1.Effect of Different Time Interventions of Yangxin Tongmai Formula (养心通脉方) on DNA Methylation in Rat Models of Premature Coronary Heart Disease with Blood Stasis Syndrome
Xing CHEN ; Zixuan YU ; Shumeng ZHANG ; Yanjuan LIU ; Shuangyou DENG ; Ying WANG ; Lingli CHEN ; Jie LI
Journal of Traditional Chinese Medicine 2025;66(11):1165-1173
ObjectiveTo observe the effect of Yangxin Tongmai Formula (养心通脉方) by midnight-noon ebb-flow administration method for rat models of premature coronary heart disease (PCHD) with blood stasis syndrome, and to explore the possible mechanism of action from the perspective of DNA methylation differential gene expression. MethodsThere were 3 SD rats in each of the blank group, model group and Yangxin Tongmai Formula group, and the rats in the model group and Yangxin Tongmai Formula group were fed with high-fat chow plus vitamin D3 by gavage plus isoproterenol hydrochloride by subcutaneous injection to construct rat models of PCHD with blood stasis syndrome. After successful modelling, rats in Yangxin Tongmai Formula group were gavaged with 18 g/(kg‧d) of Yangxin Tongmai Formula, and rats in blank group and the model group were gavaged with 4 ml/(kg‧d) of 0.9% NaCl solution, and serum samples of rats in each group were collected for DNA methylation sequencing after 3 weeks to screen for the relevant DNA methylation differentiation genes. In addition, rats with successful modelling of PCHD with blood stasis were randomly divided into model group, Yangxin Tongmai Formula with midnight-noon ebb-flow administration method group [18 g/(kg‧d) of Yangxin Tongmai Formula was gavaged twice in the heart channel period (12:00) and pericardium channel period (20:00)], the Yangxin Tongmai Formula control group [18 g/(kg‧d) of Yangxin Tongmai Formula was gavaged twice at 8:00 and 18:00] and the Atorvastatin Calcium group [atorvastatin calcium tablets solution 1.8 mg/(kg‧d) at the same intervention time as that in Yangxin Tongmai Formula control group], and set up a blank group of 8 rats in each group. The model group and blank group were gavaged with 0.9% NaCl solution 4 ml/(kg‧d) for the same time as the Yangxin Tongmai Formula control group. After 3 weeks of gavage, the blood lipids [including total cholesterol (TC), low-density lipoprotein (LDL), high-density lipoprotein (HDL)] levels of rats in each group were detected; the HE staining of myocardial tissues and thoracic aorta was used to observe the pathomorphological changes; the levels of serum inflammation indexes [tumour necrosis factor alpha (TNF-alpha), lipopolysaccharide (LPS), and interleukin 10 (IL-10)] were detected; immunoprecipitation-realtime fluorescence quantitative PCR was used to detect the relative expression of cardiac tissue screening differential genes. ResultsThe genes screened for differentially methylated regions were calmodulin 2 (Calm2), calcium voltage-gated channel subunit α1s (Cacna1s), and phospholipase Cβ1 (Plcb1). Compared with the blank group, rats in the model group showed elevated levels of TC, LDL, TNF-α and LPS, and decreased levels of HDL and IL-10 (P<0.05 or P<0.01); HE staining showed obvious swelling of myocardial fibres, accompanied by a large number of inflammatory cell infiltration, and thickening of the inner wall of the aortic vessels with internal wall damage, which was visible as a large number of lipid cholesterol crystals and obvious inflammatory cell infiltration. Compared with the model group, the TC, LDL, TNF-α and LPS contents of rats in the Yangxin Tongmai Formula with midnight-noon ebb-flow administration method group, the Yangxin Tongmai Formula control group, and the atorvastatin calcium group all reduced, and the contents of HDL and IL-10 all elevated (P<0.05), with the improvement of myocardial tissue damage and the reduction of inflammatory infiltration, and the improvement of the damage of the inner lining of the thoracic aorta and the reduction of lipid infiltration. Compared with Yangxin Tongmai Formula control group, LDL, TNF-α and LPS contents reduced, and IL-10 contents increased in the midnight-noon ebb-flow administration method group (P<0.05). Compared with the model group, the relative expression of Calm2 and Plcb1 genes decreased and the relative expression of Cacna1s gene increased in Yangxin Tongmai Formula control group and the midnight-noon ebb-flow administration method group (P<0.05); compared with the Yangxin Tongmai Formula control group, the relative expression of Calm2 gene decreased and the relative expression of Cacna1s gene increased in the midnight-noon ebb-flow administration method group (P<0.05). ConclusionThe intervention of Yangxin Tongmai Formula in the heart channel period (12:00) and pericardium channel period (20:00) was more effective in improving the blood lipid level, inhibiting inflammation, and improving myocardial tissue damage in rats of PCHD with blood stasis syndrome, and Calm2 and Cacna1s genes may be the key targets of Yangxin Tongmai Formula in intervening the blood stasis syndrome of PCHD.
2.Effect of Scutellariae Radix Combined with EGFR-TKIs on Non-small Cell Lung Cancer
Yaya YU ; Chenjing LEI ; Zhenzhen XIAO ; Qi MO ; Changju MA ; Lina DING ; Yadong CHEN ; Yanjuan ZHU ; Haibo ZHANG
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(18):106-115
ObjectiveTo investigate the effects of Scutellariae Radix combined with epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) on cell proliferation, apoptosis, cancer stem cell (CSC) marker expression, and metabolism in non-small cell lung cancer (NSCLC) cells. MethodsThe anti-tumor effects of Scutellariae Radix and EGFR-TKIs (gefitinib or osimertinib) in NSCLC cells were evaluated using the cell counting kit-8 (CCK-8) and Annexin V-FITC/propidium iodide (PI) double staining apoptosis assay. The activity of Scutellariae Radix and EGFR-TKIs in three-dimensional (3D) cultures of NSCLC cells was assessed using the CellTiter-Glo® 3D cell viability assay. The mRNA and protein expression levels of CSC markers, sex determining region y box protein 2 (SOX2) and aldehyde dehydrogenase 1 family member A1 (ALDH1A1), were detected by quantitative real-time polymerase chain reaction (Real-time PCR) and Western blot, respectively. Changes in intracellular reactive oxygen species (ROS) levels were detected by ROS staining, and the redox ratio was detected by femtosecond laser labeling free imaging (FLI). ResultsUnder both two-dimensional (2D) and 3D culture conditions, compared with the blank group and EGFR-TKI group, the combination group showed significantly reduced cell viability and increased apoptosis rate (P<0.05). Compared with the EGFR-TKI group, the mRNA and protein levels of CSC markers were significantly downregulated in the combination group (P<0.05). Additionally, the redox ratio was significantly elevated (P<0.05), and ROS levels were also increased in the combination group compared with the EGFR-TKI group. ConclusionIn NSCLC cells, Scutellariae Radix enhances the redox ratio and increases ROS levels, thereby inhibiting the expression of CSC markers and strengthening the anti-tumor effects of EGFR-TKIs. This provides a novel molecular mechanism by which Scutellariae Radix may enhance the sensitivity of targeted therapies.
3.Optimization of automated labeling method for 18F-AlF-NOTATATE and PET/CT imaging
Yu ZHANG ; Liping CHEN ; Huihui HE ; Haitian FU ; Qingbo LI ; Yanjuan WANG ; Chunyang JIN ; Chunjing YU
Chinese Journal of Nuclear Medicine and Molecular Imaging 2024;44(7):417-421
Objective:To establish an automated labeling method of 18F-AlF-1, 4, 7-triazocyclohexane-1, 4, 7-triacetic acid- D-Phe1-Tyr3-Thr8-octreotide (NOTATATE) and perform neuroendocrine tumor (NET) imaging. Methods:Based on the GE-FASTLab2 synthesis module, 18F-AlF-NOTATATE was automatically prepared by one-step chelation labeling with aluminum fluoride, and its labeling conditions were optimized. The product quality was analyzed. One patient (male, 47 years old) with lower rectal segment NET and one patient (female, 52 years old) with pancreatic NET underwent 18F-AlF-NOTATATE PET/CT imaging. Results:18F-AlF-NOTATATE was successfully prepared with a total synthesis time of 35 min. The optimized radiochemical yield was (23.8±3.1)% (without decay correction, n=3), the radioactivity was (4.63±0.68) GBq, and the radiochemical purity was >95%. The stability was good, and the product quality met the requirements. 18F-AlF-NOTATATE showed clear imaging in the patient with rectal segment NET, with SUV max of 13.3 and tumor/liver ratio of 3.3. Metastatic lesions in the liver, lymph nodes, and ribs showed high SUV max and tumor/liver ratios. The imaging of the pancreatic NET patient showed an abnormal increase in local radioactive uptake at the uncinate process of the pancreatic head, with SUV max of 5.6 and SUV max of 6.3 and the tumor/liver ratio of 2.3 after 2-hours imaging. Conclusions:Using the GE-FASTLab2 synthesis module, 18F-AlF-NOTATATE can be prepared with high activity. The preparation is simple, the method is stable, and the product has high radiochemical purity. 18F-AlF-NOTATATE exhibits good imaging performance in NET patients, providing valuable information for diagnosis, treatment, and prognosis evaluation.
4.Exploration on the Mechanism of Hydroxyl Safflower Flavin A in the Treatment of Sepsis-induced Liver Injury Based on Metabolomics and Network Pharmacology
Shifan YAN ; Bingbing PAN ; Ting YU ; Changmiao HOU ; Yu JIANG ; Fang CHEN ; Jingjing WANG ; Yanjuan LIU ; Yimin ZHU
Chinese Journal of Information on Traditional Chinese Medicine 2024;31(2):130-137
Objective To explore the mechanism of hydroxyl safflower flavin A(HSYA)in the treatment of sepsis-induced liver injury by using metabolomics and network pharmacology.Methods A total of 50 male C57BL/6 mice were randomly divided into sham-operation group(10 mice),sepsis group(20 mice)and HSYA group(20 mice).Cecal ligation and puncture was conducted to establish the sepsis-induced liver injury mouse model.The mice in HSYA group were subcutaneously injected with HSYA after 2 hours of modeling.The content of serum inflammatory factors and liver function were detected,and the pathological changes of liver tissue were observed with HE staining,UPLC-Q-TOF-MS metabolomics was used to analyze liver tissue,screening for differential metabolites using multivariate statistical methods,network pharmacology was used to predict potential targets for HSYA treatment of sepsis-induced liver injury,and conduct GO and KEGG pathway enrichment analysis on potential targets,Metabo Analyst 5.0 database was used to match differential metabolites and potential targets between the model group and HSYA group,a targets metabolite-metabolism pathway network was constructed.AutoDock Vina software was used to perform molecular docking between HSYA and core genes,and finally RT-qPCR was used to verify the expression of core genes.Results HSYA can reduce the contents of IL-6,IL-1β and TNF-α in serum,restore liver function,and alleviate the morphological alternation in liver induced by sepsis.A total of 26 differential metabolites identified by metabolomics were screened out,including flufenamic acid,cryptolepine,opthalmic acid,fenpropathrin etc.,which were mainly involved in 5 metabolic pathways such as biosynthesis of unsaturated fatty acids and alpha-linolenic acid metabolism.Network pharmacology identified 81 potential targets,2 735 items enriched in GO and 124 signaling pathways enriched in KEGG;a total of 5 differential metabolites were matched for joint analysis,corresponding to 14 targets including IL1B,STAT3,PTGS2,TP53,etc.,involved in the regulation of metabolic disorders in sepsis-induced liver injury by HSYA.Molecular docking results showed that HSYA had good binding activity to IL1B,STAT3,PTGS2 and TP53 targets.RT-qPCR results showed that HSYA could inhibit the expressions of IL1B,STAT3 and PTGS2 in liver tissue.Conclusions HSYA may inhibit the release of inflammatory cytokines,maintain metabolic homeostasis,and alleviate sepsis-induced liver injury through modulating the expressions of IL1B,STAT3,and PTGS2.
5.Construction of Dmd Gene Mutant Mice and Phenotype Verification in Muscle and Immune Systems
Min LIANG ; Yang GUO ; Jinjin WANG ; Mengyan ZHU ; Jun CHI ; Yanjuan CHEN ; Chengji WANG ; Zhilan YU ; Ruling SHEN
Laboratory Animal and Comparative Medicine 2024;44(1):42-51
Objective The aim is to utilize CRISPR/Cas9 gene editing technology to construct Dmd gene mutant mice with a point mutation in exon 23 of the Dmd gene. Subsequently, the phenotypic changes of the mice in muscles and immune systems are analyzed and verified, providing an evaluation model for Duchenne muscular dystrophy and other related diseases.MethodsBased on the sequence characteristics of exon 23 of the Dmd gene, small guide RNA (sgRNA) was designed and synthesized. Cas9 mRNA, sgRNA fragments, and oligo donor DNA were microinjected into fertilized eggs of C57BL/6J mice. After transferring the fertilized eggs to surrogate mice, F0 generation mice were born. After mating with F0 generation mice, offspring mice were obtained, and Dmd gene positive mutant (DmdMu/+) mice were obtained after genotype identification. Male hemizygous DmdMu/+(DmdMu/Y) mice were selected for phenotype validation. The body weight of live 3- and 9-month-old mice were recorded. Muscle tension was evaluated through the grid test. Hearts and semitendinosus muscles were collected, and the histopathological changes were observed using HE staining. Further, the expression of Dmd protein in muscle tissue of 9-month-old mice was analyzed by Western blotting.An acute inflammation model was established in DmdMu/Y mice using lipopolysaccharide induction. Peripheral blood from the submandibular vein was collected, and the changes in the proportion of neutrophils and monocytes were detected by flow cytometry.Results The results of genome sequencing and Western blotting confirmed the successful construction of Dmd gene point mutant mice (DmdMu/+ mice). Dmd protein expression was not detected in skeletal muscle and myocardium of DmdMu/+ mice, and it was significantly reduced compared to wild-type C57BL/6J mice (P<0.05). Compared with wild-type mice of the same background, DmdMu/Y mice at 3 and 9 months of age showed significant weight loss (P<0.01) and decreased muscle tension (P<0.05). 9-month-old DmdMu/Y mice exhibited significant pathological changes in skeletal muscle and myocardium, including widening of intermuscular space. Under normal condition, compared with wild-type mice, the proportion of neutrophils and monocytes in the peripheral blood of 3-month-old DmdMu/Y mice was significantly lower than that of wild-type mice (P<0.01). After lipopolysaccharide stimulation, the proportion of neutrophils in peripheral blood of 3-month-old DmdMu/Y mice remained significantly lower compared to that of wild-type mice (P<0.01). The proportion of neutrophils in peripheral blood of 9-month-old DmdMu/Y mice significantly decreased after lipopolysaccharide induction (P<0.01), with a trend of change observed in monocytes between groups.Conclusion The successful construction of the Dmd gene mutant mouse model has confirmed the vital function of Dmd gene in maintaining normal muscle tissue morphology and muscle tone. It preliminarily indicated that Dmd gene deletion could significantly reduce the proportion of neutrophils in peripheral blood, offering a new perspective for the study of immune system alterations in Duchenne muscular dystrophy patients.
6.High expression of VARS promotes the growth of multiple myeloma cells by causing imbalance in valine metabolism.
Rui SHI ; Wanqing DU ; Yanjuan HE ; Jian HU ; Han YU ; Wen ZHOU ; Jiaojiao GUO ; Xiangling FENG
Journal of Central South University(Medical Sciences) 2023;48(6):795-808
OBJECTIVES:
Multiple myeloma (MM) is a plasma cell malignancy occurring in middle and old age. MM is still an incurable disease due to its frequent recurrence and drug resistance. However, its pathogenesis is still unclear. Abnormal amino acid metabolism is one of the important characteristics of MM, and the important metabolic pathway of amino acids participates in protein synthesis as basic raw materials. Aminoacyl transfer ribonucleic acid synthetase (ARS) gene is a key regulatory gene in protein synthesis. This study aims to explore the molecular mechanism for ARS, a key factor of amino acid metabolism, in regulating amino acid metabolism in MM and affecting MM growth.
METHODS:
The corresponding gene number was combined with the gene expression profile GSE5900 dataset and GSE2658 dataset in Gene Expression Omnibus (GEO) database to standardize the gene expression data of ARS. GSEA_4.2.0 software was used to analyze the difference of gene enrichment between healthy donors (HD) and MM patients in GEO database. GraphPad Prism 7 was used to draw heat maps and perform data analysis. Kaplan-Meier and Cox regression model were used to analyze the expression of ARS gene and the prognosis of MM patients, respectively. Bone marrow samples from 7 newly diagnosed MM patients were collected, CD138+ and CD138- cells were obtained by using CD138 antibody magnetic beads, and the expression of ARS in MM clinical samples was analyzed by real-time RT-PCR. Human B lymphocyte GM12878 cells and human MM cell lines ARP1, NCI-H929, OCI-MY5, U266, RPMI 8266, OPM-2, JJN-3, KMS11, MM1.s cells were selected as the study objects. The expression of ARS in MM cell lines was analyzed by real-time RT-PCR and Western blotting. Short hairpin RNA (shRNA) lentiviruses were used to construct gene knock-out plasmids (VARS-sh group). No-load plasmids (scramble group) and gene knock-out plasmids (VARS-sh group) were transfected into HEK 293T cells with for virus packaging, respectively. Stable expression cell lines were established by infecting ARP1 and OCI-MY5 cells, and the effects of knockout valyl-tRNA synthetase (VARS) gene on proliferation and apoptosis of MM cells were detected by cell counting and flow cytometry, respectively. GEO data were divided into a high expression group and a low expression group according to the expression of VARS. Bioinformatics analysis was performed to explore the downstream pathways affected by VARS. Gas chromatography time-of-flight mass spectrometry (GC-TOF/MS) and high performance liquid chromatography (HPLC) were used to detect the valine content in CD138+ cells and ARP1, OCI-MY5 cells and supernatant of knockdown VARS gene in bone marrow samples from patients, respectively.
RESULTS:
Gene enrichment analysis showed that tRNA processing related genes were significantly enriched in MM compared with HD (P<0.0001). Further screening of tRNA processing-pathway related subsets revealed that cytoplasmic aminoacyl tRNA synthetase family genes were significantly enriched in MM (P<0.0001). The results of gene expression heat map showed that the ARS family genes except alanyl-tRNA synthetase (AARS), arginyl-tRNA synthetase (RARS), seryl-tRNA synthetase (SARS) in GEO data were highly expressed in MM (all P<0.01). With the development of monoclonal gammopathy of undetermined significance (MGUS) to MM, the gene expression level was increased gradually. Kaplan-Meier univariate analysis of survival results showed that there were significant differences in the prognosis of MM patients in methionyl-tRNA synthetase (MARS), asparaginyl-tRNA synthetase (NARS) and VARS between the high expression group and the low expression group (all P<0.05). Cox regression model multivariate analysis showed that the high expression of VARS was associated with abnormal overall survival time of MM (HR=1.83, 95% CI 1.10 to 3.06, P=0.021). The high expression of NARS (HR=0.90, 95% CI 0.34 to 2.38) and MARS (HR=1.59, 95% CI 0.73 to 3.50) had no effect on the overall survival time of MM patients (both P>0.05). Real-time RT-PCR and Western blotting showed that VARS, MARS and NARS were highly expressed in CD138+ MM cells and MM cell lines of clinical patients (all P<0.05). Cell counting and flow cytometry results showed that the proliferation of MM cells by knockout VARS was significantly inhibited (P<0.01), the proportion of apoptosis was significantly increased (P<0.05). Bioinformatics analysis showed that in addition to several pathways including the cell cycle regulated by VARS, the valine, leucine and isoleucine catabolic pathways were upregulated. Non-targeted metabolomics data showed reduced valine content in CD138+ tumor cells in MM patients compared to HD (P<0.05). HPLC results showed that compared with the scramble group, the intracellular and medium supernatant content of ARP1 cells and the medium supernatant of OCI-MY5 in the VARS-shRNA group was increased (all P<0.05).
CONCLUSIONS
MM patients with abnormal high expression of VARS have a poor prognosis. VARS promotes the malignant growth of MM cells by affecting the regulation of valine metabolism.
Humans
;
Valine-tRNA Ligase
;
Multiple Myeloma/genetics*
;
Metabolomics
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Amino Acids
;
RNA, Transfer
7.Effect of Reduning Injection, Shenfu Injection Combined with Gefitinib on Proliferation, Stemness Characteristics and Metabolism of Non-small Cell Lung Cancer Cells
Zhenzhen XIAO ; Yanjuan ZHU ; Yaya YU ; Lina DING ; Changju MA ; Chenjing LEI ; Yihong LIU ; Xuesong CHANG ; Yadong CHEN ; Haibo ZHANG
Chinese Journal of Experimental Traditional Medical Formulae 2023;29(18):45-53
ObjectiveTo compare and observe the effect of Reduning injection (mainly clearing heat), Shenfu injection (mainly warming Yang) combined with gefitinib on the proliferation, apoptosis, stemness characteristics and metabolism of lung cancer cells. MethodDifferent non-small cell lung cancer (NSCLC) cell lines were selected and intervened with gefitinib (5, 10, 20 μmol·L-1), Reduning injection (0.6%, 0.9%), Shenfu injection (0.6%, 0.9%), gefitinib combined with Reduning injection, and gefitinib combined with Shenfu injection. Cell proliferation in each group was detected by cell counting kit-8 (CCK-8) assay, and cell apoptosis was detected by flow cytometry. The mRNA and protein expressions of lung cancer stem cell markers sex determining region Y-box 2 (Sox2) and aldehyde dehydrogenase family 1 member A1 (ALDH1A1) were determind by real-time quantitative polymerase chain reaction (Real-time PCR) and Western blot, respectively. The redox ratio of lung cancer cells was observed by femtosecond label-free imaging (FLI) and energy metabolism instrument was used to determine the glycolysis level in cells. ResultCompared with the blank group, Reduning injection reduced the survival rate of lung cancer cells (P<0.05), increased the apoptosis rate (P<0.05), down-regulated the mRNA and protein expressions of Sox2 and ALDH1A1 (P<0.05), and up-regulated the redox ratio of cells (P<0.05), while Shenfu injection exerted no remarkable effect on the above indexes. In addition, compared with gefitinib alone, Reduning injection combined with gefitinib inhibited the survival rate of lung cancer cells (P<0.05), promoted the cell apoptosis (P<0.05), down-regulated the mRNA and protein expressions of Sox2 and ALDH1A1 (P<0.05), up-regulated the redox ratio of cells (P<0.05), and lowered the proton efflux rate of glycolysis (P<0.05), while Shenfu injection combined with gefitinib failed to affect these indexes of lung cancer cells significantly. ConclusionReduning injection may inhibit stemness characteristics of tumor cells by regulating their metabolism to enhance the proliferation-inhibiting and pro-apoptotic effects of gefitinib on lung cancer cells, while Shenfu injection had no significant enhancing effect on gefitinib. This indicates that epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) should be used in combination with heat-clearing Chinese medicines.
8.Progress in research methods or strategies of compatibility mechanism of traditional Chinese medicine prescriptions
Lei ZI ; Yanjuan LI ; Yanqin LI ; Tao WANG ; Junjie HAO ; Jie YU ; Xingxin YANG
China Pharmacy 2023;34(11):1393-1398
Compound formulas of traditional Chinese medicines (TCM), also known as prescription in clinic, refers to a form of medication in which several TCMs are selectively combined according to the certain compatibility principles and the needs of patient’s condition, based on syndrome differentiation and treatment. At present, the methods and strategies for investigating the compatibility mechanisms of TCM prescriptions mainly focus on the following two aspects: analysis of pharmacological substances (including chemical composition analysis of TCM, ingredients of TCM analysis in blood, and pharmacokinetic analysis) and pharmacological signaling pathways analysis (involving network pharmacology analysis, signal pathway indicator detection, and metabolomics analysis). In future research, the compatibility relationships of TCM prescriptions should be explored according to the principles of “Qiqing Hehe”,“ Shengjiang Fuchen”,“ Junchen Zuoshi”, and “Siqi Wuwei”. The regularity of TCM prescriptions compatibility should be shown in the change regularity of chemical components, pharmacokinetics, pharmacological pathways, and chemical compositions of various ratios of TCMs. Based on the insurance of holistic efficacy of TCM prescriptions, the underlying mechanisms of compatibility should be uncovered, which will provide references for the optimization of clinical applications of prescriptions and new directions for the creation of innovative TCM prescriptions.
9.Clinical application of 68Ga-PSMA-NYM032 PET/CT imaging in patients diagnosed initially with prostate cancer
Yanjuan WANG ; Haitian FU ; Huihui HE ; Yuanyuan MI ; Yuwei WU ; Dongsheng GE ; Chunjing YU
Chinese Journal of Nuclear Medicine and Molecular Imaging 2023;43(12):724-729
Objective:To evaluate the clinical application potential of a novel prostate specific membrane antigen (PSMA) targeted PET tracer 68Ga-PSMA-NYM032 in patients diagnosed initially with prostate cancer. Methods:A total of 63 patients (age (68.7±8.7) years) with suspected prostate cancers who received 68Ga-PSMA-NYM032 PET/CT imaging in Affiliated Hospital of Jiangnan University between March 2022 and January 2023 were enrolled prospectively. The diagnostic efficiency of 68Ga-PSMA-NYM032 PET/CT imaging was evaluated in a patient-centered manner. The ROI was drawn to obtain SUV max by semi-quantitative analysis with visual analysis, and the diagnostic threshold of SUV max was obtained by ROC curve analysis. The correlations of SUV max in primary foci with total prostate specific antigen (tPSA) and Gleason score (GS) were analyzed by Spearman rank correlation analysis. Based on the D′Amico risk stratification (prostate specific antigen (PSA)>20 μg/L and ≤20 μg/L, GS>7 and ≤7), the detection rates of metastases by 68Ga-PSMA-NYM032 PET/CT imaging in different stratifications were analyzed by Fisher exact test, and the differences between SUV max of metastases in different stratifications were determined by Mann-Whitney U test. Results:The accuracy of 68Ga-PSMA-NYM032 PET/CT imaging was 92.06%(58/63), the sensitivity was 96.55%(28/29), the specificity was 88.24%(30/34), the positive predictive value was 87.50%(28/32), the negative predictive value was 96.77%(30/31), and the optimal SUV max threshold was 6.9. 68Ga-PSMA-NYM032 showed varying degrees of high uptake in the primary foci of prostate cancer, and SUV max were positively correlated with tPSA and GS ( rs values: 0.657, 0.592, P values: <0.001, 0.001). Stratified analysis showed a statistically significant difference in the detection rate of bone metastases by 68Ga-PSMA-NYM032 PET/CT between the GS>7 and GS≤7 subgroups (9/17 vs 1/12; P=0.019), while no statistical significances were observed in the detection rates of bone metastases or lymph node metastases of another subgroups (all P>0.05). In addition, none of the differences in SUV max of metastases in patients with different stratifications were statistically significant ( z value: from -1.57 to -0.50, all P>0.05). Conclusions:68Ga-PSMA-NYM032 PET/CT imaging has good diagnostic efficacy for prostate cancer, and it may provide a new strategy for the precise diagnosis and treatment of prostate cancer. Besides, GS stratification may affect the detection rate of bone metastases by 68Ga-PSMA-NYM032 PET/CT imaging.
10.Value of pressure-strain loop in evaluating the effects of thoracic paravertebral block on left ventricular function before off-pump coronary artery bypass graft
Yanjuan ZHANG ; Haoran WANG ; Di XU ; Yu CHEN ; Chanjuan GONG
Chinese Journal of Ultrasonography 2022;31(1):13-18
Objective:To observe the effects of bilateral thoracic paravertebral block (TPVB) on left ventricular myocardial work using pressure-strain loop(PSL) in patients before off-pump coronary artery bypass graft(OPCABG).Methods:A total of 24 patients with coronary heart disease undergoing selective OPCABG were recruited in the First Affiliated Hospital of Nanjing Medical University from May to August 2021. All patients underwent ultrasound-guided TPVB preoperatively. Left ventricular global work, including global longitudinal strain(GLS), global work index(GWI), global constructive work(GCW), global waste work(GWW), global work efficiency(GWE), and regional work, including myocardial work index(MWI), myocardial work efficiency(MWE) were observed before TPVB and 20 minutes after TPVB.Results:The parameters of heart rate and left ventricular outflow tract blood flow were decreased [(69.13±10.72)bpm vs (65.46±9.66)bpm, P=0.010; (13.86±2.83)ml vs (12.72±2.60)ml, P=0.017]. The MWI in regional segments of hypokinesis and akinesis were significantly improved [hypokinesis: (1 175.76±206.64)mmHg% vs (1 349.38±462.35)mmHg%, P=0.004; akinesis: (684.94±251.39)mmHg% vs (965.35±384.33)mmHg%, P=0.001] and the MWE in regional segments of hypokinesis and akinesis were improved [hypokinesis: (87.79±7.46)% vs (90.35±6.39)%, P=0.029; akinesis: (70.24±18.03)% vs (80.15±16.65)%, P=0.021]. There were no significant changes in MWI, MWE, LVEF, GLS, GWI, GCW, GWW and GWE(all P>0.05). Conclusions:Based on PSL, the changes of left ventricular work in patients with OPCABG before and after TPVB show that TPVB can improve the blood supply of the ischemic myocardium, which provides a reliable basis for optimizing the perioperative anesthesia management.

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