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.

Loganin(LOG),a bioactive compound derived from Cornus officinalis Siebold & Zucc,has been understudied in the context of osteoarthritis(OA)treatment.In this study,we induced an inflammatory response in chondrocytes using lipopolysaccharide(LPS)and subsequently treated these cells with LOG.We employed fluorescence analysis to quantify reactive oxygen species(ROS)levels and measured the expression of NLRP3 and nuclear factor erythropoietin-2-related factor 2(NRF2)using real-time quantitative polymerase chain reaction(qRT-PCR),Western blotting,and immunofluorescence(IF)techniques.Additionally,we developed an OA mouse model by performing medial meniscus destabilization(DMM)surgery and monitored disease progression through micro-com-puted tomography(micro-CT),hematoxylin and eosin(H&E)staining,safranin O and fast green(S&F)staining,and immunohisto-chemical(IHC)analysis.Our results indicate that LOG significantly reduced LPS-induced ROS levels in chondrocytes,inhibited the activation of the NLRP3 inflammasome,and enhanced NRF2/heme oxygenase 1(HO-1)signaling.In vivo,LOG treatment mitigated cartilage degradation and osteophyte formation triggered by DMM surgery,decreased NLRP3 expression,and increased NRF2 expres-sion.These findings suggest that LOG has a protective effect against OA,potentially delaying disease progression by inhibiting the ROS-NLRP3-IL-1β axis and activating the NRF2/HO-1 pathway.

Ginger mainly contains two main categories of volatile and non-volatile components,of which the non-volatile gingerol is a general term for pungent substances in ginger,mainly containing gingerols,shogaols and other components,with a wide range of pharmacological effects.By reviewing the 2020 edition of the Pharmacopoeia of the People's Republic of China and related literature in Chinese databases such as CNKI and Wanfang,it was found that the use of the Chinese names of gingerols and shogaols was confusing,which caused certain troubles to readers and obstacles to academic exchanges.According to the naming principles of Chinese medicinal extracts,it is suggested that gingersols,6-gingerol,8-gingerol and 10-gingerol should be uniformly named as gingerols(姜酚类),6-gingerol(6-姜酚),8-gingerol(8-姜酚)and 10-gingerol(10-姜酚),respectively,and shogaols and 6-shogaol should be uniformly named as shogaols(姜烯酚类)and 6-shogaols(6-姜烯酚).The standardized use of the Chinese names of gingerols and shogaols will facilitate in-depth research and academic exchange on ginger,dried ginger,baked ginger and other ginger herbal medicines.

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.

Objective:To explore the feasibility of applying BOPPPS (B-bridge in, O-objective, P-pre-assessment, P-participatory learning, P-post-assessment, S-summary) course design mode in the teaching of internal medicine practice for nursing undergraduates.Methods:A total of 73 nursing interns of Kunming Medical University were selected as subjects and divided into the experimental group ( n=30) and the control group ( n=43). The experimental group adopted the practice teaching method based on BOPPPS model, while the control group adopted the traditional teaching method. Students' evaluation was collected by questionnaire. The students' comprehensive reasoning ability, holistic nursing skills ability and clinical nursing evaluation ability were evaluated by taking out questions from the question bank. And the results of teachers' evaluation on the participation of case study and problem solving in the process of students' internship were collected. SPSS 20.0 was used for t-test. Results:The students' evaluation of the practice process in the experimental group (86.81±2.85) was significantly better than that in the control group (82.61±3.82) ( P<0.001). The experimental group was significantly better than the control group in comprehensive reasoning of clinical thinking and assessment of holistic nursing ability ( P <0.001). Teachers' evaluation in the experimental group was better than that in the control group ( P <0.05). The overall effect of the experimental group (20.60±1.73) was significantly better than that of the control group (17.84±1.70) ( P <0.001). Conclusion:BOPPPS mode is helpful for teachers to carry out and demonstrate holistic nursing teaching with symptoms as the core according to the overall teaching objectives of nursing internal medicine, optimize the time arrangement and knowledge structure, improve the practice efficiency, and promote the establishment of holistic nursing thinking mode of students.

Objective:To investigate the feasibility and efficacy of distal arc-shaped incision of lunula combined with nail template replantation for the treatment of subungual glomus tumor.Methods:The clinical data with subungual glomus tumor treated in the Department of Orthopedics of First Affiliated Hospital of the University of Science and Technology of China from March 2019 to June 2021 were retrospectively analyzed. Each patient removed the nail, the nail bed was cut into by a distal arc-shaped incision of the lunula. After the tumor was exposed, the tumor was resected completely, the nail bed flap was reduced in situ without suturing. The nail template was made by using the 5 ml syringe barrel or the original nail and poked the drainage holes in it, then the nail template was covered on the nail bed surface, three-point suturing and pressurized fixation, routine dressing change, and the nail template was removed 3 weeks after the procedure. The visual analogue scale (VAS) of pain was recorded preoperative and one month after the operation, and nail bed healing, pain improvement, nail growth, and tumor recurrence were observed. VAS scores before and after surgery were expressed as M( Q1, Q3), and analyzed by Mann-Whitney U test, P<0.05 was considered statistically significant. Results:A total of 37 patients were enrolled, including 5 males and 32 females. The age ranged from 18 to 67 years old, with an average of 39 years old. All patients were confirmed as subungual glomus tumors by postoperative pathology, they were followed up for 6 to 36 months, with an average of 22 months. All of the patients had no obvious pain during the dressing change, after removing the nail template, the nail bed was flat and dry, and no obvious scar formation was found. All postoperative incisions were healed in one stage, the new nail recovered smoothly with a satisfactory appearance, the pain symptoms disappeared completely, and also no recurrence occurred during follow-up. The preoperative VAS score was 5.0 (4.5, 6.0), the VAS score one month after the operation was 0.0 (0.0, 0.0), and the difference was statistically significant ( Z=-7.57, P<0.001). Conclusion:The distal arc-shaped incision of the lunula for the treatment of subungual glomus tumor can effectively protect the germinal matrix of the nail bed, with sufficient tumor exposure, complete resection, and low recurrence rate. At the same time, combined with nail template replantation can significantly reduce nail bed scar formation and effectively prevent postoperative nail deformity. The method is simple, easy to operate, and has significant clinical efficacy.

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 explore the potential mechanism of Wuse Peiyuan Guben Decoction in treating chronic kidney disease-protein energy wasting(CKD-PEW). METHODS The CKD-PEW model on rats was established by using a 5/6 nephrectomy and low protein diet. Widely targeted metabolomics technology was employed for the serum metabolomics analysis on rats to identify differential metabolites and their corresponding targets, whereas network pharmacology method was utilized to predict the key chemical compositions, targets, and metabolic pathways of Wuse Peiyuan Guben Decoction in treating CKD-PEW. Furthermore, the common targets discovered using the integrated serum metabolomics and network pharmacology analysis were leveraged to construct the component-target-metabolite-pathway network, which presented the main effective chemical compositions and metabolic mechanisms of Wuse Peiyuan Guben Decoction in treating CKD-PEW. RESULTS There were 123 different metabolites between the blank group and the model group, and 50, 37, 62, and 114 different metabolites in the model group compared with the positive control compound α-ketoacid tablets, low, medium, and high dosage Wuse Peiyuan Guben Decoction groups, respectively. There were 25 potential biomarkers enriched in the metabolic pathway between the blank group and the model group by Metabo Analysis, and 2, 2, 5 and 24 potential biomarkers in the model group and the positive control compound α-ketoacid tablets, low, medium and high dosage Wuse Peiyuan Guben Decoction groups, respectively. There were 21 enriched metabolic pathways with 194 targets between the blank group and the model group, and 2 pathways with 14 targets, 2 pathways with 14 targets, 5 pathways with 38 targets, and 24 pathways with 52 targets between the model group and positive control compound α-ketoacid tablets, low, medium and high dose groups, respectively. There were 65 active pharmaceutical ingredients and 123 important targets identified by the network pharmacology analysis. The integrated serum metabolomics and network pharmacology analysis results presented that four common targets: myeloperoxidase, UDP-glucuronosyltransferases, tyrosinase, and paraoxonase-1, were regulated by the four compositions, beta-sitosterol, quercetin, naringenin, salidroside in Wuse Peiyuan Guben Decoction to impact the key biomarkers, 2-hydroxybutanoic acid, hydroquinone, 2-phenylacetamide, and dopaquinone, thereby to affect the metabolic pathways of phenylalanine, propanoate, and tyrosine to finally treat CKD-PEW. CONCLUSION The pathogenesis of CKD-PEW is associated with multiple targets and metabolic pathways, and this study has elaborated on the key effective chemical compositions and metabolic mechanisms of Wuse Peiyuan Guben Decoction in treating CKD-PEW, hopefully providing a solid theoretical and experimental foundation for medical treatment of CKD-PEW.

Objective:To investigate the feasibility and efficacy of distal arc-shaped incision of lunula combined with nail template replantation for the treatment of subungual glomus tumor.Methods:The clinical data with subungual glomus tumor treated in the Department of Orthopedics of First Affiliated Hospital of the University of Science and Technology of China from March 2019 to June 2021 were retrospectively analyzed. Each patient removed the nail, the nail bed was cut into by a distal arc-shaped incision of the lunula. After the tumor was exposed, the tumor was resected completely, the nail bed flap was reduced in situ without suturing. The nail template was made by using the 5 ml syringe barrel or the original nail and poked the drainage holes in it, then the nail template was covered on the nail bed surface, three-point suturing and pressurized fixation, routine dressing change, and the nail template was removed 3 weeks after the procedure. The visual analogue scale (VAS) of pain was recorded preoperative and one month after the operation, and nail bed healing, pain improvement, nail growth, and tumor recurrence were observed. VAS scores before and after surgery were expressed as M( Q1, Q3), and analyzed by Mann-Whitney U test, P<0.05 was considered statistically significant. Results:A total of 37 patients were enrolled, including 5 males and 32 females. The age ranged from 18 to 67 years old, with an average of 39 years old. All patients were confirmed as subungual glomus tumors by postoperative pathology, they were followed up for 6 to 36 months, with an average of 22 months. All of the patients had no obvious pain during the dressing change, after removing the nail template, the nail bed was flat and dry, and no obvious scar formation was found. All postoperative incisions were healed in one stage, the new nail recovered smoothly with a satisfactory appearance, the pain symptoms disappeared completely, and also no recurrence occurred during follow-up. The preoperative VAS score was 5.0 (4.5, 6.0), the VAS score one month after the operation was 0.0 (0.0, 0.0), and the difference was statistically significant ( Z=-7.57, P<0.001). Conclusion:The distal arc-shaped incision of the lunula for the treatment of subungual glomus tumor can effectively protect the germinal matrix of the nail bed, with sufficient tumor exposure, complete resection, and low recurrence rate. At the same time, combined with nail template replantation can significantly reduce nail bed scar formation and effectively prevent postoperative nail deformity. The method is simple, easy to operate, and has significant clinical efficacy.