1.Advances in research on relationship between indoor artificial light at night and human health
Fengrui ZHU ; Zefeng KANG ; Furong DENG
Journal of Environmental and Occupational Medicine 2024;41(2):214-218
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.
2.Explore the Mechanism of Steam-processed Polygonatum Sibiricum Polysaccharides in Prophylaxis and Treatment of Blood Deficiency Mice Model Based on Transcriptomics
Juan WANG ; Furong WANG ; Xin PENG ; Zhanyun SHEN ; Zhibiao ZHU ; Xiaoling FAN
Chinese Journal of Modern Applied Pharmacy 2024;41(3):324-331
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.
3.Targeting the chromatin structural changes of antitumor immunity
Li NIAN-NIAN ; Lun DENG-XING ; Gong NINGNING ; Meng GANG ; Du XIN-YING ; Wang HE ; Bao XIANGXIANG ; Li XIN-YANG ; Song JI-WU ; Hu KEWEI ; Li LALA ; Li SI-YING ; Liu WENBO ; Zhu WANPING ; Zhang YUNLONG ; Li JIKAI ; Yao TING ; Mou LEMING ; Han XIAOQING ; Hao FURONG ; Hu YONGCHENG ; Liu LIN ; Zhu HONGGUANG ; Wu YUYUN ; Liu BIN
Journal of Pharmaceutical Analysis 2024;14(4):460-482
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.
4.CT coronary perivascular fat attenuation combined with machine learning algorithms for diagnosis of myocardial ischemia in coronary heart disease
Yige LU ; Wei HE ; Hongyan LIN ; Furong HE ; Hanbo ZHANG ; Yao TAN ; Hongming ZHU
Chinese Journal of Arteriosclerosis 2024;32(6):514-520
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.
5.Screening and characterization of anti-SARS-CoV-2 receptor binding domain antibodies with broad-spectrum neutralizing activity
NI Wanqi ; REN Li ; JIN Changzhong ; YANG Furong ; SHEN Yumin ; WANG Shuo ; HU Caiqin ; HAO Yanling ; LIU Ying ; ZHU Biao ; SHAO Yiming ; LI Dan ; WANG Zheng
China Tropical Medicine 2024;24(3):258-
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.
6.Ultrasonography in Differential Diagnosis of Different Types of Non-Puerperal Mastitis and Analysis of Sonographic Features
Qing MA ; Yangyang ZHU ; Yingying JIA ; Zhendong LI ; Furong WANG ; Fang NIE
Chinese Journal of Medical Imaging 2024;32(5):468-472
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.
7.Mechanism of Action of Carthamus tinctorius L.Extract on Alcoholic Liver Disease Through Modulation of Nrf2/STAT3/NF-κB Signaling Pathway
Wenxuan WANG ; Xianglei FU ; Man QI ; Furong FAN ; Furong ZHU ; Yuanchuang WANG ; Kaiyue ZHANG ; Min LIU ; Shenghui CHU
Traditional Chinese Drug Research & Clinical Pharmacology 2024;35(8):1132-1141
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.
8.PPARα affects hepatic lipid homeostasis by perturbing necroptosis signals in the intestinal epithelium.
Shufang NA ; Yanjie FAN ; HongLei CHEN ; Ling LI ; Guolin LI ; Furong ZHANG ; Rongyan WANG ; Yafei YANG ; Zixia SHEN ; Zhuang PENG ; Yafei WU ; Yong ZHU ; Zheqiong YANG ; Guicheng DONG ; Qifa YE ; Jiang YUE
Acta Pharmaceutica Sinica B 2024;14(11):4858-4873
Rapid turnover of the intestinal epithelium is a critical strategy to balance the uptake of nutrients and defend against environmental insults, whereas inappropriate death promotes the spread of inflammation. PPARα is highly expressed in the small intestine and regulates the absorption of dietary lipids. However, as a key mediator of inflammation, the impact of intestinal PPARα signaling on cell death pathways is unknown. Here, we show that Pparα deficiency of intestinal epithelium up-regulates necroptosis signals, disrupts the gut vascular barrier, and promotes LPS translocation into the liver. Intestinal Pparα deficiency drives age-related hepatic steatosis and aggravates hepatic fibrosis induced by a high-fat plus high-sucrose diet (HFHS). PPARα levels correlate with TRIM38 and MLKL in the human ileum. Inhibition of PPARα up-regulates necroptosis signals in the intestinal organoids triggered by TNF-α and LPS stimuli via TRIM38/TRIF and CREB3L3/MLKL pathways. Butyric acid ameliorates hepatic steatosis induced by intestinal Pparα deficiency through the inhibition of necroptosis. Our data suggest that intestinal PPARα is essential for the maintenance of microenvironmental homeostasis and the spread of inflammation via the gut-liver axis.
9.Relationships between HER2 protein expression and imaging features in HER2 positive breast cancer patients
Chengtian FENG ; Furong HUANG ; Shiyu CAO ; Jianyu WANG ; Abiyasi NANDING ; Yongdong JIANG ; Juanying ZHU
Journal of International Oncology 2023;50(9):527-531
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.
10.Transrectal ultrasound/multiparametric magnetic resonance imaging fusion targeted biopsy for the clinically significant prostate cancer detection
Yunkai ZHU ; Yaqing CHEN ; Furong ZHONG ; Xiaoming LI ; Wenbin GUAN ; Lifeng WANG
Chinese Journal of Ultrasonography 2021;30(2):145-150
Objective:To explore the diagnostic value of transrectal ultrasound(TRUS)/multiparametric magnetic resonance imaging(mpMRI) fusion targeted biopsy(FTB) for clinically significant prostate cancer(PCa) detection by using both biopsy histopathology and radical prostatectomy histopathology as reference standards.Methods:A total of 303 consecutive patients with suspicious lesions detected by mpMBI and underwent prostate biopsy at Xinhua Hospital Affiliated to Shanghai Jiaotong University School of Medicine between November 2017 to January 2020 were retrospectively analyzed. All the suspicious lesions were sampled by TRUS/mpMRI FTB in addition with standard 12-core systematic biopsy(SB). The clinically significant PCa detection rates by TRUS/mpMRI FTB and SB were compared by using both biopsy histopathology and radical prostatectomy histopathology as reference standards.Results:The diagnosis of PCa was histologically confirmed in 189 of 303 patients, including 178 patients with clinically significant PCa and 11 patients with clinically insignificant PCa. With biopsy histopathology as reference standard, the clinically significant PCa detection rate of TRUS/mpMRI FTB was statistically higher than SB (57.1% vs 45.9%, P<0.001). Among 189 patients with biopsy proven PCa, 80 patients underwent radical prostatectomy, and the radical prostatectomy histopathology confirmed 79 patients with clinically significant PCa.With radical prostatectomy as reference standard, the clinically significant PCa detection rate of TRUS/mpMRI FTB was statistically higher than SB (91.1% vs 74.7%, P<0.001). Conclusions:Compared with SB, MRI/US FTB can offer more accurate sampling of suspicious lesions on mpMRI, and consequently improve the clinically significant PCa detection rate.


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