Value of serum complement C3 in the diagnosis of liver fibrosis associated with primary biliary cholangitis / 临床肝胆病杂志

‍ ObjectiveTo investigate the value of serum complement C3 level in determining the stage of liver fibrosis in primary biliary cholangitis （PBC）. MethodsClinical data were collected from 108 patients with PBC who attended Tianjin Second People’s Hospital and underwent liver biopsy from January 2012 to October 2022. The degree of liver fibrosis （S0-4） was assessed according to the Scheuer scoring system， with ≥S2 defined as significant liver fibrosis， ≥S3 defined as progressive liver fibrosis， and S4 defined as liver cirrhosis. The independent samples t-test was used for comparison of normally distributed continuous data between two groups， and a one-way analysis of variance was used for comparison between multiple groups； the Mann-Whitney U test was used for comparison of non-normally distributed continuous data between two groups， and the Kruskal-Wallis H test was used for comparison between multiple groups； the chi-square test or the Fisher’s exact test was used for comparison of categorical data between groups. The area under the ROC curve （AUC） was used to evaluate the efficacy of complement C3 in the diagnosis of liver fibrosis in patients with PBC. The Spearman correlation analysis was used to investigate the correlation between complement C3 and liver fibrosis stage. ResultsAmong the 108 patients with PBC， there were 87 （80.6%） female patients and 102 patients （94.4%） with positive autoantibody. As for the stage of liver fibrosis， there were 5 patients （4.6%） in S0 stage， 41 （38.0%） in S1 stage， 23 （21.3%） in S2 stage， 25 （23.1%） in S3 stage， and 14 （13.0%） in S4 stage. There was a significant difference in the level of complement C3 between the patients with different liver fibrosis stages （H=42.891， P<0.001）. The level of complement C3 gradually decreased with the aggravation of liver fibrosis， with a negative correlation between them （r=-0.565， P<0.001）. Liver stiffness measurement （LSM）， aspartate aminotransferase/alanine aminotransferase ratio， aspartate aminotransferase-to-platelet ratio index， and fibrosis-4 were negatively correlated with complement C3， with a correlation coefficient of -0.439 （P<0.001）， -0.323 （P=0.001）， -0.206 （P=0.033）， and -0.291 （P=0.002）， respectively. The multivariate logistic regression analysis showed that complement C3 level was an independent predictive factor for significant liver fibrosis， progressive liver fibrosis， and liver cirrhosis， while LSM was an independent predictive factor for significant liver fibrosis and progressive liver fibrosis. The ROC curve analysis showed that complement C3 had an AUC of 0.731， 0.832， and 0.968， respectively， in the diagnosis of significant liver fibrosis， progressive liver fibrosis， and liver cirrhosis， with a corresponding cut-off value of 1.445， 1.235， and 1.005， respectively， and complement C3 combined with LSM had an AUC of 0.811， 0.941， and 0.976， respectively， in the diagnosis of significant liver fibrosis， progressive liver fibrosis， and liver cirrhosis. There was a significant difference in AUC between complement C3 combined with LSM and complement C3 alone in the diagnosis of significant liver fibrosis （Z=2.604， P=0.009）， and there was also a significant difference in AUC between complement C3 combined with LSM and complement C3 alone in the diagnosis of progressive liver fibrosis （Z=3.033， P=0.002）； there was no significant difference in AUC between complement C3 combined with LSM and complement C3 alone in the diagnosis of liver cirrhosis （Z=1.050， P=0.294）， while There was a significant difference in AUC between complement C3 combined with LSM and LSM alone in the diagnosis of liver cirrhosis （Z=2.326， P=0.020）. ConclusionSerum complement C3 level has a certain clinical value in assessing the degree of liver fibrosis in patients with PBC， and complement C3 combined with LSM can further improve the efficacy of complement C3 or LSM in the diagnosis of liver fibrosis in PBC.

Association of serum complement C3, C4 with renal pathological lesion degree in IgA nephropathy patients / 中华肾脏病杂志

Objective:To explore the relationship between the levels of serum complement C3 and C4 and the degree of renal pathological injury in patients with IgA nephropathy (IgAN).Methods:It was a retrospective study. The clinical and pathological data of patients with primary IgAN diagnosed by renal biopsy in the Department of Nephrology of the Second People's Hospital of Qujing City, Yunnan Province from December 1, 2019 to December 31, 2022 were collected. According to the IgAN Oxford classification criteria, the patients were divided into mild renal pathological injury group (mild group, <3 pathologic types) and severe renal pathological injury group (severe group, ≥3 pathological types). The levels of serum C3 and C4 and other clinical data were compared between the two groups. Spearman correlation method was used to analyze the correlation between serum C3, C4 levels and estimated glomerular filtration rate (eGFR) during renal biopsy.Multivariate logistic regression model was used to analyze the influencing factors of the pathological injury degree in IgAN patients and the forest map depicted the effect of risk factors.Results:A total of 164 IgAN patients were included in the study, including 77 males (47.0%), aged (35.5±12.9) years old. There were 60 patients in the mild group and 104 patients in the severe group. Compared with the mild group, the patients in the severe group were older, had higher levels of serum C4, serum uric acid, low density lipoprotein cholesterol and 24 h urinary protein, higher proportions of hypertension, glucocorticoids/immunosuppressant therapy, C3 deposition in renal tissues and microscopic hematuria, and had lower hemoglobin and serum C3 level (all P<0.05). The results of Spearman correlation analysis showed that the level of serum C3 was positively correlated with eGFR ( r=0.303, P<0.001), and the level of serum C4 was negatively correlated with eGFR ( r=-0.238, P=0.002). Multivariate logistic regression analysis results showed that serum C3 (every 0.01 g/L increase, OR=0.976, 95% CI 0.957-0.996, P=0.018), serum C4 (every 0.01 g/L increase, OR=1.091, 95% CI 1.020-1.166, P=0.011), hemoglobin ( OR=0.969, 95% CI 0.950-0.988, P=0.002), and serum uric acid ( OR=1.005, 95% CI 1.001-1.009, P=0.012) were independent related factors of renal pathological damage (severe injury /mild injury) in IgAN patients. Conclusions:Serum C3 and C4 are independent related factors of the severity of renal pathological injury in IgAN patients.

Expression of type 2 complement receptor in kidney tissue of IgA nephropathy patients and the possible mechanism involved in complement C3 deposition / 中华肾脏病杂志

Objective:To explore the expression of type 2 complement receptor (CR2) in mesangial cells of the renal tissue in IgA nephropathy (IgAN) and its possible mechanism involved in complement C3 deposition.Methods:The demographic data, samples of plasma and renal tissues of primary IgAN patients diagnosed by renal biopsy in the Guangdong Provincial People's Hospital from August 2021 to May 2022 were collected. According to the fluorescent intensity of mesangial complement C3 deposition, the patients were divided into complement C3 deposition ≥2+ group and complement C3 deposition <2+ group. The circulating IgA and complement C3 levels were detected by enzyme linked immunosorbent assay (ELISA). The influencing factors of kidney prognosis, plasma IgA and complement C3 levels were compared between the two groups. Immunofluorescence was used to detect the expression of IgA, complement C3 and CR2 in the renal mesangial cells of IgAN patients and normal renal tissues around renal carcinoma. Human mesangial cells were cultured in vitro and randomly divided into control group and experimental group. The experimental group was incubated with IgA protein (2 g/L) for 8 hours. The expressions of CR2 protein and mRNA were measured by Western blotting and real-time fluorescence quantitative PCR. The biological function of differential genes was analyzed by gene ontology (GO) and Kyto encyclopedia of genes and genomes (KEGG) enrichment analysis. Results:A total of 75 patients with IgAN were included in this study, including 50 patients in the complement C3 deposition ≥2+ group and 25 patients in the complement C3 deposition <2+ group. The proportions of patients with urine red blood cell count negative, 1+, 2+ and 3+-4+ in the complement C3 deposition ≥2+ group were 2.0%, 8.0%, 18.0% 72.0%, respectively, which were more serious than those in the complement C3 deposition <2+ group (4.0%, 4.0%, 52.0%, 40.0%) ( Z=-2.320, P=0.020). Meanwhile, the proportion of S1 in Oxford pathological classification in the complement C3 deposition ≥2+ group was higher than that in the complement C3 deposition <2+ group (68.0% vs. 40.0%, χ2=5.389, P=0.020), and there were no statistically significant differences in gender, age, 24-hour urinary protein, serum creatinine, other indicators of Oxford pathological classification between the two groups. ELISA results showed that plasma IgA concentration in the complement C3 deposition ≥2+ group was higher than that in the complement C3 deposition <2+ group [3.62 (2.95, 5.53) g/L vs. 2.72 (2.15, 4.24) g/L, Z=2.405, P=0.016], and the plasma complement C3 concentration was lower than that in the complement C3 deposition <2+ group [199.6 (116.0, 328.0) mg/L vs. 319.2 (158.3, 454.5) mg/L, Z=-2.383, P=0.017]. Spearman correlation analysis showed that the complement C3 deposition intensity was positively correlated with IgA deposition intensity in mesangial area ( rs=0.441, P<0.001). Immunofluorescence results showed that there was colocalization of IgA and complement C3 in the glomeruli of IgAN patients. The expression of CR2 in the kidney was consistent with complement C3 deposition, and CR2 was colocalization with complement C3. In vitro experiments, the expression of CR2 in IgA protein group was higher than that in the control group ( P<0.05). GO and KEGG enrichment analysis found that IgA protein induced active changes in various pathways of mesangial cells. Conclusion:IgA protein induces mesangial cells to express CR2 and participates in complement C3 deposition, which may be an important mechanism of complement C3 activation in IgAN.

Clinicopathological characteristics and prognosis of idiopathic membranous nephropathy with or without C3 deposition / 中华全科医师杂志

Objective:To investigate the clinicopathological characteristics and prognosis of idiopathic membranous nephropathy (IMN) with or without C3 deposition.Methods:Clinical and pathological data of 576 patients with IMN diagnosed in Affiliated Hospital of Qingdao University from January 2017 to January 2021 were retrospectively analyzed. The patients were divided into C3 deposition group and non-C3 deposition group according to the immunofluorescence staining of C3. The clinical and pathological characteristics were compared between the two groups. Kaplan-Meier survival curve was used to compare the prognosis of the two groups.Results:A total of 576 IMN patients (male 364 (63.20%)) were enrolled, including 400 patients (69.44%) with C3 deposition and 176 patients (30.56%) without C3 deposition. Compared with the non-C3 deposition group, the levels of total blood cholesterol ( t=0.94, P=0.002) and the proportion of phospholipase A2 receptor ( χ2=9.99, P=0.002), IgG ( χ2=10.67, P=0.001), IgM ( χ2=7.00, P=0.008), IgA ( χ2=7.87, P=0.005) and C1q ( χ2=8.28, P=0.004) depositions in renal tissues was higher in C3 deposition group, while the levels of serum C3 ( t=2.87, P=0.004), albumin ( t=3.57, P<0.001) and IgG ( Z=3.55, P<0.001) were lower in C3 deposition group. There were no significant differences in other clinicopathological indicators between the two groups. The survival analysis was performed in 460 patients who were followed for>6 months, including 319 cases (69.35%) of C3 deposition and 141 cases (30.65%) of non-C3 deposition. The end point event was defined as an eGFR decline>30% or entry into end stage renal disease (ESRD). There was no statistically significant difference in treatment method between the two groups ( P>0.05). The median follow-up time was 22 (13,32) months, 327 (71.09%) patients achieved remission, and 22 patients had renal end-point events. Compared with the non-C3 deposition group, the proportion of urinary protein remission was lower ( χ2=10.85, P<0.05), the incidence of renal end-point events was higher ( χ2=5.05, P<0.05). Kaplan-Meier survival analysis showed that patients with C3 deposition had a lower cumulative remission rate (Log-rank χ2=6.68, P=0.010), and a lower cumulative renal survival than those without C3 deposition had ( χ2=5.42, P=0.020). Conclusions:Compared with patients without C3 deposition, IMN patients with C3 deposition have more severe clinical and pathological changes, lower renal cumulative remission rate, and are more likely to have poor prognosis.

Activation of the complement C3/C3aR pathway in the prefrontal cortex mediates methamphetamine addiction in rats / 中国药理学与毒理学杂志

OBJECTIVE To investigate the role of the complement C3/C3aR signaling pathway in the prefrontal cortex and colon neuroglia cell interactions during meth-amphetamine(METH)addiction,to observe the effects of TLR4 inhibitors as well as complement C3 elimination on METH reward and relapse behavior,and to explore the neuroinflammatory mechanisms of complement C3 acti-vation in METH addiction.METHODS ①A 14 d and 28 d rat METH addiction model was established to observe the effects of TLR4 antagonist ibudilast 3 mg·kg-1 and 10 mg·kg-1 on self-administration,reward motivation,relapse,and natural reward behavior in METH-trained 14 d rats and the effects of 0.02 mg·kg-1 complement C3 antago-nist on self-administration behavior in METH-trained 28 d rats.② Differences in the expression of TLR4,NF-κB,GRP94,C3,cathepsin L,CD68,and GFAP in the pre-frontal cortex of each group were examined using West-ern blotting.③ In addition,the expression of ATF6 in the prefrontal cortex of each group and the effects on neuro-nal and microglia/macrophage INOS,CD206 GRP94,and complement C3/C3aR.RESULTS ① Endoplasmic reticulum stress occurred in neurons and microglia after METH exposure depending on GRP94 and unfolded pro-tein responses to the ATF6 pathway.In addition,it acti-vates the TLR4-NF-κB pathway.② Microglia with high complement C3/C3aR expression in the prefrontal cortex were recruited to synaptic pruning and phagocytic responses around neurons with high GRP94,comple-ment C3/C3aR expression and these effects were blocked by complement C3 antagonists.③ In the rec-tum,GRP94 functions as a molecular chaperone for com-plement C3 and cathepsin L.Crosstalk occurs between enteric neurons high in GRP94,complement C3,and macrophages high in C3aR,located in the submucosa,lamina propria,and muscular,respectively,and all of these effects are blocked by complement C3 antago-nists.④ Treatment with the TLR4 antagonist ibudilast inhibits self-administration,reward motivation,and cue-or METH-priming in METH-trained 14 d rats,but fails to affect natural reward behavior.Ibudilast treatment attenu-ates the TLR4-NF-κB inflammatory pathway and comple-ments C3/C3aR pathway in the prefrontal cortex.CON-CLUSION Activation of the complement C3/C3aR signal-ing pathway by TLR4-NF-κB inflammatory signaling in the prefrontal cortex mediates the METH addiction pro-cess,providing an experimental basis for the clinical treatment of METH addiction,and targeting TLR4/NF-κB inflammatory signaling and complement C3/C3aR may be a new way to intervene in METH addiction.

The relationship between C3, C4, Th1/Th2 levels and the MG-ADL score in patients with myasthenia gravis and its efficacy in predicting the transition of ocular muscle type to systemic type / 中国医师杂志

Objective:To investigate the relationship between C3, C4, Th1/Th2 levels and the Myasthenia Gravis Daily Living Scale (MG-ADL) score in patients with myasthenia gravis (MG) and its efficacy in predicting the transition of ocular muscle type to systemic type.Methods:A retrospective study of 94 patients with ophthalmic MG admitted to Haikou People's Hospital from April 2017 to April 2020 was conducted. According to whether they had converted to systemic MG within 6 months, they were divided into transformation group ( n=35) and non-transformation group ( n=59). The levels of C3, C4 and Th1/Th2, as well as the score of MG-ADL and Quantitative Myasthenia Gravis (QMG) were compared between the two groups before and 1 and 3 months after treatment. The correlation between C3, C4 and Th1/Th2 levels and MG-ADL and OMG scores, as well as the related influencing factors of the transformation from ocular muscle type to systemic type was analyzed. The efficiency of each index in predicting the transformation from ocular muscle type to systemic type was analyzed. Results:At 1 and 3 months after treatment, the C3 and C4 in both groups were significantly higher than before treatment, and Th1/Th2 was significantly lower than before treatment; the C3 and C4 in the non-transformation group were higher than that in the transformation group, while Th1/Th2 was lower than that in the transformation group (all P<0.05). The MG-ADL and QMG scores in 2 groups at 1 and 3 months after treatment were significantly lower than those before treatment, and those in the non-transformation group were lower than those in the transformation group (all P<0.05). C3 and C4 levels were negatively correlated with MG-ADL and QMG scores (all P<0.05), while Th1/Th2 levels were positively correlated with MG-ADL and QMG scores (all P<0.05). At 1 and 3 months after treatment, C3, C4 and Th1/Th2 were the influencing factors for the transformation from ocular muscle type to systemic type (all P<0.05). The area under the curve (AUC) of C3, C4 and Th1/Th2 combined to predict the transformation from ocular muscle type to systemic type at 3 months after treatment was 0.939, and the best predictive sensitivity and specificity were 91.43% and 88.14%, respectively. Conclusions:There is a good linear relationship between C3, C4, Th1/Th2 levels and MG-ADL scores in MG patients, and it has a high efficiency in predicting the transition of ocular muscle type to systemic type.

Complement C3 Aggravates Post-epileptic Neuronal Injury Via Activation of TRPV1 / 神经科学通报·英文版

Epilepsy is a brain condition characterized by the recurrence of unprovoked seizures. Recent studies have shown that complement component 3 (C3) aggravate the neuronal injury in epilepsy. And our previous studies revealed that TRPV1 (transient receptor potential vanilloid type 1) is involved in epilepsy. Whether complement C3 regulation of neuronal injury is related to the activation of TRPV1 during epilepsy is not fully understood. We found that in a mouse model of status epilepticus (SE), complement C3 derived from astrocytes was increased and aggravated neuronal injury, and that TRPV1-knockout rescued neurons from the injury induced by complement C3. Circular RNAs are abundant in the brain, and the reduction of circRad52 caused by complement C3 promoted the expression of TRPV1 and exacerbated neuronal injury. Mechanistically, disorders of neuron–glia interaction mediated by the C3–TRPV1 signaling pathway may be important for the induction of neuronal injury. This study provides support for the hypothesis that the C3–TRPV1 pathway is involved in the prevention and treatment of neuronal injury and cognitive disorders.

Association between serum C3 and progression of renal function in IgA nephropathy / 中华肾脏病杂志

Objective:To investigate the relationship between serum C3 and progression of renal function in IgA nephropathy.Methods:A single-center retrospective cohort study was conducted in patients with IgA nephropathy confirmed by renal biopsy who were admitted to the Second People's Hospital of Shenzhen from January 2011 to June 2020 and the patients were followed up until January 2021. Patients with secondary IgA nephropathy, baseline estimated glomerular filtration rate (eGFR)<30 ml·min -1·(1.73 m 2) -1, lack of baseline serum C3 or creatinine, and follow-up time<6 months were excluded. The clinical data, laboratory examination and renal pathology were collected. The threshold effect analysis was used to obtain the cut-off point, and inflection point and 95% confidence interval were obtained using bootstrapping resampling technique. According to the cut-off point, the patients were divided into serum C3<0.97 g/L group and C3≥0.97 g/L group. The baseline data between the two groups were compared. Cox regression model was used to analyze the correlation between serum C3 level and renal function progression. Results:A total of 414 patients were enrolled in this study, with 145 males (35.0%), and age of (35.15±9.18) years old. The baseline eGFR was 77.80(46.67, 106.10) ml·min -1·(1.73 m 2) -1, and the serum C3 was (1.04 ± 0.19) g/L. There were 153 patients with serum C3<0.97 g/L and 261 patients with serum C3≥0.97 g/L. Compared to patients with serum C3≥0.97 g/L, those patients with serum C3<0.97 g/L were younger and had higher proportion of females, higher levels of hemoglobin and eGFR, and lower levels of mean arterial pressure, total cholesterol, triglyceride, serum uric acid, serum creatinine, 24 h urinary protein, IgA and C4 (all P<0.05). The relationship between serum C3 and progression of renal function was found to be U-shaped by smooth curve fitting. After adjustment for confounding factors such as age, sex, mean arterial pressure, serum uric acid, 24 h urinary protein, and renal pathology (MESTC), the results of the threshold effect and multivariate Cox regression showed, for patients with C3<0.97 g/L, the risk of renal function progression decreased by 40% for every 0.1 g/L increase of C3 ( HR=0.60, 95% CI 0.39-0.94, P=0.024), but for patients with C3≥0.97 g/L, every 0.1 g/L increase in serum C3 increased the risk of renal function progression by 27%( HR=1.27, 95% CI 1.03-1.57, P=0.027). The inflection point was 0.97(95% CI 0.92-1.01) g/L. Conclusions:Serum C3 is nonlinear correlated with the progression of renal function in patients with IgA nephropathy. Serum C3 level maintaining at 0.92-1.01 g/L is associated with better renal prognosis.

Changes in serum C3d and C5b-9 levels in elderly patients with idiopathic membranous nephropathy and their clinical significance / 中华老年医学杂志

Objective:To investigate changes in serum C3d and C5b-9 levels in elderly patients with idiopathic membranous nephropathy(IMN)and their correlations with prognosis.Methods:Two hundred thirty-one elderly patients with IMN and 96 non-elderly patients with IMN confirmed by kidney biopsy at the First Affiliated Hospital of Zhengzhou University from January 2015 to May 2017 were enrolled.During the same period, 118 healthy individuals receiving health checkups were included as controls.Patients were divided into the low C3d group( n=112)and the high C3d group( n=113)according to the median level of serum C3d.Serum C3d and C5b-9 levels were measured by enzyme-linked immunosorbent assays. Results:Serum C3d and C5b-9 levels in elderly IMN patients were 0.23(0.15, 0.45)mg/L and 0.28(0.20, 1.23)mg/L, respectively, which were higher than those in healthy controls[0.18(0.13, 0.22)mg/L, 0.22(0.16, 0.26)mg/L, respectively]( Z=-4.261 and -6.213, P<0.001). Serum C3d levels in elderly and non-elderly IMN patients were correlated negatively with the estimated glomerular filtration rate( r=-0.155 and -0.426, P=0.019 and 0.000), but positively with serum creatinine, anti-phospholipase A2 receptor(PLA2R)antibody levels and 24 h urinary protein( r=0.184, 0.326, 0.407, 0.321 and 0.145, P=0.005, 0.001, 0.000, 0.001 and 0.027). Kaplan-Meier survival analysis showed that the cumulative renal survival rate in elderly IMN patients was lower in the high C3d group than in the low C3d group(47.8% vs.70.8%, Log Rank χ2=7.399, P=0.007). Multivariate Cox regression analysis showed that high C3d levels were an independent risk factor for poor renal outcomes in elderly IMN patients( HR=2.288, 95% CI: 1.082-4.839, P=0.030). Conclusions:High serum C3d levels are associated with increases in urinary protein excretion and anti-PLA2R antibody levels, renal function decline, and poor renal outcomes in elderly IMN patients.

Effects of olanzapine versus risperidone on cognitive function and serum complement and high-sensitivity C-reactive protein levels in patients with schizophrenia / 中国基层医药

Objective:To investigate the effects of olanzapine versus risperidone on cognitive function, serum complement C3 and C4 levels and high sensitivity C-reactive protein (hs-CRP) level in patients with schizophrenia. Methods:Eighty patients with schizophrenia who received treatment in Lishui Second People's Hospital, China between September 2018 and September 2019 were included in this study. They were randomly assigned to receive treatment either with olanzapine (olanzapine group, n = 40) or risperidone (risperidone group, n = 40). Before and after treatment, the Positive and Negative Syndrome Scale (PANSS) score and the Wisconsin Card Sorting Test score were evaluated in each group. Before and after treatment, serum levels of dopamine, serotonin, norepinephrine, complement C3 and C4 and hs-CRP levels were compared between the olanzapine and risperidone groups. Results:Before treatment, there were no significant differences in PANSS and WCST scores between the two groups (both P > 0.05). After treatment, PANSS score, the number of perseverative errors and the number of random errors in each group were significantly decreased compared with before treatment [olanzapine group: (56.23 ± 9.37) points, (13.06 ± 6.26) points, (16.23 ± 6.35) points, t = 12.334, 5.885, 3.840, all P < 0.05; risperidone group: (55.98 ± 10.21) points, (13.97 ± 6.54) points, (16.31 ± 6.32) points, t = 12.044, 6.213, 3.321, all P < 0.05]. After treatment, the number of correct sorts and the number of categories in each group were significantly increased compared with before treatment [olanzapine group: (29.21 ± 2.24) points, (3.79 ± 1.12) points, t = 3.323, 2.087, both P < 0.05; risperidone group: (29.33 ± 2.35) points, (3.81 ± 1.15) points, t =2.750, 2.085, both P < 0.05]. After treatment, there were significant differences in these indexes between the two groups (all P > 0.05). Before treatment, there were no significant differences in serum levels of dopamine, serotonin and norepinephrine between the two groups (all P > 0.05). After treatment, serum levels of dopamine, serotonin and norepinephrine in each group were significantly decreased compared with before treatment [olanzapine group: (5.02 ± 0.13) μg/L, (66.24 ± 6.05) μg/L, (27.32 ± 4.05) μg/L, t = 67.800, 9.977, 5.082, all P < 0.05; risperidone group: (4.18 ± 0.12) μg/L, (63.12 ± 6.21) μg/L, (24.81 ± 4.13) μg/L, t = 99.761, 12.296, 6.882, all P < 0.05]. After treatment, there were significant differences in serum levels of dopamine, serotonin and norepinephrine between the two groups ( t = 30.029, 2.276, 6.882, all P < 0.05). Before treatment, there were no significant differences in complement C3 and C4 and hs-CRP levels between the two groups (all P > 0.05). After treatment, complement C3 and C4 and hs-CRP levels in each group were significantly increased compared with before treatment [olanzapine group: (1.12 ± 0.18) g/L, (0.24 ± 0.06) g/L, (1.09 ± 0.11) mg/L, t = 5.129, 4.049, 32.452, all P < 0.05; risperidone group: (1.13 ± 0.17) g/L, (0.25 ± 0.07) g/L, (1.10 ± 0.12) mg/L, t = 5.147, 5.164, 29.227, all P < 0.05]. After treatment, there were no significant differences in complement C3 and C4 and hs-CRP levels between the two groups ( t = 0.255, 0.686, 0.389, all P > 0.05). Conclusion:Olanzapine and risperidone have the same effects on improving the mental symptoms and cognitive function of patients with schizophrenia, but risperidone has more obvious effects on improving the body function than olanzapine.

Complement C3 Aggravates Post-epileptic Neuronal Injury Via Activation of TRPV1 / 神经科学通报·英文版

Epilepsy is a brain condition characterized by the recurrence of unprovoked seizures. Recent studies have shown that complement component 3 (C3) aggravate the neuronal injury in epilepsy. And our previous studies revealed that TRPV1 (transient receptor potential vanilloid type 1) is involved in epilepsy. Whether complement C3 regulation of neuronal injury is related to the activation of TRPV1 during epilepsy is not fully understood. We found that in a mouse model of status epilepticus (SE), complement C3 derived from astrocytes was increased and aggravated neuronal injury, and that TRPV1-knockout rescued neurons from the injury induced by complement C3. Circular RNAs are abundant in the brain, and the reduction of circRad52 caused by complement C3 promoted the expression of TRPV1 and exacerbated neuronal injury. Mechanistically, disorders of neuron-glia interaction mediated by the C3-TRPV1 signaling pathway may be important for the induction of neuronal injury. This study provides support for the hypothesis that the C3-TRPV1 pathway is involved in the prevention and treatment of neuronal injury and cognitive disorders.

Analysis of clinical and pathological features in biopsy-proven ischemic renal injury patients / 中华肾脏病杂志

Objective@#To investigate the clinical and pathological features of ischemia renal injury.@*Methods@#Patients with biopsy-proven ischemia renal injury in the Department of Nephrology, Peking University First Hospital from 2010 to 2018 were retrospectively enrolled in the present study. The demographic information and laboratory data were collected. And the severity of pathologic changes including glomeruli, arteriole and tubulo-interstitial fibrosis (IFTA) were semi-quantitatively scored. Arterioles with a ratio of inner/outer luminal diameter greater than 0.5 without hyalinosis were diagnosed as normal ones. The relationships between estimated glomerular filtration rate (eGFR), urine protein excretion and pathological changes were analyzed.@*Results@#A total of 52 patients were enrolled in the study, including 39 males (75.0%). The age of the patients was (45.0±12.7) years at biopsy. Among them, 50 patients (96.2%) had a history of hypertension with a median duration of 66 (24, 138) months. Forty-one patients (78.9%) were overweight or obese. The median urinary protein excretion was 0.75 (0.27, 1.32) g/d with 3 cases over 3 g/d. Fifteen patients (28.8%) presented with microhematuria and twenty-seven patients (51.9%) with eGFR lower than 60 ml·min-1·(1.73 m2)-1, respectively. The ratio of arteriolar inner/outer luminal diameter was 0.43±0.05 and the percentage of normal arterioles was 29.0%±17.0%. There were 21 patients (40.4%) found with arteriole hyalinosis. The ratio of arteriolar inner/outer luminal diameter correlated with the percentage of glomerular lesions (rs=-0.312, P=0.024), the semiquantitative scale of IFTA (rs=-0.291, P=0.037) and eGFR (r=0.339, P=0.014), respectively. Hypertension duration and body mass index (BMI) showed a negative correlation with the ratio of arteriolar inner/outer luminal diameter (rs=-0.303, P=0.029 and rs=-0.274, P=0.050, respectively) and a positive correlation with serum complement 3 level (rs=0.358, P=0.020 and rs=0.432, P=0.004, respectively).@*Conclusions@#Renal ischemia injury may be found in young and middle-aged patients. The characteristic of clinical features is mild to moderate proteinuria accompanied with a certain degree of eGFR decline, while a small number of patients may have microhematuria and marked proteinuria. The ratio of arteriolar inner/outer luminal diameter has a negative correlation with the percentage of glomerular lesions and the semiquantitative scale of IFTA and a positive correlation with eGFR, respectively. Hypertension and obesity are closely related to vascular lesions.

Analysis of clinical and pathological features in biopsy-proven ischemic renal injury patients / 中华肾脏病杂志

Objective To investigate the clinical and pathological features of ischemia renal injury.Methods Patients with biopsy-proven ischemia renal injury in the Department of Nephrology,Peking University First Hospital from 2010 to 2018 were retrospectively enrolled in the present study.The demographic information and laboratory data were collected.And the severity of pathologic changes including glomeruli,arteriole and tubulo-interstitial fibrosis (IFTA) were semiquantitatively scored.Arterioles with a ratio of inner/outer luminal diameter greater than 0.5 without hyalinosis were diagnosed as normal ones.The relationships between estimated glomerular filtration rate (eGFR),urine protein excretion and pathological changes were analyzed.Results A total of 52 patients were enrolled in the study,including 39 males (75.0％).The age of the patients was (45.0±12.7) years at biopsy.Among them,50 patients (96.2％) had a history of hypertension with a median duration of 66 (24,138) months.Forty-one patients (78.9％) were overweight or obese.The median urinary protein excretion was 0.75 (0.27,1.32) g/d with 3 cases over 3 g/d.Fifteen patients (28.8％)presented with microhematuria and twenty-seven patients (51.9％) with eGFR lower than 60 ml· min-1·(1.73 m2)-1,respectively.The ratio of arteriolar inner/outer luminal diameter was 0.43+0.05 and the percentage of normal arterioles was 29.0％+17.0％.There were 21 patients (40.4％) found with arteriole hyalinosis.The ratio of arteriolar inner/outer luminal diameter correlated with the percentage of glomerular lesions (rs=-0.312,P=0.024),the semiquantitative scale of IFTA (rs=-0.291,P=0.037) and eGFR (r=0.339,P=0.014),respectively.Hypertension duration and body mass index (BMI) showed a negative correlation with the ratio of arteriolar inner/outer luminal diameter (rs=-0.303,P=0.029 and rs=-0.274,P=0.050,respectively) and a positive correlation with serum complement 3 level (rs=0.358,P=0.020 and rs=0.432,P=0.004,respectively).Conclusions Renal ischemia injury may be found in young and middle-aged patients.The characteristic of clinical features is mild to moderate proteinuria accompanied with a certain degree of eGFR decline,while a small number of patients may have microhematuria and marked proteinuria.The ratio of arteriolar inner/outer luminal diameter has a negative correlation with the percentage of glomerular lesions and the semiquantitative scale of IFTA and a positive correlation with eGFR,respectively.Hypertension and obesity are closely related to vascular lesions.

Analysis on the correlation between complement C3 and C4 with optic neuritis / 国际眼科杂志(Guoji Yanke Zazhi)

@#AIM: To explore the association between serum complement C3 and C4 with optic neuritis.<p>METHODS: Case-control study design. Optic neuritis subjects(<i>n</i>=137)and control subjects(<i>n</i>=147)who attended the Eye-ENT Hospital of Fudan University from January to August 2018 were recruited. The levels of serum complement C3 and C4 was detected by Roche automatic biochemical analyzer. Univariate analysis and multivariate Logistic regression analysis were performed to compare the level of serum complement C3 and C4 between optic neuritis group and control group. ROC analysis was performed to analysis the diagnosis value of C3 and C4 to distinguish optic neuritis patients.<p>RESULTS: The levels of serum complement C3 and C4 was significant lower(<i>P</i><0.05)in optic neuritis group(96.17±17.93mg/dL),(22.41±7.53mg/dL)compared with control group(108.85±15.94mg/dL),(24.55±6.37 mg/dL). Multivariate logistic regression analysis shown that decreased level of complement C3(<i>OR</i>=1.048, <i>P</i><0.001, 95%<i>CI</i>:1.031-1.065)and C4(<i>OR</i>=1.045, <i>P</i>=0.014, 95%<i>CI</i>: 1.009-1.083)was a risk factor for optic neuritis.<p>CONCLUSION: The levels of serum complement C3 and C4 was decreased which suggested that the decreased level of complement C3 and C4 was risk factor for optic neuritis.

Analysis of the relationship between complement and lipid metabolism and bone mineral density in elderly population / 中华检验医学杂志

Objective@#To investigate the diagnostic value of serum complement level and lipid metabolism level detection in senile osteoporosis.@*Methods@#A total of 215 elderly people who underwent physical examination and bone mineral density test in Beijing Jishuitan Hospital from January 2016 to June 2016 were divided into osteoporotic group(74) and non-osteoporotic group (141) according to bone mineral density classification. The relationship between serum complement C3, complement C4, low density lipoprotein cholesterol (LDL), high density lipoprotein cholesterol (HDL), triglyceride (TG), total cholesterol (CHO) and bone mineral density were analyzed. The data were analyzed by t-test, non-parametric test, binary Logistic regression and the receiver operating characteristic (ROC) curve.@*Results@#The age and CHO,LDL, HDL, complement C3 and C4 in the osteoporosis group[(80.6±8.2)years, (4.43±1.25)mmol/L, (2.27±0.73) mmol/L, (1.33±0.39) mmol/L, (1.12±0.22) g/L, (0.29±0.09)g/L], were significantly higher than those in the non-osteoporosis group[(77.5±8.3)years,(4.04±1.02)mmol/L,(1.97±0.59)mmol/L,(1.19±0.32)mmol/L,(0.86±0.25)g/L,(0.21±0.06)g/L,t-value were 2.571,-3.848,-4.483,-3.951,-1.249,-1.185,P<0.05], and the the BMI bone mineral density T-Score value of DXA and in the osteoporosis group were significantly lower than those in the non-osteoporosis group[(22.33±3.8)kg/m2, -2.74±0.78 and (25.03±4.2)kg/m2, 0.14±0.9, while the t value was 6.151 and 4.624, respectively, P<0.05]. The level of TG in osteoporotic group was significantly lower than that in non-osteoporotic group[the median (quartile) was 1.21(0.67,1.44)mmol/L and 1.37(0.86,1.67)mmol/L, respectively, Z=-2.51, P<0.01].Gender and serum levels of HDL, LDL, C3 and C4 were independent risk factors for senile osteoporosis(OR=2.476,P=0.004;OR=1.305,P=0.038;OR=1.564,P=0.028; OR=1.018, P=0.025; OR=1.023, P=0.015, respectively). The risk of osteoporosis in women was 2.476 times higher than that in men of the same age. The corresponding risk of osteoporosis increased by1.305,1.564, 1.018 and 1.023 times as HDL, LDL, C3 and C4 increased by one unit. The areas under the ROC curve detected separately by HDL, LDL, C3 and C4 were 0.623,0.595,0.673 and 0.731 respectively, and the area under the ROC curve of the four items was 0.864.@*Conclusions@#The levels of blood lipids and complements play a great role in bone metabolism. The combined detection of blood lipid metabolism and complement can improve the diagnostic efficacy of senile osteoporosis.

Effect of renal fibrosis after macrophage depletion in C3-deficient unilateral ureteral obstruction mice / 中华肾脏病杂志

Objective@#To investigate the effect and mechanism of renal fibrosis after macrophage depletion in C3-deficient unilateral ureteral obstruction mice.@*Methods@#Renal interstitial fibrosis model was established by unilateral ureteral obstruction (UUO) in male C3-deficient mice and age-matched C57BL/6 WT mice (8-12 weeks of age). Mice were randomly divided into 4 groups, including sham operation in wild type group (WT/sham) (n=18), UUO operation in wild type group (WT/UUO) (n=18), sham operation in C3-deficient group (C3KO/sham) (n=18), and UUO operation in C3-deficient group (C3KO/UUO) (n=18). The expression of complement C3 was detected by immunohistochemical staining and renal interstitial macrophages were assessed by immunofluorescence staining. Tubulointerstitial fibrosis was observed by both HE staining and Masson staining after 14 days of UUO. Collagen accumulation and score of tubulointerstitial injury were obtained. Wild type and C3-deficient UUO mice were treated by liposome clodronate in early or late stage respectively and then interstitially infiltrated macrophages and renal fibrosis were analysed. Mice were sacrificed randomly at 3,7,14 days after UUO and obstructed kidneys were collected. Macrophage phenotype was detected by double-labeling immunofluorescence with F4/80 and iNOS for the M1, F4/80 and CD206 for the M2 macrophage subpopulation. iNOS, Arg-1 and CD206 were also detected by western blot.@*Results@#C3 deficient mice exhibited attenuated renal fibrosis, reduced collagen accumulation and tubulointerstitial injury score compared with WT mice (P<0.01). Meanwhile, macrophage depletion in early or late stage of UUO reduced renal fibrosis in WT mice, but had no effect on C3-deficient UUO mice. Decreased accumulation of M1 macrophages and expression of iNOS, increased accumulation of M2 macrophages and expression of Arg-1, CD206 were found in C3 deficient mice compared with WT mice in early stage of UUO (P<0.01).@*Conclusion@#Renal fibrosis is not reduced after depletion of macrophages in C3 deficient UUO mice due to the altered macrophage polarization.

Analysis of the relationship between complement and lipid metabolism and bone mineral density in elderly population / 中华检验医学杂志

Objective To investigate the diagnostic value of serum complement level and lipid metabolism level detection in senile osteoporosis. Methods A total of 215 elderly people who underwent physical examination and bone mineral density test in Beijing Jishuitan Hospital from January 2016 to June 2016 were divided into osteoporotic group(74) and non-osteoporotic group (141) according to bone mineral density classification. The relationship between serum complement C3, complement C4, low density lipoprotein cholesterol (LDL), high density lipoprotein cholesterol (HDL), triglyceride (TG), total cholesterol (CHO) and bone mineral density were analyzed. The data were analyzed by t-test,non-parametric test,binary Logistic regression and the receiver operating characteristic(ROC) curve. Results The age and CHO,LDL, HDL, complement C3 and C4 in the osteoporosis group[(80.6 ± 8.2)years, (4.43 ± 1.25)mmol/L, (2.27 ± 0.73) mmol/L, (1.33 ± 0.39)mmol/L, (1.12 ± 0.22)g/L, (0.29 ± 0.09)g/L], were significantly higher than those in the non-osteoporosis group[(77.5±8.3)years,(4.04±1.02)mmol/L,(1.97±0.59)mmol/L,(1.19±0.32)mmol/L,(0.86± 0.25)g/L, (0.21 ± 0.06)g/L, t-value were 2.571,-3.848,-4.483,-3.951,-1.249,-1.185, P<0.05], and the the BMI bone mineral density T-Score value of DXA and in the osteoporosis group were significantly lower than those in the non-osteoporosis group[(22.33 ± 3.8)kg/m2,-2.74 ± 0.78 and (25.03 ± 4.2)kg/m2, 0.14 ± 0.9, while the t value was 6.151 and 4.624, respectively, P<0.05]. The level of TG in osteoporotic group was significantly lower than that in non-osteoporotic group[the median (quartile) was 1.21(0.67,1.44)mmol/L and 1.37(0.86,1.67)mmol/L, respectively, Z=-2.51, P<0.01].Gender and serum levels of HDL, LDL, C3 and C4 were independent risk factors for senile osteoporosis(OR=2.476,P=0.004;OR=1.305,P=0.038;OR=1.564,P=0.028;OR=1.018, P=0.025;OR=1.023, P=0.015, respectively). The risk of osteoporosis in women was 2.476 times higher than that in men of the same age. The corresponding risk of osteoporosis increased by1.305, 1.564, 1.018 and 1.023 times as HDL, LDL, C3 and C4 increased by one unit. The areas under the ROC curve detected separately by HDL, LDL, C3 and C4 were 0.623,0.595,0.673 and 0.731 respectively, and the area under the ROC curve of the four items was 0.864. Conclusions The levels of blood lipids and complements play a great role in bone metabolism. The combined detection of blood lipid metabolism and complement can improve the diagnostic efficacy of senile osteoporosis.

Correlation Analysis between Serum Complement C3，C4 Levels and LDL-C in Patients with Premature Coronary Artery Disease / 中山大学学报(医学科学版)

@#【Objective】The aim of this study was to investigate the associations between serum complement C3，C4 and low density lipoprotein cholesterol（LDL- C）levels and early- onset coronary heart disease.【Methods】We enrolled 255 cases of coronary angiography confirmed coronary artery disease from January 2018 to September 2018. All the patients were divided into early- onset coronary heart disease group（108 cases）and late- onset coronary heart disease group（147 cases）. Besides ，100 healthy subjects were enrolled and used as controls. Serum levels of C3 ，C4 and LDL-C were analyzed by automatic biochemical analyzer.【Results】Levels of serum C3，C4 and LDL-C in early-onset coronary heart disease group，late-onset coronary heart disease group and healthy control group were significantly different（P < 0.05）. In early-onset coronary heart disease group，C3 and C4 were positively correlated with LDL-C（P < 0.05）. However ，there was no significant correlation （P > 0.05） between C3 ，C4 and LDL- C in late- onset coronary heart disease group and healthy control group.【Conclusions】The levels of C3 and C4 were positively correlated with LDL-C only in the early-onset coronary heart disease patients.

The role of complement signaling pathway in the pathogenesis of neuromyelitis optica / 中华眼底病杂志

Neuromyelitis optica (NMO) is a kind of demyelinating disorder that preferentially affects the optic nerves and spinal cord and results in permanent vision loss.NMO pathogenesis is thought to involve binding of anti-aquaporin-4 (AQP4) auto-antibodies to astrocytes,which causes complement-dependent cytotoxicity (CDC) and downstream inflammation leading to oligodendrocyte and neuronal injury.Vasculocentric deposition of activated complement is a prominent feature of NMO pathology.In recent years,a number of groups have found complements play an important role in the pathogenesis of NMO,and basic researches in NMO therapy due to its specificity and uniformity.Its inhibition would protect against proteins in the classical complement pathway so that cure the disease.This review will expound the the role of complement signaling pathway in the pathogenesis of NMO,and provide reference for a more in-depth understanding and clinical treatments of NMO.

Effect of renal fibrosis after macrophage depletion in C3 - deficient unilateral ureteral obstruction mice / 中华肾脏病杂志

Objective To investigate the effect and mechanism of renal fibrosis after macrophage depletion in C3 - deficient unilateral ureteral obstruction mice. Methods Renal interstitial fibrosis model was established by unilateral ureteral obstruction (UUO) in male C3-deficient mice and age-matched C57BL/6 WT mice (8-12 weeks of age). Mice were randomly divided into 4 groups, including sham operation in wild type group(WT/sham)(n=18), UUO operation in wild type group(WT/UUO)(n=18), sham operation in C3-deficient group(C3KO/sham)(n=18), and UUO operation in C3-deficient group(C3KO/UUO)(n=18). The expression of complement C3 was detected by immunohistochemical staining and renal interstitial macrophages were assessed by immunofluorescence staining. Tubulointerstitial fibrosis was observed by both HE staining and Masson staining after 14 days of UUO. Collagen accumulation and score of tubulointerstitial injury were obtained. Wild type and C3-deficient UUO mice were treated by liposome clodronate in early or late stage respectively and then interstitially infiltrated macrophages and renal fibrosis were analysed. Mice were sacrificed randomly at 3,7,14 days after UUO and obstructed kidneys were collected. Macrophage phenotype was detected by double-labeling immunofluorescence with F4/80 and iNOS for the M1, F4/80 and CD206 for the M2 macrophage subpopulation. iNOS, Arg-1 and CD206 were also detected by western blot. Results C3 deficient mice exhibited attenuated renal fibrosis, reduced collagen accumulation and tubulointerstitial injury score compared with WT mice (P<0.01). Meanwhile, macrophage depletion in early or late stage of UUO reduced renal fibrosis in WT mice, but had no effect on C3-deficient UUO mice. Decreased accumulation of M1 macrophages and expression of iNOS, increased accumulation of M2 macrophages and expression of Arg-1, CD206 were found in C3 deficient mice compared with WT mice in early stage of UUO (P<0.01). Conclusion Renal fibrosis is not reduced after depletion of macrophages in C3 deficient UUO mice due to the altered macrophage polarization.