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 identify potential biomarkers for proliferative diabetic retinopathy(PDR)using proteomics and transcriptomics data.Methods In this study,the proteomics dataset(PXD046630)and two transcriptomics datasets(GSE60436 and GSE102485)were derived from the aqueous humor samples and fibrovascular membranes of PDR patients,respectively.Differentially expressed genes(DEGs)were identified via R software,specifically the limma and edgeR pack-ages.The shared DEGs between PXD046630 and GSE60436 were analyzed via protein-protein interaction(PPI),Gene On-tology(GO)enrichment,and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment analyses.The key DEGs were validated in GSE102485 via receiver operating characteristic(ROC)curve analysis.A quantitative polymerase chain reaction(qPCR)assay was used to confirm the mRNA of these candidate biomarkers in human retinal microvascular endothelial cells(HRMECs)cultured in high glucose and low oxygen conditions.Results A total of 59 shared DEGs and 26 hub genes were identified from the PXD046630 and GSE60436 datasets.KEGG analysis revealed that six pathways,inclu-ding extracellular matrix-receptor interaction,proteoglycans in cancer,and complement and coagulation cascades,were enriched in 12 key DEGs.Fibronectin 1(FN1),tissue inhibitor of metalloproteinase 3(TIMP3),complement factor H(CFH),decorin(DCN),and lipoprotein receptor-related protein-2(LRP2)were identified as potential biomarkers on the basis of their AUC values being greater than 0.900(CI≥95％).The mRNA expression levels of FN1,CFH,and LRP2 were significantly increased in HRMECs cultured in high glucose and low oxygen conditions.Conclusion FN1,CFH,and LRP2 are potential biomarkers for PDR,and further studies are needed to explore their roles and therapeutic potential in PDR.

Aim To explore the effect of hydroxysafflor yellow A(HSYA)on lipocalin 2(LCN2)-induced fer-roptosis in HT22 cells and the related mechanism.Methods Thirty male Sprague-Dawley(SD)rats were used to establish the middle cerebral artery occlu-sion/reperfusion(MCAO/R)model by the suture method.The rats were randomly divided into the Sham group,the MCAO/R group,and the MCAO/R+HSYA group.The infarct area was measured by TTC staining,and the degree of neurological deficit was evaluated by the Z-Longa scoring method.The expressions of LCN2 and 24P3R in brain tissues were detected by Western blot.LCN2 protein was added to HT-22 cells,and the cells were divided into the normal group,the LCN2 group,and the LCN2+HSYA group.The optimal con-centration of LCN2-induced neuronal ferroptosis was screened by LDH assay and Western blot,and the ex-pression levels of ferritin,FPN1,GPX4,SLC7A11,COX2,and 24P3R were detected.LCN2 was knocked down by siRNA transfection,and the expressions of GPX4 and ferritin were detected.The contents of glu-tathione(GSH),malondialdehyde(MDA),GPX4,and Fe2+were determined by colorimetry,and the expres-sion of GPX4 was detected by immunofluorescence.The binding force between HSYA and LCN2 was ana-lyzed by molecular docking technology.Results Ani-mal experiments showed that HSYA could reduce the cerebral infarction area and decrease the neurological function score of MCAO/R rats.Compared with the sham group,the levels of LCN2 and 24P3R increased in the MCAO/R group,while HSYA inhibited their ex-pressions.Cell experiments showed that the optimal concentration of LCN2 to induce ferroptosis in HT22 cells was 2 μmol·L-1.After knocking down LCN2 by siRNA transfection,compared with the LCN2 group,the expression levels of GPX4 and ferritin in the siLCN2 group increased significantly.Compared with the nor-mal group,the expressions of SLC7A11,GPX4,FPN1,ferritin,and GSH in the LCN2 group decreased signifi-cantly,while the concentration of Fe2+,and the expres-sions of MDA,COX2,and 24P3R increased.HSYA could increase the expressions of SLC7A11,GPX4,FPN1,ferritin,and GSH,reduce the contents of Fe2+and MDA,and inhibit the expressions of COX2 and 24P3R.Molecular docking showed that the binding en-ergy between HSYA and LCN2 was-8.0 kJ·mol-1.Conclusion HSYA can inhibit LCN2-induced ferrop-tosis in HT22 cells through the SLC7A11/GPX4 signa-ling pathway.

Creutzfeldt-Jakob disease(CJD)is a rapidly progressive and fatal neurodegenerative disorder caused by prions,with certain infectivity and iatrogenic transmission risks.With the rapid progress and application of new dia-gnostic biomarkers and detection methods,as well as the construction and improvement of surveillance and reporting systems,the detection of CJD in patients domestically and internationally has shown an increasing trend year by year.Due to its long incubation period and heterogeneity of early symptoms,early identification and diagnosis of the disease is difficult,increasing the risk of transmission within medical institutions.Currently,there is a lack of con-sensus on the infection prevention and control of CJD.In order to timely identify and diagnose CJD as well as effec-tively block its transmission in medical institutions,this consensus summarizes 15 clinical concerns and formulates 24 specific recommendations based on the latest domestic and international research findings and clinical evidence,as well as combines with clinical practice,aiming to standardize healthcare-associated infection prevention and control measures for CJD and reduce its transmission risk in medical institutions.

Recent studies have shown that the physiological homeostasis of oral mucosal cells is regulated by the circadian clock.Dis-ruption or dysfunction of the circadian clock is closely associated with the development of oral squamous cell carcinoma(OSCC).Research based on the circadian clock offers a novel perspective on the pathogenesis and therapeutic strategies for OSCC.However,there is current-ly limited research on this topic,and people generally have insufficient understanding and recognition of the circadian clock.Given the complexity and challenges of circadian clock which is the fourth dimension of medical research,we organize relevant experts based on summarizing the current research results of circadian clock in the pathogenesis and precision diagnosis and treatment of OSCC,combining the scientific principles of the circadian clock's role and their long-term research experience,then summarizes and recommends the con-sensus opinions for the research of circadian clock in the pathogenesis mechanism and precision diagnosis and treatment of human OSCC,with the hope of providing guidance for the basic research and clinical application of circadian clock or circadian rhythm in the pathogene-sis mechanism and precision diagnosis and treatment of oral and maxillofacial squamous cell carcinoma.

Aim To explore the effect of hydroxysafflor yellow A(HSYA)on lipocalin 2(LCN2)-induced fer-roptosis in HT22 cells and the related mechanism.Methods Thirty male Sprague-Dawley(SD)rats were used to establish the middle cerebral artery occlu-sion/reperfusion(MCAO/R)model by the suture method.The rats were randomly divided into the Sham group,the MCAO/R group,and the MCAO/R+HSYA group.The infarct area was measured by TTC staining,and the degree of neurological deficit was evaluated by the Z-Longa scoring method.The expressions of LCN2 and 24P3R in brain tissues were detected by Western blot.LCN2 protein was added to HT-22 cells,and the cells were divided into the normal group,the LCN2 group,and the LCN2+HSYA group.The optimal con-centration of LCN2-induced neuronal ferroptosis was screened by LDH assay and Western blot,and the ex-pression levels of ferritin,FPN1,GPX4,SLC7A11,COX2,and 24P3R were detected.LCN2 was knocked down by siRNA transfection,and the expressions of GPX4 and ferritin were detected.The contents of glu-tathione(GSH),malondialdehyde(MDA),GPX4,and Fe2+were determined by colorimetry,and the expres-sion of GPX4 was detected by immunofluorescence.The binding force between HSYA and LCN2 was ana-lyzed by molecular docking technology.Results Ani-mal experiments showed that HSYA could reduce the cerebral infarction area and decrease the neurological function score of MCAO/R rats.Compared with the sham group,the levels of LCN2 and 24P3R increased in the MCAO/R group,while HSYA inhibited their ex-pressions.Cell experiments showed that the optimal concentration of LCN2 to induce ferroptosis in HT22 cells was 2 μmol·L-1.After knocking down LCN2 by siRNA transfection,compared with the LCN2 group,the expression levels of GPX4 and ferritin in the siLCN2 group increased significantly.Compared with the nor-mal group,the expressions of SLC7A11,GPX4,FPN1,ferritin,and GSH in the LCN2 group decreased signifi-cantly,while the concentration of Fe2+,and the expres-sions of MDA,COX2,and 24P3R increased.HSYA could increase the expressions of SLC7A11,GPX4,FPN1,ferritin,and GSH,reduce the contents of Fe2+and MDA,and inhibit the expressions of COX2 and 24P3R.Molecular docking showed that the binding en-ergy between HSYA and LCN2 was-8.0 kJ·mol-1.Conclusion HSYA can inhibit LCN2-induced ferrop-tosis in HT22 cells through the SLC7A11/GPX4 signa-ling pathway.

Creutzfeldt-Jakob disease(CJD)is a rapidly progressive and fatal neurodegenerative disorder caused by prions,with certain infectivity and iatrogenic transmission risks.With the rapid progress and application of new dia-gnostic biomarkers and detection methods,as well as the construction and improvement of surveillance and reporting systems,the detection of CJD in patients domestically and internationally has shown an increasing trend year by year.Due to its long incubation period and heterogeneity of early symptoms,early identification and diagnosis of the disease is difficult,increasing the risk of transmission within medical institutions.Currently,there is a lack of con-sensus on the infection prevention and control of CJD.In order to timely identify and diagnose CJD as well as effec-tively block its transmission in medical institutions,this consensus summarizes 15 clinical concerns and formulates 24 specific recommendations based on the latest domestic and international research findings and clinical evidence,as well as combines with clinical practice,aiming to standardize healthcare-associated infection prevention and control measures for CJD and reduce its transmission risk in medical institutions.

Tumor immunotherapy,recognized as the fourth major treatment modality alongside surgery,radiotherapy,and chemotherapy,fundamentally relies on mobilizing and enhancing the body's intrinsic immune system to achieve the precise targeting and elimination of neoplastic lesions.In this therapeutic framework,macrophages derived from blood monocyte differentiation serve as critical components of the innate immune defense system and exert profound impacts within the tumor microenvironment(TME).As the dominant inflammatory cell population infiltrating the TME,tumor-associated macrophages(TAMs)not only perform a key function in immune regulation but also serve as a paradigm for the connection between inflammation and tumors.Therapeutic strategies targeting TAMs aim to reverse the immunosuppressive milieu of the TME through multifaceted regulatory mechanisms,including cellular depletion or functional reprogramming,thereby effectively impeding tumor progression.This review systematically analyzes the intricate immune regulatory mechanisms of macrophages in tumor immunotherapy and synthesizes research advancements in major therapeutic agents targeting TAMs,aiming to provide researchers in the field of tumor immunotherapy and developers of macrophage-modulating pharmaceuticals with novel theoretical insights and practical guidelines.

OBJECTIVE To study the mechanisms and effect of sufentanil(SUF)on protection of sepsis-induced myocardial injury.METHODS The in vitro experimental models of sepsis-induced myocardial injury were estab-lished by using lipopolysaccharide(LPS).The myocardial H9C2 cells were divided into the Control group,the LPS group,the SUF-L group,the SUF-M group,the SUF-H group,the SUF-H-ComC group and the SUF-H-ML385 group;the LPS group,the SUF-L group,the SUF-M group,the SUF-H group,the SUF-H-ComC group and the SUF-H-ML385 group were the experimental groups.The cells from the experimental groups were respec-tively inoculated and incubated in culture media containing 25 mg/L of LPS,and the culture media were respec-tively added SUF with the terminal dose of 0,5,10,20,20 and 20 μmol/L;the culture media of the SUF-H-ComC was added ComC with the terminal dose of 10 μmol/L,and the culture media of the SUF-H-ML385 was added ML385 with the terminal dose of 5 μmol/L.The cells from the Control group were incubated in normal cul-ture media.The same amount of culture media and CCK-8 reagent without containing myocardial H9C2 cells were assigned as the blank group.The cell viability was determined by CCK-8 method,the levels of reactive oxygen species(ROS),malondialdehyde(MDA),lactate dehydrogenase(LDH),superoxide dismutase(SOD)and gluta-thione peroxidase(GSH-Px)were detected.The Fe2+level of the cells was detected by iron ion colorimetric meth-od.The levels of interleukin(IL)-1β,IL-6 and tumor necrosis factor-α(TNF-α)in supernatant fluid of the culture media were detected with the use of enzyme-linked immunosorbent assay.The expression levels of adenosine 5'-monophosphate-activated protein kinas(AMPK),phosphorylated-AMPK(p-AMPK),nuclear factor erythroid 2-related factor 2(Nrf2)and heme oxygenase-1(HO-1)were detected by means of Western Blot.RESULTS The cell viability of the LPS group was lower than that of the Control group;the levels of ROS,MDA,LDH,Fe2+,IL-1β,IL-6 and TNF-α of the LPS group were higher than those of the Control group;the levels of SOD and GSH-Px of the LPS group were lower than those of the Control group;the expression levels of p-AMPK/AMPK,Nrf2 and HO-1 proteins of the LPS group were lower than those of the Control group(P＜0.05).As compared with the LPS group,the cell viability of the SUF-L group,the SUF-M group and the SUF-H group was succes-sively increased,the levels of ROS,MDA,LDH,Fe2+,IL-1β,IL-6 and TNF-α were successively reduced,the levels of SOD and GSH-Px were successively elevated,and the expression levels of p-AMPK/AMPK,Nrf2 and HO-1 proteins were successively increased(P＜0.05).AMPK pathway inhibitor and Nrf2 pathway inhibitor could reverse the viability of SUF-affecting LPS-induced myocardial H9C2 cells,levels of ROS,MDA,LDH,Fe2+,SOD,GSH-Px,IL-1β,IL-6 and TNF-α and downregulated the expression levels of p-AMPK/AMPK,Nrf2 and HO-1 proteins(P＜0.05).CONCLUSION SUF can improve the sepsis-induced myocardial injury,and the mecha-nism may be associated with activation of AMPK/Nrf2/HO-1 signaling pathways,inhibition of ferroptosis,oxi-dative stress injury and inflammatory reactions.

Objective:To evaluate the clinical equivalence between a domestic calcipotriol/betamethasone dipropionate ointment and the originator product in the treatment of stable plaque psoriasis.Methods:A multicenter, randomized, double-blind, three-arm, parallel-group, active- and placebo-controlled study was conducted, and 449 patients aged 18 - 65 years with stable plaque psoriasis were enrolled from 25 hospitals (such as the First Affiliated Hospital of China Medical University). Eligible patients had a baseline physician's global assessment (PGA) score of ≥ 3 points, baseline body surface area (BSA) involvement of 5% - 30%, and a target lesion psoriasis area and severity index (TL-PASI) for plaque elevation of ≥ 3 points. Participants were randomly assigned in a 2:2:1 ratio to the test group ( n = 179), reference group ( n = 180), and placebo group ( n = 90), and applied the domestic calcipotriol/betamethasone dipropionate ointment, originator product, and ointment base respectively, once daily in the evening for 4 weeks. Efficacy and safety were assessed at weeks 1, 2, and 4. The primary efficacy endpoints were the treatment success rates and clinical success rates in each group at week 4. The per-protocol set (PPS) was used for the primary efficacy analysis, and the intention-to-treat (ITT) set for supplementary efficacy analysis. Equivalence between the test and reference preparations was tested using the Cochran-Mantel-Haenszel method adjusted for randomization strata. Superiority of the test and reference preparations over the placebo was also tested. Measurement data were compared among the 3 groups using analysis of variance or non-parametric tests, while treatment success rates, clinical success rates, and incidence rates of adverse reactions were compared using the chi-square test. Results:The ITT, PPS, and safety sets included 447, 420, and 448 patients, respectively. In the ITT set, patients were aged 43.6 ± 12.8 years, including 320 (71.6%) males and 127 (28.4%) females, and the disease duration was 11.21 ± 9.05 years; 316 (70.7%) had a PGA score of 3 points and 131 (29.3%) had a PGA score of 4 - 5 points. No significant differences in the baseline characteristics (including age, sex, disease duration and disease severity) were observed among the 3 groups (all P > 0.05). Based on the PPS analysis, the treatment success rates were 57.9% (99/171) in the test group, 50.3% (86/171) in the reference group, and 7.7% (6/78) in the placebo group, and the clinical success rates were 57.9% (99/171), 50.3% (86/171), and 10.3% (8/78), respectively; both the test and reference groups were superior to the placebo group in both treatment and clinical success rates (all P < 0.001) ; the rate differences for treatment success (90% confidence interval [ CI]: -1.3% - 16.4%) and clinical success (90% CI: -1.3% - 16.3%) between the test and reference groups were entirely within the pre-defined equivalence margin (-20% - 20%). Subgroup analyses by baseline PGA scores: for patients with a baseline PGA score of 3 points, the treatment success rates in the test, reference, and placebo groups were 60.8% (73/120), 52.1% (62/119), and 11.1% (6/54), respectively, and the corresponding clinical success rates were 61.7% (74/120), 53.8% (64/119), and 13% (7/54), respectively; the test and reference groups did not differ significantly in treatment or clinical success rates (both P > 0.05), but both showed higher success rates than the placebo group (all P < 0.001) ; the results of statistical comparisons among the 3 groups in patients with a baseline PGA score of 4 - 5 points were consistent with those observed in patients with a baseline PGA score of 3 points. The percentage reductions in PGA and TL-PASI scores from baseline to weeks 1, 2, and 4 showed significant differences among the 3 groups, which were significantly higher in the test and reference groups than in the placebo group (all P < 0.001), but did not differ between the test and reference groups (all P > 0.05). The primary adverse reactions were local skin reactions, such as pruritus, pain, and erythema. The incidence rates of adverse reactions were 8.9% (16/179) in the test group, 7.3% (13/179) in the reference group, and 7.8% (7/90) in the placebo group, with no significant difference among the 3 groups ( P > 0.05) . Conclusions:The domestic calcipotriol/betamethasone dipropionate ointment demonstrated clinical equivalence to the originator product in the treatment of stable plaque psoriasis, and the two agents exhibited comparable efficacy for patients with varying degrees of disease severity, and were comparable in the speed and degree of clinical improvement, with similar favorable safety profiles.