1.Mechanism by which KRT18 interacts with mRNA and long non-coding RNA to regulate intervertebral disc nucleus pulposus cell injury
Zhongyuan LIU ; Yang LI ; Zhiwen ZHANG
Chinese Journal of Tissue Engineering Research 2025;29(2):312-321
BACKGROUND:Differentially expressed RNA-binding proteins in the intervertebral disc plays a key role in intervertebral disc degeneration,and decreased levels of the RNA-binding protein KRT18 are associated with degenerative disc disease,but its specific role in the nucleus pulposus cells has not yet been fully determined. OBJECTIVE:To investigate the interaction of KRT18 with mRNA and long non-coding RNA on nucleus pulposus cells of the intervertebral disc and its mechanism. METHODS:Normal and degenerated nucleus pulposus cells were obtained from nucleus pulposus samples of patients undergoing interbody fusion for lumbar fracture or intervertebral disc degeneration.iRIP-seq,functional enrichment analysis,and DNA microarray analysis were performed to identify the mRNA and long non-coding RNA binding with KRT18.Subsequently,KRT18 was knocked down in nucleus pulposus cells based on the analysis results,and the expression levels of related genes were detected at the protein and RNA levels through protein immunoblotting and qRT-PCR,respectively. RESULTS AND CONCLUSION:Through iRIP-seq analysis,we identified abundant KRT18 binding sites within the GUAAUC and AGCCUC sequences,indicating that KRT18 may be involved in regulating RNA transcription,translation,stability or play a role in cell signaling pathways.It can stably bind to mature mRNA,among which highly expressed genes include CRLF1,IGFBP4,etc.At the same time,the peak genes of long non-coding RNA binding with it include SNHG25,SNHG12,NEAT1,USP32,EIF4A2 and CDH4.Most of these genes are involved in various biological processes such as apoptosis and inflammation,and can mediate related pathways of extracellular matrix metabolism.KRT18 can regulate their stability,transport,translation,splicing and other functions,thus affecting gene expression and cell function.We further verified through experiments the knockdown of KRT18 in nucleus pulposus cells,and found that the level of extracellular matrix metabolism was inhibited and unbalanced,resulting in intervertebral disc degeneration in vitro.This study investigated the regulatory mechanism of KRT18 from the perspective of its binding with mRNA and long non-coding RNA for the first time,and speculated the potential function of KRT18 in the pathogenesis of intervertebral disc degeneration,laying a foundation for future research on the key functions of KRT18.
2.Analysis of the efficacy of lumbar cistern drainage in the treatment of paraplegia after endovascular repair of acute aortic dissection
Yidong HUANG ; Zhiwen ZHANG ; Wenrui LI ; Lei JIN ; Hai FENG ; Jun ZHANG
International Journal of Surgery 2024;51(7):466-470
Objective:To evaluate the efficacy of lumbar cisterna drainage(LCD) in treating paraplegia after thoracic endovascular aortic repair(TEVAR) for acute aortic dissection.Methods:A retrospective descriptive study was used to analyze 4 patients with aortic dissection who developed paraplegia after transthoracic aortic stent graft repair (TEVAR) admitted to Beijing Friendship Hospital Affiliated to Capital Medical University from May 2015 to May 2022. There were 3 males and 1 females, aged between 38 and 65 years old. All patients with paraplegia after TEVAR were treated with LCD. Follow-up was carried out by outpatient and telephone for 12 months. The imaging indicators and clinical efficacy were observed.Results:Two patients were fully recovered before discharge, one patient was completely recovered by about 3 months after surgery, and one patient still had reduced sensation and grade 4 muscle strength at 12 months of follow-up. The CT angiography of all 4 patients did not show any evidence of endoleak, and there was no enlargement of the distal dissecting aneurysm.Conclusion:Lumbar cisterna drainage can alleviate or cure paraplegia caused by spinal cord ischemia after TEVAR for acute aortic dissection.
3.Overview of systematic reviews of prevention and management of medication errors in adult patients
Zhide MAI ; Mo YI ; Ke LI ; Jianxia ZHANG ; Zhiwen WANG
Chinese Journal of Modern Nursing 2024;30(20):2716-2723
Objective:To overview the systematic reviews of prevention and management measures of medication errors, so as to provide evidence support for clinical decision-making for medical staff.Methods:Cochrane Library, Australia Joanna Briggs Institute Evidence-based Healthcare Center database, CINAHL, PubMed, Embase, CNKI, SinoMed, Wanfang database and VIP database were searched by computer to search for systematic reviews of prevention and management measures of medication errors, and the search period was from establishment of the databases to June 30, 2023. Two researchers with systematic evidence-based training applied A Measure Tool to Assess Systematic Reviews 2 (AMSTAR 2) to evaluate the literature quality, and Grades of Recommendations Assessment, Development and Evaluation (GRADE) was used to evaluate the quality of outcome indicators.Results:Finally, a total of 19 systematic reviews were included. The overall quality evaluation using AMSTAR 2 was relatively low, with one article rated as high-quality, one article rated as low-quality and 17 articles rated as extremely low-quality. According to the evidence quality evaluation results of GRADE system for 55 outcome indicators of 19 systematic reviews, 3 pieces of evidence were medium, 27 pieces of evidence were low and 25 pieces of evidence were extremely low, indicating an overall low quality of evidence.Conclusions:The related researches on prevention and management of medication errors have been carried out extensively, and the computer system is one of the effective measures to reduce medication errors. The effectiveness of measures such as administration process modification, doctor/nurse education and training, double check, pharmacist intervention, automated dispensing cabinet/ automated pump and drug display is still unclear and needs to be further confirmed by large sample size and high-quality studies.
4.Research progress of traditional Chinese and Western medicine non-pharmacological prevention strategies for acute high altitude disease
Li LI ; Peipei LU ; Zhiwen CAO ; Bo WEN ; Shanshan SHEN ; Zirong WANG ; Yong TAN ; Cheng LYU
Chinese Critical Care Medicine 2024;36(6):669-672
Acute high altitude disease (AHAD) is a general term for a series of clinical reactions that occur when the body fails to adapt to the low-pressure hypoxic environment of high altitudes. Mild cases can cause symptoms such as headache, nausea and vomiting, while more severe cases can lead to life-threatening conditions such as pulmonary edema, cerebral edema and other critical conditions that can be fatal. With the increasing demand for high altitudes deployment, understanding the common preventive measures of AHAD can reduce its morbidity or mortality to a certain extent, which is of great benefit to those who reside temporarily at high altitudes. In recent years, as people's health awareness has improved, there has been a growing attention towards non-pharmacological methods of disease prevention. At the same time, non-pharmacological therapy has significant therapeutic effects in preventing and treating high-altitude diseases, which has attracted the attention of researchers in this field. This review summarizes the major non-pharmacological preventive components of modern medicine and outlines the current non-pharmacological approaches to AHAD from the perspective of traditional Chinese medicine, intending to serve clinical purposes and improve the onset and prognosis of AHAD.
5.Intravascular Ultrasound Evaluated Efficacy of"L-Sandwich"Technique in the Percutaneous Coronary Intervention of True Bifurcation Lesions in Coronary Artery Disease:a Proof-of-concept Study
Muwei LI ; Ming NIE ; Quan GUO ; Zhiwen ZHANG ; Lixin RAO ; Liang PENG ; Cao MA
Chinese Circulation Journal 2024;39(6):547-553
Objectives:To investigate the intravascular ultrasound(IVUS)evaluated efficacy of the"L-sandwich"technique in the percutaneous coronary intervention treatment of true bifurcation lesions of coronary artery. Methods:Ninety-nine patients with true bifurcation lesions(medina type 1.1.1)of the coronary arteries were divided into the L-sandwich group(n=38),the double-stent group(n=32),and the main vessel(MV)single-stent with side branch(SB)drug-coated balloon(DCB)only group(n=29).The primary study endpoint was the loss of late lumen area(LLAL)in the MV,SB ostium and SB shaft at 12 months,and the secondary endpoints were minimum lumen area(MLA)at each site and major adverse cardiac events(MACE)at 12 months.As this is a proof-of-concept study,statistical analyses were performed in the as-treated(AT)analysis set. Results:At 12-month follow-up,there was no statistically significant difference in the MV LLAL among patients in the"L-sandwich"technique group,the double stent technique group,and the MV DES with SB DCB technique group([0.12±0.42]mm2 vs.[0.07±0.38]mm2 vs.[-0.01±0.31]mm2,P=0.419).Similarly,there was no statistically significant difference in the LLAL at the SB shaft([-0.11±0.45]mm2 vs.[-0.10±0.28]mm2 vs.[0.24±1.04]mm2,P=0.078],with the maximum LLAL observed in the double stent technique group and the minimum in the"L-sandwich"technique group([-0.48±0.78]mm2 vs.[0.45±0.64]mm2 vs.[0.14±1.37]mm2,P<0.001).The MV MLA was similar among the three groups([8.39±1.65]mm2 vs.[8.28±0.98]mm2 vs.[8.02±1.37]mm2,P=0.565),while the maximum MLA at the SB ostium was observed in the double stent technique group and the minimum in the MV DES with SB DCB group([5.08±0.74]mm2 vs.[5.63±0.80]mm2 vs.[3.57±1.35]mm2,P<0.001).In terms of MLA at the SB shaft,the"L-sandwich"technique group was similar to the double stent technique group,while the MV DES with SB DCB group exhibited the minimum MLA([5.94±0.72]mm2 vs.[5.86±0.59]mm2 vs.[3.74±1.07]mm2,P<0.001).Two patients in the double stent technique group underwent target vessel revascularization,there was no MACE in the other two groups(P=0.118). Conclusions:The"L-sandwich"technique is safe and feasible for the treatment of coronary bifurcation lesions.Compared with double-stent group,the SB ostium has a smaller LLAL at the time of review,and there is no significant difference in the MLA of each site,and the operation steps are significantly simplified.Use of the"L-sandwich"technique is associated with a better branching benefit compared with MV single-stent group.The"L-sandwich"technique could be used as a remedial procedure for severe entrapment in the setting of branching with DCB alone.
6.Small cell prostate carcinoma and high-grade invasive urothelial carcinoma of the bladder combined with small cell bladder carcinoma: a case report
Xungang LI ; Wensheng ZHANG ; Xinxi DENG ; Zhiwen LE ; Jia ZENG
Chinese Journal of Urology 2024;45(3):225-226
Small cell carcinoma of the prostate is a rare and highly malignant tumor of the urinary system. It is less common for prostate small cell carcinoma coexisting with bladder carcinoma. One such case was reported in this paper. The patient underwent ultrasound-guided transrectal prostate biopsy, and transurethral bladder endoscopy + bladder tumor electric resection. Postoperative pathology and immunohistochemistry showed prostate small cell carcinoma accompanied by high-grade invasive urothelial carcinoma of the bladder and small cell carcinoma. The patient underwent local bladder perfusion chemotherapy, relying on etoposide plus lobaplatin systemic chemotherapy and toripalimab immunotherapy. Prostate MRI, cystoscopy, and prostate-specific antigen (PSA) were performed 12 months after operation. The size of the lesions in the prostate and seminal vesicles had decreased, and there was a significant reduction in PSA levels. Additionally, no masses were detected in the bladder.
7.Quality evaluation of Siraitiae fructus standard decoction based on UPLC fingerprint and multi-index determination
Fangping ZHANG ; Cuijie WEI ; Xiaoxia LIU ; Wenkai XIE ; Yuanyuan CHEN ; Zhiwen DUAN ; Yongwei FENG ; Minyou HE ; Roushan CHEN ; Dongmei SUN ; Lin ZHOU ; Zhenyu LI
China Pharmacist 2024;28(11):397-405
Objective To establish an ultra-high performance liquid chromatography(UPLC)fingerprint and multi-index content determination method of Siraitiae fructus standard decoction.Methods 15 batches of Siraitiae fructus from different producing areas were collected,Siraitiae fructus standard decoction was prepared according to Technical Requirements for Quality Control and Standardization of Traditional Chinese Medicine Formula Granules,and the extract rate was calculated.UPLC was used to establish the fingerprint of 15 batches of Siraitiae fructus standard decoction and determine the contents of 11-O-mogroside V,kaempferitrin and mogroside V,which were the main effective components.The chemometrics analysis was used to evaluate the quality of Siraitiae fructus standard decoction and find possible quality markers.Results The extraction rate of 15 batches Siraitiae fructus standard decoction ranged from 24.79%to 34.95%.There were 16 common peaks in the fingerprint,and 4 components were identified.The Siraitiae fructus standard decoction was divided into 2 categories by chemometrics analysis,among which samples from Liuzhou,Guangxi were in one category and samples from Guilin,Guangxi were in another category.Seven differential markers were screened out under the condition of variable importance projection value,and the order was as follows:peak 8>peak 7>peak 5>peak 12(kaempferitrin)>peak 1>peak 13>peak 4.The contents of kaempferitrin,11-O-mogroside V and mogroside V in samples from Guilin,Guangxi were slightly higher than those in samples from Liuzhou,Guangxi.Conclusion The UPLC fingerprint and content determination method established in this study are feasible,which can provide a basis for the quality evaluation of Siraitiae fructus.The results of principal component analysis show that kaempferol is likely to become a quality marker of Siraitiae fructus.
8.Research progress on the mechanism of traditional Chinese medicine intervening in esophageal cancer by microRNA regulation
Zhiwen SHEN ; Liqun LI ; Mingyao XU ; Xin LIU ; Jing HUANG ; Xiaoning ZHANG ; Jiaqi YIN ; Sheng XIE
China Pharmacy 2024;35(8):1016-1022
Esophageal cancer (EC) is a common malignant tumor of the digestive system with an extremely poor prognosis. MicroRNA (miRNA) is an important regulator in tumor occurrence and development, and can participate in malignant biological behaviors such as tumor cell proliferation, invasion, metastasis and apoptosis. Traditional Chinese medicine has the characteristics of accurate curative effects, wide range of effects, and few side effects. The review uses miRNA as the entry point to systematically elaborate on the mechanism of traditional Chinese medicine-mediated miRNA intervening in EC. The results showed that active ingredients of traditional Chinese medicine (including curcumin, Tussilago farfara polysaccharides, Atractylodes macrocephala polysaccharides and ophiopogonin B) and Dougen guanshitong oral liquid could up-regulate the expressions of miRNAs such as miRNA-532-3p (miR-532-3p), miR-551b-3p, miR-99a, miR-34a, miR-199a-3p and miR-377; and the active ingredients/parts of traditional Chinese medicine (including chrysin and Actinidia arguta extract), and Chinese herbal formulas (including Chaihu shugan san combined with Xuanfu daizhe decoction and Modified jupi zhuru decoction) could down-regulate the expressions of miRNAs such as miR-199a-3p, miR-451 and miR-21, which could regulate the expressions of signaling pathways (phosphoinositide 3-kinase/protein kinase B, etc.) or their downstream protein(zinc-finger and homeobox protein 1, etc.) or enzymes(thymidine kinase-1, etc.), inhibit the proliferation, invasion and metastasis of EC cells and induce apoptosis, thereby ultimately achieving the purpose of preventing the disease from aggravating.
9.Study on quality evaluation of Buddleja officinalis from different habitats based on HPLC fingerprint and content determination
Cuijie WEI ; Xiaoxia LIU ; Zhiwen DUAN ; Yongwei FENG ; Xiaozhou JIA ; Yueyi LIANG ; Xiangdong CHEN ; Dongmei SUN ; Zhenyu LI
International Journal of Traditional Chinese Medicine 2024;46(2):215-221
Objective:To establish UPLC fingerprint method and 2 contents determination methods of Buddleja officinalis; To provide a reference for improving the quality control standard and evaluation of Buddleja officinalis from different habitats.Methods:UPLC method was used to establish the fingerprints of 17 batches of Buddleja officinalis. The similarity evaluation, clustering analysis, principal component analysis and orthogonal partial least squares discriminant analysis were used to compare the quality differences of Buddleja officinalis from different habitats. The contents of acteoside and linarin in Buddleja officinalis were determined.Results:There were 12 common peaks in UPLC fingerprints of Buddleja officinalis, six of which were identified as echinacoside, acteoside, cynaroside, isoacteoside, linarin, and apigenin. The fingerprint similarity of 17 batches of Buddleja officinalis was more than 0.9; Buddleja officinalis from different habitats were classified into 2 groups. Five differential markers were determined by OPLS-DA analysis. The order of significance was acteoside > peak 3 > echinacoside > isoacteoside > linarin. Edgeworthia chrysantha was identified by the method of fingerprint as counterfeit. The results of content determination showed that the content of Buddleja officinalis in Hubei and Sichuan was the high and stable.Conclusion:The method can effectively analyze the differences of Buddleja officinalis from different habitats, and provide reference for the quality control of Buddleja officinalis.
10.Phosphatidic acid-enabled MKL1 contributes to liver regeneration: Translational implication in liver failure.
Jiawen ZHOU ; Xinyue SUN ; Xuelian CHEN ; Huimin LIU ; Xiulian MIAO ; Yan GUO ; Zhiwen FAN ; Jie LI ; Yong XU ; Zilong LI
Acta Pharmaceutica Sinica B 2024;14(1):256-272
Liver regeneration following injury aids the restoration of liver mass and the recovery of liver function. In the present study we investigated the contribution of megakaryocytic leukemia 1 (MKL1), a transcriptional modulator, to liver regeneration. We report that both MKL1 expression and its nuclear translocation correlated with hepatocyte proliferation in cell and animal models of liver regeneration and in liver failure patients. Mice with MKL1 deletion exhibited defective regenerative response in the liver. Transcriptomic analysis revealed that MKL1 interacted with E2F1 to program pro-regenerative transcription. MAPKAPK2 mediated phosphorylation primed MKL1 for its interaction with E2F1. Of interest, phospholipase d2 promoted MKL1 nuclear accumulation and liver regeneration by catalyzing production of phosphatidic acid (PA). PA administration stimulated hepatocyte proliferation and enhanced survival in a MKL1-dependent manner in a pre-clinical model of liver failure. Finally, PA levels was detected to be positively correlated with expression of pro-regenerative genes and inversely correlated with liver injury in liver failure patients. In conclusion, our data reveal a novel mechanism whereby MKL1 contributes to liver regeneration. Screening for small-molecule compounds boosting MKL1 activity may be considered as a reasonable approach to treat acute liver failure.

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