ObjectiveThe malaria parasites remodel the host erythrocyte structure by exporting parasite proteins that interact with the membrane skeleton proteins of red blood cells (RBCs), facilitating their intracellular survival and pathogenicity. Skeleton-binding protein 1 (SBP1) is a conserved exported protein across Plasmodium species. In Plasmodium falciparum, SBP1 has been reported to interact with erythrocyte membrane skeleton proteins 4.1R and spectrin, while its contribution to erythrocyte remodeling and parasite virulence in Plasmodium berghei (Pb) remains unclear. This study aims to determine whether PbSBP1 associates with the host cytoskeletal protein 4.1R and to investigate its role in the remodeling of host RBCs and the pathogenicity of Plasmodium berghei. MethodsIn Plasmodium berghei, the relationship between PbSBP1 and the erythrocyte cytoskeletal protein 4.1R was examined using co-immunoprecipitation. A Pbsbp1 gene knockout mutant of Plasmodium berghei (Pbsbp1∆) was generated based on the principle of double crossover homologous recombination. The deformability of erythrocytes infected with Pbsbp1∆ parasites was assessed using microfluidic methods. Microchannels with an array of cylindrical pillars were used to detect modifications in infected RBC deformability. The infected RBCs were squashed between the rows and recovered between the columns and the transit velocity (μm/s) of infected RBCs travelling through the microchannel was recorded. The component of the erythrocyte membrane skeleton junctional complex, tropomodulin (TMOD), was fluorescently labeled, and the cytoskeletal network of infected erythrocytes was imaged using super-resolution stochastic optical reconstruction microscopy (STORM) to analyze ultrastructural changes in the cytoskeleton of wild-type (WT) and Pbsbp1∆-infected erythrocytes. Actin-based junctional complexes were displayed as individual clusters by the labeled TMOD in the STORM images, and the cluster densities and distances between adjacent clusters of infected RBCs were calculated. Additionally, rodent malaria models (BALB/c mice) and experimental cerebral malaria models (C57BL/6 mice) were employed to monitor the growth of Pbsbp1∆ and WT parasites during the intraerythrocytic stage and their capacity to induce cerebral malaria in mice. ResultsPbSBP1 may participate in the remodeling of infected erythrocytes through direct or indirect interaction with the erythrocyte cytoskeletal protein 4.1R. Microfluidic assays revealed that the deformability of erythrocytes infected with Pbsbp1∆ parasites was significantly enhanced compared to those infected with WT parasites. STORM imaging further demonstrated that the ultrastructure of the erythrocyte cytoskeleton in Pbsbp1∆-infected cells was altered relative to that in WT-infected erythrocytes. The distances between nearest neighbors of clusters had a tendency to increase while the cluster densities were decreased in Pbsbp1∆-infected RBCs compared to WT-infected RBCs. Subsequent phenotypic analysis indicated that the growth rate of Pbsbp1∆ parasites during the intraerythrocytic stage was significantly slower than that of WT parasites, and their ability to induce cerebral malaria in mice was also attenuated. These findings suggest that PbSBP1 is involved in the remodeling of the erythrocyte membrane skeleton, likely through its direct or indirect interaction with protein 4.1R, thereby regulating the deformability of infected erythrocytes and influencing the pathogenicity of the blood-stage parasites. ConclusionThis study establishes a role for PbSBP1 in host erythrocyte remodeling and parasite virulence, providing new research strategies for the prevention and treatment of malaria.

Objectives: . Idiopathic sudden sensorineural hearing loss (ISSNHL) is a significant cause of hearing loss. Intratympanic steroid injection (ITSI) is commonly used as an initial or salvage treatment; however, the lack of a standardized treatment protocol has resulted in variability in clinical practice. In addition, no efficient prediction model currently exists to support personalized management. Therefore, this study aimed to develop tailored management strategies for ISSNHL using a machine-learning model. Methods: . This retrospective multicenter cohort study was conducted between January 2015 and December 2020, with data analysis performed between January 2021 and March 2024. Patients were selected based on the International Classification of Diseases, 10th Revision criteria for ISSNHL, along with relevant medication and procedure codes. Patients with pure-tone audiogram results not meeting ISSNHL criteria, better initial hearing in the affected ear, an identifiable etiology, no post-treatment audiogram, or delayed treatment (>6 weeks) were excluded. We included 770 patients diagnosed with ISSNHL who received ITSI. The primary outcome was the area under the receiver operating characteristic curve for prediction performance. Recovery status was determined using the last pure-tone audiogram. Modeling was conducted on the Quanta for Medical Care AI platform using five machine-learning algorithms and a nested cross-validation framework, in which feature selection and hyperparameter tuning were performed in the inner folds and model performance was evaluated in the outer folds. Results: . A random forest classifier outperformed the other models in predicting hearing outcomes, achieving an area under the receiver operating characteristic curve of 0.788. Time to ITSI was the most influential treatment-related factor, with ITSI administered within 10 days of hearing loss being associated with better outcomes. This model can be used to provide personalized prognostic estimates under different treatment protocols. Conclusion . The machine-learning-based prediction model facilitates personalized treatment strategies and timely treatment adjustments for ISSNHL, thereby optimizing the likelihood of complete recovery.

Processed electroencephalogram (EEG) indices, such as the Bispectral Index, have markedly influenced anesthesia practice as they translate brain activity into simple numerical indices. Nevertheless, as the manufacturing algorithms are not disclosed, the underlying neurophysiology remains obscured. Additionally, these indices are often affected by electromyographic contamination, pharmacological variability, and patient-specific EEG heterogeneity. In contrast, an EEG spectrogram, or density spectral array, preserves the frequency- and time-resolved structures of cortical oscillations. This information is presented in a form that is both physiologically meaningful and clinically interpretable. In this review, we trace the evolution of anesthesia from an index-based to a spectrogram-guided approach, and summarize the clinical rationale for adopting the latter. Key applications of this approach include the use of frontal alpha power as a biomarker of cortical stability and postoperative brain health, the identification of nociceptive arousal through alpha dropout and beta or delta arousal patterns, and individualized titration of multimodal or age-specific anesthetic management. Although current devices lack standardized quantitative alpha metrics and have limited sensitivity for low-frequency brain wave components, structured EEG education programs have proven to be effective in terms of fostering spectrogram literacy among anesthesiologists. By combining neurophysiological precision with bedside practicality, the EEG spectrogram represents a pivotal advance toward individualized, mechanism-based, and brain-protective anesthesia, transforming anesthetic monitoring from mere algorithmic abstraction to cortical insight.

ObjectiveThis study aimed to elucidate the mechanistic role of Staphylococcus aureus in the pathogenesis of atopic dermatitis (AD), a chronic inflammatory skin disorder characterized by pruritus and barrier dysfunction. A key focus was screening traditional Chinese medicine (TCM) active components with dual antibacterial and antipruritic efficacy, followed by systematic evaluation of their in vitro antibacterial activity. Additionally, a novel drug delivery system was constructed to enable localized efficient drug delivery, inhibiting S. aureus proliferation and alleviating its induced pruritus, thereby providing new strategies for targeted AD therapy. MethodsMale C57BL/6J mice aged 6-8 weeks (body weight 18-22 g) were used to establish an AD model via repeated oxazolone sensitization. On day 14, microbial samples were collected from the lesional area (1 cm²) using sterile cotton swabs, followed by vortex mixing, serial dilution, and plating on 5% sheep blood agar plates (incubated at 37°C for 24 h). Single colonies with complete transparent β-hemolytic zones were isolated and identified as vancomycin-intermediate S. aureus (VISA) via 16S rRNA sequencing. An S. aureus mono-infection animal model was then established by applying gauze saturated with bacterial suspension (McFarland turbidity 0.1) to the nape and back skin of mice. The pruritic phenotype and inflammatory cell infiltration induced by S. aureus were evaluated using comprehensive approaches including behavioral assays (e.g., scratching frequency recording), hematoxylin-eosin (HE) staining, and toluidine blue staining. The in vitro antibacterial efficacy of the TCM monomer pseudolaric acid B (PAB) and double network hydrogel (DN) was separately assessed by disk diffusion assay, while the minimum inhibitory concentration (MIC) of PAB was determined via broth dilution method. Further validation of the pharmacodynamic characteristics of the composite system (PAB@DN, composed of PAB and DN) was conducted through behavioral assays, HE staining, and dermatitis scoring, with its drug release profile evaluated by mass spectrometry analysis. Based on scratching behavioral analysis and dermatitis scoring, the optimal ratio and concentration of PAB@DN were optimized. ResultsThe S. aureus load in AD lesional tissues was significantly higher than in normal skin ((5.3±0.33)×10⁶ CFU vs. (3.6±0.26)×10⁷ CFU, P<0.001). In the S. aureus mono-infection group, mice exhibited a 6.7-fold increase in scratching frequency compared to the control group. HE staining revealed marked epidermal thickening ((10.4±2.39) μm vs. (85.6±1.95) μm, P<0.000 1), and toluidine blue staining showed a 23-fold increase in mast cell degranulation. Pseudolaric acid B exhibited a significant concentration-dependent inhibitory effect onS. aureus growth, with its in vitro antibacterial effect being 57% that of the antibiotic cefepime (inhibition zone diameter: PAB (1.885±0.036) cm vs. cefepime (3.636±0.005) cm, P<0.000 1) and a minimum inhibitory concentration (MIC) of 1 g/L. The carrier double network hydrogel (DN) itself lacked direct antibacterial activity (no significant difference in inhibition zone diameter compared to the control) but effectively ameliorated the dry symptoms of AD-like lesions. The PAB@DN composite system demonstrated a synergistic effect compared to individual components, resulting in a 50% reduction in scratching behavior, an 86% decrease in dermatitis score, and a 60% reduction in epidermal thickening. It also reduced the S. aureus load in mouse skin by approximately 34%, with the optimal effective formulation being PAB at 1 g/L loaded onto DN. ConclusionS. aureus colonization plays a critical driving role in the onset and progression of AD. Using an S. aureus infection model, this study confirmed that the pseudolaric acidB-hydrogel composite delivery system (PAB@DN) can effectively alleviate S. aureus-induced pruritus and skin damage, providing experimental evidence for microbiota-targeted therapy of AD.

ObjectiveThe present study aimed to investigate alterations in white matter microstructure and spontaneous neural activity in male college smokers, and to further explore their associations with nicotine dependence. Given that adolescence and early adulthood represent critical periods for brain maturation, particularly for white matter development, understanding the neural correlates of smoking behavior during this stage is of substantial importance for both neuroscience and public health. MethodsA total of 115 male undergraduate students were initially recruited for this study. After quality control and exclusion procedures, 52 male college smokers and 42 demographically matched healthy non-smokers were included in the final analysis. All participants underwent multimodal magnetic resonance imaging (MRI), including diffusion tensor imaging (DTI) and resting-state functional MRI (rs-fMRI). White matter fiber tracts were reconstructed using the automated fiber quantification (AFQ) method, which enables precise identification and quantification of major fiber bundles. Eighteen major white matter tracts were segmented for each participant. Along the core trajectory of each tract, 100 equidistant nodes were sampled. Fractional anisotropy (FA) was calculated at each node to assess white matter microstructural integrity, while amplitude of low-frequency fluctuation (ALFF) was computed to evaluate spontaneous neural activity within white matter tracts. Between-group differences in FA and ALFF were assessed using two-sample t-tests, with appropriate corrections applied for multiple comparisons. Furthermore, Pearson correlation analyses were conducted to examine the relationships between imaging-derived metrics (FA and ALFF values in regions showing significant group differences) and nicotine dependence severity, as measured by the Fagerström test for nicotine dependence (FTND). ResultsCompared with healthy non-smokers, male college smokers exhibited significantly increased FA values in several white matter tracts, including the left thalamic radiation, right corticospinal tract, forceps major of the corpus callosum, left uncinate fasciculus, and right arcuate fasciculus. These findings suggest altered microstructural organization or increased directional coherence within these pathways. In addition, smokers demonstrated significantly elevated ALFF values in the forceps major, right uncinate fasciculus, and left arcuate fasciculus, indicating enhanced spontaneous neural activity in these white matter regions. Correlation analyses revealed that FA values in the left thalamic radiation and right corticospinal tract were negatively correlated with FTND scores, suggesting that higher levels of nicotine dependence were associated with reduced microstructural integrity or altered fiber organization in these regions. In contrast, ALFF values in the forceps major and right uncinate fasciculus were positively correlated with FTND scores, indicating that greater nicotine dependence was associated with increased spontaneous neural activity in specific white matter pathways. ConclusionThe present study provides evidence that male college smokers exhibit distinct alterations in both white matter microstructure and functional activity. These abnormalities are not uniformly distributed but rather localized to specific fiber tracts implicated in sensorimotor processing, interhemispheric communication, and higher-order cognitive and emotional regulation. Importantly, the observed associations between imaging metrics and nicotine dependence severity suggest that these structural and functional alterations may reflect neurobiological mechanisms underlying addiction. The combination of AFQ-based tract profiling and multimodal MRI offers a sensitive approach for detecting subtle changes along white matter pathways, highlighting its potential utility in identifying neuroimaging biomarkers of nicotine dependence. Overall, these findings indicate that smoking during early adulthood may disrupt ongoing white matter maturation, potentially leading to long-term consequences for brain function. This study provides novel insights into the neural basis of nicotine dependence and underscores the importance of early intervention and prevention strategies targeting young smokers.

Objective This study reports on the obligatory parasitism of water mites Arrenurus sp. on Anopheles messeae at the Manzhouli Port, Inner Mongolia, China. Methods Duing July 2024, a survey on the mosquito diversity was conducted at the Manzhouli Port. Captured mosquitoes and their ectoparasites were identified to species level. Results A total of 1840 adult mosquitoes were collected, representing species from three genera: Culex(Cx. modestus, Cx. pipiens pallens), Aedes(Ae. dorsalis, Ae. flavidorsalis, Ae. flavescens), and Anopheles (An. messeae). Among all the mosqutioes specimens,3 out of 150 captured An. messeae were found to carry ectoparasitic mites, with number of 2,4,27 mites separately. Morphological and molecular identification reached the same result as water mites(Hydrachnidiae, Hydracrina). COI gene sequence showed 94% similarity with the closest species Arrenurus truncatellus. Conlusions Literature review suggests water mites are host-specific parasitism of mosquito species and herein with the first record of Arrenurus sp. parasiting on An. Messeae in the most high-latitude region globally.

Objective To understand the epidemiological characteristics and trends of postoperative pneumonia(POP)in tertiary general hospitals in Jiangsu Province,and provide theoretical basis for carrying out targeted pre-vention and control measures.Methods Surgery patients from 22 tertiary general hospitals in 12 cities in north,central,and south of Jiangsu Province from January 1,2022 to December 31,2023 were chosen as studied subjects,occurrence of POP was analyzed and compared.Results A total of 848 274 surgical procedures were performed in 22 hospitals,and 3 606 cases of POP occurred,with an incidence of 0.43％.The incidence in 2023 was 0.37％,which was lower than that in 2022(0.49％),with statistically significant difference(P＜0.001).The top three de-partments with high incidence of POP were neurosurgery(6.71％),cardiothoracic surgery(2.91％),and general surgery(0.77％).Among hospitals of different grades,the incidence of POP in tertiary first-class hospitals was 0.44％,which was higher than that in other tertiary hospitals(0.37％).There was no statistically significant difference in the incidence of POP between municipal and district/county hospitals(P＞0.05).The incidence of POP in hospitals with a bed:infection control full-time staff ratio＜200∶1 was lower than that in hospitals with the ratio ≥200∶1(0.39％vs 0.47％,P＜0.001),while the incidence of POP in hospitals with a proportion ≥30％of full-time staff being doctors was higher than that in hospitals with a proportion＜30％(0.45％vs 0.36％,P＜0.001).The incidence of POP in male patients was higher than that in female patients(0.62％vs 0.26％,P＜0.001).The incidence of POP in elderly patients aged≥65 was higher than that in patients aged＜65(0.73％vs 0.26％,P＜0.001).A total of 2 667 strains of infectious pathogens were detected,with the top three being Acine-tobacter baumannii,Klebsiella pneumoniae,and Pseudomonas aeruginosa,accounting for 28.95％,22.72％,and 15.45％,respectively.The detection rates of carbapenem-resistant Acinetobacter baumannii(CRAB),carba-penem-resistant Klebsiella pneumoniae(CRKP),and carbapenem-resistant Pseudomonas aeruginosa(CRPA)were 60.75％,21.45％,and 32.28％,respectively.The detection rate of CRKP decreased in 2023 compared with 2022,with statistically significant difference(P＜0.05).Conclusion The overall incidence of POP in tertiary general hos-pitals in Jiangsu Province is relatively low,but there are significant differences among different hospitals.There-fore,perioperative prevention and control measures should be carried out based on the epidemiological characteristics of patients.

A recombinant adenovirus(rAd)for expression of Mycobacterium tuberculosis(M.tb)c-di-AMP phosphodiesterase CnpB was constructed,and its induced humoral immune response was detected.The codon-optimized gene of M.tb CnpB was cloned into the adenoviral plasmid pcADV.The recombinant plasmid pcADV-CnpB was transfected into HEK293T cells,and expression was detected with Western blot.The recombinant plasmid pcADV-CnpB and the backbone plasmid were co-transfected into HEK293T cells to obtain the recombinant adenovirus rAd-CnpB.rAd-CnpB was amplified in HEK293T cells,and the target protein expression of rAd-CnpB was detected with Western blot and immunofluorescence.Mice were immunized with rAd-CnpB intranasally,and their sera and bronchoalveolar lavage fluid(BALF)were collected.ELISA was used to detect levels of antigen-specific antibodies.Restriction enzyme digestion and sequencing indicated that the recombinant plasmid pcADV-CnpB was successfully constructed and led to protein expression in eukaryotic cells.rAd-CnpB was packaged and produced in HEK293T cells.After amplification and purification,rAd-CnpB with a titer of 5.53×1010 PFU/mL was obtained.rAd-CnpB led to CnpB expression in HEK293T cells.Intranasal immunization with rAd-CnpB increased levels of IgG and secretory IgA in BALF and led to high levels of IgG in sera.rAd-CnpB,the recombinant adenovirus for expression of c-di-AMP phosphodiesterase CnpB was successfully constructed,and was found to induce antigen-specific humoral and mucosal immune responses through mucosal immunization.Thus,rAd-CnpB may be used in further research on new TB vaccine strategies.

To understand the epidemiological and clinical features of patients with non-tuberculous mycobacteria(NTM)lung disease in a hospital for infectious diseases in Xinjiang,and to provide basis for prevention and control of NTM in Xinjiang.The strain distribution,epidemiological features and clinical features of 78 patients with NTM lung disease in the Sixth People′s Hospital of Xinji-ang Uygur Autonomous Region were analysed from June 2021 to June 2024,and a comparative analysis of the clinical features of 156 patients with pulmonary tuberculosis in this hospital during the same period was performed.Among 78 patients with NTM lung disease,the bacteria identified by molecular biology accounted for the top three cases:24 cases of Mycobacterium avium intracellulare complex,16 cases of Mycobacterium Kansaii and 11 cases of Mycobacterium Gordonae.There was no statistically significant difference in gender(χ2=0.009),age(χ2=2.670),smoking history(χ2=0.064),and BMI(χ2=0.896)between the NTM lung disease group and the pulmonary tuberculosis group(P>0.05).However,there were statistically significant differences in the combined bronchiectasis(χ2=19.068),immune-related indicators CD4(Z=-3.498)and CD3(Z=-3.187),and chest CT cavities on imaging(χ2=9.308)be-tween the two groups(P<0.05).There was no statistically significant difference in clinical symptoms such as cough(χ2=0.188)and expectoration(χ2=0.044)between the two groups(P>0.05).The common underlying diseases of NTM lung disease were diabetes mellitus(23.08%),hypertension(21.79%),bronchiectasis(20.51%)and others.The common clinical symptoms of NTM lung disease include cough,sputum,fatigue,poor appetite and others.The common manifestations of chest CT in NTM lung disease were Patchy cord shadows(62.82%),nodule(51.28%),pleural thickening(46.15%),calcification(41.03%)and others.Multivariate Logistic regression analysis showed that bronchiectasis(OR=8.019)is risk factor for NTM lung disease.The dominant strains of NTM in this study were My-cobacterium avium intracellulare complex,Mycobacterium kansasii and Mycobacterium Gordonae.NTM lung disease and pulmonarytuber-culosis have similar clinical manifestations and are difficult to distinguish,especially for patients with bronchiectasis,it is necessary to actively investigate NTM lung disease,provide basis for early diagnosis and treatment of NTM lung disease,and gradually form a system-atic and standardized NTM lung disease diagnosis and treatment system according to local conditions.

To study the epidemiological characteristics of dengue fever(DF)cases and the molecular characteristics of local dengue virus(DENV)in Fujian from 2019 to 2022,and provide evidence for the prevention and control of DF.Statistically analyzed the demographic and epidemiological characteristics of imported and local DF cases.The locally prevalent strains from various regions and some imported strains were sequenced to analyze homology and construct phylogenetic trees by using software MEGA(version 6.0).A total of 1 661 DF cases,including 699 imported cases and 962 local cases were reported in Fujian from 2019 to 2022.The imported cases were mainly concentrated from June to October,whereas the local cases were mainly concentrated from August to October.All 10 cities in Fujian had imported cases reported,and local cases had been reported in all regions except Longyan.The male to female ratio in the imported cases(4.07∶1)was higher than that in the local cases(0.95∶1),and the median age of the imported cases(43 years old)was lower than that of the local cases(46 years old).The imported cases mainly came from Cambodia locally prevalent strains of DENV1 all belonged to genotypeⅠ,which may originate from other provinces or Southeast Asian countries such as Cambodia.The first locally prevalent cases of DENV4 were found in Putian,and the phylogenetic trees of DENV4 E gene showed that the locally prevalent strains of DENV4 in Putian were genotypeⅡ,which may originate from Singapore.They face a high risk of local DF outbreaks caused by imported DF cases,and the local epidemic areas appear a certain degree of spreading trend.It is necessary to strengthen the multi-sectoral cooperation and improve supervision systems.Timely discovery and tracing of cases to provide a basis for scientific prevention and control of DF.