1.Cytoplasmic and nuclear NFATc3 cooperatively contributes to vascular smooth muscle cell dysfunction and drives aortic aneurysm and dissection.
Xiu LIU ; Li ZHAO ; Deshen LIU ; Lingna ZHAO ; Yonghua TUO ; Qinbao PENG ; Fangze HUANG ; Zhengkun SONG ; Chuanjie NIU ; Xiaoxia HE ; Yu XU ; Jun WAN ; Peng ZHU ; Zhengyang JIAN ; Jiawei GUO ; Yingying LIU ; Jun LU ; Sijia LIANG ; Shaoyi ZHENG
Acta Pharmaceutica Sinica B 2025;15(7):3663-3684
This study investigated the role of the nuclear factor of activated T cells c3 (NFATc3) in vascular smooth muscle cells (VSMCs) during aortic aneurysm and dissection (AAD) progression and the underlying molecular mechanisms. Cytoplasmic and nuclear NFATc3 levels were elevated in human and mouse AAD. VSMC-NFATc3 deletion reduced thoracic AAD (TAAD) and abdominal aortic aneurysm (AAA) progression in mice, contrary to VSMC-NFATc3 overexpression. VSMC-NFATc3 deletion reduced extracellular matrix (ECM) degradation and maintained the VSMC contractile phenotype. Nuclear NFATc3 targeted and transcriptionally upregulated matrix metalloproteinase 9 (MMP9) and MMP2, promoting ECM degradation and AAD development. NFATc3 promoted VSMC phenotypic switching by binding to eukaryotic elongation factor 2 (eEF2) and inhibiting its phosphorylation in the VSMC cytoplasm. Restoring eEF2 reversed the beneficial effects in VSMC-specific NFATc3-knockout mice. Cabamiquine-targets eEF2 and inhibits protein synthesis-inhibited AAD development and progression in VSMC-NFATc3-overexpressing mice. VSMC-NFATc3 promoted VSMC switch and ECM degradation while exacerbating AAD development, making it a novel potential therapeutic target for preventing and treating AAD.
2.The hard tissue thickness of primary teeth studied by CBCT
Panxi WANG ; Jinyi LI ; Zhengyang LI ; Shuqi ZHANG ; Qingyu GUO ; Fei LIU
Journal of Practical Stomatology 2024;40(5):703-707
Objective:To analyze the hard tissue thickness in the crown of primary teeth by CBCT.Methods:The CBCT imaging data of 47 children were included,and the hard tissue thickness of primary teeth was measured by MIMICS software.SPSS 22.0 was used for data analysis.Results:The average thickness in the mesial surfaces was the smallest(P<0.01),except for the libial surface of maxillary central incisor and the distal surface of mandibular first primary molar.In primary anteriors,the thickness in the same sur-face of maxillary teeth was greater than that of mandibular teeth significantly(P<0.01)except for the libial surface of primary canine.In primary molars,the thickness of hard tissue in the same part of the distal and lingual side of the maxillary teeth was greater than that of the mandibular teeth(P<0.01),and the thickness in the buccal side of maxillary teeth was lower than that of the mandibular teeth(P<0.01).Conclusion:The distribution of hard tissue thickness of primary teeth in different position is different.
3.Effectiveness of robot-assisted minimally invasive and open freehand transforaminal lumbar interbody fusion in treatment of single-level degenerative lumbar spondylolisthesis and the influence on adjacent segment degeneration.
Song GUO ; Ye ZHANG ; Jun SHANG ; Lei MENG ; Dongfeng LI ; Zhengyang LI ; Mingyue WANG
Chinese Journal of Reparative and Reconstructive Surgery 2024;38(11):1379-1385
OBJECTIVE:
To compare the effectiveness of robot-assisted minimally invasive transforaminal lumbar interbody fusion (MIS-TLIF) and open freehand TLIF for the treatment of single-level degenerative lumbar spondylolisthesis (DSL) and analyse the influence on postoperative adjacent segmental degeneration (ASD).
METHODS:
The clinical data of 116 patients with L 4、5 DLS who were admitted between November 2019 and October 2021 and met the selection criteria were retrospectively analyzed. According to the surgical methods, they were divided into the robotic group (45 cases, who underwent robot-assisted MIS-TLIF) and the open group (71 cases, who underwent open freehand TLIF). There was no significant difference in baseline data such as gender, age, body mass index, DLS Meyerding grading, and preoperative Pfirrmann grading, Weishaupt grading, L 3, 4 intervertebral disc height (DH), L 3, 4 intervertebral mobility, sagittal parameters [including pelvic incidence (PI), lumbar lordosis (LL), sacral slope (SS), pelvic tilt (PT)], and Cage height ( P>0.05). The grade of facet joint violation (FJV) by pedicle screws on the superior articular process was assessed postoperatively. Sagittal parameters, L 3, 4 DH, L 3, 4 DH loss, and L 3, 4 intervertebral mobility were measured preoperatively and at last follow-up in order to determine whether ASD occurred. Based on the occurrence of postoperative ASD, logistic regression analysis was used to identify the risk factors for ASD after TLIF.
RESULTS:
Patients in both groups were followed up 21-47 months, with a mean of 36.1 months; there was no significant difference in the follow-up time between the two groups ( P>0.05). The occurrence of postoperative FJV was significantly better in the robotic group than in the open group ( P<0.05). At last follow-up, the difference in the change values of sagittal parameters PI, PT, SS, and LL was not significant when comparing the two groups of patients ( P>0.05); the change values of L 3, 4 DH and L 3, 4 DH loss in the robotic group were smaller than those in the open group, and the change value of L 3, 4 intervertebral mobility was larger than that in the open group, and the differences were significant ( P<0.05). At last follow-up, ASD occurred in 8 patients (17.8%) in the robotic group and 35 patients (49.3%) in the open group, and the difference in ASD incidence between the two groups was significant ( P<0.05). logistic regression analysis showed that open surgery, preoperative Pfirrmann grading Ⅳ-Ⅴ, preoperative Weishaupt grading ≥2, and postoperative FJV grading ≥1 were risk factors for the development of ASD after TLIF ( P<0.05).
CONCLUSION
Compared with traditional open surgery, orthopedic robot-assisted MIS-TLIF in the treatment of single-level DLS can more accurately insert pedicle screws, reduce the loss of DH and the occurrence of FJV, and effectively reduce the incidence of mid-postoperative ASD. Preoperative disc and synovial joint degeneration in adjacent segments, nonrobotic-assisted minimally invasive therapy, and FJV are risk factors for ASD after TLIF.
Humans
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Spinal Fusion/methods*
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Spondylolisthesis/surgery*
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Lumbar Vertebrae/surgery*
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Minimally Invasive Surgical Procedures/methods*
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Robotic Surgical Procedures/methods*
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Male
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Treatment Outcome
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Female
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Intervertebral Disc Degeneration/surgery*
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Retrospective Studies
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Postoperative Complications/etiology*
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Risk Factors
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Middle Aged
4.IKKβ mediates homeostatic function in inflammation via competitively phosphorylating AMPK and IκBα.
Juan LIU ; Yuxin ZHUANG ; Jianlin WU ; Qiang WU ; Meixian LIU ; Yue ZHAO ; Zhongqiu LIU ; Caiyan WANG ; Linlin LU ; Yingjiao MENG ; Kawai LEI ; Xiaojuan LI ; Qibiao WU ; Elaine Lai-Han LEUNG ; Zhengyang GUO ; Liang LIU ; Ting LI
Acta Pharmaceutica Sinica B 2022;12(2):651-664
Inhibitor of nuclear factor kappa-B kinase subunit beta (IKKβ) is one of important kinases in inflammation to phosphorylate inhibitor of nuclear factor kappa-B (IκBα) and then activate nuclear factor kappa-B (NF-κB). Inhibition of IKKβ has been a therapeutic strategy for inflammatory and autoimmune diseases. Here we report that IKKβ is constitutively activated in healthy donors and healthy Ikkβ C46A (cysteine 46 mutated to alanine) knock-in mice although they possess intensive IKKβ-IκBα-NF-κB signaling activation. These indicate that IKKβ activation probably plays homeostatic role instead of causing inflammation. Compared to Ikkβ WT littermates, lipopolysaccharides (LPS) could induce high mortality rate in Ikkβ C46A mice which is correlated to breaking the homeostasis by intensively activating p-IκBα-NF-κB signaling and inhibiting phosphorylation of 5' adenosine monophosphate-activated protein kinase (p-AMPK) expression. We then demonstrated that IKKβ kinase domain (KD) phosphorylates AMPKα1 via interacting with residues Thr183, Ser184, and Thr388, while IKKβ helix-loop-helix motifs is essential to phosphorylate IκBα according to the previous reports. Kinase assay further demonstrated that IKKβ simultaneously catalyzes phosphorylation of AMPK and IκBα to mediate homeostasis. Accordingly, activation of AMPK rather than inhibition of IKKβ could substantially rescue LPS-induced mortality in Ikkβ C46A mice by rebuilding the homeostasis. We conclude that IKKβ activates AMPK to restrict inflammation and IKKβ mediates homeostatic function in inflammation via competitively phosphorylating AMPK and IκBα.
5.Auxiliary role of Python-based handover database in online teaching activities for medical clerks
Hongbin GUO ; Zhengyang WANG ; Yingfeng WAN ; Xinwei LI ; Yirong WANG
Chinese Journal of Medical Education Research 2022;21(6):694-697
Objective:To evaluate the auxiliary role of the Python-based handover database in online teaching activities for medical clerks and to complete the teaching tasks during the COVID-19 epidemic.Method:Sixteen teachers were randomized into two groups, experimental group and control group, with 8 ones in each group. The experimental group used the self-built handover database, while the control group used the hospital's HIS system. To make multimedia courseware for medical students, suitable cases were screened. The time to acquire cases and picture data, and the index like numbers were statistically analyzed, and the quality of multimedia courseware was scored. All the data were analyzed by SPSS 25.0 statistical software.Results:The time for the two groups of teachers to acquire target cases during making multimedia coursewares were (8.88±3.48) min and (43.50±5.26) min respectively; the time to obtain the pictures were (5.62±1.92) min and (30.25±5.39) min; the numbers of obtained pictures were (11.12±2.17) and (6.12±2.80); and the scores of coursewares were (92.62 ± 4.93) points and (84.75 ± 6.20) points respectively, all with significant differences.Conclusion:The application of the self-made handover database can significantly improve the speed of teachers' access to related teaching data, and also can improve the quality of multimedia courseware.
6.Relationship between macrophage capping protein and gastric cancer cell's proliferation and migration ability
Xiang GAO ; Xiangmei CHEN ; Ting ZHANG ; Jing ZHANG ; Mo CHEN ; Zhengyang GUO ; Yanyan SHI ; Fengmin LU ; Shigang DING
Journal of Peking University(Health Sciences) 2017;49(3):489-494
Objective: To investigate the effect of macrophage-capping protein (CapG) on migration and proliferation of human gastric cancer cell line.Methods: Real-time PCR method was used to detect the expression of CapG gene in four gastric cancer cell lines, and AGS cells with low expression and transfection were selected as the research objects.Specific primers were designed for CapG and recombinant plasmids synthesized.A lentivirus packaging system which could express CapG was constructed, and a cell line stably expressing CapG was established by infecting human gastric cancer cell line AGS cells.The effect of overexpression of CapG gene on the growth and proliferation of AGS cells was analyzed by CCK8 assay.Cells cratch and Transwell assay were used to analyze the effect of overexpression of CapG gene on AGS cell migration.Results: After the overexpression of CapG, the growth rate of AGS cells was slightly lower than that of the control group, but there was no significant difference between the two groups (t=2.424, P=0.073).Scratch test showed that the average narrowing distance of the scratches in the CapG experimental group was significantly reduced compared with the control group, the average narrowing distance of the CapG experimental group and the control group was 336.99 μm and 45.54 μm, the difference was statistically significant (t=14.97, P=0.004).The average number of cell penetra-ting membrane in the CapG experimental group and the eGFP control group was 176 and 70, the number of the cells in the CapG experimental group was significantly higher than that of the control group (t=40.00, P<0.001).Conclusion: The overexpression of CapG gene has no significant effect on the growth and proliferation of AGS cells of gastric cancer cell line.Overexpression of CapG gene can promote the migration of AGS cells of gastric cancer cell lines.
7.Proton pump inhibitors and risk of hip fracture: a systematic review
Ying ZHANG ; Xiaofeng YU ; Gansheng ZHANG ; Zhengyang GUO ; Ziyan ZHANG ; Shangmin ZHAO
Chinese Journal of General Practitioners 2015;14(3):212-217
Objective To explore the effects of using proton pump inhibitors (PPIs) on the outcomes of hip fracture.Methods Searches were conducted through Medline,Embase,Cochrane Library and Chinese Biomedical Literature Database to identify the studies of the association between PPIs exposure and hip fracture.Quality of studies was assessed using the Newcastle-Ottawa Quality Assessment Scale.Pooled odds ratios (ORs) and 95% confidence interval (CIs) were calculated for the risk of hip fracture associated with current exposure of PPIs.And several subgroups were analyzed by dosing duration,dose,osteoporosis and corticosteroid usage to explore potential study heterogeneities.All statistical analyses were performed with STATA software.Results Among 11 publications included for final analysis,there were a total of 1 107 577 subjects with an average age of over 60 years.A positive relationship existed between PPIs exposure and hip fracture with an OR of 1.46 (95% CI:1.26-1.70,P =0.000) as compared with nonPPI-users,especially those on concurrent corticosteroid and PPIs.A significantly increased risk of hip fracture was found in the group of a short-term duration for under 1 year (OR =1.18,95% CI:1.01-1.38,P =0.041),medium-term for 1-3 years (OR =1.23,95% CI:1.01-1.49,P =0.038) and longer duration for over 6 years (OR =1.38,95% CI:1.27-1.50,P =0.000).Furthermore,concurrent use of PPIs was not associated with an increased risk of hip fracture in a definite dose-response manner.As compared with non-PPI-users,no significantly increased risk of hip fracture was found in PPI-users with osteoporosis (P > 0.05).Publication bias was not present.Conclusions Use of PPIs may be somewhat associated with an increased risk of hip fracture.Considering potential adverse effects,clinicians should prescribe cautiously PPIs for high-risk patients,especially elders.
8.Surveillance and forecast system of schistosomiasis in Jiangsu Province ⅥDetection technology of water infectivity based on enrichment of Schistosoma japonicum cercariae on water surface
Guoli QU ; Jianrong DAI ; Yuantian XING ; Wei WANG ; Zhenkun YANG ; Zhengyang ZHAO ; Na GUO ; Leping SUN ; Yousheng LIANG
Chinese Journal of Schistosomiasis Control 2014;(5):510-513
Objective To explore the enrichment technique of Schistosoma japonicum cercariae on the water surface,so as to establish a new method combined with the existing technology to detect the cercarial infested water body quickly and sensitive-ly. Methods Soybean oil,gasoline,kerosene and isophorone were screened as expanding agents. The cercariae were enriched by the thrust of the expanding agents when diffusing on the water surface,and PE adsorption film and C-6 film were applied to seize them so as to determine the infectivity of the water quickly. The relationship between the dose of expanding agents and dif-fusion radius were explored. Results Gasoline,kerosene and isophorone were suitable expanding agents,and the diffusion ef-fect of isophorone was the best. After the enrichment by the expanding agents,the detection rate of cercariae of the method seiz-ing cercariae with the film significantly improved in the water. Conclusion This new method could effectively improve the de-tection rate of the cercarial infested water and is suitable for the low-degree infested water.
9.Radiotherapy and chemoradiotherapy in patient with N1 esophageal carcinoma
Zhengyang XU ; Kuaile ZHAO ; Jianxin GUO ;
China Oncology 2001;0(02):-
Purpose:To compare the survival and toxicities of concureent chemoradiotherapy followed by adjuvant chemotherapy in patients with N1 esophageal carcinoma. Analysis was made for reasons of failure in the patients with N1 esophageal carcinoma. Methods:From August 1998 to August 2000,65 eligible patients with N1 esophageal carcinoma were randomized into the following arms: 33 patients were randomized to concurrent chemoradiotherapy arm, 32 patients to radiotherapy followed by chemotherapy. The schedules of radiotherapy were the same, which were conventional fractionation, total dose 60~70 Gy. The regimen of chemotherapy all consisted of DDP and 5 FU,4 cycles. It started on the first day of radiotherapy, and 15 days after radiotherapy chemoradiotherapy was given. Results:The survival rates at 1,2 and 3 years were 60.2%,43.5% and 25.9% in the concurrent chemoradiotherapy arm, 66.3%, 22.5% and 11.3% in the radiotherapy followed by chemoradiotherapy arm, respectively ( P =0.109). 18.2% in the radiotherapy followed by chemoradiotherapy arm had grad Ⅲ esophagitis, while the concurrent group had 43.7% P

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