infection (ARI). However, diagnosis pathway of ARI has still not reached a consensus and its impact on prognosis needs to be further explored. METHODS: ESAR is a multicenter, open-label, randomized controlled, non-inferiority clinical trial on evaluating the diagnosis performance and its impact on prognosis of ARI between mNGS and multiplex PCR. Enrolled patients will be divided into two groups with a ratio of 1:1. Group I will be directly tested by mNGS. Group II will firstly receive multiplex PCR, then mNGS in patients with severe infection if multiplex PCR is negative or inconsistent with clinical manifestations. All patients will be followed up every 7 days for 28 days. The primary endpoint is time to initiate targeted treatment. Secondary endpoints include incidence of significant events (oxygen inhalation, mechanical ventilation, etc.), clinical remission rate, and hospitalization length. A total of 440 participants will be enrolled in both groups. DISCUSSION: ESAR compares the efficacy of different diagnostic strategies and their impact on treatment outcomes in ARI, which is of great significance to make precise diagnosis, balance clinical resources and demands, and ultimately optimize clinical diagnosis pathways and treatment strategies. Trial registration Clinicaltrial.gov, NCT04955756, Registered on July 9th 2021.

Experimental determination of nanocomposite grating structures by light- and neutron-diffraction in the multi-wave-coupling regime.

We experimentally demonstrate how to accurately retrieve the refractive index profile of photonic structures by standard diffraction experiments and use of the rigorous coupled-wave analysis in the multi-wave coupling regime, without the need for taking any auxiliary data. In particular, we show how the phases of the Fourier components of a periodic structure can be fully recovered by deliberately choosing a probe wavelength of the diffracting radiation much smaller than the lattice constant of the structure. In the course of our demonstration, we accurately determine the slight asymmetry of the structure of nanocomposite phase gratings by light and neutron diffraction measurements.

Obesity is a risk factor for central precocious puberty: a case-control study.

BACKGROUND: Obesity is an important underlying cause of central precocious puberty (CPP), but previous large studies are flawed by using just age and breast examination to diagnose CPP. We aimed to determine whether overweight and obesity in childhood increases hormonally diagnosed CPP. METHODS: Our retrospective, case-control study recruited 846 children diagnosed as having CPP and randomly sampled 1650 healthy control subjects in Xingtai Third Hospital in China between November 2018 and March 2021. Information was obtained from an electronic medical record and questionnaire investigated in the outpatient visit. Observations were made before the a priori hypothesis. Unconditional logistic regression for analysis was used to determine whether overweight and obesity status and duration of overweight/obesity were associated with CPP. RESULTS: Overweight and obesity were significantly associated with increased odds of CPP among girls, even after adjusting for birth weight, exclusive breastfeeding for 6 month, household income, maternal overweight, paternal overweight, and maternal menarche age (overweight: the adjusted odds ratio (aOR) (95%CI): 1.92 (1.16, 3.24), p = 0.02; obesity: aOR (95%CI): 1.78 (1.13, 3.48), p = 0.03). Furthermore, the effects of overweight and obesity were significant when ongoing for 1 to 2 years, 2 to 3 years, and greater than 3 years, but not at less than 1 year. For boys, association between obesity and increased odds of CPP was observed (aOR (95%CI): 1.68 (1.09, 3.75), p = 0.03). The effects of overweight and/or obesity were only significant when ongoing for greater than 2 years. CONCLUSIONS: Prolonged overweight and obesity in early childhood may be risk factors for CPP, especially in girls. Weight loss might be an important approach for the prevention of precocious puberty in children.

Controlling amplified spontaneous emission of quantum dots by polymerized nanostructure interfaces.

We report a new polymer/colloidal-quantum-dot (CQD) film with a nanostructured interface, which is fabricated through a template-assisted photopolymerization method, toward the use of amplified spontaneous emission. It is experimentally demonstrated that the amplified spontaneous emission of CQDs is able to be manipulated by changing the nanostructured polymeric interface with a weak scattering ability. The dependences of emission wavelength and threshold on the size of the nanostructure and CQD layer thickness are investigated.

Transcriptome analysis revealed potential mechanisms of differences in physiological stress responses between caged male and female magpies.

BACKGROUND: Under caged conditions, birds are affected more severely by environmental stressors such as dietary structure, activity space, human disturbances, and pathogens, which may be reflected in the gene expression in peripheral blood or other tissues. Elucidating the molecular mechanism of these stress responses will help improve animal welfare. RESULTS: In the present study, the blood transcriptomes of six male and five female caged magpies (Pica pica) were sequenced, and a total of ~ 100 Gb in clean reads were generated using the Illumina HiSeq 2000 sequencer. A total of 420,291 unigenes were identified after assembly, of which 179,316 were annotated in five databases, 7471 were assigned to 269 Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways, and 566 were assigned to the Clusters of Orthologous Groups (COG) functional classification "defense mechanisms". Analysis of differentially expressed genes (DEGs) showed that 2657 unigenes were differentially expressed between males and females (q < 0.1), and these DEGs were assigned to 45 KEGG pathways involving stress resistance, immunity, energy metabolism, reproduction, lifespan regulation, and diseases. Further analysis revealed that females might be more sensitive to stress through upregulation of c-Jun N-terminal kinases (JNKs) and 5'AMP-activated protein kinase (AMPK), and were also possibly more sensitive to dynamic changes in energy. Females expressed higher major histocompatibility complex (MHC) class II levels than males, enhancing resistance to pathogens, and the DEGs related to reproduction included MAPK, CaMK, CPEB, and Cdc25. The genes related to stress, energy, and immunity were also likely related to the regulation of longevity. The upregulated JNKs in females might prolong lifespan and relieve antioxidant stress. Females may also activate the AMPK pathway and implement dietary restrictions to prolong lifespan, whereas males may upregulate SIRT1 and CRAB to increase lifespan. CONCLUSIONS: Female magpies might be more sensitive to stress and dynamic changes in energy thus enhanced resistance to pathogens, and the genes related to stress, energy, and immunity were also possibly related to the regulation of longevity. Further confirmations with techniques such as RT-qPCR and western blot are necessary to validate the above arguments.

Measurement of polymerization-shrinkage evolution during curing in photopolymer with a white-light Fabry-Pérot interferometer.

We propose a simple method of measuring polymerization-shrinkage evolution during curing in photopolymer. The real-time spectral fringe analysis of a broadband beam transmitted through a Fabry-Pérot etalon supported by a photopolymer film provides the shrinkage evolution during curing. For the proof-of-principle demonstration a blue-sensitized nanoparticle-polymer composite material is used. It is shown that the measured shrinkage dynamics are well correlated with the photo-calorimetric conversion dynamics of monomer to polymer. We also discuss a discrepancy in steady-state shrinkage between our proposed and holographic Bragg-angle detuning measurements.

Nanoparticle polymer composite volume gratings incorporating chain transfer agents for holography and slow-neutron optics.

We demonstrate twofold enhancement of the saturated refractive index modulation (Δn(sat)) recorded in a photopolymerizable nanoparticle-acrylate polymer composite film by incorporating thiols acting as chain transfer agents. The chain transfer reaction of thiols with (meth)acrylate monomer reduces the polymer crosslinking density and facilitates the mutual diffusion of nanoparticles and monomer during holographic exposure. These modifications provide increased density modulations of nanoparticles and the formed polymer, resulting in the enhancement of Δn(sat) as high as 1.6×10(-2) at a wavelength of 532 nm. The incorporation of thiols also leads to shrinkage suppression and to improvement of the grating's spatial frequency response. Such simultaneous improvement is very useful for holographic applications in light and neutron optics.

Effects of chain-transferring thiol functionalities on the performance of nanoparticle-polymer composite volume gratings.

We report influences of varying functionalities of thiols as chain transfer agents on the spatial frequency response, polymerization shrinkage, and thermal stability of a volume grating recorded in a photopolymerizable ZrO2 nanoparticle-polymer composite film. It is shown that a substantial increase in the saturated refractive index modulation is realized at high spatial frequencies by doping with multifunctional thiols. Moreover, the incorporation of multifunctional thiols considerably suppresses polymerization shrinkage of recorded volume gratings and thermal changes in refractive index and film thickness as compared with the case of mono-thiol. These results indicate that multifunctional thiols provide effective control of the properties of nanoparticle-polymer composite volume gratings for various applications in light and neutron optics.

Comparison of the free and bound phenolic profiles and cellular antioxidant activities of litchi pulp extracts from different solvents.

BACKGROUND: The phenolic contents and antioxidant activities of fruits could be underestimated if the bound phenolic compounds are not considered. In the present study, the extraction efficiencies of various solvents were investigated in terms of the total content of the free and bound phenolic compounds, as well as the phenolic profiles and antioxidant activities of the extracts. METHODS: Five different solvent mixtures were used to extract the free phenolic compounds from litchi pulp. Alkaline and acidic hydrolysis methods were compared for the hydrolysis of bound phenolic compounds from litchi pulp residue. The phenolic compositions of the free and bound fractions from the litchi pulp were identified using HPLC-DAD. The antioxidant activities of the litchi pulp extracts were determined by oxygen radical absorbance capacity (ORAC) and cellular antioxidant activity (CAA) assays. RESULTS: Of the solvents tested, aqueous acetone extracted the largest amount of total free phenolic compounds (210.7 mg GAE/100 g FW) from litchi pulp, followed sequentially by aqueous mixtures of methanol, ethanol and ethyl acetate, and water itself. The acid hydrolysis method released twice as many bound phenolic compounds as the alkaline hydrolysis method. Nine phenolic compounds were detected in the aqueous acetone extract. In contrast, not all of these compounds were found in the other four extracts. The classification and content of the bound phenolic compounds released by the acid hydrolysis method were higher than those achieved by the alkaline hydrolysis. The aqueous acetone extract showing the highest ORAC value (3406.9 µmol TE/100 g FW) for the free phenolic extracts. For the CAA method, however, the aqueous acetone and methanol extracts (56.7 and 55.1 µmol QE/100 g FW) showed the highest levels of activity of the five extracts tested. The ORAC and CAA values of the bound phenolic compounds obtained by acid hydrolysis were 2.6- and 1.9-fold higher than those obtained using the alkaline hydrolysis method. CONCLUSIONS: The free and bound phenolic contents and profiles and antioxidant activities of the extracts were found to be dependent on the extraction solvent used. Litchi exhibited good cellular antioxidant activity and could be a potentially useful natural source of antioxidants.

Biclustering of Log Data: Insights from a Computer-Based Complex Problem Solving Assessment.

Computer-based assessments provide the opportunity to collect a new source of behavioral data related to the problem-solving process, known as log file data. To understand the behavioral patterns that can be uncovered from these process data, many studies have employed clustering methods. In contrast to one-mode clustering algorithms, this study utilized biclustering methods, enabling simultaneous classification of test takers and features extracted from log files. By applying the biclustering algorithms to the "Ticket" task in the PISA 2012 CPS assessment, we evaluated the potential of biclustering algorithms in identifying and interpreting homogeneous biclusters from the process data. Compared with one-mode clustering algorithms, the biclustering methods could uncover clusters of individuals who are homogeneous on a subset of feature variables, holding promise for gaining fine-grained insights into students' problem-solving behavior patterns. Empirical results revealed that specific subsets of features played a crucial role in identifying biclusters. Additionally, the study explored the utilization of biclustering on both the action sequence data and timing data, and the inclusion of time-based features enhanced the understanding of students' action sequences and scores in the context of the analysis.

Diagnostic Classification Models for Testlets: Methods and Theory.

Diagnostic classification models (DCMs) have seen wide applications in educational and psychological measurement, especially in formative assessment. DCMs in the presence of testlets have been studied in recent literature. A key ingredient in the statistical modeling and analysis of testlet-based DCMs is the superposition of two latent structures, the attribute profile and the testlet effect. This paper extends the standard testlet DINA (T-DINA) model to accommodate the potential correlation between the two latent structures. Model identifiability is studied and a set of sufficient conditions are proposed. As a byproduct, the identifiability of the standard T-DINA is also established. The proposed model is applied to a dataset from the 2015 Programme for International Student Assessment. Comparisons are made with DINA and T-DINA, showing that there is substantial improvement in terms of the goodness of fit. Simulations are conducted to assess the performance of the new method under various settings.

A feature refinement and adaptive generative adversarial network for thermal infrared image colorization.

Colorizing thermal infrared images poses a significant challenge as current methods struggle with issues such as unrealistic color saturation and limited texture. To address these challenges, we propose the Feature Refinement and Adaptive Generative Adversarial Network (FRAGAN). Our approach enhances the detailed, semantic, and contextual capabilities of image coloring by combining multi-level interactions that integrate the lost detailed information from the encoding stage with the semantic information from the decoding stage. Additionally, we introduce the Residual Feature Refinement Module (RFRM) to improve both the accuracy and generalization ability of the model, thereby elevating the quality of colorization results. The Feature Adaptation Module (FAM) is employed to mitigate sub-region information loss during downsampling. Furthermore, we introduce the Trinity Attention Module (TAM) to accurately capture the spatial and channel-wise interaction features of local semantic information. Extensive experimentation on the KAIST dataset and the FLIR dataset demonstrates the superiority of our proposed FRAGAN methodology, surpassing both the performance metrics and visual quality of current state-of-the-art methods. The colorized images generated by our proposed FRAGAN exhibit enhanced clarity and realism. Our code and models are available at GitHub.

A novel top-down strategy for in situ construction of vertically oriented hexagonal NiCr LDHs nanosheet arrays with intercalated sulfate ions on Nichrome fiber for selective solid-phase microextraction of phenolic compounds in water samples.

BACKGROUND: Phenolic compounds (PCs) are a class of polar aromatic pollutants with high toxicity in environmental water. Generally the efficient sample preparation is essential for the quantification of ultra-trace target PCs in real water sample before appropriative instrumental analysis. SPME is a convenient, solvent-free and time-saving miniaturized technique and has been recognized as a green alternative to conventional extraction techniques. In SPME, however, commercial fused-silica fibers are limited to the fragility, operation temperature, extraction capacity and selectivity as well as lifetime. Therefore, the development of new SPME fibers is always needed to overcome such limitations. RESULTS: We presented a novel top-down strategy for in situ construction of vertically oriented hexagonal sulfate intercalated NiCr layered double hydroxide nanosheet arrays (NiCr LDHs-SO4 NSAs) on the Nichrome (NiCr) substrate by hydrothermal treatment in NaOH solution containing (NH4)2S2O8. The results showed that much shorter hydrothermal time was needed for the construction of NiCr@NiCr LDHs-SO4 NSAs fiber in the presence of (NH4)2S2O8. Moreover, the unique NiCr LDHs-SO4 NSAs coating offered open access structure, and thereby more available surface area for adsorption. The resulting fiber exhibited better extraction efficiency for phenolic compounds (PCs), faster mass transfer rate, higher mechanical stability, and longer service life than original NiCr@NiCr LDHs NSs fiber and typical commercially fused-silica fibers. After optimizing conditions, the SPME-HPLC-UV method demonstrated a linear range from 0.05 µg L-1 to 200 µg L-1 with LODs of 0.015-0.156 µg L-1 (S/N = 3) and LOQs of 0.048-0.498 µg L-1 (S/N = 10), as well as good repeatability (3.06%-5.22%) and fiber-to-fiber reproducibility (4.32%-6.49%). SIGNIFICANCE: The developed SPME-HPLC-UV method with the constructed fiber was applied to the preconcentration and detection of different types of PCs in real water samples, showing satisfactory recoveries ranging from 86.20% to 107.8% with RSDs of 3.18%-6.69%. This study provides a new strategy for in situ construction of bimetallic hydroxides and their derived nanocomposite coatings on the NiCr fiber substrate in practical SPME application.

Ultrasound-assisted rapid growth of chemically bonded bifunctional mesoporous covalent organic framework submicrospheres on a nickel-chromium alloy support for efficient solid-phase microextraction of bisphenols from water and milk samples.

A layer-by-layer chemical bonding strategy was developed for fast in situ growth of bifunctional mesoporous covalent organic framework submicrospheres (COF SMSs) on the nickel-chromium alloy (Ni-Cr) fiber substrate via the ultrasound-assisted Schiff-base reaction for the first time. COF SMSs showed well-defined morphology, extraordinary high surface area (1211 m2·g-1) and narrow mesopore (2.50 nm) as well as excellent stability. Furthermore, the resulting Ni-Cr fiber presented outstanding adsorption capability and improved selectivity for bisphenols (BPs). Consequently, an attractive SPME-HPLC-UV approach with the Ni-Cr@Ni-Cr LDHs NSs@COF SMSs fiber was proposed for rapid preconcentration and sensitive determination of BPs. By optimizing adsorption parameters, the SPME-HPLC-UV method presented good linearity for five BPs in the ranges of 0.02-200 ng·mL-1 with coefficients of determination (R2) higher than 0.999. Limits of detection and limits of quantitation were obtained from 0.003 ng·mL-1 to 0.006 ng·mL-1 and from 0.010 to 0.019 ng·mL-1, respectively. Moreover, the intra-day and inter-day precision expressed as relative standard deviations (RSDs) was 1.57-3.52 % and 2.65-4.38 % for the proposed method with a single fiber, respectively. RSDs of the proposed method with different duplicate fibers were 3.25-6.72 %. The proposed SPME-HPLC-UV method was available for efficient preconcentration and sensitive detection of five BPs from real water and milk samples. The relative recoveries at three spiking levels of BPs were achieved in the range of 80.00-118.8 % with RSDs below 7.81 %. In addition, the prepared fiber still exhibited satisfactory adsorption performance after 120 adsorption-desorption cycles.

Population-Based Influenza Vaccine Effectiveness Against Laboratory-Confirmed Influenza Infection in Southern China, 2023-2024 Season.

Background: In China, the 2022-2023 influenza season began earlier and was characterized by higher levels of influenza activity and co-circulation of various respiratory pathogens compared with seasons before the coronavirus disease 2019 (COVID-19) pandemic. Timely and precise estimates of influenza vaccine effectiveness (IVE) against infections can be used to guide public health measures. Methods: A test-negative study was conducted to estimate IVE against laboratory-confirmed influenza using data from the CHinese Electronic health Records Research in Yinzhou (CHERRY) study that prospectively integrated laboratory, vaccination, and health administrative data in Yinzhou, southern China. We included patients who presented influenza-like illness and received nucleic acid tests and/or antigen tests between October 2023 and March 2024. Estimates of IVE were adjusted for age, gender, month of specimen submitted, chronic comorbidities, and hospitalization status. Results: A total of 205 028 participants, including 96 298 influenza cases (7.6% vaccinated) and 108 730 influenza-negative controls (13.4% vaccinated), were eligible for this analysis. The estimates of IVE were 49.4% (95% CI, 47.8%-50.9%), 41.9% (95% CI, 39.8%-44.0%), and 59.9% (95% CI, 57.9%-61.9%) against overall influenza, influenza A, and influenza B, respectively. A lower IVE was observed for individuals aged 7-17 years (38.6%), vs 45.8% for 6 months-6 years, 46.7% for 18-64 years, and 46.1% for ≥65 years. Vaccination reduced the risk of infection by 44.4% among patients with chronic comorbidities. IVEs varied by epidemic weeks with the changes in influenza activity levels and the switch of dominant influenza strains. Conclusions: Influenza vaccination in the 2023-2024 season was protective against infection for the entire population.

Real-world effectiveness of seasonal influenza vaccination and age as effect modifier: A systematic review, meta-analysis and meta-regression of test-negative design studies.

BACKGROUND: Under the global risk of epidemic rebound of influenza after COVID-19 outbreak, the study aimed to provide a comprehensive evaluation of the seasonal influenza vaccine effectiveness (IVE) and to explore the potential effect modifiers. METHODS: We searched for test-negative design studies with IVE estimates published between January 1, 2017 and December 31, 2022. We estimated pooled IVE using random-effects meta-analysis, and conducted meta-regression with study site, age, sex and comorbidity as explanatory variables. RESULTS: We identified 2429 publications and included 191 in the meta-analysis. The pooled IVE was 41.4 % (95 % CI: 39.2-43.5 %) against any influenza. For specific strains, the IVE was 55.4 % (95 % CI: 52.7-58.1 %) against A/H1N1, 26.8 % (95 % CI: 23.5-29.9 %) against A/H3N2, 47.2 % (95 % CI: 38.1-54.9 %) against B/Yamagata, and 40.6 % (95 % CI: 23.7-53.7 %) against B/Victoria, and the effectiveness against A/H3N2 was significantly lower than A/H1N1 (p < 0.0001) and B/Yamagata (p < 0.0001). The pooled IVE was 39.2 % (95 % CI: 36.5-41.9 %) in preventing influenza-associated outpatient visit and 43.7 % (95 % CI: 39.7-47.4 %) in preventing influenza-related hospitalization. The IVE against any influenza was 48.6 % (95 % CI: 44.7-52.2 %) for children aged < 18 years, 36.7 % (95 % CI: 31.9-41.1 %) for adults aged 18-64 years, and 30.6 % (95 % CI: 26.2-34.8 %) for elderly aged ≥65 years. Meta-regression revealed that the IVE was associated with the average age of study participants, in which both young adults [relative odds ratio (ROR) = 1.225, 95 % confidence interval (CI): 1.099-1.365, p = 0.0002] and elderly (ROR = 1.245, 95 % CI: 1.083-1.431, p = 0.002) manifested a significantly decreased effectiveness compared with children. CONCLUSIONS: Influenza vaccines provided moderate protection against laboratory-confirmed influenza and related outpatient visit and hospitalization. However, the effectiveness may vary substantially by virus type and age group, suggesting the necessity to tailor vaccination strategies especially for older individuals and against the A/H3N2 strain, and to promote annual immunization and annual analysis of vaccine effectiveness.