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With the rapid increase in the prevalence rate of nonalcoholic fatty liver disease (NAFLD), new treatment methods are needed to prevent disease progression to liver fibrosis, liver cirrhosis, and liver cancer. Although great efforts have been made to clarify the pathological mechanisms of NAFLD disease progression, there are still no effective treatment methods at present. Bile acids (BAs) regulate systemic metabolism by activating nuclear receptors and G protein-coupled receptors and have been identified as important signaling molecules involved in lipid, glucose, and energy metabolism. Dysregulation of BA homeostasis is associated with the severity of NAFLD. This article summarizes the important ligands in BA metabolism and their role in the progression of NAFLD, in order to provide a basis for the treatment of NAFLD by targeting BA messengers.
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OBJECTIVE@#Acetaminophen (APAP) overdose is a common cause of liver injury. This study aimed to investigate the protective effect of honokiol (Hon) against APAP-induced hepatotoxicity and its potential mechanism.@*METHODS@#C57BL/6 mice were administrated with Hon (10 and 30 mg/kg) after APAP (300 mg/kg) treatment. On 1.5 h and 5 h after Hon treatment, mice were sacrificed. Serum and liver were collected. And then, liver injury-related indexes, APAP metabolism-related indexes, mitochondrial respiratory chain function-related indexes, and mitochondrial membrane function-related protein expression were evaluated.@*RESULTS@#It was found that Hon significantly decreased serum alanine aminotransferase (ALT)/aspartate aminotransferase (AST) activity and glutathione (GSH) depletion, increased hepatic catalase (CAT) and GSH peroxidase (GSH-Px) activities, reduced hepatic MDA and 3-nitrotyrosine contents, inhibited hepatic CYP1A2 activity and APAP protein adducts (APAP-CYS) formation. Meanwhile, oxidative phosphorylation capacity of complex I and electron transfer capacity of complex IV in mitochondrial respiratory chain was increased, whereas the release of H2O2 in the mitochondria was decreased following Hon treatment. Furthermore, Hon markedly down-regulated p-JNK in both cytosol and mitochondria, and obviously inhibited the release of apoptosis inducing factor (AIF) and endonuclease G (EndoG) from mitochondria to cytosol.@*CONCLUSION@#Hon alleviated APAP-induced liver injury through the following pathways: Reducing the production of APAP-CYS by inhibiting CYP1A2 activity; Ameliorating hepatic oxidative stress by increasing the levels of hepatic CAT, GSH-Px and GSH; Improving mitochondrial respiratory chain function by promoting oxidative phosphorylation capacity of complex I and electron transfer capacity of complex IV; Improving the function of mitochondrial membrane by inhibiting p-JNK and its translocation to mitochondria, thereby reducing the release of AIF and EndoG.
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Objective:To explore the association between serum high density lipoprotein subtype 3 cholesterol (HDL3-C) levels and the severity and in-stent restenosis of patients with coronary artery disease.Methods:124 patients with coronary artery diseases and 62 healthy controls were included in this clinical case-control retrospective study. Participants were hospitalized from November 2020 to November 2021 at Jinling Hospital, Medical School of Nanjing University were enrolled. Patients with coronary artery disease were as follows: 28 patients with acute coronary syndrome and 96 patients with stable coronary heart disease. Serum HDL3-C levels as well as total cholesterol (TC), triglyceride (TG), high-density lipoprotein cholesterol (HDL-C) and low-density lipoprotein cholesterol (LDL-C) levels were determined. According to the coronary artery angiography results of all patients at the time of admission, Gensini scores were calculated and patients were divided into in-stent restenosis group ( n=22), no in-stent stenosis group ( n=23) and non-stent implantation group ( n=79). The correlation between HDL3-C levels and other parameters was analyzed by Pearson or Spearman correlation analyses. Multivariate Logistic regression analyses were used to determine the impact of HDL3-C on the in-stent restenosis of coronary artery diseases. Results:Compared with controls, serum levels of HDL3-C and HDL-C were significantly decreased in patients with coronary artery diseases (all P<0.05). There was a significantly negative correlation between HDL3-C levels and Gensini scores ( r=-0.201, P=0.043). Among patients with coronary artery disease, serum levels of HDL3C, TC and TG in the in-stent restenosis group were significantly lower than in no in-stent stenosis group as well as than in the non-stent implantation group (all P<0.05). Multivariate Logistic regression analyses showed that after adjusting for age, sex, lipid-lowering drugs and TC, TG, LDLC parameters, HDL3-C ( OR=0.885, 95% CI 0.791-0.990, P=0.033) and HDL-C ( OR=0.018, 95% CI 0.001-0.426, P=0.013) levels were both independently associated with the occurrence of coronary artery disease; only HDL3-C levels (no in-stent stenosis group as the reference: OR=0.833, 95% CI 0.698-0.994, P=0.042; non-stent implantation group as the reference: OR=0.812, 95% CI 0.685-0.963, P=0.017) were independently associated with the presence of in-stent restenosis ( P<0.05). Conclusions:Serum HDL3-C levels are decreased in patients with coronary artery disease, especially in patients with in-stent restenosis. HDL3-C levels are associated with the severity of coronary artery lesions and the presence of in-stent restenosis of coronary arteries.
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New techniques in clinical lipid measurements, such as vertical auto profile, nuclear magnetic resonance spectroscopy, electrospray differential mobility analysis and liquid chromatography-mass spectrometry/mass spectrometry, are becoming increasingly mature. Clinical application of these new techniques significantly promoted the use of new lipid parameters including the particle concentrations of low-density lipoprotein/high-density lipoprotein and other lipoprotein subtype in the risk stratification of atherosclerotic cardiovascular disease and in the efficacy monitoring of lipid-regulating therapy, above progress is helpful on developing new individualized and precise lipid management strategies. This review analyzed and summarized the research progress of the new techniques for lipid measurements in recent years, aiming to provide evidence to develop new ideas for the individualized and accurate lipid management in clinical practice.
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Atherosclerotic cardiovascular disease (ASCVD) is the leading cause of death of urban and rural residents in China, and dyslipidemia is the most important pathogenic risk factor for the occurrence and development of ASCVD. Faced with the increasing ASCVD burden in China, there is an urgent need to improve the lipid management in China. Clinical blood lipid testing is an important component of lipid management, and the accurate test results are a fundamental requirement for effective lipid management. The "China guidelines for clinical lipid profile testing" and "China guidelines for lipid management (2023)" are newly published. With the continuous updating of concepts on clinical lipid profile testing and lipid management, it is essential to further strengthen the communication and cooperation between clinical medicine and laboratory medicine, widely promote and apply the new concepts of updated guidelines, in order to better guide clinical practice, comprehensively improve the level of clinical lipid profile testing and lipid management in China, and assist in the standardized prevention and treatment of ASCVD in China and the early arrival of the turning points.
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Objective:To understand the reported incidence level, change of the trend, epidemic characteristics and spatial clustering of scrub typhus in Nanjing, to explore key seasons, populations and areas for prevention and control, and to guide formulation of scientific and precise prevention and control strategies and measures.Methods:The reported data of scrub typhus in Nanjing from January 1, 2011 to December 31, 2020 were collected in the "Infectious Disease Surveillance System" from Chinese Center for Disease Control and Prevention. The reported incidence level and change of the trend were analyzed, and the seasonal, population and spatial distribution characteristics were described. Global spatial autocorrelation analysis was carried out by ArcGIS 10.3 software, and the spatial clustering scanning was carried out by using FleXScan 3.1.2 software.Results:A total of 192 cases of scrub typhus were reported in Nanjing from 2011 to 2020. Median annual reported incidence was 0.21/100 000 (0.12/100 000 - 0.49/100 000). Totally 87.5% (168/192) of cases were reported from October to November, and the peak occurred in November (57.8%, 111/192). Among these cases, males accounted for 64.1% (123/192); and the median age was 59 years old (6 - 84 years old). The groups ≥60 years old and 45 - 59 years old accounted for 47.9% (92/192) and 31.2% (60/192), respectively, which accounted for 79.2% (152/192) in all groups. Farmers accounted for 43.8% (84/192), household chores and unemployed people accounted for 16.7% (32/192), retired persons accounted for 15.6% (30/192) and workers accounted for 6.8% (13/192), which accounted for 82.8% (159/192) in all occupations. The top four areas in the total number of reported cases were Jiangning District (23.4%, 45/192), Luhe District (22.9%, 44/192), Gulou District (10.4%, 20/192) and Jiangbei New Area (8.9%, 17/192), which accounted for 65.6% (126/192) in all districts. According to global spatial autocorrelation analysis, Moran's I = 0.34 ( Z = 5.90, P < 0.001). FlexScan 3.1.2 software scanned and detected two spatial clusters areas, the first-class of cluster area covered three streets in Jiangning District, one street in Yuhuatai District and two streets in Pukou District [restricted log likelihood ratio ( RLLR) = 26.91, P < 0.001]. The second-class of cluster area included six townships/streets in Luhe District and four streets in Jiangbei New Area ( RLLR = 26.48, P < 0.001). All the cluster areas were agriculture-related. Conclusions:The reported incidence level of scrub typhus in Nanjing is low and stable which belongs to a typical autumn epidemic area. The middle-aged and elderly population is the key population and the agriculture-related area is key area. It is suggested that scrub typhus should be included in the management of statutory or regional key infectious diseases in Nanjing. Additionally, training on diagnosis and treatment technology and information report management of scrub typhus need to be carried out, and comprehensive prevention and control interventions such as health education, personal protection, rodent prevention and control and vector control should be strengthened and implemented in the high incidence season.
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Objective:To improve the understanding of the clinical features of toxic encephalopathy associated with diquat poisoning.Methods:This study collected and analyzed the diagnosis and treatment process of 7 patients with acute diquat poisoning combined with central nervous system complications admitted to the First Affiliated Hospital of Zhengzhou University from April 2021 to April 2022. "Diquat" and "Poisoning" were used as keywords to search in CNKI, Wanfang database and PubMed database, and the literature of previous cases was reviewed for summary analysis.Results:Among the 7 patients in our hospital, there were 2 males and 5 females, with an average age of 31 years (range14-57) and an average dose of 23.14 g [(10-40)g]. During the treatment, 3 patients developed irritability and convulsions, 3 patients occurred coma, and one had generalized tonic-clonic seizures. Four patients died and 3 survived, of which 2 patients returned to normal life and study, and one remained abnormal mental behavior (currently in long-term follow-up). All three survivors developed neurological symptoms later than those who died, and were awake about 30 days after taking the drug.Conclusions:Toxic encephalopathy associated with diquat poisoning has rapid progression, poor prognosis and high mortality. This study found that the survival rate of patients with > 48 h of first onset of neurological symptoms is much higher than that of patients with ≤ 48 h of first onset of neurological symptoms, while sex, age, estimated oral dose, and type of presentation of neurological symptoms for the first time have little effect on the survival rate of hospital discharge. The earlier neurological symptoms appear, the greater the likelihood of a poor prognosis.
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Objective:To investigate the occurrence of ureteral stricture in patients with ureteral calculi after pneumatic ballistic lithotripsy and its influence on the prognosis of patients.Methods:Using retrospective study method, 42 patients with ureteral calculi who underwent pneumatic ballistic lithotripsy in the Eighth Hospital of Wuhan from August 2018 to August 2020 and developed ureteral stricture were included in the stricture group, 60 patients with ureteral calculi who received the same surgical treatment in the Eighth Hospital of Wuhan without postoperative ureteral stricture were regarded as the non-stricture group. The general data, recurrence at 6 months and 1 year after operation and quality of life score at 1 year after operation were compared between the two groups. The measurement data were expressed by mean ±standard deviation ( ± s), independent sample t-test was used for inter-group comparison, and Chi-square test was used for inter-group comparison of counting data. Univariate and multivariate Logistic regression analysis were used to evaluate the risk factors of ureteral stricture in patients with ureteral calculi after pneumatic ballistic lithotripsy, and the receiver operating characteristic (ROC) curve was used to evaluate the predictive value of the influencing factors on postoperative ureteral stricture. Results:The results of univariate analysis showed that the proportion of patients with disease course ≥ 3 months, maximum diameter of stones > 2 cm, multiple stones, incarcerated stones and inflammatory mucosa-wrapped stones in the stricture group were significantly higher than those in the non-stricture group ( P<0.05). Multivariate Logistic regression analysis showed that the course of disease ≥ 3 months, the maximum diameter of stones > 2 cm, multiple stones, incarcerated stones and inflammatory mucosa-wrapped stones were all risk factors for postoperative ureteral stricture ( P<0.05). The area under the ROC curve of each factor predicting postoperative ureteral stricture were 0.685 (95% CI: 0.602-0.768), 0.743 (95% CI: 0.685-0.801), 0.812 (95% CI: 0.749-0.875), 0.853 (95% CI: 0.801-0.905), 0.726 (95% CI: 0.673-0.779), all have high predictive value ( P<0.001). The recurrence rate at 6 months after operation in the stricture group [16.67% (7/42)] and the total recurrence rate [23.81% (10/42)] were significantly higher than those in the non-stricture group [3.33% (2/60), 8.33% (5/60)], the differences were statistically significant ( P<0.05). One year after operation, the physiological function (67.42±9.64), physiological function (71.35±10.16) and overall health score (73.49±10.31) were significantly lower than those in the non-stricture group (76.39±9.42, 75.34±9.26, 79.86±10.24), the differences were statistically significant ( P<0.05). Conclusion:The occurrence of ureteral stricture after pneumatic ballistic lithotripsy increases the risk of recurrence in patients with ureteral stones. Identifying the risk factors that affect patients with ureteral stricture after surgery is conducive to timely and effective intervention measures to improve the prognosis and quality of life of patients.
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Extracellular vesicles (EV) miRNAs are a class of small non-coding RNAs that are encapsulated in membrane-containing vesicles from a variety of cells, and which can mediate intercellular communication and transfer of functional molecules. EV miRNAs in circulation can be served as novel molecular markers for cancer diagnosis, monitoring and prognosis, and also the most promising liquid biomarkers for clinical translation and utility currently, while optimal research strategy is crucial for identifying valuable EV miRNAs in clinical study. Moreover, EV miRNAs have recently also been implicated in cancer progression as direct regulators of metabolic reprogramming, mesenchymal-to-epithelial transition, angiogenesis, anti-cancer immune response and drug resistance in the tumor microenvironment. Study on some key EV miRNAs involving in those processes may highlight their potential utility as liquid biopsies in early diagnosis, companion diagnosis, metastasis, therapeutic control, prognosis analysis as their therapeutic potential for patients with cancer.
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Objective:To compare the difference between serum lipoprotein(a) [Lp(a)] particle concentration and mass concentration in chronic kidney disease (CKD) patients and healthy controls, and to analyze the concentration distribution of the deviations between the two measurement methods.Methods:Serum Lp(a) particle concentration and mass concentration were respectively detected in 196 patients with CKD and 97 healthy controls from Eastern Theater General Hospital during June 2018 to December 2019. The upper limit of reference value for Lp(a) particle concentration was set as 75 nmol/L and the upper limit of reference value for mass concentration was set as 300 mg/L, the difference on the positive rates of Lp(a) particle concentration and mass concentration in each group were compared. According to the quartile of Lp(a) concentration in patients with CKD, the patients were divided into 4 groups, and the results derived from the two methods were compared among groups.Results:Serum Lp(a) particle concentration (25.7 [10.5, 75.4] nmol/L vs 19.2[8.1-50.2] nmol/L, P=0.021) and mass concentration (157[64, 432] mg/L vs 127[50-274] mg/L, P=0.023) were significantly higher in patients with CKD than those in healthy controls. The positive rate of Lp(a) particle concentration was significantly lower than that of mass concentration (25.0%[48/196] vs 37.2%[73/196], P=0.009) in CKD patients. The positive rate of Lp(a) particle concentration and mass concentration was similar in healthy controls (18.6%[18/97] vs 22.7%[22/97], P=0.478). The overestimation rate of Lp(a) mass concentration in CKD patients was significantly higher than that in healthy controls (12.8%[25/196] vs 4.1%[4/97], P=0.020). Lp(a) mass concentration of group Ⅲ in CKD patients was between 157.00-432.25 mg/L, the positive rate of Lp(a) particle concentration was significantly lower than that of mass concentration (4.1%[2/49] vs 49%[24/49], P<0.001), and the overestimation rate (44.9%[22/49]) of Lp(a) mass concentration in this group was also the highest (all P<0.001). According to the conversion factor provided by the reagent manual of Lp(a) particle concentration, the test results were converted into mass concentration. The actual mass concentration of Lp(a) in CKD patients grouped by quartile was significantly higher than that after Lp(a) particle concentration conversion (all P<0.05). Conclusions:The positive rate of serum Lp(a) particle concentration is significantly lower than that of mass concentration in CKD patients and the obvious overestimation deviation of Lp(a) mass concentration is observed in this analysis.
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Exosomal microRNAs (miRNAs) from various cell sources in the cardiovascular system are involved in the regulation of diverse biological processes such as angiogenesis, myocardial remodeling, inflammation and plaque rupture, and may function as promising liquid biomarkers for atherosclerotic cardiovascular diseases (ASCVD). Expression analysis of exosomal miRNAs can be employed for monitoring ASCVD progression and evaluating treatment efficiency. This review focused on recent research advances regarding exosomal miRNAs in the field of ASCVD laboratory medicine, and summarized the future research trends and application prospects of circulating exosomal miRNAs in the field of ASCVD.
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The RNA m6A modification is not only an important strategy for mammal cells′ epigenetic regulation, but also the focus and hotspot of current research. Increasing evidence have revealed that the RNA m6A modification is closely related to the occurrence, development, invasion and metastasis of human malignancy. The levels of RNA m6A modification and the changes of related modification enzymes in peripheral blood can provide clues for tumor diagnosis, monitoring and prognosis, and also the most potential novel-molecular indicator for accurate diagnosis and treatment of patients with multi-kinds of tumors. The emergence of novel detection-technology enables measurement of the whole level, high-throughput sequencing and quantitative detection of specific gene fragments or sites of RNA m6A modification. Research on novel high-throughput detection and single-gene RNA methylation editing technology to detect the modification level of specific gene m6A can provide ideas for further developing new indicators of accurate diagnosis and treatment of patients with tumor.
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The orbitofrontal cortex (OFC) is involved in diverse brain functions via its extensive projections to multiple target regions. There is a growing understanding of the overall outputs of the OFC at the population level, but reports of the projection patterns of individual OFC neurons across different cortical layers remain rare. Here, by combining neuronal sparse and bright labeling with a whole-brain florescence imaging system (fMOST), we obtained an uninterrupted three-dimensional whole-brain dataset and achieved the full morphological reconstruction of 25 OFC pyramidal neurons. We compared the whole-brain projection targets of these individual OFC neurons in different cortical layers as well as in the same cortical layer. We found cortical layer-dependent projections characterized by divergent patterns for information delivery. Our study not only provides a structural basis for understanding the principles of laminar organizations in the OFC, but also provides clues for future functional and behavioral studies on OFC pyramidal neurons.
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Objective:To investigate the association between the cerebral microbleeds(CMBs)and CHA 2DS 2-VASc score in patients with non-valvular atrial fibrillation(NVAF), and to analyze the related risk factors for CMBs. Method:This was a retrospective case-control study.A total of 164 patients with NVAF who had performed brain magnetic resonance susceptibility weighted imaging in Zhejiang Hospital from January 2015 to December 2017 were included.Based on the presence of CMBs, all patients were divided into the CMBs group(n=43, 26.2%)and the non-CMBs group(n=121, 73.8%). We collected the data about clinical characteristics, CHA2DS2-VASc score and number of CMBs.The association between CMBs and CHA2DS2-VASc score was analyzed by Spearman linear test.The Logistic regression analyses was used to evaluate the association between CMBs and the risk factors, including age, hypertension, etc.Results:The incidence of CMBs was markedly increased with the increase of CHA 2DS 2-VASc score( P<0.05). Besides, the rate of CMBs ≥5 was also positively associated with CHA 2DS 2-VASc score( P<0.05). Patients in the CMBs group was significantly older than those in the non-CMBs group[(81.0±8.1)years vs.(75.4±11.2)years, P<0.01]. There were significantly differences in rates of hypertension(83.7% vs. 63.2%), moderate-severe leukoaraiosis(44.2% vs.33.9%), anticoagulant therapy(34.9% vs.19.0%)and median CHA 2DS 2-VASc score(4 vs.3)between the CMBs group and the non-CMBs group(all P<0.05). Logistic regression analyses showed that age and anticoagulant therapy were the independent risk factors of CMBs in NVAF patients(all P<0.05). Conclusion:CMBs is strongly associated with CHA 2DS 2-VASc score in patients with NVAF.Age and anticoagulant therapy are its independent risk factors.It is necessary to detect the possibility of CMBs in old NVAF patients with high CHA 2DS 2-VASc score before and during anticoagulant therapy.
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Objective:To analyze serum levels of complement 1q (C1q) in patients with acute ischemic stroke (AIS) and transient ischemic attack (TIA), and to assess the association of serum C1q with the neurological deficit severity of AIS and the subsequent stroke risk after TIA, and to investigate the predictive and discriminative values of serum C1q for AIS and TIA.Methods:Clinical case-control study. Serum C1q levels were determined in 65 AIS, 61 TIA patients and 66 healthy controls from Jinling Hospital affiliated to Medical School of Nanjing University during January 2016 to March 2017. Their serum levels of total cholesterol (TC), triglycerides (TG), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol, glucose, high-sensitivity C-reactive protein (hs-CRP), interleukin 6 (IL-6) and procalcitonin (PCT) were also detected. The NIHSS scores of AIS patients and ABCD3-I scores of TIA patients were calculated. Spearman correlation analyses and stepwise linear regression analyses were performed to investigate the association of serum C1q levels with NIHSS and ABCD3-I scores. Logistic regression analyses were performed to investigate the predictive and discriminative values of serum C1q for AIS and TIA patients. Results:Compared with controls [C1q:175.50(164.00-196.50)mg/L, TG: 0.91(0.71-1.19)mmol/L, HDL-C:(1.43±0.23)mmol/L], serum levels of C1q [AIS: 199.00(180.00-218.00)mg/L; TIA: 184.00(174.50-202.75)mg/L) and TG(AIS: 1.36(0.91-2.00)mmol/L; TIA: 1.31(0.90-2.01) mmol/L] were significantly increased in AIS and TIA patients(all P<0.05), while HDL-C[AIS: (1.08±0.41) mmol/L; TIA: (1.08±0.42) mmol/L] were significantly decreased(all P<0.001). Levels of C1q, hs-CRP[AIS:4.10(2.15-15.05)mg/L; TIA:1.40(0.63-3.88)mg/L],IL-6 [AIS: 10.88(7.21-32.96) ng/L; TIA: 7.07(6.18-9.82)ng/L] and PCT [AIS: 0.06(0.04-0.11)μg/L; TIA: 0.20(0.20-0.04)μg/L] in AIS patients were significantly higher than that in TIA patients(all P<0.05). C1q levels [AIS:203.00(183.25-219.75)mg/L; TIA: 181.00(1 666.50-206.00)mg/L] in severe AIS patients (NIHSS≥6) were significantly higher than that in mild AIS patients (NIHSS<6)( P=0.031). C1q levels[AIS:197.00(180.00-219.00)mg/L; TIA: 182.00(167.50-195.50)mg/L] in high-risk TIA patients (ABCD3-I>3) were significantly higher than that in low-risk TIA patients (ABCD3-I≤3)( P=0.018). After adjusting for age, gender, other lipid/lipoprotein and glucose parameters, C1q levels in AIS patients were independently linked(adjusted R2=0.704) to TC (β=0.524, P=0.078),TG (β=0.0.439, P=0.0.017) levels and NIHSS (β=0.372, P=0.039); C1q levels in TIA patients were independently linked (adjusted R2=0.505) to TG (β=0.535, P<0.001) levels and ABCD3-I (β=0.406, P<0.001); high C1q levels were closely associated with AIS( OR=1.035, 95 %CI1.014-1.056, P=0.001) and TIA ( OR=1.023, 95 %CI1.003-1.044, P=0.025) presence, and could also clearly differentiate between AIS and TIA( OR=1.013, 95 %CI1.000-1.026, P=0.049). Conclusions:Serum C1q levels were significantly elevated in AIS and TIA patients, especially in AIS patients. Serum C1q were independently linked to NIHSS of AIS patients and ABCD3-I of TIA patients, and may be function as a novel risk biomarker for predicting and differentiating AIS and TIA.
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Atherosclerotic cardiovascular disease (ASCVD) remains the leading cause of death globally. The complement system is a bridge connecting innate and adaptive immunity. A variety of complement components may participate in the occurrence and development of atherosclerosis by affecting inflammatory responses, vascular remodeling and thrombosis. In recent years, the clinical values of complement levels, complement activation products and complement regulatory proteins have become increasingly prominent, and the application of complement-related biomarkers could provide an important reference for the diagnosis, prediction, risk assessment and prognosis evaluation of ASCVD. In this review, we focused on the pathophysiological mechanism of the complement system involved in ASCVD and the application of complement-related biomarkers associated with risk of ASCVD.
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The residual cardiovascular disease (CVD) risk is the term applied to the cardiovascular events remain prevalent among individuals with low or normal LDL-C, normal blood pressure and glucose. Therefore, while controlling traditional risk factors, the CVD residual risk is constantly being discovered, which is crucial for further reducing CVD events. Lipoprotein (a), TRLs and their residues, HDL-C, hypersensitive CRP and homocysteine have been found to be CVD residual risk factors. Whether gene-related factors and some new non-traditional factors can predict residual CVD risk have also become the current research hotspots. Focusing on the residual risk factors of cardiovascular disease can provide new ideas for further reducing CVD events.
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Objective@#To investigate the effect of IFN-γ on the expression of IL-33 in colon cancer CT26 cells. @*Methods@#CT26 cells were treated with IFN-γ and IFN-γ combined with PKA inhibitor H89, respectively, and a negative control group (NC, untreated) was set up at the same time. The mRNA expression levels of PKA, CREB and IL-33 in CT26 cells were detected by qRT-PCR. The expression levels of PKA, CREB, p-CREB and IL-33 proteins in CT26 cells were determined by western blot. The localization of CREB protein in CT26 cells was analyzed by the immunofluorescence confocal microscopy. @*Results@#The relative expression levels of PKA, CREB and IL-33 mRNA in the IFN-γ-treated group were 2.50±0.11, 3.10±0.08 and 2.80±0.22, respectively, which were significantly higher than those in the NC group (P＜0.05). The relative expression levels of PKA, CREB and IL-33 mRNA in the IFN-γ combined with H89 treatment group were 0.21±0.02, 0.59±0.05 and 0.35±0.04, respectively, which were significantly lower than those in the NC group and IFN-γ-treated group (P＜0.05). The expression levels of PKA, CREB and IL-33 proteins detected by western blot were consistent with that of mRNA. Immunofluorescence confocal results showed that the expression level of CREB in the IFN-γ-treated group was significantly higher than that in the NC group, and that the expression level of CREB in the IFN-γ combined with H89 treatment group was significantly lower than that in the IFN-γ-treated group. @*Conclusion@#IFN-γ may induce the expression of IL-33 in colon cancer CT26 cells via the PKA-CREB pathway.
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Objective The aim of this experiment was to explore the effect and mechanism of intestinal microbiota on shaping the growth performance by fecal microbiota transplantation from pigs to pseudo-germ-free mice. Methods Thirty-six barrows with a similar initial body weight of 30 kg were raised for 42 days(ad libitum)within individual metabolic cages. Feed intake and body weight of each pig were recorded every week to calculate the feed conversion rate and average daily gain. At the end of the experiment,feed conversion ratio and average daily gain were integrated to divide the pigs into 3 groups, namely, high growth performance(HP), moderate growth performance(MP)and low growth performance(LP)groups. Feces were collected to calculate the total intestinal nutrient digestibility and prepare for fecal microbiota transplantation to pseudo-germ-free mice, which were induced with several antibiotics for four weeks. Fecal microbiome structure was assayed by profiling V3-V4 region of the 16S rRNA gene. Results Fecal microbiota transplantation from pigs to pseudo-germ-free mice resulted in reappearance of the original phenotype. Compared with the LP pigs, the microbial species richness and microbial diversity in feces were higher in the HP pigs. The HP pigs had improved digestibility of gross energy(P =0.01)and higher abundance of Methanobrevibacter. Enterococcus and Akkermansia were also more abundant in the recipient pseudo-germ-free mice from the HP pigs which may be correlated with a high energy utilization. Conclusions Fecal microbiota transplantation from pigs to mice results in reappearance of the original phenotype and microbial species richness,microbial diversity,and their growth ability. Different nutritional metabolism is shown among pigs with different feed efficiency and the HP pigs have improved energy utilization(P=0.01). At the same time, the bacteria correlated with high energy utilization are more abundant in feces of HP pigs than in LP pigs.
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Objective To investigate serum complement 1q (C1q) levels in the patients with coronary artery disease (CAD),and evaluate its clinical values in predicting and discriminating acute coronary syndrome (ACS) and stable coronary artery disease (SCAD).Methods A total of 52 ACS patients,66 SCAD patients and 54 healthy controls were enrolled in this study.Their serum C1q and oxidized low-density lipoprotein (ox-LDL) levels were detected by an immune turbidimetric method and an enzyme linked immunosorbent assay,respectively.Their serum total cholesterol,triglyceride,high-density lipoprotein cholesterol and low-density lipoprotein cholesterol levels were also determined.Then,the Gensini scores in CAD patients were calculated,and the clinical values of Clq in predicting and discriminating ACS and SCAD were evaluated by stepwise multiple linear regression analysis and Logistic regression analysis.Results Serum C1q and ox-LDL levels in ACS (C1q:t =4.405,P＜0.001;ox-LDL:Z=5.941,P＜0.001) and SCAD (C1q:t =2.320,P=0.022;ox-LDL:Z =4.119,P ＜0.001) patients were significantly higher than those in healthy controls.Moreover,serum C1q (t =2.344,P =0.021) and ox-LDL (Z =2.166,P =0.030) levels in ACS patients were significantly higher than that in SCAD patients.Serum C1 q levels were positively correlated with serum ox-LDL (r =0.246,P =0.028) and TG (r =0.232,P =0.002) levels and Gensini scores (r =0.341,P =0.020) in ACS patients.The stepwise multiple regression analysis showed that serum ox-LDL levels were still independently correlated with serum C1 q levels in ACS patients (β =0.676,P =0.045,adjusted R2 =0.380) after adjusting for age,gender and other biochemical markers.The Logistic regression analysis showed that the increased serum C1q and ox-LDL levels were closely related to the occurrence of ACS (C1q:OR =1.05,95％ CI =1.03-1.08,P ＜ 0.001;ox-LDL:OR =1.18,95％ CI =1.08-1.29,P ＜0.001) and SCAD (C1q:OR =1.04,95％CI=1.01-1.06,P=0.003;ox-LDL:OR=I.11,95％CI=1.03-1.18,P=0.004),and that they could discriminate ACS and SCAD (C 1 q:OR =1.01,95 ％ CI =1.00-1.03,P =0.022;ox-LDL:OR =1.06,95 ％ CI =1.01-1.12,P =0.023).Conclusion Serum C1q levels increase significantly in CAD patients,and that of ACS patients is significantly higher than SCAD patients.In ACS patients,serum C1q levels are independently correlated with ox-LDL levels.Serum C1q levels may be served as a novel biomarker for the prediction and discrimination of ACS and SCAD.