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.

ObjectiveTo establish the multi-technique characteristic profiles of Alumen by X-ray diffraction（XRD）， Fourier-transform infrared spectroscopy（FTIR） and thermogravimetric-differential thermal analysis（TG-DTA）， and to explore the spectral characteristics for rapid identification of Alumen and its potential adulterant， Ammonium alum. MethodsA total of 27 batches of Alumen samples from 8 production regions were collected for preliminary identification based on visual characteristics. The PDF standard cards of XRD were used to differentiate Alumen from A. alum， and the XRD characteristic profiles of Alumen were established， and then the common peaks were screened. Based on hierarchical clustering analysis（HCA） and orthogonal partial least squares-discriminant analysis（OPLS-DA）， the characteristic information that could be used for identification of Alumen was selected with variable importance in the projection（VIP） value>1. FTIR characteristic profiles of Alumen were established， and key wavenumbers for identification were screened by HCA and OPLS-DA with VIP value>1. Meanwhile， the thermogravimetric differences between Alumen and A. alum were analyzed by TG-DTA， and the thermogravimetric traits that could be used for identification were screened. ResultsAlumen and A. alum could not be effectively distinguished by traits alone. However， by comparing the PDF standard cards of XRD， 15 batches of Alumen and 12 batches of A. alum could be distinguished. In the XRD profiles， 10 characteristic peaks were confirmed， corresponding to diffraction angles of 14.560°， 24.316°， 12.620°， 32.122°， 17.898°， 34.642°， 27.496°， 46.048°， 40.697° and 21.973°. In the FTIR profiles， 4 wavenumber ranges（399.193-403.050， 1 186.010-1 471.420， 1 801.190-2 620.790， 3 612.020-3 997.710 cm^-1） and 12 characteristic wavenumbers（1 428.994， 1 430.922， 1 432.851， 1 434.779， 1 436.708， 1 438.636， 1 440.565， 1 442.493， 1 444.422， 1 446.350， 1 448.279， 1 450.207 cm^-1） were identified. In the TG-DTA profiles， there were characteristic decomposition peaks of ammonium ion and mass reduction features near 555.34 ℃ for A. alum. These characteristics could serve as important criteria for distinguishing the authenticity of Alumen. ConclusionXRD， FTIR and TG-DTA can be used to rapidly detect Alumen and A. alum， and combined with the discriminant features selected through chemometrics， the rapid and accurate identification of Alumen and A. alum can be achieved. The research findings provide new approaches for the rapid identification of Alumen.

OBJECTIVE To analyze the medication needs of parents of pediatric children in our hospital regarding drug instructions， and explore improvement strategies， thereby providing a basis for clinically guiding the rational use of drugs in pediatric patients. METHODS A self-designed questionnaire was used to randomly select the parents of pediatric patients in the pediatric outpatient and emergency departments of our hospital from July 1st to September 30th， 2024. A randomized face-to-face survey was conducted regarding their willingness to read drug instructions， their current understanding status， and their needs. The survey results were then statistically analyzed. RESULTS A total of 300 questionnaires were distributed in this survey， and 299 valid questionnaires were recovered， with an effective recovery rate of 99.7%. Before medication， the parents who “always” and “often” read the drug instructions in detail accounted for 39.1% （117 respondents） and 35.1% （105 respondents）， respectively. Statistically significant differences were observed in the willingness to read drug instructions among respondents with varying educational levels and occupations （P＜0.05）. Among the 299 respondents， only 48 people （16.1%）“ fully understood” the drug instructions， and the average understanding score of all the respondents was （3.77±0.83） points. The stronger the respondents’ willingness to read drug instructions， the higher their understanding scores of drug instructions （P＜0.05）. A total of 256 respondents thought that drug instructions were of great help to themselves， and the average helpfulness rating score of all the respondents was （4.28±0.78） points. Under the conditions of varying ages， educational levels， occupations， and willingness to read drug instructions， statistically significant differences were observed in the scores representing the degree of helpfulness of drug instructions to the respondents （P＜0.05）. Respondents paid the most attention to content in drug instructions such as “dosage and administration method”，“ adverse reactions”， and “indications and therapeutic categories”. The most difficult sections for them to understand included “chemical structure and properties”， “pharmacological and toxicological effects” ， and “pharmacokinetics”， etc. The demographic characteristics of the respondents were not significantly associated with the content areas of drug instructions they most desired to see improved （P＞0.05）. Most respondents （86.0%） hoped to improve the instructions mainly by “simplifying professional terms to make them more accessible”. Others included “highlighting key information” （60.5%） and “providing more detailed medication guidance” （49.2%）， etc. CONCLUSIONS Parents of pediatric patients in our hospital have a high demand for drug instructions but low comprehension. The pharmacy department should make targeted improvements to drug instructions based on parents’ actual needs， helping them accurately obtain medication knowledge and reduce potential medication safety risks.

The study aims to explore the methods for preparing nanocomplexes of Prussian blue nanoparticles (PBNPs) with UNO peptide (UNO-PBNPs) and the functions of the nanocomplexes targeting M2-type macrophages in vitro. PBNPs were prepared by the hydrothermal synthesis method. Subsequently, the peptide UNO (CSPGAKVRC) targeting the mannose receptor was modified on their surface by a heterobifunctional coupling approach. The morphological characteristics of nanoparticles were observed by scanning and transmission electron microscopy. Additionally, their particle size, Zeta potential, and dispersion stability were assessed. The structural characteristics of nanoparticles were analyzed by X-ray diffraction and other techniques. The biological safety of the nanoparticles was evaluated by the CCK-8 assay and hemolysis experiments. Moreover, the targeting performance of UNO-PBNPs towards M2-type macrophages was assessed in vitro. The results showed that the synthesized UNO-PBNPs exhibited uniform cubic morphology, with an average particle size of (202.00±4.21) nm. They were negative charged, well dispersed, and stable. At concentrations ≤ 200 μg/mL, the synthesized UNO-PBNPs led to the hemolysis rate below 5%, demonstrating excellent biocompatibility. The laser confocal imaging results showed that after co-incubation with M2-type macrophages, the FITC-labeled UNO-PBNPs were effectively accumulated in the cells, presenting a distinct fluorescence signal. Quantitative analysis by flow cytometry showed that the intracellular mean fluorescence intensity (6 019.00±346.04) of UNO-PBNPs was higher than that (4 054.00±379.14) of unmodified PBNPs (P < 0.001). In summary, the UNO-PBNPs prepared in this study exhibited a targeting effect on M2-type macrophages, providing a potential method for targeted delivery of PBNPs in the tumor microenvironment and laying a foundation for the remodeling of the tumor immunosuppressive microenvironment.
Ferrocyanides/chemistry* ; Nanoparticles/chemistry* ; Macrophages/drug effects* ; Peptides/chemistry* ; Particle Size ; Animals ; Mannose Receptor ; Mice ; Lectins, C-Type ; Mannose-Binding Lectins ; Receptors, Cell Surface

Bongkrekic acid(BA)is a toxin with stable properties and no distinctive smell.It exists in common foods such as fermented edible grain products,potato products,spoiled tremella fuciformis and auricularia polytricha,as well as auricularia polytricha that has been soaked too long.It can easily cause food poisoning.At present,there is still a lack of complete method to detect BA,and no spe-cific antidote of BA has been found.Therefore,BA poisoning is easy to be misdiagnosed or missed diagnosed,and its mortality rate remains high.In recent years,studies have revealed the toxic mecha-nism of BA and found that BA can inactivate some enzymes containing thiol groups(-SH)and in-hibit the synthesis and transport of adenosine triphosphate(ATP),causing damage to liver,kidney,brain and other parenchymal organs.This article reviews the autopsy cases and literature of deaths caused by BA poisoning at home and abroad,systematically summarizes the epidemiology,clinical manifestations,pathological changes,toxicological mechanisms,detection methods,forensic diagnostic key points and challenges of BA in forensic medicine,with the aim of providing a reference for foren-sic identification of related cases.

Objective To investigate the relationship between serum microRNA-30a-5p(miR-30a-5p),Runt-associated transcription factor 2(RUNX2)and the severity and prognosis of patients with sepsis-induced acute lung injury(ALI).Methods A total of 193 patients with sepsis-induced ALI(ALI group)and 54 pa-tients with simple sepsis(non-ALI group)admitted to the Fifth Affiliated Hospital of Xinjiang Medical Uni-versity from January 2021 to February 2024 were selected,and the patients with sepsis-induced ALI were di-vided into a mild ALI group(57 cases),a moderate ALI group(64 cases),and a severe ALI group(72 cases)according to the oxygenation index,and were divided into a death group(71 cases)and a survival group(122 cases)according to the 28 day prognosis situation.Serum miR-30a-5p level was detected by real time fluores-cent quantitative PCR,serum RUNX2 level was detected by enzyme-linked immunosorbent assay,and the binding sites of miR-30a-5p and RUNX2 were predicted by online database.Pearson's correlation coefficient was used to analyze the correlation between miR-30a-5p and RUNX2 in patients with sepsis-induced ALI,and Spearman's correlation coefficient was used to analyze the correlation between serum miR-30a-5p,RUNX2 levels and oxygenation index in patients with sepsis-induced ALI.With the prognosis of patients with sepsis-induced ALI as the dependent variable,multivariate unconditional Logistic regression was used to determine their influencing factors,and receiver operating characteristic curve was plotted to evaluate the prognostic val-ue of serum miR-30a-5p and RUNX2 levels in patients with sepsis-induced ALI.Results Compared with the non-ALI group,serum miR-30a-5p level was lower and RUNX2 level was higher in the ALI group(t=-11.749,11.691,P＜0.001).There was a binding site between miR-30a-5p and RUNX2 at the 3'-untranslat-ed region 3 348-3 354.miR-30a-5p was negatively correlated with RUNX2 in patients with sepsis-induced ALI(r=-0.759,P＜0.001).The level of serum miR-30a-5p increased in the severe ALI group,the moderate ALI group and the mild ALI group in turn(P＜0.001),and the level of RUNX2 decreased in the severe ALI group,the moderate ALI group and the mild ALI group in turn(P＜0.001).Oxygenation index was negative-ly correlated with serum miR-30a-5p level(r=-0.749,P＜0.001),and positively correlated with RUNX2 level in patients with sepsis-induced ALI(r=0.723,P＜0.001).Independent protective factors for death in patients with sepsis-induced ALI were increased oxygenation index(OR=0.988,95％CI:0.981-0.996,P＜0.05),elevated miR-30a-5p(OR=0.814,95％CI:0.744-0.892,P＜0.05),and independent risk factors were increased Sequential Organ Failure Assessment(SOFA)score(OR=1.391,95％CI:1.116-1.734,P＜0.05),elevated blood lactate(OR=1.824,95％CI:1.211-2.748,P＜0.05),and elevated RUNX2(OR=1.366,95％CI:1.170-1.595,P＜0.05).The area under the curve of serum miR-30a-5p and RUNX2 levels combined to predict the death in patients with sepsis-induced ALI was 0.895(95％CI:0.842-0.934),which was greater than 0.788(95％CI:0.724-0.844)of serum miR-30a-5p and 0.786(95％CI:0.721-0.842)of RUNX2 levels alone(Z=4.015,3.746,P＜0.001).Conclusion Increased miR-30a-5p level and decreased RUNX2 level are associated with the aggravation of the disease and the increased risk of death in patients with sepsis-induced ALI.The combination of serum miR-30a-5p and RUNX2 levels has relatively high value in pre-dicting the prognosis of patients with sepsis-induced ALI.

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.