Long-term outcomes of survivors with influenza A H1N1 virus-induced severe pneumonia and ARDS: a single-center prospective cohort study.

Introduction: Systematic evaluation of long-term outcomes in survivors of H1N1 is still lacking. This study aimed to characterize long-term outcomes of severe H1N1-induced pneumonia and acute respiratory distress syndrome (ARDS). Method: This was a single-center, prospective, cohort study. Survivors were followed up for four times after discharge from intensive care unit (ICU) by lung high-resolution computed tomography (HRCT), pulmonary function assessment, 6-minute walk test (6MWT), and SF-36 instrument. Result: A total of 60 survivors of H1N1-induced pneumonia and ARDS were followed up for four times. The carbon monoxide at single breath (DLCO) of predicted values and the 6MWT results didn't continue improving after 3 months. Health-related quality of life didn't change during the 12 months after ICU discharge. Reticulation or interlobular septal thickening on HRCT did not begin to improve significantly until the 12-month follow-up. The DLCO of predicted values showed negative correlation with the severity degree of primary disease and reticulation or interlobular septal thickening, and a positive correlation with physical functioning. The DLCO of predicted values and reticulation or interlobular septal thickening both correlated with the highest tidal volume during mechanical ventilation. Levels of fibrogenic cytokines had a positive correlation with reticulation or interlobular septal thickening. Conclusion: The improvements in pulmonary function and exercise capacity, imaging, and health-related quality of life had different time phase and impact on each other during 12 months of follow-up. Long-term outcomes of pulmonary fibrosis might be related to the lung injury and excessive lung fibroproliferation at the early stage during ICU admission.

MiR-150 levels are related to in-hospital mortality in non-HIV Pneumocystis pneumonia patients.

Pneumocystis pneumonia (PCP) is a common opportunistic infection that occurs in immunocompromised patients. Compared with HIV patients, PCP in non-HIV patients tends to follow up a more urgent course and poorer prognosis. Therefore, markers that could predict survival of PCP patients in non-HIV population are of great value. MiRNA-150 has been widely studied in many diseases since it has been identified as a vital regulator of immune cell differentiation and activation. We thus conduct this study aiming to evaluate the prognostic value of miR-150 level in non-HIV PCP. First, the expression levels of miR-150 were compared between PCP patients and healthy volunteers. The miR-150 levels in immune cells were also detected in PCP mouse models. Then the prognostic value of miR-150 was further assessed in another PCP population (n = 72). The expression levels of miR-150 were measured by reverse transcription real-time PCR (RT-PCR) technique. Our data demonstrated significantly decreased miR-150 expression levels in PCP patients and mouse models compared to controls. The miR-150 levels also decreased in various immune cells of PCP mouse models. With a cut-off value of 3.48, the area under the curve, sensitivity, specificity of miR-150 to predicate PCP mortality were 0.845, 68.2% and 96.0%, respectively. In conclusion, miR-150 expression value might serve as a potential biomarker to identify PCP patients at high risk of death.

Pneumocystis pneumonia (PCP) remains a fatal risk for immunosuppressed patients. MiR-150 takes part in immune regulation, and thus is involved in infection control. Our study indicated that the miR-150 expression may act as a potential biomarker for predicting mortality of PCP patients.

The systemic immune-inflammation index is significantly associated with the severity of silicosis: a 9-year retrospective study in Beijing.

Background: Silicosis shows an increasing trend with the development of new industries. However, the potential biomarkers for predicting the disease severity are lacking. A novel inflammatory marker, the systemic immune-inflammation Index (SII), has not been studied in silicosis. Methods: In this retrospective study, we used data from a big database platform of a tertiary general hospital in Beijing, which was established based on the electronic medical records of the hospital. The clinical data of adult patients diagnosed with silicosis at the Department of Occupational Medicine and Toxicology from 2013 to 2022 were collected. The data extracted from the database were in de-identified form. Only patients with a first diagnosis of silicosis and without conditions that might affect the parameters of routine blood tests were included in the analysis. Analyses were performed to assess the relationship between SII and the advanced stage of silicosis. Results: A total of 246 participants were included in the study. Most of the patients were exposed to silica particles during excavation and digging (n = 149, 60.6%). SII level was significantly higher in patients with advanced stages of silicosis. A multivariate logistic regression analysis revealed that a higher SII level was associated with the advanced stage of silicosis [odds ratio (OR) = 1.002; 95% confidence interval (CI): 1.000-1.003, p < 0.001] after adjusting for all covariates. The best cutoff value of SII was 444.1. The results of the subgroup analysis also showed a significant correlation between SII level over 444.1 and the advanced stage of silicosis in groups stratified by gender, history of smoking, and duration of silica exposure. Moreover, our results showed a significant but weak negative correlation between the level of SII and some lung function parameters in silicosis. Conclusion: Higher SII is associated with the advanced stage of silicosis and impaired lung function. More long-term, large-scale studies are needed to confirm these findings.

Dynamics of host immune responses and a potential function of Trem2hi interstitial macrophages in Pneumocystis pneumonia.

BACKGROUND: Pneumocystis pneumonia (PCP) is a life-threatening opportunistic fungal infection with a high mortality rate in immunocompromised patients, ranging from 20 to 80%. However, current understanding of the variation in host immune response against Pneumocystis across different timepoints is limited. METHODS: In this study, we conducted a time-resolved single-cell RNA sequencing analysis of CD45+ cells sorted from lung tissues of mice infected with Pneumocystis. The dynamically changes of the number, transcriptome and interaction of multiply immune cell subsets in the process of Pneumocystis pneumonia were identified according to bioinformatic analysis. Then, the accumulation of Trem2hi interstitial macrophages after Pneumocystis infection was verified by flow cytometry and immunofluorescence. We also investigate the role of Trem2 in resolving the Pneumocystis infection by depletion of Trem2 in mouse models. RESULTS: Our results characterized the CD45+ cell composition of lung in mice infected with Pneumocystis from 0 to 5 weeks, which revealed a dramatic reconstitution of myeloid compartments and an emergence of PCP-associated macrophage (PAM) following Pneumocystis infection. PAM was marked by the high expression of Trem2. We also predicted that PAMs were differentiated from Ly6C+ monocytes and interacted with effector CD4+ T cell subsets via multiple ligand and receptor pairs. Furthermore, we determine the surface markers of PAMs and validated the presence and expansion of Trem2hi interstitial macrophages in PCP by flow cytometry. PAMs secreted abundant pro-inflammation cytokines, including IL-6, TNF-α, GM-CSF, and IP-10. Moreover, PAMs inhibited the proliferation of T cells, and depletion of Trem2 in mouse lead to reduced fungal burden and decreased lung injury in PCP. CONCLUSION: Our study delineated the dynamic transcriptional changes in immune cells and suggests a role for PAMs in PCP, providing a framework for further investigation into PCP's cellular and molecular basis, which could provide a resource for further discovery of novel therapeutic targets.

PHGDH knockdown increases sensitivity to SR1, an aryl hydrocarbon receptor antagonist, in colorectal cancer by activating the autophagy pathway.

Colorectal cancer (CRC) has emerged as the third most prevalent and second deadliest cancer worldwide. Metabolic reprogramming is a key hallmark of cancer cells. Phosphoglycerate dehydrogenase (PHGDH) is over-expressed in multiple cancers, including CRC. Although the role of PHGDH in metabolism has been extensively investigated, its effects on CRC development remains to be elucidated. In the present study, it was demonstrated that PHGDH expression was significantly up-regulated in colorectal cancer. PHGDH expression was positively correlated with that of the aryl hydrocarbon receptor (AhR) and its target genes, CYP1A1 and CYP1B1, in CRC cells. Knockdown of PHGDH reduced AhR levels and activity, as well as the ratio of reduced to oxidized glutathione. The selective AhR antagonist stemregenin 1 induced cell death through reactive oxygen species-dependent autophagy in CRC cells. PHGDH knockdown induced CRC cell sensitivity to stemregenin 1 via the autophagy pathway. Our findings suggest that PHGDH modulates AhR signaling and the redox-dependent autophagy pathway in CRC, and that the combination of inhibition of both PHGDH and AhR may be a novel therapeutic strategy for CRC.

Nanozyme-based inulin@nanogold for adhesive and antibacterial agent with enhanced biosafety.

Nanozymes with oxidase or peroxidase-mimicking activity have emerged as a promising alternative for disinfecting resistant pathogens. However, further research and clinical applications of nanozymes are hampered by their low in vivo biosafety and biocompatibility. In this study, inulin-confined gold nanoparticles (IN@AuNP) are synthesized as an antibacterial agent via a straightforward in situ reduction of Au3+ ions by the hydroxyl groups in inulin. The IN@AuNP exhibits both peroxidase-mimicking and oxidase-mimicking catalytic activities, of which the maximum reaction velocity (Vmax) for H2O2 is 2.66 times higher than that of horseradish peroxidase. IN@AuNP can catalyze the production of reactive oxygen species (ROS), resulting in effective antibacterial behavior against both Gram-negative (Escherichia coli) and Gram-positive (Staphylococcus aureus) bacteria. Abundant hydroxyl groups retained in inulin endow the nanozyme with high adhesion to bacteria, reducing the distance between the captured bacteria and ROS, achieving an antibacterial ratio of 100 % within 1 h. Importantly, due to the natural biosafety and non-absorption of the dietary fiber inulin, as well as the inability of inulin-trapped AuNP to diffuse, the IN@AuNP exhibits high biosafety and biocompatibility under physiological conditions. This work is expected to open a new avenue for nanozymes with great clinical application value.

KDM4B down-regulation facilitated breast cancer cell stemness via PHGDH upregulation in H3K36me3-dependent manner.

Despite recent advances have been made in clinical treatments of breast cancer, the general prognosis of patients remains poor. Therefore, it is imperative to develop a more effective therapeutic strategy. Lysine demethylase 4B (KDM4B) has been reported to participate in breast cancer development recently, but its exact biological role in breast cancer remains unclear. Here, we observed that KDM4B was down-regulated in human primary BRCA tissues and the low levels of KDM4B expression were correlated with poor survival. Gain- and loss-of-function experiments showed that KDM4B inhibited the proliferation and metastasis of breast cancer cells. Besides, knockdown of KDM4B promoted the epithelial-mesenchymal transition (EMT) and cell stemness in breast cancer cells. Mechanistically, KDM4B down-regulates PHGDH by decreasing the enrichment of H3K36me3 on the promoter region of PHGDH. Knockdown of PHGDH could significantly reversed proliferation, migration, EMT, and cell stemness induced by KDM4B silencing in breast cancer cells. Collectively, we propose a model for a KDM4B/PHGDH axis that provides novel insight into breast cancer development, which may serve as a potential factor for predicting prognosis and a therapeutic target for breast cancer.

Hotspots and frontiers of human resource allocation research in public hospitals:a CiteSpace-based analysis of domestic and international studies / 现代医院

Objective To investigate the current status,evolving hotspots,and emerging trends in the field of human re-source allocation research in public hospitals,both domestically and internationally,to provide a reference for future research di-rections in China.Methods CiteSpace was used to conduct a visual analysis of the research literature on human resource alloca-tion in public hospitals based on China National Knowledge Infrastructure(CNKI)and the Web of Science(WOS).The analysis encompassed co-authorship,institutional collaboration,keyword co-occurrence and clustering,and burst detection.Results A total of 1 417 Chinese articles and 981 international articles were included.Domestic research in this field focused more on healthcare reform and management,resource allocation,hierarchical diagnosis,and treatment,and informatization and efficiency improvement.On the contrary,international research primarily centered on the employee satisfaction,healthcare system quality,work environment and medical staff.Future trends in domestic research included cost reduction,efficiency enhancement,and a greater emphasis on public welfare in public hospitals,while international research was beginning to explore the influence of polit-ical concepts in this field.Conclusion Compared to international research,domestic research needs to further improve its theo-retical and localized understanding,broaden its research scope,explore the interdisciplinary collaboration opportunities,and delve into research directions such as the application of artificial intelligence and automation technology in healthcare services,management of a diverse workforce,and innovative management techniques and applications.

Prediction of Ki-67 expression status in breast cancer based on ultrasound radiomics combined with clinicopathologic features / 中华超声影像学杂志

Objective:To investigate the prediction of the tumor proliferation antigen(Ki-67) expression status in breast cancer patients based on ultrasound radiomics combined with clinicopathologic features.Methods:Breast cancer patients who underwent 2D ultrasound and Ki-67 examination from January 2018 to February 2022 in Changzhou Second People′s Hospital, Nanjing Medical University were retrospectively analyzed. Among them, 427 patients from Chengzhong campus were randomly divided into training and validation sets in the ratio of 8∶2, and 229 patients from Yanghu campus were used as an independent external test set. Radiomics features were extracted from the region of interest of 2D ultrasound images, and the Mann-Whitney U test, recursive feature elimination, and minimum absolute shrinkage and selection operators were used to perform feature dimensionality reduction and to establish a radiomics score(Rad-score). Subsequently, single/multifactor logistic regression regression analyses were used to construct a joint prediction model based on Rad-score and clinicopathological features. Model performance and utility were assessed using the subject operating characteristic area under the curve (AUC), calibration curve, and decision curve analyses. Results:The AUCs of the joint model for predicting Ki-67 expression status in breast cancer in the training, validation, and test sets were 0.858, 0.797, and 0.802, respectively, which were superior to those of the radiomics (0.772, 0.731, and 0.713) and clinical models (0.738, 0.750, and 0.707). Calibration curve and decision curve analyses indicated that the joint model had good calibration and clinical value.Conclusions:A joint model based on ultrasound radiomics and clinicopathological features can effectively predict the Ki-67 expression status of breast cancer, which is expected to become a non-invasive tool for Ki-67 detection and provide clinicians with an important auxiliary diagnostic and therapeutic decision-making basis.

Mode of Interdisciplinary Research of Traditional Chinese Medicine： Learn from the Study of Biological Characteristics and Mathematical Representation of the Transformation from Phlegm-Dampness Constitution to Dyslipidemia / 中医杂志

The current interdisciplinary research on traditional Chinese medicine （TCM） often comes from the simple combination of TCM application needs and mature engineering technology. Actually， higher goal of cross-disciplinary research should be the win-win development of TCM and interdisciplinary majors. In detail， to enhance the innovative development of original thinking mode of TCM， meanwhile， to stimulate the innovation of interdisciplinary majors with medical tasks. Previously， we successfully performed the research on the objective representation of pre-disease and disease state of dyslipidemia in population with phlegm-dampness constitution. Taking this project as an example， this paper discusses the methodology on scientific issue positioning， key medical tasks selection， interdisciplinary theory， and technology exploration， to expounds the research design and ideas which could be generalized in other cross-disciplinary research of TCM.

Characteristics and prognostic implications of peripheral blood lymphocyte subsets in patients with anti-MDA5 antibody positive dermatomyositis-interstitial lung disease.

OBJECTIVES: To examine the characteristics of blood lymphocyte subsets in dermatomyositis-interstitial lung disease (DM-ILD) inflicted patients with positive anti-melanoma differentiation-associated gene 5 (anti-MDA5), as well as its prognosis value in this set of patients. METHODS: Data were retrospectively collected from 253 DM-ILD patients from three hospitals in China between January 2016 to January 2021. Patients were grouped into anti-MDA5 antibody positive group (MDA5+ DM-ILD) and anti-MDA5 antibody negative group (MDA5- DM-ILD) based on myositis-specific autoantibody test results. Demographic characteristics, lymphocyte subsets patterns and other clinical features were compared between the two groups. The association of lymphocyte subsets with 180-day mortality was investigated using survival analysis in MDA5+ DM-ILD. RESULTS: Out of 253 eligible patients with DM-ILD, 59 patients were anti-MDA5+ and 194 were anti-MDA5-. Peripheral blood lymphocyte count, CD3+ count, percentage of CD3+, CD3+CD4+ count, and CD3+CD8+ count was lower in MDA5+ DM-ILD than in MDA5- DM-ILD- (all P < 0.001) as well as CD3-CD19+ count (P = 0.04). In MDA5+ DM-ILD, CD3+CD8+ count ≤ 49.22 cell/µL (HR = 3.81, 95%CI [1.20,12.14]) and CD3-CD19+ count ≤ 137.64 cell/µL (HR = 3.43, 95%CI [1.15,10.24]) were independent predictors of mortality. CD3+CD8+ count ≤ 31.38 cell/µL was associated with a higher mortality risk in all DM-ILD patients (HR = 8.6, 95%CI [2.12,31.44]) after adjusting for anti-MDA5 and other clinical characteristics. CONCLUSION: Significant lymphocytes decrease was observed in MDA5+ DM-ILD patients. CD3+CD8+ cell count was associated with worse prognosis in both MDA5+ DM-ILD and all DM-ILD patients.

Psittacosis caused severe community-acquired pneumonia accompanied by acute hypoxic respiratory failure: a multicenter retrospective cohort study from China.

INTRODUCTION: Psittacosis can cause severe community-acquired pneumonia (CAP). The clinical manifestations of psittacosis range from subclinical to fulminant psittacosis with multi-organ failure. It is essential to summarize the clinical characteristic of patients with severe psittacosis accompanied by acute hypoxic respiratory failure (AHRF). METHODS: This retrospective study included patients with severe psittacosis caused CAP accompanied by AHRF from 19 tertiary hospitals of China. We recorded the clinical data, antimicrobial therapy, respiratory support, complications, and outcomes. Chlamydia psittaci was detected on the basis of metagenomic next-generation sequencing performed on bronchoalveolar lavage fluid samples. Patient outcomes were compared between the treatment methods. RESULTS: This study included 45 patients with severe CAP and AHRF caused by psittacosis from April 2018 to May 2021. The highest incidence of these infections was between September and April. There was a history of poultry contact in 64.4% of the patients. The median PaO2/FiO2 of the patients was 119.8 (interquartile range, 73.2 to 183.6) mmHg. Four of 45 patients (8.9%) died in the ICU, and the median ICU duration was 12 days (interquartile range, 8 to 21) days. There were no significant differences between patients treated with fluoroquinolone initially and continued after the diagnosis, fluoroquinolone initially followed by tetracycline, and fluoroquinolone combined with tetracycline. CONCLUSION: Psittacosis caused severe CAP seems not rare, especially in the patients with the history of exposure to poultry or birds. Empirical treatment that covers atypical pathogens may benefit such patients, which fluoroquinolones might be considered as an alternative.

Nutritional status in patients with active pulmonary tuberculosis and new nutritional risk screening model for active tuberculosis: a national, multicenter, cross-sectional study in China.

Background: Tuberculosis (TB) remains a significant challenge for public health and is closely associated with malnutrition; however, few studies have attempted to screen malnutrition among TB patients. The study aimed to evaluate the nutrition status and build a new nutritional screening model for active TB. Methods: A retrospective, multicenter, large cross-sectional study was conducted in China from 1 January 2020 to 31 December 2021. All included patients diagnosed with active pulmonary TB (PTB) were evaluated both by Nutrition Risk Screening 2002 (NRS 2002) and Global Leadership Initiative on Malnutrition (GLIM) criteria. Univariate and multivariate analyses were conducted to screen the risk factors associated with malnutrition, and a new screening risk model, mainly for TB patients, was constructed. Results: A total of 14,941 cases meeting the inclusion criteria were entered into the final analysis. The malnutrition risk rate among PTB patients in China was 55.86% and 42.70%, according to the NRS 2002 and GLIM, respectively. The inconsistency rate between the two methods was 24.77%. A total of 11 clinical factors, including elderly, low body mass index (BMI), decreased lymphocyte cells, taking immunosuppressive agents, co-pleural TB, diabetes mellitus (DM), human immunodeficiency virus (HIV), severe pneumonia, decreased food intake within a week, weight loss and dialysis were identified as independent risk factors of malnutrition based on multivariate analyses. A new nutritional risk screening model was constructed for TB patients with a diagnostic sensitivity of 97.6% and specificity of 93.1%. Conclusions: Active TB patients have severe malnutrition status according to screening by the NRS 2002 and GLIM criteria. The new screening model is recommended for PTB patients as it is more closely tailored to the characteristics of TB.

Metabolomic Profiling of Lungs from Mice Reveals the Variability of Metabolites in Pneumocystis Infection and the Metabolic Abnormalities in BAFF-R-Deficient Mice.

Purpose: The incidence of Pneumocystis pneumonia (PCP) in patients without human immunodeficiency virus (HIV) has been increasing. In this study, we aimed to investigate the metabolic changes in Pneumocystis infection and the metabolic abnormalities in B-cell-activating factor receptor (BAFF-R)-deficient mice with Pneumocystis infection. Methods: The important function of B cells during Pneumocystis infection is increasingly recognized. In this study, a Pneumocystis-infected mouse model was constructed in BAFF-R-/- mice and wild-type (WT) mice. Lungs of uninfected WT C57BL/6, WT Pneumocystis-infected, and BAFF-R-/- Pneumocystis-infected mice were used for metabolomic analyses to compare the metabolomic profiles among the groups, with the aim of exploring the metabolic influence of Pneumocystis infection and the influence of mature B-cell deficiency during infection. Results: The results indicated that many metabolites, mainly lipids and lipid-like molecules, were dysregulated in Pneumocystis-infected WT mice compared with uninfected WT C57BL/6 mice. The data also demonstrated significant changes in tryptophan metabolism, and the expression levels of key enzymes of tryptophan metabolism, such as indoleamine 2,3-dioxygenase 1 (IDO1), were significantly upregulated. In addition, B-cell development and function might be associated with lipid metabolism. We found a lower level of alitretinoin and the abnormalities of fatty acid metabolism in BAFF-R-/- Pneumocystis-infected mice. The mRNA levels of enzymes associated with fatty acid metabolism in the lung were upregulated in BAFF-R-/- Pneumocystis-infected mice and positively correlated with the level of IL17A, thus suggesting that the abnormalities of fatty acid metabolism may be associated with greater inflammatory cell infiltration in the lung tissue of BAFF-R-/- Pneumocystis-infected mice compared with the WT Pneumocystis-infected mice. Conclusion: Our data revealed the variability of metabolites in Pneumocystis-infected mice, suggesting that the metabolism plays a vital role in the immune response to Pneumocystis infection.

Research on Supply Chain Financial Risk Prevention Based on Machine Learning.

Artificial intelligence (AI) proves decisive in today's rapidly developing society and is a motive force for the evolution of financial technology. As a subdivision of artificial intelligence research, machine learning (ML) algorithm is extensively used in all aspects of the daily operation and development of the supply chain. Using data mining, deductive reasoning, and other characteristics of machine learning algorithms can effectively help decision-makers of enterprises to make more scientific and reasonable decisions by using the existing financial index data. At present, globalization uncertainties such as COVID-19 are intensifying, and supply chain enterprises are facing bankruptcy risk. In the operation process, practical tools are needed to identify and opportunely respond to the threat in the supply chain operation promptly, predict the probability of business failure of enterprises, and take scientific and feasible measures to prevent a financial crisis in good season. Artificial intelligence decision-making technology can help traditional supply chains to transform into intelligent supply chains, realize smart management, and promote supply chain transformation and upgrading. By applying machine learning algorithms, the supply chain can not only identify potential risks in time and adopt scientific and feasible measures to deal with the crisis but also strengthen the connection and cooperation between different enterprises with the advantage of advanced technology to provide overall operation efficiency. On account of this, the paper puts forward an artificial intelligence-based corporate financial-risk-prevention (FRP) model, which includes four stages: data preprocessing, feature selection, feature classification, and parameter adjustment. Firstly, relevant financial index data are collected, and the quality of the selected data is raised through preprocessing; secondly, the chaotic grasshopper optimization algorithm (CGOA) is used to simulate the behavior of grasshoppers in nature to build a mathematical model, and the selected data sets are selected and optimized for features. Then, the support vector machine (SVM) performs classification processing on the quantitative data with reduced features. Empirical risk is calculated using the hinge loss function, and a regular operation is added to optimize the risk structure. Finally, slime mould algorithm (SMA) can optimize the process to improve the efficiency of SVM, making the algorithm more accurate and effective. In this study, Python is used to simulate the function of the corporate business finance risk prevention model. The experimental results show that the CGOA-SVM-SMA algorithm proposed in this paper achieves good results. After calculation, it is found that the prediction and decision-making capabilities are good and better than other comparative models, which can effectively help supply chain enterprises to prevent financial risks.

Berberine Inhibits Atherosclerosis by Regulating Lipophagy Via Targeting Wnt5a/NPC1 Signaling Pathway / 中国实验方剂学杂志

ObjectiveTo investigate the regulatory effect and molecular mechanism of berberine （BBR） on lipophagy in the prevention and treatment of atherosclerotic （AS） lesions in mice. MethodFifty apolipoprotein E-knockout （ApoE-/-） mice were randomly divided into an AS model group， an atorvastatin group （5 mg·kg-1）， and low-， medium-， and high-dose BBR groups （2.5， 5， 10 mg·kg-1）. Ten C57BL/6J mice were assigned to the control group. After 12 weeks， hematoxylin-eosin （HE） and oil red O staining were performed to assess the histopathological changes of AS plaques in the aorta. Biochemical analysis was used to measure serum lipid levels， and enzyme-linked immunosorbent assay （ELISA） was employed to measure the levels of inflammatory cytokines interleukin-6 （IL-6） and tumor necrosis factor-α （TNF-α）， oxidative stress marker reactive oxygen species （ROS）， and serum lipophagy marker Beclin1 and microtubule-associated protein 1 light chain 3 Ⅱ （LC3Ⅱ）. The xanthine oxidase method was used to measure serum superoxide dismutase （SOD） activity. Immunohistochemistry （IHC） was used to detect the distribution of wingless-type MMTV integration site family member 5a （Wnt5a） and Nieman Pick type C1 （NPC1） in the aorta， and Western blot was used to determine the protein expression of Wnt5a and NPC1 in the aorta. ResultCompared with the control group， the AS model group showed significant AS plaque formation， significantly elevated levels of serum total cholesterol （TC）， triglycerides （TG）， low-density lipoprotein cholesterol （LDL-C）， IL-6， TNF-α， and ROS， aortic Wnt5a distribution and protein expression （P<0.01）， and significantly reduced levels of serum high-density lipoprotein cholesterol （HDL-C）， SOD， Beclin1， LC3Ⅱ， and aortic NPC1 distribution and protein expression （P<0.01）. Compared with the AS model group， the atorvastatin group， and high- and medium-dose BBR groups showed a significant reduction in AS plaque area （P<0.05， P<0.01）， significantly decreased levels of serum TC， TG， LDL-C， IL-6， TNF-α， ROS， and aortic Wnt5a distribution and protein expression （P<0.05， P<0.01）， and significantly increased levels of serum HDL-C， SOD， Beclin1， LC3Ⅱ， and aortic NPC1 distribution and protein expression （P<0.05， P<0.01）. There was no statistically significant difference in the above indicators between the atorvastatin group and the medium-dose BBR group. ConclusionBBR can competitively bind to Wnt5a to activate NPC1 expression， upregulate lipophagy levels， reduce blood lipids， and inhibit the release of inflammatory mediators and oxidative stress damage， thereby exerting a preventive and therapeutic effect on AS.

Physical exercise suppresses hepatocellular carcinoma progression by alleviating hypoxia and attenuating cancer stemness through the Akt/GSK-3β/β-catenin pathway / 中西医结合学报

OBJECTIVE@#Physical exercise, a common non-drug intervention, is an important strategy in cancer treatment, including hepatocellular carcinoma (HCC). However, the mechanism remains largely unknown. Due to the importance of hypoxia and cancer stemness in the development of HCC, the present study investigated whether the anti-HCC effect of physical exercise is related to its suppression on hypoxia and cancer stemness.@*METHODS@#A physical exercise intervention of swimming (30 min/d, 5 d/week, for 4 weeks) was administered to BALB/c nude mice bearing subcutaneous human HCC tumor. The anti-HCC effect of swimming was assessed in vivo by tumor weight monitoring, hematoxylin and eosin (HE) staining, and immunohistochemistry (IHC) detection of proliferating cell nuclear antigen (PCNA) and Ki67. The expression of stemness transcription factors, including Nanog homeobox (NANOG), octamer-binding transcription factor 4 (OCT-4), v-Myc avian myelocytomatosis viral oncogene homolog (C-MYC) and hypoxia-inducible factor-1α (HIF-1α), was detected using real-time reverse transcription polymerase chain reaction. A hypoxia probe was used to explore the intratumoral hypoxia status. Western blot was used to detect the expression of HIF-1α and proteins related to protein kinase B (Akt)/glycogen synthase kinase-3β (GSK-3β)/β-catenin signaling pathway. The IHC analysis of platelet endothelial cell adhesion molecule-1 (CD31), and the immunofluorescence co-location of CD31 and desmin were used to analyze tumor blood perfusion. SMMC-7721 cells were treated with nude mice serum. The inhibition effect on cancer stemness in vitro was detected using suspension sphere experiments and the expression of stemness transcription factors. The hypoxia status was inferred by measuring the protein and mRNA levels of HIF-1α. Further, the expression of proteins related to Akt/GSK-3β/β-catenin signaling pathway was detected.@*RESULTS@#Swimming significantly reduced the body weight and tumor weight in nude mice bearing HCC tumor. HE staining and IHC results showed a lower necrotic area ratio as well as fewer PCNA or Ki67 positive cells in mice receiving the swimming intervention. Swimming potently alleviated the intratumoral hypoxia, attenuated the cancer stemness, and inhibited the Akt/GSK-3β/β-catenin signaling pathway. Additionally, the desmin+/CD31+ ratio, rather than the number of CD31+ vessels, was significantly increased in swimming-treated mice. In vitro experiments showed that treating cells with the serum from the swimming intervention mice significantly reduced the formation of SMMC-7721 cell suspension sphere, as well as the mRNA expression level of stemness transcription factors. Consistent with the in vivo results, HIF-1α and Akt/GSK-3β/β-catenin signaling pathway were also inhibited in cells treated with serum from swimming group.@*CONCLUSION@#Swimming alleviated hypoxia and attenuated cancer stemness in HCC, through suppression of the Akt/GSK-3β/β-catenin signaling pathway. The alleviation of intratumoral hypoxia was related to the increase in blood perfusion in the tumor. Please cite this article as: Xiao CL, Zhong ZP, Lü C, Guo BJ, Chen JJ, Zhao T, Yin ZF, Li B. Physical exercise suppresses hepatocellular carcinoma progression by alleviating hypoxia and attenuating cancer stemness through the Akt/GSK-3β/β-catenin pathway. J Integr Med. 2023; 21(2): 184-193.

Research progress of nuclear medicine imaging in the diagnosis of lymphoma drug-associated early lung injury / 中华放射医学与防护杂志

Drug-associated lung injury (DALI) is one of the important factors affecting the prognosis of patients with lymphoma, and early identification and timely intervention for DALI are essential. Currently, the commonly used imaging examinations, e. g. high-resolution computed tomography, and laboratory tests all have hysteresis, so that the lung injury may be irreversible. Nuclear medicine imaging provides functional and metabolic information for DALI before morphological changes, so that the opportunity for early clinical intervention can be obtained. This article reviews the application of nuclear medicine imaging in lymphoma DALI.

Analysis of clinical characteristics and treatment status of atopic dermatitis in a children's hospital in Beijing from 2015 to 2019 / 中华预防医学杂志

To analyze the clinical characteristics and treatment status of atopic dermatitis (AD) in children in the outpatient department of a children's hospital in Beijing from 2015 to 2019. This study used a cross-sectional study method to retrospectively analyze the data of AD patients who visited the Dermatology outpatient department of Beijing Children's Hospital, Capital Medical University, from April 2015 to April 2019. A total of 1 926 AD patients aged 0-17.5 years old living in Beijing and its surrounding areas were included, and the general situation, severity and distribution of AD disease, clinical characteristics and severity of AD, relevant influencing factors of AD onset, AD disease prognosis and treatment status were recorded. SAS 9.4, SPSS19.0, and R software were used for data processing, and descriptive statistical analysis, Chi-square test, Analysis of Variance, and correspondence analysis were used for statistical analysis. The results showed that the male to female ratio of AD patients in children included in this study was 1.4∶1; 79.0% (1 522/1 926), 86.1%(1 658/1 926), 91.3%(1 758/1 926), and 97.3%(1 907/1 926) of AD onset at the age of 6 months, 1 year, 2 years, and 5 years, respectively; mild of AD patients accounted for 13.2% (255/1 926)(SCORAD score 0-24), moderate of AD patients accounted for 50.1%(965/1 926) (SCORAD score 25-50), and severe of AD patients accounted for 36.7% (706/1 926)(SCORAD score>50).The age of severe AD patients were younger than mild and moderate AD patients. The face, head, trunk, and lower limbs were common areas of onset for moderate to severe AD, while the hands, feet, and ears were common areas of onset for severe AD patients. Temperature changes, hot water factors, mental and emotional states, and spring and winter were the main aggravation factors of AD;35.2% (678/1 926) aggravated and 61.8% (1 191/1 926) persistent. The more frequent bathing, the less severity of AD disease (χ2=29.791,P<0.001); 28.0% (520/1 856) of AD patients have no moisturizing habits, which were correlated with the severity of AD disease (χ2=15.908, P<0.05); the proportion of combined treatment medications in children with moderate to severe AD was significantly higher than mild AD patients. In conclusion, the patients with AD who went to specialist clinics were mainly moderate to severe patients and developed disease before the age of 5 years from 2015 to 2019.The severity of AD were mainly moderate to severe, and most of these patients had poor disease control. Traditional treatment plans had limitations. Identifying the clinical characteristics and treatment status of childhood AD would help us to carry out more targeted prevention and management work.