1.Machine learning identification of LRRC15 and MICB as immunodiagnostic markers for rheumatoid arthritis
Yanhu TIAN ; Xinan HUANG ; Tongtong GUO ; Rusitanmu·Ahetanmu ; Jiangmiao LUO ; Yao XIAO ; Chao WANG ; Weishan WANG
Chinese Journal of Tissue Engineering Research 2025;29(11):2411-2420
BACKGROUND:Rheumatoid arthritis is a chronic autoimmune disease.Early diagnosis is crucial for preventing disease progression and for effective treatment.Therefore,it is of significance to investigate the diagnostic characteristics and immune cell infiltration of rheumatoid arthritis. OBJECTIVE:Based on the Gene Expression Omnibus(GEO)database,to screen potential diagnostic markers of rheumatoid arthritis using machine learning algorithms and to investigate the relationship between the diagnostic characteristics of rheumatoid arthritis and immune cell infiltration in this pathology. METHODS:The gene expression datasets of synovial tissues related to rheumatoid arthritis were obtained from the GEO database.The data sets were merged using a batch effect removal method.Differential expression analysis and functional correlation analysis of genes were performed using R software.Bioinformatics analysis and three machine learning algorithms were used for the extraction of disease signature genes,and key genes related to rheumatoid arthritis were screened.Furthermore,we analyzed immune cell infiltration on all differentially expressed genes to examine the inflammatory state of rheumatoid arthritis and investigate the correlation between their diagnostic characteristics and infiltrating immune cells. RESULTS AND CONCLUSION:In both rheumatoid arthritis and normal synovial tissues,we identified 179 differentially expressed genes,with 124 genes up-regulated and 55 genes down-regulated.Enrichment analysis revealed a significant correlation between rheumatoid arthritis and immune response.Three machine learning algorithms identified LRRC15 and MICB as potential biomarkers of rheumatoid arthritis.LRRC15(area under the curve=0.964,95%confidence interval:0.924-0.992)and MICB(area under the curve=0.961,95%confidence interval:0.923-0.990)demonstrated strong diagnostic performance on the validation dataset.The infiltration of 13 types of immune cells was altered,with macrophages being the most affected.In rheumatoid arthritis,the majority of proinflammatory pathways in immune cell function were activated.Immunocorrelation analysis revealed that LRRC15 and MICB had the strongest correlation with M1 macrophages.To conclude,this study identified LRRC15 and MICB as potential diagnostic markers for rheumatoid arthritis,with strong diagnostic performance and significant correlation with immune cell infiltration.Machine learning and bioinformatics analysis deepened the understanding of immune infiltration in rheumatoid arthritis and provided new ideas for the diagnosis and treatment of rheumatoid arthritis.
2.Influences of Cell-ECM Adhesion on Migration of Tumor Cells Regulated by ECM Stiffness: A Model Study
Ying ZHANG ; Yulan WANG ; Kaiqun WANG ; Yan WEI ; Di HUANG ; Weiyi CHEN ; Yanhu SHAN
Journal of Medical Biomechanics 2021;36(4):E604-E611
Objective To study the influence of cell-extracellular matrix (ECM) adhesion on migration of tumor cells regulated by ECM stiffness. Methods The cellular Potts model (CPM) was established to simulate tumor cell growth and cellular immune feedback system. The effects from mechanical behavior of cells on cell-ECM adhesion were observed, and the migration of tumor cells under different ECM was analyzed. Results The ECM stiffness could influence the migration rate of tumor cells. The change of ECM stiffness regulated the adhesion force between cells and ECM, and the change of adhesion force would influence the migration rate of cells. Conclusions The migration and distribution patterns of cells are closely related to the adhesion and stiffness of ECM. The increase in ECM stiffness can effectively promote the migration rate of tumor cells, and the further increase in ECM stiffness inhibits the migration of tumor cells. These findings may further reveal dynamic changes of ECM, adhesion and mechanical performance of tumor cell migration.
3.Effect of donor dexmedetomidine preconditioning on renal function of patients undergoing living-related kidney transplantation
Bo FENG ; Yanhu XIE ; Xuebing ZHANG ; Delong WANG ; Ling ZHOU ; Xiaoqing CHAI
Chinese Journal of Anesthesiology 2020;40(5):618-621
Objective:To evaluate the effect of donor dexmedetomidine preconditioning on the renal function of patients undergoing living-related kidney transplantation.Methods:Sixty American Society of Anesthesiologists physical status Ⅲ-Ⅳ patients, regardless of gender, aged 20-64 yr, with body mass of 18.5-28.0 kg/m 2, undergoing living-related kidney transplantation, were selected.Sixty corresponding donors, of American Society of Anesthesiologists physical status Ⅰ or Ⅱ, regardless of gender, aged 20-64 yr, with body mass index of 18.5-28.0 kg/m 2, were selected.The patients and donors were divided into 2 groups using a random number table method: control group (group C) and dexmedetomidine group (group D), with 30 pairs in each group.Before induction of anesthesia, dexmedetomidine was intravenously infused over 10 min in a loading dose of 1 μg/kg followed by an intravenous infusion of 0.5 μg·kg -1·h -1 until the time point when the renal artery was blocked immediately in the donors of group D, while the equal volume of normal saline was given instead until the time point when the renal artery was blocked immediately in the donors of group C. In both groups, total intravenous anesthesia was applied in donors and recipients, Nacotrend values were maintained at 40-60 during operation, mean arterial pressure and heart rate were maintained within the normal range, and dopamine was intravenously infused when necessary.The warm ischemia time and cold ischemia time of donor kidneys were recorded in the two groups.Peripheral venous blood samples were collected from the donors immediately before renal artery occlusion and from the recipients before renal artery opening (T 0) and at 1, 12 and 24 h after renal artery opening (T 1-3) to determine the serum creatinine (Cr), urea nitrogen (BUN) and cysteine protease inhibitor C (CysC) concentrations.The intraoperative volume of fluid infused, urine volume and consumption of propofol, remifentanil and dopamine were recorded in the receptors of two groups. Results:There was no significant difference in the concentrations of Cr, BUN and CysC and warm ischemia time and cold ischemia time of kidneys in between the two groups of donors ( P>0.05). There was no significant difference in the consumption of propofol, remifentanil and dopamine, volume of fluid infused and urine volume during surgery between the two groups of recipients ( P>0.05). Compared with group C, the concentrations of Cr, BUN and CysC were significantly decreased in at T 1 in group D ( P<0.05). Conclusion:Donor dexmedetomidine preconditioning is helpful in improving the perioperative renal function of patients undergoing living-related kidney transplantation.
4.Effects of flurbiprofen axetil administered at different time points on oxygenation in patients undergoing one-lung ventilation
Jun MA ; Wei ZHANG ; Di WANG ; Yanhu XIE ; Min XU ; Yunxiang WU ; Xiaoqing CHAI
Chinese Journal of Anesthesiology 2017;37(2):143-146
Objective To evaluate the effects of flurbiprofen axetil administered at different time points on oxygenation in the patients undergoing one-lung ventilation (OLV).Methods Ninety patients of both sexes,aged 45-64 yr,of American Society of Anesthesiologists physical status Ⅰ or Ⅱ,undergoing elective thoracoscope-assisted pulmonary lobectomy,were assigned into 3 groups (n =30 each) using a random number table:control group (group C),preoperative administration group (group F1) and intraoperative administration group (group F2).Flurbiprofen axetil (10 mg/ml) and fat emulsion 10 ml were injected intravenously at 15 min before operation in F1 and C groups,respectively.Flurbiprofen axetil 10 ml was intravenously injected immediately after the beginning of OLV in group F2.At 15 min before operation (T1),15 and 30 min of OLV (T2,3),and 15 min after restoration of two-lung ventilation (T4),airway peak pressure (Ppeak) and dynamic lung compliance (Cdyn) were recorded,arterial blood samples were collected for blood gas analysis.The arterial oxygen partial pressure (PaO2) was recorded,and the oxygenation index (OI) and intrapulmonary shunt (Qs/Qt) were calculated.The concentrations of thromboxane B2 (TXB2) and 6-keto-prostaglandin F1α (6-K-PGF1α) in serum were measured by enzyme-linked immunosorbent assay,and TXB2/6-K-PGF1α ratio was calculated.The development of interrupting OLV due to SpO2<90% and postoperative dyspnea,pulmonary infection,atelectasis and length of hospital stay were recorded.Results Compared with group C,PaO2 and OI were significantly increased,and Qs/Qt was decreased at T2,3,the serum concentrations of TXB2 and 6-K-PGF1α were decreased,and TXB2/6-K-PGF1α ratio was increased at T2-4,the incidence of interrupting OLV was decreased (P<0.05),and no significant change was found in the parameters mentioned above in group F2 (P>0.05).Compared with group F1,PaO2 and OI were significantly decreased at T2,3,Qs/Qt was increased at T2,and the serum concentrations of TXB2 and 6-K-PGF1α were increased,and TXB2/6-K-PGF1α ratio was decreased at T2-4 in group F2 (P<0.05).There was no significant difference in the incidence of postoperative dyspnea,pulmonary infection and atelectasis and length of hospital stay between the three groups (P>0.05).Conclusion Flurbiprofen axetil injected at 15 min before operation can significantly improve oxygenation and prevent the development of hyoxemia in the patients undergoing OLV,however,flurbiprofen axetil administered immediately after the beginning of OLV has no such effect.
5.The hypertriglyceridaemic-waist phenotype in relation to carotid artery atherosclerosis in patients with type 2 diabetes mellitus
Lei ZHANG ; Yanhu DONG ; Meihua XU ; Juanjuan LI ; Xiaoqiang WANG ; Na WANG
Chinese Journal of Endocrinology and Metabolism 2012;28(1):21-23
Among 2625 patients with type 2 diabetes,body mass index,systolic blood pressure,HbA1C,triglyceride,ApoB,serum uric acid,highly-sensitive C reactive protein,tumor necrosis factor α levels,and common carotid artery intima-media thickness in hypertriglyceridemic-waist ( HTWC ) phenotype group were higher than those in non-HTWC group,while high-density lipoprotein cholesterol and ApoA1 levels were lower( all P<0.05 ).HTWC phenotype was an independent risk factor for atherosclerosis of carotid artery in patients with type 2 diabetes mellitus (OR 1.45,95%CI 1.07-1.96).
6.The relationship between waist to stature ratio and hypertension, diabetes, and dyslipidemia in Qingdao
Yuan JING ; Yanhu DONG ; Ting HAN ; Lei ZHANG ; Na WANG ; Yamei ZHU ; Meihua XU
Chinese Journal of Internal Medicine 2012;51(9):683-686
ObjectiveTo evaluate the relationship between waist to stature ratio (WSR) and hypertension,diabetes,dyslipidemia in Qingdao. MethodsData were collected from a 2001 - 2007 Qingdao area diabetes survey,population-based cross-sectional study,and 30 712 Chinese adults aged > 18 years old were enrolled.Correlation analysis of BMI,WSR,hip circumference,waist circumference,waist to hip ratio (WHR) with blood glucose,blood pressure,blood lipid were conducted.ROC curve analysis in diabetes,bypertension,dyslipidemia and multivariate logistic regression analysis were also conducted.ResultsAnthropometric indicators were related with hypertension,diabetes and dyslipidemia in both men and women.Comparing with other anthropometric indicators,WSR was found to have the largest area under the ROC curve and the best cut-off point of WSR was 0.52.Multivariate logistic regression analysis showed that, after controlling age, disease history, physicalactivity, sex, thediabeteshypertension and dyslipidemia risk OR of WSR≥0.52 were largest.ConclusionsAnthropometric indicators intimately related with cardiovascular risk factors in Qingdao region,and may predict and evaluate the risk of cardiovascular disease.WSR may be the best index for predicting cardiovascular risk factors in Qingdao area.The optimal WSR cut off point for identifying cardiovascular risk factors clustering is 0.52.
7.Effects of different anesthesia methods on inflammatory cytokines in elderly patients during peroperative period
Changwei WEI ; Xiuzhen LIU ; Zhuoqiang WANG ; Hongyue WANG ; Jian CHEN ; Yanhu GE ; Jun WANG
Clinical Medicine of China 2012;28(9):907-910
Objective To explore the two different anesthesia methods on hemodynamics and inflammatory cytokines in elderly patients during peroperative period.MethodsFifty elderly patients with Knee Replacement( ASA Ⅰ,Ⅱ )were randomly divided into general anesthesia group( group A,n =25 ) and combined general and epidural anesthesia group( group B,n =25 ).The changes of mean arterial pressure(MAP) and heart rate ( HR ) were monitored before induction of anesthesia ( T1 ),at intubation ( T2 ),during skin incision ( T3 ) and at the time of extubation ( T4 ),at 30 min after extubation ( T5 ).Blood samples were taken from artery for determination of plasma TNF-α,IL-6,IL-10 concentrations before tourniquet inflation ( T5 ),10 min after tourniquet deflation(T6),30 min after tourniquet deflation (T7)and 30 min after operation (T8)by enzymelinked immunosorbent assay(ELISA).ResultsThe MAP and HR of patients in two groups at T2,T3,T4 were all increased when compared with T1 [ group A:HR:( 94.3 ± 10.4 ) bpm,( 96.4 ± 12.7 ) bpm,(93.3 ± 11.1 )bpm vs(62.6 ±7.3)bpm;MAP:( 18.8 ±3.4)kPa,( 19.6 ±3.4)kPa,( 17.8 ±2.0)kPa vs ( 14.5 ± 1.5)kPa,P<0.05;group B:HR(76.2 ±6.5)bpm,(70.1 ± 9.7) bpm,(71.5 ± 8.3) bpm vs(64.6 ± 8.4) bpm;MAP:( 16.3 ± 2.5 ) kPa,( 15.3 ± 1.2) kPa,( 14.8 ± 1.4) kPa vs ( 14.1 ± 1.3 ) kPa,P < 0.05 ].There was significant difference on MAP and H R between group A and group B( F =11.957,9.745;P < 0.05 ).The level of plasma TNF-α,IL-6 and IL-10 were significantly increased at T6 to T8 compared with T5 in both groups[ groupA:TNF-α:(4.36 ±0.18) ng/L,(7.54 ± 1.23) ng/L,(10.35 ±2.21 )ng/L vs (2.26 ±0.16) ng/L; groupA:IL-6:(4.32 ±0.21 ) ng/L,( 8.35 ± 1.26 ) ng/L,( 10.23 ± 2.23 ) ng/L vs ( 1.36 ± 0.08 ) ng/L; groupA:IL-10:(5.32±1.10) ng/L,(7.56 ± 1.36) ng/L,(8.63 ± 2.21) ng/L vs (1.25 ± 0.03) ng/L; groupB:TNF-α:(3.43 ±0.06)ng/L,(5.24 ±2.10) ng/L,(7.68 ± 1.43) ng/L vs(2.22 ±0.15) ng/L;groupB:IL-6:(3.41 ±0.08 ) ng/L,(5.34 ± 1.34 ) ng/L,( 8.54 ± 2.03 ) ng/L vs ( 1.28 ± 0.04 ) ng/L; groupB:IL-10:( 7.28 ± 1.22 )ng/L,( 10.53 ± 2.14)ng/L,( 12.45 ± 2.03 )ng/L vs( 1.31 ± 0.04)ng/L,P < 0.05 ].And there was significant difference on TNF-α,IL-6 and IL-10 between group A and group B( F =7.889,3.554,5.443,respectively,P <0.05).ConclusionCompared with general anesthesia group,combined general and epidural anesthesia group can ensure hemodynamic stability of elderly patients during peroperative period very well and can reduce the releasing of inflammatory cytokins,it is a viable and an ideal method.
8.Clinical research on ulinastatin on respiratory dynamics improvement in patients with myasthenia gravis
Xiuzhen LIU ; Changwei WEI ; Zhuoqiang WANG ; Yanhu GE ; Jun WANG ; Jie DING ; Jian CHEN ; Yan ZHANG
Clinical Medicine of China 2012;28(9):903-906
ObjectiveTo observe the changes of the respiratory dynamics during expand thymectomy,and to explore the protection of ulinastatin on pulmonary function.MethodsSixty patients with myasthenia gravis( Ossermann Ⅰ,Ⅱ b)undergoing expand thymectomy were randomly divided into control group( group C,n =30)and ulinastatin group( group U,n =30).Patients in ulinastatin group received intravenous injection of ulinastatin 4000 U/kg in 20 ml physiological saline immediately after entering operating room and pumped ulinastatin 2000 U/( kg · h)to the end of the operation continuously.Patients in control group received the same volume of normal saline.Heart rate ( HR ),mean arterial pressure ( MAP ),lung compliance,airway peak pressure,plateau airway pressure,inspiratory and expiratory resistance were monitored before induction of anesthesia( T1 ),during skin incision ( T2),at 30 min after operation ( T3 ) and at 60 min after operation (T4),at the end of operation before extubation(T5).ResultsCompared with T1,HR and MAP at T2 in two groups were increased obviously [ group U HR:( 90.2 ± 13.5 ) bpm vs ( 78.6 ± 10.4 ) bpm,MAP:( 15.5 ± 2.3 ) kPa vs ( 12.1 ± 1.5)kPa;group C HR:(94.3 ± 15.4)bpm vs(81.6 ± 12.2)bpm,MAP:( 16.8 ± 2.6) kPa vs( 12.6 ±1.8)kPa,P < 0.05 )].There was no significant difference on HR,MAP at each time between the two groups (P >0.05).At T3,T4,T5,the lung compliance was significantly decreased when compared with T1 [ group U:T3,T4,TS(51.23 ± 12.33) ml/cm H2O,(50.35 ± 13.29) ml/cm H2O and(50.65 ± 13.16) ml/cm H2O vs T1 (53.69 ± 14.34) ml/cm H2O;group C:T3,T4,T5(41.56 ± 11.20)ml/cm H2O,(42.02 ± 10.12) ml/cm H2O and(39.85 ± 10.31 ) ml/cm H2O vs T1 ( 53.45 ± 15.21 ) ml/cm H2O; P < 0.05 ) ].Airway peak pressure,plateau airway pressure,inspiratory and expiratory resistance at T3,T4,T5 were obviously increased compared with T1 in two groups [ airway peak pressure:group U:( 13.04 ± 2.14 ) cm H2O,( 13.12 ± 2.42 ) cm H2O,(13.22±2.48)cm H2O,vs(12.04 ±2.12)cm H2O;group C:(16.25 ±3.27)cm H2O,(15.56 ±4.34)cm H2 O,( 16.64 ± 3.45 ) cm H2O,vs ( 13.12 ± 2.32 ) cm H2O; plateau airway pressure:group U:( 10.54 ±2.46) cm H2O,( 11.76 ± 3.11 ) cm H2O,( 12.02 ± 3.25 ) cm H2 O,vs ( 9.48 ± 2.13 ) cm H2O; group C:(15.02 ±3.87)cm H2O,( 15.51 ± 3.13) cm H2O,( 15.67 ± 3.02) cm H2O,vs (9.25 ± 1.26) cm H2O;inspiratory resistance:group U:( 8.56 ± 2.52 ) cm H2O,( 9.31 ± 3.06 ) cm H2O,( 8.44 ± 2.45 ) cm H2O,vs (8.25 ±2.20)cm H2O;group C:(11.52 ±3.06)cm H2O,(12.16 ±3.02)cm H2O,(12.83 ±3.14)vs ( 8.31 ± 2.24 ) cm H2O ; expiratory resistance:group U:( 10.22 ± 2.24 ) cm H2O,( 10.34 ± 2.66 ) cm H2O,(10.27 ± 2.22) cm H2O,vs(8.46 ± 2.37) cm H2O; group C:(14.43 ±3.18)cm H2O,(14.56 ±3.32)cm H2O,( 14.46 ± 3.52 ) cm H2O,vs ( 8.55 ± 2.18 ) cm H2O; P < 0.05 ) ].The increased degree of lung compliance and the decreased degree of airway peak pressure,plateau airway pressure,inspiratory and expiratory resistance at the time of T3,T4,T5 and T1 in ulinastatin group were all significantly higher than those in control group(F=6.167,3.138,4.137,5.217,4.361,respectively,P <0.05).ConclusionUlinastatin can improve respiratory dynamics,reduce lung injury,and play a protective role in patients with myasthenia gravis.
9.The baseline characteristics of patients with type 2 diabetes initiating insulin detemir:the Chinese cohort from the SOLVETM study
Changyu PAN ; Linong JI ; Juming LU ; Wenying YANG ; Zhiguang ZHOU ; Dajin ZOU ; Qiuhe JI ; Ping HAN ; Jie LIU ; Qiang LI ; Benli SU ; Yanbing LI ; Zhengnan GAO ; Penghua WANG ; Shinan YIN ; Yanhu DONG ; Tao YANG ; Kan SUN ; Hong LI ; Xu HONG ; Jing LIN ; Jingmei SHI ; Xiaojie YANG ; Hui FANG ; Xiaodong YAN
Chinese Journal of Internal Medicine 2012;(12):957-961
Objective To characterize the baseline status of Chinese diabetic patients based on data derived from Chinese cohort from SOLVETM study.Methods Patients with type 2 diabetes initiating basal insulin detemir at the decision of the physician were eligible for the study.Data on demographics,medical history,glycemic profile and treatment regimen at baseline were collected by physicians.Results A total of 3272 patients [female 42%,male 58%,mean age (56.2 ± 10.8) years] were included in the study.Their BMI was (25.3 ± 3.3) kg/m2.The duration of diabetes was 4.0 (0.1-27.0) years,and the duration of treatment with oral antidiabetic drugs (OADs) was 3.0(0.0-20.2) years.The proportions of subjects with diabetic macro-and micro-vascular complications were 15.8% (515 cases) and 27.1% (866 cases),respectively.The hemoglobin Al c (HbAl c) at baseline was (8.33 ± 1.70) %,and the fasting blood glucose (FPG) was (9.5 ± 2.6) mmol/L.Conclusions A large proportion of patients with type 2 diabetes remain in poor glycemic control,and the prevalence of diabetic complications is high,which requires optimal therapeutic strategy for the patients with suboptimal glycemic control.
10.Effect of synthetic intervention on schizophrenic outpatients re-entry community
Yanhu WANG ; Chaojuan MU ; Xinsheng CHAI ; Chongquan ZHENG ; Jingxuan ZHANG ; Zheng WENG ; Jisheng TANG
Chinese Journal of Health Management 2010;04(6):362-365
Objective To investigate the effect of synthetic intervention on community re-entry of outpatients with schizophrenia. Methods Two hundred and eighty-four patients were randomly assigned to the intervention group (n = 143 ) and the control group (n = 141 ). The participants in the intervention group received mental health education, medication consultation, skill training and family-based psychological intervention for 1 year. The control group was followed up through clinic visits. At baseline,half a year and the end of the year,all the subjects completed the Social Support Rating Scale (SSRS) and the Positive and Negative Syndrome Scale (PANSS). Results The scores of SSRS and PANSS at baseline were not significantly different between the two groups. At the end of the year,the score of SSRS (32. 85 ± 12. 18) ,the objective support subscale (9. 15± 4. 18 ) ,the subjective support subscale ( 16. 92±7. 34) and the support utility subscale (6. 77±2. 09 ) in the intervention group were significantly increased when compared with the control group ( 31.05±8. 35,7. 77±4. 36,13.46±7.87,6. 23±2. 12, all P < 0.05 ). The score of PANSS (38. 88 ±9. 58 ), the positive subseale (7.40 ±1.12 ), the negative subscale ( 11. 32±5.92 ) and the general psychopathology subscale (20. 16±5. 19 ) in the intervention group showed significant difference with the control group (46. 88 ±16. 37,8.60 ±3. 19,13.52±7. 81,24. 76±8. 08 ,all P <0. 01 ). At the end of the year,the relapse of psychotic symptoms in the intervention and the control group was 18. 18% and 34. 75% ,respectively ( χ2 = 10. 03, P < 0. 01 ). Conclusion The study results suggest that synthetic intervention could be effective for schizophrenic outpatients in community re-entry.

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