OBJECTIVE To systematically evaluate the influential factors for all-cause mortality in patients with carbapenem-resistant Gram-negative bacteria （CR-GNB） treated with polymyxin B. METHODS PubMed， Embase， the Cochrane Library， Web of Science， Wanfang Data， VIP， CBM and CNKI were searched to collect clinical studies on all-cause death within 30 days or 28 days after treatment with polymyxin B in patients with CR-GNB infection from database establishment to July 2025. After literature screening， data extraction and evaluation of literature quality， meta-analysis was performed using RevMan 5.4 software. RESULTS A total of 12 studies were included， involving 1 326 patients， among whom 529 patients died， with a mortality rate of 39.89%. Meta-analysis results showed that combined with cardiovascular disease [OR＝2.06， 95%CI （1.37， 3.09）， P ＝0.005 ] ， increased Sequential Organ Failure Assessment （SOFA） score [OR＝1.20， 95%CI （1.07， 1.35）， P ＝0.003 ] ， mechanical ventilation [OR＝2.35， 95%CI （1.65， 3.34）， P ＜0.001 ] ， continuous renal replacement therapy （CRRT） [OR＝2.58， 95%CI （1.67， 3.97）， P ＜0.001 ] ， bloodstream infection [OR＝3.24， 95%CI （2.19， 4.78）， P ＜0.001 ] ， multiple-site infection [OR＝1.51， 95%CI （1.03， 2.20）， P ＝0.03 ] ， septic shock [OR＝3.19， 95%CI （1.94， 5.24）， P ＜0.001 ] ， use of vasoactive drugs [OR＝2.90， 95%CI （1.97， 4.27）， P ＜0.001 ] ， and the occurrence of acute kidney injury （AKI） [OR＝2.17， 95%CI （1.41， 3.36）， P ＜0.001 ] were risk factors for all-cause mortality in patients with CR-GNB infection treated with polymyxin B. Conversely， an extended duration of polymy xin B treatment [OR＝0.92， 95%CI （0.86， 0.99）， P ＝0.03 ] and early administration after CR-GNB infection [OR＝0.47， 95%CI （0.25， 0.85）， P ＝0.01 ] were protective factors. CONCLUSIONS Patients with cardiovascular disease， receiving mechanical ventilation or CRRT， having bloodstream infection， multiple-site infection or septic shock， combining with vasoactive drugs， with AKI and increased SOFA scores have a higher risk of all-cause mortality. Conversely， extending the duration of polymyxin B treatment （beyond 7 days） and early administration within 48 hours after confirmed CR-GNB infection can significantly reduce the risk of all-cause mortality.

AIM: To explore preoperative risk factors affecting residual astigmatism after Toric intraocular lens(IOL)implantation, and construct and verify a clinically applicable prediction model.METHODS: This retrospective study included patients who underwent Toric IOL implantation at Puyang Oilfield General Hospital and the Second People's Hospital of Puyang City from October 2023 to August 2025. Patients were categorized into two groups according to residual astigmatism at 3 mo postoperatively: >0.25 D group and ≤0.25 D group. Preoperative clinical data and ocular parameters of the two groups were collected and compared. Multivariate Logistic regression analysis was used to screen risk factors, and a nomogram prediction model was established accordingly. Receiver operating characteristic(ROC)curve, calibration curve, and Hosmer-Lemeshow test were adopted to evaluate discrimination, calibration, and clinical applicability of the model. Bootstrap method was applied for internal validation.RESULTS: Totally 103 patients(103 eyes)were included, with 72 patients(72 eyes)in the group with residual astigmatism ≤0.25 D, including 38 males and 34 females, with an average age of 67.35±6.12 y; There were 31 cases(31 eyes)in group with residual astigmatism >0.25 D, including 19 males and 12 females, with an average age of 69.87±6.45 y. The proportion of patients with a history of diabetes, as well as the values for axial length, horizontal corneal diameter, flat corneal curvature(K1), steep corneal curvature(K2), astigmatic axis and proportion of lens nuclear hardness grade III-IV were significantly higher in the residual astigmatism group >0.25 D than those in the residual astigmatism ≤0.25 D group(all P<0.05). Multivariate analysis identified increased horizontal corneal diameter, higher K1 value, higher K2 value, and higher lens nuclear hardness(grade III-IV)as independent risk factors for postoperative residual astigmatism >0.25 D(all P<0.05). The nomogram constructed from these factors demonstrated that the area under the ROC curve(AUC)was 0.794, with a sensitivity of 80.31% and a specificity of 75.20%. The concordance index(C-index)of internal validation was 0.865. Calibration curve and Hosmer-Lemeshow test(χ2=5.231, P=0.734)indicated good consistency between predicted and actual values of the model.CONCLUSION: The nomogram model established based on horizontal corneal diameter, K1, K2 and lens nucleus hardness exhibits favorable predictive performance. It can effectively predict the risk of residual astigmatism prior to Toric IOL surgery, providing reference for individualized clinical surgical planning.

Objective: To define the mechanism by which swine TRIM25 restricts vesicular stomatitis virus replication. Methods: Porcine 3D4/21 cells with TRIM25 overexpression or knockdown were infected with vesicular stomatitis virus. Viral replication was quantified by immunoblotting, quantitative reverse transcription polymerase chain reaction, and 50% tissue culture infectious dose assays. Type I interferon signaling was assessed by transcript quantification, interferon-beta and interferon-stimulated response element reporter assays, and co-immunoprecipitation.Viral RNA binding was tested by RNA immunoprecipitation. Results: TRIM25 overexpression reduced viral RNA and infectious titers, whereas TRIM25 knockdown increased replication (p < 0.01). TRIM25 increased interferon-beta and interferon-stimulated gene expression and enhanced interferon-beta and interferonstimulated response element promoter activity (p < 0.01). Mechanistically, TRIM25 promoted Lys63-linked ubiquitination of RIG-I and increased phosphorylation of TANK-binding kinase 1 and interferon regulatory factor 3. TRIM25 also bound vesicular stomatitis virus genomic RNA, and binding required the C-terminal region. Conclusions and Relevance: Porcine TRIM25 restricts vesicular stomatitis virus replication by amplifying type I interferon signaling and directly binding viral RNA.

Objective: To understand the changing trends and related factors of knowledge, attitude and practice (KAP) regarding the three major infectious diseases (acquired immunodeficiency syndrome, tuberculosis, hepatitis B) among freshmen in Jiangsu from 2019 to 2022, so as to provide a reference basis for the health education of infectious diseases in schools. Methods: From 2019 to 2022, a total of 33 944 freshmen from 20 universities in Jiangsu Province were randomly selected for four consecutive years to investigate their KAP levels online through self designed questionnaires on three major infectious diseases. The multiple linear regression model was used to analyze the changing trends of students KAP levels of the three major infectious diseases, and to explore the influencing factors of KAP. Results: From 2019 to 2022, the knowledge scores(18.0±3.1,18.4±3.2,18.7±3.2,18.8±3.2), related to the three major infectious diseases showed an upward trend ( F=436.50, P <0.01), and the positive attitude reporting rates were 81.77%, 81.46%, 82.68% and 81.74%, respectively. The reporting rates of positive practice were 80.11%, 79.25%, 79.08 % and 79.04%, respectively. Multiple linear regression showed that school type, parental education level, mother s occupation, average income per person in family and living arrangements during high school all had an impact on the knowledge ( β = -1.510 -0.559), attitudes ( β =-0.043-0.065) and practice ( β =-0.028-0.027) of the three major infectious diseases ( P < 0.05 ). The family residence areas only affected the reporting rate of positive attitude scores ( β =0.002-0.065), and whether only children or not affected the reporting rate of positive practice scores ( β =0.009)( P <0.05). The knowledge score showed an upward trend ( β= 0.297, P <0.01), the positive attitude reporting rate showed no statistically significant change ( β=0.001, P =0.22), and the positive practice reporting rate showed a downward trend ( β=-0.005, P <0.01). Conclusions Freshman in Jiangsu Province from 2019 to 2022 have shown a separation in KAP scores regarding the three major infectious diseases. Targeted measures should be taken to improve their health practice level.

ObjectiveTo investigate the effects of foliar fertilizer of nano-calcium carbonate and calcium nitrate tetrahydrate on the agronomic traits， carbohydrate and endogenous hormone contents of Dendrobium officinale planted for 1 year under greenhouse cultivation， in order to provide scientific basis for fertilization to improve the yield and quality of D. officinale. MethodsSingle-factor experimental design was adopted. Starting from early spring， D. officinale was treated with foliar spraying according to corresponding fertilizers. Three treatment groups were established based on different fertilizers， namely， a blank group（clear water）， a nano-calcium carbonate group（0.727 g·L^-1 nano-calcium carbonate water-soluble fertilizer）， and a calcium nitrate tetrahydrate group（1.091 g·L^-1 calcium nitrate tetrahydrate water-soluble fertilizer）. The frequency of spraying was three times per month， and the entire treatment process lasted for nine months. The effects of various treatments on the traits and relative chlorophyll content of D. officinale were dynamically monitored. Sampling was conducted at three specific time points：August 2， 2023， September 8， 2023， and November 1， 2023， respectively. The contents of glucose and mannose in D. officinale stems were determined by high performance liquid chromatography（HPLC）， the content of soluble sugars in D. officinale stems and leaves was determined by phenol method， and enzyme-linked immunosorbent assay（ELISA） was used to detect the concentrations of cytokinin and auxin. ResultsCompared with the blank group， the treatments with nano-calcium carbonate and calcium nitrate tetrahydrate could significantly increase stem length， stem node number， leaf number， and tiller number. Among them， during the harvesting period in November， the stem length and tiller number， which are indicators related to the yield of D. officinale， increased by 60.85% and 19.23% after treatment with calcium nitrate tetrahydrate， and by 32.54% and 28.85% after treatment with nano-calcium carbonate， respectively. Compared with the blank group， treatments with nano-calcium carbonate and calcium nitrate tetrahydrate could promote the accumulation of sucrose in the stems and leaves of D. officinale to varying degrees， as well as the accumulation of polysaccharides， mannose， and glucose in the stems. In addition， nano-calcium carbonate treatment also facilitated the accumulation of fructose in the stems and leaves of D. officinale. Specifically， during the harvesting period in November， polysaccharides and mannose， which were the main active ingredients in D. officinale stems， increased by 28.48% and 29.36% after treatment with calcium nitrate tetrahydrate， and by 39.91% and 82.62% after treatment with nano-calcium carbonate， respectively. In addition， compared with the blank group， the concentrations of auxin in the stems and leaves of D. officinale were significantly increased after treatment with calcium nitrate tetrahydrate（P<0.05）. Similarly， the concentrations of cytokinin and auxin in the stems of D. officinale were also elevated after treatment with nano-calcium carbonate. Correlation analysis further indicated that elongation growth and tillering of D. officinale stems after foliar spraying of nano-calcium carbonate and calcium nitrate tetrahydrate might be related to the accumulation of carbohydrates in the stems and leaves and the synergistic effect of auxin and cytokinin. ConclusionIn production practice， spraying nano-calcium carbonate and calcium nitrate tetrahydrate can promote the accumulation of cytokinin， auxin， and carbohydrate contents in the stems and leaves of D. officinale， and promote tillering and elongation growth of the stems.

Objective To explore the effective substances that specifically bind to RSV-F protein in the water extract of Forsythia suspensa,and verify its effect.Methods Surface plasmon resonance(SPR)affinity fishing technology was used to enrich,regenerate and recover the active components that specifically bind to RSV-F protein in the water extract of Forsythia suspensa.The recovered samples were analyzed and identified by UHPLC-MS/MS,and the active components that stably bind to F protein were screened by molecular docking,molecular dynamics simulation and SPR affinity detection,and then returned to animal experiments for pharmacodynamics verification.BALB/c mice were randomly divided into normal group,model group,positive control group,protocatechuic acid group and verbascoside group.In the experimental group,RSV was dripped into the nose to make models.Each drug group began to be given intragastric intervention on the day of modeling,and samples were taken after 4 days.HE staining was used to observe the pathological changes of lung tissue,and ELISA was used to detect the changes of inflammatory factors in lung tissue.Results A variety of active components in the aqueous extract of Forsythia suspensa could bind to RSV-F protein,among which the results of verbascoside and protocatechuic acid were more stable.In vivo pharmacodynamics experiments showed that the lung tissue of the model group had obvious pathological changes and the level of inflammatory factors increased,and the pathological state was improved after the intervention of verbascoside and protocatechuic acid compared with the normal group.Conclusion Forsythia suspensa can interfere with the expression of RSV-F protein through many active components such as verbascoside and protocatechuic acid,which may be the material basis of its anti-RSV.

Objective To establish mouse models exposed to different doses of neodymium oxide via tracheal instillation,and to investigate the mechanisms underlying brain tissue damage induced by neodymium oxide exposure in mice.Methods Forty-eight male C57/BL6 mice were randomly assigned to four groups:the control group,the low-dose group,the medium-dose group,and the high-dose group.The low-dose,medium-dose,and high-dose groups received 62.5 mg/mL,125 mg/mL,and 250 mg/mL neodymium oxide,respectively,via non-exposed tracheal instillation.The control group received an equivalent volume of saline using the same administration method.After 35 days,the mice were euthanized,and brain tissues were collected.RT-PCR was used to assess the mRNA expression changes of Claudin-5 and Occludin.Western blot analysis was performed to evaluate the expression changes of Claudin-5 and Occludin tight junction proteins,as well as the expression changes of MMP-2 and MMP-9 in the brain tissues.Additionally,the expression of the RhoA/ROCK2 signaling pathway and downstream cofilin protein was examined.Changes in oxidative stress markers,including MDA,T-AOC,and NO,were measured using a kit method.Results The mRNA expression of Claudin-5 was significantly reduced in the middle-dose and high-dose groups compared to the control group(P<0.05).Similarly,the mRNA expression of Occludin was significantly lower in the low-dose,medium-dose,and high-dose groups compared to the control group(P<0.05).Additionally,the protein expression of Claudin-5,MMP-2,and Occludin was significantly decreased in the low-dose,medium-dose,and high-dose groups compared to the control group(P<0.05).The protein expression of MMP-9 and RhoA was also signifi-cantly lower in the medium-dose and high-dose groups compared to the control group(P<0.05).Furthermore,the protein expression of ROCK2 and p-cofilin in the high-dose group was significantly lower than that in the control group(P<0.05).The content of MDA and T-AOC was significantly lower in the medium-dose and high-dose groups compared to the control group(P<0.05),and the content of NO in the high-dose group was significantly lower than that in the control group(P<0.05).Conclusion Exposure to neodymium oxide results in increased permeability of the blood-brain barrier in mice,leading to oxidative stress,inflammatory responses,and activation of the RhoA/ROCK2 signaling pathway.

OBJECTIVES: Exposure to rare earth elements (REEs) has been linked to various systemic diseases, but their impact on the offspring blood-brain barrier (BBB) via the gut-brain axis remains unclear. This study aims to investigate the effects of maternal exposure to neodymium oxide (Nd₂O₃) on the BBB integrity of offspring rats, and to evaluate the potential protective role of bifidobacterium tetrad viable tablets (BTVT) against Nd₂O₃-induced intestinal and BBB damage. METHODS: Healthy adult SD rats were mated at a 1:1 male-to-female ratio, with the day of vaginal plug detection marked as gestational day 0. A total of 60 pregnant rats were randomly assigned to the following groups: Control, 50 mg/(kg·d) Nd₂O₃, 100 mg/(kg·d) Nd₂O₃, 200 mg/(kg·d) Nd₂O₃, and 200 mg/(kg·d) Nd₂O₃ + BTVT group. Treatments were administered by daily oral gavage throughout pregnancy and lactation. On postnatal day 21 (weaning), offspring feces, brain, and colon tissues were collected. Hematoxylin and eosin (HE) staining was used to assess structural changes in brain and intestinal tissues. Short-chain fatty acids (SCFAs) in feces were quantified by gas chromatography-mass spectrometry (GC-MS). Evans Blue (EB) dye extravasation assessed BBB permeability. Gene and protein expression levels of tight junction proteins occludin and zonula occludens-1 (ZO-1) were measured by reverse transcription PCR (RT-PCR) and Western blotting (WB), respectively. Neodymium levels in brain tissue were determined via inductively coupled plasma mass spectrometry (ICP-MS). RESULTS: HE staining revealed that maternal Nd₂O₃ exposure caused mucosal edema, increased submucosal spacing, and lymphocyte infiltration in offspring colon, as well as neuronal degeneration and vacuolization in brain tissue. BTVT intervention alleviated these changes. GC-MS analysis showed that levels of acetic acid, propionic acid, butyric acid, and isobutyric acid significantly decreased, while valeric acid and isovaleric acid increased in offspring of Nd₂O₃-exposed mothers (P<0.05). BTVT significantly restored levels of acetic, propionic, and isobutyric acids and reduced valeric acid content (P<0.05). EB permeability was significantly elevated in Nd₂O₃-exposed offspring brains (P<0.05), but reduced with BTVT treatment (P<0.05). RT-PCR and WB showed downregulation of occludin and ZO-1 expression following Nd₂O₃ exposure (P<0.05), which was reversed by BTVT (P<0.05). ICP-MS results indicated significantly increased brain neodymium levels in offspring from all Nd₂O₃-exposed groups (P<0.05), while BTVT significantly reduced neodymium accumulation compared to the 200 mg/(kg·d) Nd₂O₃ group (P<0.05). CONCLUSIONS Maternal exposure to Nd₂O₃ during pregnancy and lactation disrupts intestinal health and BBB integrity in offspring, elevates brain neodymium accumulation, and induces neuronal degeneration. BTVT effectively mitigates Nd₂O₃-induced intestinal and BBB damage in offspring, potentially through modulation of the gut-brain axis.
Animals ; Female ; Blood-Brain Barrier/pathology* ; Pregnancy ; Rats, Sprague-Dawley ; Rats ; Male ; Neodymium/toxicity* ; Prenatal Exposure Delayed Effects/prevention & control* ; Lactation ; Maternal Exposure/adverse effects* ; Brain

Rapid developments in biotechnology have led researchers to seek new method to improve the efficiency and accuracy of biomedical research and drug development,promoting interdisciplinary integration.Recent advancements in artificial intelligence(AI)technologies have brought unprecedented opportunities to this field.The integration of various AI models allows researchers to better utilize multi-omics data,identify disease phenotypes,interpret animal behavior,assess treatment effects,improve experimental designs,reduce the use of experimental animals,enhance animal facility management,and improve animal welfare.This article reviews the advancements in AI biomedical research over the past decade and discusses its contributions to disease phenotype identification,the selection and design of experimental animal models,animal behavior analysis,and animal facility management.It also points out the challenges related to data standardization,AI model selection and interpretability,the extrapolation process from AI models to animal experiments and clinical practice,as well as ethical considerations in using AI in sensitive areas involving human genetics and personalized medicine.This review aims to help researchers and practitioners in relevant fields understand the current state and opportunities of AI development,thus providing support for its broader application.

Objective:To evaluate the training efficacy of the autonomic nervous system stability assessing and enhancing capsule (hereinafter referred to as the EC), and to study the difference in physiological indicators for autonomic nervous system stability training between the EC and a non-capsule environment.Methods:A total of 1 478 male military pilots under autonomic nervous system stability training between February 2022 and February 2024 were selected before they completed training sessions in both the EC and a non-capsule environment. The pre-training time-domain and frequency-domain indices of heart rate variability (HRV) and the 0.1 Hz index were compared with the post-training ones, and across difficulty levels (low, moderate, and high). The difference that the EC made in relaxation training was analyzed.Results:①Time-domain indices of HRV were of statistical significance in the main effects of training difficulty, those of training environments, and their interactions ( F=4.40-160.80, all P<0.05 or 0.01). Simple effect analysis revealed that in the same phase of training the standard deviation of all NN intervals (SDNN) at the low level of difficulty in the EC was lower than in the non-capsule environment. However, all time-domain indices after training were higher in the EC than in the non-capsule environment. The differences were statistically significant (all P<0.05 or 0.01).②For frequency-domain HRV indices, significant differences were observed in both the main effect of training difficulty and the interactions ( F=4.40-1 524.33, all P<0.01). Very low frequency power (VLF), high frequency (HF), the ratio of low frequency to high frequency (LF/HF), normalized low frequency (LFnorm), and normalized high frequency (HFnorm) were significantly different in the main effect of training environments ( F=4.24, 12.00, 6.91, 23.39, 23.39, P=0.040, <0.001, =0.009, <0.001, <0.001). Simple effect analysis revealed that at the same level of training difficulty, the EC delivered significantly lower values of LF and LFnorm but higher values of HF and HFnorm than the non-capsule environment before training (all P<0.05). VLF across levels of training difficulty and LF/HF at the high level of difficulty level were significantly lower in the EC than in the non-capsule environment. After training, total power, VLF, LF, HF, and HFnorm were significantly higher in the EC than in the non-capsule environment, but LF/HF and LFnorm were significantly lower (all P<0.05). ③For the 0.1 Hz index, significant differences were observed in both the main effect of training difficulty and the interactions ( F=2 147.75, 6.63, both P<0.001). Subsequent simple effect analysis revealed that at the same level of training difficulty, 0.1 Hz indices of pilots in the EC were lower than in the non-capsule environment before and after training (all P<0.01). Conclusions:During the autonomic nervous system stability training, the EC can effectively and quickly regulate and alleviate pilots′ fatigue and stress. Furthermore, it provides sustained autonomic nervous system training, thereby stabilizing pilots′ autonomic nervous system.