1.Study design and rationale of the TXL-CAP trial: a randomized, double-blind, placebo-controlled, multicenter clinical trial assessing the effect of Tongxinluo capsules on the stability of coronary atherosclerotic plaques.
Mei NI ; Yun TI ; Yan QI ; Meng ZHANG ; Dayue Darrel DUAN ; Chen YAO ; Zhen-Hua JIA ; Yun ZHANG ; Pei-Li BU
Journal of Geriatric Cardiology 2025;22(7):615-624
Recent clinical trials have demonstrated a protective effect in using traditional Chinese medicine Tongxinluo (TXL) capsule to treat atherosclerosis. However, clinical evidence of the effects of TXL treatment on coronary plaque vulnerability is unavailable. In response, we developed this study to investigate the hypothesis that on the basis of statin therapy, treatment with TXL capsule may stabilize coronary lesions in patients with acute coronary syndrome (ACS). The TXL-CAP study was an investigator-initiated, randomized, double-blind clinical trial conducted across 18 medical centers in China. Patients with ACS aging from 18 to 80 years old who had a non-intervened coronary target lesion with a fibrous cap thickness (FCT) < 100 μm and lipid arc > 90° as defined by optical coherence tomography (OCT) were recruited. A total of 220 patients who met the selection criteria but did not meet the exclusion criteria will be finally recruited and randomized to receive treatment with TXL (n = 110) or placebo (n = 110) for a duration of 12 months. The primary endpoint was the difference in the minimum FCT of the coronary target lesion between TXL and placebo groups at the end of the 12-month follow-up. Secondary endpoints included: (1) changes of the maximum lipid arc and length of the target plaque, and the percentage of lipid, fibrous, and calcified plaques at the end of the 12-month period; (2) the incidence of composite cardiovascular events and coronary revascularization within the 12 months; (3) changes in the grade and scores of the angina pectoris as assessed using the Canadian Cardiovascular Society (CCS) grading system and Seattle angina questionnaire (SAQ) score, respectively; and (4) changes in hs-CRP serum levels. The results of the TXL-CAP trial will provide additional clinical data for revealing whether TXL capsules stabilizes coronary vulnerable plaques in Chinese ACS patients.
2.FLASH Interacts with Promyelocytic Leukemia Protein Ⅳ(PML Ⅳ)and Enhances the SUMOylation of p53
Meng-Ni WANG ; Zhen-Zhen XIONG ; Zhi-Ying WANG ; Jian-Hua WU ; Xiao-Zhong SHI
Chinese Journal of Biochemistry and Molecular Biology 2024;40(10):1426-1440
As a unique gene in the genome,FLASH(FADD-like interleukin-1β-converting enzyme asso-ciated huge protein)/CASP8AP2 is involved in multiple cellular processes,including apoptosis,histone gene pre-mRNA processing,transcriptional regulation,and cell cycle progression.Clinical studies have shown that FLASH is a valuable prognostic marker for acute lymphoblastic leukemia,and a crucial factor for the survival of various cancer cells.Therefore,in-depth research into the function of FLASH may offer new perspectives for the treatment of related diseases.Our previous research identified FLASH as a bind-ing partner of p53,demonstrating that FLASH enhances the transcriptional activity of p53.Here we fur-ther investigate the molecular mechanisms of the interaction between FLASH and p53,revealing that the p53-K386R mutation(SUMOylation residue)attenuated its interaction with FLASH(aa 51-200)and FLASH-SIM(SUMO-interacting motif)(aa 1 534-1 806)significantly.However,SUMO can bind to FLASH-SIM directly,instead of FLASH(aa 51-200).Subsequent research shows that overexpression of FLASH in cells enhances global SUMO1 conjugation and p53-SUMO1 conjugation,therefore providing a plausible explanation for the underlying mechanism of FLASH enhancing the transcriptional activity of p53.Since promyelocytic leukemia protein nuclear body(PML NB)serves as subcellular reactors for SUMO conjugation within the cell,and the PML Ⅳ isoform can specifically enhance the SUMO modifica-tion of p53,we have investigated the interaction between FLASH and PML Ⅳ,and elucidated the struc-tural basis of their interaction:both FLASH-N3A(501-802)and FLASH-C2(1 807-1 981)bind to PML Ⅳ(aa 228-633).Further investigations reveal that they can synergistically enhance global SUMO1 modification as well as SUMO1 modification of p53.The interaction between FLASH and tumor suppres-sors p53 or PML Ⅳ enriches our understanding of its function and reveals the potential mechanism of FLASH in tumor development,therefore offering novel insights into cancer diagnosis and treatment.
3.Progress of traditional Chinese medicine monomers in the treatment of respiratory diseases by intervening nucleotide binding and oligomerization domain-like receptor protein 3 inflammasome
Hua-Yang PAN ; Xu-Ming LUO ; Fu-Qi MA ; Zhen-Hua NI ; Xiong-Biao WANG ; Yu-Hua LIN
The Chinese Journal of Clinical Pharmacology 2024;40(12):1839-1843
Adequate inflammation can effectively eliminate harmful substances and prevent disease as a self-protective measure to prevent further damage to the body,while abnormally activated inflammation is detrimental to the body.Nucleotide binding and oligomerization domain-like receptor protein 3(NLRP3)inflammasome that participates in inflammatory responses are closely related to many physiological and pathological processes and play an important role in the occurrence and development of pulmonary diseases.This article mainly reviewed the activation mechanism and hypothesis of NLRP3 inflammasome,as well as the research on treating respiratory diseases by interfering with NLRP3 inflammasome.
4.Evolution and research progress of traditional Chinese medicine processing by roasting.
Zhen-Ni QU ; Chun-Yan XIE ; Qian ZHOU ; Peng GAO ; Dian-Hua SHI ; Yan-Peng DAI
China Journal of Chinese Materia Medica 2024;49(24):6604-6624
Roasting is a characteristic traditional Chinese medicine(TCM)processing technology, which has a long history. A large number of ancient books recorded the varieties and processing methods of roasted TCM. However, with the evolution of the times, there are relatively few studies on this processing technology in modern times. By consulting works related to herbs of the past, this study collected a total of 119 kinds of TCM roasting methods recorded in 123 ancient books and systematically summarized the historical evolution and development of TCM roasting methods. At the same time, the inclusion of roasted varieties in Chinese Pharmacopoeia of different editions, National Traditional Chinese Medicine Processing Specification(1988 edition), and provincial TCM processing specifications was sorted out. This paper reviews the research progress of the process, quality control, chemical composition, pharmacological action, and clinical application of roasted TCM and analyzes the evolution of the roasting technology, in order to provide a literature basis for optimizing roasting process parameters, establishing the quality standard of roasted decoction pieces, explaining the processing theory of roasting, and promoting rational clinical application.
Drugs, Chinese Herbal/chemistry*
;
Medicine, Chinese Traditional/history*
;
Humans
;
Quality Control
;
History, Ancient
;
Hot Temperature
5.Research progress of button battery ingestion in children.
Feng Zhen ZHANG ; Qing Chuan DUAN ; Gui Xiang WANG ; Jing ZHAO ; Hua WANG ; Hong Bin LI ; Xin NI ; Jie ZHANG
Chinese Journal of Otorhinolaryngology Head and Neck Surgery 2023;58(4):394-398
Child
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Humans
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Infant
;
Esophagus
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Electric Power Supplies
;
Eating
;
Foreign Bodies
6.Clinical characteristics and serious complications of esophageal button battery ingestion in the pediatric on 83 cases.
Feng Zhen ZHANG ; Qing Chuan DUAN ; Gui Xiang WANG ; Xiao Jian YANG ; Wei ZHANG ; Jing ZHAO ; Hua WANG ; Hong Bin LI ; Xin NI ; Jie ZHANG
Chinese Journal of Otorhinolaryngology Head and Neck Surgery 2023;58(5):481-485
Objective: To analyze the clinical characteristics and complications of esophageal foreign bodies of button battery ingestion in children. Methods: A retrospective descriptive study included 83 children who were hospitalized in our hospital on account of button battery ingestion from January 2011 to December 2021. There were 50 males (60.2%) and 33 females (39.8%). The age ranged from 7.6 months to one month off 10 years, with a median age of 18 months. The data of patient demographics and time from ingestion to admission, location, symptoms, management, complications, and follow-up outcome were recorded. SPSS17.0 software was used for statistical analysis. Results: Seventy-two children (86.7%) were younger than 3 years old. The time from ingestion to admission ranged from 1 h to 2 months, with a median time of 8 h. Among the 63 children who were first diagnosed in our hospital, the most common clinical symptoms were nausea and vomiting (32 cases, 50.8%), dysphagia (31 cases, 49.2%), salivation (11 cases, 17.5%) and fever (10 cases, 15.9%). Seventy-three of 83 cases had complete preoperative diagnostic tests, and 55 cases (75.3%) were diagnosed by X-ray. In 56 cases (76.7%), the foreign badies were impacted in the upper third of esophagus. In 72 cases (86.7%), the foreign badies were removed by rigid esophagoscopy. 23 (27.7%) had serious complications, including tracheoesophageal fistula in 15 cases(TEF;65.2%), vocal cord paralysis (VCP;34.8%) in 8 cases, esophageal perforation in 3 cases (EP;13.0%), hemorrhage in 3 cases(13.0%), mediastinitis in 3 cases (13%), and periesophageal abscess in 1 case (4.3%). There were significant differences in the exposure time of foreign bodies and unwitnessed ingestion by guardians in the complications group (P<0.05). 2 cases died (2.4%)respectively due to arterial esophageal fistula bleeding and respiratory failure caused by stent displacement during the treatment of tracheoesophageal fistula. Conclusion: Accidental button battery ingestion can be life-threatening. and it mostly happens in children under 3 years old. Serious complications may happen cause of non-specific clinical manifestations and unwitnessed ingestions. Anterior and lateral chest X-ray is the first examination choice. Tracheoesophageal fistula is the most common serious complication.
Male
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Female
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Child
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Humans
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Infant
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Child, Preschool
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Tracheoesophageal Fistula/etiology*
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Retrospective Studies
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Foreign Bodies/diagnosis*
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Eating
7. Relationship between Fok polymorphism of vitamin-D receptor gene and hypertensive disorder complicating pregnancy in Han nationality of Qinghai province
Zhen WU ; Qian DUAN ; Ming YUAN ; Xue-Ni WANG ; Wen-Jing CHEN ; Jian-Hua LI ; Zhen WU ; Yu-Qin LI ; Yu-Qin E-LUO-JI
Acta Anatomica Sinica 2023;54(3):313-318
[ Abstract] Objective To investigate the relationship between single nucleotide polymorphism (SNP) Fok (rs2228570 / rs10735810) of vitamin D receptor (VDR) gene and hypertensive disorder complicating pregnancy (HDCP) in Han nationality women of Qinghai province. Methods A total of 137 Han nationality HDCP subjects (HDCP group) and 146 Han nationality normal pregnant subjects (control group) were selected from Qinghai province. The Fok polymorphism typing in HCDP group and control group was analyzed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) . The mutation was confirmed by sequencing. SPSS 19. 0 statistical software was used to test whether there were significant differences between two groups in general clinical data, genotype and allele frequency distribution. Results The frequency of FF Ff ff genotype of Fok in HDCP group and control group were 51. 82%, 37. 96%, 10. 22% and 34. 93%, 43. 15%, 21. 92% respectively (
8.Optimization of TLC identification for Cirsii Herba and research on changes in quality properties "carbonizing retains characteristics" of its charred product
Qi LU ; Tian-Ze ZHANG ; Juan-Juan ZHU ; Zhen-Ni QU ; Chun-Meng XU ; Yan-Peng DAI ; Dian-Hua SHI
Chinese Traditional Patent Medicine 2023;45(12):4024-4029
AIM To optimize the TLC identification method for Cirsii Herba and to study the changes in quality properties"carbonizing retains characteristics"of Cirsii Herba Carbonisata.METHODS After the improvement of thin layer plate and solvent in the TLC identification based on the Chinese Pharmacopoeia 2020 Edition for Cirsii Herba,Cirsii Herba Carbonisata had its TLC identification method and UPLC fingerprint established for the determination of its content of buddleoside and acacetin as well.RESULTS We used silica gel G plate,and the solvent of toluene-acetone-formic acid-methanol(6 ∶ 3 ∶ 0.5 ∶ 2.5)for TLC identification of Cirsii Herba.The content variations of buddleoside and acacetin in Cirsii Herba and its differently charred products were consistent with the result of the TLC identification.CONCLUSION The improved TLC identification method for Cirsii Herba is of lower cost and less solvent toxicity compared to the method in the Chinese Pharmacopoeia 2020 Edition,and can identify the changes in quality properties"carbonizing retains characteristics"of differently charred Cirsii Herba,therefore it can be used to control the quality of Cirsii Herba Carbonisata in the market.
9.Effects of the ITGA2B Nonsense Mutation (c.2659C > T, p.Q887X) on Platelet Function in a Mouse Model of Glanzmann's Thrombasthenia Generated with CRISPR/Cas9 Technology.
Fei YANG ; Miao JIANG ; Zeng-Hua LIN ; Zhan-Li XIE ; Zhen-Ni MA ; Li YANG ; Hong LIU ; Zhao-Yue WANG ; Lu ZHOU
Journal of Experimental Hematology 2022;30(2):559-564
OBJECTIVE:
To construct a mouse model of Glanzmann's thrombasthenia (GT) with ITGA2B c.2659 C>T (p.Q887X) nonsense mutation by CRISPR/Cas9 technology, and then further explore the expression and function of glycoprotein αIIbβ3 on the surface of platelet membrane.
METHODS:
The donor oligonucleotide and gRNA vector were designed and synthesized according to the ITGA2B gene sequence. The gRNA and Cas9 mRNA were injected into fertilized eggs with donor oligonucleotide and then sent back to the oviduct of surrogate mouse. Positive F0 mice were confirmed by PCR genotyping and sequence analysis after birth. The F1 generation of heterozygous GT mice were obtained by PCR and sequencing from F0 bred with WT mice, and then homozygous GT mice and WT mice were obtained by mating with each other. The phenotype of the model was then further verified by detecting tail hemorrhage time, saphenous vein bleeding time, platelet aggregation, expression and function of αIIbβ3 on the surface of platelet.
RESULTS:
The bleeding time of GT mice was significantly longer than that of WT mice (P<0.01). Induced by collagen, thrombin, and adenosine diphosphate (ADP), platelet aggregation in GT mice was significantly inhibited (P<0.01, P<0.01, P<0.05). Flow cytometry analysis showed that the expression of αIIbβ3 on the platelet surface of GT mice decreased significantly compared with WT mice (P<0.01), and binding amounts of activated platelets to fibrinogen were significantly reduced after thrombin stimulation (P<0.01). The spreading area of platelet on fibrinogen in GT mice was significantly smaller than that in WT mice (P<0.05).
CONCLUSION
A GT mouse model with ITGA2B c.2659 C>T (p.Q887X) nonsense mutation has been established successfully by CRISPR/Cas9 technology. The aggregation function of platelet in this model is defective, which is consistent with GT performance.
Animals
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CRISPR-Cas Systems
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Codon, Nonsense
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Disease Models, Animal
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Fibrinogen/genetics*
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Humans
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Integrin alpha2/genetics*
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Mice
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Oligonucleotides
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Platelet Glycoprotein GPIIb-IIIa Complex/genetics*
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RNA, Guide
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Thrombasthenia/genetics*
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Thrombin/genetics*
10.Effectiveness and safety of the home-made umbrella-shaped Octoparms inferior vena cava filter in the prevention of pulmonary embolism
Boxiang ZHAO ; Jianlong LIU ; Gaojun TENG ; Caifang NI ; Hao XU ; Zhen LI ; Shuiting ZHAI ; Yanrong ZHANG ; Hua XIANG ; Weizhu YANG ; Jianping GU
Chinese Journal of Radiology 2022;56(5):556-562
Objective:To evaluate the effectiveness and safety of the home-made umbrella-shaped Octoparms inferior vena cava filter in the prevention of pulmonary embolism.Methods:A multicenter, randomized, positive parallel controlled, non-inferiority clinical trial was conducted in ten hospitals in China from October 2017 to March 2019. A total of 188 subjects were enrolled according to the same inclusion and exclusion criteria in different institutes. The 188 subjects were randomly divided into the trial group or the control group according to 1∶1 by the central randomization system, with 94 cases in each group. Octoparms inferior vena cava filter was used in the trial group, and the Celect inferior vena cava filter in the control group. The primary effective index was clinical success rate,including the clinical success rate of filter placement and filter retrieval. The secondary index included the rate of manual success of the delivery sheath system,incidence of pulmonary embolism(within 6 months), incidence of filter fracture,migration (>20 mm),tilt(>15°) on insertion/retrieval,and the situation of inferior vena cava flow(within 6 months). Safety evaluation included the incidence of filter related complications and device-related adverse events immediately after surgery and during follow-up.Results:The success rate of implantation was 100% in 188 subjects. Filter retrieval was performed in 87 cases (92.55%) in the trial group and 91 cases (96.81%) in the control group. The clinical success rate of the trial group was 97.87%(92/94) and that of the control group 98.94%(93/94). There was no significant difference between the two groups (χ 2=0.77, P=0.380). The success rate of delivery sheath system was 96.81%(91/94) and 98.94%(93/94) in the trail group and the control group,respectively. There was no significant difference between the two groups( P=0.621). There was 1 case (1.22%) of new asymptomatic pulmonary embolism in the trial group after filter placement and 2 cases (2.44%) in the control group. There was no significant difference between the two groups ( P>0.05). No filter fracture or migration (>20 mm) occurred in either group. The tilting of filter (>15°) was found in 1 case (1.06%) in the test group and 1 case (1.06%) in the control group when the filter was placed. The tilting of filter (>15°) was found in 0 case in the test group and 2 cases (2.44%) in the control group when the filter was retrieved. There was no significant difference between the two groups ( P>0.05). Inferior vena cava thrombosis before filter retrieval was found in 5 cases (5.75%) in trial group and 3 cases (3.30%) in control group. There was no significant difference between the two groups ( P=0.489). There were no immediate serious complications during filter placement/removal in either group. No filter obstruction,migration,deformation,penetration and occlusion of inferior vena cava. The incidence of device-related adverse events was low in both group. There was no significant difference between the two groups ( P>0.05). Conclusion:The home-made umbrella-shaped Octoparms inferior vena cava filter is effective and safe in preventing pulmonary embolism, and is not worse than Celect filter.

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