With the acceleration of global urbanization, the intensity and coverage of artificial light at night (ALAN) are increasing, and its service duration is obviously prolonged. ALAN exposure is not only related to the occurrence and development of cardiovascular, metabolic, sleep, myopia, and mental diseases, but also may induce cancer. Previous studies have focused on the health effects of outdoor ALAN, but people spend more than 80% of their lives indoors, hence it is of great significance to understand the relationship between indoor ALAN and population health to create a healthy indoor environment and protect the health of the population.

OBJECTIVE To explore the mechanism of steam-processed Polygonatum sibiricum polysaccharides(SPSP) in prophylaxis and treatment of mice with blood deficiency syndrome(BDS) by RNA sequencing(RNA-seq) technology. METHODS The mice were randomly divided into five groups(10 mice in each group), namely normal group, model group, SPSP groups(0.1, 0.4 g·kg−1), Danggui Buxue oral liquid(DOL) group. BDS model was induced in mice by acetylphenyl-hydrazine and cyclophosphamide. Blood routine, body weight and body temperature were tested after a consecutive administration for 14 d. The differential expressed genes(DEGs) related to anti-BDS by SPSP were screened through the transcriptome sequencing of the hepatic tissue in BDS mice. Functional annotation and enrichment analysis were performed to screen out the gene expression signaling pathways related to the treatment of SPSP on BDS mice. Quantitative polymerase chain reaction(qPCR) was used to verify the experiment. RESULTS Compared with the model group, SPSP(0.4 g·kg−1) could elevate the blood routine indexes such as red blood cell, white blood cell, hemoglobin, platelet, mean corpuscular hemoglobin concen-tration(P<0.01), and reverse the body weight and body temperature to normal(P<0.01 or P<0.05). The result of transcriptomic analysis showed that the underlying mechanism was mainly related to hematopoietic cell line, retinol metabolism, steroid hormone biosynthesis, platelet activation, B cell receptor signaling pathway, and leukocyte transendothelial migration, etc. The result of qPCR showed that SPSP(0.4 g·kg−1) could elevate the expression of JAK1, STAT1 and GATA1 mRNA (P<0.01 or P<0.05). CONCLUSION SPSP has therapeutic effects on BDS. The key DEGs in the treatment of BDS by SPSP are mainly related to the restoration of hematopoietic function, regulation of hormone and immune function. The mechanism of SPSP on treatment of BDS might be the regulation of JAK1/STAT1 signaling pathway.

convalescents, and to screen for broad-spectrum neutralizing antibodies against the SARS-CoV-2 RBD. Methods Using biotinylated RBD as a molecular probe, flow cytometry was employed to perform single-cell sorting of B cells from peripheral blood mononuclear cells (PBMCs) of convalescents. The obtained B cells were lysed and subjected to reverse transcription, followed by nested PCR amplification of the heavy and light chains of antibodies was conducted using random primers. The amplified products were cloned into corresponding expression vectors, and the respective matched heavy-light chain plasmids were co-transfected into 293F cells for expression. Monoclonal antibodies were then purified using Protein A column chromatography. Neutralization experiments were conducted with the wild-type (WT) pseudovirus, and antibodies with IC50<0.1 μg/mL were selected for further testing of neutralizing breadth and potency against the wild-type (WT), Beta variant (B.1.351), Delta variant (B.1.617.2), and currently prevalent pseudovirus strains (XBB, BA.5, BF.7). Results A total of 21 RBD-specific monoclonal B cells were obtained from two recovered patients, resulting in the isolation of 13 pairs of antibody light/heavy chains. Nine antibodies were successfully expressed, with P1-A1, P1-B6, and P1-B9 exhibiting IC50 values below 0.1 μg/mL against the pseudovirus of the wild-type strain (WT). Specifically, P1-B6 effectively neutralized the wild-type strain (WT), Beta variant (B.1.351), and Delta variant (B.1.617.2), with IC50 values reaching 0.01 μg/mL. P1-B9 demonstrated effective neutralization against the wild-type strain (WT), Beta variant (B.1.351), Delta variant (B.1.617.2), and Gamma variant (P.1) pseudoviruses, with IC50 values of 0.42 μg/mL, 0.63 μg/mL, 0.28 μg/mL, and 2.50 μg/mL, respectively. Additionally, P1-B6 exhibited good neutralization against BA.5 and BF.7 pseudoviruses, with IC50 values of 0.06 μg/mL and 0.09 μg/mL, respectively. Conclusions Infection with the SARS-CoV-2 WT strain can induce the generation of neutralizing antibodies with broad-spectrum activity. Generating these broadly neutralizing antibodies does not require an excessively high somatic hypermutation. The obtained antibodies can be used as candidates for SARS-CoV-2 diagnosis and prevention.

Epigenomic imbalance drives abnormal transcriptional processes,promoting the onset and progression of cancer.Although defective gene regulation generally affects carcinogenesis and tumor suppression networks,tumor immunogenicity and immune cells involved in antitumor responses may also be affected by epigenomic changes,which may have significant implications for the development and application of epigenetic therapy,cancer immunotherapy,and their combinations.Herein,we focus on the impact of epigenetic regulation on tumor immune cell function and the role of key abnormal epigenetic processes,DNA methylation,histone post-translational modification,and chromatin structure in tumor immunogenicity,and introduce these epigenetic research methods.We emphasize the value of small-molecule inhibitors of epigenetic modulators in enhancing antitumor immune responses and discuss the challenges of developing treatment plans that combine epigenetic therapy and immuno-therapy through the complex interaction between cancer epigenetics and cancer immunology.

Aim To explore the feasibility of using machine learning algorithms combined with coronary computed tomography(CT)derived perivascular fat attenuation index(FAI)and plaque information to evaluate myocardial ischemia in stable coronary heart disease patients.Methods A retrospective analysis was conducted on the clinical and imaging data of patients who underwent preoperative coronary CT angiography(CCTA),invasive coronary angiography(ICA),and flow reserve fraction(FFR)measurements at Zhongshan Hospital Affiliated to Fudan University from April 2019 to October 2021.206 patients with stable coronary heart disease were selected.The semi-automatic plaque analysis software was used for quantification of plaque and lumen parameters and perivascular FAI measurement,with man-ual delineation of a 40 mm segment of the coronary artery starting 10 mm from the ostium for perivascular FAI measure-ment.Differences in plaque characteristics,perivascular FAI,and coronary perivascular FAI between stable coronary heart disease patients with FFR≤0.8 and FFR＞0.8 were compared.The diagnostic performance of combining perivascu-lar FAI,coronary perivascular FAI,and plaque features using machine learning algorithms for myocardial ischemia in stable coronary heart disease patients was evaluated through ROC curves.Results 206 stable coronary heart disease patients were divided into FFR≤0.8 group(50 cases)and FFR＞0.8 group(156 cases).The mean periplaque FAI of patients with FFR≤0.8 was-69.28±5.65 HU,significantly higher than that of patients with FFR＞0.8 at-80.10±7.75 HU(P＜0.001).Further analysis was conducted using machine learning models,including XGBoost,random forest,and Logistic regression models,all of which had an accuracy rate of over 0.8 in diagnosing myocardial ischemia.Among them,the XGBoost model performed the best with an accuracy of 0.903,an F1 value of 0.774,and an AUC of 0.931,in-dicating its high effectiveness in diagnosing myocardial ischemia.Conclusion The combination of FAI and machine learning algorithm XGBoost model is a new method for diagnosing myocardial ischemia,which has better diagnostic value in evaluating myocardial ischemia in stable coronary heart disease patients.

Purpose To explore the value of ultrasonography in distinguishing periductal mastitis(PDM)from granulomatous lobular mastitis(GLM)and summarize the sonographic features of non-puerperal mastitis(NPM).Materials and Methods The ultrasonographic findings of 134 NPM(84 PDM,50 GLM)patients treated in the Second Hospital of Lanzhou University from July 2016 to June 2021 were retrospectively analyzed.Comparing PDM and GLM sonograms,the difference of lesion number,lesion side,lesion orientation,distance from the nipple,long diameter,thick diameter,aspect ratio,boundary,edge,edge,shape,internal echo,peripheral high echo halo,rear echo,calcification,internal blood flow,ipsilateral axillary lymph node enlargement,and summarize the characteristics of NPM according to the lesion morphology and internal echo.Results There was no statistical difference between PDM and GLM(P＞0.05).But the probability of PDM combined with ipsilateral axillary lymph node enlargement was slightly higher than that of GLM(x2=4.209,P=0.040).The ultrasonography of 134 cases of NPM lesions was divided into 7 types according to the morphology and echo changes.The abscess type was more common in GLM than in PDM(x2=4.928,P=0.026).Conclusion There is no significant difference between PDM and GLM.In the case that PDM and GLM cannot be distinguished clinically and radiologically,it is recommended to perform puncture biopsy to determine the pathological type before treatment,which may be more conducive to obtaining the best prognosis for patients.In addition,the classification of NPM into 7 types is helpful for sonographers to grasp the ultrasonographic characteristics of NPM to diagnose NPM early.

Objective To investigate the effects of Carthamus tinctorius L.extract(CTLE)on the levels of oxidative stress and inflammation in mice with ethanol-induced alcoholic liver disease and its mechanism of action.Methods SPF-grade C57BL/6 male mice were randomly divided into four groups:control group,model group,low-CTLE group(50 mg·kg-1),and high-CTLE group(100 mg·kg-1).The control group was given Lieber-Decarli liquid diet,and the other groups were given Lieber-Decarli alcohol diet to construct a chronic alcoholic liver injury model in mice.Serum and liver tissues of mice were collected and serum biochemical indexes of mice were detected.HE and oil red O staining were applied to observe pathological changes in mouse liver tissues.Real-time fluorescence quantitative PCR and Western Blot were used to detect the mRNA and protein expression levels of Keap1/Nrf2 and STAT3/NF-κB pathway-related factors.Results Compared with the model group,the ALT,AST,LDL-C,and MDA levels were significantly reduced(P＜0.05,P＜0.01),while the levels of HDL-C,SOD,and GSH were increased dramatically in the administered group(P＜0.05,P＜0.01),which indicated that CTLE has specific protective and antioxidant effects on alcoholic liver injury in mice.HE staining and oil red O staining showed that the hepatic lesions and lipid deposition of mice were ameliorated.It enhances the antioxidant and anti-inflammatory effects of the body by activating the mRNA and protein expression levels of antioxidant factors related to the Keap1/Nrf2 pathway and inhibiting the mRNA and protein expression levels of inflammatory factors related to STAT3/NF-κB pathway(P＜0.05,P＜0.01).Conclusion It was shown that CTLE could exert anti-oxidative stress and anti-inflammatory effects through regulating Keap1/Nrf2 and STAT3/NF-κB signaling pathways to attenuate alcoholic liver injury in mice.This study may provide a new idea for the treatment of alcoholic liver disease and the subsequent study of molecular mechanisms.

Objective:To investigate the relationships between the expression level of human epidermal growth factor receptor 2 (HER2) in HER2-positive breast cancer and the characteristics of ultrasound imaging and mammography.Methods:The imaging data of 486 patients with HER2-positive breast cancer treated in the Harbin Medical University Cancer Hospital from January 2014 to December 2021 were retrospectively collected. The relationships between the expression level of HER2 and the imaging features of breast ultrasound and mammography were analyzed.Results:49.38% (240/486) of HER2-positive breast cancer patients were HER2 2+, and 50.62% (246/486) of HER2-positive breast cancer patients were HER2 3+. The age of HER2 2+ patients [ (52.88±1.16) years] was older than the age of HER2 3+ patients [ (49.59±1.00) years], and there was a statistically significant difference ( t=18.07, P<0.001) . There was a statistically significant difference of menstrual status between HER2 2+ patients and HER2 3+ patients ( χ2=4.42, P=0.036) . There were statistically significant differences in the ultrasonography showed burr sign ( χ2=8.37, P=0.010) , posterior echo ( χ2=9.68, P=0.017) , axillary lymph node enlargement ( χ2=15.77, P<0.001) between HER2 2+ patients and HER2 3+ patients. There was a statistically significant difference in the mammography showed whether there were lumps between HER2 2+ patients and HER2 3+ patients ( χ2=15.81, P<0.001) . Conclusion:The expression level of HER2 in HER2-positive breast cancer patients is related to burr sign, posterior echo, and axillary lymph node enlargement shown by ultrasound, as well as lumps shown by mammography, which can provide certain information for clinical prediction of malignant degree of breast cancer, prognosis and individualized treatment plan.

Objective:To investigate the impacts of astragaloside Ⅳ (AS-Ⅳ) on in- vitro proliferation and angioblastic differentiation of human umbilical cord blood-derived mesenchymal stem cells (hUCBMSCs), providing a basis for further research about the effects of AS-Ⅳ on mesenchymal stem cells (MSCs)-mediated angiogenesis. Methods:The hUCBMSCs were extracted from umbilical cord blood of normal full-term infants and subcultured. Osteoblasts, chondroblasts, and lipoblasts were induced, differentiated and identified. At the same time, the surface antigens CD44, CD73, and CD105 on hUCBMSCs were determined by flow cytometry. The successfully identified hUCBMSCs were cultured and treated with a series concentrations of AS-Ⅳ (0, 50, 100, 200, 300, and 400 mg/L). The optimum concentration of AS-Ⅳ for cell proliferation in hUCBMSCs was confirmed. In another experiment, hUCBMSCs were randomly divided into the experimental group and the control group. The cells in the experiment group were treated with the optimum concentration of AS-Ⅳ, and those in the control group were treated with equal volume of PBS. The impact of AS-Ⅳ on the proliferation of hUCBMSCs was detected using the cell counting kit (CCK-8). Besides, the impact of AS-Ⅳ on the angioblastic differentiation of hUCBMSCs was examined using the matrigel in- vitro tube formation assay. CD31 and von willebrand factor (vWF) expressions were determined using immunofluorescence after hUCBMSCs differentiated towards endothelial cells. Results:Under the light microscope, hUCBMSCs had clear edges and arranged orderly, showing a typical long fusiform structure. Flow cytometry confirmed that hUCBMSCs had surface markers of mesenchymal stem cells. The optimum concentration of AS-Ⅳ for the proliferation of MSCs was 300 mg/L. The OD values of the control and experimental groups were (0.51±0.01) and (0.98±0.05), respectively, with statistical significance ( t=15.96, P<0.05), indicating that the proliferation ability of the experimental group was enhanced. Compared with the control group, the tube density and the length of the tube network in vitro in the experimental group were higher, with statistically significant difference [(629.80±52.94)mm vs (110.36±13.19)mm, P<0.05]. Compared with the control group, the expression of CD31 and vWF increased in the experimental group after AS-Ⅳ induced hUCBMSCs differentiation ( t=13.64, 13.18, P<0.05). Conclusions:AS-Ⅳ has no toxicity to human umbilical cord blood mesenchymal stem cells, and can improve their proliferation function, and induce hUCBMSCs to differentiate into endothelial cells.

Objective:To investigate the effect of Astragaloside Ⅳ-mediated Endothelial progenitor cells derived exosomes (EPC-Exos) on the biological function of EPC-Exos damaged by high glicose.Methods:EPCs from human umbilical cord blood were isolated and cultured in vitro. the EPC-Exos secreted by EPCs were extracted by ultracentrifugation combined with ultrafiltration, and identified by specific markers CD9, CD63 and CD81, respectively. After the cells were cultured for 24 hours with AS-IV at 100 mg/L and PBS at the same volume, the morphological characteristics of EPC-Exos were observed by transmission electron microscope. Human endothelial cells were isolated, cultured and identified in vitro. The identified endothelial cells were pretreated with 30 mmol/L glucose for 120 h and randomly divided into experimental group and control group, at the same time set the normal group. The cells were cultured for 24 hours, the effects of EPC-Exos on proliferation, adhesion, migration and angiogenesis of endothelial cells damaged by high glucose were observed by using cell counting kit-8 (CCK-8) Cell Proliferation Assay Kit, cell scratch test, adhesion assay and in vitro angiogenesis assay by Matrigel. Results:Compared with the normal group, the proliferation, migration, adhesion and tubulogenesis of human endothelial cells in the control group were significantly lower ( t=24.35, 6.80, 10.65, 9.62, P<0.05). Compared with the control group, the proliferation, adhesion, migration and tubulogenesis of human endothelial cells in the experimental group were significantly enhanced ( t=30.68, 5.99, 5.40, 8.25, P<0.05). Conclusions:EPC-Exos mediated by AS-Ⅳ can significantly improve the biological function of human endothelial cells damaged by high glucose and has the potential to modulate endothelial neovascularization in diabetic rats.