Publications by authors named "Cui Cai"

12 Publications

  • Page 1 of 1

Bedaquiline-containing regimens in patients with pulmonary multidrug-resistant tuberculosis in China: focus on the safety.

Infect Dis Poverty 2021 Mar 19;10(1):32. Epub 2021 Mar 19.

Department of Tuberculosis, The Second Affiliated Hospital of Hainan Medical University, Haikou, People's Republic of China.

Background: World Health Organization recommends countries introducing new drug and short treatment regimen for drug resistant tuberculosis (DR-TB) should develop and implement a system for active pharmacovigilance that allows for detection, reporting and management of adverse events. The aim of the study is to evaluate the frequency and severity of adverse events (AEs) of bedaquiline-containing regimen in a cohort of Chinese patients with multidrug-resistant (MDR)/extensively drug-resistant (XDR)-TB based on active drug safety monitoring (aDSM) system of New Drug Introduction and Protection Program (NDIP).

Methods: AEs were prospectively collected with demographic, bacteriological, radiological and clinical data from 54 sites throughout China at patient enrollment and during treatment between February, 2018 and December, 2019. This is an interim analysis including patients who are still on treatment and those that have completed treatment. A descriptive analysis was performed on the patients evaluated in the cohort.

Results: By December 31, 2019, a total of 1162 patients received bedaquiline-containing anti-TB treatment. Overall, 1563 AEs were reported, 66.9% were classified as minor (Grade 1-2) and 33.1% as serious (Grade 3-5). The median duration of bedaquiline treatment was 167.0 [interquartile range (IQR): 75-169] days. 86 (7.4%) patients received 36-week prolonged treatment with bedaquiline. The incidence of AEs and serious AEs was 47.1% and 7.8%, respectively. The most frequently reported AEs were QT prolongation (24.7%) and hepatotoxicity (16.4%). There were 14 (1.2%) AEs leading to death. Out of patients with available corrected QT interval by Fridericia's formula (QTcF) data, 3.1% (32/1044) experienced a post-baseline QTcF ≥ 500 ms, and 15.7% (132/839) had at least one change of QTcF ≥ 60 ms from baseline. 49 (4.2%) patients had QT prolonged AEs leading to bedaquiline withdrawal. One hundred and ninety patients reported 361 AEs with hepatotoxicity ranking the second with high occurrence. Thirty-four patients reported 43 AEs of hepatic injury referred to bedaquiline, much lower than that referred to protionamide, pyrazinamide and para-aminosalicylic acid individually.

Conclusions: Bedaquiline was generally well-tolerated with few safety concerns in this clinical patient population without any new safety signal identified. The mortality rate was generally low. These data inform significant positive effect to support the WHO recent recommendations for the wide use of bedaquiline.
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http://dx.doi.org/10.1186/s40249-021-00819-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7977294PMC
March 2021

Patient pathway analysis of tuberculosis diagnostic delay: a multicentre retrospective cohort study in China.

Clin Microbiol Infect 2021 Jul 6;27(7):1000-1006. Epub 2021 Jan 6.

Department of Infectious Diseases, Huashan Hospital, Fudan University, Shanghai, China. Electronic address:

Objectives: Delay in diagnosis of tuberculosis (TB) is an important but under-appreciated problem. Our study aimed to analyse the patient pathway and possible risk factors of long diagnostic delay (LDD).

Methods: We enrolled 400 new bacteriologically diagnosed patients with pulmonary TB from 20 hospitals across China. LDD was defined as an interval between the initial care visit and the confirmation of diagnosis exceeding 14 days. Its potential risk factors were investigated by multivariate logistic regression and multilevel logistic regression. Hospitals in China were classified by increasing size, from level 0 to level 3. TB laboratory equipment in hospitals was also evaluated.

Results: The median diagnostic delay was 20 days (IQR: 7-72 days), and 229 of 400 patients (57.3%, 95%CI 52.4-62.1) had LDD; 15% of participants were diagnosed at the initial care visit. Compared to level 0 facilities, choosing level 2 (OR 0.27, 95%CI 0.12-0.62, p 0.002) and level 3 facilities (OR 0.34, 95%CI 0.14-0.84, p 0.019) for the initial care visit was independently associated with shorter LDD. Equipping with smear, culture, and Xpert at initial care visit simultaneously also helped to avoid LDD (OR 0.28, 95%CI 0.09-0.82, p 0.020). The multilevel logistic regression yielded similar results. Availability of smear, culture, and Xpert was lower in level 0-1 facilities than in level 2-3 facilities (p < 0.001, respectively).

Conclusions: Most patients failed to be diagnosed at the initial care visit. Patients who went to low-level facilities initially had a higher risk of LDD. Improvement of TB laboratory equipment, especially at low-level facilities, is urgently needed.
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http://dx.doi.org/10.1016/j.cmi.2020.12.031DOI Listing
July 2021

Modified Si-Jun-Zi-Tang Attenuates Airway Inflammation in a Murine Model of Chronic Asthma by Inhibiting Teff Cells via the mTORC1 Pathway.

Front Pharmacol 2019 27;10:161. Epub 2019 Feb 27.

Department of Respiratory Diseases, Affiliated Hangzhou First People's Hospital, Nanjing Medical University, Hangzhou, China.

Modified Si-Jun-Zi-Tang (MSJZT), a multi-herb formulation, is frequently used in traditional Chinese medicine for patients during the remission stage of asthma. However, the pharmacological basis underlying the effects of MSJZT on asthma has yet to be elucidated. This study aims at evaluating the anti-asthmatic effects of MSJZT and investigating its possible mechanism. A chronic murine model of asthma was established by sensitization and repeated challenge with ovalbumin (OVA) in female BALB/c mice, followed with oral administration of MSJZT during remission, and then mouse were re-challenged by OVA. The chemical profile of MSJZT was analyzed by high-performance liquid chromatography. The characteristic features of allergic asthma, including airway hyperreactivity, histopathology, cytokine levels (IL-4, -5, -13, -17, and INF-γ), T regulatory (Treg) lymphocytes (Foxp3+CD4+CD25+), and T effector (Teff) lymphocytes (Foxp3-CD25+CD4+) in bronchoalveolar lavage fluid (BALF), and downstream proteins of mTORC1/2 signaling pathway were examined. MSJZT markedly suppressed airway hyper-responsiveness to aerosolized methacholine, and reduced levels of IL-4, IL-5, and IL-13 in the BALF. Histological studies showed that MSJZT significantly reduced inflammatory infiltration in lung tissues. The percentage and absolute number of Teff cells were suppressed to a remarkable level by MSJZT without affecting Treg cells. Furthermore, MSJZT effectively inhibited the mTORC1 activity, but exerted limited effects on mTORC2, as assessed by the phosphorylation of the mTORC1 and mTORC2 substrates, S6 ribosomal protein, p70 S6 kinase, mTOR S2481, and Akt, respectively. MSJZT attenuated chronic airway inflammation in a mouse model of asthma by inhibiting Teff cells, which occurred, at least in part, via modulation of the mTORC1 signaling pathway.
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http://dx.doi.org/10.3389/fphar.2019.00161DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6400882PMC
February 2019

Combined Effects of Chronic Obstructive Pulmonary Disease and Depression on Spatial Memory in Old Rats.

Chin Med Sci J 2018 Dec;33(4):260-266

Department of Geriatrics,Hangzhou First People's Hospital, Hangzhou 310006, China.

Objective To investigate the combined effects of chronic obstructive pulmonary disease (COPD) and depression on spatial memory in old rats, aiming to better understand the comorbidity of the two diseases in geriatric patients. Methods The SD rats were assigned into five groups: adult control group (n=6), elderly control group (n=6), elderly COPD group (n=6), elderly depression group (n=6) and elderly COPD with depression group (n=6). Smoking and chronic unpredictable mild stress (CUMS) with solitary support were used to induce COPD model, depression model, respectively, and the both were applied for the comorbidity model. Learning and memory deficits were assessed by Morris water maze (MWM) test. The activity of superoxide dismutase (SOD) and the content of malondialdehyde (MDA) in serum and hippocampus tissue were determined by Xanthinoxidase method and Thiobarbituric acid reaction (TBAR) method, respectively. Results The results of pulmonary histology, lung function, open-field test and sucrose consumption demonstrated the comorbidity models of COPD and depression in elderly rats were successfully established using smoking and CUMS with solitary support. Compared with the elderly control group, the group of COPD with depression had obviously longer time of latency and longer travel distance to reach the platform in MWM test (LSD-t=-10.116, P=0.000; LSD-t=-6.448, P=0.000). The SOD activity in serum and hippocampus decreased significantly (LSD-t=2.629, P=0.014; LSD-t=2.215, P=0.044) and the MDA content in serum and hippocampus increased significantly (LSD-t=-2.140, P=0.042; LSD-t=-2.070, P=0.049) in elderly COPD with depression group. Conclusions COPD in comorbidity of depression could induce spatial memory deficit in old rats. The mechanisms might be related to the overloaded and free radical metabolic imbalance. These results suggest a potential therapeutic target for comorbidity of COPD and depression in geriatric patients.
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http://dx.doi.org/10.24920/003470DOI Listing
December 2018

Astragaloside IV Ameliorates Airway Inflammation in an Established Murine Model of Asthma by Inhibiting the mTORC1 Signaling Pathway.

Evid Based Complement Alternat Med 2017 25;2017:4037086. Epub 2017 Oct 25.

Department of Respiratory Diseases, Hangzhou First People's Hospital, The Fourth Clinical College of Zhejiang Chinese Medical University, Hangzhou, Zhejiang 310006, China.

Astragaloside IV (AS-IV), a main active constituent of , has been confirmed to have antiasthmatic effects. However, it remained unclear whether the beneficial effects of AS-IV on asthma were attributed to the mTOR inhibition; this issue was the focus of the present work. BALB/c mice were sensitized and challenged with ovalbumin followed with 3 weeks of rest/recovery and then reexposure to ovalbumin. AS-IV was administrated during the time of rest and reexposure. The characteristic features of allergic asthma, including airway hyperreactivity, histopathology, cytokines (IL-4, IL-5, IL-13, IL-17, and INF-), and CD4CD25Foxp3Treg cells in bronchoalveolar lavage fluid (BALF), and downstream proteins of mTORC1/2 signaling were examined. AS-IV markedly suppressed airway hyperresponsiveness and reduced IL-4, IL-5, and IL-17 levels and increased INF- levels in the BALF. Histological studies showed that AS-IV markedly decreased inflammatory infiltration in the lung tissues. Notably, AS-IV inhibited mTORC1 activity, whereas it had limited effects on mTORC2, as assessed by phosphorylation of mTORC1 and mTORC2 substrates S6 ribosomal protein, p70 S6 Kinase, and Akt, respectively. CD4CD25Foxp3Treg cells in BALF were not significantly changed by AS-IV. Together, these results suggest that the antiasthmatic effects of AS-IV were at least partially from inhibiting the mTORC1 signaling pathway.
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http://dx.doi.org/10.1155/2017/4037086DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5676443PMC
October 2017

[Effects of icariin on Bcl-2 and Bax protein expressions and eosinophils apoptosis in bronchial asthmatic mice].

Zhongguo Zhong Xi Yi Jie He Za Zhi 2011 Sep;31(9):1248-53

Lab of Integrative Medicine for Lung, Inflammation and Cancer, Huashan Hospital, Fudan University, Shanghai 200040.

Objective: To study the effects of icariin on Bcl-2 and Bax protein expressions and eosinophils apoptosis in bronchial asthmatic mice.

Methods: 48 female Balb/c mice were randomly divided into 6 groups, i.e., the normal control group, the model group, the Dexamethasone group, the low dose icariin group, the middle dose icariin group, and the high dose icariin group, 8 mice in each group. Bronchial asthma in mice were induced by intraperitoneal sensitization and challenged with nebulized ovalbumin (OVA). The mice of each treatment group were administrated with different doses of icariin by peritoneal injection from the first asthma sensitization (the 3rd week after the modeling) to the day before killing once every other day, while mice in the normal control group were administrated with physiological saline. The mice were killed after 6 weeks of treatment. The apoptosis of eosinophils and the Bcl-2 and Bax protein expressions of the lung tissues were detected by TUNEL and immunohistochemical assay respectively.

Results: As compared with the model group, the apoptosis ratio of eosinophils were higher in the rest four treatment groups (P<0.05). The Bcl-2 protein positive areas in the lung tissues and the airway wall were significantly lowered (P<0.05). The Bax protein positive area significantly increased (P<0.05).

Conclusion: In bronchial asthmatic mice, icariin could enhance the apoptosis of eosinophils and lessen their infiltration by decreasing the expression of Bcl-2 protein and increasing the expression of Bax protein in lung.
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September 2011

Astrocytes express N-methyl-D-aspartate receptor subunits in development, ischemia and post-ischemia.

Neurochem Res 2010 Dec 30;35(12):2124-34. Epub 2010 Nov 30.

Neuroscience Research Institute, Peking University, 100191 Beijing, China.

The expression of the N-methyl-D-aspartate receptor (NMDA-R) in astrocytes is controversial. The receptor is commonly considered neuron-specific. We showed that astrocytes in primary cultures differentially expressed mRNA of NMDA-R subunits, NR1, NR2A and NR2B, in development, ischemia and post-ischemia. One-week-old cultures expressed detectable NR1 mRNA, which fell significantly at 2 weeks and became barely detectable at 4 weeks. NR2A and NR2B mRNA were both significantly up-regulated from 1 to 2 weeks. In 4 weeks, 2 h of ischemia caused a significant up-regulation of NR1 and NR2B mRNA; while 6 h caused down-regulation of NR2A mRNA. Under 3 h of post-ischemia, only NR1 mRNA was increased. Ischemia induced the expression of major NMDA-R effecter, nitric oxide synthase 1, which was unaffected by AMPA-R antagonist CNQX, but dose-dependently inhibited by NMDA-R specific antagonist MK-801. These findings reflected that astrocyte could express inducible functional NMDA receptors without the presence of neurons.
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http://dx.doi.org/10.1007/s11064-010-0325-xDOI Listing
December 2010

Inflammatory airway features and hypothalamic-pituitary-adrenal axis function in asthmatic rats combined with chronic obstructive pulmonary disease.

Chin Med J (Engl) 2010 Jul;123(13):1720-6

Lab of Integrative Medicine for Lung, Inflammation and Cancers, Huashan Hospital, Fudan University, Shanghai 200040, China.

Background: Bronchial asthma (BA) and chronic obstructive pulmonary disease (COPD) are both inflammatory airway diseases with different characteristics. However, there are many patients who suffer from both BA and COPD. This study was to evaluate changes of inflammatory airway features and hypothalamic-pituitary-adrenal (HPA) axis function in asthmatic rats combined with COPD.

Methods: Brown Norway (BN) rats were used to model the inflammatory airway diseases of BA, COPD and COPD + BA. These three models were compared and evaluated with respect to clinical symptoms, pulmonary histopathology, airway hyperresponsiveness (AHR), inflammatory cytokines and HPA axis function.

Results: The inflammatory airway features and HPA axis function in rats in the COPD + BA model group were greatly influenced. Rats in this model group showed features of the inflammatory diseases BA and COPD. The expression of inflammatory cytokines in this model group might be up or downregulated when both disease processes are present. The levels of corticotrophin releasing hormone mRNA and corticosterone in this model group were both significantly decreased than those in the control group (P < 0.05).

Conclusions: BN rat can be used as an animal model of COPD + BA. By evaluating this animal model we found that the features of inflammation in rats in this model group seem to be exaggerated. The HPA axis functions in rats in this model group have been disturbed or impaired, which is prominent at the hypothalamic level.
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July 2010

Structural insights into fibronectin type III domain-mediated signaling.

J Mol Biol 2007 Mar 11;367(2):303-9. Epub 2006 Oct 11.

Department of Prosthodontics, School of Dentistry, University of North Carolina, Chapel Hill, NC 27599, USA.

The alternatively spliced type III extradomain B (EIIIB) of fibronectin (FN) is expressed only during embryogenesis, wound healing and tumorigenesis. The biological function of this domain is unclear. We describe here the first crystal structure of the interface between alternatively spliced EIIIB and its adjacent FN type III domain 8 (FN B-8). The opened CC' loop of EIIIB, and the rotation and tilt of EIIIB allow good access to the FG loop of FN-8, which is normally hindered by the CC' loop of FN-7. In addition, the AGEGIP sequence of the CC'' loop of EIIIB replaces the NGQQGN sequence of the CC' loop of FN-7. Finally, the CC'' loop of EIIIB forms an acidic groove with FN-8. These structural findings warrant future studies directed at identifying potential binding partners for FN B-8 interface, linking EIIIB to skeletal and cartilaginous development, wound healing, and tumorigenesis, respectively.
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http://dx.doi.org/10.1016/j.jmb.2006.10.017DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2583400PMC
March 2007

[Analyses of subset, activated state and expression pattern of 24 repertoire TCR Vbeta of peripheral blood T lymphocytes in convalescence patients with severe acute respiratory syndrome (SARS)].

Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi 2005 Jan;21(1):114-7

Central Laboratory, Guangdong Provincial TCM Hospital, Guangzhou 510120, China.

Aim: To study the function of lymphocytes and the expression pattern of 24 repertoire TCR Vbeta in the convalescent patients with severe acute respiratory syndrome(SARS) after treatment by combination of traditional Chinese and Western medicine.

Methods: T lymphocyte subsets, activated states of T and B lymphocytes, and expressions of CD3(+) and 24 TCR Vbeta subfamilies in 76 convalescent SARS patients were detected by flow cytometry.

Results: The percentages of CD3(+) and CD4(+) T cells were lower than normal reference (P<0.05 and P<0.01, respectively). The percentage of CD8(+) T lymphocytes was higher than normal reference (P<0.01),while the percentage of CD8(+)/CD28(-) T cells (Ts) in 49 convalescent SARS patients increased, and that of CD8(+)/CD28(+) T cells (Tc) in 39 patients decreased. The percentage of activated T cells (Ta,CD3(+)/HLA-DR(+)) in 36 convalescent SARS patients and the percentage of activated B cells (Ba, CD3(-)/HLA-DR(+)) in 30 convalescent SARS patients were higher than normal references. Expression of TCR Vbeta14 was the commonest in 24 TCR Vbeta repertoire both in SARS patients and normal controls, followed by TCR Vbeta5.3 in SARS patients, but Vbeta20 in normal controls. Besides, the expressions of TCR Vbeta1, Vbeta5.2, Vbeta5.3, Vbeta7.2, Vbeta9, Vbeta11, Vbeta13.1, Vbeta13.2, Vbeta17, Vbeta18, Vbeta22 and Vbeta23 in SARS group were all significantly higher than those in normal group. And the expressions of TCR Vbeta4, Vbeta22 and Vbeta23 in SARS patients treated with glucocorticoid(>1 000 U) were higher than those in SARS patients without treatment.

Conclusion: Increased Ts cell may lead to increased CD8(+) T cells in convalescent SARS patients. The suppressor factors secreted by Ts cells may decrease CD3(+) and CD4(+) T cells. Expression of TCR Vbeta on T cells from convalescent SARS patients were different from normal controls. The increased Ta and Ba expressions may be associated with activation of T and B cells.
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January 2005

[Study on T cell subsets and their activated molecules from the convalescent SARS patients during two follow-up surveys].

Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi 2004 May;20(3):322-4

The Central Laboratory, Guangdong Provincial Hospital of TCM, Guangzhou 510120, China.

Aim: To explore the changes of peripheral blood T cell subsets and their activated molecules in convalescent SARS patients.

Methods: In two follow-up surveys of the SARS patients discharged from our hospital, the changes of CD3(+), CD4(+), CD8(+), CD8(+) CD28(+), CD8(+) CD28(-), CD3(+) CD25(+), CD3(+) CD69(+), CD3(+) HLA-DR(+)T cells and the ratio of CD4(+)/CD8(+) T cells in peripheral blood of SARS patients treated unitedly with Chinese and Western medicines were detected by flow cytometry.

Results: In two follow-up surveys, the percentages of CD3(+), CD4(+), CD8(+) CD28(+) T cells and the ratio of CD4(+)/CD8(+) T cells were remarkably lower than those of normal values(P<0.05), while the percentage of CD8(+) CD28 (-) T cells was higher(P<0.01). As for the percentages of CD3(+), CD8(+), CD4(+)/CD8(+), CD3(+) CD25(+), CD3(+) CD69(+) and CD3(+) HLA-DR(+) T cells, there was marked difference between 1st and 2nd follow-up results, but for other molecules there was no notable difference.

Conclusion: The convalescent SARS patients' immune function gradually recovers, and the effect of SARS virus on activation of T cells gradually disappears.
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May 2004

Transcriptional coactivation of bone-specific transcription factor Cbfa1 by TAZ.

Mol Cell Biol 2003 Feb;23(3):1004-13

Department of Periodontology, University of North Carolina, Chapel Hill, North Carolina 27599, USA.

Core-binding factor 1 (Cbfa1; also called Runx2) is a transcription factor belonging to the Runt family of transcription factors that binds to an osteoblast-specific cis-acting element (OSE2) activating the expression of osteocalcin, an osteoblast-specific gene. Using the yeast two-hybrid system, we identified a transcriptional coactivator, TAZ (transcriptional coactivator with PDZ-binding motif), that binds to Cbfa1. A functional relationship between Cbfa1 and TAZ is demonstrated by the coimmunoprecipitation of TAZ by Cbfa1 and by the fact that TAZ induces a dose-dependent increase in the activity of osteocalcin promoter-luciferase constructs by Cbfa1. A dominant-negative construct of TAZ in which the coactivation domains have been deleted reduces osteocalcin gene expression down to basal levels. NIH 3T3, MC 3T3, and ROS 17/2.8 cells showed the expected nuclear localization of Cbfa1, whereas TAZ was distributed throughout the cytoplasm with some nuclear localization when transfected with either Cbfa1 or TAZ. Upon cotransfection by both Cbfa1 and TAZ, the transfected TAZ shows predominant nuclear localization. The dominant-negative construct of TAZ shows minimal nuclear localization upon cotransfection with Cbfa1. These data indicate that TAZ is a transcription coactivator for Cbfa1 and may be involved in the regulation of osteoblast differentiation.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC140696PMC
http://dx.doi.org/10.1128/MCB.23.3.1004-1013.2003DOI Listing
February 2003
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