Long-term hypertension causes excessive vascular remodeling and leads to adverse cardiovascular events. Balance of ubiquitination and deubiquitination has been linked to several chronic conditions, including pathological vascular remodeling. In this study, we discovered that the expression of ubiquitin-specific protease 25 (USP25) is significantly up-regulated in angiotensin II (Ang II)-challenged mouse aorta. Knockout of Usp25 augments Ang II-induced vascular injury such as fibrosis and endothelial to mesenchymal transition (EndMT). Mechanistically, we found that USP25 interacts directly with Forkhead box O3 (FOXO3) and removes the K63-linked ubiquitin chain on the K258 site of FOXO3. We also showed that this USP25-mediated deubiquitination of FOXO3 increases its binding to light chain 3 beta isoform and autophagosomic-lysosomal degradation of FOXO3. In addition, we further validated the biological function of USP25 by overexpressing USP25 in the mouse aorta with AAV9 vectors. Our studies identified FOXO3 as a new substrate of USP25 and showed that USP25 may be a potential therapeutic target for excessive vascular remodeling-associated diseases.

Objective:To present the surgical details of manual double-layer suturing in patients with obesity combined type 2 diabetes mellitus by three-incision laparoscopic single-anastomosis duodenal-jejunal bypass with sleeve gastrectomy .Methods:Clinical data and follow-up information of 52 obesity combined type 2 diabetes mellitus patients (BMI 27.59-43.71 kg/m2) who underwent three-incision laparoscopic single-anastomosis duodenal-jejunal bypass with sleeve gastrectomy from Jan 2019 to Jul 2022 at Beijing Shijitan hospital were retrospectively analyzed.Results:The procedure was successful in all patients. The median operative time was 120 (90, 120) min, and the median intraoperative bleeding was 20.0 (10.0, 27.5) ml. No fistula or serious surgical complications were observed in the patients at 1 month postoperatively. Compared with the preoperative period, the patient's weight decreased [(93.22±15.21) kg vs. (69.97±11.06) kg, t=21.707, P<0.01], BMI decreased [(33.11±4.09) kg/m 2vs. (24.86±2.95) kg/m 2, t=23.224, P<0.01], and the patient's fasting glucose level decreased [9.52 (7.57, 12.96) mmol/L vs. 5.47 (4.66, 6.39) mmol/L, Z=6.11, P<0.01]. The remission rate of various obesity comorbidities was greatly improved. Conclusion:Under the condition of three-incision laparoscopy, the pure manual duodenal and jejunal double-layer suture method is safe, feasible, and effective for patients with obesity combined with type 2 diabetes mellitus.

ObjectiveTo explore the imbalance of paravertebral muscle group for patients with unilateral lumbar disc herniation. MethodsFrom January, 2022 to January, 2023, 30 patients with unilateral lumbar disc herniation (observation group) and 30 healthy people matching in general data (control group) were measured the tension and stiffness of multifidus and erector spinae with MyotonPRO, while the observation group was assessed with Visual Analogue Scale (VAS) for pain and Japanese Orthopaedic Association (JOA) score, and the time of disease was also recorded. ResultsThe mean of bilateral tension and hardness of multifidus and erector spinae was more in the observation group than in the control group (|t| > 5.407, P < 0.001), and the tension and hardness of multifidus and erector spinae of the affected side were more than those of the unaffected side in the observation group (|t| > 11.219, P < 0.001). The tension and hardness of multifidus and erector spinae of the affected side were positively correlated with VAS score (r > 0.942, P < 0.001), and negatively correlated with JOA score (|r| > 0.886, P < 0.001). ConclusionThe tension and hardness of multifidus and erector spinae of the affected side increase after unilateral lumbar disc herniation, resulting in asymmetry.

ObjectiveTo evaluate the inter-rater and test-retest reliability of echo intensity of ultrasound image for quality of quadriceps femoris in patients with knee osteoarthritis (KOA). MethodsFrom March to December, 2021, 33 patients with unilateral KOA in Guangdong Provincial Second Hospital of Traditional Chinese Medicine were included. Ultrasound was used to observe the cross sections of rectus femoris (RF), vastus medialis (VM) and vastus lateralis (VL), and the images were saved. Two independent raters analyzed the average gray value of the picture with the Image J. One of the raters repeated the measurement. The intra-class correlation coefficient (ICC), standard error of measurement (SEM), minimum detectable change (MDC) and coefficient of variation (CV) were calculated and the Bland-Altman charts were drawn. ResultsThe gray value was higher in the RF, VM and VL in the affected side than in the healthy side (t > 2.262, P < 0.05). The inter-rater reliability was excellent, with ICC 0.982 to 0.995, SEM 1.60 to 3.82, CV 1.49% to 5.90%, and MDC value 4.43 to 10.59. The test-retest reliability of the rater was excellent, with ICC 0.969 to 0.990, SEM 2.37 to 5.41, CV 2.22% to 4.84%, and MDC value 6.57 to 15.00. Bland-Altman charts analysis showed that the consistency was good. ConclusionThe quadriceps femoris muscle quality is different between the affected and the healthy sides in patients with unilateral KOA. It is reliable to evaluate muscle echo intensity by Image J.

Objective:To investigate the alterations of resting-state functional connectivity (RSFC) in ventral tegmental area (VTA) and substantia nigra (SN) among male smokers, and its correlation with clinical characteristics of smoking.Methods:The resting-state functional magnetic resonance data of 131 subjects recruited from January 2014 to December 2018 were analyzed retrospectively, including 76 smokers (smoking group) and 55 non-smokers (control group). VTA/SN was selected as regions of interest (ROI), and then calculated RSFC between VTA/SN and the whole brain.Based on SPM12 software, independent sample t-test was conducted to compare the differences in RSFC between smoking group and control group.Based on SPSS 22.0 software, Pearson correlation analysis was used to investigate the relationships between the RSFC of brain regions with significant differences and Fagerstr?m test for nicotine dependence (FTND) score, pack-year of smokers. Results:Compared with control group, the results showed decreased RSFC between VTA and the brain regions related default mode network (DMN)(including posterior cingulate cortex, right anterior cuneiform lobe, bilateral superior temporal gyrus, right middle temporal gyrus and right inferior parietal lobule), and regions of limbic system(including right marginal lobe and right angular gyrus), right calcarine (MNI: x, y, z=24, -55, -14) and left insula(MNI: x, y, z=-35, -11, 9) in smoking group(GRF corrected, voxel level P<0.005, cluster level P<0.05). Taking SN as the seed, there was no significant difference between smoking group and control group ( P>0.05). RSFC of VTA-left superior temporal gyrus was positively correlated with pack-year( r=0.243, P=0.034) and FTND ( r=0.282, P=0.014). VTA-left insula RSFC was positively correlated with FTND ( r=0.316, P=0.006). Conclusion:The RSFC in the mesolimbic system and the VTA-DMN circuit exist abnormal changes in smokers.To some extent, it may explain the reward deficits and dysfunction of emotion regulation in smokers, which may provide clues for further understanding the mechanism of tobacco addiction.

Objective:To fulfill the automatic radiolabeling of the norepinephrine transporter (NET) trancer 18F-meta-fluorobenzylguanidine (mFBG), and explore the 18F-mFBG PET/CT imaging effect of pheochromocytoma. Methods:On the basis of the chemical structure of mFBG, a spirocyclic iodonium ylide was used as the precursor to undergo a 3-step reaction sequence (radiofluorination, deprotection and neutralization) on AllinOne synthesis module. Purification by high performance liquid chromatography and formulation were conducted to generate 18F-mFBG. The corresponding quality control tests of 18F-mFBG product was performed. Afterwards, a postoperative patient with pheochromocytoma underwent 18F-mFBG PET/CT imaging. Results:The radiosynthesis was accomplished within 70 min, and 18F-mFBG was obtained in (17.8±2.4)% non-decay-corrected radiochemical yield ( n=5), with radiochemical purity >97% and molar activity >59.2 GBq/μmol. Sterility test, bacterial endotoxins test, abnormal toxicity test and the acetonitrile residue all met the requirements of Pharmacopoeia of the People′ s Republic of China (2020 Volume Ⅳ). The 18F-mFBG PET/CT imaging disclosed high uptake in pheochromocytoma and clear localization of lesions. Conclusions:The automatic radiolabeling of the NET targeted tracer 18F-mFBG is successfully realized by commercially available synthesis module, and the production quality meets all requirements for clinical translation. 18F-mFBG has a potential to image neuroendocrine lesions in clinical setting.

ObjectiveTo test the inter-tester reliability and test-retest reliability of MyotonPRO for evaluating neck and shoulder muscle performance parameters in patients with unilateral chronic neck pain, observe the difference of muscle performance between the healthy and affected sides of patients with chronic neck pain, and analyze the factors that cause the imbalance of muscle performance in patients with chronic neck pain. MethodsFrom January to June, 2023, 32 patients with unilateral chronic neck pain in Guangdong Second Traditional Chinese Medicine Hospital were selected. Two testers used the same MyotonPRO equipment to measure the muscle tone, muscle hardness and muscle elasticity on both sides of the sternocleidomastoid muscle and the upper trapezius muscle in the relaxed position. Tester 1 repeated the measurement after an interval of 30 minutes, and Tester 2 was measured within the time interval between the two measurements of Tester 1. The intraclass correlation coefficient (ICC), standard error of mean (SEM) and minimum detectable change (MDC) were calculated simultaneously. The measurement results were plotted into Bland-Altman diagram and systematic bias analysis was performed. The difference in muscle characteristics between the affected side and the healthy side was compared. At the same time, the Visual Analogue Scale (VAS) score and body mass index (BMI) of the subjects were collected for correlation analysis. ResultsExcept the sternocleidomastoid muscle elasticity of the affected side (ICC = 0.697), the inter-tester reliability of all other parameters was high to very high (ICC = 0.719 to 0.952, SEM = 0.04 to 6.53, MDC = 0.12 to 18.11). The test-retest reliability of all parameters was high (ICC = 0.883 to 0.981, SEM = 0.03 to 5.72, MDC = 0.09 to 15.84). Bland-Altman plot analysis showed that the scatter distribution was consistent. The muscle tone, muscle hardness and muscle elasticity of sternocleidomastoid muscle and upper trapezius muscle were higher on the affected side than on the healthy side (t > 2.846, P < 0.05). The asymmetry index of tension, hardness and elasticity of upper trapezius muscle and sternocleidomastoid muscle was significantly positively correlated with VAS score and BMI (r > 0.385, P < 0.05). ConclusionMyotonPRO has good inter-tester reliability and retest reliability in evaluating the muscle performance of both sides of patients with chronic neck pain. The muscle tone, muscle hardness and muscle elasticity of sternocleidomastoid muscle and upper trapezius muscle on the affected side were higher than on the healthy side, and the difference of muscle performance was positively correlated with pain and BMI.

Currently the main treatment of acute myeloid leukemia (AML) is chemotherapy combining hematopoietic stem cell transplantation. However, the unbearable side effect of chemotherapy and the high risk of life-threatening infections and disease relapse following hematopoietic stem cell transplantation restrict its application in clinical practice. Thus, there is an urgent need to develop alternative therapeutic tactics with significant efficacy and attenuated adverse effects. Here, we revealed that umbilical cord-derived mesenchymal stem cells (UC-MSC) efficiently induced AML cell differentiation by shuttling the neutrophil elastase (NE)-packaged extracellular vesicles (EVs) into AML cells. Interestingly, the generation and release of NE-packaged EVs could be dramatically increased by vitamin D receptor (VDR) activation in UC-MSC. Chemical activation of VDR by using its agonist 1α,25-dihydroxyvitamin D3 efficiently enhanced the pro-differentiation capacity of UC-MSC and then alleviated malignant burden in AML mouse model. Based on these discoveries, to evade the risk of hypercalcemia, we synthetized and identified sw-22, a novel non-steroidal VDR agonist, which exerted a synergistic pro-differentiation function with UC-MSC on mitigating the progress of AML. Collectively, our findings provided a non-gene editing MSC-based therapeutic regimen to overcome the differentiation blockade in AML.

Objective:To investigate the clinical efficacy of extreme lateral interbody fusion (XLIF) in comparison with traditional posterior lumbar fusion in the treatment of lumbar infectious diseases.Methods:A retrospective study was conducted to analyze the clinical data of 30 patients with lumbar infectious disease who had been treated at Department of Spinal Surgery, The Third Hospital of Hebei Medical University from May 2017 to November 2019. There were 18 males and 12 females with an age of (53.3 ± 12.5) years. According to surgical procedures, the patients were divided into group A of 13 cases subjected to XLIF and group B of 17 cases subjected to posterior radical debridement plus lumbar fusion plus internal fixation. The 2 groups were compared in terms of demographic data like age and gender, intraoperative indexes, intervertebral fusion rate, and complications, as well as visual analogue scale (VAS) and Oswestry disability index (ODI) at 3, 6, and 12 months after operation.Results:There was no statistically significant difference between the 2 groups in the general clinical data before operation, showing comparability ( P>0.05). The operation time in group A was significantly shorter than that in group B [(88.5 ± 13.6) min versus (124.1 ± 15.4) min], and the intraoperative blood loss in group A significantly less than that in group B [(66.9 ± 18.4) mL versus (461.8 ± 150.6) mL] ( P<0.05). The VAS and ODI at 3, 6, and 12 months after operation in both groups were significantly lower than those before operation ( P<0.05). The VAS and ODI at 3 months after surgery in group A [2 (2, 2) points and 15.2% ± 5.0%] were significantly lower than those in group B [3 (2, 3) points and 19.5% ± 6.2%] ( P<0.05). There was no significant difference in the fusion rate between groups A and B at 12 months after operation (13 versus 16) ( P>0.05). Postoperatively, left thigh numbness and weakness was reported in 1 case in group A while 2 cases of cerebrospinal fluid fistula and 1 case of poor wound healing were observed in group B, showing no significant difference in the incidence of complications between the 2 groups ( P>0.05). Conclusion:Compared with the traditional posterior lumbar surgery, XLIF demonstrates advantages of less intraoperative blood loss, less tissue damage, shorter operation time, faster postoperative recovery in the treatment of lumbar infectious diseases with no obvious intraspinal abscess or nerve compression.

Clinical data of a case of Epstein-Barr virus-associated smooth muscle tumor with non-human immunodeficiency virus/transplantation admitted in the Department of Nephrology and Rheumatology, Hunan Children′s Hospital in May 2020 were retrospectively analyzed.The 6 years and 7 months old girl presented with bilateral hip pain for more than 1 year.Imaging examination revealed multiple nodular lesions in the central nervous system and lungs.Arthritis was the first manifestation in this case, and as a result, the patient was misdiagnosed as juvenile idiopathic arthritis.Finally, the patient was pathologically diagnosed as Epstein-Barr virus-associated smooth muscle tumor, which was a rare tumor associated with immunosuppression.