Objective To investigate the temporal changes in pathological damage and macrophage polarization in liver and spleen tissues of mice infected with Angiostrongylus cantonensis, and to preliminarily unravel the peripheral immune responses during the early stage of A. cantonensis infection. Methods Forty female BALB/c mice at ages of 6 to 8 weeks were randomly divided into four groups, including the control group and 7-, 14-, and 21-day infection groups, with 10 mice in each group. Each mouse in the infection groups was inoculated with 30 third-stage (L3) larvae of A. cantonensis by oral gavage, and five mice were randomly selected from each infection group on days 7, 14, and 21 post-infection, while mice in the control group were given the same volume of physiological saline and five mice were randomly selected from the control group on the day of oral gavage. Mouse liver and spleen tissues were sampled. The histopathological changes of mouse liver and spleen tissues were observed using hematoxylin and eosin (HE) staining, and the percentage of positive staining area and the co-localization positive rates of the macrophage surface antigens F4/80, CD86, and CD206 were quantified in mouse liver and spleen tissues using immunohistochemical and immunofluorescence staining. In addition, five mice were collected from each infection group on days 7, 14, and 21 post-infection, and five mice were collected from the control group on the day of oral gavage. Mouse liver and spleen tissues were sampled for detection of macrophage markers CD86 and CD206 and macrophage phenotyping using flow cytometry, and the expression of M1 macrophage markers, including inducible nitric oxide synthase (Nos2), tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β) and M2 markers, including arginase 1 (Arg1), mannose receptor C-type 1 (Mrc1) and chitinase-like protein 3 (Chil3) was quantified in mouse liver and spleen tissues using real-time quantitative PCR (RT-qPCR) assay. Results Proliferative lesions of the hepatocyte were observed in mouse liver tissues and the follicular structures of the mouse spleen white pulp were disrupted 21 days post-infection with A. cantonensis. Immunohistochemical staining showed that there were significant differences in the percentages of F4/80, CD86 and CD206 positive staining areas in the liver and spleen tissues among the four groups of mice (F = 242.40, 197.14, 183.19, 157.65, 242.35 and 146.24; all P values < 0.001), and the percentages of positive staining in the liver and spleen tissues of mice in the 14-day infection group [(4.45 ± 0.51)%, (3.74 ± 0.67)%, (8.32 ± 0.72)%, (16.56 ± 1.14)%, (11.62 ± 0.52)%, and (8.29 ± 0.72)%, respectively] and the 21-day infection group [(3.70 ± 0.11)%, (3.22 ± 0.43)%, (11.53 ± 1.03)%, (12.59 ± 1.05)%, (9.02 ± 0.83)%, and (11.67 ± 1.10)%, respectively] were higher than in the control group [(0.35 ± 0.16)%, (0.40 ± 0.02)%, (0.93 ± 0.05)%, (2.78 ± 0.26)%, (2.33 ± 0.20)%, and (1.85 ± 0.20)%, respectively] (all P values < 0.05). Immunofluorescence staining showed significant differences in the positive rates of F4/80 co-localization with CD86 and CD206 in mouse liver and spleen tissues among the four groups (F = 24.42, 25.28, 54.51 and 130.55; all P values < 0.001). Flow cytometry detected significant differences in the proportions of CD86⁺ and CD206⁺ macrophages in mouse liver and spleen tissues among the four groups (F = 67.98, 18.41, 29.77, 172.80; all P values < 0.001), and the proportions of CD206⁺ macrophages in the liver and spleen of the 21-day infection group were significantly higher than those in the control group [(9.25 ± 2.55)% vs (3.83 ± 0.72)%, and (4.22 ± 0.56)% vs (0.47 ± 0.18)%, respectively] (both P values < 0.05). In addition, RT-qPCR assay quantified significant differences in the relative mRNA expression of M1 macrophage markers (IL-1β, TNF-α and Nos2) and M2 macrophage markers (Arg1, Chil3 and Mrc1) in mouse liver and spleen tissues among the four groups (F = 41.30, 31.82, 199.33, 19.96, 62.01, 119.76, 23.67, 95.90, 72.27, 82.59, 123.41 and 29.75; all P values < 0.05). Conclusions A. cantonensis infection may cause progressive pathological damage in mouse liver and spleen tissues, accompanied by dynamic temporal changes in macrophage polarization. M1 macrophage polarization predominates at the early stage of A. cantonensis infection and shifts towards M2 polarization at the later stages, suggesting that M2 polarization may participate in immune regulation at late stages of A. cantonensis infection by suppressing excessive inflammatory responses and promoting tissue repair.

Objectives: . This study aimed to investigate the regulatory functions of gamma-aminobutyric acid (GABA)ergic neural circuits from the inferior colliculus (IC) to the medial geniculate body (MGB) in salicylate-induced tinnitus. Methods: . Mice were treated with salicylate to induce tinnitus, and tinnitus-like behaviors were evaluated via gap prepulse inhibition of acoustic startle. Using combined viral tracing methodologies, we identified and mapped the pathways and connections from the IC to the MGB. Furthermore, we employed Gq-coupled human M3 designer receptors exclusively activated by designer drugs (DREADDs) and Gi-coupled human M4 DREADDs to achieve targeted excitation or suppression of GABAergic neurons in the IC and MGB. Following the administration of clozapine N-oxide, which binds to these receptors, we modulated these neural circuits to assess their impact on tinnitus severity in a mouse model. Results: . Our findings demonstrated that mice exposed to salicylate exhibited tinnitus-like behaviors. GABAergic neurons projecting retrogradely from the MGB to the IC were primarily concentrated in the external nucleus of the IC. After clozapine N-oxide administration, chemogenetic activation of IC-MGB GABAergic neurons aggravated salicylate-induced tinnitus. Additionally, activation of GABAergic neurons between the IC and MGB induced the perception of tinnitus even without salicylate. However, chemogenetic inhibition of the IC-MGB GABAergic circuit did not reverse salicylate-induced tinnitus. Conclusion . These findings suggest that activation of the IC-MGB GABAergic neural circuit may contribute to tinnitus generation through a mechanism distinct from that of salicylate-induced tinnitus. This study provides novel insights into the mechanisms underlying tinnitus.

Objective: To investigate the association between brain and muscle Arnt like protein 1( BMAL 1) gene and ambulatory blood pressure (ABP) parameters in college students, and to explore the influence of the interaction between the gene and weight status on the ABP levels, so as to provide reference for early prevention of chronic cardiovascular diseases related to hypertension. Methods: During September 2022 to June 2024, a total of 510 college students were recruited from a university in Changsha, China for on site questionnaire investigation, physical examination, ABP monitoring and genotyping testing. Multiple linear regression method was used to explore the association between the BMAL 1 gene and ABP indicators. An interaction term was included in the general linear model of multiple linear regression to analyze the interactive effects of BMAL 1 gene polymorphisms and weight status on ABP levels. Results: The prevalence of abnormal 24 hour blood pressure, abnormal daytime blood pressure, and abnormal nighttime blood pressure were 3.3%, 3.1%, and 3.9%, respectively. Multiple linear regression analysis showed that the BMAL 1/rs7950226 polymorphism was positively correlated with the 24 hour diastolic blood pressure(DBP) and the daytime DBP level after adjusting for gender, age, and body mass index( β =0.87,0.99, both P <0.05). Also, interaction between BMAL 1/ rs 11022775 and weight status on the nighttime DBP level ( P interaction =0.03) was found. The CC genotype carriers had significantly higher nighttime DBP level ( β =3.52, P <0.05) among overweight/obesity college students, but no differences in nocturnal DBP levels were observed between CC genotype carriers and TT+CT genotype carriers among college students with normal body weight( P > 0.05). Conclusions The rs 7950226 polymorphism is associated with 24 hours DBP and daytime DBP levels. Significant interaction between rs 11022775 with weight status on the nighttime DBP level is found among college students.

Background Although hand-arm vibration syndrome has traditionally been reported more frequently in colder northern regions, recent cases in Guangdong Province, a subtropical region in the south, exhibit a certain degree of clustering in terms of industry distribution and company size, and for a period of time, they account for a high proportion of the total number of cases reported nationwide. Objective To describe the occupational exposure profile of hand-transmitted vibration (HTV) in Guangdong Province in 2025 and to compare exposure levels across industries, enterprise sizes, and occupational categories. Methods Data were sourced from the Guangdong Provincial Occupational Health Quality Control Platform, to which occupational health technical service institutions across Guangdong Province submitted relevant reports in 2025. The dataset included employers with documented HTV hazards, measurement results, and the number of exposed workers. Exposure levels were categorized into four grades according to the 4-h energy-equivalent frequency-weighted vibration acceleration: Grade I (<1 m·s⁻²), Grade II (1-2.5 m·s⁻²), Grade III (>2.5-5 m·s⁻²), and Grade IV (>5 m·s⁻²). Results A total of 12468 employers with identifiable HTV exposure were identified through the platform in 2025, of which 11710 (93.92%) were in the manufacturing sector. By enterprise scale, 274 (2.20%) were large, 934 (7.49%) were medium-sized, 8 749 (70.17%) were small, and 2511 (20.14%) were micro-sized enterprises, with small enterprises accounting for the largest proportion. Among 22298 job posts with identified HTV exposure, grinding, assembly, polishing, burnishing, and welding were the most common tasks. The M (P₂₅, P₇₅) 4-h energy-equivalent frequency-weighted acceleration [a(4)] was 2.1 (1.5, 2.7) m·s⁻², with values ranging from 0.1 to 16.2 m·s⁻². Exposure levels were distributed as follows: Grade I, 2835 posts (12.71%); Grade II, 12761 posts, (57.23%); Grade III, 6690 posts, (30.00%); and Grade IV, 12 posts (0.05%), with Grade Ⅱ posts accounting for the largest proportion. Within the manufacturing sector, 21013 exposed job posts were identified, accounting for 94.24% of all exposed posts. Twelve job posts exceeded the occupational exposure limit, of which nine were polishing positions. A total of 115955 workers were exposed to HTV, primarily in manufacturing (110879; 95.62%). Among the exposed workers, 21237, 23454, 65047, and 6217 were employed in large, medium, small, and micro-sized enterprises, respectively. Grinding, assembly, polishing, deburring, and welding were the five most common occupational categories among the exposed workers. The distribution of worker by exposure grade was similar to that of exposed posts: Grade I, 11921 workers (10.28%); Grade II, 65463 workers (56.46%); Grade III, 38447 workers (33.16%); and Grade IV, 124 workers (0.11%). Conclusion In Guangdong Province, HTV exposure is mainly concentrated in the manufacturing sector, particularly in metal product manufacturing, and commonly involves tasks such as grinding, assembly, and polishing. Both exposed enterprises and exposed workers are predominantly concentrated in small enterprises. Grade II exposure accounts for the largest proportion of both exposed job posts and exposed workers, and some workers are at a risk of developing hand-arm vibration syndrome. These findings suggest that targeted occupational management and comprehensive control measures should be strengthened to reduce HTV exposure and prevent hand-arm vibration syndrome.

Objective To enhance the mechanical properties of trichiral honeycomb sandwich structures and satisfy the design criteria for vertebral implant structures.Methods A chiral-like honeycomb sandwich structure with an auxiliary support structure was constructed for optimal design.The finite element method was used to study the influence of the auxiliary support structure on the chiral-like honeycomb sandwich structure and the relationship between the support position and mechanical property parameters.Furthermore,the influence of the deformation mechanism of different structures on mechanical properties was discussed.Results All chiral-like honeycomb sandwich structures exhibited enhanced mechanical properties in comparison to trichiral honeycomb sandwich structures.The mechanical properties of the chiral-like dCW honeycomb sandwich structure with the auxiliary support structure positioned perpendicular to the ligament were optimal,and this position represented the optimal support position.When the volume was used as a control variable,the compressive stiffness,stiffness-to-mass ratio,and transverse strain of the chiral-like honeycomb sandwich structure in the x1 direction were significantly correlated with the change of the support position,and all of them were positively correlated.Conclusions As a novel chiral-like honeycomb structure,it provides a biomechanical basis for the optimal design and clinical application of honeycomb sandwich structures as vertebral implant structures.

Objective:To investigate the effects of hip replacement on human β-defensin 3 (HBd-3) and N-arachidonoylethanolamine (AEA) levels in older adult patients with intertrochanteric femoral fractures.Methods:This study was a retrospective analysis. A total of 110 older adult patients with intertrochanteric femoral fractures who received treatment at Xi'an Labor Union Hospital from March 2021 to December 2023. Based on the different treatment methods, patients were assigned to either the hip replacement group ( n = 55, hip replacement) or the control group ( n = 55, intramedullary nail fixation). The operation time, postoperative bed rest duration, hospital stay, and weight-bearing time were recorded for both groups. The levels of malondialdehyde, aldosterone, tumor necrosis factor-alpha, HBd-3, AEA, and calcitonin gene-related peptide were measured before and 3 days after surgery. Behaviors were evaluated using the 6-point behavioral rating scale before and 14 days after surgery. Hip function was evaluated using the Mayo hip function score before and 3 months after surgery. Complications were recorded for both groups. Results:The operation time in the hip replacement group was significantly longer than that in the control group [(75.58 ± 7.19) minutes vs. (60.03 ± 5.75) minutes, t = -12.53, P < 0.001]. However, postoperative bed rest duration, hospital stay, and weight-bearing time in the hip replacement group were (8.35 ± 1.63) days, (13.18 ± 2.32) days, and (6.19 ± 1.51) days, respectively, which were significantly shorter than those in the control group [(16.28 ± 2.02) days, (15.65 ± 3.15) days, (42.21 ± 6.67) days, t = 22.68, 4.68, 39.06, all P < 0.001]. The levels of malondialdehyde and aldosterone in the hip replacement group were (14.89 ± 3.06) U/L and (37.80 ± 3.80) ng/L, respectively, which were significantly lower than those in the control group [(16.73 ± 3.42) U/L, (40.85 ± 4.24) ng/L, t = 2.97, 3.97, both P < 0.05]. Additionally, the levels of tumor necrosis factor-α and HBd-3 in the hip replacement group were (18.85 ± 3.25) ng/L and (0.93 ± 0.15), respectively, which were significantly lower than those in the control group [(24.40 ± 4.43) ng/L, (1.22 ± 0.30), t = 7.49, 6.41, both P < 0.001]. The level of calcitonin gene-related peptide in the hip replacement group was significantly lower than that in the control group [(73.81 ± 12.26) ng/L vs. (89.39 ± 14.43) ng/L, t = 6.40, P < 0.001]. The level of anandamide in the hip replacement group was significantly higher than that in the control group [(112.65 ± 18.35) ng/L vs. (95.28 ± 14.07) ng/L, t = -5.57, P < 0.001]. The 6-point behavioral rating scale score in the hip replacement group was significantly lower than that in the control group [(1.05 ± 0.32) vs. (2.28 ± 0.67), t = 12.29, P < 0.05]. The Mayo hip function score for patients in the hip replacement group was significantly higher than that in the control group [(85.12 ± 4.33) vs. (79.38 ± 4.12), t = 7.12, P < 0.001]. The incidence of complications in the hip replacement group was significantly lower than that in the control group [1.82% (1/55) vs. 14.55% (8/55), χ2 = 4.36, P < 0.05]. Conclusions:Hip replacement therapy for older adult patients with intertrochanteric femoral fractures can shorten hospital stays, promote the reduction of postoperative stress responses and inflammation, downregulate HBd-3 and AEA levels, facilitate early functional rehabilitation, improve hip function, reduce complications, and enhance prognosis.

Stress refers to the non-specific responses of a stimulated body to different stressors and the subsequent maintenance or restoration of internal environmental homeostasis.Adverse stress reactions lead to general balance disruption and may cause digestive,neurological,and endocrine disorders,and decreased immune capacity,which seriously impact host health.As the core compo-nent of intestinal micro-ecology,the intestinal flora can greatly alter its own composition,distribu-tion,function,metabolic product output,and other aspects during stress,which cause disorders and aggravate homeostatic imbalance in internal environments.While the intestinal flora is of great sig-nificance to animal medicine and agricultural production,little is known about stress and its impact on intestinal flora.Therefore,we briefly reviewed the impact of stress on animal intestinal flora in combination with the latest research and provided theoretical insights on intestinal health research.

Objective To estimate the prevalence of calcified nodule(CN)among patients with coronary artery disease(CAD)and identify the possible risk factors associated with an increased CN risk.Methods Databases include PubMed,Web of Science and Embase was conducted to identify studies reporting the prevalence and/or risk factors of CN.For this databases,the search was from inception to January 1,2024.Data analyses was performed using R statistical Software 4.2.2.Results A total of 46 studies involving 17 926 patients were included.Among them,13 studies with 4 187 patients reported both the prevalence and associated risk factors.The overall prevalence of CN was found to be 5.72％(95％CI 4.47％-7.31％),while in studies reporting both the prevalence and risk factors,the CN prevalence was slightly higher at 8.72％(95％CI 6.43％-11.71％).Hypertension(OR 1.75,95％CI 1.29-2.37),diabetes(OR 1.84,95％CI 1.46-2.33),chronic kidney disease(OR 2.50,95％CI 1.67-3.74),and hemodialysis(OR 7.77,95％CI 4.77-12.67)were associated with an elevated CN risk(all P＜0.001).Conversely,obesity(OR 0.39,95％CI 0.18-0.83)and history of smoking(OR 0.61,95％CI 0.47-0.80)were linked to a decreased CN risk(both P＜0.05).Conclusions The overall prevalence of CN is relatively low among patients with CAD.However,the prevalence of CN is influenced by a variety of clinical factors.Further research is warranted to elucidate the underlying mechanisms.

With the deepening understanding of the pathogenesis of psoriasis, small-molecule drugs targeting the key Janus kinase (JAK) -tyrosine kinase (TYK) 2 pathway have gained increasing interest. TYK2-related pathways play an important role in the pathogenesis of psoriasis, while they are not involved in modulating broad biological effects, making them one of the potential therapeutic targets for the efficient and safe treatment of psoriasis. How to improve the selectivity and specificity of TYK2 inhibitors to minimize adverse reactions associated with the inhibition of other pathways has been one of the key directions for development of drugs targeting TYK2 in recent years. This review summarizes the role of TYK2 pathway in the pathogenesis of psoriasis, the modes of action of TYK2 inhibitors (competitive or allosteric inhibition), and the latest clinical research progress.

This study investigated the drug resistance and genetic relationships among strains co-existing in animals,the environ-ment,and the living quarters of employees at large-scale pig farms in certain regions of Shandong Province,to provide a scientific ba-sis for elucidating the transmission mechanisms of drug-resistant bacteria through bacterial traceability analysis.Samples were col-lected from two pig farms,and bacteria were isolated and purified.The species of the isolated strains were identified via 16S rRNA gene sequencing.Antimicrobial susceptibility testing was conducted with a VITEK-2 Compact system and the disk diffusion method for strains present in pigs,the environment,and living areas.Furthermore,whole-genome sequencing was performed on the Illumina Miniseq platform to annotate drug resistance genes,and multilocus sequence typing(MLST)and core genome single nucleotide poly-morphism(cgSNP)analyses were used to trace the resistant strains.Three species—Staphylococcus aureus,Pseudomonas aeruginosa,and Bacillus cereus—were isolated and cultured from animals,the environment,and employee living areas,and their distributions were analyzed.These strains exhibited diverse drug resistance spectra and genetic diversity.Additionally,the strains displayed highly consistent resistance profiles,resistance genes,ST types,and SNP loci in pig urine,soil both inside and outside the facility,human drinking water,and the cafeteria and dormitories.Our findings indicated a potential risk of transmission of opportunistic pathogens be-tween the pig farming area and the living quarters.Particular attention should be paid to the environmental transmission of methicillin-resistant Staphylococcus aureus.