OBJECTIVE To establish the an optimal prediction model for carbapenem-resistant Acinetobacter bau-mannii(CRAB)infection in ICU patients based on machine learning(ML)so as to help clinicians to diagnose and make decisions.METHODS The clinical data were collected from the patients who were hospitalized in ICUs of a three-A hospital from Jan.1,2017 to Dec.31,2024 and were randomly divided into the training set and the test set in a 7∶3 ratio.The characteristic variables were selected by means of LASSO regression analysis in combina-tion with multivariate logistic regression analysis.Five types of M L classification models were integrated,the opti-mal model was analyzed and identified.The performance of the prediction model for CRAB infection in the ICU patients was evaluated with the use of sensitivity,specificity,accuracy,areas under receiver operating characteris-tic curves(AUCs),calibration curves,Hosmer-Lemeshow test and decision curve analysis(DCA).The outputs of the ML models were interpreted by Shapley additive explanations(SHAP)and permutation importance.RESULTS A total of 2 904 patients were enrolled in the study,695(23.93％)of whom had CRAB infection.The AUC of XGBoost model was highest in the training set and the test set,respectively(0.994 and 0.907).The result of Hosmer-Lemeshow test showed that the calibration curves of the XGBoost model indicated that the predicated risk was highly con-sistent with the observed risk(x2=7.323 and 4.609,P=0.513 and 0.764,respectively).The DCA curves showed that the XGBoost model performed best within the whole range of threshold,with the highest net profit.The length of ICU stay,use of tigecycline,central venous catheterization,use of carbapenems and use of ventilator were determined as the major predictive factors by means of SHAP.CONCLUSIONS The XGBoost model is established and interpreted by SHAP.It provides bases for screening of the ICU patients at high risk of CRAB infection.

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 compare the induction effects of direct treatment with low-temperature plasma(LTP)and treatment with plasma-activated medium(PAM)on immunogenic cell death(ICD)of melanoma cells.Methods After direct treatment of melanoma cell line B16F10 with LTP and treatment of it with PAM for 24 hours,cell viability was detected by MTT assay.Flow cytometry was used to detect cell apoptosis and the expression of calreticulin(CRT)on the cell surface.The adenosine triphosphate(ATP)content in the culture medium was detected by an ATP detection kit.The content of high-mobility group box 1(HMGB1)in the cell culture medium was detected by ELISA.B16F10 cells treated with LTP were co-cultured with immature dendritic cells(DC)DC2.4 cell line,and flow cytometry was used to detect DC surface molecules CD80 and CD86.Results Compared with the control group,both direct treatment and indirect treatment could lead to a decrease in the viability of B16F10 cells,an increase in the apoptosis rate,an increase in intracellular ROS,an increase in CRT expression,and an increase in the secretion of ATP and HMGB1(P＜0.05).At the same treatment time,the expression of CRT and the release of ATP in B16F10 cells directly treated with LTP were higher than those indirectly treated with PAM(P＜0.05).Compared with the DC2.4 group,the expression proportion of the DC cell maturation marker molecule CD80 was significantly increased in LTP-120s group,LTP-180s group,PAM-120s group,and PAM-180s group.The expression proportion of the DC cell maturation marker molecule CD86 was significantly increased in LTP-120s group,LTP-180s group,and PAM-180s group,and the difference was statistically significant(P＜0.05).Conclusion Both direct treatment with LTP and indirect treatment with PAM can induce ICD in melanoma cells.The direct treatment with LTP has a better induction effect.

Objective To analyze the antiviral effect of molnupiravir against influenza virus in vitro and in vivo.Methods The antiviral ability of molnupiravir against influenza virus strain H1N1 PR8 was detected in vitro and in vivo.H uman non-small cell lung cancer cell line(A549 cells)was used as an in vitro model of PR8 infection.The antiviral effects of molnupiravir on virus replication,protein synthesis,and viral particle formation were analyzed using real-time fluorescence quantitative polymerase chain reaction(qRT-PCR),Western blot(WB)assay,and plaque assay.PR8 nose-dripping infected C57BL/6 female mice were used as an in vivo infection model.The antivi-ral ability of molnupiravir was evaluated by detecting viral load,pathological changes,and immunohistochemistry in the control group,administration group,inoculation group,and inoculation-administration group.Results In vitro test results showed that molnupiravir had no significant inhibitory effect on influenza virus replication,protein syn-thesis,and virus particle formation(all P＞0.05).In vivo test results showed that compared with mice infected with H1N1 alone,the viral load in the lung tissue of mice treated with molnupiravir declined significantly,and the extent of pathological changes was milder.Immunohistochemical detection showed a significant weakening in nuclear protein(NP)antigen signal,and the expression levels of interferon(IFN)-α,interleukin(IL)-4,and IL-6 in the lungs were lower(all P＜0.01).Conclusion As a precursor with antiviral activity,molnupiravir can not exert anti-viral activity in lung-derived cells cultured in vitro,but can be transformed into an active form in the host,which significantly decreases the ability of H1N1 influenza virus to proliferate in the lungs and thereby alleviates the da-mage of virus to lung tissue.

OBJECTIVE To establish the an optimal prediction model for carbapenem-resistant Acinetobacter bau-mannii(CRAB)infection in ICU patients based on machine learning(ML)so as to help clinicians to diagnose and make decisions.METHODS The clinical data were collected from the patients who were hospitalized in ICUs of a three-A hospital from Jan.1,2017 to Dec.31,2024 and were randomly divided into the training set and the test set in a 7∶3 ratio.The characteristic variables were selected by means of LASSO regression analysis in combina-tion with multivariate logistic regression analysis.Five types of M L classification models were integrated,the opti-mal model was analyzed and identified.The performance of the prediction model for CRAB infection in the ICU patients was evaluated with the use of sensitivity,specificity,accuracy,areas under receiver operating characteris-tic curves(AUCs),calibration curves,Hosmer-Lemeshow test and decision curve analysis(DCA).The outputs of the ML models were interpreted by Shapley additive explanations(SHAP)and permutation importance.RESULTS A total of 2 904 patients were enrolled in the study,695(23.93％)of whom had CRAB infection.The AUC of XGBoost model was highest in the training set and the test set,respectively(0.994 and 0.907).The result of Hosmer-Lemeshow test showed that the calibration curves of the XGBoost model indicated that the predicated risk was highly con-sistent with the observed risk(x2=7.323 and 4.609,P=0.513 and 0.764,respectively).The DCA curves showed that the XGBoost model performed best within the whole range of threshold,with the highest net profit.The length of ICU stay,use of tigecycline,central venous catheterization,use of carbapenems and use of ventilator were determined as the major predictive factors by means of SHAP.CONCLUSIONS The XGBoost model is established and interpreted by SHAP.It provides bases for screening of the ICU patients at high risk of CRAB infection.

Objective To analyze the antiviral effect of molnupiravir against influenza virus in vitro and in vivo.Methods The antiviral ability of molnupiravir against influenza virus strain H1N1 PR8 was detected in vitro and in vivo.H uman non-small cell lung cancer cell line(A549 cells)was used as an in vitro model of PR8 infection.The antiviral effects of molnupiravir on virus replication,protein synthesis,and viral particle formation were analyzed using real-time fluorescence quantitative polymerase chain reaction(qRT-PCR),Western blot(WB)assay,and plaque assay.PR8 nose-dripping infected C57BL/6 female mice were used as an in vivo infection model.The antivi-ral ability of molnupiravir was evaluated by detecting viral load,pathological changes,and immunohistochemistry in the control group,administration group,inoculation group,and inoculation-administration group.Results In vitro test results showed that molnupiravir had no significant inhibitory effect on influenza virus replication,protein syn-thesis,and virus particle formation(all P＞0.05).In vivo test results showed that compared with mice infected with H1N1 alone,the viral load in the lung tissue of mice treated with molnupiravir declined significantly,and the extent of pathological changes was milder.Immunohistochemical detection showed a significant weakening in nuclear protein(NP)antigen signal,and the expression levels of interferon(IFN)-α,interleukin(IL)-4,and IL-6 in the lungs were lower(all P＜0.01).Conclusion As a precursor with antiviral activity,molnupiravir can not exert anti-viral activity in lung-derived cells cultured in vitro,but can be transformed into an active form in the host,which significantly decreases the ability of H1N1 influenza virus to proliferate in the lungs and thereby alleviates the da-mage of virus to lung tissue.

Objective To compare the induction effects of direct treatment with low-temperature plasma(LTP)and treatment with plasma-activated medium(PAM)on immunogenic cell death(ICD)of melanoma cells.Methods After direct treatment of melanoma cell line B16F10 with LTP and treatment of it with PAM for 24 hours,cell viability was detected by MTT assay.Flow cytometry was used to detect cell apoptosis and the expression of calreticulin(CRT)on the cell surface.The adenosine triphosphate(ATP)content in the culture medium was detected by an ATP detection kit.The content of high-mobility group box 1(HMGB1)in the cell culture medium was detected by ELISA.B16F10 cells treated with LTP were co-cultured with immature dendritic cells(DC)DC2.4 cell line,and flow cytometry was used to detect DC surface molecules CD80 and CD86.Results Compared with the control group,both direct treatment and indirect treatment could lead to a decrease in the viability of B16F10 cells,an increase in the apoptosis rate,an increase in intracellular ROS,an increase in CRT expression,and an increase in the secretion of ATP and HMGB1(P＜0.05).At the same treatment time,the expression of CRT and the release of ATP in B16F10 cells directly treated with LTP were higher than those indirectly treated with PAM(P＜0.05).Compared with the DC2.4 group,the expression proportion of the DC cell maturation marker molecule CD80 was significantly increased in LTP-120s group,LTP-180s group,PAM-120s group,and PAM-180s group.The expression proportion of the DC cell maturation marker molecule CD86 was significantly increased in LTP-120s group,LTP-180s group,and PAM-180s group,and the difference was statistically significant(P＜0.05).Conclusion Both direct treatment with LTP and indirect treatment with PAM can induce ICD in melanoma cells.The direct treatment with LTP has a better induction effect.

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.

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

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.