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.

Myocardial fibrosis is a serious cause of heart failure and even sudden cardiac death. However, the mechanisms underlying myocardial ischemia-induced cardiac fibrosis remain unclear. Here, we identified that the expression of sterile alpha and TIR motif containing 1 (SARM1), was increased significantly in the ischemic cardiomyopathy patients, dilated cardiomyopathy patients (GSE116250) and fibrotic heart tissues of mice. Additionally, inhibition or knockdown of SARM1 can improve myocardial fibrosis and cardiac function of myocardial infarction (MI) mice. Moreover, SARM1 fibroblasts-specific knock-in mice had increased deposition of extracellular matrix and impaired cardiac function. Mechanically, elevated expression of SARM1 promotes the deposition of extracellular matrix by directly modulating P4HA1. Notably, by using the Click-iT reaction, we identified that the increased expression of ZDHHC17 promotes the palmitoylation levels of SARM1, thereby accelerating the fibrosis process. Based on the fibrosis-promoting effect of SARM1, we screened several drugs with anti-myocardial fibrosis activity. In conclusion, we have unveiled that palmitoylated SARM1 targeting P4HA1 promotes collagen deposition and myocardial fibrosis. Inhibition of SARM1 is a potential strategy for the treatment of myocardial fibrosis. The sites where SARM1 interacts with P4HA1 and the palmitoylation modification sites of SARM1 may be the active targets for anti-fibrosis drugs.

Objective:To investigate the clinical effect of free anterolateral thigh perforator flap(ALTPF) in reconstruction of temporal scalp defect after blood circulation reconstruction surgery for moyamoya disease.Methods:From May 2020 to July 2022, 7 patients with scalp defect after revascularisation of moyamoya disease were treated in Department of Hand and Foot Microsurgery, Henan Provincial People’s Hospital (People’s Hospital of Zhengzhou University). The patients were 4 males and 3 females, aged 33-59 years old, at 43 years old in average. There were 5 defects in left tempus and 2 in right tempus. The sizes of scalp defect were 4.5 cm × 5.5 cm-7.5 cm × 9.5 cm. Debridement and VSD management were primarily performed. After wounds were stabilised, ultrasound location of perforator vessels of ALTPFs was performed. Having confirmed that the perforator vessels were suitable for the surgical requirements, flap transfers were then performed. The descending branch of the lateral femoral circumflex artery was end-to-side anastomosed with the superficial temporal artery, and the descending branch of the lateral femoral circumflex vein was end-to-end anastomosed with the superficial temporal vein. Postoperative follow-up was conducted through outpatient clinic visits, telephone and WeChat reviews. Appearance, texture of ALTPFs and the flap donor sites were observed in follow-ups. Comparisons of the changes of nervous system before and after surgery were made. Cognitive function of the patients was assessed with the Mini Mental State Examination (MMSE), together with the Activities of Daily Living (ADL) .Results:All 7 flaps survived. One flap had vascular compromise 6 hours after surgery, and was rectified after surgical intervention. All the patients were included in the postoperative follow-up for 7-33 (average 19) months. All flaps had good appearance with soft texture. There was no obvious difference in colour comparing with the skin around the recipient region. The donor sites healed well without hypertrophic scar. Examinations of nervous system of the patients were found the same as that before surgery. Using Manual Muscle Testing (MMT), the average limb muscle strength of the patients was 4 before surgery and 4 after surgery, without change; Using the Ashworth assessment scale, the average preoperative and postoperative limb muscle tension in this group of patients was 1, without change; The Berg balance scale was used to evaluate the patient's balance function, with an average score of 42 before surgery and 42 after surgery, without any changes; There was no change in limb sensation before and after surgery; Using the MMSE, the average preoperative score and postoperative score of this group of patients were 25 points, without any change. Using the modified Barthel index scoring standard, the average preoperative score for this group of patients was 75 points, and the average postoperative score was 79 points, and the ADL of the patient had improved to various levels.Conclusion:Reconstruction of scalp defect with free ALTPF after revascularisation of moyamoya disease has obvious advantages, such as it closes the wound quickly, prevents infection and achieves a good appearance. This surgical procedure can produce a good clinical effect.

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.

Objective:To investigate the surgical method and clinical effect of one-stage repair of soft tissue defects of dorsum of hand and multiple fingers by using the polyfoliate conjoined anterolateral thigh perforator flap (ALTP) .Methods:From November, 2015 to September, 2019, 9 cases of soft tissue defects of dorsum of hand and multiple fingers were treated, including 8 males and 1 female. The average age was 32 years old. Causes of injury: 4 cases of thermal injury, 3 cases of strangulation injury, and 2 cases of traffic accident injury. Location of injury: 7 cases of right hand, 2 cases of left hand. Three cases of dorsum of hand with 1st-4th fingers, 3 cases with 2nd-5th fingers, 2 cases with 2nd-4th fingers, and 1 case with 3rd-5th fingers; All with bone, joint and tendon exposure. There were 6 cases with fracture or joint dislocation. All of them had no obvious defect of bone and joint. VSD was used to cover them after debridement. According to the shape and size of the wound, all flaps were designed to repair the soft tissue defect as the polyfoliate conjoined ALTP. The flap size was 7 cm×13 cm-12 cm×17 cm. Regular outpatient, telephone and Wechat follow-up were carried out to evaluate the flap survival, appearance, color elasticity, donor scar, sensory recovery, finger function recovery and patient satisfaction.Results:Nine cases of flap survived well. The average followed-up time was 12 (6-18) months. The postoperative followed-up revealed satisfactory shapes of the flaps, protective touch and recovery of functions. The donor site had good healing and no effect on function. In the last followed-up, according to the trial criteria for function evaluation of upper limbs by Chinese Society of Hand Surgery, 5 cases were excellent, 3 cases were good, and 1 case was fair. The hand function recovered well and returned to work and daily life on average 6 weeks after operation.Conclusion:The polyfoliate conjoined ALTP can repair the soft tissue defect of hand dorsum with multiple fingers at one stage, and the flap is in good shape. There is no need to divide the fingers. It is one of the ideal methods to repair the soft tissue defect of hand dorsum.

Objective To explore the value of gemstone spectral imaging (GSI)in quantitative evaluation of Lauren classification of gastric cancer.Methods Fifty-two patients with gastric cancer confirmed by gastroscopy underwent contrast-enhanced spectral CT imaging preoperatively.The monoergic and iodine-based images were obtained by GSI Viewer software,CT value and iodine concentration (IC)of the lesions were measured,and normalized iodine concentration (NIC)was calculated.With the reference of postoperative pathology,data were analyzed by LSD method of one-way analysis of variance.Results The IC,NIC,spectrum curve slope of 40-70 keV,40-140 keV and 70-140 keV energy range of intestinal type,mixed type and diffuse type carcinoma in the arterial phase were 12.86±6.80 (100 μg/mL),0.13±0.06 ,2.50±1.26 ,0.99±0.51 ,0.34±0.20 ,18.54±6.49 (100 μg/mL),0.19±0.07, 3.56±1.24,1.42±0.50,0.50±0.18 and 24.52±9.68 (100 μg/mL),0.24±0.09,4.73±1.76,1.90±0.73,0.68±0.29,respectively. The values of intestinal type were all significantly lower than those of diffuse type (P <0.05).Comparison between intestinal-mixed type and mixed-diffuse type,the other parameters were no significant differences except IC between intestinal-mixed type (P=0.037).Conclusion The slope of spectrum curve,iodine concentration,and normalized iodine concentration could be helpful for preoperative evaluation of Lauren classification of gastric cancer.

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.

Objective To evaluate in vivo tracking of swine mesenchymal stem cells (MSCs) la-beled with super paramagnetic iron oxide (SPIO) in intraportal transplantation by a clinical 1.5T MR.Methods MSCs were isolated from swine and cultured as well as expanded, which were then incuba-ted with SPIO (Feridex I. V.). Prussian blue staining was performed for showing intracelluar irons.To establish a swine model of acute liver necrosis, 0.5 g/kg of D-galactosamine was administrated to 10 pigs. MSCs(labeled cells in six, unlabeled cells in four)were injected into liver via portal veins. MR imaging was performed with a clinical 1.5T MR immediately before and at 6 h, 3 d, 7 d, 14 d after transplantation, respectively. Results Prussian blue staining of SPIO labeled MSCs could be effec-tively labeled and the labeling efficiency was almost 100%. Signal intensity loss in liver by SPIO labe-ling on FFE sequence persisted until 14 days after transplantation. Histological analysis by Prussian blue staining showed homing of labeled MSCs in liver after 14 days, primarily distributing in hepatic sinusoids and liver parenchyma. Conclusion MSCs can be labeled with SPIO in vitro successfully.MRI can monitor magnetically labeled MSCs transplanted into liver.