1.Global progress in peptide radiopharmaceutical research and China's opportunities
Xue-yao CHEN ; Bo-yang ZHANG ; Kuan HU ; Rui WANG
Acta Pharmaceutica Sinica 2023;58(12):3477-3489
Radiopharmaceutical is an essential component of nuclear medicine and molecular imaging, as well as a key component of precision medicine. The United States Food and Drug Administration (FDA) has recently approved the marketing of several peptide-based radiopharmaceuticals, sparking a global trend of research in this area and propelling nuclear medicine into the precision theranostic era. This has created a new wave of technological competition in the field of nuclear medicine. It is the responsibility of Chinese scientists in the radiopharmaceutical field to capitalize on this opportunity, leverage the momentum, and strengthen their independent innovation capability in order to stay ahead in the future global nuclear science and technology competition. This review provides an overview of the remarkable progress made in the research, development, and translation of global peptide-based radiopharmaceuticals. It examines the advantages of peptide-based radiopharmaceuticals and outlines the current hot targets and progress in drug development in this field. Additionally, it proposes six opportunities for China to overtake others in the field of peptide-based radiopharmaceuticals and achieve technological self-reliance, based on interdisciplinary collaboration and independent innovation. Lastly, the future prospect of peptide-based radiopharmaceuticals is discussed.
2.Effects of electro-acupuncture on expression of triggering receptor expressed on myeloid cells 1 in ankle joint synovial tissue of acute gouty arthritis rats.
Chao-Nan ZHANG ; Xue-Kuan HUANG ; Yan LUO ; Juan JIANG ; Lei WAN ; Ling WANG
Journal of Southern Medical University 2015;35(1):133-136
OBJECTIVETo investigate the effects of electro-acupuncture (EA) on the expression of triggering receptor expressed on myeloid cell (TREM)l in ankle joint synovial tissue of acute gouty arthritis (AGA) rats.
METHODSForty male SD rats were randomly divided into 4 groups: normal, AGA, medication and EA group, 10 rats in each group. AGA model was established by induced monosodium urate (MSU) method, except the normal group. Tow days before AGA model was established, normal and AGA groups were lavaged with normal saline (20 ml/kg), medication group was lavaged with colchicine solution (20 ml/kg), EA(1.5-2 Hz, D.-D.wave, 9v; 1-3 rnA) was applied to "Sanyinjiao" (SP6), "jiexi" (ST41) and "Kunlun" (BL60) for 20 min, once daily;continuously for 9 days. Then observed the changes in dysfunction, and the content of TNF-α and IL-lβ detected by ELISA, the expression of TREM-l detected by immunohistochemistry and western blot.
RESULTSCompared to the normal group, the AGA group of the dysfunction index increased significantly (P<0.01), the content of TNF-α and IL-lβ increased significantly (P<0.05), the expression of TREM-l in synovial tissue increased significantly (P<0.05); the medication and EA groups compared to the AGA group, the dysfunction index decreased significantly (P<0.01), the content of TNF-α and IL-lβ decreased significantly (P<0.05), the expression of TREM-l in synovial tissue decreased significantly (P<0.05); there were not statistically significant between the medication and EA group (P>0.05).
CONCLUSIONEA treating AGA may be through down-regulating the expression of TREM -1 in synovial tissue.
Animals ; Ankle Joint ; metabolism ; pathology ; Arthritis, Gouty ; metabolism ; therapy ; Electroacupuncture ; Interleukin-1beta ; metabolism ; Male ; Rats ; Rats, Sprague-Dawley ; Receptors, Immunologic ; metabolism ; Synovial Membrane ; metabolism ; Triggering Receptor Expressed on Myeloid Cells-1 ; Tumor Necrosis Factor-alpha ; metabolism
3.Analysis of the electromyographic characteristics on shoulder fatigue caused by lifting load.
Peng-fei ZHAO ; Qiang MA ; Xue-wei CHEN ; Kuan ZHANG ; Ting-ting AI ; Ze-ming MAN
Chinese Journal of Industrial Hygiene and Occupational Diseases 2012;30(7):501-503
OBJECTIVETo analyze and evaluate the fatigue of shoulder skeletal muscle caused by different lifting loads with surface electromyography (sEMG).
METHODSAccording to the loading standard of1 Repetition Maximum (1RM), ten male volunteers performed 3 tasks of upper limb flexion, i.e. 10%, 50% and 90%-1RM. During action process, the signals of Upper Trapezius (UT), Lower Trapezius (LT), Serratus Anterior (SA) and Anterior Deltoid (AD) were recorded by sEMG. The Mean Amplitude (MA) served as an index to evaluate the changes in skeletal muscle fatigue.
RESULTSThe scores of Borg were 15.6, 15.9 and 15.2 for 3 loads of 10%-1RM, 50%-1RM and 90%-1RM, respectively (P > 0.05). The mean amplitudes (MAs) of Upper Trapezius, Lower Trapezius, Anterior Deltoid and Serratus Anterior in shoulders increased obviously. Under the load intensity of 10%-1RM, the MAs of Upper Trapezius and Anterior Deltoid increased significantly (P < 0.05), which were 0.898 and 0.736, respectively. After the exhaustion, the contribution of mean amplitude in shoulder muscle did not change significantly (P > 0.05).
CONCLUSIONThe low-load action for long time can induce easily the fatigue of upper trapezius and anterior deltoid.
Adult ; Electromyography ; Humans ; Lifting ; Male ; Muscle Fatigue ; physiology ; Muscle, Skeletal ; physiology ; Shoulder ; physiology ; Workload
4.Topic model for Chinese medicine diagnosis and prescription regularities analysis: case on diabetes.
Xiao-Ping ZHANG ; Xue-Zhong ZHOU ; Hou-Kuan HUANG ; Qi FENG ; Shi-Bo CHEN ; Bao-Yan LIU
Chinese journal of integrative medicine 2011;17(4):307-313
Induction of common knowledge or regularities from large-scale clinical data is a vital task for Chinese medicine (CM). In this paper, we propose a data mining method, called the Symptom-Herb-Diagnosis topic (SHDT) model, to automatically extract the common relationships among symptoms, herb combinations and diagnoses from large-scale CM clinical data. The SHDT model is one of the multi-relational extensions of the latent topic model, which can acquire topic structure from discrete corpora (such as document collection) by capturing the semantic relations among words. We applied the SHDT model to discover the common CM diagnosis and treatment knowledge for type 2 diabetes mellitus (T2DM) using 3 238 inpatient cases. We obtained meaningful diagnosis and treatment topics (clusters) from the data, which clinically indicated some important medical groups corresponding to comorbidity diseases (e.g., heart disease and diabetic kidney diseases in T2DM inpatients). The results show that manifestation sub-categories actually exist in T2DM patients that need specific, individualised CM therapies. Furthermore, the results demonstrate that this method is helpful for generating CM clinical guidelines for T2DM based on structured collected clinical data.
Diabetes Mellitus, Type 2
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diagnosis
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therapy
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Diagnosis, Differential
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Humans
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Medicine, Chinese Traditional
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Models, Theoretical
5.Factors influencing the diagnose on causes of dyspepsia in central area of Shaanxi province.
Xing WANG ; Kuan-xue ZHANG ; Jin-yan LUO ; Bo-yuan MEN ; Yan ZHOU
Chinese Journal of Epidemiology 2003;24(8):715-718
OBJECTIVETo investigate the proportions of functional dyspepsia (FD) and structural diseases within the dyspeptic outpatients in hospitals of different ranking in central area Shaanxi province, and to explore the safety in adopting "symptom and treatment" algorithm used in Western countries.
METHODSA clinical epidemiology survey was carried out by means of a stratified sample of 3 019 dyspeptic outpatients through standardized questionnaire. All of the patients were followed for 4 - 24 weeks, and finally received their diagnoses through a consistent criteria.
RESULTSProportionally, FD in all the outpatients took up 44.8% with 44.7% benign organic causes and 10.5% malignant diseases. In the patients who had marked alarm symptoms, the proportion of benign and malignant diseases rose to 52.1% and 29.2%, respectively. They were significantly higher than those without alarm symptoms (39.2%, 2.9%) (P < 0.01). All of the dyspeptic patients were divided into 7 groups according to different ages. 64.5% of FD patients were younger than 25 years and the rate of FD declined with age. It was found that only four patients below 35 years old had malignance. The number of cases increased significantly in age 35 - 45 group and reached 30.8% in 65 - 74 group.
CONCLUSIONThere were some differences noticed within dyspeptic patterns between local area in China and Western countries, and the "symptom and treatment" approach was not entirely suitable to the local area in China.
Adolescent ; Adult ; Age Factors ; Aged ; Aged, 80 and over ; Child ; China ; epidemiology ; Dyspepsia ; diagnosis ; epidemiology ; etiology ; Esophageal Motility Disorders ; complications ; diagnosis ; epidemiology ; Female ; Follow-Up Studies ; Humans ; Male ; Middle Aged ; Prevalence ; Stomach Diseases ; complications ; diagnosis ; epidemiology
6.Expression of 8-hydroxy-2-deoxy guanosine, thioredoxin reductase 1 and glutathione peroxidase 1 in myocardium of autopsy patients with Keshan disease
Jun-rui, PEI ; Ming-fa, LIU ; Yang, LIU ; Hong-qi, FENG ; Zhi-yi, ZHANG ; Ling-wang, ZHOU ; Xue-kuan, ZHONG ; Tong, WANG
Chinese Journal of Endemiology 2012;31(6):631-634
Objective In this study,we investigated the relationship between oxidative stress,selenoproteins level and onset of Keshan disease (KD) through detecting the expression of 8-hydroxy-2-deoxy guanosine (8-OH-dG),thioredoxin reductase 1 (TrxR1) and glutathione peroxidase 1 (GPx1) in myocardial tissue.Methods Myocardium samples of autopsy patients including 8 cases of KD (KD group included 4 acute KD and 4 chronic KD) and 9 cases of non-KD (control group) were immunohistochemically stained for 8-OH-dG,TrxR1 and GPx1.The staining intensities subsequently quantified by using Olympus Image-Pro Plus 6.0 software.Results The positive rate of 8-OH-dG expression in myocardial nuclei was higher in the case group[(68.6 ± 20.4)%] than that of the control group[(2.4 ± 1.5)%,t =8.515,P < 0.05].In addition,the positive rate of 8-OH-dG expression in acute KD[(91.7 ± 3.7)%] was significantly higher than that of chronic KD[(53.2 ± 7.9)%,t =6.409,P<0.05].The distribution of TrxR1 and GPx1 was not associated with the distribution of myocardial damage.The expression of these two selenoproteins in KD group (401340 ± 59865,497590 ± 197082) were both lower than that of control group(2790300 ± 379298,1348400 ±615840; t =-28.493,-6.016,respectively,all P<0.01).Conclusions Oxidative damage is detected in myocardium tissue of KD,and 8-OH-dG expression is associated with the degree of myocardial damage in KD.Selenoproteins,TrxR1 and GPx1,may be closely related to the pathogenesis of KD.
7.Influence of lncRNA ZFAS1 on cisplatin sensitivity in glioma via miR-193b-3p regulation
Hui ZHANG ; Kuan-Yun ZHENG ; Li-Na QI ; Zi-Jiao XUE
The Chinese Journal of Clinical Pharmacology 2024;40(12):1774-1778
Objective To investigate the role of long non-coding RNA(lnc RNA)ZFAS1 in glioma cells'sensitivity to cisplatin and its underlying mechanisms.Methods By analyzing the knockdown of ZFAS1 on the sensitivity of glioma cells to cisplatin using real-time fluorescence quantitative polymerase chain reaction(qRT-PCR)experiments,and the cells were divided into sh-NC group(transfected with sh-NC lentiviral plasmid),sh#1 group(transfected with sh-ZFAS1-1 lentiviral plasmid)and sh#2 group(transfected with sh-ZFAS1-2 lentiviral plasmid).Dual luciferase experiments verified the interaction between ZFAS1 and miR-193b-3p,and the cells were divided into ZFAS1-WT+NC inhibitor group(transfected with ZFAS1 wild-type plasmid and NC inhibitor),ZFAS1-WT+miR-193b-3p inhibitor group(transfected with ZFAS1 wild-type plasmid and miR-193b-3p inhibitor),ZFAS1-Mut+NC inhibitor group(transfected with ZFAS1 mutant plasmid and NC inhibitor)and ZFAS1-Mut+miR-193b-3p inhibitor group(transfected with ZFAS1 mutant plasmid and miR-193b-3p inhibitor).Cell counting kit-8(CCK-8)and terminal deoxynucleotidly transferase mediated labeling(TUNEL)experiments were used to analyze the effect of ZFAS1/miR-193b-3p on the sensitivity of glioma cells to cisplatin,and the cells were divided into blank control group(0 μg·mL-1 cisplatin treatment of U251 cells),0.5 μg·mL-1 cisplatin+sh-NC+NC inhibitor group(0.5 μg·mL-1 cisplatin treatment of U251 cells co-transfected with sh-NC lentiviral plasmid and NC inhibitor),0.5 μg·mL-1 cisplatin+sh#1+NC inhibitor group(0.5 μg·mL-1cisplatin treatment of U251 cells co-transfected with sh-NC lentiviral plasmid and NC inhibitor),and 0.5 μg·mL-1 cisplatin+sh#1+miR-193b-3p inhibitor group(0.5 μg·mL-1 cisplatin treatment of U251 cells co-transfected with sh-ZFAS1-1 lentiviral plasmid and miR-193b-3p inhibitor).Results The results of the experiment showed that the expression levels of ZFAS1 in the sh-NC group,sh#1 group and sh#2 group were 1.00±0.17,0.48±0.06 and 0.68±0.08.The fluorescence activities of ZFAS 1-WT+NC inhibitor group,ZFAS1-WT+miR-193b-3p inhibitor group,ZFAS1-Mut+NC inhibitor group and ZFAS1-Mut+miR-193b-3p inhibitor group were 1.00±0.10,1.45±0.11,1.02±0.09 and 0.97±0.13.The proliferation rates at 72 h for the blank control group,0.5 μg·mL-1 cisplatin+sh-NC+NC inhibitor group,0.5 μg·mL-1 cisplatin+sh#1+NC inhibitor group and 0.5 μg·mL-1cisplatin+sh# 1+miR-193b-3p inhibitor group were(100.00±14.13)%,(96.62±9.82)%,(60.56±6.08)%and(78.64±7.22)%;while the apoptosis rates at 72 h were(9.52±1.11)%,(10.12±1.34)%,(16.08±1.52)%and(12.22±1.19)%.Comparied between blank control group and 0.5 μg·mL-1 cisplatin+sh-NC+NC inhibitor group,0.5 μg·mL-1 cisplatin+sh#1+NC inhibitor group and 0.5 μg·mL-1 cisplatin+sh # 1+miR-193b-3p inhibitor group,the differences were statistically significant(all P<0.05).Conclusion This study reveals the important role of ZFAS1 in cisplatin sensitivity in glioma and elucidates its mechanism of influencing drug sensitivity through the regulation of miR-193b-3p.
8.Sequence analysis of the connexin 26 genes from a deafness family with A1555G mutation in Huaiyin.
Hai-Jun ZHANG ; Chun-Hong XU ; Yi-Ju ZHANG ; Su-Ying ZHAO ; Xue-Xia GENG ; Yun-Feng SHAN ; Gang FAN ; Guang-Qian XING ; Xiang-Nian SHAN ; Xing-Kuan BU
Chinese Journal of Otorhinolaryngology Head and Neck Surgery 2005;40(9):678-683
OBJECTIVETo ascertain whether connexin 26 (Cx26) gene was a nuclear modifier gene in an extensive family with matrilineal nonsyndromic deafness associated with A1555G mutation in Huaiyin, China.
METHODSFollowing PCR-restriction fragment length polymorphism (PCR-RFLP) with ApaI restriction enzyme, Cx26 genes from 26 cases, with A1555G mitochondrial mutations in this family, and 62 controls (including 2 patrilineal relatives, 10 spouse controls and 50 unrelated controls), were sequenced.
RESULTSCompared with the reference sequence of Cx26 gene, totally four kinds of nucleotide changes,79G -->A, 109G-->A, 341G-->A and 235delC, were detected in a heterozygous form. However, the former three were previously reported polymorphisms, and only the 235delC was a previously described recessive mutation associated with most autosomal nonsyndromic sensorineural hearing loss in Japan and China. Further study showed that the heterozygous 235delC mutation existed in both one individual with mild hearing loss and two individuals with normal hearing. Clinical characterization showed that 235delC mutation did not seem to modify the deafness phenotype due to the A1555G mutation. Moreover, this 235delC mutation was deduced to derive from a married-in control. Finally, there were no co-segregation between the phenotypes of hearing loss and the genotypes for Cx26 genes based on the four kinds of nucleotide changes.
CONCLUSIONSThe heterozygous 235delC mutation of the Cx26 gene may not modulate the severity of hearing loss associated with A1555G mutation and Cx26 gene is unlikely to be a modifier gene for hearing loss due to A1555G mitochondrial mutation in this Chinese family.
Adolescent ; Adult ; Case-Control Studies ; Child ; Child, Preschool ; China ; epidemiology ; Connexin 26 ; Connexins ; genetics ; Deafness ; epidemiology ; ethnology ; genetics ; Female ; Genotype ; Humans ; Infant ; Infant, Newborn ; Male ; Middle Aged ; Mutation ; Pedigree ; Phenotype ; Polymorphism, Restriction Fragment Length ; Sequence Analysis ; Young Adult
9.Anatomic study of the hypoglossal nerve in hypoglossal-facial nerve anastomosis.
Tian-hong PENG ; Da-chuan XU ; Hua LIAO ; Xue-lei LI ; Si-xin OUYANG ; Song-qing FAN ; Xin-kuan ZHANG
Journal of Southern Medical University 2006;26(5):659-663
OBJECTIVETo determine the optimal position of hypoglossal nerve in hypoglossal-facial nerve anastomosis and the eligibility of hypoglossal-facial nerve anastomosis with the cervical loop.
METHODSThe cervical course and adjacent structures of the hypoglossal nerve were observed on 21 adult cadavers. The hypoglossal nerve and facial nerve were taken from 3 fresh specimens, and the number of the fasciculus and the cross-sectional area of the nerve were measured.
RESULTSThe facial nerve trunk were monofascicular with a cross-sectional area of 5.1-/+0.2 (range 4.6-5.7) mm(2). The number of the fasciculus and the cross-sectional areas of the nerve trunk and the fasciculus were 1.6-/+0.8 (range 1-4) mm(2) , 7.5-/+0.7 mm(2) (range 6.8-8.0) mm(2), and 4.7-/+0.6 (4.1-5.5) mm(2), respectively, at the proximal segment of the hypoglossal nerve, 3.6-/+0.5 (1-5) mm(2) , 5.6-/+0.5 (4.9-6.1) mm(2) , and 1.6-/+0.4 (0.9-2.2) mm(2) at the distal segment, and 2.4-/+0.8 (1-3) mm(2), 1.1-/+0.7 (0.6-2.2) mm(2), and 0.5-/+0.3 (0.3-1.2) mm(2) at the cervical loop.
CONCLUSIONThe cervical loop is inadequate for facial nerve anastomosis and the proximal segment is large enough to allow partial harvesting of the hypoglossal nerve for neurotisation of the facial nerve.
Anastomosis, Surgical ; methods ; Cadaver ; Facial Nerve ; anatomy & histology ; surgery ; Humans ; Hypoglossal Nerve ; anatomy & histology ; surgery ; Nerve Transfer ; methods
10.Peptide nucleic acids arrest the growth of gastric cancer cells SGC7901.
Kuan WANG ; Qi-Fan ZHANG ; Xi-Shan WANG ; Ying-Wei XUE ; Da PANG ; Song-Bin FU
Chinese Medical Journal 2004;117(4):566-570
BACKGROUNDPeptide nucleic acid (PNA) has many characteristics useful in molecular biology. This paper described an effective way to raise the cell ingestion rate of PNA so as to kill gastric cancer cells.
METHODSHeteroduplexes of PNAs and oligonucleotides, wrapped by Lipofectamine 2000, were used to infect SGC7901 cells. The inhibitive effect of heteroduplexes was evaluated by analyzing cell clone forming and cell growth rate. Telomerase activity of SGC7901 cells was detected by polymerase chain reaction enzyme-linked immunosorbent assay (PCR-ELISA) and silver staining assay.
RESULTSPNAs showed a dose-dependent inhibition of cell proliferation. The percentage of proliferation inhibition was 99.4% after 7 days; the rate of cloning inhibition was 98.2% after 8 days; whereas for oligonucleotide groups, at the same concentration, the percentages were 50.1% and 67.5% respectively. Antisense PNA-DNA-Lipofectamine 2000 group (AP-D-L group) exhibited significantly different percentages from the control groups (P < 0.05). The test result indicated that telomerase activity of the AP-D-L group was inhibited (P < 0.05). At the same time, the impact on cell morphology was observed.
CONCLUSIONSThe results showed that PNAs are potent antisense reagents. The telomerase-associated therapies are very promising for the treatment of malignant tumours.
Cell Division ; drug effects ; Cell Line, Tumor ; DNA-Binding Proteins ; Humans ; Peptide Nucleic Acids ; therapeutic use ; Stomach Neoplasms ; pathology ; therapy ; Telomerase ; antagonists & inhibitors ; metabolism ; Transfection