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.The Cell Division Cycle 73(Cdc73)Deletion Mutant Inhibits Sexual Reproduction and Mitosis of Fission Yeast Cells
Meng-Nan LIU ; Xin BAI ; Wen YU ; Xin-Lin LI ; Xiang DING ; Yi-Ling HOU
Chinese Journal of Biochemistry and Molecular Biology 2024;40(6):807-818
		                        		
		                        			
		                        			The cdc73(cell division cycle 73)gene encodes the RNA polymerase Ⅱ cofactor Cdc73 in fis-sion yeast(Schizosaccharomyces Pombe),and is involved in G2 checkpoint activation and regulates the cell cycle.However,whether Cdc73 regulates cell mitotic dynamics is unknown.In this study,fluores-cent protein labeling and live cell imaging techniques were used to investigate the effects of cdc73 deletion on sexual reproduction and the dynamics of microtubules,actin,mitochondria,and histones during mito-sis.The results showed that in sexual reproduction,cdc73 deletion resulted in a 14.23%increase in the length of ascospores and a 64.08%decrease in the number of cells producing four spores.Analysis of the live cell imaging results revealed that,in mitosis,the elongation length of microtubules in anaphase was shortened by 11.21%,and the elongation time was reduced by 17.39%;the formation and contraction rates of actin rings decreased by 33.33%and 26.09%,respectively,and the formation and contraction times were prolonged by 58.00%and 40.38%,respectively.Meanwhile,the expression levels of actin ring,mitochondrion,and histones also increased.This study revealed the cdc73 deletion inhibits spindle elongation and delays actin ring formation and contraction in mitosis,which provides some scientific basis for further exploring the involvement of Cdc73 in regulating microtubule and actin dynamics in cell divi-sion.
		                        		
		                        		
		                        		
		                        	
3.Retrospective Study of The Outcome of Primary Repair of Arteriovenous Fistula (AVF) Aneurysm and Pseudoaneurysm in Secondary Hospital Setting (Kajian Retrospektif Pembaikian Primer Ateriovenous Fistula (AVF) Aneurisma dan Pseudoaneurisma di Hospital Sekunder)
Ong Xin Zen ; Ling Li Fan ; Philip Ding Hsin Loong ; Chong Kar Hon ; Goh Neng Xiang
Malaysian Journal of Health Sciences 2023;21(No.1):9-14
		                        		
		                        			
		                        			Aneurysms and pseudoaneurysm are commonly encountered with arteriovenous vascular access for haemodialysis. 
They are difficult complications to manage. Due to the limited number of vascular centers available, patients were 
unable to seek treatment until further complications arise. The technique of partial aneurysmectomy and primary repair 
was adopted as the method of repair in this study. A total of 20 cases underwent the surgery from 2019 to 2020. Among 
the 20 cases, one patient had two pseudoaneurysms at different location which requires her to undergo the procedure 
twice. The successful cannulation rate post repair was 70% whereas the overall complication rate was 35% which might 
be attributed to the small sample size. Overall, this study demonstrated that AVF aneurysm and pseudoaneurysm can be 
safely treated with this approach and can be done effectively in non-vascular centers by general surgeons.
		                        		
		                        		
		                        		
		                        	
4.Terpinen-4-ol inhibits proliferation of VSMCs exposed to high glucose via regulating KLF4/NF-κB signaling pathway.
Li HE ; Lin ZHANG ; Ju ZHANG ; Hong JIANG ; Yong-Xiang HE ; Dong-Guo LENG ; Ying-Xin GONG ; Ding YANG ; Yan SONG ; Chuan-Yin XIONG ; Yan-Yan ZHANG
China Journal of Chinese Materia Medica 2023;48(9):2530-2537
		                        		
		                        			
		                        			This study aimed to observe the effect of terpinen-4-ol(T4O) on the proliferation of vascular smooth muscle cells(VSMCs) exposed to high glucose(HG) and reveal the mechanism via the Krüppel-like factor 4(KLF4)/nuclear factor kappaB(NF-κB) signaling pathway. The VSMCs were first incubated with T4O for 2 h and then cultured with HG for 48 h to establish the model of inflammatory injury. The proliferation, cell cycle, and migration rate of VSMCs were examined by MTT method, flow cytometry, and wound healing assay, respectively. The content of inflammatory cytokines including interleukin(IL)-6 and tumor necrosis factor-alpha(TNF-α) in the supernatant of VSMCs was measured by enzyme-linked immunosorbent assay(ELISA). Western blot was employed to determine the protein levels of proliferating cell nuclear antigen(PCNA), Cyclin D1, KLF4, NF-κB p-p65/NF-κB p65, IL-1β, and IL-18. The KLF4 expression in VSMCs was silenced by the siRNA technology, and then the effects of T4O on the cell cycle and protein expression of the HG-induced VSMCs were observed. The results showed that different doses of T4O inhibited the HG-induced proliferation and migration of VSMCs, increased the percentage of cells in G_1 phase, and decreased the percentage of cells in S phase, and down-regulated the protein levels of PCNA and Cyclin D1. In addition, T4O reduced the HG-induced secretion and release of the inflammatory cytokines IL-6 and TNF-α and down-regulated the expression of KLF4, NF-κB p-p65/NF-κB p65, IL-1β, and IL-18. Compared with si-NC+HG, siKLF4+HG increased the percentage of cells in G_1 phase, decreased the percentage of cells in S phase, down-regulated the expression of PCNA, Cyclin D1, and KLF4, and inhibited the activation of NF-κB signaling pathway. Notably, the combination of silencing KLF4 with T4O treatment further promoted the changes in the above indicators. The results indicate that T4O may inhibit the HG-induced proliferation and migration of VSMCs by down-regulating the level of KLF4 and inhibiting the activation of NF-κB signaling pathway.
		                        		
		                        		
		                        		
		                        			NF-kappa B/metabolism*
		                        			;
		                        		
		                        			Interleukin-18/metabolism*
		                        			;
		                        		
		                        			Proliferating Cell Nuclear Antigen/genetics*
		                        			;
		                        		
		                        			Cyclin D1/metabolism*
		                        			;
		                        		
		                        			Tumor Necrosis Factor-alpha/metabolism*
		                        			;
		                        		
		                        			Muscle, Smooth, Vascular
		                        			;
		                        		
		                        			Cell Proliferation
		                        			;
		                        		
		                        			Signal Transduction
		                        			;
		                        		
		                        			Cytokines/metabolism*
		                        			;
		                        		
		                        			Glucose/metabolism*
		                        			
		                        		
		                        	
5.Comparison of the predictive value of Padua and the IMPEDE assessment scores for venous thromboembolism in patients with newly diagnosed multiple myeloma: A single institution experience.
Li Juan FANG ; Xiao Dong YAO ; Min Qiu LU ; Bin CHU ; Lei SHI ; Shao GAO ; Qiu Qing XIANG ; Yu Tong WANG ; Xi LIU ; Yue Hua DING ; Yuan CHEN ; Mengzhen WANG ; Xin ZHAO ; Weikai HU ; Kai SUN ; Li BAO
Chinese Journal of Hematology 2023;44(5):395-400
		                        		
		                        			
		                        			Objective: To compare the predictive efficacy of the two thrombosis risk assessment scores (Padua and IMPEDE scores) in venous thromboembolism (VTE) within 6 months in patients with newly diagnosed multiple myeloma (NDMM) in China. Methods: This study reviewed the clinical data of 421 patients with NDMM hospitalized in Beijing Jishuitan Hospital from April 2014 to February 2022. The sensitivity, specificity, accuracy, and Youden index of the two scores were calculated to quantify the thrombus risk assessment of VTE by the Padua and IMPEDE scores. The receiver operating characteristics curves of the two evaluation scores were drawn. Results: The incidence of VTE was 14.73%. The sensitivity, specificity, accuracy, and Youden index of the Padua score were 100%, 0%, 14.7%, and 0% and that of the IMPEDE score was 79%, 44%, 49.2%, and 23%, respectively. The areas under the curve of Padua and IMPEDE risk assessment scores were 0.591 and 0.722, respectively. Conclusion: IMPEDE score is suitable for predicting VTE within 6 months in patients with NDMM.
		                        		
		                        		
		                        		
		                        			Humans
		                        			;
		                        		
		                        			Venous Thromboembolism/etiology*
		                        			;
		                        		
		                        			Multiple Myeloma/diagnosis*
		                        			;
		                        		
		                        			Risk Assessment
		                        			;
		                        		
		                        			Risk Factors
		                        			;
		                        		
		                        			ROC Curve
		                        			;
		                        		
		                        			Retrospective Studies
		                        			
		                        		
		                        	
6.Association of hs-CRP with frailty and its components among the elderly over 65 years old in 9 longevity areas of China.
Jun Xin LIU ; Yuan WEI ; Jin Hui ZHOU ; Jun WANG ; Hao Can SONG ; Xin Wei LI ; Chang Zhen XIANG ; Yi Bo XU ; Cong DING ; Zhen Yu ZHONG ; Zheng ZHANG ; Yu Fei LUO ; Feng ZHAO ; Chen CHEN ; Jing Bo PI
Chinese Journal of Preventive Medicine 2023;57(5):626-633
		                        		
		                        			
		                        			Objective: To investigate the association of the levels of high sensitivity C-reactive protein (hs-CRP) with frailty and its components among the elderly over 65 years old in 9 longevity areas of China. Methods: Cross-sectional data from the Health Ageing and Biomarkers Cohort Study (HABCS, 2017-2018) were used and the elderly over 65 years old were included in this study. Through questionnaire interview and physical examination, the information including demographic characteristics, behavior, diet, daily activity, cognitive function, and health status was collected. The association between hs-CRP and frailty and its components in the participants was analyzed by multivariate logistic regression model and restrictive cubic spline. Results: A total of 2 453 participants were finally included, the age was (84.8±19.8) years old. The median hs-CRP level was 1.13 mg/L and the prevalence of frailty was 24.4%. Compared with the low-level group (hs-CRP<1.0 mg/L), the OR (95%CI) value of the high-level group (hs-CRP>3.0 mg/L) was 1.79 (1.35-2.36) mg/L. As for the components, the hs-CRP level was also positively associated with ADL disability, IADL disability, functional limitation and multimorbidity. After adjusting for confounding factors, compared with the low-level group, the OR (95%CI) values of the high-level group for the four components were 1.68 (1.25-2.27), 1.88 (1.42-2.50), 1.68 (1.31-2.14) and 1.39 (1.12-1.72), respectively. Conclusion: There is a positive association between the levels of hs-CRP and the risk of frailty among the elderly over 65 years old in 9 longevity areas of China. The higher hs-CRP level may increase the risk of frailty by elevating the risk of four physical functional disabilities, namely ADL disability, IADL disability, functional limitation and multimorbidity.
		                        		
		                        		
		                        		
		                        			Humans
		                        			;
		                        		
		                        			Aged
		                        			;
		                        		
		                        			Aged, 80 and over
		                        			;
		                        		
		                        			C-Reactive Protein/analysis*
		                        			;
		                        		
		                        			Frailty/epidemiology*
		                        			;
		                        		
		                        			Cohort Studies
		                        			;
		                        		
		                        			Cross-Sectional Studies
		                        			;
		                        		
		                        			China/epidemiology*
		                        			
		                        		
		                        	
7.Chemical constituents in Dolomiaea plants and their pharmacological activities: a review.
Yan-Hui LYU ; Wei CHEN ; Yan-Ping WEI ; Xin-Tong WEI ; Jie WANG ; Qian-Qian DING ; Zhan-Hong LI ; Ji-Xiang HE ; Xian-Peng ZU
China Journal of Chinese Materia Medica 2023;48(6):1463-1482
		                        		
		                        			
		                        			Dolomiaea plants are perennial herbs in the Asteraceae family with a long medicinal history. They are rich in chemical constituents, mainly including sesquiterpenes, phenylpropanoids, triterpenes, and steroids. The extracts and chemical constituents of Dolomiaea plants have various pharmacological effects, such as anti-inflammatory, antibacterial, antitumor, anti-gastric ulcer, hepatoprotective and choleretic effects. However, there are few reports on Dolomiaea plants. This study systematically reviewed the research progress on the chemical constituents and pharmacological effects of Dolomiaea plants to provide references for the further development and research of Dolomiaea plants.
		                        		
		                        		
		                        		
		                        			Plant Extracts/pharmacology*
		                        			;
		                        		
		                        			Asteraceae
		                        			;
		                        		
		                        			Triterpenes
		                        			;
		                        		
		                        			Sesquiterpenes/pharmacology*
		                        			;
		                        		
		                        			Anti-Inflammatory Agents
		                        			;
		                        		
		                        			Phytochemicals/pharmacology*
		                        			
		                        		
		                        	
8.Comparison of early clinical outcomes between SuperCap and direct anterior approaches for total hip arthroplasty.
Wen-Ju CHANG ; Hai DING ; Fen-Dou LIU ; Xiang LI ; Xin-She ZHOU ; Li-Jia PEI ; Yang LIU ; Zhi-Yan WANG
China Journal of Orthopaedics and Traumatology 2023;36(11):1030-1035
		                        		
		                        			OBJECTIVE:
		                        			To compare the short-term clinical efficacy of SuperCap approach and direct anterior approach in total hip arthroplasty.
		                        		
		                        			METHODS:
		                        			Clinical data of 70 patients who underwent minimally invasive SuperCap approach and DAA THA in January 2016 to June 2017 were retrospective analyzed. These patients were divided into two groups:SuperCap approach group(SuperCap group) and direct anterior approach group(DAA group). There were 15 males and 15 females in SuperCap group, aged from 45 to 71 years old, and the follow-up time ranged from 24 to 30 months. There were 24 males and 16 females in Group B, aged from 51 to 76 years and the follow-up time ranged from 24 to 36 months. Hemoglobin level of the 3rd day after operation, transfusion rate, acetabular abduction angle, anteversion angle and creatine kinase level of the 3rd day after operation, Harris score of 3 months and the last time, VAS score of 1 week and the last time were recorded and compared. Complications were recorded at the final follow-up.
		                        		
		                        			RESULTS:
		                        			All patients were followed up, the follow-up time of SuperCap group ranged from 24 to 30 months, that of DAA group ranged from 24 to 36 months. No significant differences were found in hemoglobin level on the 3rd day after operation, transfusion rate, Harris score or VAS score between two group (P>0.05). There was no significant difference in Harris score between 3 months after operation and the final follow-up in both groups (P>0.05). There were no significant difference in VAS scores of 6 weeks after operation and on the final follow-up neither(P>0.05). The level of creatine kinase in SuperCap group was significant lower than that in DAA group(P<0.05). Until the final follow-up, there was no significant difference in the incidence of complications between the two groups(P>0.05).
		                        		
		                        			CONCLUSION
		                        			The clinical effect of minimally invasive SuperCap approach after total hip arthroplasty is comparable to that of DAA approach with less soft tissue injury. Patients can recover rapidly after operation and it is a safe and effective surgical approach for surgeons with short learning curve.
		                        		
		                        		
		                        		
		                        			Male
		                        			;
		                        		
		                        			Female
		                        			;
		                        		
		                        			Humans
		                        			;
		                        		
		                        			Middle Aged
		                        			;
		                        		
		                        			Aged
		                        			;
		                        		
		                        			Arthroplasty, Replacement, Hip
		                        			;
		                        		
		                        			Retrospective Studies
		                        			;
		                        		
		                        			Antiviral Agents
		                        			;
		                        		
		                        			Treatment Outcome
		                        			;
		                        		
		                        			Creatine Kinase
		                        			;
		                        		
		                        			Hemoglobins
		                        			
		                        		
		                        	
9.Clinical characteristics and prognosis of patients with therapy-related myelodysplastic syndrome and acute myeloid leukemia arising from malignant tumors.
Xu Sheng XU ; Hong DING ; Xin ZHANG ; Yi LIAO ; He LI ; Qin Yu LIU ; Jia Zhuo LIU ; Li ZHANG ; Jie HUANG ; Yu Ping GONG ; Hong Bing MA ; Bing XIANG ; Yang DAI ; Li HOU ; Xiao SHUAI ; Ting NIU ; Yu WU
Chinese Journal of Hematology 2023;44(9):742-748
		                        		
		                        			
		                        			Objective: To investigate the clinical characteristics, cytogenetics, molecular biology, treatment, and prognosis of patients with therapy-related myelodysplastic syndrome and acute myeloid leukemia (t-MDS/AML) secondary to malignancies. Methods: The clinical data of 86 patients with t-MDS/AML in West China Hospital of Sichuan University between January 2010 and April 2023 were retrospectively analyzed. The clinical characteristics, primary tumor types, and tumor-related therapies were analyzed. Results: The study enrolled a total of 86 patients with t-MDS/AML, including 67 patients with t-AML, including 1 patient with M(0), 6 with M(1), 27 with M(2), 9 with M(3), 12 with M(4), 10 with M(5), 1 with M(6), and 1 with M(7). Sixty-two patients could be genetically stratified, with a median overall survival (OS) of 36 (95% CI 22-52) months for 20 (29.9%) patients in the low-risk group and 6 (95% CI 3-9) months for 10 (14.9%) in the intermediate-risk group. The median OS time was 8 (95% CI 1-15) months in 32 (47.8%) patients in the high-risk group. For patients with non-acute promyelocytic leukemia (APL) and AML, the median OS of the low-risk group was 27 (95% CI 18-36) months, which was significantly longer than that of the non-low-risk group (χ(2)=5.534, P=0.019). All 9 APL cases were treated according to the initial treatment, and the median OS was not reached, and the 1-, 2-, and 3-year OS rates were 100.0%, (75.0±6.2) %, and (75.0±6.2) % respectively. Of the 58 patients with non-APL t-AML (89.7%), 52 received chemotherapy, and 16 achieved complete remission (30.8%) after the first induction chemotherapy. The 1-, 2-, and 3-year OS rates of the non-APL t-AML group were (42.0 ± 6.6) %, (22.9±5.7) %, and (13.4±4.7) %, respectively. The median OS of patients who achieved remission was 24 (95% CI 18-30) months, and the median OS of those who did not achieve remission was 6 (95% CI 3-9) months (χ(2)=10.170, P=0.001). Bone marrow CR was achieved in 7 (53.8%) of 13 patients treated with vineclar-containing chemotherapy, with a median OS of 12 (95% CI 9-15) months, which was not significantly different from that of vineclar-containing chemotherapy (χ(2)=0.600, P=0.437). In 19 patients with t-MDS, the 1-, 2-, and 3-year OS rates were (46.8±11.6) %, (17.5±9.1) %, and (11.7±9.1) % with a median OS of 12 (95% CI 7-17) months, which was not significantly different from that in t-AML (χ(2)=0.232, P=0.630) . Conclusions: Breast cancer, bowel cancer, and other primary tumors are common in patients with t-MDS/AML, which have a higher risk of adverse genetics. Patients with APL had a high induction remission rate and a good long-term prognosis, whereas patients without APL had a low remission rate and a poor long-term prognosis.
		                        		
		                        		
		                        		
		                        			Humans
		                        			;
		                        		
		                        			Retrospective Studies
		                        			;
		                        		
		                        			Leukemia, Myeloid, Acute/drug therapy*
		                        			;
		                        		
		                        			Leukemia, Promyelocytic, Acute/therapy*
		                        			;
		                        		
		                        			Prognosis
		                        			;
		                        		
		                        			Myelodysplastic Syndromes/drug therapy*
		                        			;
		                        		
		                        			Neoplasms, Second Primary/drug therapy*
		                        			;
		                        		
		                        			Remission Induction
		                        			;
		                        		
		                        			Antineoplastic Combined Chemotherapy Protocols/therapeutic use*
		                        			
		                        		
		                        	
10.Effects of moxibustion at Yongquan (KI 1) on cognition function and lower limb motor function in patients with post-stroke cognitive impairment of kidney essence deficiency.
Yan-Sheng YE ; Qing-Tang YANG ; Ding-Yu ZHU ; Kai-Xiang DENG ; Hui-Juan LIN ; Xin ZHANG ; Ting JI ; Meng-Zhen ZHUO ; Yu-Mao ZHANG
Chinese Acupuncture & Moxibustion 2023;43(9):1018-1022
		                        		
		                        			OBJECTIVE:
		                        			To observe the effects of moxibustion at Yongquan(KI 1) on the cognitive function and lower limb motor function in patients with post-stroke cognitive impairment of kidney essence deficiency.
		                        		
		                        			METHODS:
		                        			Eighty-four patients with post-stroke cognitive impairment of kidney essence deficiency were randomly divided into an observation group(42 cases,1 case dropped off)and a control group(42 cases,1 case dropped off).The control group was treated with medication,electroacupuncture,rehabilitation training and repetitive transcranial magnetic stimulation(rTMS);on the basis of the treatment as the control group,moxibustion at bilateral Yongquan(KI 1)was adopted in the observation group.Both groups were treated once a day,5 days a week with 2-day interval,4 weeks were required. The Montreal cognitive assessment (MoCA) score, mini-mental state examination (MMSE) score, Fugl-Meyer assessment-lower extremity (FMA-LE) score, Berg balance scale (BBS) score, functional independence measure (FIM) score, modified fall efficacy scale (MFES) score and scale for the differentiation of syndromes of vascular dementia (SDSVD) score before and after treatment were observed in the two groups.
		                        		
		                        			RESULTS:
		                        			After treatment,the MoCA, MMSE, FMA-LE, BBS, FIM and MFES scores were higher than those before treatment in both groups (P<0.05), and the scores in the observation group were higher than those in the control group (P<0.05). After treatment,the SDSVD scores were lower than those before treatment in both groups (P< 0.05), and the SDSVD score in the observation group was lower than that in the control group (P< 0.05).
		                        		
		                        			CONCLUSION
		                        			Moxibustion at Yongquan(KI 1) can improve the cognitive function and motor and balance function of lower limbs in patients with post-stroke cognitive impairment of kidney essence deficiency,reduce the risk of fall and improve the quality of life.
		                        		
		                        		
		                        		
		                        			Humans
		                        			;
		                        		
		                        			Cognition
		                        			;
		                        		
		                        			Cognitive Dysfunction/therapy*
		                        			;
		                        		
		                        			Dementia, Vascular
		                        			;
		                        		
		                        			Kidney
		                        			;
		                        		
		                        			Lower Extremity
		                        			;
		                        		
		                        			Moxibustion
		                        			;
		                        		
		                        			Quality of Life
		                        			;
		                        		
		                        			Stroke/complications*
		                        			
		                        		
		                        	
            

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