1.Pharmacokinetics of Total Alkaloids of Corydalis saxicola in Depression Model Rats
Huaxi HANG ; Meishuang YU ; Yu YE ; Qian HUANG ; Yiran WANG ; Xuewen SHAO ; Peiyao CHEN ; Yang CAO ; Guoliang DAI ; Wenzheng JU
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(14):175-183
ObjectiveTo investigate the effect of total alkaloids of Corydalis saxicola on a rat model of lipopolysaccharide(LPS)-induced depression, as well as the pharmacokinetic characteristics of 8 of its major components. MethodTwenty-four male SD rats were randomly divided into normal group, model group, fluoxetine group(10 mg·kg-1) and total alkaloids of C. saxicola group(210 mg·kg-1), with 6 rats in each group. In addition to the normal group, the rats were injected intraperitoneally with LPS to establish the inflammation model of depression, and the drug administration was started 1 week after modeling, and the administration groups were gavaged according to the corresponding dose, and the normal and model groups were intragastric administration with equal volume of distilled water, and the administration was performed along with the modeling. After two weeks of continuous administration, the effect of total alkaloids of C. saxicola on the behavior of depressed rats were tested by sucrose preference, forced swimming and open field experiments, the levels of tumor necrosis factor-α(TNF-α), interleukin(IL)-1β and IL-6 in serum of rats were determined by enzyme-linked immunosorbent assay(ELISA), the histopathological changes of rat hippocampus were observed by hematoxylin-eosin(HE) staining. After the last administration, blood was collected from orbit according to the set time, and ultra-high performance liquid chromatography-triple quadrupole tandem mass spectrometry(UPLC-QqQ-MS) was established to simultaneously detect the concentrations of dehydrocavidine, tetrahydropalmatine, coptisine, palmatine, jatrorrhizine, berberine, berberrubine and epiberberine in plasma, and drug-time curves were drawn. The pharmacokinetic parameters were analyzed by DAS 2.0 software. ResultCompared with the normal group, the model group exhibited a decrease in sucrose preference rate, total distance traveled in the open field, as well as an increase in swimming immobility time and serum inflammatory factor expression(P<0.01). In contrast, compared with the model group, rats in each administration group showed an increase in sucrose preference rate and total distance traveled in the open field, a decrease in swimming immobility time, and a reduction in serum inflammatory factor expression(P<0.05, P<0.01). Additionally, HE staining results revealed that neurons in the hippocampus of rats from the model group were characterized by loss, disorganization and residual vacuoles, whereas those from the total alkaloids of C.saxicola group displayed an increase in number with orderly arrangement and clear cytoplasm. Pharmacokinetic results showed that the time to peak(tmax) and half-life(t1/2) of the 8 active ingredients were 0.19-2.06 h and 3.71-8.70 h after continuous administration of total alkaloids of C. saxicola. Among them, the area under the curve(AUC0-∞) of tetrahydropalmatine was the highest and the t1/2 was the shortest, and the AUC0-∞ of coptisine, palmatine, jatrorrhizine, berberine, berberrubine and epiberberine were low. The curves of dehydrocavidine, coptisine, palmatine, berberine and epiberberine showed obvious double peak phenomenon. ConclusionTotal alkaloids of C. saxicola can improve the depression-like behavior of rats, inhibit the expression of inflammatory factors in serum, improve the pathological injury of hippocampus, and has the antidepressant effect. Meanwhile, the effective site is absorbed quickly and eliminated slowly in the depressed model rats, and the efficacy is maintained for a long time.
2.Renewal of embryonic and neonatal-derived cardiac-resident macrophages in response to environmental cues abrogated their potential to promote cardiomyocyte proliferation via Jagged-1-Notch1.
Rong CHEN ; Shiqing ZHANG ; Fang LIU ; Lin XIA ; Chong WANG ; Siamak SANDOGHCHIAN SHOTORBANI ; Huaxi XU ; Subrata CHAKRABARTI ; Tianqing PENG ; Zhaoliang SU
Acta Pharmaceutica Sinica B 2023;13(1):128-141
Cardiac-resident macrophages (CRMs) play important roles in homeostasis, cardiac function, and remodeling. Although CRMs play critical roles in cardiac regeneration of neonatal mice, their roles are yet to be fully elucidated. Therefore, this study aimed to investigate the dynamic changes of CRMs during cardiac ontogeny and analyze the phenotypic and functional properties of CRMs in the promotion of cardiac regeneration. During mouse cardiac ontogeny, four CRM subsets exist successively: CX3CR1+CCR2-Ly6C-MHCII- (MP1), CX3CR1lowCCR2lowLy6C-MHCII- (MP2), CX3CR1-CCR2+Ly6C+MHCII- (MP3), and CX3CR1+CCR2-Ly6C-MHCII+ (MP4). MP1 cluster has different derivations (yolk sac, fetal liver, and bone marrow) and multiple functions population. Embryonic and neonatal-derived-MP1 directly promoted cardiomyocyte proliferation through Jagged-1-Notch1 axis and significantly ameliorated cardiac injury following myocardial infarction. MP2/3 subsets could survive throughout adulthood. MP4, the main population in adult mouse hearts, contributed to inflammation. During ontogeny, MP1 can convert into MP4 triggered by changes in the cellular redox state. These findings delineate the evolutionary dynamics of CRMs under physiological conditions and found direct evidence that embryonic and neonatal-derived CRMs regulate cardiomyocyte proliferation. Our findings also shed light on cardiac repair following injury.
3.Association of energy metabolic markers with the short-term risk of spontaneous bacterial peritonitis in patients with decompensated hepatitis B virus-related liver cirrhosis
Xiumin CHEN ; Shenglong LIN ; Xiangmei WANG ; Huaxi MA ; Dongqing ZHANG ; Ziyuan LIAO ; Minghua LIN ; Haibing GAO
Journal of Clinical Hepatology 2022;38(6):1311-1316
Objective To investigate the association of energy metabolic markers with the risk of spontaneous bacterial peritonitis (SBP) in patients with decompensated hepatitis B virus-related liver cirrhosis (HBV-LC). Methods A retrospective analysis was performed for the clinical data of the patients with decompensated HBV-LC who were admitted to Mengchao Hepatobiliary Hospital of Fujian Medical University from November 2017 to November 2019, and baseline clinical parameters and energy metabolic markers were compared between the patients with SBP and those without SBP within 2 weeks after admission. A multivariate logistic regression analysis was performed to investigate the risk factors for SBP. The t -test was used for comparison of normally distributed continuous data between two groups, and the Kruskal-Wallis H test was used for comparison of non-normally distributed continuous data between two groups; the Fisher's exact test was used for comparison of categorical data between two groups. The receiver operating characteristic (ROC) curve was plotted to evaluate the diagnostic efficiency of the newly established logistic regression model, and with the corresponding point of Youden index as the cut-off value, the DeLong test was used to compare the area under the ROC curve (AUC). Results A total of 50 patients with decompensated HBV-LC were included, among whom 23 (46%) developed SBP within 2 weeks after admission and 27 (54%) had no SBP during hospitalization. Compared with the non-SBP patients, the SBP patients had significantly lower triglyceride, prealbumin, and prothrombin time activity (PTA) and significantly higher international normalization ratio, C-reactive protein (CRP), and Model for End-Stage Liver Disease score (all P < 0.05). Comparison of baseline energy metabolic markers showed that compared with the non-SBP patients, the SBP patients had significantly lower respiratory quotient (RQ) [0.79(0.76-0.86) vs 0.85(0.79-0.91), P =0.041] and carbohydrate oxidation (CHO) rate [20.50%(15.25%-41.05%) vs 41.6%(22.25%-68.05%), P =0.041]. The multivariate logistic regression analysis showed that PTA was an independent risk factor for SBP in the patients with decompensated HBV-LC during hospitalization (odd ratio=0.004, P =0.008), and the regression model established based on the variables including PTA, CRP, RQ, and CHO had an AUC of 85.0% and a cut-off value of 0.60 at the maximum Youden index, with a specificity of 85.19% and a sensitivity of 73.91%, suggesting that this model had a better discriminatory ability than CRP (AUC=74.5%, P =0.049) and procalcitonin (AUC=56.4%, P < 0.01). Conclusion There are significant reductions in the energy metabolic markers RQ and CHO in the patients with decompensated HBV-LC who develop SBP within a short term, and their combination with PTA, CRP, and CHO/RQ ratio can help clinicians identify the patients at a high risk of SBP in the early stage and enhance nutrition support for such patients.
4.Abnormal spontaneous brain functional activity in adult patients with amblyopia: a resting-state functional magnetic resonance imaging study.
Xia CHEN ; Meng LIAO ; Ping JIANG ; Longqian LIU ; Qiyong GONG
Journal of Biomedical Engineering 2022;39(4):759-766
Amblyopia is a visual development deficit caused by abnormal visual experience in early life, mainly manifesting as defected visual acuity and binocular visual impairment, which is considered to reflect abnormal development of the brain rather than organic lesions of the eye. Previous studies have reported abnormal spontaneous brain activity in patients with amblyopia. However, the location of abnormal spontaneous activity in patients with amblyopia and the association between abnormal brain function activity and clinical deficits remain unclear. The purpose of this study is to analyze spontaneous brain functional activity abnormalities in patients with amblyopia and their associations with clinical defects using resting-state functional magnetic resonance imaging (fMRI) data. In this study, 31 patients with amblyopia and 31 healthy controls were enrolled for resting-state fMRI scanning. The results showed that spontaneous activity in the right angular gyrus, left posterior cerebellum, and left cingulate gyrus were significantly lower in patients with amblyopia than in controls, and spontaneous activity in the right middle temporal gyrus was significantly higher in patients with amblyopia. In addition, the spontaneous activity of the left cerebellum in patients with amblyopia was negatively associated with the best-corrected visual acuity of the amblyopic eye, and the spontaneous activity of the right middle temporal gyrus was positively associated with the stereoacuity. This study found that adult patients with amblyopia showed abnormal spontaneous activity in the angular gyrus, cerebellum, middle temporal gyrus, and cingulate gyrus. Furthermore, the functional abnormalities in the cerebellum and middle temporal gyrus may be associated with visual acuity defects and stereopsis deficiency in patients with amblyopia. These findings help explain the neural mechanism of amblyopia, thus promoting the improvement of the treatment strategy for amblyopia.
Adult
;
Amblyopia/pathology*
;
Brain
;
Brain Mapping
;
Humans
;
Magnetic Resonance Imaging/methods*
;
Visual Acuity
5.Respiratory virus infection and risk factors in children with bronchial asthma
Lixue LI ; Pingkang WANG ; Xiang ZHANG ; Yaqin CHEN ; Tao WANG
Journal of Public Health and Preventive Medicine 2022;33(3):154-156
Objective To understand the etiological characteristics and risk factors of respiratory virus infection in children with bronchial asthma, and to provide theoretical basis for the prevention and treatment of respiratory virus infection in children with bronchial asthma. Methods A total of 374 children with bronchial asthma who were treated in Jianyang People's Hospital from December 2018 to December 2020 were enrolled. Pharyngeal swabs were collected from the outpatient children on the day of treatment, and 2 mL of nasopharyngeal secretions were collected from the hospitalized children within 24 hours by negative pressure aspirator. Seven viral antigens including RSV, ADV, IVA, IVB, PIVI, PIV II, and PIV III were detected. According to whether the virus test results were positive or not, they were divided into the experimental group (n=191) and the control group (n=183). Logistic regression analysis was used to screen the risk factors of respiratory virus infection in children with bronchial asthma. Results Among the 374 samples, the virus positive rate was 51.07% (191/374), and the top 3 virus species in the positive samples were RSV, ADV, and PIV III, accounting for 41.36% (79/191), 30.36% (58/191), and 9.42% (18/191), respectively. In addition, IVA accounted for 5.24% (10/191), PIV II accounted for 5.24% (10/191), PIVI accounted for 3.66% (7/191), and IVB accounted for 1.57% (3 /191). The positive rates of virus were 47.96% (94/196) and 54.49% (97/178) in male and female children, respectively, with no significant difference (χ2=1.597,P>0.05). The positive rate of 1~3 years old children was significantly higher than that of >3 years old group (χ2=6.412,P<0.05). There were significant differences in the frequency of asthma attack, intravenous glucocorticoid application and the onset season between the two groups (P<0.05). Further analysis showed that the frequency of asthma attack >3 times, intravenous glucocorticoid application and onset season were independent risk factors for respiratory virus infection in children with bronchial asthma (P<0.05). Conclusion The infection season of acute respiratory tract infection in children with asthma is mainly concentrated in autumn and winter, with RSV as the main viral pathogen. Targeted preventive measures should be given to children with bronchial asthma who have more than 3 asthma attacks and intravenous glucocorticoid application, which can reduce respiratory virus infection in children with asthma.
6.IL-10 producing regulatory B cells ameliorated cardiac hypertrophy of viral myocarditis mice
Shiqing ZHANG ; Jia CHEN ; Lin XIA ; Zhaoliang SU ; Huaxi XU ; Fang LIU
Chinese Journal of Microbiology and Immunology 2021;41(5):345-352
Objective:To explore the mechanism of B10 cell involved in cardiomyocyte hypertrophy following myocarditis, and to develop potential therapeutic strategies.Methods:BALB/c mice infected with Coxsackie virus B3 induced viral myocarditis model. The expression of angiotensin (ANG)Ⅱ and its receptor in myocarditis mice was detected. The changes of B10 cells in the hearts of control mice and myocarditis mice were analyzed by flow cytometry. After losartan was administered to myocarditis mice, the degree of myocardial inflammation was detected by HE staining, the expression of inflammatory factors was detected by ELISA, the myocardial hypertrophy was detected by wheat germ agglutinin (WGA) staining, and the changes of B10 cells in the heart were analyzed by flow cytometry. The levels of cardiac troponin T (C-TNT) and high mobility group box 1 (HMGB1) protein in neonatal mouse cardiomyocytes treated with ANGⅡ and ANGⅡ+ IL-10 were detected. Cardiomyocytes were treated with ANGⅡ, ANGⅡ+ B10 cells, ANGⅡ+ B10 cells + IL-10 receptor antibody and ANGⅡ+ B cells to detect C-TNT protein levels, and Annexin-V/PI was used to detect the apoptosis of cardiomyocytes. Cardiomyocytes were treated with oxidized HMGB1, reduced HMGB1 and disulfide HMGB1, and C-TNT expression was detected.Results:Coxsackievirus B3 infection caused cardiac hypertrophy, high expression of ANGⅡ and its receptor, and transient increase of B10 cells in mice. Losartan treatment blocked the angiotensin receptor, reduced expansion of B10 cells. B10 cells alleviated apoptosis of cardiomyocytes and inhibited the production of HMGB1 induced by ANGⅡ patch by producing IL-10, thus alleviating viral myocarditis and cardiac hypertrophy.Conclusions:B10 cells may play an important role in myocardial protection in myocarditis.
7.Translational application of neuroimaging in major depressive disorder: a review of psychoradiological studies.
Ziqi CHEN ; Xiaoqi HUANG ; Qiyong GONG ; Bharat B BISWAL
Frontiers of Medicine 2021;15(4):528-540
Major depressive disorder (MDD) causes great decrements in health and quality of life with increments in healthcare costs, but the causes and pathogenesis of depression remain largely unknown, which greatly prevent its early detection and effective treatment. With the advancement of neuroimaging approaches, numerous functional and structural alterations in the brain have been detected in MDD and more recently attempts have been made to apply these findings to clinical practice. In this review, we provide an updated summary of the progress in translational application of psychoradiological findings in MDD with a specified focus on potential clinical usage. The foreseeable clinical applications for different MRI modalities were introduced according to their role in disorder classification, subtyping, and prediction. While evidence of cerebral structural and functional changes associated with MDD classification and subtyping was heterogeneous and/or sparse, the ACC and hippocampus have been consistently suggested to be important biomarkers in predicting treatment selection and treatment response. These findings underlined the potential utility of brain biomarkers for clinical practice.
Brain/diagnostic imaging*
;
Depressive Disorder, Major/diagnostic imaging*
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Humans
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Magnetic Resonance Imaging
;
Neuroimaging
;
Quality of Life
8.Abnormal static and dynamic brain function in patients with temporomandibular disorders: a resting-state functional magnetic resonance imaging study.
Yuan Yuan YIN ; Fei LI ; Shu Shu HE ; Song CHEN
West China Journal of Stomatology 2021;39(6):682-689
OBJECTIVES:
This study was conducted to investigate the brain function of patients with temporomandibular disorders (TMD) by combining the static and dynamic amplitudes of low-frequency fluctuation (ALFF).
METHODS:
Thirty patients with TMD and 20 healthy controls were enrolled. All the participants completed their questionnaires, received clinical examinations, and underwent resting-state functional magnetic resonance imaging scanning. We compared the static and dynamic ALFF between the patients and healthy controls by conducting a two-sample
RESULTS:
The patients with TMD showed increased static and dynamic ALFF in the posterior cingulate cortex compared with that of the controls (whole-brain level, uncorrected
CONCLUSIONS
Our findings revealed that the resting-state brain function of the posterior cingulate cortex and the medial orbitofrontal cortex of patient with TMD increased. These changes probably indicated the potential central mechanisms underlying the increased self-relevant thoughts, negative emotion, and abnormal emotion regulation in TMD.
Brain/diagnostic imaging*
;
Humans
;
Magnetic Resonance Imaging
;
Temporomandibular Joint Disorders/diagnostic imaging*
9.Energy metabolism characteristic with risk of secondary bacterial infection in patients with hepatitis B virus-related chronic liver disease
Shenglong LIN ; Minghua LIN ; Xiangmei WANG ; Xiumin CHEN ; Hanhui YE ; Huaxi MA ; Dongqing ZHANG ; Wenjun WU ; Jiahuang LIN ; Ziyuan LIAO ; Ruidan ZHENG ; Haibing GAO
Chinese Journal of Hepatology 2021;29(6):558-564
Objective:To investigate and analyze the energy metabolism characteristics and the correlation between energy metabolism and the risk of secondary bacterial infection in patients with hepatitis B virus-related chronic liver disease (HBV-CLD).Methods:Data of 183 cases admitted to the Mengchao Hepatobiliary Hospital of Fujian Medical University from November 2017 to November 2020 were retrospectively analyzed. 79 cases of chronic hepatitis B, 51 cases of hepatitis B-related liver cirrhosis, and 53 cases of hepatitis B-related liver failure were collected. Among them patients with liver failure and decompensated liver cirrhosis were defined as severe liver disease group. The Quark RMR indirect calorimetry (COSMED Corporation, Italy) was used to exam the patients' energy metabolism condition, and the incidences of secondary bacterial infection of the patients during hospitalization were recorded. Shapiro-Wilk test and normal QQ plot were used to analyze the normal distribution of continuous variable data, which was consistent with the normal distribution and was described by mean ± standard deviation. In addition, if it did not conform to the normal distribution, the median and interquartile distance were used to describe it. Levene’s test was used to test the homogeneity of variance of the data, which was consistent with the normal distribution. The t-test was used to compare the means of the two groups of samples. One-way analysis of variance was used to compare the mean values of the three groups of samples, and then the Tukey's test was used to compare the two groups. If the variance was uneven or did not conform to the normal distribution, the Wilcoxon rank sum test was used to compare the differences between the two groups. Kruskal-Wallis test (H test) was used to compare the differences between the three groups of samples, and then the Dunnett’s test (Z test) was used for comparison between the two groups. Categorical variable data were analyzed using chi-square test. Logistic regression analysis was used to screen independent risk factors, and the criteria for variable inclusion ( P < 0.05). Results:The respiratory entropy (RQ) and non-protein respiratory entropy (npRQ) of the three groups had statistically significant difference ( P < 0.05). Among them, the RQ and npRQ of the chronic hepatitis B group were higher than hepatitis B-related liver cirrhosis group and hepatitis B-related liver failure group. There were statistically significant differences in fat oxidation rate (FAT%) and carbohydrate oxidation rate (CHO%) between the three groups ( P < 0.05). Compared with hepatitis B-related liver cirrhosis group and hepatitis B-related liver failure group, chronic hepatitis B group ( P < 0.05) had lower FAT% and higher CHO%. There were no statistically significant differences in the measured and predicted resting energy expenditure and protein oxidation rate (PRO%) between the three groups. The incidence of secondary bacterial infection in patients with severe liver disease was 48.39% (45/93). Compared with the non-infected group, the RQ and npRQ values ??of the infected group were significantly decreased ( P < 0.05), while FAT% was significantly increased ( P < 0.05). Logistic regression analysis showed that glutamyltransferase, cholesterol, and npRQ were independent risk factors for secondary bacterial infections in patients with severe liver disease. Glutamyltransferase elevation, and cholesterol and npRQ depletion had suggested an increased risk of secondary bacterial infection. Subgroup analysis of patients with hepatitis B-related liver failure also showed that compared with non-infected group, RQ value and npRQ value of secondary bacterial infection group were significantly decreased ( P < 0.05), while FAT% was significantly increased ( P < 0.05). Conclusion:Patients with hepatitis B virus-related chronic liver disease generally have abnormal energy metabolism. Low RQ, npRQ, CHO% and high FAT% are related to the severity of the disease; while npRQ reduction is related to the risk of secondary bacterial infection in patients with severe liver disease, and thus can be used as a clinical prognostic indicator.
10.Hyperinsulinemic Hypoglycemia after Bariatric Surgery
Songhao HU ; Hanlin TANG ; Huaxi WANG ; Zhiyong DONG ; Shuwen JIANG ; Cunchuan WANG ; Xiaomei CHEN ; Wah YANG
Journal of Metabolic and Bariatric Surgery 2020;9(1):1-6
Postprandial hyperinsulinemic hypoglycemia (PHH) is one of the serious complications after bariatric surgery, it can lead life-threatening neuroglycopenic symptoms, such as seizures, disorientation, impairment of version and loss of consciousness without any premonitory. The presentation, prevalence, diagnosis, pathology and treatment are reviewed in this summary.


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