1.The lysine methyltransferase SMYD2 facilitates neointimal hyperplasia by regulating the HDAC3-SRF axis.
Xiaoxuan ZHONG ; Xiang WEI ; Yan XU ; Xuehai ZHU ; Bo HUO ; Xian GUO ; Gaoke FENG ; Zihao ZHANG ; Xin FENG ; Zemin FANG ; Yuxuan LUO ; Xin YI ; Ding-Sheng JIANG
Acta Pharmaceutica Sinica B 2024;14(2):712-728
Coronary restenosis is an important cause of poor long-term prognosis in patients with coronary heart disease. Here, we show that lysine methyltransferase SMYD2 expression in the nucleus is significantly elevated in serum- and PDGF-BB-induced vascular smooth muscle cells (VSMCs), and in tissues of carotid artery injury-induced neointimal hyperplasia. Smyd2 overexpression in VSMCs (Smyd2-vTg) facilitates, but treatment with its specific inhibitor LLY-507 or SMYD2 knockdown significantly inhibits VSMC phenotypic switching and carotid artery injury-induced neointima formation in mice. Transcriptome sequencing revealed that SMYD2 knockdown represses the expression of serum response factor (SRF) target genes and that SRF overexpression largely reverses the inhibitory effect of SMYD2 knockdown on VSMC proliferation. HDAC3 directly interacts with and deacetylates SRF, which enhances SRF transcriptional activity in VSMCs. Moreover, SMYD2 promotes HDAC3 expression via tri-methylation of H3K36 at its promoter. RGFP966, a specific inhibitor of HDAC3, not only counteracts the pro-proliferation effect of SMYD2 overexpression on VSMCs, but also inhibits carotid artery injury-induced neointima formation in mice. HDAC3 partially abolishes the inhibitory effect of SMYD2 knockdown on VSMC proliferation in a deacetylase activity-dependent manner. Our results reveal that the SMYD2-HDAC3-SRF axis constitutes a novel and critical epigenetic mechanism that regulates VSMC phenotypic switching and neointimal hyperplasia.
2.Finite element analysis of reamed versus undreamed proximal femoral nail antirotation-Ⅱ in treatment of 31-A3 intertrochanteric femur fracture
Zemin LIU ; Dong WANG ; Yan LI ; Min LIU ; Bin CHEN ; Caoqi WANG ; Xin LYU ; Yonghong ZHANG
Chinese Journal of Tissue Engineering Research 2024;28(30):4770-4776
BACKGROUND:There is controversy regarding the need for marrow reaming in intertrochanteric fractures of the femur.Some believe that unreaming shortens operative time,reduces bleeding,and decreases intraoperative risk in elderly patients,but there is no basis for whether this move reduces the effectiveness of intramedullary nail support.Others believe that reaming allows for the selection of thicker diameter intramedullary nails for better mechanical support,but basic studies have shown that this approach carries risks such as fat embolism and destruction of bone(especially in elderly patients with osteoporosis). OBJECTIVE:To analyze the mechanical distribution characteristics of reamed and unreamed proximal femoral nail antirotation-Ⅱ in the treatment of type 31-A3 intertrochanteric fractures by finite element analysis. METHODS:A healthy volunteer was included,and CT scans of his femur were obtained in DICOM format,and the files were sequentially imported into Mimics,Geomagic Wrap,SolidWorks,Hypermesh,and Ansys software for processing.The A3.1,A3.2,and A3.3 intertrochanteric fracture models were obtained and assembled with 9 mm,11 mm diameter,and 170 mm length intramedullary nails,respectively,followed by assigning material properties,setting the interaction relationship of each contact surface and defining the load and boundary conditions,and then solved.The femoral stress distribution,internal fixation stress distribution,femoral displacement,and internal fixation displacement were observed in different models. RESULTS AND CONCLUSION:(1)The femoral stress was less than that of unreamed intramedullary nail fixation for each type of fracture,and the maximum stress value of the femur for A3.3 fracture was greater than that of A3.1 and A3.2.(2)The internal fixation stress was greater than that of unreamed intramedullary nail fixation for each type of fracture,and the maximum stress value of internal fixation for A3.3 fracture was greater than that of A3.1.(3)Reamed versus unreamed intramedullary nailing has less effect on femoral and internal fixation displacement and more effect on stress.(4)It is indicated that the use of reamed intramedullary nail fixation results in a reduction in femoral stress,an increase in the stress borne by the internal fixation as a whole,and a reduction in the stress borne by the distal locking nail.The use of reamed intramedullary nail fixation may provide better treatment results compared to unreamed intramedullary nail fixation.
3.Advancements in research on the regulation of bone metabolism by adipose browning
Zemin LIU ; Dong WANG ; Xin LYU ; Yonghong ZHANG
Chinese Journal of Orthopaedics 2024;44(3):186-192
Bone metabolism includes the processes of bone formation and bone resorption, both of which maintain bone metabolic homeostasis in the body. Adipose browning is a biological process that converts energy-storing white fat into thermogenic brown fat, which is induced by environment, exercise, nutrients, and signaling molecules. Adipose browning regulates bone metabolism in vivo and affects osteogenic and osteoblastic capacity through the secretion of adipokines such as fibroblast growth factor-21, adiponectin, insulin-like growth factor-1, and bone morphogenetic proteins. Adipose browning can also affect bone metabolism through immune pathways mediated by the gut microbiota. The browning ability of fat decreases in the aging body, which is related to the imbalance of bone metabolism in the state of osteoporosis. In children and adolescents, fat browning is active and bone metabolism is maintained in a healthy state. Exercise and supplementation of nutrients (capsaicin, resveratrol, quercetin, etc.) can promote the browning of adipose tissue and maintain brown adipose tissue, which plays a positive role in bone metabolism. In the future, it is of great significance to clarify the specific regulatory mode between adipose browning and bone metabolism for the treatment of bone metabolism-related diseases by intervening adipose browning.
4.The effect of patient's body shape and image acquisition mode on the radiation dose and image quality in percutaneous coronary angiography
Hai QIAN ; Yuqin ZHANG ; Yan XU ; Dexing HU ; Zemin CEN ; Kenan LOU
Journal of Interventional Radiology 2024;33(6):599-603
Objective To investigate the effect of patient's body shape and image acquisition mode on the radiation dose and image quality in percutaneous coronary angiography.Methods A total of 40 patients,who received selective percutaneous coronary angiography at the Ningbo Medical Center Lihuili Hospital of China between January 2022 and June 2023,were selected for this study.The patients were randomly divided into conventional group(including 11 males and 9 females,using coronary angiography mode to make image acquisition)and low-dose group(including 14 males and 6 females,using electrophysiological mode to make image acquisition).The patient's basic information,body size data,and the various radiation dose data were collected.The image quality rating scale for assessing the image quality was formulated.The independent sample t-test and Mann-Whitney U test were used for the comparison between the two groups.Pearson correlation analysis method was used to make correlation analysis.Results The larger the patient's chest circumference was,the higher the radiation dose would be,there was a positive linear relationship between the patient's chest circumference and the radiation dose.All the radiation dose parameters in the low-dose group were significantly lower than those in the conventional group(P<0.01),and its reduction percentage was 48.51%-60.74%.No statistically significant difference in image quality score existed between the two groups(P>0.0l),and in both groups the image quality was rated as good or better,meeting the requirements of intervention procedures.Conclusion In percutaneous coronary angiography the radiation dose is influenced by multiple factors including patient's body shape,image acquisition mode,exposure time,etc.Optimizing the image acquisition mode can remarkably reduce the radiation dose while maintaining the image quality and protecting the health of patients and operators.(J Intervent Radiol,2024,33:599-603)
5.Summary of the best evidence for pelvic floor muscle training in the prevention and treatment of postpartum urinary incontinence
Jiayu ZHANG ; Xin YAN ; Haoran DUAN ; Yao FENG ; Zekun YAO ; Zemin ZHANG ; Xue BAI
Chinese Journal of Modern Nursing 2024;30(12):1604-1611
Objective:To summarize the evidence of pelvic floor muscle training for the prevention and treatment of postpartum urinary incontinence, providing guidance and reference for clinical practice.Methods:According to the "6S" pyramid model, clinical decision-making, guidelines, and systematic reviews on pelvic floor muscle training for the prevention and treatment of postpartum urinary incontinence were searched in UpToDate, British Medical Journal (BMJ) Best Practice, National Institute for Health and Care Excellence, Scottish Intercollegiate Guideline Network, New Zealand Guideline Group, Guidelines International Network, Medlive, Joanna Briggs Institute (JBI) Evidence-Based Health Care Center Database, Cochrane Library, professional association website, Embase, PubMed, Web of Science, China National Knowledge Infrastructure, China Biology Medicine disc, WanFang Data, and VIP. The search period was from March 2013 to March 2023. Two trained researchers evaluated the quality of literature and integrated and extracted evidence.Results:A total of 22 articles were included, including 8 clinical decision-making, 6 guidelines, 7 systematic reviews, and 1 expert consensus. Twenty-one best pieces of evidence were summarized from 5 aspects, consisting of risk factors, prevention, evaluation, treatment and health guidance for postpartum urinary incontinence.Conclusions:The best evidence for the prevention and treatment of postpartum urinary incontinence through pelvic floor muscle training summarized is convenient for medical and nursing staff to conduct scientific urinary incontinence assessment, pelvic floor muscle training education and guidance for pregnant and postpartum women.
6.Effects of long non-coding RNA H19 regulating miRNA-675 and PTEN on the cell proliferation of glioma
Ping LIU ; Ningning ZHANG ; Ying ZHANG ; Ranxin HUANG ; Yuexiang ZHANG ; Lulu LI ; Zemin QIN ; Xiuling WANG ; Sulan WANG ; Jianlan CHANG ; Junyan YU
Cancer Research and Clinic 2024;36(11):863-868
Objective:To investigate the effect of long non-coding RNA (lncRNA) H19 regulating miRNA-675 (miR-675) and phosphatase and tensin homologue-deleted chromosome ten gene (PTEN) on the cell proliferation of glioma.Methods:Glioma cell lines U87-MG and U251 were chosen. The siRNA online design tool wad used to design small interfering RNA (siRNA) targeting H19. U87-MG and U251 cell lines with the stable knockdown of H19 were constructed (the stable knockdown of H19 group), and the cells randomly transfected with siRNA plasmid were taken as the control group, and normal cultured cells were treated as the blank group. Additionally, miR-675 and control microRNA were transfected into U87-MG and U251 with the stable knockdown of H19 (the overexpressing miR-675 group and the corresponding control group). Quantitative real-time polymerase chain reaction (qRT-PCR) was used to detect the relative expression levels of miR-675 and H19 in each group; the methyl thiazolyl tetrazolium (MTT) assay was used to detect the cell proliferation ability; the dual luciferase reporter gene assay was used to verify the targeting relationship between miR-675 and PTEN; Western blot was used to detect the relative expression level of PTEN protein.Results:The MTT assay results showed that the proliferation ability of U87-MG and U251 cells in the stable knockdown of H19 group was lower than that of the corresponding control group; and the differences in cell proliferation ability of all the groups after 48 h of culture were statistically significant (all P < 0.05). qRT-PCR detection results showed that the relative expression level of miR-675 in U251 cells in the stable knockdown of H19 group and the corresponding control group was 0.329±0.009 and 1.043±0.087, respectively, and the difference was statistically significant ( t = 14.15, P < 0.001); the relative expression level of miR-675 in U87-MG cells in the stable knockdown of H19 group and the corresponding control group was 0.299±0.009 and 1.027±0.106, respectively, and the difference was statistically significant ( t = 11.85, P < 0.001); the relative expression level of miR-675 in U87-MG and U251 cells in the stable knockdown of H19 group was lower than that of the corresponding control group. The dual luciferase reporter gene assay verified that miR-675 could bind to the 3'-UTR of PTEN. Western blot detection results showed that the relative expression level of PTEN protein in U87-MG and U251 cells in the stable knockdown of H19 group was higher than that of the corresponding control group and the blank group; in the U87-MG and U251 cells in the stable knockdown of H19 group, the relative expression level of PTEN in the overexpressing miR-675 group was lower than that of the corresponding blank group and the control group. In the U87-MG and U251 cells in the stable knockdown of H19 group, the cell proliferation ability of the overexpressing miR-675 group was higher than that of the corresponding blank group and the control group; the differences in cell proliferation ability of all the groups after 48 h of culture were statistically significant (all P < 0.05). Conclusions:lncRNA H19 may regulate the cell proliferation of glioma cells through the miR-675-PTEN signaling pathway.
7.Effect of Microemulsion on Content of Index Components in Different Phases of Zexietang Extract
Yanjing WANG ; Zemin OU ; Lin YAN ; Yao ZHANG ; Zicheng WANG ; Yi CHENG ; Yan TONG ; Dewen LIU ; Jinyu WANG
Chinese Journal of Experimental Traditional Medical Formulae 2023;29(20):134-140
ObjectiveTo investigate the effect of microemulsion on the distribution of index components in different phases of Zexietang extract based on high performance liquid chromatography(HPLC) and phase separation process. MethodParticle size meter and transmission electron microscope were used to characterize the colloidal particles in blank microemulsion, aqueous extract of Zexietang and microemulsion extract of Zexietang. The phase separation process was established by high-speed centrifugation and dialysis, and based on this process, the aqueous extract and microemulsion extract of Zexietang were separated into the true solution phase, the colloidal phase and the precipitation phase, respectively. The contents of six components, including atractylenolide Ⅲ, atractylenolide Ⅱ, 23-acetyl alisol C, alisol A, alisol B and alisol B 23-acetate, were determined by HPLC with the mobile phase of water(A)-acetonitrile(B) for gradient elution(0-5 min, 40%-43%B; 5-20 min, 43%-45%B; 20-45 min. 45%-60%B; 45-75 min, 60%-80%B). The solubility of the index components in water and microemulsion was determined by saturation solubility method. ResultThe colloidal particles in the aqueous extract, microemulsion extract and blank microemulsion were all spherical, and the particle size, polydispersity index(PDI) and Zeta potential of the colloidal particles were in the order of aqueous extract >microemulsion extract >blank microemulsion. The results of phase separation showed that the colloidal phase and the true solution phase could be completely separated by dialysis for 2.5 h, and the phase separation process was tested to be stable and feasible. Compared with the aqueous extract of Zexietang, the use of microemulsion as an extraction solvent could increase the contents of atractylenolide Ⅲ, 23-acetyl alisol C, atractylenolide Ⅱ , alisol A, alisol B and alisol B 23-acetate by 3.75, 6.82, 35.47, 10.66, 35.41, 27.75-fold, and could increase the extraction efficiencies of the latter five constituents by 2.03, 1.15, 1.70, 6.43, 5.53 times. The solubility test showed that the microemulsion could significantly improve the solubility of atractylenolide Ⅱ, alisol A, alisol B and alisol B 23-acetate, but it had less effect on the solubility of atractylenolide Ⅲ and 23-acetyl alisol C. ConclusionMicroemulsion can improve the extraction efficiency and increase the distribution of the index components in the colloidal phase state of Zexietang to different degrees, providing a reference for the feasibility of microemulsion as an extraction solvent for traditional Chinese medicine.
8.Comparative Analysis of Serum Pharmacochemistry of Alismatis Rhizoma Before and After Salt Processing Based on UPLC-Q-TOF-MS
Lin YAN ; Zemin OU ; Yanjing WANG ; Yao ZHANG ; Yi CHENG ; Zicheng WANG ; Dewen LIU ; Jinyu WANG ; Zhenshan MA ; Yan TONG
Chinese Journal of Experimental Traditional Medical Formulae 2023;29(23):122-130
ObjectiveBased on serum pharmacochemistry and ultra performance liquid chromatography-quadrupole-time-of-flight mass spectrometry(UPLC-Q-TOF-MS) the transitional components in the serum of rats after intragastric administration of water extract of Alismatis Rhizoma(AR)and salt-processed Alismatis Rhizoma(SAR) were compared. MethodSD rats were randomly divided into blank group, AR group(10 g·kg-1) and SAR group(10 g·kg-1), 3 rats in each group, the administration groups were given AR and SAR aqueous extracts by gavage, respectively, and the blank group was given an equal volume of drinking water by gavage once in the morning and once in the evening, for 3 consecutive days. Sixty minutes after the last administration, blood was collected from the eye orbits, and the serum samples were prepared. The serum samples were prepared on an ACQUITY UPLC BEH C18 column(2.1 mm×50 mm, 1.7 μm) with the mobile phase of acetonitrile(A)-0.1% formic acid aqueous solution(B) in a gradient elution(0-10 min, 10%-50% A; 10-27 min, 50%-95%A; 27-27.1 min, 95%-10% A; 27.1-30 min, 10%A), the data were collected at a flow rate of 0.3 mL·min-1 in positive ion mode with a scanning range of m/z 100-1 200. Based on the self-constructed chemical composition library of AR, the total ion flow diagrams and secondary MS fragmentation information of the aqueous extracts of AR and SAR, as well as the administered serum and the blank serum, were compared with each other by UNIFI 1.9.2, so as to deduce the possible blood-migrating constituents and their cleavage patterns in the aqueous extracts, and the response intensity ratios of each chemical component were calculated before and after processing. ResultA total of 20 components, including 5 prototypical components and 15 metabolites, were analyzed and deduced from the serum of rats given aqueous extract of AR. And 14 components, including 5 prototypical components and 9 metabolites, were analyzed and deduced from the serum of rats given aqueous extract of SAR. Of these, 13 components were common to both of them, including 5 prototypical components and 8 metabolites. The 5 prototypical components were 16-oxoalisol A, alisol A 24-acetate, alisol A, alisol B and alisol C. The metabolites were mainly involved in phase Ⅰ metabolism(oxidation) and phase Ⅱ metabolism(glucuronidation). There was a big change in the intensity of response of the common components before and after salt-processing, and the response intensities of the prototypical components, 16-oxoalisol A, alisol B and alisol C, were elevated, while the type and response intensity of metabolites were generally decreased, and it was hypothesized that the metabolic rate of terpenoids might be slowed down after salt-processing of AR, so that the blood-migrating constituents could participate in the metabolism of the body more in the form of prototypes. ConclusionSalt-processing of AR may promote the absorption of prototypical components into the blood by slowing down the metabolic rate of terpenoids, which can provide support for the research on material basis of AR and SAR.
9.Identification of lipid droplets in gut bacteria.
Kai ZHANG ; Chang ZHOU ; Zemin LI ; Xuehan LI ; Ziyun ZHOU ; Linjia CHENG ; Ahmed Hammad MIRZA ; Yumeng SHI ; Bingbing CHEN ; Mengwei ZHANG ; Liujuan CUI ; Congyan ZHANG ; Taotao WEI ; Xuelin ZHANG ; Shuyan ZHANG ; Pingsheng LIU
Protein & Cell 2023;14(2):143-148
10.Exploring the mechanism of moxibustion in myocardial protection of rats with long-term fatigue exercise based on the classical pyroptosis pathway
Shiling LÜ ; Ruida LI ; Zemin ZHANG ; Xin WANG ; Yulei LIANG ; Wenli LI ; Dongyun SUN
Journal of Acupuncture and Tuina Science 2023;21(2):121-128
Objective: To explore the possible mechanism of moxibustion in myocardial protection of rats undergoing long-term fatigue exercise based on observing the classical pyroptosis pathway mediated by nuclear factor kappa-B (NF-κB)/nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3)/cysteinyl aspartate specific proteinase 1 (Caspase-1).Methods: A total of 50 specific-pathogen-free male Sprague-Dawley rats were bought. Ten unqualified rats were excluded, and the remaining 40 rats were divided into a normal group, a normal + Shenque (CV8) group, a model group, a model + non-meridian non-point group, and a model + Shenque (CV8) group according to the random number table method, with 8 rats in each group. Except for rats in the normal group and the normal + Shenque (CV8) group, rats in the other three groups were trained with an incline running table exercise protocol to create a long-term fatigue exercise model, 1 h/time, once a day for 5 d with 2 d off, for a total of 8 weeks. Rats in the normal group received no modeling or intervention. Rats in the normal + Shenque (CV8) group were not modeled but received mild moxibustion at Shenque (CV8); those in the model group were modeled only without intervention; those in the model + non-meridian non-point group received moxibustion at non-meridian and non-point spots after the modeling; those in the model + Shenque (CV8) group received moxibustion at Shenque (CV8) after modeling. The above moxibustion interventions were performed for 15 min/time once daily, for 5 d with 2 d off per week and a total of 8 weeks. Blood was collected from the femoral artery 4 h after the last exercise, and the serum interleukin (IL)-1β and IL-18 levels were measured. The NF-κB, NLRP3, apoptosis-associated speck-like protein containing a CARD (ASC), Caspase-1, and gasdermin D (GSDMD) expression levels were detected by Western blotting. Myocardial morphology and pyroptosis were observed by hematoxylin-eosin (HE) staining and electron microscopy. Results: The HE staining results showed that the myocardial cells in the model group and the model + non-meridian non-point group were disorganized with blurred transverse lines, widened interstitial spaces, interstitial edema, and inflammatory cell infiltration. The structure of myocardial cells in the model + Shenque (CV8) group was clearly visible, with slightly widened interstitial spaces and occasional infiltration of inflammatory cells in the interstitium. Compared with the normal group, the serum IL-1β and IL-18 levels were increased, and myocardial NF-κB, NLRP3, ASC, Caspase-1, and GSDMD expression levels were elevated in the model group and the model + non-meridian non-point group (P<0.01). Compared with the model group, the above indicators did not change significantly in the model + non-meridian non-point group, while all the above indicators were decreased in the model + Shenque (CV8) group (P<0.01). Compared with the model + non-meridian non-point group, all the above biochemical indicators were decreased in the model + Shenque (CV8) group (P<0.01). Transmission electron microscopy showed that the mitochondria number was increased in the model group and the model + non-meridian non-point group, some of the mitochondrial lumen was irregularly enlarged, the cell membrane structure was unclear, and chromatin was aggregated. The mitochondria number was increased, the swelling was reduced, and the nuclear membrane structure was more intact in the model + Shenque (CV8) group. Conclusion: Moxibustion at Shenque (CV8) regulates the NF-κB/NLRP3/Caspase-1 pathway and reduces the pyroptosisin the myocardium of rats with long-term fatigue exercise, thus reducing the myocardial injury caused by long-term fatigue exercise.

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