1.Deubiquitinase JOSD2 alleviates colitis by inhibiting inflammation via deubiquitination of IMPDH2 in macrophages.
Xin LIU ; Yi FANG ; Mincong HUANG ; Shiliang TU ; Boan ZHENG ; Hang YUAN ; Peng YU ; Mengyao LAN ; Wu LUO ; Yongqiang ZHOU ; Guorong CHEN ; Zhe SHEN ; Yi WANG ; Guang LIANG
Acta Pharmaceutica Sinica B 2025;15(2):1039-1055
Inflammatory bowel disease (IBD) is a chronic inflammatory disorder of the gastrointestinal tract, which increases the incidence of colorectal cancer (CRC). In the pathophysiology of IBD, ubiquitination/deubiquitination plays a critical regulatory function. Josephin domain containing 2 (JOSD2), a deubiquitinating enzyme, controls cell proliferation and carcinogenesis. However, its role in IBD remains unknown. Colitis mice model developed by dextran sodium sulfate (DSS) or colon tissues from individuals with ulcerative colitis and Crohn's disease showed a significant upregulation of JOSD2 expression in the macrophages. JOSD2 deficiency exacerbated the phenotypes of DSS-induced colitis by enhancing colon inflammation. DSS-challenged mice with myeloid-specific JOSD2 deletion developed severe colitis after bone marrow transplantation. Mechanistically, JOSD2 binds to the C-terminal of inosine-5'-monophosphate dehydrogenase 2 (IMPDH2) and preferentially cleaves K63-linked polyubiquitin chains at the K134 site, suppressing IMPDH2 activity and preventing activation of nuclear factor kappa B (NF-κB) and inflammation in macrophages. It was also shown that JOSD2 knockout significantly exacerbated increased azoxymethane (AOM)/DSS-induced CRC, and AAV6-mediated JOSD2 overexpression in macrophages prevented the development of colitis in mice. These outcomes reveal a novel role for JOSD2 in colitis through deubiquitinating IMPDH2, suggesting that targeting JOSD2 is a potential strategy for treating IBD.
2.Clinical features of critically ill pregnant and parturient women infected with chronic hepatitis B virus: An analysis of 41 cases
Yuhao JU ; Wen LI ; Yu WANG ; Lingyan XIAO ; Yishan ZHENG ; Guorong HAN
Journal of Clinical Hepatology 2024;40(2):258-263
ObjectiveTo investigate the clinical features and outcomes of critically ill pregnant and parturient women with chronic hepatitis B virus (HBV) infection, and to provide clinical experience for the rescue of critically ill pregnant and parturient women and the prevention and treatment of the severe exacerbation of liver disease. MethodsA total of 41 pregnant and parturient women with chronic HBV infection who were admitted to Department of Critical Care Medicine, Nanjing Second Hospital, from March 2013 to March 2023 were enrolled in this study, and their clinical data were collected through the electronic medical record system of hospital to summarize the main causes of transfer to the intensive care unit (ICU), the causes of death, and treatment. The independent-samples t test was used for comparison of normally distributed continuous data between two groups, and the Mann-Whitney U test was used for comparison of non-normally distributed continuous data between two groups. The chi-square test was used for comparison of categorical data between two groups. ResultsAmong the 41 patients, 13 (31.71%) did not receive regular antenatal examination and 8 (19.51%) with a high viral load (HBV DNA ≥2×105 IU/mL) did not receive antiviral therapy. Cesarean section was the main mode of delivery in 32 patients (78.05%); 23 patients (56.10%) had premature delivery, and 5 patients died (12.20%). The top three causes of transfer to the ICU were liver failure, postpartum hemorrhage, and hypertensive disorders of pregnancy. Liver failure mainly occurred in late pregnancy, with hepatic encephalopathy as the most common complication (28.57%) and intrahepatic cholestasis of pregnancy as the most common comorbidity (21.43%); among the 14 patients with liver failure, 6 (42.86%) received regular antenatal examination, and 13 (92.86%) did not receive antiviral therapy before admission. The mean length of ICU stay was 3.31±1.65 days for the patients with postpartum hemorrhage, among whom the patients with severe liver disease had coagulation disorders before delivery, which were difficult to correct after 48 hours of treatment. ConclusionPregnant and parturient women with chronic HBV infection tend to have complex conditions and a relatively high mortality rate. For pregnant and parturient women with chronic HBV infection, assessment of liver status, regular antenatal examination, and timely antiviral therapy are of vital importance to reduce severe exacerbation and mortality rate.
3.Protective effect of Humanin on rotenone-induced dopamine neuron toxicity
Yaohui SHAN ; Qifu ZHANG ; Jin CHENG ; Feng YE ; Xi ZHANG ; Wenpei YU ; Xiaogang WANG ; Yuanpeng ZHAO ; Guorong DAN ; Mingliang CHEN ; Yan SAI
Journal of Army Medical University 2024;46(7):670-677
Objective To investigate the mechanism and protective effect of Humanin(HN)on rotenone(Rot)-induced toxic damage for dopamine neurons.Methods The Rot-poisened PC12 cell model was constructed,and the control group,the Rot poisening group,the HN pretreated Rot poisening group,and the HN treatment group were set up.ELISA was used to detect the content of HN inside and outside of Rot-infected cells,CCK-8 assay was used to detect cell viability,and ATP detection kit was used to detect the intracellular ATP content.Dichloro-dihydro-fluorescein diacetate(DCFH-DA)assay was used to detect the level of reactive oxygen species(ROS)in cells.Western blotting was performed to detect the expression level of mitochondrial autophagy regulatory proteins Pink1,Parkin,p62,LC3,mitochondrial biogenesis regulatory protein PGC1α,division/fusion regulatory proteins OPA1,MFN2,DRP1,p-DRP1 and antioxidant stress regulatory proteins Keap1 and Nrf2.HBAD-mcherry-EGFP-LC3 adenovirus transfected cells was used to observed the number of autophagosomes and autophagolysosomes.Results The results showed that the intracellular concentration of HN in PC12 in the Rot poisening group was significantly higher than that in the control group(P<0.05);Compared with the control group,the Rot poisening group had significantly decreased activity of PC12 cells,decreased ATP content and increased production of ROS.After the poisen of Rot in PC12 cells,the expression of Pink1 and p-Parkin,the ratio of LC3Ⅱ/LC3Ⅰ and the expression of p-DRP1 in mitochondrial fusion protein was increased,while the expression of p62,the expression of mitochondrial biogenesis protein PGC1 α,mitochondrial fusion proteins MFN2 and OPA1,and antioxidant stress proteins Keap1 and Nrf2 were decreased(all P<0.05).The number of autophagosomes and autophagolysosomes in PC12 cells in the Rot poisening group was higher than that in the control group(P<0.05),and HN pretreatment(20 μmol/L)could significantly improve the changes mentioned above caused by Rot poisening(P<0.05).Conclusion HN ameliorates Rot-induced toxic damage for dopamine neurons by inhibiting mitophagy and mitochondrial division and promoting mitochondrial biogenesis and fusion,and anti-oxidative stress.
4.Establishment and application of measurement range of main blood quality indicators in provincial blood stations
Zixuan ZHANG ; Ying CHANG ; Xiaotong ZHANG ; Qingming WANG ; Yuan ZHANG ; Yue LIU ; Qinghua TIAN ; Ka LI ; Guorong LI ; Lixia CHEN ; Junhua SUN ; Yu KANG ; Pingchen HAN ; Xinyu ZHAO ; Song LI
Chinese Journal of Blood Transfusion 2024;37(8):918-926
Objective To obtain the monitoring measurement range of quality indicators of red blood cells,plasma and derivatives and leukocyte-reduced apheresis platelets provided by blood stations in Hebei province,explore the distribution of monitoring values and the change of monitoring level,so as to further strengthen the homogenization construction of quality control laboratories in blood stations in Hebei.Methods In 2023,the sampling data of 12 blood stations in Hebei from 2015 to 2022 were collected,scatter plots were made and the range markers were set,and the"mean±SD"line was taken as the upper limit and lower limit of the measurement range.In 2024,the monitoring values in 2023 were added,and the changes of two measurement ranges were compared to analyze the stability and overall level.Results Comparison of the measurement range from 2015 to 2022 and the measurement range from 2015 to 2023 showed that the standard deviation of the content of deleukocyte suspension of red blood cells-hemoglobin,washed erythrocyte-hemoglobin,washed erythrocyte-su-pernatant protein,cryoprecipitate coagulation factor-FⅧ,fresh frozen plasma-FⅧ,leukocyte-reduced apheresis platelets-leukocyte residue and leukocyte-reduced apheresis platelet-red blood cell concentration decreased from 8.132 to 7.993,6.252 to 6.104,0.273 to 0.267,57.506 to 56.276,0.920 to 0.892,0.653 to 0.644 and 2.653 to 2.603,respectively.The narrowing of the standard deviation range of the above items led to more concentrated monitoring values and reduced disper-sion.Comparison of the measurement range from 2015 to 2022 and the measurement range from 2015 to 2023 showed that the mean value of leukocyte residue of the deleukocyte suspension of red blood cells,hemoglobin content of the wash eryth-rocyte,protein content of supernatant of the wash erythrocyte,hemolysis rate of the wash erythrocyte,FⅧ content of the cryoprecipitate coagulation factor,plasma protein content of the fresh frozen plasma,FⅧ content of the fresh frozen plasma,platelet content of the leukocyte-reduced apheresis platelets changed from 0.362 to 0.476,44.915 to 44.861,0.280 to 0.283,0.137 to 0.142,133.989 to 133.271,60.262 to 60.208,1.301 to 1.277 and 3.036 to 3.033,respectively,and was closer to the national standard line,which reflects an increase in the number of unqualified monitoring values or values close to the national standard line in 2023.The long-term qualified rate of coagulation items was low,and no improvement has been ob-served.The stability of biochemical items has been enhanced but overall deviation has occurred,with the average value close to the national standard line.The possibility of subsequent testing failure has increased.The counting items showed no obvi-ous common characteristics.Conclusion The use of"mean±SD"in the analysis can visually display the distribution of mo-nitoring values of different items in Hebei,forming an indicator measurement range covering the past nine years.It shows the characteristics of each item,and provides reference for subsequent quality control laboratory data analysis of each blood sta-tions to takes active measures to improve the monitoring level.
5.Fetal facial ultrasound plane recognition based on real-time object detection network and its application
Zhonghua LIU ; Weifeng YU ; Xiuming WU ; Hao XUE ; Guorong LÜ ; Xiaoli WANG ; Peizhong LIU
Chinese Journal of Medical Physics 2024;41(2):247-252
Objective To explore the role of an artificial intelligence(AI)model based on real-time object detection network in fetal facial ultrasound examination.Methods With the normal fetal facial ultrasound standard plane(FFUSP)at 20-24 weeks of gestation as the research object,a FFUSP recognition model based on real-time object detection network was constructed.The recognition accuracy of the model for FFUSP and the anatomical structures were analyzed,and the clinical value was evaluated by analyzing its performance in identifying FFUSP in 119 cases of fetal ultrasound images.Results The overall precision,recall rate,mAP@.5 and mAP@.5:.95 of the AI model were 97.8%,98.5%,98.1%and 61.0%,respectively.The clinical validation showed that the AI model had a sensitivity,specificity,positive predictive value,negative predictive value and accuracy of 100.0%,98.5%,87.4%,100.0%and 98.7%for facial anatomy recognition,and the results were highly consistent with the classification of fetal ultrasound experts(k=0.925,P<0.001).The recognition accuracy of the model for 3 types of standard planes reached 100%;and the average speed of dynamic video detection was 33.93 frames per second.Conclusion The FFUSP recognition model based on real-time object detection network exhibits excellent performance,and it can be applied to real-time ultrasound diagnosis,teaching and intelligent quality evaluation.
6.Research progress of suffering assessment tools for palliative care patients
Mengke CAO ; Benyan ZHANG ; Guorong LI ; Jing GAO ; Yu WANG ; Xinming DONG ; Cuiping XU
Chinese Journal of Practical Nursing 2023;39(2):157-161
Suffering is prevalent in the palliative care population and is an important factor affecting the quality of life of palliative care patients and their family caregivers. In this paper, we review the assessment content, measurement methods, current application status and advantages and disadvantages of suffering assessment tools for palliative care patients, analyze the problems of current suffering assessment tools for palliative care patients and make suggestions, aiming to provide reference for palliative suffering treatment in China.
7.Extraction of effective components of Psoralea corylifolia and efficacy evaluation in the treatment of vitiligo
Xuemei YU ; Zhenghua WU ; Guorong FAN
China Pharmacy 2023;34(14):1676-1680
OBJECTIVE To extract the effective components of Psoralea corylifolia and evaluate its efficacy in the treatment of vitiligo. METHODS The concentrations of psoralen, isopsoralen, neobavaisoflavone, corylin, psoralidin, corylifolinin, and bakuchiol in P. corylifolia extract were determined by ultra-performance liquid chromatography. Based on the analytic hierarchy process (AHP) and Plackett-Burman design, with the concentrations of the 7 components as evaluation indexes and the crushing degree, ethanol concentration, and soaking time as factors, the extraction process of P. corylifolia was optimized by Box-Behnken response surface methodology and the validation test was conducted. Zebrafish were divided into blank control group, positive control group (8-methoxypsoralen, 10.8 μg/mL), and low-, medium-, and high-concentration groups of P. corylifolia extract (500, 1 000, 2 000 μg/mL), with 6 fish in each group. The effects of P. corylifolia extract on the melanin production of zebrafish were studied by density analysis. RESULTS The best extraction process was P. corylifolia powder over 60 meshes and soaked in 80% ethanol for 72 hours. The average comprehensive score of three validation experiments was 98.27, with an RSD of 1.36%, and the relative error was 1.02% compared with the predicted value of the fitting equation (97.28). Compared with the blank control group, the melanin pigmentation of zebrafish in the low-, medium-, and high-concentration groups of P. corylifolia extract was significantly increased (P<0.01). CONCLUSIONS The optimized extraction process of P. corylifolia is reasonable and feasible, and the obtained P. corylifolia extract can significantly promote the production of melanin in zebrafish.
8.Risk stratification value of HEART score combined with serial cardiac troponin in emergency patients with chest pain
Yao YU ; Dongxu CHEN ; Fengqing LIAO ; Yannan ZHOU ; Canguang CAI ; Humaerbieke ALIMA· ; Chen CHEN ; Siying ZHOU ; Chenling YAO ; Guorong GU
Chinese Journal of Emergency Medicine 2023;32(4):531-539
Objective:To explore the risk stratification value of HEART score combined with cardiac troponin (cTn) in emergency patients with chest pain.Methods:A total of 11 583 patients with chest pain who visited the Emergency Department of Zhongshan Hospital Affiliated to Fudan University from January to December 2019 were retrospectively collected. Patients who unfinished 0 h high-sensitivity cardiac troponin T (hs-cTnT) or electrocardiogram diagnosed ST-segment elevation myocardial infarction (STEMI) or lost to follow-up were excluded, and 7 057 patients were finally included. The final diagnosis of chest pain and the occurrence of major adverse cardiovascular events within 6 mon (6 m MACEs) were followed up by telephone and medical history. The HEART score of each patient was calculated by two attending physicians, and the patients were divided into the low-risk group (0-3 points), intermediate-risk group (4-6 points) and high-risk group (7-10 points) according to the final score. The risk stratification performance and safety of HEART score were observed and analyzed. A total of 1 884 patients who completed serial hs-cTnT tests were divided into groups according to HEART score (≤3 as low-risk group) and HEART score combined with serial hs-cTnT pathway (HEART score ≤3 and two hs-cTnT measurements <0.03 ng/mL as the low-risk group). The sensitivity (SE), specificity (SP), positive predictive value (PPV) and negative predictive value (NPV) of each diagnostic method were calculated to compare the diagnostic performance of the two predictive values.Results:The patients were divided into 3 groups by HEART score : 2 765 (39.2%) patients in the low-risk group, 3 438 (48.7%) in the intermediate-risk group, and 854 (12.1%) in the high-risk group. The incidence of 6 m MACEs in each group was 1.2%, 18% and 55.3%, respectively. When the low-risk threshold was 2, 23.1% of patients entered the low-risk group and the incidence of 6 m MACEs was 0.9%. The receiver operating characteristic (ROC) curve was drawn to evaluate the predictive performance of the HEART score for 6 m MACEs, and the final AUC was 0.831 ( P=0.006, 95% CI: 0.819-0.843). Regarding the occurrence of NSTEMI at the time of this visit, 4 (0.8%) patients were misdiagnosed by using the HEART score alone. Combined with serial troponin detection, the diagnostic SE and NPV were both 100%; at the same time, the diagnostic SE and NPV of 6 m MACEs in patients increased from 98.1% (95% CI: 96.9%-99.1%), 97.9% (95% CI: 96.2%-99%) to 99.1% (95% CI: 97.9%-99.7%) and 98.9% (95% CI: 97.4%-99.6%), the diagnosis SE and NPV of 6 m myocardial infarction and cardiac death in patients increased from 98% (95% CI: 96%-99.2%), 98.6% (95% CI: 97%-99.4%) to 99.2% (95% CI: 97.6%-99.8%) and 99.3% (95% CI: 98.1%-99.9%). Conclusions:The HEART score can be used for risk assessment in emergency patients with chest pain, and a threshold of 2 is recommended for the low-risk group. The diagnostic performance of HEART score combined with serial cTn is better than that of HEART score alone.
9.Construction and validation of early warning model for acute aortic dissection
Fengqing LIAO ; Chenling YAO ; Guorong GU ; Yao YU ; Dongxu CHEN ; Yannan ZHOU ; Canguang CAI ; Humaerbieke ALIMA· ; Chen CHEN ; Siying ZHOU ; Zhenju SONG ; Chaoyang TONG
Chinese Journal of Emergency Medicine 2023;32(7):874-880
Objective:To investigate the clinical characteristics of patients with acute aortic dissection (AAD) through a retrospective and observational study, and to construct an early warning model of AAD that could be used in the emergency room.Methods:The data of 11 583 patients in the Emergency Chest Pain Center from January to December 2019 were retrospectively collected from the Chest Pain Database of Zhongshan Hospital Affiliated to Fudan University. Inclusion criteria: patients with chest pain who attended the Emergency Chest Pain Center between January and December 2019. Exclusion criteria were 1) younger than 18 years, 2) no chest/back pain, 3) patients with incomplete clinical information, and 4) patients with a previous definite diagnosis of aortic dissection who had or had not undergone surgery. The clinical data of 9668 patients with acute chest/back pain were finally collected, excluding 53 patients with previous definite diagnosis of AAD and/or without surgical aortic dissection. A total of 9 615 patients were enrolled as the modeling cohort for early diagnosis of AAD. The patients were divided into the AAD group and non-AAD group according to whether AAD was diagnosed. Risk factors were screened by univariate and multivariate logistic regression, the best fitting model was selected for inclusion in the study, and the early warning model was constructed and visualized based on the nomogram function in R software. The model performance was evaluated by accuracy, specificity, sensitivity, positive likelihood ratio and negative likelihood ratio. The model was validated by a validation cohort of 4808 patients who met the inclusion/exclusion criteria from January 2020 to June 2020 in the Emergency Chest Pain Center of the hospital. The effect of early diagnosis and early warning model was evaluated by calibration curve.Results:After multivariate analysis, the risk factors for AAD were male sex ( OR=0.241, P<0.001), cutting/tear-like pain ( OR=38.309, P<0.001), hypertension ( OR=1.943, P=0.007), high-risk medical history ( OR=12.773, P<0.001), high-risk signs ( OR=7.383, P=0.007), and the first D-dimer value ( OR=1.165, P<0.001), Protective factors include diabetes( OR=0.329, P=0.027) and coronary heart disease ( OR=0.121, P<0.001). The area under the ROC curve (AUC) of the early diagnosis and warning model constructed by combining the risk factors was 0.939(95 CI:0.909-0.969). Preliminary validation results showed that the AUC of the early diagnosis and warning model was 0.910(95 CI:0.870-0.949). Conclusions:Sex, cutting/tear-like pain, hypertension, high-risk medical history, high-risk signs, and first D-dimer value are independent risk factors for early diagnosis of AAD. The model constructed by these risk factors has a good effect on the early diagnosis and warning of AAD, which is helpful for the early clinical identification of AAD patients.
10.Microdissected peroneal artery perforator flap for repair soft tissue defect of dorsal fingers
Shaoxiao YU ; Wanggao ZHOU ; Guorong CHEN ; Zhenwei ZHANG ; Wenyi WU ; Xuelang YE ; Jinhao ZENG ; Yuhai KE
Chinese Journal of Microsurgery 2022;45(6):617-621
Objective:To investigate the clinical effect of microdissected peroneal artery perforator flap in repair of soft tissue defect of dorsal side of the fingers.Methods:From August 2015 to July 2020, 19 patients with soft tissue defects on dorsal fingers were treated with microdissected peroneal artery perforator flap. The area of wound defect was 3.8 cm×1.5 cm-5.8 cm×3.0 cm, with exposure of phalanges and tendons. The size of flaps was 4.0 cm×1.8 cm-6.0 cm×3.3 cm. According to the size of soft tissue defects on the dorsal side of the fingers, the flaps were designed with the perforating branch of peroneal artery in the centre. The length and width of a flap were 0.2-0.3 cm bigger and wider than the area of defect. The perforator vessels with a length of 2.0-3.0 cm were arvested in the superficial layer of deep fascia. Most of the adipose tissues of the flap were removed under microscope, and the small arteries between adipose tissues were protected. The flaps were used to cover the defects of fingers. The perforator artery of the flap was anastomosed with the proper palmar digital artery of the recipient site, the accompanying vein of the perforator artery was anastomosed with the dorsal digital vein of the recipient site, and the cutaneous nerve in the flap was anastomosed with the dorsal digital nerve. The donor sites were directly pulled together and sutured intermittently. Outpatient and WeChat follow-up were conducted after operation, including wound healing, flap survival, flap sensation, donor site recovery, and flexion and extension functions of the fingers. Functional recovery was evaluated according to the Evaluation Standard of Upper Limb Partial Functional of Hand Surgery of Chinese Medical Association.Results:All wounds healed in Ⅰ stage, and all 19 flaps survived. The follow-up ranged from 9 to 25 months, with an average of 11.5 months. The appearance of the flaps was satisfactory and the texture was good. Sensation recoveried to S 4 in 4 paitients, S 3 in 9 patients and S 2 in 6 patients, and with only a linear scar was left in the donor sites. The hand function recovery was evaluated according to the Trial Criteria of Upper Limb Function Evaluation of the Hand Surgery Society of the Chinese Medical Association, with 18 cases were excellent and 1 was good. Conclusion:The microdissected peroneal artery perforator flap is an ideal surgical method to repair the soft tissue defect of dorsal side of the fingers, which has good shape and simple operation, avoids the secondary thinning and plastic surgery and offers good therapeutic effects.

Result Analysis
Print
Save
E-mail