1.USP25 ameliorates vascular remodeling by deubiquitinating FOXO3 and promoting autophagic degradation of FOXO3.
Yanghao CHEN ; Bozhi YE ; Diyun XU ; Wante LIN ; Zimin FANG ; Xuefeng QU ; Xue HAN ; Wu LUO ; Chen CHEN ; Weijian HUANG ; Hao ZHOU ; Gaojun WU ; Yi WANG ; Guang LIANG
Acta Pharmaceutica Sinica B 2025;15(3):1643-1658
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.
2.Quality control protocol for adult overweight and obesity screening in health management (examination) institutions (2025 edition)
Jianling FAN ; Tiejun WANG ; Pengfei YANG ; Keke DING ; Xiaoning HAO ; Sunfang JIANG ; Ankang LÜ ; Jianping LU ; Sheng RONG ; Weibin SHI ; Shengwei SUN ; Yan TAN ; Qilei TU ; Zhiping WANG ; Bing WANG ; Jianyun WANG ; Weijian WANG ; Yan WANG ; Qun XU ; Chenli ZHANG ; Fan ZHANG ; Ping ZHANG ; Yansong ZHENG ; Jieru ZHOU ; Dan CHEN ; Jiaoyang ZHENG
Chinese Journal of Clinical Medicine 2025;32(6):1097-1111
Obesity, as a chronic recurrent disease, has become a major public health challenge in China. To implement the requirements of the Healthy China Initiative (2019—2030), under domestic guidelines or consensus statements on overweight and obesity, and in alignment with the latest scientific advances globally, the Quality control protocol for adult overweight and obesity screening in health management (examination) institutions (2025 edition) was developed. This protocol was drafted by the Health Management Center of Shanghai Changzheng Hospital and formulated through multiple rounds of deliberation by experts in China’s health examination quality control field. The protocol establishes unified standards for screening facilities, personnel qualifications, and measurement or testing procedures. It defines specific screening items, outlines a standardized screening pathway, and sets requirements for the final medical review, ensuring the scientific validity, effectiveness, and safety of the screening process. The implementation of this protocol will enhance the consistency of weight management practices for adults across health examination institutions and strengthen the quality control of overweight and obesity screening programs.
3.Source and application of seed cells in bioartificial liver support system
Xuejing ZHU ; Weijian HUANG ; Hexin YAN
Journal of Clinical Hepatology 2024;40(2):246-251
So far, there are still no specific treatment methods for severe hepatitis and liver failure, resulting in a mortality rate of over 70%, and they are the difficulties in the treatment of critical illness in China and globally. Liver transplantation is currently the most effective treatment method for end-stage liver disease, but only 1% — 2% of patients can receive the opportunity for organ transplantation. The bioartificial liver support system utilizes external mechanical, physical, and biological devices to remove various harmful substances accumulated in the patient’s body, compensate for the metabolic functions of the liver, supplement necessary substances, improve internal environment, promote the recovery of liver function, help patients get through the critical period, and save time for liver transplantation, and therefore, it is considered one of the important methods for the treatment of end-stage liver disease. Since hepatocytes are the core element of bioartificial liver, this article summarizes the sources of liver seed cells, 3D culture methods, and corresponding bioreactor culture systems and hopes to gradually solve the core issue of large-scale in vitro preparation of hepatocytes to obtain hepatocytes with adequate quantity and quality, which urgently needs to be addressed in clinical application.
4.Loganin inhibits the ROS-NLRP3-IL-1β axis by activating the NRF2/HO-1 pathway against osteoarthritis
Miao LI ; Jiacong XIAO ; Baihao CHEN ; Zhaofeng PAN ; Fanchen WANG ; Weijian CHEN ; Qi HE ; Jianliang LI ; Shaocong LI ; Ting WANG ; Gangyu ZHANG ; Haibin WANG ; Jianfa CHEN
Chinese Journal of Natural Medicines (English Ed.) 2024;22(11):977-990
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.
5.Impact of residual cholesterol on the progression of arteriosclerosis in individuals receiving physical examination
Zhaoqin DONG ; Fuliang YI ; Yujuan YING ; Weijian MAO ; Yuanfang ZHU ; Yang GAO ; You YOU
Chinese Journal of Health Management 2024;18(9):686-692
Objective:To investigate the impact of residual cholesterol (RC) on the progression of arteriosclerosis in individuals receiving physical examination.Methods:A cross-sectional study. Participants aged 18 years and above who underwent arteriosclerosis testing at the Health Management Center of Zigong Fourth People′s Hospital from January to December 2023 were selected as the subjects of the study. A total of 9 016 subjects were included in this study, of whom 6 213 were considered to have arteriosclerosis. The physical examination conclusions, basic information (age, gender, body mass index, waist circumference, blood pressure, history of hypertension, history of smoking and drinking), and biochemical indicators (lipids, fasting blood glucose, liver and kidney function) were extracted in those individuals. Based on the examination results, the subjects were categorized into arteriosclerosis and normal groups. The RC levels of the participants were calculated using a formula and then the subjects were categorized into binary and quartile RC groups. Additionally, four regression models were used to analyze the impact of RC levels on the progression of arteriosclerosis while adjusting for various confounding factors.Results:The RC level was (0.63±0.44) mmol/L in the normal group and (0.76±0.61) mmol/L in the arteriosclerosis group. Based on level of RC, the normal group was divided into two subgroups: 652 individuals with elevated RC level and 2 241 with normal RC level. In the arteriosclerosis group, there were 2 069 individuals with elevated RC level and 4 144 with normal RC level. Grouped according to quartiles of RC level, the number of individuals with RC in the Q1-Q4 interval in the normal group was 838 (28.97%), 752 (25.99%), 760 (26.27%), and 543 (18.77%), respectively, showing a gradual decreasing trend. The number of individuals with RC in the Q1-Q4 interval in the arteriosclerosis group was 1 414 (22.76%), 1 438 (23.15%), 1 589 (25.58%), and 1 771 (28.51%), respectively, showing a gradual increasing trend. The difference between the groups was statistically significant ( P<0.05). After adjusting for various factors by four regression models, it was found that elevated RC levels increased the risk of arteriosclerosis progression, with a odds ratio ( OR) of 1.381, 1.242, 1.233, and 1.214, respectively. Additionally, individuals in the Q4 RC level quartile had 1.502, 1.318, 1.311, and 1.284-times higher risk of arteriosclerosis progression when compared to those in the Q1 quartile. Conclusion:The impact of RC on the progression of arteriosclerosis tend to stabilize and remain consistent, indicating that elevated RC is an independent risk factor for the progression of arteriosclerosis.
6.Value of synthetic MRI in the differential diagnosis of parotid gland tumors
Zanxia ZHANG ; Shujian LI ; Yong ZHANG ; Weijian WANG ; Manli SONG ; Wenhao WANG ; Baohong WEN ; Jingliang CHENG
Journal of Practical Radiology 2024;40(3):361-364
Objective To investigate the application value of quantitative relaxation parameters based on synthetic MRI technology in the differential diagnosis of parotid gland tumors.Methods Conventional MRI and synthetic MRI data of 59 patients with patho-logically confirmed parotid gland tumors were analyzed retrospectively.T1,T2,and proton density(PD)values of the tumor were extracted from T1,T2 and PD mapping.The differences in quantitative relaxation parameters of pleomorphic adenomas,Warthin tumors,and malignant tumors were further compared.Diagnostic performance of each quantitative relaxation parameter was assessed and com-pared via receiver operating characteristic(ROC)curve and DeLong test.Results T2 value was significantly higher in pleomorphic adenomas than that in malignant tumors(P<0.05).The T1,T2,and PD values of pleomorphic adenomas and malignant tumors were significantly higher than those of Warthin tumors(P<0.05).The area under the curve(AUC)of the T2 value in differentia-ting pleomorphic adenomas from malignant tumors was 0.794.The AUC for T1 value(0.939)in differentiating Warthin tumors from malignant tumors was significantly higher than that of T2(0.873,P=0.341)and PD(0.927,P=0.891)values,without sta-tistically significant difference.The AUC for T2 value(0.968)in differentiating pleomorphic adenomas from Warthin tumors was significantly higher than that of T1(0.931,P=0.360)and PD(0.876,P=0.120)values,without statistically significant difference.Conclusion Quantitative relaxation parameters based on synthetic MRI technology may contribute to differentiating pleomorphic adenomas,Warthin tumors,and malignant tumors of the parotid gland.
7.Multi spiral CT findings of intraductal papillary neoplasm of the bile duct and its benign and malignant differentiation
Zhaoxia ZHOU ; Jianhua WANG ; Weijian ZHOU ; Xiuchao HE
Journal of Practical Radiology 2024;40(3):398-401
Objective To investigate the multi spiral computed tomography(MSCT)characteristics of intraductal papillary neo-plasm of the bile duct(IPNB)and to distinguish the benign and malignant ones.Methods The MSCT and clinical data of 23 patients with IPNB confirmed by pathology were analyzed retrospectively.According to the pathology,they were divided into benign and malignant groups,including 12 cases of benign group(7 cases with low to medium grade intraepithelial neoplasia,and other 5 cases with high grade intraepithelial neoplasia)and 11 cases of malignant group with invasive carcinoma.All patients underwent plain and tri-phasic enhanced CT scans of upper abdomen.The enhanced scan included arterial phase,portal phase and delayed phase.The location,size,growth mode,enhancement type,invasion and metastasis,bile duct manifestations and bile duct stones were analyzed.Independent sample t-test was used to count the transverse diameter,longitudinal diameter and aspect ratio of tumor.Chi square test was used to compare the difference in other parameters between benign and malignant groups.Results There were no significant differences between benign and malignant IPNB groups in the location of the disease,the transverse diameter of the tumor,the dilatation of the bile duct and the presence of the stones(P>0.05).However,the significant differences in tumor growth mode,tumor longitudinal diameter and aspect ratio,enhancement type,invasion of bile duct wall and bile duct truncation were found(P<0.05).Conclusion Benign IPNB is common,while the IPNB with diffuse growth,progressive enhancement,invasion of bile duct wall and extrabiliary structures,and distant metastasis may indicate malignance,and the final diagnosis depends on the pathology.
8.Application of autologous dentin particles combined with PRF in tooth extraction site preservation:A case report
Hanying LIANG ; Weijian ZHONG ; Guowu MA
Journal of Practical Stomatology 2024;40(1):128-130
Undicalcified autologous dentin particles(UADP)combined platelet rich fibrin(PRF)were used in a case after extraction of the left mandibular second molar for tooth extraction site preservation.CBCT images at 3,9 and 24 months after operation showed that the bone mass maintenance effect was obvious.Histological sections showed a large number of new bone formation around dentin particles.
9.Landmark Achievements in Treating Solid Tumors with Immune Checkpoint Inhibitors
The Journal of Practical Medicine 2024;40(2):272-277
Tumor metastasis is a primary cause of death among solid tumor patients.Interventions such as chemotherapy with cytotoxic drugs and other targeted therapies focusing on specific genes or tumorigenesis can induce tumor shrinkage in most cases.However,these interventions do not substantially prolong the lives of patients.In recent years,immunotherapy has made significant breakthroughs in treating solid tumors with the introduction of immune checkpoint inhibitors(ICIs),following the clinical use of Ipilimumab,the first anti-tumor drug with ICIs initially approved in 2011.Currently,four types of ICIs including CTLA-4,PD-1,PD-L1,and LAG3 have been clinically applied and have demonstrated specificity towards more than 20 types of solid tumors.The significance of ICIs lies in their superiority to conventional drugs in three aspects:(1)They can prolong the survival of late-stage patients and even achieve"clinical cure";(2)They allow patients with rare tumors access a pan-tumor treatment based on specific biomarkers;and(3)They can free a majority of patients from invasive surgical approaches to preserve organ functions,thereby improving patient's quality of life.This article provides a summary of multiple clinical research projects and explores the clinical evidence derived from the notable achievements related to the three advantages.
10.Effect of individualized PEEP regulated by driving pressure on infant one-lung ventilation during thoracic surgery
Weijian HUANG ; Yang LI ; Haiyan WANG ; Jing LIU ; Hui LUO ; Zurong HU
The Journal of Practical Medicine 2024;40(3):360-364
Objective To explore the effect of protective ventilation strategies based on individualized positive end expiratory pressure(PEEP)regulated by driving pressure(Pd)in infants under OLV.Methods Sixty infants undergoing elective thoracoscopic surgery were randomly divided into the control group and driving pressure group,with 30 cases in each group.The two groups were compared in terms of MAP,HR,tidal volume(Vt),PEEP,Pd,airway peak pressure(Ppeak),and static lung compliance(Cs),and arterial blood gas during OLV before the artificial pneumothorax(T0),10 min(T1),30 min(T2),and 60 min(T3)after the artificial pneumothorax,and right at the end of the artificial pneumothorax(T4).Results There were no significant differences in MAP,HR,and Vt between the two groups at all the time points(P>0.05).Both groups showed the increase in Pd and Ppeak and decresase in Cs at T1,T2,and T3(all P<0.05).PaO2 and OI in both group were decreased and PaCO2 was increased at T2(all P<0.05).Compared with the control group,the driving pressure group presented lower Pd and Ppeak,higher PEEP and Cs at T1,T2,and T3(P<0.05),and higher PaO2 and OI(P<0.05)and no significant differences in PaCO2 and FiO2 at T2(P<0.05).The rate of rescue ventilation during OLV was lower in the driving pressure group(2 cases)than in the control group(9 cases)(6.9%versus 32.4%,P<0.05).There was no significant difference in the inci-dence of postoperative complications between the two groups(P<0.05).Conclusion The individualized positive end expiratory pressure(PEEP)regulated by Pd can optimize the PEEP settings upon infant individuals under OLV and improve the compliance and oxygenation of ventilated lung.

Result Analysis
Print
Save
E-mail