OBJECTIVE: To investigate the effect of zedoarondiol on neovascularization of atherosclerotic (AS) plaque by exosomes experiment. METHODS: ApoE^-/- mice were fed with high-fat diet to establish AS model and treated with high- and low-dose (10, 5 mg/kg daily) of zedoarondiol, respectively. After 14 weeks, the expressions of anti-angiogenic protein thrombospondin 1 (THBS-1) and its receptor CD36 in plaques, as well as platelet activation rate and exosome-derived miR-let-7a were detected. Then, zedoarondiol was used to intervene in platelets in vitro, and miR-let-7a was detected in platelet-derived exosomes (Pexo). Finally, human umbilical vein endothelial cells (HUVECs) were transfected with miR-let-7a mimics and treated with Pexo to observe the effect of miR-let-7a in Pexo on tube formation. RESULTS: Animal experiments showed that after treating with zedoarondiol, the neovascularization density in plaques of AS mice was significantly reduced, THBS-1 and CD36 increased, the platelet activation rate was markedly reduced, and the miR-let-7a level in Pexo was reduced (P<0.01). In vitro experiments, the platelet activation rate and miR-let-7a levels in Pexo were significantly reduced after zedoarondiol's intervention. Cell experiments showed that after Pexo's intervention, the tube length increased, and the transfection of miR-let-7a minics further increased the tube length of cells, while reducing the expressions of THBS-1 and CD36. CONCLUSION Zedoarondiol has the effect of inhibiting neovascularization within plaque in AS mice, and its mechanism may be potentially related to inhibiting platelet activation and reducing the Pexo-derived miRNA-let-7a level.
Animals ; MicroRNAs/genetics* ; Exosomes/drug effects* ; Plaque, Atherosclerotic/genetics* ; Neovascularization, Pathologic/genetics* ; Human Umbilical Vein Endothelial Cells/metabolism* ; Humans ; Blood Platelets/drug effects* ; Apolipoproteins E/deficiency* ; Thrombospondin 1/metabolism* ; CD36 Antigens/metabolism* ; Platelet Activation/drug effects* ; Male ; Mice ; Mice, Inbred C57BL

OBJECTIVE: Hepatocellular carcinoma (HCC) is sensitive to ferroptosis, a new form of programmed cell death that occurs in most tumor types. However, the mechanism through which ferroptosis modulates HCC remains unclear. This study aimed to investigate the oncogenic role and prognostic value of FANCD2 and provide novel insights into the prognostic assessment and prediction of immunotherapy. METHODS: Using clinicopathological parameters and bioinformatic techniques, we comprehensively examined the expression of FANCD2 macroscopically and microcosmically. We conducted univariate and multivariate Cox regression analyses to identify the prognostic value of FANCD2 in HCC and elucidated the detailed molecular mechanisms underlying the involvement of FANCD2 in oncogenesis by promoting iron-related death. RESULTS: FANCD2 was significantly upregulated in digestive system cancers with abundant immune infiltration. As an independent risk factor for HCC, a high FANCD2 expression level was associated with poor clinical outcomes and response to immune checkpoint blockade. Gene set enrichment analysis revealed that FANCD2 was mainly involved in the cell cycle and CYP450 metabolism. CONCLUSION To the best of our knowledge, this is the first study to comprehensively elucidate the oncogenic role of FANCD2. FANCD2 has a tumor-promoting aspect in the digestive system and acts as an independent risk factor in HCC; hence, it has recognized value for predicting tumor aggressiveness and prognosis and may be a potential biomarker for poor responsiveness to immunotherapy.
Humans ; Carcinoma, Hepatocellular/diagnosis* ; Liver Neoplasms/diagnosis* ; Immunotherapy ; Fanconi Anemia Complementation Group D2 Protein/metabolism* ; Prognosis ; Male ; Female ; Middle Aged ; Biomarkers, Tumor/metabolism*

Objective To evaluate the efficacy of Compound Fipronil Spot-on Solution in repelling canine ticks.Methods A total of 140 dogs infested with ticks were randomly selected from regions in southern and northern China and assigned to four groups:southern test drug group,southern control drug group,northern test drug group,and northern control drug group.Each group comprised 35 dogs.Each dog was administered the prescribed dose.The number of ticks was counted on days 1,7,14,21,and 28 following the administration.The negative conversion and average reduction rates of the tick population were then subjected to statistical analyse.Results The mean efficacy of the test drug was 100%in both the southern and northern cohorts,28 days post-treatment.The control drug showed comparable efficacy,reaching a mean reduction of 100%in both regions by the same time point.No additional clinical manifestations or adverse events were observed across all treated dogs.Conclusions Compound Fipronil Spot-on Solutions effectively treats and prevents ticks in dogs in different regions of China.A single dose remains effective for up to 28 days,thus providing a convenient,effective solution.

Objective To investigate the expression and significance of heat shock protein 70(HSP70),apoptosis-associated speck-like protein(ASC),and vitamin D in children with febrile seizures(FS).Methods A total of 200 children with FS admitted to our hospital from June 2022 to December 2023 were selected as FS group,including 158 cases of simple FS and 42 cases of complex FS.Another 200 febrile children without FS were selected as fever group,and 50 healthy children were selected as control group.The differences in HSP70,ASC mRNA,and vitamin D expression a-mong the three groups were compared.The differences in HSP70,ASC mRNA,and vitamin D ex-pression at different time points in children with different types of FS were compared.The influencing factors and predictive value of complex FS were analyzed.Results At admission,the expression lev-els of HSP70 and ASC mRNA gradually decreased,while the vitamin D levels gradually increased in the FS group,fever group,and control group,with statistically significant between-group differences(P＜0.01).One hour after admission,the levels of HSP70 and ASC mRNA in both the complex FS group and the simple FS group were lower than those at admission(P＜0.01).The levels of HSP70 and ASC mRNA in the complex FS group at admission and 1 hour after admission were higher than those in the simple FS group,while the vitamin D level was lower(P＜0.01).Multivariate Logistic regression analysis showed that elevated HSP70 and ASC mRNA levels at admission were independ-ent risk factors for complex FS(P＜0.001),while elevated vitamin D level was an independent protective factor for complex FS(P＜0.001).The area under the curve(AUC)for HSP70,ASC mRNA,and vitamin D in assessing complex FS were 0.785(95％CI,0.721 to 0.840),0.766(95％CI,0.701 to 0.823),and0.760(95％CI,0.695 to 0.817),respectively.The combined AUC of HSP70,ASC mRNA,and vitamin D for assessing complex FS was 0.915,with a sensitivity of 90.48％and a specificity of 81.65％.The AUC of combined assessment of complex FS by vari-ous factors was greater than that of HSP70,ASC mRNA,and vitamin D alone(Z=2.743,2.749,3.086,P=0.006,0.006,0.002).Conclusion The levels of HSP70 and ASC mRNA are elevat-ed,while the vitamin D level is reduced in children with complex and simple FS.The combined as-sessment of HSP70,ASC mRNA,and vitamin D at admission has high value in assessing complex FS.

ObjectiveThe distribution of water content in plant leaves is an important indicator for measuring plant physiology and biochemistry, and it is also an important basis for formulating drought resistance strategies in the field of agricultural science. Microwave imaging has high contrast and sensitivity in the distribution and variation of water content, while ultrasound imaging has high resolution. Based on this, this paper proposes a non-destructive microwave thermoacoustic imaging (TAI) technology that combines the advantages of microwave and ultrasound imaging, and uses this technology to carry out non-destructive testing research on the distribution of plant leaf water content, which is of great significance for achieving precise irrigation, developing water-saving agriculture, and improving water resource utilization. MethodsThis study constructs a two-dimensional transmissive TAI system with an excitation frequency of 3.0 GHz and a lateral resolution of 0.406 μm. Based on active heating technology (150°C hot air, 90 s), 3 sets of mandala leaf moisture loss processes were simulated, and their TAI images were quantitatively analyzed. ResultsThe results showed that heating caused local moisture loss and reduced thermoacoustic signals, verifying the feasibility of non-destructive detection of plant leaf water content changes based on TAI, which achieves non-destructive detection of water content distribution in leaves of Datura, Crassocephalum crepidioides and Perilla. The results are consistent with magnetic resonance imaging (MRI). ConclusionThis study contributes to achieve precise irrigation and provides technical support for studying the response characteristics of plants to the environment under normal and stress environments. Especially when combined with non-contact ultrasound detection technology, remote sensing of plant leaf water content can be achieved, which has more practical value.

Objective This study aimed to evaluate whether the onset of the plateau phase of slow hepatitis B surface antigen decline in patients with chronic hepatitis B treated with intermittent interferon therapy is related to the frequency of dendritic cell subsets and expression of the costimulatory molecules CD40,CD80,CD83,and CD86. Method This was a cross-sectional study in which patients were divided into a natural history group(namely NH group),a long-term oral nucleoside analogs treatment group(namely NA group),and a plateau-arriving group(namely P group).The percentage of plasmacytoid dendritic cell and myeloid dendritic cell subsets in peripheral blood lymphocytes and monocytes and the mean fluorescence intensity of their surface costimulatory molecules were detected using a flow cytometer. Results In total,143 patients were enrolled(NH group,n = 49;NA group,n = 47;P group,n = 47).The results demonstrated that CD141/CD1c double negative myeloid dendritic cell(DNmDC)/lymphocytes and monocytes(%)in P group(0.041[0.024,0.069])was significantly lower than that in NH group(0.270[0.135,0.407])and NA group(0.273[0.150,0.443]),and CD86 mean fluorescence intensity of DNmDCs in P group(1832.0[1484.0,2793.0])was significantly lower than that in NH group(4316.0[2958.0,5169.0])and NA group(3299.0[2534.0,4371.0]),Adjusted P all<0.001. Conclusion Reduced DNmDCs and impaired maturation may be associated with the onset of the plateau phase during intermittent interferon therapy in patients with chronic hepatitis B.

Objective To explore characteristics of clinical parameters and cytokines in patients with drug-induced liver injury(DILI)caused by different drugs and their correlation with clinical indicators. Method The study was conducted on patients who were up to Review of Uncertainties in Confidence Assessment for Medical Tests(RUCAM)scoring criteria and clinically diagnosed with DILI.Based on Chinese herbal medicine,cardiovascular drugs,non-steroidal anti-inflammatory drugs(NSAIDs),anti-infective drugs,and other drugs,patients were divided into five groups.Cytokines were measured by Luminex technology.Baseline characteristics of clinical biochemical indicators and cytokines in DILI patients and their correlation were analyzed. Results 73 patients were enrolled.Age among five groups was statistically different(P=0.032).Alanine aminotransferase(ALT)(P=0.033)and aspartate aminotransferase(AST)(P=0.007)in NSAIDs group were higher than those in chinese herbal medicine group.Interleukin-6(IL-6)and tumor necrosis factor alpha(TNF-α)in patients with Chinese herbal medicine(IL-6:P<0.001;TNF-α:P<0.001)and cardiovascular medicine(IL-6:P=0.020;TNF-α:P=0.001)were lower than those in NSAIDs group.There was a positive correlation between ALT(r=0.697,P=0.025),AST(r=0.721,P=0.019),and IL-6 in NSAIDs group. Conclusion Older age may be more prone to DILI.Patients with NSAIDs have more severe liver damage in early stages of DILI,TNF-α and IL-6 may partake the inflammatory process of DILI.

Receptor-interacting serine/threonine-protein kinase 1 (RIPK1) functions as a key regulator in inflammation and cell death and is involved in mediating a variety of inflammatory or degenerative diseases. A number of allosteric RIPK1 inhibitors (RIPK1i) have been developed, and some of them have already advanced into clinical evaluation. Recently, selective RIPK1i that interact with both the allosteric pocket and the ATP-binding site of RIPK1 have started to emerge. Here, we report the rational development of a new series of type-II RIPK1i based on the rediscovery of a reported but mechanistically atypical RIPK3i. We also describe the structure-guided lead optimization of a potent, selective, and orally bioavailable RIPK1i, 62, which exhibits extraordinary efficacies in mouse models of acute or chronic inflammatory diseases. Collectively, 62 provides a useful tool for evaluating RIPK1 in animal disease models and a promising lead for further drug development.

Objective To elucidate the efficacy and possible mechanism of Qingchang mixture in ameliorating postoperative abdominal adhesions in rats.Methods Seventy-five Sprague-Dawley rats were randomly allocated into five experimental groups:the control group,the sham-operated group,the model group,the Qingchang mixture treatment group and the sodium hyaluronate treatment group.Except the control group and the sham-operated group,the other three groups were treated with cecal abrasion method to establish the rat model of abdominal adhesion.In the sodium hyaluronate group,2 mL sodium hyaluronate gel was meticulously applied to the injured abdominal wall and cecum prior to abdominal closure.Following successful establishment of adhesion model,the Qingchang mixture group received a daily oral gavage of 2 mL Qingchang mixture(14.58 g/kg),while the other four groups were given equal volume normal saline administration.In each group,five rats were euthanized on postoperative days 3,7 and 14 to assess abdominal adhesions using Nair's scoring system.Adhesive tissue or normal peritoneal tissue were harvested on postoperative day 7,and mRNA expression levels of interleukin-4(IL-4),signal transducer and activator of transcription 6(STAT-6)and interferon-γ(IFN-γ)were quantified via fluorescence-based real-time PCR.Concurrently,Western blot analysis was employed to evaluate protein expression levels of IL-4,interleukin-10(IL-10),STAT-6 and IFN-γ.Pathological alterations in adhesive tissue were visualized using hematoxylin-eosin(HE)staining under light microscopy,and inflammation and fibrotic changes were assessed accordingly.Results Compared with the blank and sham-operated groups,mRNA and protein expression levels of IL-4 and STAT-6 were significantly downregulated in the model group,protein expression level of IL-10 was also reduced.Conversely,the mRNA and protein expression levels of IFN-γ,as well as the inflammation and fibrosis scores were significantly elevated(P＜0.05).In comparison to the model group,IL-4 and STAT-6 mRNA and protein expression levels were increased in the Qingchang mixture group and the hyaluronic acid group,along with an increase in IL-10 protein expression.Conversely,these groups exhibited a significant reduction in Nair's scores,inflammation scores,fibrosis scores,and IFN-γ mRNA and protein expression levels were decreased(P＜0.05).Conclusion Qingchang mixture appears to suppress the development of postoperative peritoneal adhesions,likely through mechanism that involves modulating the expression of T-helper 1 and T-helper 2 cytokines,thereby attenuating inflammatory response.

Objective To monitor the susceptibility of clinical isolates to antimicrobial agents in tertiary hospitals in major regions of China in 2022.Methods Clinical isolates from 58 hospitals in China were tested for antimicrobial susceptibility using a unified protocol based on disc diffusion method or automated testing systems.Results were interpreted using the 2022 Clinical &Laboratory Standards Institute(CLSI)breakpoints.Results A total of 318 013 clinical isolates were collected from January 1,2022 to December 31,2022,of which 29.5％were gram-positive and 70.5％were gram-negative.The prevalence of methicillin-resistant strains in Staphylococcus aureus,Staphylococcus epidermidis and other coagulase-negative Staphylococcus species(excluding Staphylococcus pseudintermedius and Staphylococcus schleiferi)was 28.3％,76.7％and 77.9％,respectively.Overall,94.0％of MRSA strains were susceptible to trimethoprim-sulfamethoxazole and 90.8％of MRSE strains were susceptible to rifampicin.No vancomycin-resistant strains were found.Enterococcus faecalis showed significantly lower resistance rates to most antimicrobial agents tested than Enterococcus faecium.A few vancomycin-resistant strains were identified in both E.faecalis and E.faecium.The prevalence of penicillin-susceptible Streptococcus pneumoniae was 94.2％in the isolates from children and 95.7％in the isolates from adults.The resistance rate to carbapenems was lower than 13.1％in most Enterobacterales species except for Klebsiella,21.7％-23.1％of which were resistant to carbapenems.Most Enterobacterales isolates were highly susceptible to tigecycline,colistin and polymyxin B,with resistance rates ranging from 0.1％to 13.3％.The prevalence of meropenem-resistant strains decreased from 23.5％in 2019 to 18.0％in 2022 in Pseudomonas aeruginosa,and decreased from 79.0％in 2019 to 72.5％in 2022 in Acinetobacter baumannii.Conclusions The resistance of clinical isolates to the commonly used antimicrobial agents is still increasing in tertiary hospitals.However,the prevalence of important carbapenem-resistant organisms such as carbapenem-resistant K.pneumoniae,P.aeruginosa,and A.baumannii showed a downward trend in recent years.This finding suggests that the strategy of combining antimicrobial resistance surveillance with multidisciplinary concerted action works well in curbing the spread of resistant bacteria.