Cuproptosis, a recently identified form of regulated cell death triggered by excess intracellular copper, has emerged as a promising cytotoxic strategy for cancer therapy. However, the therapeutic efficacy of copper ionophores such as elesclomol (ES) is often hindered by cellular copper homeostasis mechanisms that limit copper influx and cuproptosis induction. To address this challenge, we developed a nanoagent utilizing outer membrane vesicle (OMV) derived from Akkermansia muciniphila (Akk) for co-delivery of antioxidant 1 copper chaperone (Atox1)-targeting siRNA and ES (siAtox1/ES@OMV) to tumors. In vitro, we demonstrated that Atox1 knockdown via siRNA significantly disrupted copper export mechanisms, resulting in elevated intracellular copper levels. Simultaneously, ES facilitated efficient copper influx and mitochondrial transport, leading to Fe-S cluster depletion, increased proteotoxic stress, and robust cuproptosis. In vivo, siAtox1/ES@OMV achieved targeted tumor delivery and induced pronounced cuproptosis. Furthermore, leveraging the immunomodulatory properties of OMVs, siAtox1/ES@OMV promoted T-cell infiltration and the activation of tumor-reactive cytotoxic T cells, enhancing tumor immune responses. The combination of siAtox1/ES-induced cuproptosis and immunogenic cell death synergistically suppressed tumor growth in both subcutaneous breast cancer and orthotopic rectal cancer mouse models. This study highlights the potential of integrating copper homeostasis disruption with a copper ionophore using an immunomodulatory OMV-based vector, offering a promising combinatorial strategy for cancer therapy.

Objective:To analyze and compare the health education efforts of respiratory infectious diseases at home and abroad.Methods:The literature related to health education and popular science of respiratory infectious diseases included in the databases of China National Knowledge Infrastructure (CNKI) and Web of Science (WOS) from January 1, 2003 to December 31, 2023 was searched. A total of 4 686 articles were retrieved in CNKI, 1 540 articles unrelated to the theme were excluded, and 3 146 Chinese articles were obtained. In the WOS database, 7 724 articles were retrieved, 3 685 articles about the clinical mechanism of diseases, pharmacology, and other research topics were excluded, and 4 039 English articles were obtained. The information of annual publications, institutions, authors and keywords was analyzed by using CiteSpace visualization software, and the publication status, research hotspots and development trends of health education related to respiratory infectious diseases at home and abroad were analyzed.Results:Since 2003, the number of publications in health education on respiratory infectious diseases at home and abroad had shown a fluctuating growth trend, and in 2020, the field showed a sharp growth trend at home and abroad. There was no core author group in this field in China, and the network density of domestic authors was 0.006 5, and the network density of foreign authors was 0.009 6. The domestic institutions were mainly the Center for Disease Control and Prevention and medical institutions, including Guangzhou Chest Hospital (29 articles) and the Chinese Center for Disease Control and Prevention (10 articles); Foreign research institutions were mainly higher education institutions, including the University of London (91 articles) and Harvard University (67 articles). The network density of domestic was 0.001 3, and the network density of foreign publishing institutions was 0.026 3, the network density was greater than that of Chinese publishing institutions. The emergence of "COVID-19" "Avian influenza" "Knowledge, Attitude, Practice" and "mental health" in China had strong burst (burst intensity: 46.41, 12.12, 10.33, 8.5); "Coronavirus" "coverage" "Avian influenza" and "COVID-19 vaccine" in foreign countries had strong burst (burst intensity: 14.34, 11.06, 10.73, 10.02).Conclusions:At present, the health education of respiratory infectious diseases at home and abroad has received great attention. But the cooperation between domestic authors and research institutions is loose, and the close collaboration needs to be strengthened. There are differences in the research focus of health education on respiratory infectious diseases at home and abroad.

Objective:To analyze changes in plasma amino acid profiles in adolescents and adults with atopic dermatitis (AD) by targeted metabolomics, to further analyze differences in plasma amino acid profiles between AD patients with elevated total IgE levels and those with normal total IgE levels, as well as between AD patients with and without allergic rhinitis, and to explore the pathogenesis of AD from the perspective of metabolic pathways.Methods:From December 2021 to June 2022, 40 AD patients aged > 12 years were collected as research subjects from the Department of Dermatology, the First Affiliated Hospital of Jinzhou Medical University, and 30 healthy checkup examinees served as a control group at the same time. Plasma samples were obtained from the subjects, and high-performance liquid chromatography-mass spectrometry was performed to detect levels of metabolites in the plasma samples. Principal component analysis (PCA) and orthogonal partial least square-discriminant analysis (OPLS-DA) were carried out to analyze data and screen out differential metabolites with the variable weight value (VIP) of the first principal component being > 1 in the OPLS-DA model and the P value being < 0.05 in the t test. Possible abnormal metabolic pathways were analyzed using MetaboAnalyst 5.0 software, and differential metabolic pathways were defined as those with an impact value of > 0.1 and a P value of < 0.05. Results:PCA and OPLS-DA model analysis showed that metabolites were well differentiated among the groups, and differential metabolites and metabolic pathways were screened out. Concretely speaking, 12 differential metabolites and 8 differential metabolic pathways were identified by comparing the AD group with the control group, among which differential metabolites included arginine (metabolic levels: 28.257 ± 11.517 μmol/L vs. 21.038 ± 8.500 μmol/L, VIP = 1.32, P = 0.001), ornithine (47.597 ± 18.158 μmol/L vs. 36.937 ± 5.813 μmol/L, VIP = 1.26, P < 0.001) and histidine (78.322 ± 14.971 μmol/L vs. 100.694 ± 32.419 μmol/L, VIP = 1.33, P < 0.001), and differential metabolic pathways included arginine biosynthesis (impact = 0.482, P < 0.001) and histidine metabolism (impact = 0.221, P < 0.001). Comparisons between the AD group with elevated IgE levels and those with normal IgE levels showed 5 differential metabolites and 3 differential metabolic pathways, among which differential metabolites included lysine (313.998 ± 61.252 μmol/L vs. 285.330 ± 58.388 μmol/L, VIP = 2.25, P < 0.001) and glycine (200.807 ± 53.320 μmol/L vs. 187.056 ± 50.941 μmol/L, VIP = 1.40, P = 0.014), and differential metabolic pathways included the glyoxylate and dicarboxylate metabolic pathway (impact = 0.105, P = 0.001) ; by comparing the AD group with and without allergic rhinitis, 6 differential metabolites and 3 differential metabolic pathways were identified, among which the arginine biosynthesis metabolic pathway was highlighted (impact = 0.116, P < 0.001) . Conclusion:The plasma amino acid metabolites in adolescents and adults with AD were different from those in healthy controls, and elevated plasma levels of arginine and ornithine and decreased plasma level of histidine may be involved in the pathogenesis of AD; increased plasma levels of lysine and glycine were associated with AD with elevated IgE levels; the arginine biosynthetic metabolic pathway was related to AD complicated by allergic rhinitis.

Natural killer (NK) cells are an important part of the body's innate immune system. As the first line of defense against pathogens, they need to be transformed into a mature state under the control of various cell signaling molecules and transcription factors to play cytotoxic and immune regulatory roles. Under the interaction of activated receptors and inhibitory receptors, NK cells are activated to perform a direct cell killing effect by secreting perforin and granzyme, or indirectly eliminate pathogenic microorganisms in the body by secreting various cytokines, such as type I and type II interferons. These functions of NK cells play a very important role in antiviral and anti-autoimmune diseases, especially in anti-tumor.
Humans ; Killer Cells, Natural ; Interferon-gamma ; Apoptosis ; Autoimmune Diseases ; Cytokines

Animals ; Antigens, Surface/genetics* ; Cell Communication/genetics* ; Copulation/physiology* ; Fallopian Tubes/metabolism* ; Female ; Fertilization/genetics* ; GPI-Linked Proteins/genetics* ; Gene Expression Regulation ; Genes, Reporter ; Green Fluorescent Proteins/metabolism* ; Litter Size ; Luminescent Proteins/metabolism* ; Male ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; Mitochondria/metabolism* ; Reproduction/genetics* ; Signal Transduction ; Sperm Count ; Sperm Motility/genetics* ; Spermatozoa/metabolism* ; Uterus/metabolism*

BACKGROUND: Mis Seven implant has become more and more popular in oral implant restoration, and the clinical application in dentate-deficient patients remains to be studied. OBJECTIVE: To explore the short-term effects of the Mis Seven implant system on fixed restorations in dentition loss. METHODS: Nineteen patients undergoing fixed dental prostheses with the Mis Seven system due to dentition loss at the Department of Implants of the Stomatological Hospital of Guangzhou Medical University between April 2015 and December 2017 were included. Three patients had missing maxillary and maxillary dentition and unilateral maxillary teeth. Six patients were loss of maxillary dentition, and there were 10 cases of unilateral mandibular dentition missing. The total dental implants were 134. All cases were implanted and fixed for one stage. Clinical examination, alveolar bone and inter-implant image performance and post-load repair effect at 6, 12 and 24 months of follow-up were used as evaluation indicators. RESULTS AND CONCLUSION: (1) In 134 implants, failure was in 2 cases due to surrounding tissue infection. The success rate of before implant restoration was 98.51％, and the success rate after repair was 100％. (2) The stability of dentition of 19 patients was good, showing good occlusion. No mechanical complications or biological complications occurred. The stability of the restoration was 100％. (3) The vertical absorption of bone tissue around all implants was less than 0.2 mm at 6, 12, 24 months after repair, suggesting that the implant has no obvious edge bone resorption. The gingival tissues around all implants were healthy, and no unhealed inflammation or hyperkeratosis appeared. (4) These results imply that the Mis Seven system in the dentition defect fixation exhibits good short-term clinical results.

Objective The concentrations of Th1/Th2/Th17 cytokines were compared in acute and chronic patients with brucellosis in order to understand the immune characteristics of acute and chronic brucellosis. Methods Using forward-looking design, 35 acute and 35 chronic patients with brucellosis were selected before treatment from the Endemic Disease Prevention and Control Center of Wulanchabu City as the research subjects with 25 local healthy persons as the healthy control group from March to June 2018. Enzyme linked immunosorbent assay (ELISA) method was used to determine the serum levels of Th1 cell cytokines interferon-γ(IFN-γ), tumor necrosis factor-α(TNF-α), and interleukin-12 (IL-12); Th2 cell cytokines interleukin-4 (IL-4), interleukin-6 (IL-6), and interleukin-10 (IL-10);and Th17 cell cytokines interleukin-17 (IL-17). Results There were totally 25 patients in the control group, aged (46.48 ± 9.74) years, 15 males and 10 females;35 patients with acute brucellosis, aged(54.00 ± 7.65) years, 23 males and 12 females; and 35 patients with chronic brucellosis, aged (49.04 ± 8.24) years, 22 males and 13 females. The means of IFN-γ[(280.50 ± 40.48), (462.79 ± 47.94), (431.91 ± 40.39) ng/L], TNF-α[(292.17 ± 31.45), (481.21 ± 43.14), (433.70 ± 41.23) ng/L], IL-12 [(45.13 ± 5.55), (70.74 ± 7.58), (62.56 ± 5.73) ng/L], IL-4 [(383.24 ± 53.98), (606.11 ± 51.86), (550.66 ± 51.56) ng/L], IL-6 [(14.48 ± 2.17), (23.54 ± 2.39), (21.89 ± 2.26) ng/L], IL-10 [(140.48 ± 110.97), (464.49 ± 52.10), (404.73 ± 52.10) ng/L], and IL-17 [(13.71 ± 1.58), (23.79 ± 2.15), (21.37 ± 2.26) ng/L] were significantly different between control group, acute brucellosis group and chronic brucellosis group (F = 126.13, 152.58, 106.81, 139.28, 113.80, 155.86, 152.91, P < 0.05). Compared to control group, the levels of the seven cytokines in acute brucellosis and chronic brucellosis groups were significantly increased before treatment (P < 0.05). The levels of all of the seven cytokines in acute brucellosis group were significantly increased compared to chronic brucellosis group before treatment (P < 0.05). Conclusions There is a difference in the expression of Th1/Th2/Th17 cytokines in patients with acute and chronic brucellosis group. In the acute brucellosis group, the cell immunity induced by Th1 cells and the humoral immunity guided by Th2 cells are stronger than those in chronic brucellosis group.

Objective: To investigate the value of short tandem repeat (STR) genotyping in the diagnostic workup of molar and non-molar gestations with correlation of histological characteristics. Methods: Six hundred and fifty-six cases were selected based on clinically suspected hydropic abortion and/or molar pregnancy from July 2015 to September 2017 at Beijing Obstetrics and Gynecology Hospital. DNA was extracted from dissected chorionic villi and paired maternal endometrial FFPE tissue samples by Simplex OUP™ FFPE DNA Tissue Kit. STR genotyping was performed by PowerPlex 16 HS system. Results: DNA genotyping was informative in 649 of 656 cases, leading to identification of 215 hydatidiform mole gestations and 434 non-molar gestations. Most of non-molar gestations (375 cases, 86.4%) were diploid hydropic abortion. Various trisomy syndromes were found (53 cases, 12.2%), including trisomy 2, 3, 4, 7, 8, 13, 16 and 21. Only 2(0.5%) digynic triploid gestations were detected. Moreover, 4 cases (0.9%) of uniparental disomies (homologous or heterologous) were found. There were 196 cases with histologic diagnostic suspicious of hydatidiform moles were accurate sub-classified. Among them, 59 cases hydatidiform moles were under-diagnosed as diploid hydropic abortions, and 28 cases diploid hydropic abortions were over-diagnosed as hydatidiform moles.Compared with partial moles(PHM), there were no specific histomorphological features between the various types of non-molar gestations and partial moles for definitive diagnostic separation. There was no significant difference in the expression of p57^kip2 among PHM, trisomy and diploid hydropic abortions group (P=0.247). Conclusions STR genotyping can distinguish non-molar gestations from early hydatidiform moles, and efficiently avoid misdiagnosis based only on histological evaluation. Therefore, using STR genotyping, not only can the overdiagnosis of non-molar pregnancy be avoided, but also individualized management can be offered to patients including monitoring of serum hCG.

Objective To explore the feasibility of low concentration contrast medium and low-voltage combined with adaptive statistical iterative reconstruction(ASRI)technique in enhanced CT imaging of solitary pulmonary nodules. Methods A total of 40 patients with solitary pulmonary nodules who underwent routine exam-inations and were pathologically confirmed from February 2015 to February 2017 were collected and divided into conventional group(conventional dose,high osmolar contrast,using filtered back projection reconstruction)and low dose group(low voltage,low concentration isotonic contrast,iterative reconstruction). Results Subjective scoring of conventional group(3.97 ± 0.57)and low dose group(4.01 ± 0.54)indicated no statistical significance (P > 0.05). No significant difference was found regarding to reconstructed image quality,SNR and CNR in both two groups.The dose length product(DLP)and effective dose(ED)in low dose group were lower than those in the conventional group[(283.52 ± 11.50)mGy/cm vs(370.74 ± 29.56)mGy/cm;(3.65 ± 0.32)mSV vs(5.11±0.25) mSV],and the difference was statistically significant(P < 0.05). Conclusions Low concentration isotonic con-trast agent(iodixanol 270 mgI/L)and low voltage(100 kV)combined with ASIR technology could satisfy the clini-cal need in enhanced CT imaging of solitary pulmonary nodule.

Objective To study the CYP2C19 genotype in patients with acute coronary syndrome(ACS) complicated with diabetes mellitus(DM)receiving percutaneous coronary intervension(PCI)by polymerase chain reaction(PCR),and to evaluate the efficacy of Ticagrelor in CYP2C19 gene polymorphism. Methods A total of 494 ACS patients with DM were enrolled. The patients were divided into routine treatment group and individual treatment group. Routine treatment group received 0.1 g/d aspirin/d and 75 mg/d of Clopidogrel. CYP2C19 gene polymorphism was examined in individual treatment group.(*1/*1)was classified into fast metabolic type,mutant heterozygous type(*1/*2,*1/*3)into intermediate metabolic type and mutant pure type (*2/*2,*2/*3,*3/*3) into slow metabolic type. Fast metabolic type received aspirin 0.1 g/d and Clopidogrel 75 mg/d,and intermediate and slow metabolic type received aspirin 0.1 g/d and Ticagrelor 90 mg bid for 12 months or more to observe the inci-dence of adverse cardiovascular events ,bleeding and other adverse reactions in 2 groups. Results The incidence of cardiac death ,recurrent myocardial infarction and angina pectoris ,stroke ,stent thrombosis and target vessel revascularization in routine treatment group was significantly higher than that in individual treatment group(P <0.05). There was no significant difference between two groups in terms of major bleeding and secondary bleeding (P > 0.05). The minimum bleeding rate was slightly higher in intermediate metabolic type in individual treatment group but without significantly difference when compared with that in fast metabolic type and slow metabolic type (both P>0.05). Conclusion Without elevating the risk of bleeding within 12 months,the efficacy of Ticagrelor is not affected by CYP2C19 gene polymorphism in patients with ACS complicated with DM after PCI.