Conventional chemotherapy based on cytotoxic drugs is facing tough challenges recently following the advances of monoclonal antibodies and molecularly targeted drugs. It is critical to inspire new potential to remodel the value of this classical therapeutic strategy. Here, we fabricate bisphosphonate coordination lipid nanogranules (BC-LNPs) and load paclitaxel (PTX) to boost the chemo- and immuno-therapeutic synergism of cytotoxic drugs. Alendronate in BC-LNPs@PTX, a bisphosphonate to block mevalonate metabolism, works as both the structure and drug constituent in nanogranules, where alendronate coordinated with calcium ions to form the particle core. The synergy of alendronate enhances the efficacy of paclitaxel, suppresses tumor metastasis, and alters the cytotoxic mechanism. Differing from the paclitaxel-induced apoptosis, the involvement of alendronate inhibits the mevalonate metabolism, changes the mitochondrial morphology, disturbs the redox homeostasis, and causes the accumulation of mitochondrial ROS and lethal lipid peroxides (LPO). These factors finally trigger the ferroptosis of tumor cells, an immunogenic cell death mode, which remodels the suppressive tumor immune microenvironment and synergizes with immunotherapy. Therefore, by switching paclitaxel-induced apoptosis to mevalonate metabolism-triggered ferroptosis, BC-LNPs@PTX provides new insight into the development of cytotoxic drugs and highlights the potential of metabolism regulation in cancer therapy.

B-cell lymphoma is a group of hematological malignancies characterized by variable genetic and biological features and clinical behaviors. The tumor microenvironment (TME) is a complex network in tumors, which consists of surrounding blood vessels, extracellular matrix, immune and non-immune cells, and signaling molecules. Increasing evidence has shown that the TME, especially immune cells within, is a double-edged sword, acting either as a tumor killer or as a promoter of tumor progression. These pro-tumor activities are driven by subpopulations of immune cells that express typical markers but have unique transcriptional characteristics, making tumor-associated immune cells good targets for human anti-cancer therapy by ablating immunosuppressive cells or enhancing immune-activated cells. Thus, exploring the role of immune cells in the TME provides distinct insights for immunotherapy in B-cell lymphoma. In this review, we elucidated the interaction between immune cells and tumor cells and their function in the initiation, progression, and prognosis of B-cell lymphoma, from preclinical experiments to clinical trials. Furthermore, we outlined potential therapeutic approaches and discussed the potential clinical value and future perspectives of targeting immune cells in patients with B-cell lymphoma.

Background::Although significant advances have been made in the treatment of multiple myeloma (MM), leading to unprecedented response and survival rates among patients, the majority eventually relapse, and a cure remains elusive. This situation is closely related to an incomplete understanding of the immune microenvironment, especially monocytes/macrophages in patients with treatment-na?ve MM. The aim of this study was to provide insight into the immune microenvironment, especially monocytes/macrophages, in patients with treatment-na?ve MM.Methods::This study used the single-cell RNA sequencing (scRNA-seq) data of both patients with MM and heathy donors to identify immune cells, including natural killer (NK) cells, T cells, dendritic cells (DCs), and monocytes/macrophages. Transcriptomic data and flow cytometry analysis of monocytes/macrophages were used to further examine the effect of monocytes/macrophages in treatment-na?ve MM patients.Results::A significant difference was observed between the bone marrow (BM) immune cells of the healthy controls and treatment-na?ve MM patients through scRNA-seq. It is noteworthy that, through an scRNA-seq data analysis, this study found that interferon (IFN)-induced NK/T cells, terminally differentiated effector memory (TEMRA) cells, T-helper cells characterized by expression of IFN-stimulated genes (ISG +Th cells), IFN-responding exhausted T cells, mannose receptor C-type 1 (MRC1) + DCs, IFN-responding DCs, MHCII + DCs, and immunosuppressive monocytes/macrophages were enriched in patients with treatment-na?ve MM. Significantly, transcriptomic data of monocytes/macrophages demonstrated that "don’t eat me" -related genes and IFN-induced genes increase in treatment-na?ve MM patients. Furthermore, scRNA-seq, transcriptomic data, and flow cytometry also showed an increased proportion of CD16 + monocytes/macrophages and expression level of CD16. Cell-cell communication analysis indicated that monocytes/macrophages, whose related important signaling pathways include migration inhibitory factor (MIF) and interleukin 16 (IL-16) signaling pathway, are key players in treatment-na?ve MM patients. Conclusions::Our findings provide a comprehensive and in-depth molecular characterization of BM immune cell census in MM patients, especially for monocytes/macrophages. Targeting macrophages may be a novel treatment strategy for patients with MM.

Integrase inhibitors (INSTIs) are the newest class of antiretroviral drug which are available to people living with the human immunodeficiency virus (HIV). Since 2007, five types of INSTIs have been marketed: Raltegravir, Elvitegravir, Dolutegravir, Bictegravir and Cabotegravir, all of which were approved by the US Food and Drug Administration (FDA) for use in the initiation of antiretroviral therapy (ART) in treatment-na?ve individuals. Compared with other types of antiretroviral drugs, INSTIs have better efficacy and tolerability, so many countries around the world have listed INSTIs-containing regimens as the preferred regimen for HIV ART. In recent years, with the widespread use of INSTIs, some research data suggest that INSTIs may have some adverse effects (AEs), such as central nervous system symptoms, abnormal lipid metabolism, weight gain, abnormal liver and kidney function, etc. This review summarizes the current use of INSTIs in people living with the HIV, and highlights the clinical efficacy and their AEs among the five types of INSTIs in China.

Objective:To investigate the pollution levels and influencing factors of polybrominated diphenyl ethers (PBDEs) in household dust in five cities in northern China.Methods:Based on the "Chinese Indoor Environment and Health Surveillance" project carried out by the National Institute of Environmental Health, Chinese Center for Disease Control and Prevention in 2018-2019, during the warm season (April 2018 to September 2018) and the cold season (November 2018 to March 2019), Lanzhou in Northwest China, Shijiazhuang in North China, Panjin in Northeast China, Luoyang in Central China, and Qingdao in East China were selected as the research sites. A total of 87 families were recruited to study residences in real-life scenarios. At the same time, dust samples were collected to detect the concentration of PBDEs. The level of household environmental indicators was measured, and the residential building characteristics and family behavior habits were collected through questionnaires. A total of 142 valid dust samples and 140 valid questionnaires were obtained. The differences in PBDE concentrations across seasons, wind zones, residential building characteristics, and family habits were analyzed. The exploratory factor analysis was performed to investigate the possible sources of PBDEs, and multivariate linear regression was used to explore the factors influencing PBDEs in household dust.Results:The M ( Q1,Q3) of total PBDE concentrations in 142 household dust samples in five cities was 144.51 (106.61, 222.65) ng/g in the warm season and 145.10 (98.57, 180.65) ng/g in the cold season, respectively. There were seasonal differences in the concentration of ∑ 12PBDEs in Luoyang and Shijiazhuang ( P<0.01). The concentration of BDE-71 was highest among PBDE homologues, followed by BDE-66 and BDE-47. Three factors were extracted by exploratory factor analysis in the warm season, and the cumulative variance contribution rate was 67.90%. The multivariate linear regression showed that the house completion less than ten years [ β (95% CI): 0.186 (0.013, 0.359)], infrequent home cooking [ β (95% CI):-0.342 (-0.570, -0.114)], and increased residential PM 10 concentration [ β (95% CI): 0.001 (0.000, 0.002)] during the warm season, as well as the house far from driveway [ β (95% CI): 0.093 (0.013, 0.172)], house area less than 90 m 2 [ β (95% CI):-0.138 (-0.264, -0.013)], and lower residential xylene concentration [ β (95% CI):-0.006 (-0.011, -0.001)] during the cold season might be related to the elevated concentrations of ∑ 12PBDEs in household dust. Conclusion:The pollution of PBDEs in household dust in five northern cities is at a medium to high level. Years of house completion, frequency of cooking at home, residential PM 10 concentration, distance from house to driveway, house area, and residential xylene concentration may influence household PBDE concentrations.

Objective:To investigate the pollution levels and influencing factors of polybrominated diphenyl ethers (PBDEs) in household dust in five cities in northern China.Methods:Based on the "Chinese Indoor Environment and Health Surveillance" project carried out by the National Institute of Environmental Health, Chinese Center for Disease Control and Prevention in 2018-2019, during the warm season (April 2018 to September 2018) and the cold season (November 2018 to March 2019), Lanzhou in Northwest China, Shijiazhuang in North China, Panjin in Northeast China, Luoyang in Central China, and Qingdao in East China were selected as the research sites. A total of 87 families were recruited to study residences in real-life scenarios. At the same time, dust samples were collected to detect the concentration of PBDEs. The level of household environmental indicators was measured, and the residential building characteristics and family behavior habits were collected through questionnaires. A total of 142 valid dust samples and 140 valid questionnaires were obtained. The differences in PBDE concentrations across seasons, wind zones, residential building characteristics, and family habits were analyzed. The exploratory factor analysis was performed to investigate the possible sources of PBDEs, and multivariate linear regression was used to explore the factors influencing PBDEs in household dust.Results:The M ( Q1,Q3) of total PBDE concentrations in 142 household dust samples in five cities was 144.51 (106.61, 222.65) ng/g in the warm season and 145.10 (98.57, 180.65) ng/g in the cold season, respectively. There were seasonal differences in the concentration of ∑ 12PBDEs in Luoyang and Shijiazhuang ( P<0.01). The concentration of BDE-71 was highest among PBDE homologues, followed by BDE-66 and BDE-47. Three factors were extracted by exploratory factor analysis in the warm season, and the cumulative variance contribution rate was 67.90%. The multivariate linear regression showed that the house completion less than ten years [ β (95% CI): 0.186 (0.013, 0.359)], infrequent home cooking [ β (95% CI):-0.342 (-0.570, -0.114)], and increased residential PM 10 concentration [ β (95% CI): 0.001 (0.000, 0.002)] during the warm season, as well as the house far from driveway [ β (95% CI): 0.093 (0.013, 0.172)], house area less than 90 m 2 [ β (95% CI):-0.138 (-0.264, -0.013)], and lower residential xylene concentration [ β (95% CI):-0.006 (-0.011, -0.001)] during the cold season might be related to the elevated concentrations of ∑ 12PBDEs in household dust. Conclusion:The pollution of PBDEs in household dust in five northern cities is at a medium to high level. Years of house completion, frequency of cooking at home, residential PM 10 concentration, distance from house to driveway, house area, and residential xylene concentration may influence household PBDE concentrations.

Vaccines are among the most effec-tive measures for preventing infectious diseases and play a crucial role in controlling the spread of these diseases.Adjuvants,serving as auxiliary com-ponents in vaccines,are indispensable in the vac-cine development process.Ideal adjuvants not only enhance the immune response,enabling the body to achieve optimal protective immunity but also play important roles in reducing the dosage of im-munogens and lowering vaccine production costs.To meet the demands of novel vaccines,many new types of adjuvants have been developed.However,there is still a lack of adjuvants that are safe,effec-tive,easy to prepare,highly pure,and suitable for a variety of vaccines in clinical settings.This article categorizes adjuvants and summarizes their mecha-nisms of action and characteristics,focusing on tra-ditional aluminum salt adjuvants and more modern lipid-based and nucleic acid-based adjuvants.The summary is based on a computer search of data-bases including PubMed,Embase,The Cochrane Li-brary,CNKI(China National Knowledge Infrastruc-ture),VIP Database,and Wanfang Database,using English search keywords such as Adjuvants,Vac-cine,Vaccine Adjuvant,aluminum salts,MF59,AS03,Toll-like receptor agonist,etc.,and corre-sponding Chinese search terms.The aim is to pro-vide references for the development and applica-tion of adjuvants.

Objective:To construct radiomics models of micro-calcification in carotid plaques, and compare their diagnostic values.Methods:Fifty-two patients with large atherosclerotic cerebral infarction admitted to Department of Neurology, Third Affiliated Hospital of Soochow University from May 2017 to November 2019 were enrolled. All patients underwent conventional carotid artery Doppler ultrasound to detect carotid plaques and Micropure? ultrasound to detect micro-calcifications in the plaques. A cross-section image with maximum numbers of micro-calcifications was chosen when there were micro-calcifications in carotid plaques; otherwise, a cross-section image with the largest area of the plaque was chosen. After all images were normalized by Photoshop software, the plaques were delineated as regions of interest using MaZda 4.6 software and 283 texture features of the plaques were automatically extracted. The texture features with the strongest predictive value were selected through consistency analysis (intrclass correlation coefficient [ICC]>0.75), two-sample t-test, Least absolute shrinkage and selection operator (Lasso) regression. The predictive models were constructed by RandomForest (RF) and Support vector machine (SVM) classifiers. The training set and test set were divided by 7: 3 to analyze the classification accuracy. Receiver operating characteristic (ROC) curves were used to calculate the area under the curve (AUC) to evaluate the diagnostic values of the models. Delong test was used to compare the difference between the diagnostic values of the 2 classifiers in test set. Results:A total of 148 plaque images from 52 patients were enrolled, including 104 plaques with micro-calcification and 44 plaques without micro-calcification. Nine texture features were finally selected after ICC analysis, T test and Lasso regression: 5 image gray histogram features were mean, variance, skewness, kurtosis and 99 th percentile (Perc. 99%); 1 autoregressive model feature was Teta3, and 3 wavelet transform features were WavEnLH_s-3, WavEnLH_s-4, and WavEnLH_s-6. With RF classifier, accuracy of the diagnostic model was 0.93, enjoying AUC of 0.92; with SVM classifier, that was 0.91, enjoying AUC of 0.90; Delong test showed that the diagnostic values of the 2 classifiers in test set were significantly different ( Z=1.000, P=0.320). Conclusion:Radiomic models constructed by RF and SVM classifiers can identify micro-calcification in carotid plaques, and the 2 classifiers share equivalent diagnostic values.

Objective:Considering the large amount and poor quality of clinical data, this study aims to explore the establishment of high-quality research database and its role in real-world research by taking the establishment of lymphoma research database as an example.Methods:The expert opinions in the field of lymphoma were collected, and the relevant guidelines and standards were referenced to establish a standard medical knowledge dataset. The electronic diagnosis and treatment data of lymphoma patients treated in Peking University Cancer Hospital from February 2005 to December 2020 were retrospectively extracted, the deep Learning, natural language processing were adopted to build a dynamic intelligent information integration and processing system of " lymphoma database based on electronic medical record system - biological sample information database - extended genetic information database" .Results:The research database not only meets the research needs of clinical researchers, but also realizes the management of traces in the whole process of application, approval, traceability and analysis of hospital medical record data and biological sample data. The total number of research variables in the database was 668, and the structured variables accounted for 46.0%. On December 25, 2021, there were 68 687 lymphoma patients in the database, the ratio of male to female patients was 8/9, and the proportion of patients with ≥3 visits accounted for 23.0%. In addition, researchers can superimpose searches in the database according to the target conditions, display the targeted medical records according to research hypothesis, and then establish a research cohort, conducting statistical modeling, and mining data information.Conclusions:By integrating management processes and using new natural language artificial intelligence technology to establish a high-level evidence-based database, it is helpful for the interconnection and resource sharing of hospital information systems, so as to achieve the purpose of providing reliable and detailed data for real-world research.

Objective:To study the effect of compound Lactobacillus acidophilus on the apoptosis of intestinal epithelial cells and expression of proliferating cell nuclear antigen (PCNA) in rats with necrotizing enterocolitis, so as to provide some theoretical reference for the application of compound Lactobacillus acidophilus in the prevention and treatment of necrotizing enterocolitis(NEC) for newborn infants. Methods:Thirty-six 48-hour old newborn SD rats were randomly divided into normal group, model group and intervention group, with 12 rats in each group.The NEC model was established by hypoxia and cold stimulation for 3 days, and the intervention group was given the compound Lactobacillus acidophilus at the same time; after the model was established, all the rats were sacrificed after 12 hours of fasting and their intestinal tissues were excised by terminal-deoxynucleoitidyl transferase mediated nick end labeling (TUNEL) method to determine the condition of apoptosis and to detect expression of the PCNA gene in the intestinal tissues by fluorescent quantitative PCR. Results:(1) The apoptosis rates of the intestinal tissues: in the model group, the normal group and the intervention group were (88.33±2.77)%, (4.75±0.75)% and (44.41±4.81)%, respectively, and the differences had statistical significance(all P<0.05). (2) The PCNA expression in the intestinal tissue by real-time PCR in the model group, normal group and intervention group were (9.28±3.26)×10 -4, (15.35±1.91)×10 -4 and (12.09±3.06)×10 -4, respectively, and the differences had statistical significance(all P<0.05). Conclusions:The apoptosis rate of intestinal epithelial cells increases and PCNA expression decreases when NEC occurs.Compound Lactobacillus acidophilus can reduce apoptosis, promote intestinal epithelial cell proliferation, and thus help to reduce the risk and severity of NEC in neonatal rats.