1.Application value of a multi-dimensional digital monitoring platform for perioperative period in gastric cancer patients
Jiayu LI ; Zhiwei JIANG ; Gang WANG ; Huafeng PAN ; Miaomiao GE ; Haifeng WANG ; Pengyan XU ; Yuling CAI ; Nan HAIOU ; Cheng ZHANG
Chinese Journal of Digestive Surgery 2024;23(4):601-608
Objective:To investigate the application value of a multi-dimensional digital moni-toring platform for perioperative period in gastric cancer patients.Methods:The retrospective cohort study was conducted. The clinical data of 50 patients who underwent laparoscopic radical gastrec-tomy in The Affiliated Hospital of Nanjing University of Chinese Medicine from July 2022 to January 2024 were collected. There were 35 males and 15 females, aged (64±12)years. All patients followed the concept of enhanced recovery after surgery, and the multi-dimensional digital monitoring platform based on wearable monitoring equipment was used to implement perioperative management measures. Observation indicators: (1) results of heart rate variability (HRV) monitoring; (2) results of blood glucose and blood oxygen monitoring; (3) results of exercise and sleep monitoring; (4) results of body composition monitoring. Measurement data with normal distribution were represented as Mean± SD, and measurement data with skewed distribution were represented as M(IQR). Repeated measurement data were analyzed using the repeated ANOVA. Measurement data with skewed distri-bution were transformed to normal distribution by SPSS transformation function before testing. For comparison between pre- and postoperation, paired sample t test was used for measurement data with normal distribution, and nonparametric Wilcoxon signed rank sum test was used for measure-ment data with skewed distribution. Results:(1) Results of HRV monitoring. From preoperation to the third day after surgery, the standard deviation normal to normal heart beat of 50 patients was changed from(103±26)ms to(101±36)ms, the mean of the standard deviations of normal to normal heart beat calculated per 5 min segment was changed from (45±16)ms to(33±12)ms, the number of pairs of adjacent NN intervals differing by more than 50 ms in the entire recording was changed from 6.02%(4.96%) to 5.79%(4.20%), the low frequency power was changed from 376.78(468.96)ms 2 to 742.79(525.20)ms 2, the high frequency power was changed from 273.61(273.58)ms 2 to 397.48(164.87)ms 2, the ratio of low frequency power to high frequency power was changed from 1.6±0.5 to 1.6±0.6, showing significant differences in above indicators before and after operation ( F=34.43, 26.15, 24.58, 5.51, 6.11, 6.02, P<0.05). (2) Results of blood glucose and blood oxygen monitoring. From preoperation to the third day after surgery, the blood glucose of 50 patients was changed from 6.75(2.05)mmol/L to 6.90(2.63)mmol/L, showng a significant difference before and after operation ( F=45.84, P<0.05). The blood oxygen was changed from 97.00%(5.00%) to 97.50%(3.00%), showing no significant difference before and after operation ( F=2.25, P>0.05). (3) Results of exercise and sleep monitoring. From preoperation to the third day after surgery, the number of steps fo 50 pati-ents was changed from 3 043(1 224) to 1 473(767), sleep duration was changed from(8.2±1.1)hours to(7.3±0.8)hours, sleep score was changed from 80±10 to 78±5,showing significant differences in above indicators before and after operation ( F=716.46, 29.02, 47.32, P<0.05).(4) Results of body composition monitoring. The body weight of 50 patients was changed from (63±8)kg to(61±8)kg before and after operation, body fat rate was changed from 24%±8% to 22%±9%, muscle mass was changed from 43 (12)kg to 41(17)kg, body mass index was changed from (23.0±2.6)kg/m 2 to(22.1±2.5)kg/m 2, showing significant differences in above indicators before and after operation ( t=8.19, 3.00, Z=-2.78, t=7.34, P<0.05), while there was no significant difference in basal metabolic indicators from (1 390±134)kcal to (1 379±139)kcal before and after operation ( t=1.02, P>0.05). Conclusion:The multi-dimensional digital monitoring platform for preoperative period can accurately monitor the perioperative stress level and evaluate the postoperative recovery of gastric cancer patients, which can present the visual results.
2.Economic toxicity studies in patients with head and neck cancer:a scoping review
Ping XU ; Miaomiao ZHANG ; Rong YAN ; Kai JIANG ; Wenhui LIU ; Jun′ai XIANG
Chinese Journal of Practical Nursing 2024;40(30):2394-2401
Objective:To understand the status, evaluation methods and risk factors of economic toxicity in patients with head and neck cancer, in order to provide reference for the construction of follow-up intervention programs.Methods:This scoping review was conducted under the Joanna Briggs Institute in Australia guidelines. Relevant studies were searched in PubMed, Embase, Web of Science, Cochrane Library, Scopus, CINAHL, China National Knowledge Infrastructure, Wanfang Database, VIP Database and Chinese Biomedical Literature Database. Chinese and English literature was screened and summarized from inception to September 21, 2023.Results:A total of 14 articles were included, and the economic toxicity of patients with head and neck cancer was more serious.The evaluation methods were mainly divided into scale evaluation and database data calculation. The risk factors of economic toxicity in patients with head and neck cancer included three aspects: demographic factors such as young age, low education and low income; disease and treatment-related factors such as tumor location in larynx/hypopharynx, current/past use of tube feeding, advanced tumor/distant metastasis; social support factors such as insufficient social security, and so on.Conclusions:Future studies should pay more attention to economic toxicity in patients with head and neck cancer, standardize the selection of assessment tools to reduce heterogeneity, and develop individualized intervention measures for the risk factors of economic toxicity in patients with head and neck cancer, in order to reduce the occurrence of economic toxicity in patients with head and neck cancer.
3.Astrocytes regulate glial scar formation in cerebral ischemic stroke
Ting YANG ; Zhibin DING ; Nan JIANG ; Hongxia HAN ; Miaomiao HOU ; Cungen MA ; Lijuan SONG ; Xinyi LI
Chinese Journal of Tissue Engineering Research 2024;28(1):131-138
BACKGROUND:Cerebral ischemic stroke is one of the main fatal and disabling diseases in the clinic,but only a few patients benefit from vascular recanalization in time,so it is urgent to explore new and effective therapy.As one of the critical pathological changes of ischemic stroke,the glial scar formed mainly by astrocytes is one major cause that hinders axonal regeneration and neurological recovery at the late stage of stroke. OBJECTIVE:To elucidate the pathological process and crucial signal regulatory mechanism of astrocytes in the formation of glial scar after ischemic stroke,as well as the potential therapeutic targets,to provide a theoretical reference for intervening astrocytic scar formation against ischemic stroke effectively,and novel strategies for promoting post-stroke rehabilitation. METHODS:The relevant articles published in CNKI,PubMed and Web of Science databases from 2010 to 2022 were retrieved.The search terms were"Ischemic stroke,Brain ischemi*,Cerebral ischemi*,Astrocyt*,Astroglia*,Glial scar,Gliosis,Astrogliosis"in Chinese and English.Finally,78 articles were included after screening and summarized. RESULTS AND CONCLUSION:(1)Astrocytes play an important role in the maintenance of central nervous system homeostasis.After ischemic stroke,astrocytes change from a resting state to an active state.According to the different severities of cerebral ischemic injury,astrocyte activation changes dynamically from swelling and proliferation to glial scar formation.(2)Mature astrocytes are stimulated to restart the cell cycle,then proliferate and migrate to lesions,which is the main source of the glial scar.Neural stem cells in the subventricular zone,neuron-glial antigen 2 precursor cells and ependymal precursor cells in the brain parenchyma can also differentiate into astrocytes.Endothelin-1,aquaporin 4,ciliary neurotrophic factor and connexins are involved in this process.In addition,chondroitin sulfate proteoglycan,as the main component of the extracellular matrix,forms the dense glial scar barrier with proliferated astrocytes,which hinders the polarization and extension of axons.(3)Activation or inhibition of crucial signal molecules involved in astrocyte activation,proliferation,migration and pro-inflammation functions regulate the glial scar formation.Transforming growth factor beta 1/Smad and Janus kinase/signal transducer and activator of transcription 3 are classical pathways related to astrogliosis,while receptor-interacting protein 1 kinase and glycogen synthase kinase 3β are significant molecules regulating the inflammatory response.However,there are relatively few studies on Smad ubiquitination regulatory factor 2 and Interleukin-17 and their downstream signaling pathways in glial scar formation,which are worthy of further exploration.(4)Drugs targeting astrogliosis-related signaling pathways,cell proliferation regulatory proteins and inflammatory factors effectively inhibit the formation of glial scar after cerebral ischemic stroke.Among them,the role of commonly used clinical drugs such as melatonin and valproic acid in regulating glial scar formation has been verified,which makes it possible to use drugs that inhibit glial scar formation to promote the recovery of neurological function in patients with stroke.(5)Considering the protective effects of glial scar in the acute phase,how to choose the appropriate intervention chance of drugs to maintain the protective effect of the glial scar while promoting nerve regeneration and repair in the local microenvironment is the direction of future efforts.
4.Study of brain regions of normal tension glaucoma patients by functional con-nectivity technology in resting-state functional magnetic resonance imaging based on V1 region seed point
Miaomiao ZANG ; Caimei FAN ; Jian JIANG ; Yi SHAO ; Lijun WANG ; Luyao ZENG ; Cheng YI ; Tianshuo WU ; Hanlin LI
Recent Advances in Ophthalmology 2024;44(2):112-117
Objective To study the brain functional connectivity(FC)changes in patients with normal tension glau-coma(NTG)and healthy volunteers using FC technique of resting-state functional magnetic resonance imaging(rs-fMRI)based on V1 region seed point(ROI),so as to explore the pathogenesis and early diagnosis of NTG.Methods Fourteen NTG patients(NTG group)who met the inclusion criteria and 14 healthy controls(HCs group)were enrolled.The clinical data of all subjects were collected,and rs-fMRI was performed in both groups.The magnetic resonance data was pre-pro-cessed by software,and bilateral A1 regions were taken as the ROI to analyze their correction with the whole brain voxel time series and obtain the FC value between the ROI and the whole brain by comparison of FC values in resting state be-tween the groups.Pearson correlation analysis was used to explore the relationship between FC value in the brain regions with significant differences with the ROI and clinical variables in the NTG group.Results Compared with the subjects in the HCs group,there were no statistically significant differences in age,gender,body weight,cup-disc ratio and 24 h mean intraocular pressure of patients in the NTG group(all P>0.05),and there were statistically significant differences in the best corrected visual acuity(BCVA)of both eyes and peripapillary retinal nerve fiber layer thickness(RNFLT)(all P<0.05).The Pearson correlation analysis showed that FC value of the brain regions with abnormal FC to V1 region were cor-related with RNFLT in the NTG group(P<0.05).ROI1-left superior frontal gyrus,ROI1-right superior frontal gyrus,ROI2-left cingulate gyrus and ROI2-right middle frontal gyrus were significantly positively correlated with RNFLT(all P<0.05).Compared with the HCs group,the brain regions with reduced FC to the right ROI in the NTG group were the left superior frontal gyrus and right superior frontal gyrus;the brain regions with reduced FC to the left ROI were the left cingulate gyrus and right middle frontal gyrus.Conclusion Compared to healthy individuals,NTG patients have significant changes in the functional connections between certain specific brain regions and V1 region,including bilateral superior frontal gyrus,left cingulate gyrus,and middle frontal gyrus.The changes in brain functional activity may be caused by visual dysfunction caused by NTG,leading to functional impairment of the visual and cognitive emotion processing brain regions,which may be one of the potential neuropathological mechanisms in NTG patients.
5.Bioinformatics analysis on key genes related to prognosis,diagnosis,and immune cell infiltration of hepatocellular carcinoma and their potential therapeutic drugs
Jinlian LI ; Lanzhen HUANG ; Xishi HUANG ; Kangzhi LI ; Jiali JIANG ; Miaomiao ZHANG ; Qunying WU
Journal of Jilin University(Medicine Edition) 2024;50(4):1062-1075
Objective:To screen the key genes related to the prognosis,diagnosis,and immune infiltration of the hepatocellular carcinoma(HCC)patients by bioinformatics analysis methods,and to analyze their potential therapeutic drugs.Methods:The HCC gene expression profile data and corresponding clinical informations of the HCC patients were downloaded from the Gene Expression Omnibus(GEO)database and The Cancer Genome Atlas(TCGA)database.The R software package limma was used to screen the differentially expressed genes(DEGs)in HCC.Gene Ontology(GO)functional enrichment analysis and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment analysis were performed on the DEGs.The STRING database was used to construct the protein-protein interaction(PPI)network;the Cytoscape software was used to visualize the PPI network and screen the key genes;Kaplan-Meier survival curve and LASSO regression algorithm were used to identify the key genes related to the HCC prognosis;external data sets were used to validate their expressions and analyze the diagnostic efficacy;CIBERSORT algorithm was used to detect the relationship between the expression of prognosis-related key genes and HCC immune cell infiltration.The MiRNet and Network Analyst databases were used to construct the microRNA(miRNA)-key gene mRNA and transcription factors(TFs)-key gene mRNA molecular regulatory networks;CMap database was used to screen the potential small molecule drugs for HCC treatment.Results:A total of 146 DEGs were screened,including 30 upregulated genes and 116 downregulated genes.The GO functional enrichment analysis and KEGG pathway enrichment analysis results showed that the DEGs were significantly enriched in biological processes(BP)such as steroid,alkene compound,and hormone metabolism,as well as signaling pathways such as retinol metabolism,drug metabolism-cytochrome P450(CYP450),complement and coagulation cascades.The PPI network analysis identified 14 key genes,among which formimidoyltransferase cyclodeaminase(FTCD),secreted phosphoprotein 2(SPP2),thrombin-antithrombin complex(TAT),complement C6(C6),and cytochrome CYP450 family member 2C9(CYP2C9)were significantly associated with the prognosis,clinical pathological stage,and histological grade of the HCC patients and also had high diagnostic efficacy for HCC and were closely related to immune cell infiltration in HCC.Hsa-mir-182-5p,CUT-like homeobox 1(CUX1),early growth response 1(EGR1),SMAD family member 4(SMAD4),and tumor protein P53(TP53)were identified as the important regulators targeting the above-mentioned prognosis-related key genes.DL-thiorphan,promethazine,and apigenin may have the therapeutic effects on HCC.Conclusion:FTCD,SPP2,TAT,C6,and CYP2C9 may be the potential targets for the diagnosis,prognosis,and treatment of HCC.Three predicted small molecule drugs,DL-thiorphan,promethazine,and apigenin,may provide the references for the development of therapeutic drugs for HCC.
6.Genetic variation and distribution characteristics of thalassemia in people of childbearing age in Hubei Province
Runhong XU ; Hui LI ; Yayun QIN ; Yufei JIANG ; Meiqi YI ; Guoqiang SUN ; Miaomiao CHEN ; Jieping SONG
Chinese Journal of Endemiology 2023;42(4):280-285
Objective:To study the genetic variation and distribution characteristics of thalassemia in people of childbearing age in Hubei Province, and to provide clinical basis for the local government decision-making departments to formulate and promote appropriate policies for prevention and control of thalassemia.Methods:Venous blood samples were collected from 44 849 people of childbearing age in hospitals in Hubei Province from May 13, 2019 to August 17, 2021. PCR-flow fluorescence hybridization and PCR+diversion hybridization were used to screen thalassemia genes. Spouses of those who tested positive were also tested for thalassemia genes. When both spouses carried the same type of thalassemia gene, the amniotic fluid of pregnant women was extracted for prenatal diagnosis and followed up.Results:Among the 44 849 people of childbearing age, 2 286 cases were diagnosed as thalassemia gene carriers through genetic testing, and the total detection rate was 5.10% (2 286/44 849). Among them, 1 488 cases were diagnosed as α-thalassemia, and the detection rate was 3.32% (1 488/44 849); 767 cases were diagnosed as β-thalassemia, and the detection rate was 1.71% (767/44 849); 31 cases were diagnosed as α-thalassemia combined with β-thalassemia, and the detection rate was 0.07% (31/44 849). The top three genotypes of α-thalassemia were -α 3.7/αα, -- SEA/αα, and -α 4.2/αα, accounting for 58.06% (864/1 488), 26.14% (389/1 488), and8.74% (130/1 488), respectively. The top three genotypes of β-thalassemia were β IVS-Ⅱ-654/β N, β CD41-42/β N, and β CD17/β N, accounting for 41.72% (320/767), 21.25% (163/767), and 16.04% (123/767), respectively. The main genotypes of α-thalassemia combined with β-thalassemia were -α 3.7/αα complex β IVS-Ⅱ-654/β N and -α 3.7/αα complex β CD41-42/β N, accounting for 29.03% (9/31) and 16.13% (5/31), respectively. A total of 59 people of childbearing age were conducted prenatal diagnosis, among fetus, there were 4 cases of severe thalassemia (2 cases of severe α-thalassemia, 2 cases of severe β-thalassemia), 5 cases of intermediate α-thalassemia, 5 cases of intermediate or severe β-thalassemia, 19 cases of mild thalassemia (8 cases of mild α-thalassemia, 11 cases of mild β-thalassemia), 13 cases of stationary α-thalassemia, and 1 case of stationary α-thalassemia combined with mild β-thalassemia, there were 12 cases without α-thalassemia or β-thalassemia genes. After follow-up, 4 cases of severe thalassemia, 2 cases of intermediate α-thalassemia, and 5 cases of intermediate or severe β-thalassemia were terminated pregnancy by the joint decision of both parents. Conclusions:In Hubei Province, the detection rate of thalassemia is high, and α-thalassemia is the main mutation type. The combination of thalassemia gene screening and prenatal diagnosis is of great significance in reducing the birth rate of children with thalassemia.
7.Distinct mononuclear diploid cardiac subpopulation with minimal cell-cell communications persists in embryonic and adult mammalian heart.
Miaomiao ZHU ; Huamin LIANG ; Zhe ZHANG ; Hao JIANG ; Jingwen PU ; Xiaoyi HANG ; Qian ZHOU ; Jiacheng XIANG ; Ximiao HE
Frontiers of Medicine 2023;17(5):939-956
A small proportion of mononuclear diploid cardiomyocytes (MNDCMs), with regeneration potential, could persist in adult mammalian heart. However, the heterogeneity of MNDCMs and changes during development remains to be illuminated. To this end, 12 645 cardiac cells were generated from embryonic day 17.5 and postnatal days 2 and 8 mice by single-cell RNA sequencing. Three cardiac developmental paths were identified: two switching to cardiomyocytes (CM) maturation with close CM-fibroblast (FB) communications and one maintaining MNDCM status with least CM-FB communications. Proliferative MNDCMs having interactions with macrophages and non-proliferative MNDCMs (non-pMNDCMs) with minimal cell-cell communications were identified in the third path. The non-pMNDCMs possessed distinct properties: the lowest mitochondrial metabolisms, the highest glycolysis, and high expression of Myl4 and Tnni1. Single-nucleus RNA sequencing and immunohistochemical staining further proved that the Myl4+Tnni1+ MNDCMs persisted in embryonic and adult hearts. These MNDCMs were mapped to the heart by integrating the spatial and single-cell transcriptomic data. In conclusion, a novel non-pMNDCM subpopulation with minimal cell-cell communications was unveiled, highlighting the importance of microenvironment contribution to CM fate during maturation. These findings could improve the understanding of MNDCM heterogeneity and cardiac development, thus providing new clues for approaches to effective cardiac regeneration.
Animals
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Mice
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Diploidy
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Heart
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Myocytes, Cardiac/metabolism*
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Cell Communication
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Gene Expression Profiling
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Mitochondria
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Regeneration
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Mammals/genetics*
8.Epidemiological characteristics of public health emergency events of varicella in China, 2006-2021
Miaomiao WANG ; Yuehua HU ; Meiying YOU ; Xinmei CHEN ; Tianqi WANG ; Xinyu LIU ; Chengdong XU ; Zhuojun JIANG ; Xudong LI ; Dapeng YIN
Chinese Journal of Epidemiology 2023;44(12):1893-1898
Objective:To understand the epidemiological characteristics of public health emergency events (PHEE) of varicella in China from 2006 to 2021 and related response performances.Methods:The data of varicella PHEE in 31 provinces of China from 2006 to 2021 were collected through the Public Health Emergency Management Information System, Microsoft Excel 2019 software and SPSS 26.0 statistical software were used to conduct descriptive epidemiological, statistical analysis on the time, area, location distribution, scale and epidemic management.Results:A total of 11 443 PHEE involving 341 048 related cases were reported from 2006 to 2021, with an annual attack rate of 1.78%-3.80% and a total attack rate of 2.33% (341 048/14 624 042). The number of PHEE and related cases of varicella decreased from 1 107 (35 349) in 2007 to 262 (6 884) in 2012 ( Z=-2.40, P<0.001), then increased year by year to 1 318 (42 649) in 2019 ( Z=2.58, P<0.001), with a significant decline since 2020. The varicella PHEE in China presents the seasonal characteristics,the peak is from April to June and from October to December, respectively. The sub-peak of varicella PHEE in eastern China generally appears 1-2 months earlier than in central and western China. Varicella PHEE reports are mainly distributed in eastern China, the attack rate is relatively high in western China, school-reported varicella PHEE was 88.26% of the total reports (10 099/11 443). The epidemic scale of varrcella PHEE typically range from 10 to 29 cases per year among the given outbreaks. The M ( Q1, Q3) of average number of cases, average duration, and average reporting interval of PHEE were 23 (16,35), 20 (14, 26) days, and 9 (5,19) days, respectively, and the reporting interval was positively correlated with the duration ( r=0.854, P<0.001). Conclusions:The varicella PHEE in China from 2006 to 2021 has not been effectively controlled. Schools are the key places to prevent and control varicella PHEE. Improving the sensitivity of varicella PHEE monitoring, strengthening the timely disposal of varicella epidemic, and promoting varicella vaccination are effective measures to prevent and control varicella PHEE.
9.Role and Mechanism of Chinese Medicinal Materials and Their Compound Formulas with Effects of Replenishing Qi, Activating Blood, and Dispelling Stasis in Prevention and Treatment of Heart Failure
Jiaping CHEN ; Xinglong MIU ; Miaomiao DING ; Yangyan SU ; Changxiao LIU ; Jiang MA ; Xin HE
Chinese Journal of Experimental Traditional Medical Formulae 2022;28(21):221-234
Heart failure with high prevalence is the endpoint of many cardiovascular diseases. Once diagnosed, patients usually need lifelong medication, which seriously affects their quality of life. The drugs commonly used to treat heart failure include angiotensin-converting enzyme inhibitors, beta-blockers, aldosterone receptor antagonists, and diuretics. However, the long-term use of those drugs can lead to side effects such as hypotension, depletion of body fluid, and electrolyte imbalance and even increase mortality. According to the theory of traditional Chinese medicine (TCM), Qi deficiency and blood stagnation is the major cause of heart failure and when Qi is not moving, blood is not flowing. Therefore, the TCM clinical treatment of heart failure uses the Chinese medicinal materials which replenish Qi, activate blood, and dispell stasis to treat both internal cause and external symptoms. Recent studies have demonstrated that Chinese herbal medicines such as Astragali Radix, Ginseng Radix et Rhizoma, Notoginseng Radix et Rhizoma, Salviae Miltiorrhizae Radix et Rhizoma, Angelicae Sinensis Radix, as well as the compound formulas such as Buyang Huanwutang, Simiao Yongantang, Qili Qiangxin capsules, and Qishen Yiqi drops, play a significant role in the prevention and treatment of heart failure via replenishing Qi, activating blood, and dispelling stasis. Inhibition of oxidative stress and inflammatory responses, mitigation of myocardial fibrosis, improvement of calcium cycling, and protection of mitochondrial function represent the key mechanisms for the treatment of heart failure with Chinese medicinal materials. Focusing on the pathogenic mechanisms and signaling pathways of heart failure, this paper systematically describes the pharmacological effects, molecular mechanisms, and research progress in the clinical application of Chinese medicinal herbs with effects of replenishing Qi, activating blood, and dispelling stasis and their compound formulas in the prevention and treatment of heart failure, aiming to provide scientific evidence for the development and clinical use of anti-heart failure Chinese medicinal materials.
10.The generation of PD-L1 and PD-L2 in cancer cells: From nuclear chromatin reorganization to extracellular presentation.
Zhiwei FAN ; Changyue WU ; Miaomiao CHEN ; Yongying JIANG ; Yuanyuan WU ; Renfang MAO ; Yihui FAN
Acta Pharmaceutica Sinica B 2022;12(3):1041-1053
The immune checkpoint blockade (ICB) targeting on PD-1/PD-L1 has shown remarkable promise in treating cancers. However, the low response rate and frequently observed severe side effects limit its broad benefits. It is partially due to less understanding of the biological regulation of PD-L1. Here, we systematically and comprehensively summarized the regulation of PD-L1 from nuclear chromatin reorganization to extracellular presentation. In PD-L1 and PD-L2 highly expressed cancer cells, a new TAD (topologically associating domain) (chr9: 5,400,000-5,600,000) around CD274 and CD273 was discovered, which includes a reported super-enhancer to drive synchronous transcription of PD-L1 and PD-L2. The re-shaped TAD allows transcription factors such as STAT3 and IRF1 recruit to PD-L1 locus in order to guide the expression of PD-L1. After transcription, the PD-L1 is tightly regulated by miRNAs and RNA-binding proteins via the long 3'UTR. At translational level, PD-L1 protein and its membrane presentation are tightly regulated by post-translational modification such as glycosylation and ubiquitination. In addition, PD-L1 can be secreted via exosome to systematically inhibit immune response. Therefore, fully dissecting the regulation of PD-L1/PD-L2 and thoroughly detecting PD-L1/PD-L2 as well as their regulatory networks will bring more insights in ICB and ICB-based combinational therapy.

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