1.Breast cancer phenotype affects accuracy of MRI response evaluation after neoadjuvant chemotherapy
Zhuanzhuan GUO ; Bing ZHANG ; Li ZHANG ; Zhe LEI ; Wenbing LIANG ; Quanxin YANG ; Xin CHEN
Journal of Xi'an Jiaotong University(Medical Sciences) 2024;45(4):552-559
Objective To evaluate which factors may affect magnetic resonance imaging(MRI)performance in the detection of pathologic complete response(pCR)after neoadjuvant chemotherapy(NAC).Methods This retrospective study involved 89 patients diagnosed with invasive breast carcinoma who received NAC at The Second Affiliated Hospital of Xi'an Jiaotong University from July 2019 to December 2021.Breast MRI was performed before and after NAC.Based on the pathological results obtained surgery after the completion NAC and using Miller-Payne classification as the evaluation standard,the patients were divided into two subgroups:pCR and non-pathological complete response(npCR).Chi-square test was used to compare the MRI characteristics of pre-NAC lesions between the two groups.ROC curve analysis was made to analyze the accuracy,sensitivity,specificity,positive predictive value,and negative predictive value of MRI after NAC;the diagnostic performance of MRI in predicting pCR in different tumor subtypes was analyzed.We made univariate and multivariate analyses of factors affecting radiographic complete response(rCR)and pCR concordance.Results MRI analysis after NAC showed rCR in 20 cases(22.5%)and pCR in 28 cases(31.5%).Considering rCR as a"positive"result of MRI analysis,MRI assessment was accurate in 79 cases,including 19 true positive cases and 60 true negative cases.MRI assessment was inaccurate in 10 cases,including 9 false negative cases and 1 false positive case.The sensitivity,specificity,accuracy,positive predictive value,and negative predictive value of MRI assessment of pCR were 67.86%,98.36%,88.76%,95.00%,and 86.96%.MRI had the lowest diagnostic efficiency in evaluating pCR of ERBB2+breast cancer after NAC.Single factor analysis showed that estrogen receptor(ER),clinical stage,background parenchymal enhancement,and maximum tumor diameter all affected the consistency of rCR and pCR(P<0.05).Multivariate Logistic regression analysis showed that the independent influencing factor affecting the consistency of rCR and pCR was clinical stage.Conclusion MRI demonstrated good accuracy in predicting pCR after NAC in the breast cancer patients examined.Pre-treatment MRI characteristics and tumor subtypes may be related to the diagnostic accuracy of post-NAC MRI in breast cancer patients.
2.Baicalein:A potential GLP-1R agonist improves cognitive disorder of diabetes through mitophagy enhancement
Liu NA ; Cui XIN ; Yan WENHUI ; Guo TINGLI ; Wang ZHUANZHUAN ; Wei XIAOTONG ; Sun YUZHUO ; Liu JIEYUN ; Xian CHENG ; Ma WEINA ; Chen LINA
Journal of Pharmaceutical Analysis 2024;14(8):1189-1204
There is increasing evidence that the activation of glucagon-like peptide-1 receptor(GLP-1R)can be used as a therapeutic intervention for cognitive disorders.Here,we have screened GLP-1 R targeted com-pounds from Scutellaria baicalensis,which revealed baicalein is a potential GLP-1 R small-molecule agonist.Mitophagy,a selective autophagy pathway for mitochondrial quality control,plays a neuro-protective role in multiple cognitive impairment diseases.We noticed that Glp1r knock-out(KO)mice present cognitive impairment symptoms and appear worse in spatial learning memory and learning capacity in Morris water maze(MWM)test than their wide-type(WT)counterparts.Our mechanistic studies revealed that mitophagy is impaired in hippocampus tissue of diabetic mice and Glp1r KO mice.Finally,we verified that the cognitive improvement effects of baicalein on diabetic cognitive dysfunction occur through the enhancement of mitophagy in a GLP-1 R-dependent manner.Our findings shed light on the importance of GLP-1 R for cognitive function maintenance,and revealed the vital significance of GLP-1R for maintaining mitochondrial homeostasis.Furthermore,we identified the therapeutic potential of baicalein in the treatment of cognitive disorder associated with diabetes.
3.A network Meta-analysis of efficacy and safety of different administration routes of recombinant human endostatin in the treatment of non-small cell lung cancer with malignant pleural effusion
Zhuanzhuan XU ; Chaochao TU ; Zhangqin GONG ; Yingao GUO ; Mingli TU
China Pharmacist 2024;27(4):697-710
Objective To systematically evaluate the efficacy and safety of different administration methods of recombinant human endostatin(Endostatin)in the treatment of malignant pleural effusion in non-small cell lung cancer(NSCLC),and to provide more evidence-based bases for the clinical standardization of the use of Endostatin beyond the drug specification.Methods PubMed,The Cochrane Library,Web of Science,Embase,ChiCTR,VIP,CNKI,WanFang,and SinoMed databases were searched by computer for randomized controlled trials(RCT)of Endostatin alone or combined with chemotherapy for malignant pleural effusion in NSCLC.Network Meta-analysis was performed using Stata 14.0 software.Results A total of 50 RCTs involving 3 429 patients were included,covering 5 intervention measures.Network Meta-analysis showed that in terms of clinical effectiveness,there was no statistically significant difference between Endostatin(thoracic perfusion)+chemotherapeutic drug(thoracic perfusion or intravenous drip)and Endostatin(intravenous drip)+chemotherapeutic drug(thoracic perfusion or intravenous drip),and Endostatin(thoracic perfusion)and chemotherapeutic drug(thoracic perfusion)(P>0.05);there were statistically differences between Endostatin(thoracic perfusion)+chemotherapeutic drug(thoracic perfusion or intravenous drip)and Endostatin(thoracic perfusion)[OR=3.44,95%CI(2.29,4.50),P<0.05],and Endostatin(thoracic perfusion)+chemotherapeutic drug(thoracic perfusion or intravenous drip)and chemotherapeutic drug(thoracic perfusion)[OR=3.78,95%CI(3.16,4.51),P<0.05](P<0.05).The surface under the cumulative ranking curve(SUCRA)showed that Endostatin(thoracic perfusion)+chemotherapeutic drug(thoracic perfusion or intravenous drip)>Endostatin(intravenous drip)+chemotherapeutic drug(thoracic perfusion or intravenous drip)>Endostatin(thoracic perfusion)>chemotherapeutic drug(thoracic perfusion)>chemotherapeutic drug(intravenous drip).In terms of adverse effects,such as gastrointestinal reaction,and reduction of white blood cells and platelets,there was no statistically significant difference among the different interventions(P>0.05).Conclusion Endostatin either by pleural instillation or combined with first-line chemotherapy drugs significantly improves clinical efficacy in malignant pleural effusion in NSCLC,and it is better and safer with thoracic perfusion efficacy.
4.Transcriptome analysis of baicalin interfering with IBV replication in CEK cells in vitro
Xiaohui GUO ; Weiqing LI ; Zhuanzhuan WANG ; Yining LIU ; Weixin LI ; Guangming CHEN ; Wanying FENG ; Qinghui JIA ; Zhaoxing ZHANG
Chinese Journal of Veterinary Science 2024;44(7):1473-1482
In order to understand the difference and expression of genes in CEK cells before and af-ter baicalin interferes with IBV,further reveal and analyze the mechanism of baicalin interfering IBV replication in CEK cells in vitro.After IBV infected CEK cells for 2 h,9.75 mg/L baicalin liq-uid was added to interfere with CEK cells,which was recorded as the baicalin(H-IBV)group,and three replicate wells were set in the control group and the IBV(IBV)infection group.After 36 h culture,cell samples were collected and subject to transcriptome for sequencing.The results showed that there were 102 differentially expressed genes in H-IBV group compared with IBV in-fection group,among which 48 genes weresignificantly up-regulated and 54 genes were significantly down-regulated.Through functional annotation in GO and KEGG databases,it was found that dif-ferentially expressed genes were mainly annotated in biological processes such as cellular proces-ses,biological regulation,metabolism,and secondary pathways such as viral infectious diseases,signal transduction and interaction.Retinol metabolism pathway,phospholipid transfer to mem-brane,IL-27 mediated signaling pathway,MDA5/RIG-I and Toll-like receptor signaling pathway were significantly enriched in CEK cells,and the production of type Ⅰ interferon and interferon al-pha and the process of antiviral infection were also positively regulated.There were more differen-tial genes enriched in nucleic acid catalysis,immune system,and reaction,and interbiological reac-tion.Through the STRING network interaction map,it was found that most immune-related genes could form a 36-node interaction network centered on IRF7,TLR3 and STAT1.Therefore,com-pared with IBV group,the differentially expressed genes after baicalin treatment were mainly an-notated and enriched in the biological process,and the immune system and response were en-hanced,mainly through the positive regulation of IRF7 in the MDA5/RIG-I receptor signaling pathway and the inhibition of TLR3 signal transduction in the Toll-like receptor signaling path-way.Positive regulation of IL-27 mediated pathway and regulation of JAK-STAT signaling path-way were supplemented by activation of the expression of IRF7,TLR3,STAT1 and other related genes,and interaction with corresponding downstream proteins to promote the expression of IFN-α and regulatory cytokines,coupled with negative regulation of viral(defense)response and viral processes.Thus,baicalin interferes with IBV replication in CEK cells.
5.Effect of 131I therapy on the clinical outcome of patients with differentiated thyroid cancer evaluated as indeterminate response after surgery
Ningning ZHAO ; Zhuanzhuan MU ; Wenting GUO ; Xing WEI ; Yansong LIN
Chinese Journal of Nuclear Medicine and Molecular Imaging 2023;43(12):736-740
Objective:To investigate the effect of 131I therapy on the clinical outcome of patients with differentiated thyroid cancer (DTC) who were evaluated as indeterminate response (IDR) after surgery and before 131I therapy. Methods:A total of 281 DTC patients (89 males, 192 females, age (38.4±10.2)years ) assessed as IDR before 131I therapy and after total or near-total thyroidectomy in the Department of Nuclear Medicine of Peking Union Medical College Hospital from April 2009 to March 2022 were retrospectively analyzed. Patients were divided into 131I therapy group ( 131I group) and just thyroid stimulating hormone (TSH) suppressive therapy group (TSH group) according to whether receiving 131I therapy, and the efficacies of two groups at the end of follow-up were compared. Subgroup analysis was conducted in different risk stratifications (low-risk, moderate-risk and high-risk), positive thyroglobulin antibody (TgAb) group (TgAb≥115 kU/L) and negative TgAb group (TgAb<115 kU/L). For patients with positive TgAb, the duration and rate for TgAb declining to negative level under the 2 regimens were compared. Independent-sample t test, Mann-Whitney U test, χ2 test and Fisher exact test were performed to compare the differences between groups. Results:Median follow-up time was 39(6-146) months. There was no statistical difference between patients in 131I group and TSH group in baseline characteristics, and the efficacies at the end of follow-up was similar between the 2 groups ( χ2=6.50, P=0.075). For low-, moderate- and high-risk stratification, there were also no statistical differences of response to 2 regimens ( P=0.221; χ2=4.21, P=0.223; χ2=3.01, P=0.274). Similar results were showed for patients with positive and negative TgAb ( n=50, n=231; χ2=4.02, P=0.242; χ2=3.14, P=0.341). For patients with positive TgAb, the duration and rate for TgAb declining to negative level were not statistically different either between 2 regimens (71.0%(22/31) vs 14/19, χ2=0.04, P=0.836; 7.0(5.0, 9.3) vs 7.0(5.0, 7.3) months, z=-0.89, P=0.375). Conclusion:For DTC patients assessed as IDR after surgery, 131I therapy may not provide more benefit than follow-up with TSH suppressive therapy.