1.Role of exosomal miR-320c in gingerol-mediated defense against Staphylococcus aureus infection
Zhencai XING ; Mengxue XU ; Xiang KONG ; Jinghan SUN ; Zhen MA ; Yu GAO ; Siyuan DU ; Hong ZHENG ; Yakun LIU
Acta Universitatis Medicinalis Anhui 2026;61(5):795-802
ObjectiveTo investigate the inhibitory effect of gingerol, an active component of ginger, on Staphylococcus aureus (S. aureus) infection, and to preliminarily explore its mechanism related to extracellular vesicles (EVs). MethodsS.aureus infection models were established in human umbilical vein endothelial cell (HUVECs), Vero E6 cells, and C57BL/6 mice. Experimental groups included control, infection, and gingerol-treated groups. Bacterial load and VE-cadherin protein expression were detected using immunofluorescence and Western blot. EVs were isolated by size exclusion chromatography and characterized by transmission electron microscopy and nanoparticle tracking analysis. miRNA sequencing was performed on EVs. ResultsGingerol treatment significantly reduced the bacterial load in both in vitro and in vivo infection models and upregulated VE-cadherin expression. miRNA sequencing of EVs revealed that S. aureus infection upregulated the expression of hsa-miR-320c, while gingerol treatment reversed this abnormal expression. Bioinformatic analysis further predicted that the target genes of hsa-miR-320c were significantly enriched in cell junction-related pathways. ConclusionGingerol exhibits clear antibacterial and host-protective effects, by regulating hsa-miR-320c in EVs to maintain endothelial barrier integrity.
2.International clinical practice guideline on the use of traditional Chinese medicine for functional dyspepsia (2025).
Sheng-Sheng ZHANG ; Lu-Qing ZHAO ; Xiao-Hua HOU ; Zhao-Xiang BIAN ; Jian-Hua ZHENG ; Hai-He TIAN ; Guan-Hu YANG ; Won-Sook HONG ; Yu-Ying HE ; Li LIU ; Hong SHEN ; Yan-Ping LI ; Sheng XIE ; Jin SHU ; Bin-Fang ZENG ; Jun-Xiang LI ; Zhen LIU ; Zheng-Hua XIAO ; Jing-Dong XIAO ; Pei-Yong ZHENG ; Shao-Gang HUANG ; Sheng-Liang CHEN ; Gui-Jun FEI
Journal of Integrative Medicine 2025;23(5):502-518
Functional dyspepsia (FD), characterized by persistent or recurrent dyspeptic symptoms without identifiable organic, systemic or metabolic causes, is an increasingly recognized global health issue. The objective of this guideline is to equip clinicians and nursing professionals with evidence-based strategies for the management and treatment of adult patients with FD using traditional Chinese medicine (TCM). The Guideline Development Group consulted existing TCM consensus documents on FD and convened a panel of 35 clinicians to generate initial clinical queries. To address these queries, a systematic literature search was conducted across PubMed, EMBASE, the Cochrane Library, China National Knowledge Infrastructure (CNKI), VIP Database, China Biology Medicine (SinoMed) Database, Wanfang Database, Traditional Medicine Research Data Expanded (TMRDE), and the Traditional Chinese Medical Literature Analysis and Retrieval System (TCMLARS). The evidence from the literature was critically appraised using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach. The strength of the recommendations was ascertained through a consensus-building process involving TCM and allopathic medicine experts, methodologists, pharmacologists, nursing specialists, and health economists, leveraging their collective expertise and empirical knowledge. The guideline comprises a total of 43 evidence-informed recommendations that span a range of clinical aspects, including the pathogenesis according to TCM, diagnostic approaches, therapeutic interventions, efficacy assessments, and prognostic considerations. Please cite this article as: Zhang SS, Zhao LQ, Hou XH, Bian ZX, Zheng JH, Tian HH, Yang GH, Hong WS, He YY, Liu L, Shen H, Li YP, Xie S, Shu J, Zeng BF, Li JX, Liu Z, Xiao ZH, Xiao JD, Zheng PY, Huang SG, Chen SL, Fei GJ. International clinical practice guideline on the use of traditional Chinese medicine for functional dyspepsia (2025). J Integr Med. 2025; 23(5):502-518.
Dyspepsia/drug therapy*
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Humans
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Medicine, Chinese Traditional/methods*
;
Practice Guidelines as Topic
;
Drugs, Chinese Herbal/therapeutic use*
3.Comparation on efficacy of transverse process-lateral pedicle approach and curved vertebroplasty in the treatment of osteoporotic vertebral compression fracture
Li LI ; Zhen YIN ; Jie GAO ; Fei XU ; Tao XIE ; Xiang′an KONG ; Jianjun CHU
Chinese Journal of Trauma 2025;41(1):43-50
Objective:To compare the efficacy of the transverse process-lateral pedicle approach and curved vertebroplasty in the treatment of osteoporotic vertebral compression fracture (OVCF).Methods:A retrospective cohort study was conducted to analyze the clinical data of 66 patients with OVCF admitted to the Second People′s Hospital of Hefei from December 2021 to June 2023, including 9 males and 57 females aged 60-89 years [(75.6±7.5)years]. The injured segments included T 11 in 17 patients, T 12 in 17, L 1 in 17, and L 2 in 15. Among them, 33 patients underwent vertebroplasty via the transverse process-lateral pedicle approach (lateral approach group), while other 33 patients underwent curved vertebroplasty (curved group). The surgical duration, number of X-ray fluoroscopy, bone cement injection volume, and length of hospital stay were compared between the two groups. Additionally, the restoration efficiency of vertebral height and the correction degree of spinal scoliosis Cobb angle at 2 days postoperatively were compared between the two groups. The changes in serum levels of stress factors including noradrenaline, adrenaline, and cortisol preoperatively and at 2 days postoperatively, the visual analogue scale (VAS) and Oswestry disability index (ODI) preoperatively, at 2 days, 6 months postoperatively, and at the last follow-up were compared between the two groups. The incidence of complications was assessed in the two groups. Results:All the patients were followed up for 12-14 months [(13.2±0.5)months]. The surgical duration and number of X-ray fluoroscopy in the lateral approach group were (30.9±4.1)minutes and (5.9±3.3)times, which were significantly lower than (35.8±3.9)minutes and (9.9±4.4)times in the curved group ( P<0.01). There were no statistically significant differences between the two groups in terms of bone cement injection volume, length of hospital stay, restoration efficiency of vertebral height at 2 days postoperatively, or the correction degree of spinal scoliosis Cobb angle ( P>0.05). The levels of noradrenaline, adrenaline, and cortisol at 2 days postoperatively were (57.3±4.8)ng/ml, (49.9±4.2)ng/ml, (159.3±20.5)nmol/L in the lateral approach group, and (64.3±4.5)ng/ml, (58.3±4.4)ng/ml, (183.5±21.2)nmol/L in the curved group, which were all significantly increased compared with those preoperatively [(42.3±3.5)ng/ml, (38.5±2.8)ng/ml, (128.4±12.3)nmol/L in the lateral approach group and (42.0±3.5)ng/ml, (39.0±3.0)ng/ml, (128.5±12.3)nmol/L in the curved group] ( P<0.01). There were no significant differences between the two groups in terms of the levels of noradrenaline, adrenaline, and cortisol preoperatively ( P>0.05). The levels of noradrenaline, adrenaline, and cortisol at 2 days postoperatively in the lateral approach group were significantly lower than those in the curved group ( P<0.01). The VAS scores for low back pain in the lateral approach group and the curved group were 3(2, 5)points and 5(3, 6)points at 2 days postoperatively, 3(2, 4)points and 3(2, 4)points at 6 months postoperatively, and 2(2, 3)points and 2(2, 4)points at the last follow-up, which were all significantly lower than those preoperatively [7(7, 9)points and 8(6, 9)points] ( P<0.05). Moreover, the VAS scores for low back pain were further decreased over time postoperatively ( P<0.05). The ODI values in the lateral approach group and curved group were (33.4±4.4)% and (33.7±4.3)% at 2 days postoperatively, (23.8±1.6)% and (23.8±1.7)% at 6 months postoperatively, and (15.6±0.9)% and (15.6±0.9)% at the last follow-up, which were all significantly lower than (67.4±4.3)% and (67.5±4.3)% preoperatively ( P<0.05). Moreover, the ODI values were further decreased over time postoperatively ( P<0.05). There were no significant differences between the two groups in terms of the VAS scores for low back pain or ODI values preoperatively, at 2 days, 6 months postoperatively or at the last follow-up ( P>0.05). The complication rate was 12.1% (4/33) in the lateral approach group, which was significantly lower than 51.5% (17/33) in the curved group ( P<0.05). Conclusion:Although both the transverse process-lateral pedicle approach vertebroplasty and the curved vertebroplasty can achieve good therapeutic effects in the treatment of OVCF, the former has shorter surgical duration, fewer times of X-ray fluoroscopy, lower trauma stress levels at 2 days postoperatively, and fewer complications.
4.POU2F1 inhibits miR-29b1/a cluster-mediated suppression of PIK3R1 and PIK3R3 expression to regulate gastric cancer cell invasion and migration.
Yizhi XIAO ; Ping YANG ; Wushuang XIAO ; Zhen YU ; Jiaying LI ; Xiaofeng LI ; Jianjiao LIN ; Jieming ZHANG ; Miaomiao PEI ; Linjie HONG ; Juanying YANG ; Zhizhao LIN ; Ping JIANG ; Li XIANG ; Guoxin LI ; Xinbo AI ; Weiyu DAI ; Weimei TANG ; Jide WANG
Chinese Medical Journal 2025;138(7):838-850
BACKGROUND:
The transcription factor POU2F1 regulates the expression levels of microRNAs in neoplasia. However, the miR-29b1/a cluster modulated by POU2F1 in gastric cancer (GC) remains unknown.
METHODS:
Gene expression in GC cells was evaluated using reverse-transcription polymerase chain reaction (PCR), western blotting, immunohistochemistry, and RNA in situ hybridization. Co-immunoprecipitation was performed to evaluate protein interactions. Transwell migration and invasion assays were performed to investigate the biological behavior of GC cells. MiR-29b1/a cluster promoter analysis and luciferase activity assay for the 3'-UTR study were performed in GC cells. In vivo tumor metastasis was evaluated in nude mice.
RESULTS:
POU2F1 is overexpressed in GC cell lines and binds to the miR-29b1/a cluster promoter. POU2F1 is upregulated, whereas mature miR-29b-3p and miR-29a-3p are downregulated in GC tissues. POU2F1 promotes GC metastasis by inhibiting miR-29b-3p or miR-29a-3p expression in vitro and in vivo . Furthermore, PIK3R1 and/or PIK3R3 are direct targets of miR-29b-3p and/or miR-29a-3p , and the ectopic expression of PIK3R1 or PIK3R3 reverses the suppressive effect of mature miR-29b-3p and/or miR-29a-3p on GC cell metastasis and invasion. Additionally, the interaction of PIK3R1 with PIK3R3 promotes migration and invasion, and miR-29b-3p , miR-29a-3p , PIK3R1 , and PIK3R3 regulate migration and invasion via the phosphatidylinositol 3-kinase/protein kinase B/mammalian target of rapamycin (PI3K/Akt/mTOR) pathway in GC cells. In addition, POU2F1 , PIK3R1 , and PIK3R3 expression levels negatively correlated with miR-29b-3p and miR-29a-3p expression levels in GC tissue samples.
CONCLUSIONS
The POU2F1 - miR-29b-3p / miR-29a-3p-PIK3R1 / PIK3R1 signaling axis regulates tumor progression and may be a promising therapeutic target for GC.
MicroRNAs/metabolism*
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Humans
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Stomach Neoplasms/pathology*
;
Cell Line, Tumor
;
Cell Movement/physiology*
;
Phosphatidylinositol 3-Kinases/metabolism*
;
Animals
;
Mice
;
Octamer Transcription Factor-1/metabolism*
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Mice, Nude
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Class Ia Phosphatidylinositol 3-Kinase/metabolism*
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Neoplasm Invasiveness
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Gene Expression Regulation, Neoplastic/genetics*
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Male
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Immunohistochemistry
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Female
5.Dissecting Social Working Memory: Neural and Behavioral Evidence for Externally and Internally Oriented Components.
Hanxi PAN ; Zefeng CHEN ; Nan XU ; Bolong WANG ; Yuzheng HU ; Hui ZHOU ; Anat PERRY ; Xiang-Zhen KONG ; Mowei SHEN ; Zaifeng GAO
Neuroscience Bulletin 2025;41(11):2049-2062
Social working memory (SWM)-the ability to maintain and manipulate social information in the brain-plays a crucial role in social interactions. However, research on SWM is still in its infancy and is often treated as a unitary construct. In the present study, we propose that SWM can be conceptualized as having two relatively independent components: "externally oriented SWM" (e-SWM) and "internally oriented SWM" (i-SWM). To test this external-internal hypothesis, participants were tasked with memorizing and ranking either facial expressions (e-SWM) or personality traits (i-SWM) associated with images of faces. We then examined the neural correlates of these two SWM components and their functional roles in empathy. The results showed distinct activations as the e-SWM task activated the postcentral and precentral gyri while the i-SWM task activated the precuneus/posterior cingulate cortex and superior frontal gyrus. Distinct multivariate activation patterns were also found within the dorsal medial prefrontal cortex in the two tasks. Moreover, partial least squares analyses combining brain activation and individual differences in empathy showed that e-SWM and i-SWM brain activities were mainly correlated with affective empathy and cognitive empathy, respectively. These findings implicate distinct brain processes as well as functional roles of the two types of SWM, providing support for the internal-external hypothesis of SWM.
Humans
;
Memory, Short-Term/physiology*
;
Male
;
Female
;
Empathy/physiology*
;
Young Adult
;
Magnetic Resonance Imaging
;
Adult
;
Brain/diagnostic imaging*
;
Brain Mapping
;
Facial Expression
;
Social Behavior
;
Facial Recognition/physiology*
;
Social Perception
;
Personality/physiology*
6.Comparation on efficacy of transverse process-lateral pedicle approach and curved vertebroplasty in the treatment of osteoporotic vertebral compression fracture
Li LI ; Zhen YIN ; Jie GAO ; Fei XU ; Tao XIE ; Xiang′an KONG ; Jianjun CHU
Chinese Journal of Trauma 2025;41(1):43-50
Objective:To compare the efficacy of the transverse process-lateral pedicle approach and curved vertebroplasty in the treatment of osteoporotic vertebral compression fracture (OVCF).Methods:A retrospective cohort study was conducted to analyze the clinical data of 66 patients with OVCF admitted to the Second People′s Hospital of Hefei from December 2021 to June 2023, including 9 males and 57 females aged 60-89 years [(75.6±7.5)years]. The injured segments included T 11 in 17 patients, T 12 in 17, L 1 in 17, and L 2 in 15. Among them, 33 patients underwent vertebroplasty via the transverse process-lateral pedicle approach (lateral approach group), while other 33 patients underwent curved vertebroplasty (curved group). The surgical duration, number of X-ray fluoroscopy, bone cement injection volume, and length of hospital stay were compared between the two groups. Additionally, the restoration efficiency of vertebral height and the correction degree of spinal scoliosis Cobb angle at 2 days postoperatively were compared between the two groups. The changes in serum levels of stress factors including noradrenaline, adrenaline, and cortisol preoperatively and at 2 days postoperatively, the visual analogue scale (VAS) and Oswestry disability index (ODI) preoperatively, at 2 days, 6 months postoperatively, and at the last follow-up were compared between the two groups. The incidence of complications was assessed in the two groups. Results:All the patients were followed up for 12-14 months [(13.2±0.5)months]. The surgical duration and number of X-ray fluoroscopy in the lateral approach group were (30.9±4.1)minutes and (5.9±3.3)times, which were significantly lower than (35.8±3.9)minutes and (9.9±4.4)times in the curved group ( P<0.01). There were no statistically significant differences between the two groups in terms of bone cement injection volume, length of hospital stay, restoration efficiency of vertebral height at 2 days postoperatively, or the correction degree of spinal scoliosis Cobb angle ( P>0.05). The levels of noradrenaline, adrenaline, and cortisol at 2 days postoperatively were (57.3±4.8)ng/ml, (49.9±4.2)ng/ml, (159.3±20.5)nmol/L in the lateral approach group, and (64.3±4.5)ng/ml, (58.3±4.4)ng/ml, (183.5±21.2)nmol/L in the curved group, which were all significantly increased compared with those preoperatively [(42.3±3.5)ng/ml, (38.5±2.8)ng/ml, (128.4±12.3)nmol/L in the lateral approach group and (42.0±3.5)ng/ml, (39.0±3.0)ng/ml, (128.5±12.3)nmol/L in the curved group] ( P<0.01). There were no significant differences between the two groups in terms of the levels of noradrenaline, adrenaline, and cortisol preoperatively ( P>0.05). The levels of noradrenaline, adrenaline, and cortisol at 2 days postoperatively in the lateral approach group were significantly lower than those in the curved group ( P<0.01). The VAS scores for low back pain in the lateral approach group and the curved group were 3(2, 5)points and 5(3, 6)points at 2 days postoperatively, 3(2, 4)points and 3(2, 4)points at 6 months postoperatively, and 2(2, 3)points and 2(2, 4)points at the last follow-up, which were all significantly lower than those preoperatively [7(7, 9)points and 8(6, 9)points] ( P<0.05). Moreover, the VAS scores for low back pain were further decreased over time postoperatively ( P<0.05). The ODI values in the lateral approach group and curved group were (33.4±4.4)% and (33.7±4.3)% at 2 days postoperatively, (23.8±1.6)% and (23.8±1.7)% at 6 months postoperatively, and (15.6±0.9)% and (15.6±0.9)% at the last follow-up, which were all significantly lower than (67.4±4.3)% and (67.5±4.3)% preoperatively ( P<0.05). Moreover, the ODI values were further decreased over time postoperatively ( P<0.05). There were no significant differences between the two groups in terms of the VAS scores for low back pain or ODI values preoperatively, at 2 days, 6 months postoperatively or at the last follow-up ( P>0.05). The complication rate was 12.1% (4/33) in the lateral approach group, which was significantly lower than 51.5% (17/33) in the curved group ( P<0.05). Conclusion:Although both the transverse process-lateral pedicle approach vertebroplasty and the curved vertebroplasty can achieve good therapeutic effects in the treatment of OVCF, the former has shorter surgical duration, fewer times of X-ray fluoroscopy, lower trauma stress levels at 2 days postoperatively, and fewer complications.
7.Transcatheter Aortic Valve Replacement in Patients With Pure Native Aortic Regurgitation: Results From a Multicenter Registry Study
Xiaofei GAO ; Juan ZHANG ; Xiangquan KONG ; Jing CHEN ; Xiang CHEN ; Longyan ZHANG ; Xinyong CAI ; Jiancheng ZHU ; Nailiang TIAN ; Zhen GE ; Bin WANG ; Qing ZHOU ; Xi SU ; Lang HONG ; Yan WANG ; Hong JIANG ; Junjie ZHANG ; Shaoliang CHEN
Cardiology Discovery 2024;04(2):134-141
Objective::Patients with untreated severe aortic regurgitation (AR) have a high risk of mortality. Transfemoral transcatheter aortic valve replacement (TF-TAVR) is a treatment option for AR; however, the safety and efficacy of this technique have not been sufficiently established. This study aimed to evaluate the clinical and anatomical variables correlating with device success of TF-TAVR using a self-expanding valve system for pure AR.Methods::Patients with pure native severe AR who underwent TF-TAVR using a self-expanding valve system were registered at 5 Chinese centers. The primary endpoint was device success at 1 month after TAVR. The secondary endpoint was the composite of major adverse cardiovascular events (MACE) at 6 months, including all-cause death, ischemic stroke, emergency conversion to cardiac surgery, and permanent pacemaker implantation. Echocardiography was used to analyze the left ventricular function before the TAVR procedure and during follow-up. Multivariable logistic regression and Cox regression analyses were performed to find relevant independent risk factors.Results::Between September 2019 and February 2022, 79 patients with AR were enrolled in the study. At 1 month, device success was achieved in 60 (75.9%) patients. By 6 months, 29 (36.7%) patients had MACE. Echocardiography revealed improved left ventricular function after TAVR. Multivariate regression analysis demonstrated that the Society of Thoracic Surgeons risk score (odds ratio 0.760, 95% confidence interval (CI): 0.584-0.989; P = 0.041) and annulus perimeter (odds ratio 0.888, 95% CI: 0.796-0.992; P = 0.035) were 2 predictors of device success. Moreover, annulus perimeter (<80.2 mm), but not Society of Thoracic Surgeons risk score, was associated with a significant reduction in MACE at 6 months (hazard ratio 2.223, 95% CI: 1.060-4.659; P = 0.028). Conclusions::TF-TAVR using a self-expanding valve system appears to be a safe and feasible treatment for patients with pure native severe AR, particularly those with a less enlarged annulus.
8.Transcatheter Aortic Valve Replacement in Patients With Pure Native Aortic Regurgitation: Results From a Multicenter Registry Study
Xiaofei GAO ; Juan ZHANG ; Xiangquan KONG ; Jing CHEN ; Xiang CHEN ; Longyan ZHANG ; Xinyong CAI ; Jiancheng ZHU ; Nailiang TIAN ; Zhen GE ; Bin WANG ; Qing ZHOU ; Xi SU ; Lang HONG ; Yan WANG ; Hong JIANG ; Junjie ZHANG ; Shaoliang CHEN
Cardiology Discovery 2024;04(2):134-141
Objective::Patients with untreated severe aortic regurgitation (AR) have a high risk of mortality. Transfemoral transcatheter aortic valve replacement (TF-TAVR) is a treatment option for AR; however, the safety and efficacy of this technique have not been sufficiently established. This study aimed to evaluate the clinical and anatomical variables correlating with device success of TF-TAVR using a self-expanding valve system for pure AR.Methods::Patients with pure native severe AR who underwent TF-TAVR using a self-expanding valve system were registered at 5 Chinese centers. The primary endpoint was device success at 1 month after TAVR. The secondary endpoint was the composite of major adverse cardiovascular events (MACE) at 6 months, including all-cause death, ischemic stroke, emergency conversion to cardiac surgery, and permanent pacemaker implantation. Echocardiography was used to analyze the left ventricular function before the TAVR procedure and during follow-up. Multivariable logistic regression and Cox regression analyses were performed to find relevant independent risk factors.Results::Between September 2019 and February 2022, 79 patients with AR were enrolled in the study. At 1 month, device success was achieved in 60 (75.9%) patients. By 6 months, 29 (36.7%) patients had MACE. Echocardiography revealed improved left ventricular function after TAVR. Multivariate regression analysis demonstrated that the Society of Thoracic Surgeons risk score (odds ratio 0.760, 95% confidence interval (CI): 0.584-0.989; P = 0.041) and annulus perimeter (odds ratio 0.888, 95% CI: 0.796-0.992; P = 0.035) were 2 predictors of device success. Moreover, annulus perimeter (<80.2 mm), but not Society of Thoracic Surgeons risk score, was associated with a significant reduction in MACE at 6 months (hazard ratio 2.223, 95% CI: 1.060-4.659; P = 0.028). Conclusions::TF-TAVR using a self-expanding valve system appears to be a safe and feasible treatment for patients with pure native severe AR, particularly those with a less enlarged annulus.
9.Safety and efficacy of the early administration of levosimendan in patients with acute non-ST-segment elevation myocardial infarction and elevated NT-proBNP levels: An Early Management Strategy of Acute Heart Failure (EMS-AHF).
Feng XU ; Yuan BIAN ; Guo Qiang ZHANG ; Lu Yao GAO ; Yu Fa LIU ; Tong Xiang LIU ; Gang LI ; Rui Xue SONG ; Li Jun SU ; Yan Ju ZHOU ; Jia Yu CUI ; Xian Liang YAN ; Fang Ming GUO ; Huan Yi ZHANG ; Qing Hui LI ; Min ZHAO ; Li Kun MA ; Bei An YOU ; Ge WANG ; Li KONG ; Jian Liang MA ; Xin Fu ZHOU ; Ze Long CHANG ; Zhen Yu TANG ; Dan Yu YU ; Kai CHENG ; Li XUE ; Xiao LI ; Jiao Jiao PANG ; Jia Li WANG ; Hai Tao ZHANG ; Xue Zhong YU ; Yu Guo CHEN
Chinese Journal of Internal Medicine 2023;62(4):374-383
Objectives: To investigated the safety and efficacy of treating patients with acute non-ST-segment elevation myocardial infarction (NSTEMI) and elevated levels of N-terminal pro-hormone B-type natriuretic peptide (NT-proBNP) with levosimendan within 24 hours of first medical contact (FMC). Methods: This multicenter, open-label, block-randomized controlled trial (NCT03189901) investigated the safety and efficacy of levosimendan as an early management strategy of acute heart failure (EMS-AHF) for patients with NSTEMI and high NT-proBNP levels. This study included 255 patients with NSTEMI and elevated NT-proBNP levels, including 142 males and 113 females with a median age of 65 (58-70) years, and were admitted in the emergency or outpatient departments at 14 medical centers in China between October 2017 and October 2021. The patients were randomly divided into a levosimendan group (n=129) and a control group (n=126). The primary outcome measure was NT-proBNP levels on day 3 of treatment and changes in the NT-proBNP levels from baseline on day 5 after randomization. The secondary outcome measures included the proportion of patients with more than 30% reduction in NT-proBNP levels from baseline, major adverse cardiovascular events (MACE) during hospitalization and at 6 months after hospitalization, safety during the treatment, and health economics indices. The measurement data parameters between groups were compared using the t-test or the non-parametric test. The count data parameters were compared between groups using the χ² test. Results: On day 3, the NT-proBNP levels in the levosimendan group were lower than the control group but were statistically insignificant [866 (455, 1 960) vs. 1 118 (459, 2 417) ng/L, Z=-1.25,P=0.21]. However, on day 5, changes in the NT-proBNP levels from baseline in the levosimendan group were significantly higher than the control group [67.6% (33.8%,82.5%)vs.54.8% (7.3%,77.9%), Z=-2.14, P=0.03]. There were no significant differences in the proportion of patients with more than 30% reduction in the NT-proBNP levels on day 5 between the levosimendan and the control groups [77.5% (100/129) vs. 69.0% (87/126), χ²=2.34, P=0.13]. Furthermore, incidences of MACE did not show any significant differences between the two groups during hospitalization [4.7% (6/129) vs. 7.1% (9/126), χ²=0.72, P=0.40] and at 6 months [14.7% (19/129) vs. 12.7% (16/126), χ²=0.22, P=0.64]. Four cardiac deaths were reported in the control group during hospitalization [0 (0/129) vs. 3.2% (4/126), P=0.06]. However, 6-month survival rates were comparable between the two groups (log-rank test, P=0.18). Moreover, adverse events or serious adverse events such as shock, ventricular fibrillation, and ventricular tachycardia were not reported in both the groups during levosimendan treatment (days 0-1). The total cost of hospitalization [34 591.00(15 527.46,59 324.80) vs. 37 144.65(16 066.90,63 919.00)yuan, Z=-0.26, P=0.80] and the total length of hospitalization [9 (8, 12) vs. 10 (7, 13) days, Z=0.72, P=0.72] were lower for patients in the levosimendan group compared to those in the control group, but did not show statistically significant differences. Conclusions: Early administration of levosimendan reduced NT-proBNP levels in NSTEMI patients with elevated NT-proBNP and did not increase the total cost and length of hospitalization, but did not significantly improve MACE during hospitalization or at 6 months.
Male
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Female
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Humans
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Aged
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Natriuretic Peptide, Brain
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Simendan/therapeutic use*
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Non-ST Elevated Myocardial Infarction
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Heart Failure/drug therapy*
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Peptide Fragments
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Arrhythmias, Cardiac
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Biomarkers
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Prognosis
10.The mechanism of S100A7 inducing the migration and invasion in cervical cancer cells.
Tian TIAN ; Zhen HUA ; Yan KONG ; Ling Zhi WANG ; Xiang Yu LIU ; Yi HAN ; Xue Min ZHOU ; Zhu Mei CUI
Chinese Journal of Oncology 2023;45(5):375-381
Objective: To investigate the mechanism of S100A7 inducing the migration and invasion in cervical cancers. Methods: Tissue samples of 5 cases of cervical squamous cell carcinoma and 3 cases of adenocarcinoma were collected from May 2007 to December 2007 in the Department of Gynecology of the Affiliated Hospital of Qingdao University. Immunohistochemistry was performed to evaluate the expression of S100A7 in cervical carcinoma tissues. S100A7-overexpressing HeLa and C33A cells were established with lentiviral systems as the experimental group. Immunofluorescence assay was performed to observe the cell morphology. Transwell assay was taken to detect the effect of S100A7-overexpression on the migration and invasion of cervical cancer cells. Reverse transcription-quantitative real-time polymerase chain reaction (RT-qPCR) was used to examine the mRNA expressions of E-cadherin, N-cadherin, vimentin and fibronectin. The expression of extracellular S100A7 in conditioned medium of cervical cancer cell was detected by western blot. Conditioned medium was added into Transwell lower compartment to detect cell motility. Exosomes were isolated and extracted from the culture supernatant of cervical cancer cell, the expressions of S100A7, CD81 and TSG101 were detected by western blot. Transwell assay was taken to detect the effect of exosomes on the migration and invasion of cervical cancer cells. Results: S100A7 expression was positively expressed in cervical squamous carcinoma and negative expression in adenocarcinoma. Stable S100A7-overexpressing HeLa and C33A cells were successfully constructed. C33A cells in the experimental group were spindle shaped while those in the control group tended to be polygonal epithelioid cells. The number of S100A7-overexpressed HeLa cells passing through the Transwell membrane assay was increased significantly in migration and invasion assay (152.00±39.22 vs 105.13±15.75, P<0.05; 115.38±34.57 vs 79.50±13.68, P<0.05). RT-qPCR indicated that the mRNA expressions of E-cadherin in S100A7-overexpressed HeLa and C33A cells decreased (P<0.05) while the mRNA expressions of N-cadherin and fibronectin in HeLa cells and fibronectin in C33A cells increased (P<0.05). Western blot showed that extracellular S100A7 was detected in culture supernatant of cervical cancer cells. HeLa cells of the experimental group passing through transwell membrane in migration and invasion assays were increased significantly (192.60±24.41 vs 98.80±47.24, P<0.05; 105.40±27.38 vs 84.50±13.51, P<0.05) when the conditional medium was added into the lower compartment of Transwell. Exosomes from C33A cell culture supernatant were extracted successfully, and S100A7 expression was positive. The number of transmembrane C33A cells incubated with exosomes extracted from cells of the experimental group was increased significantly (251.00±49.82 vs 143.00±30.85, P<0.05; 524.60±52.74 vs 389.00±63.23, P<0.05). Conclusion: S100A7 may promote the migration and invasion of cervical cancer cells by epithelial-mesenchymal transition and exosome secretion.
Female
;
Humans
;
Uterine Cervical Neoplasms/pathology*
;
HeLa Cells
;
Fibronectins/metabolism*
;
Culture Media, Conditioned
;
Carcinoma, Squamous Cell/metabolism*
;
Adenocarcinoma
;
Cadherins/metabolism*
;
RNA, Messenger/metabolism*
;
Cell Movement
;
Epithelial-Mesenchymal Transition/genetics*
;
Cell Line, Tumor
;
Cell Proliferation
;
S100 Calcium Binding Protein A7/metabolism*

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