1.Protein-centric omics analysis reveals circulating complements linked to non-viral liver diseases as potential therapeutic targets
Yingzhou SHI ; Hang DONG ; Shiwei SUN ; Xiaoqin WU ; Jiansong FANG ; Jianbo ZHAO ; Junming HAN ; Zhongyue LI ; Huixiao WU ; Luna LIU ; Wanhong WU ; Yang TIAN ; Guandou YUAN ; Xiude FAN ; Chao XU
Clinical and Molecular Hepatology 2024;30(1):80-97
Background/Aims:
To evaluate the causal correlation between complement components and non-viral liver diseases and their potential use as druggable targets.
Methods:
We conducted Mendelian randomization (MR) to assess the causal role of circulating complements in the risk of non-viral liver diseases. A complement-centric protein interaction network was constructed to explore biological functions and identify potential therapeutic options.
Results:
In the MR analysis, genetically predicted levels of complement C1q C chain (C1QC) were positively associated with the risk of autoimmune hepatitis (odds ratio 1.125, 95% confidence interval 1.018–1.244), while complement factor H-related protein 5 (CFHR5) was positively associated with the risk of primary sclerosing cholangitis (PSC;1.193, 1.048– 1.357). On the other hand, CFHR1 (0.621, 0.497–0.776) and CFHR2 (0.824, 0.703–0.965) were inversely associated with the risk of alcohol-related cirrhosis. There were also significant inverse associations between C8 gamma chain (C8G) and PSC (0.832, 0.707–0.979), as well as the risk of metabolic dysfunction-associated steatotic liver disease (1.167, 1.036–1.314). Additionally, C1S (0.111, 0.018–0.672), C7 (1.631, 1.190–2.236), and CFHR2 (1.279, 1.059–1.546) were significantly associated with the risk of hepatocellular carcinoma. Proteins from the complement regulatory networks and various liver diseaserelated proteins share common biological processes. Furthermore, potential therapeutic drugs for various liver diseases were identified through drug repurposing based on the complement regulatory network.
Conclusions
Our study suggests that certain complement components, including C1S, C1QC, CFHR1, CFHR2, CFHR5, C7, and C8G, might play a role in non-viral liver diseases and could be potential targets for drug development.
2.Characteristics of TCM syndrome elements and syndromes of hypertension with insomnia in the real world
Chunqiu ZHU ; Xiaoya LI ; Hui LI ; Junming FAN ; Hui QING ; Yongshu DONG ; Weifeng CUI
International Journal of Traditional Chinese Medicine 2023;45(12):1482-1489
Objective:To analyze the distribution of TCM syndrome elements and syndromes in patients with hypertension with insomnia (HWI) in the real world.Methods:A cross-sectional study and retrospectively enrolled. The positive symptoms and TCM syndrome type entries of 359 patients with HWI who were collected from Henan Integrated Medicine Hospital,Henan Provincial People's Hospital,the First Affiliated Hospital of Henan University of Chinese Medicine from December 2020 to August 2022 were retrospectively studied. Based on factor analysis dimension reduction and systematic cluster analysis, the TCM syndrome elements and potential syndrome types of patients were summarized. The Latern 5.0 software was used to establish a latent structure model and comprehensive clustering based on the mountain climbing method (LTM-EAST) algorithm, and analyze and judge the common syndrome types, providing a basis for proposing the clinical common syndrome types of this disease.Results:Factor analysis extracted 14 common factors, and the cumulative contribution rate was 63.254%. Among the 36 symptom variables with frequency ≥ 70, more than half of the patients with hypertension and insomnia were upset, irritable, less sleepy, dreamy, dizzy, palpitations, stuffy chest, dry mouth, easy to wake up, and tired. The tongue color was mainly light red tongue and red tongue. The tongue is mainly thin and greasy. The first three pulse conditions are string pulse, number pulse and slippery pulse. The disease location and syndrome elements of hypertension with insomnia were mainly liver (52.09%), heart (33.43%), spleen (26.46%) and kidney (23.68%); The disease syndrome elements are mainly phlegm dampness (34.54%), yin deficiency (29.25%), heat (fire) (25.35%), and qi stagnation (25.07%). Ten syndrome types are obtained by frequency statistics, nine syndrome types are obtained by factor clustering, and seven syndrome types are inferred by implicit structure clustering. Among the syndrome types inferred by the above three methods, there are seven syndrome types that recur at least twice, which can be identified as the common syndrome type of hypertension with insomnia.Conclusions:The common clinical symptoms of HWI are upset and irritable, less sleep, more dreams, dizziness, palpitations, stuffy chest, dry mouth, easy to wake up, mental fatigue and body tiredness. The disease location and syndrome elements are mainly in liver, heart, spleen and kidney. The disease mainly involves phlegm dampness, yin deficiency, heat and qi stagnation. The common clinical syndrome types are liver depression transforming fire type, yin deficiency and yang hyperactivity type, phlegm dampness intrinsic type, yin deficiency and internal heat type, heart and gallbladder qi deficiency type, heart and spleen deficiency type, and heart kidney disjunction type.
3.Preoperative ascending aorta diameter and prognosis analysis of patients with acute type A aortic dissection
Yuduo WU ; Ming GONG ; Lizhong SUN ; Lianjun HUANG ; Yongmin LIU ; Junming ZHU ; Tianxiang GU ; Ruixin FAN ; Ximing QIAN ; Yihua HE ; Hongjia ZHANG
Chinese Journal of Thoracic and Cardiovascular Surgery 2022;38(4):235-240
Objective:To investigate the preoperative ascending aorta diameter in patients with acute type A aortic dissection in the Chinese population, compares and analyze the differences in preoperative blood biomarkers, and evaluate the impact of the preoperative ascending aorta diameter in this part of patients on the short-term prognosis of patients.Methods:A collection of 641 patients with acute type A aortic dissection who were enrolled in the " Acute Aortic Syndrome High-Risk Early Warning and Intervention Study" project from January 2018 to January 2020 were collected. Divide the patients into two groups (group Ⅰ<55 mm, group Ⅱ≥55 mm) according to the preventive intervention value of ascending aorta diameter recommended by the guideline for studying preoperative ascending aorta diameter difference in blood biomarkers and the influence of ascending aorta diameter on the short-term prognosis of patients. All patients had CT scans to assess the diameter of the ascending aorta before operation.Results:In this study, all patients with acute type A aortic dissection had a mean preoperative ascending aorta diameter of (46.9±9.7)mm. The preoperative ascending aorta diameter of all patients was less than 55 mm, accounted for 84.1%. Male patients were more likely to have aortic dissection than females; most patients' age was less than 60 years old. The preoperative blood inflammatory index counts were higher in the ascending aorta diameter ≥55 mm group. However, the long-term prognosis of patients with different ascending aorta diameters before surgery was not apparent in this study. The preoperative survival rate and short-term survival rate of patients with ascending aorta diameter <55 mm were higher than those of other groups, but the difference was not statistically significant.Conclusion:In patients with acute type A aortic dissection, the diameter of the ascending aorta is usually less than 55 mm. Moreover, the blood inflammatory index counts are high in the preoperative ascending aorta diameter ≥55 mm group. Meanwhile, patients with smaller ascending aorta diameter have better survival rate and short-term prognosis.
4.Preoperative risk factors for the onset of acute Stanford type A aortic dissection in a multicenter study: A retrospective cohort study
Yuduo WU ; Ming GONG ; Lizhong SUN ; Lianjun HUANG ; Yongmin LIU ; Junming ZHU ; Tianxiang GU ; Ruixin FAN ; Ximing QIAN ; Hongjia ZHANG
Chinese Journal of Clinical Thoracic and Cardiovascular Surgery 2022;29(08):986-991
Objective To evaluate the preoperative risk factors for acute Stanford type A aortic dissection (ASTAAD) patients in our country by collecting multi-center data. Methods We consecutively enrolled 700 patients who underwent surgery for ASTAAD in the multi-center hospital database from January 2018 to January 2020. According to the ascending aorta size (AAS), the patients were divided into two groups: a group AAS≥55 mm and a group AAS< 55 mm. Univariate and multivariate logistic regression analyses were used to investigate the related preoperative risk factors for the onset of ASTAAD. Results According to the exclusion criteria, a total of 621 patients were finally enrolled, including 453 males and 168 females with an average age of 48.24±11.51 years, and 509 (81.94%) patients had AAS< 55 mm. Univariate and multivariate statistical analyses showed that smoking, hypertension, preoperative cardiac troponin I, and left ventricular ejection fraction were related to the occurrence of ASTAAD. The mortality rate of the patient during hospitalization was 13.04% (81 patients). Conclusion In clinical practice, various preoperative risk factors affect ASTAAD patients, which should be paid attention to. Comprehensive evaluation and an individualized analysis of patients and timely prevention and intervention improve patients' survival rate.
5.Moderating effect of sense of coherence between occupational stress and depression
Hao CHEN ; Bo YE ; Lei WANG ; Yanxia WEI ; Junming DAI ; Junling GAO ; Fan WANG ; Hua FU
Chinese Journal of Preventive Medicine 2020;54(8):844-848
Objective:To explore the moderating effect of sense of coherence in the relationship between occupational stress and depression.Methods:From June to September in 2018, migrant workers were purposively selected from the urban (including office buildings, shopping malls, barber shops or restaurants and other service enterprises) and suburban (including microelectronics, internet, clothing processing and art design and other factories) areas of Shanghai. A total of 3 034 people were investigated and 2 573 valid questionnaires were collected. Patient health questionnaire (PHQ), sense of coherence questionnaire (SOC) and job content questionnaire (JCQ) were used to investigate the levels depression, sense of coherence and occupational stress. Hierarchical regression analysis was used to analyze the moderating effect of sense of coherence on occupational stress and depression, and SPSS PROCESS macro program and Bootstrap method were used to further explore the moderating effect of sense of coherence.Results:The age of total 2 573 migrant workers was (28.24±7.33) years old and 49.79% of them were males. The scores of depression, occupational stress and sense of coherence were 6.67±4.74, 28.45±4.38 and 62.02±10.89, respectively. The depression level was positively correlated with occupational stress ( r=0.33, P=0.007), and negatively correlated with sense of coherence ( r=-0.53, P=0.003). The hierarchy regression analysis suggested that the interaction between occupational stress and sense of coherence was associated with depression symptom (β=-0.07, P=0.001). Bootstrap analysis showed that occupational stress was not associated with depression symptom with high level of sense of sense of coherence (β=0.04, 95% CI=-0.01-0.10), while occupational stress was associated with depression symptom with low level of sense of sense of coherence (β=0.19, 95% CI=0.14-0.23). Conclusion:The high level of sense of coherence has a moderating effect on the relationship between occupational stress and depressive symptoms, while the low level of sense of coherence does not have this effect.
6.Moderating effect of sense of coherence between occupational stress and depression
Hao CHEN ; Bo YE ; Lei WANG ; Yanxia WEI ; Junming DAI ; Junling GAO ; Fan WANG ; Hua FU
Chinese Journal of Preventive Medicine 2020;54(8):844-848
Objective:To explore the moderating effect of sense of coherence in the relationship between occupational stress and depression.Methods:From June to September in 2018, migrant workers were purposively selected from the urban (including office buildings, shopping malls, barber shops or restaurants and other service enterprises) and suburban (including microelectronics, internet, clothing processing and art design and other factories) areas of Shanghai. A total of 3 034 people were investigated and 2 573 valid questionnaires were collected. Patient health questionnaire (PHQ), sense of coherence questionnaire (SOC) and job content questionnaire (JCQ) were used to investigate the levels depression, sense of coherence and occupational stress. Hierarchical regression analysis was used to analyze the moderating effect of sense of coherence on occupational stress and depression, and SPSS PROCESS macro program and Bootstrap method were used to further explore the moderating effect of sense of coherence.Results:The age of total 2 573 migrant workers was (28.24±7.33) years old and 49.79% of them were males. The scores of depression, occupational stress and sense of coherence were 6.67±4.74, 28.45±4.38 and 62.02±10.89, respectively. The depression level was positively correlated with occupational stress ( r=0.33, P=0.007), and negatively correlated with sense of coherence ( r=-0.53, P=0.003). The hierarchy regression analysis suggested that the interaction between occupational stress and sense of coherence was associated with depression symptom (β=-0.07, P=0.001). Bootstrap analysis showed that occupational stress was not associated with depression symptom with high level of sense of sense of coherence (β=0.04, 95% CI=-0.01-0.10), while occupational stress was associated with depression symptom with low level of sense of sense of coherence (β=0.19, 95% CI=0.14-0.23). Conclusion:The high level of sense of coherence has a moderating effect on the relationship between occupational stress and depressive symptoms, while the low level of sense of coherence does not have this effect.
7. Treatment strategies of complex lesions in patients with acute Stanford type A dissection of important branches involvement
Guimin ZHANG ; Jianming XIA ; Yi SUN ; Lihua FAN ; Yuyin DUAN ; Songhua YU ; Bingsong DUAN ; Bin LI ; Song MEI ; Long ZHOU ; Hongbo HUANG ; Jiayu LI ; Qiuzhe GUO ; Junming ZHU
Chinese Journal of Surgery 2017;55(4):251-254
Acute Stanford type A aortic dissection with important branches involved is more complex, could lead to organ malperfusion syndrome even organ failure. The understanding of pathological anatomy, classification, staging, and the pathophysiological change has increasingly mature, but not complete. In addition, the treatment strategy for complex lesions is diversified, some questions may not reach consensus. Fully understanding of the anatomical and pathophysiology is very important for surgeons to choose reasonable treatment strategy. As the rapid development of the basic research, imaging techniques and the concept of surgery procedures, the manage technique of Stanfrod type A dissection and branch vessels at the same time is getting seriously, the related issues also need further discussions.
8.Protective effect of imatinib on myocardial fibrosis in uremic rats
Li WANG ; Hongchun SHEN ; Junming FAN
Chongqing Medicine 2016;(3):313-316
Objective To evaluate the effect of imatinib in improving myocardial fibrosis in uremic rats through regulating the expression of PDGFRα.Methods Seventy two rats were divided into three groups ,which were Sham group ,5/6 group and 5/6+I group .All The rats in 5/6 group underwent the 5/6 nephrectomy and the rats in 5/6+I group were given imatinib by ga‐vage after the operation of 5/6 nephrectomy .Hearts were harvested for HE and Sirius red staining at 8 weeks post surgery .The ex‐pression of PDGFRαwas assessed with immunohistological staining .The real‐time PCR was employed to detect the PDGFRαmR‐NA level in hear samples .Results The urine protein ,Scr ,BUN of the 5/6 group and 5/6+I group were higher than that of Sham group(P<0 .01) .The myocardial pathological score in Sham group was significantly lower than that of 5/6 group (P<0 .01) ,and the score in 5/6+I group was significantly lower than that of 5/6 group (P<0 .01) .The collagen volume fraction (CVF) in 5/6 group was significantly higher than that in Sham group (P<0 .01) .And the CVF in 5/6+ I group was higher than that in Sham group (P<0 .05) ,but lower than that of 5/6 group (P<0 .05) .The expression ratio of PDGFRαmRNA and staining rate in 5/6 group and 5/6+I group were both much higher than that in Sham group (P<0 .01) ,and the expression in 5/6+I group was signif‐icantly lower than that in 5/6 group (P<0 .05) .Conclusion These data suggest that the tyrosine kinase inhibitor imatinib reduces heart injury and attenuates myocardial fibrosis in uremic rat by mechanisms associated with the inhibition of the expression of PDGFRα.
9.Effects of bone morphogenetic protein 2 signal pathway on renal artery calcification in progression of diabetic nephropathy
Chunmei QIN ; Weihua WU ; Jian LIU ; Junming FAN ; Caipan GONG ; Xiao WEI ; Santao OU
Chinese Journal of Nephrology 2016;32(3):173-179
Objeetive To explore the effects of renal artery calcification on the progression of diabetic nephropathy (DN),the activation and its role of bone morphogenetic protein 2(BMP2) signal pathway in renal artery of rats.Methods Sixty male SD rats were randomly divided into control group(CON group),DN group and DN with vascular calcification group (DN+VDN group).Rats of group DN and DN + VDN were fed with high sugar and fat diet and injected with streptozocin (STZ) into abdominal cavity to induce diabetes.After diabetic models were successfully made,rats of group DN+ VDN were treated by vitamin D3 plus nicotine.The rats were sacrificed at 8th,12th and 16th week respectively and the levels of renal function,blood glucose and 24 h urinary protein (24-h Upro) were measured.The pathologic changes to the renal artery were observed by yon-Kossa staining and the calcium content was detected by calcium assay kit.The pathologic changes to the kidney were observed by HE.Immunohistochemistry was applied to detect the protein expression of BMP2/Smad1/Runx2/ Osterix signal pathway in the renal artery and real-time PCR were applied to detect the mRNA expression levels of BMP2 and Runx2.Results The calcium content and the deposition of black granules in DN group were significantly higher than those in group CON and lower than DN + VDN group at each time point (P < 0.05).The renal function indices in group DN and group DN+VDN were gradually increased in 8th,12th and 16th weeks,and were higher than those in group CON (P < 0.05).Compared with that in DN group,although the level of BUN,Scr,Cys C and 24-h Upro in DN+VDN group rats were higher at different time point,the level of Cys C at each time point and the level of 24-h Upro in the 16th week showed significant differences (P < 0.05).The pathological damages of the kidney in group DN and DN+VDN showed a continual worsening trend and the pathological changes of the kidney in group DN+VDN were more serious than those in group DN.Furthermore,the levels of BMP2/Smad1/Runx2/Osterix signal protein and BMP2,Runx2 mRNA in DN rats were higher than those in CON group,lower than DN+VDN group at each time point (P < 0.05).Correlation analysis demonstrated that calcium content was positively correlated with serum BUN,Scr,Cys C,24-h Upro and the expression of BMP2,Runx2 mRNA (r=0.835,0.705,0.829,0.897,0.641,0.683,P < 0.01,respectively).Conclusion Renal artery calcification may participate in and promote the progression of DN,and the BMP2 signal pathway may be an important regulating factor in DN with renal artery calcification.
10.Research on radix notoginseng for improving CKD rat renal fibrosis
Ying XU ; Li WANG ; Linmei JI ; Hongchun SHEN ; Sijing CHENG ; Junming FAN ; Dan WEN
Chongqing Medicine 2016;45(33):4625-4628
Objective To investigate the effects of notoginseng and guiding medicinals mediated notoginseng for improving the renal inter stitial fibrosis in rats with chronic kidney-disease(CKD)by regulating TGF-β signaling pathway.Methods A total of 100 male SD rats were randomly divided into five groups:normal group(NOR,n =20),model group(CKD,n =20),radix notogin-seng group(RN,n =20),radix notoginseng plus platycodi group (RNP) and radix notoginseng plus cinnamon group (RNC,n =20).Except for the NOR group,the CKD rat model in other groups was established by adenine gavage.After modeling,the NOR group and CKD group were given the same volume of normal saline by gavage,while the group RN,RNP and RNC were given corresponding drugs by gavage,for 4 weeks.After 4 weeks,the rats in each group were sacrificed for collecting serum and detecting the renal function(serum Scr,BUN),the renal tissues were taken for conducting HE and Masson staining.Then the renal tissue pathological damage severity was observed.The expressions of FN and LN in kidney tissue were detected by immunohistochemistry and the expressions of TGF-[β,α-SMA were detected by Western blot method.Results Compared with the NOR group,the model group exhibited the renal dysfunction(P<0.01),renal interstitial severe fibrosis manifestation and increased collagen deposition(P<0.05),and the expression of kidney tissues α-SMA(P<0.01),TGF-β(P<0.01),FN and LN were significantly increased.Compared with the model group,the renal function in various treatment groups was improved,Scr(P<0.01)and BUN(P<0.01)were significantly decreased,the renal interstitial fibrosis degree was reduced,collagen desposition was decreased(P<0.05),renal tissue α-SMA(P< 0.05),TGF-β(P<0.05),FN and LN expression were reduced to some extent,in which the effect of RNC group was stronger than that of the RN group and RNP group.Conclusion Notoginseng and guiding medicinals mediated notoginseng can retard the progression of renal interstitial fibrosis caused by adenine in CKD rat in varying degrees,its mechanism maybe reduce the expression of TGF-β protein.

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