1.The role of tofacitinib in early atherosclerosis in mice with systemic lupus erythematosus
Qu CHEN ; Fengmei GE ; Zhao LI ; Qiushuang ZHANG ; Xue WU ; Qi CHEN ; Saiqi LI ; Xuebin WANG ; Xiuqing YAN
Chinese Journal of Rheumatology 2024;28(2):106-112
		                        		
		                        			
		                        			Objective:To investigate the effect of tofacitinib on early atherosclerosis of patients with systemic lupus erythematosus and explore the possible relationship between lupus nephritis and early atherosclerosis of systemic lupus erythematosus.Methods:Sixteen 8-week-old female MRL/lpr mice with a body weight of 20~25 g were selected and randomly divided into the treatment group and placebo group, with 8 mice in each group. The treatment group diluted tofacitinib by normal saline, and given at a dose of 10 mg·kg -1·d -1, and the placebo group (starch tablets) administered the medication in the same way as the treatment group for a total of 8 weeks. The ELISA method was applied to detect serum anti-dsDNA antibody levels in the two groups of mice. Bradford method protein concentration was used to determine the level of urine protein in mice. Automatic biochemical analyzer was used to detect blood lipids, urea nitrogen, serum creatinine, complement C3, complement C4 levels. Western blotting was used to determine the protein expression levels of monocyte chemoattractant protein-1 (MCP-1), non-receptor protein tyrosine kinase family 1 (JAK1), signal transducer and activator of transcription 1 (STAT1) and signal transducer and activator of transcription 2 (STAT2) in aortic and kidney tissues. After the aortic arch section were prepared, oil red O was used to stain the sections, and the vascular plaque area and intimal thickness were evaluated by ImageJ software. The kidneys were dissected and stained with HE, and the active lesions of lupus nephritis were evaluated using the glomerular activity scoring system. SPSS 23.0 software was used for statistical analysis, in which the between-group comparison was performed using two independent samples t-test, and the correlation analysis was performed using the Spearman method. Results:①The serum anti-dsDNA antibody expression level in the treatment group [(5.2±1.0) U/ml] was lower than that in the placebo group [(6.9±1.2) U/ml], ( Z=-3.07, P=0.008), and the levels of complement C3 and complement C4 were higher than those in the placebo group [(293±10) mg/L vs. (260±19) mg/L, Z=2.72, P=0.017]; (16±6) mg/L vs. (8±9) mg/L, Z=3.78, P=0.006]. There was no significant difference in serum BUN and Scr between the treatment group and the placebo group [(10.6±0.7) mmol/L vs. (11.5±1.1) mmol/L, Z=-1.96, P=0.071; (17±5) μmol/L vs. (22±6) μmol/L, Z=-1.79, P=0.095]. ② Compared with the placebo group, the levels of LDL, TC and TG in the treatment group decreased [(0.83±0.15) mmol/L vs. (1.08±1.05) mmol/L, Z=-3.95, P=0.001; (2.90±0.08) mmol/L vs. (1.81±0.97) mmol/L, Z=-5.17, P=0.001; (1.10±0.08) mmol/L vs. (1.60±0.42) mmol/L, Z=-3.23, P=0.013], and HDL level increased [(2.02±0.99) mmol/L vs. (1.81±0.97) mmol/L, Z=4.42, P=0.001]. ③ Compared with the placebo group, the levels of aortic MCP-1, JAK1, STAT1 and STAT2 in the treatment group were reduced [(0.17±0.30) vs. (0.23±0.05), Z=-3.06, P=0.009; (0.83±0.09) vs. (1.05±0.19), Z=-3.07, P=0.008; (0.77±0.07) vs. (0.94±0.13), Z=-2.83, P=0.014; (0.70±0.07) vs. (0.82±0.09), Z=-2.83, P=0.013], the aortic plaque area and aortic intimal thickness were lower than those in the placebo group [(12±31) μm 2vs. (1 242±1 101) μm 2, Z=-3.12, P=0.016; (63±7) μm vs. (82.10±8.06) μm, Z=-5.13, P<0.001]. ④ Compared with the placebo group, the urine protein level and glomerulonephritis activity score in the treatment group were decreased [(0.08±0.03) mg/mL vs. (0.20±0.11) mg/mL, Z=-3.08, P=0.015; (1.79±0.38) vs. (2.79±0.14) points, Z=-7.08, P<0.001)], and renal tissue MCP-1, JAK1, STAT1.Compared with the placebo group, STAT2 levels were reduced [(0.364±0.040) vs. (0.425±0.021), Z=-3.85, P=0.003; (0.689±0.074) vs. (0.838±0.068), Z=-4.19, P=0.001; (0.508±0.070) vs. (0.646±0.019), Z=-2.85, P=0.015; (0.618±0.062) vs. (0.740±0.101), Z=-2.94, P=0.013. ⑤ The glomerular mobility scores of the two groups were positively correlated with LDL, TCHO, TG, aortic plaque area and aortic intimal thickness ( r=0.51, P=0.043; r=0.79, P<0.001; r=0.64, P=0.008; r=0.82, P<0.001; r=0.74, P=0.001), and negatively correlated with HDL ( r=-0.53, P=0.036). The urine protein levels in the two groups were positively correlated with LDL, TC, TG, aortic plaque area and aortic intimal thickness ( r=0.67, P=0.004; r=0.68, P=0.004; r=0.53, P=0.033; r=0.80, P<0.001; r=0.74, P=0.001), and negatively correlated with HDL ( r=-0.57, P=0.021). Conclusion:The severity of lupus nephritis is correlated with atherosclerosis and dyslipidemia in the early stage of systemic lupus erythematosus. Tofacitinib may reduce the degree of early arteriosclerosis and lupus nephritis in MRL/LPR mice, and reduce blood lipid levels, which may be effective in improving the prognosis of SLE and improving the survival rate of patients.
		                        		
		                        		
		                        		
		                        	
2.Clinical application of ultrasound combined with DSA-guided implantation of totally implantable venous access port via upper arm vein approach in chemotherapy for patients with malignant tumors
Guangxin JIN ; Fangqin ZHANG ; Yawen WANG ; Yan GUO ; Xiaoxia QIU ; Xuebin ZHANG
Journal of Interventional Radiology 2024;33(7):733-737
		                        		
		                        			
		                        			Objective To evaluate the technical feasibility and safety of upper arm vein approach in the implantation of totally implantable venous access port(TIVAP)under the guidance of ultrasound combined with DSA.Methods The clinical data of 1 546 patients with malignant tumors,who received TIVAP implantation via upper arm vein access under the guidance of ultrasound combined with DSA at the Affiliated Renji Hospital,School of Medicine of Shanghai Jiao Tong University of China between January 2020 and January 2022,were retrospectively analyzed.The implantation success rate,single-puncturing success rate,operation time,and complications were compared between the PICC catheterization room and the DSA operating room.Results The technical success rate in the 1546 patients was 100%,with a single-puncturing success rate of 99.48%.In 766 patients the TIVAP implantation was performed in the PICC catheterization room(PICC group),and in 780 patients the TIVAP implantation was carried out in the DSA operating room(DSA group).The mean operation time in the DSA group was(20.1±1.3)min,which was obviously shorter than(25.4±1.9)min in the PICC group,and the incidence of primary catheter misplacement in the DSA group was 0%,which was remarkably lower than 0.78%in the PICC group(P<0.05).No statistically significant differences in the incidences of complications,including infection,thrombosis,upper limb movement disorder,catheter occlusion,exposure of infusion port body,and overturn of infusion port body,existed between the two groups(P>0.05).Conclusion Ultrasound-guided TIVAP via upper arm vein approach is a safe and effective infusion route for patients with malignancy receiving chemotherapy.The combination use of ultrasound guidance and intraoperative DSA guidance can reduce the operation time as well as the incidence of operation-related complications.
		                        		
		                        		
		                        		
		                        	
3.Identification and clearance of high-level drug-resistant Salmonella Kentucky ST198.2-1 from an occupational health examinee
Yan ZHONG ; Jingfang RUAN ; Xiachan QIN ; Bei WEI ; Yue LIU ; Min ZHOU ; Xuebin XU
Chinese Journal of Laboratory Medicine 2024;47(9):1094-1097
		                        		
		                        			
		                        			A 49-year-old female examinee, employed at a paper company in Guigang, Guangxi (engaged in the production of napkins), visited the Qintang District People′s Hospital in Guigang on June 11, 2023, to apply for a health certificate. Salmonella was isolated during a physical examination screening for enteric pathogens ( Salmonella, Shigella), and repeated use of empirical antibacterial drugs failed to eradicate the pathogen. A reference laboratory identified the two isolates as S. Kentucky ST198 by performing serotyping, drug resistance phenotyping, and whole genome sequencing. Based on the regional serotype database of Salmonella in China, a phylogenetic tree of S. Kentucky ST198 resistance genotypes was constructed, defining both isolated strains as high-level drug-resistant ST198.2-1 subclade clones. Following a multidisciplinary consultation and based on antimicrobial susceptibility test results, the treatment was adjusted to amoxicillin/clavulanate and azithromycin. On August 19, three consecutive negative test results confirmed the eradication of Salmonella Kentucky.
		                        		
		                        		
		                        		
		                        	
4.Campylobacter fetus subsp. fetus ST20 isolated and identified from the bacteremia patient
Bei WEI ; Fen GAO ; Yue LIU ; Yan ZHONG ; Yanfang LI ; Deju QIN ; Jincheng ZHOU ; Xuebin XU
Chinese Journal of Laboratory Medicine 2024;47(9):1102-1105
		                        		
		                        			
		                        			A 72-year-old female patient was admitted to the emergency department of Qintang District People′s Hospital of Guigang City in August 2023 due to chills and fever, abdominal distension and pain, diarrhea, cough and shortness of breath for 1 day. She had a history of chronic obstructive and pulmonary heart disease, stage Ⅲ hypertension, and ceftazidime allergy. Clinical diagnosis of acute bacterial infection of chronic obstructive pneumonia was made and levofloxacin combined with piperacillin/tazobactam were given as symptomatic treatment. The blood culture reported Campylobacter fetus after four days, and the patient was cured and discharged after seven days with negative blood culture. The morphology and mass spectrometry identification of the strain were consistent with the definition of Campylobacter fetus. Whole genome sequencing predicted the multi-site sequence type as Campylobacter fetus subsp. fetus( Cff) ST20, carrying the tetracycline resistance gene tet (O/M/O), 18 flagella genes (including rpoN gene from Campylobacter jejuni. these genes were not found in the other two Campylobacter fetus subspecies), and six virulence genes (including like-typhoidal toxin and typhoid toxin genes). The pathogen has the ecological characteristics of parasitic farmed animal colonization and the biological characteristics of high mobility and virulence. These attributes facilitated its entry into the bloodstream via the fecal-oral route, leading to invasive infections.
		                        		
		                        		
		                        		
		                        	
5.Analysis of CT signs of acquired immune deficiency syndrome-associated pneumocystis jirovecii pneumonia
Ya GAO ; Gangfeng LI ; Xuebin LEI ; Weiqiang YAN ; Guangbin CUI
Journal of Practical Radiology 2023;39(12):1949-1952
		                        		
		                        			
		                        			Objective To explore the common CT signs of acquired immune deficiency syndrome(AIDS)-associated pneumocystis jirovecii pneumonia(PJP).Methods The chest CT data of 123 patients with AIDS-associated PJP were analyzed retrospectively.Results Multifocal lesions in both lungs were found in all cases.Distribution characteristics were as follows:diffuse and symmetrical distribution in both lungs in 100 cases(81.3%),diffuse and asymmetrical distribution in both lungs in 15 cases(12.2%),and scattered distribution in both lungs in 8 cases(6.5%).The density and morphological features were as follows:ground glass opacity in 120 cases(97.6%);"lunate arch sign"in 25 cases(20.3%);pulmonary interstitial proliferation in 103 cases(83.7%);crazy paving pattern in 14 cases(11.4%);patchy or consolidation shadow in 55 cases(44.7%);pulmonary cysts in 26 cases(21.1%);and nodular in 26 cases(21.1%).Other rare signs included pleural effusion in 11 cases,pericardial effusion in 6 cases,mediastinal and hilar lymphadenopathy in 9 cases,and mediastinal emphysema in 1 case.Conclusion The chest CT manifestations of AIDS-associated PJP have certain characteristics,including diffuse and symmetrical distribution of lesions in both lungs,as well as ground glass opacity and interstitial hyperplasia as common signs,especially,"lunate arch sign"and pulmonary cysts are more specific signs.
		                        		
		                        		
		                        		
		                        	
6.Study on the correlation of integr in associated protein and disease activity and bone destruction in patients with rheumatoid arthritis
Xue WU ; Fang SHI ; Xiuqing YAN ; Fengmei GE ; Zhao LI ; Qiushuang ZHANG ; Qu CHEN ; Qi CHEN ; Xuebin WANG
Chinese Journal of Rheumatology 2022;26(9):603-607
		                        		
		                        			
		                        			Objective:To analyze the serum levels of integrin-associated proteins (CD47) in patients with rheumatoid arthritis (RA), and to explore its association with disease activity and bone destruction in RA.Methods:Serum and clinical data were collected from 65 RA patients and 25 healthy subjects. RA patients were grouped into low, moderate, and high bone erosion groups according to 7-joint ultrasonography score (US7). The levels of serum CD47, thrombospondin-1 (TSP-1) and receptor activator of nuclear factor-κB ligand (RANKL) were measured by enzyme-linked immunosorbnent assay (ELISA) in patients with RA and healthy subjects. The statistical analysis was carried out with independent t-test, analysis of variance, nonparametric rank sum test, pearson or Spearman correlation and logistic regression. Results:① The Serum levels of CD47, TSP-1, and RANKL were higher in the RA group than in the healthy controls ( P<0.01). ② In RA patients, serum CD47 level was positively correlated with disease course ( r=0.301, P<0.05), C-reactionprotein (CRP)( r=0.316, P<0.05), number of tender joints (TJC) ( r=0.254, P<0.05), number of swollen joints (SJC) ( r=0.316, P<0.05), disease activity score in 28 joints (DAS28) ( r=0.255, P<0.05), RANKL ( r=0.252, P<0.05) and TSP-1 ( r=0.260, P<0.05). Serum TSP-1 level was positively correlated with CRP ( r=0.299, P<0.05), TJC ( r=0.335, P<0.01), DAS28 ( r=0.315, P<0.05), RANKL ( r=0.305, P<0.05). ③ The disease course [ OR(95% CI)=1.048(1.033, 1.017)] and TSP-1 [ OR(95% CI)=1.013(1.000, 1.026)] were independently relevant factors affecting bone destruction. Conclusion:CD47 levels is significantly higher in RA patients than in healthy controls, and is associated with disease activity and bone destruction. CD47 may be involved in the bone destruction process of RA by acting on TSP-1.
		                        		
		                        		
		                        		
		                        	
7. Conditional Deletion of Foxg1 Alleviates Demyelination and Facilitates Remyelination via the Wnt Signaling Pathway in Cuprizone-Induced Demyelinated Mice
Fuxing DONG ; Dajin LIU ; Feiyu JIANG ; Yaping LIU ; Xiuxiang WU ; Xuebin QU ; Jing LIU ; Yan CHEN ; Ruiqin YAO ; Fuxing DONG ; Hongbin FAN
Neuroscience Bulletin 2021;37(1):15-30
		                        		
		                        			
		                        			 The massive loss of oligodendrocytes caused by various pathological factors is a basic feature of many demyelinating diseases of the central nervous system (CNS). Based on a variety of studies, it is now well established that impairment of oligodendrocyte precursor cells (OPCs) to differentiate and remyelinate axons is a vital event in the failed treatment of demyelinating diseases. Recent evidence suggests that Foxg1 is essential for the proliferation of certain precursors and inhibits premature neurogenesis during brain development. To date, very little attention has been paid to the role of Foxg1 in the proliferation and differentiation of OPCs in demyelinating diseases of the CNS. Here, for the first time, we examined the effects of Foxg1 on demyelination and remyelination in the brain using a cuprizone (CPZ)-induced mouse model. In this work, 7-week-old Foxg1 conditional knockout and wild-type (WT) mice were fed a diet containing 0.2% CPZ w/w for 5 weeks, after which CPZ was withdrawn to enable remyelination. Our results demonstrated that, compared with WT mice, Foxg1-knockout mice exhibited not only alleviated demyelination but also accelerated remyelination of the demyelinated corpus callosum. Furthermore, we found that Foxg1 knockout decreased the proliferation of OPCs and accelerated their differentiation into mature oligodendrocytes both in vivo and in vitro. Wnt signaling plays a critical role in development and in a variety of diseases. GSK-3β, a key regulatory kinase in the Wnt pathway, regulates the ability of β-catenin to enter nuclei, where it activates the expression of Wnt target genes. We then used SB216763, a selective inhibitor of GSK-3β activity, to further demonstrate the regulatory mechanism by which Foxg1 affects OPCs in vitro. The results showed that SB216763 clearly inhibited the expression of GSK-3β, which abolished the effect of the proliferation and differentiation of OPCs caused by the knockdown of Foxg1. These results suggest that Foxg1 is involved in the proliferation and differentiation of OPCs through the Wnt signaling pathway. The present experimental results are some of the first to suggest that Foxg1 is a new therapeutic target for the treatment of demyelinating diseases of the CNS. 
		                        		
		                        		
		                        		
		                        	
8.Prediction model of recovery time after gynecological robotic surgical procedures
Yi LIU ; Yongzhong TANG ; Chengxuan QUAN ; Dong HUANG ; Wen OUYANG ; Xuebin YAN
Journal of Chinese Physician 2021;23(12):1805-1809
		                        		
		                        			
		                        			Objective:In order to accurately evaluate the postoperative rehabilitation of gynecological robotic surgery, a prediction model for evaluating postanesthesia care unit (PACU) extubation time and hospital stay in gynecological robotic surgery was established.Methods:The clinical data of gynecological patients who underwent robotic surgery in Xiangya Third Hospital of Central South University from October 2015 to May 2017 were retrospectively analyzed, and the data were screened to evaluate the postoperative recovery of patients from two aspects: PACU extubation time and postoperative hospital stay. Binary logistic regression was used to screen out the factors affecting PACU extubation time and postoperative hospital stay, and the prediction model was preliminarily established and verified.Results:Finally, there were 456 patients and 30 variables analyzed in the binary logistics regression. According to these variables, the prediction model of the postoperative recovery evaluation after gynecological robotic surgical procedures was established. Among them, age, intraoperative amount of atracurium and midazolam were independent risk factors affecting PACU extubation time (all P<0.05). American Society of Anesthesiologists (ASA) grade, intraoperative amount of midazolam, intraoperative bleeding and operation time were independent risk factors affecting postoperative hospital stay (all P<0.05). All models passed Hosmer lemeshow test (all P>0.05); The areas under the receiver operating characteristic curve (ROC) were 0.647 and 0.806, respectively. Conclusions:The prediction model of PACU extubation time and the postoperative hospitalization time has been established.
		                        		
		                        		
		                        		
		                        	
9.Evaluation of Smart Dose's predictive effectiveness on vancomycin blood concentration
Yan LI ; Lizhi CHEN ; Xuebin WANG ; Yunyun YANG ; Xiaolin YANG ; Zhuo WANG
Journal of Pharmaceutical Practice 2021;39(2):164-168
		                        		
		                        			
		                        			Objective To evaluate clinical utility of the personalized drug delivery decision support system, Smart Dose, applied to the monitoring of therapeutic drugs in Chinese population. Methods Use Smart Dose system to predict the trough concentration of vancomycin in patients, analyze the difference between the predicted value and the measured value of the trough concentration, and to evaluate the prediction performance of the system for vancomycin blood concentration. Results Smart Dose adjusts the difference between the predicted value of concentration and the measured value, the average percentage error, and the average absolute percentage error is less than the difference between the predicted value of initial concentration and the measured value. The difference between the initial concentration prediction value and the measured value of the neurosurgery group was smaller than that of the non-neurosurgery group, and the prediction efficiency was better than that of the non-neurosurgery group. The predicted initial concentration of the high trough concentration group and the low-age group (<59 years old) are closer to the measured value. The predictive performance of different BMI for the initial concentration is similar. Conclusion Smart Dose system is more suitable for predicting the adjusted concentration of vancomycin; When used for initial concentration prediction, the prediction values of neurosurgery group, high trough concentration, and low age group are more accurate. Different BMI has similar performance in predicting initial concentration.
		                        		
		                        		
		                        		
		                        	
10.Study on the correlation of extracellular matrix metalloproteinase inducer and atherosclerosis in patients with systemic lupus erythematosus
Qiushuang ZHANG ; Xiuqing YAN ; Fengmei GE ; Zhao LI ; Min ZHAO ; Xue WU ; Xuebin WANG
Chinese Journal of Rheumatology 2021;25(4):236-240
		                        		
		                        			
		                        			Objective:To Studythe extracellular matrix metalloproteinase inducer (CD147) changes in patients with systemic lupus erythematosus (SLE), and to study thecorrelation of CD147 level and athero-sclerosis in SLE.Methods:Eighty patients with SLE in total were divided into intimal thickening group, (24 cases, group A) and normal intimal group (56 cases, group B) according to carotid intimamedia thickness (IMT) checked by carotid ultrasonography. In addition, their age, bodymass index, blood pressure, seral total cholesterol (TC), high density liptein cholestero (HDL-C), low density lipoprotein cholestero (LDL-C), triglyceride (TG), urinary protein quantitative test(24 h), erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), anticardiolipin antibody, serum creatinine level, course of the disease, and treatment regimens were collected. Thirty-five healthy people were set as the control group (group C). The levels of serum CD147 were measured by enzyme-linked immuno sorbent assay (ELISA) in 3 groups. The correlation between the serum CD147 level of SLE patients and atherosclerosis was analyzed. The statistical analysis was carried out with independent t-test, chi-square test, analysis of variance, Spearman correlation and Logistic regression. Results:① Levels of serum CD147 in group A [ (238±30) pg/ml] were significantly higher than those in group B [(198±30) pg/ml] and group C [(150±26) pg/ml, F=67.908, P<0.01]. ② Body mass index, hypertensive ratio,total blood cholesterol,urine protein quantitative test (24 h), systemic lupus erythematosus disease activity index (SLEDAI), serum CD147 index in group A were significantly higher than those in group B ( P<0.05). ③ In Logistic regression analysis, serum CD147 [ OR (95% CI)=1.039(1.014, 1.065), P<0.05], urine protein quantitative (24 h) [ OR (95% CI)=2.598(1.033, 6.534), P<0.05] were independently relevant factors affecting carotid artery IMT. Conclusion:Serum CD147 is an independent risk factor for carotid intimamedia thickness in SLE patients.
		                        		
		                        		
		                        		
		                        	
            
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