1.Hemorrhagic cystitis in children undergoing hematopoietic stem cell transplantation Clinical characteristics and risk factors
Honggui XU ; Jianpei FANG ; Shaoliang HUANG ; Dunhua ZHOU ; Chun CHEN ; Ke HUANG ; Yang LI
Chinese Journal of Tissue Engineering Research 2008;12(8):1596-1600
BACKGROUND: Hemorrhagic cystitis (HC) is one of common complications in patients undergoing hematopoietic stem cell transplantation (HSCT). It is of great value for improvement in the HSCT outcome to describe the clinical characteristics of HC and risk factors. OBJECTIVE: To investigate the incidence of HC in children after HSCT, and to analyze its clinical characteristics and risk factors.DESIGN: Case analysis SETTING: Center of Hematopoietic Stem Cell Transplantation, Department of Pediatrics, Second Affiliated Hospital of Sun Yat-sen University.PARTICIPANTS: Experiments were performed at the Center of Hematopoietic Stem Cell Transplantation, Department of Pediatrics of Second Affiliated Hospital of Sun Yat-sen University from October 1998 to June 2004. Eighty-eight patients receiving umbilical cord blood transplantation (UCBT) and peripheral blood stem cell transplantation (PBSCT) were enrolled; 49 were males and 39 were females. The age ranged from 2 to 18 years with an average of 8.0 years. Guardians of child patients signed informed consents. The experimental procedures were approved by Medical Ethics Committee.METHODS: ①Conditioning regimens included combination of cyclophosphamide (CY, 120-200 mg/kg) with busulphan (BU, 14-20 mg/kg)-based chemotherapy and combination of CY with total body irradiation (TBI, 2-8 Gy) or total lymphoid irradiation (TLI, 2-8 Gy)-based radiotherapy. ②HC was defined according to the criteria proposed by references 7 and 8. The incidence, clinical characteristics, laboratory examination, treatment and outcome for HC were described. The association of various clinical factors including age, gender, human leucocyte antigen (HLA) typing, diseases for transplant, the type of stem cell, the type of transplantation, the occurrence of acute graft-versus-host disease (aGVHD) and cytomegalovirus (CMV) infection with the development of HC were examined.MAIN OUTCOME MEASURES: ①Incidence of HC, ②HC patient characteristics and laboratory examination, ③HC treatment and outcome, and ④risk factors analysis. RESULTS: All 88 patients were included in the final analysis. ①The incidence of HC: 16 patients (18.2%, 16/88) developed HC post-transplant with the severity graded as mild in 11 cases (68.7%) and severe in 5 cases (31.3%). ②HC patient characteristics and laboratory examination: All had hematuria and 8 cases (50.0%) had typical pollakisuria, urinary urgency, odynuria and gross hematuria; 10 cases (62.5%) had gross hematuria and 11 had proteinuria (+ to +++); Leucocytes were detected in 7 cases. ③Treatment and outcome: All patients recovered at a median of 13.5 days (range 2-53 days). ④Risk factors analysis: The incidence of HC was significantly higher in the group of ≥ 6 years old, presence of aGVHD and development of cytomegalo-virus (CMV) infection (P < 0.05-0.01). CONCLUSION: ①HC has its own clinical characteristics following HSCT in children but with good prognosis. ②The risk factors for HC are ≥ 6 years old, presence of aGVHD and CMV infection.
2.Exploration of hapten-induced atopic dermatitis murine models for non-clinical pharmacodynamics study of drugs
Hao SONG ; Chun-zheng WANG ; Fan-fan ZHOU ; You WU ; Ke TANG ; Ying GUO
Acta Pharmaceutica Sinica 2023;58(12):3655-3668
Atopic dermatitis (AD) is a chronic, relapsing, inflammatory dermatosis with a variety of clinical manifestations and difficult to cure. Currently, many AD drug candidates have entered the research and development pipeline. In order to provide technical specifications for the clinical development of AD drugs, the Center for Drug Evaluation of National Medical Products Administration released the "Technical Guidelines for Clinical Trials of Drugs for AD Treatment" (Draft for Comments) in November 2022. Non-clinical pharmacodynamics evaluation is an important research before the drug enters clinical trials. Oxazolone (OXA)- and 2,4-dinitro-fluorobenzene (DNFB)-induced models are the most popular classical hapten-induced AD murine models, but variations of modeling are existing in the methods from different studies, including sensitization sites, haptens' dosages, the period of challenges, and the skin lesions severity evaluation as well. In this study, the investigation of OXA- and DNFB-induced AD murine models with various conditions of modeling was performed to compare the characteristics of hapten-induced AD murine models in the pathological process and severity according to the appearance of AD patients, and the guidance of pharmacodynamics evaluation of AD-therapeutic drugs in clinical trials as well, which may provide a proposal for AD treatment drug candidates in the non-clinical pharmacodynamics evaluation. All animal experiments were approved by the Animal Care & Welfare Committee of Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College (approval No.: 00007782 and 00007784).
3.Distribution, combination, and evolution of syndromic etiologies of erectile dysfunction.
Jian-Guo XUE ; Qian FAN ; Yu-Chun ZHOU ; Ke-Qin NING ; Jin-Song WANG ; Ting-Song BIAN
National Journal of Andrology 2014;20(9):830-833
OBJECTIVETo explore the distribution, combination and evolution of various syndromic etiologies of erectile dysfunction (ED) based on the syndrome etiology theory.
METHODSUsing the ED Syndromic Etiology Scale, we collected the clinical data on the Chinese medicine diagnoses of 297 cases of ED, extracted the core syndromic etiologies by analysis of principal components and factors, and analyzed the patterns of distribution, combination, and evolution of ED syndromic etiologies according to the general information of the patients.
RESULTSThrough analysis of principal components and factors, 9 core syndromic etiologies were extracted, i. e. , liver constraint with qi stagnation, kidney yin deficiency, damp-heat, liver constraint transforming into liver-fire, blood stasis, kidney yang deficiency, heart-spleen paired deficiency, qi-yin paired deficiency, and phlegm-damp. Each of these syndrome etiologies exhibited its own specific distribution patterns. Of the total number of cases studied, 51.52% had 2 or 3 core syndromic etiologies and 36.03% had only one.
CONCLUSIONIn the early stage of ED, its syndromic etiologies are usually liver constraint with qi stagnation, kidney yin deficiency, damp-heat, liver constraint transforming into liver-fire, and blood stasis. With the natural progres- sion of the disease, its syndromic etiologies gradually evolve into kidney yang deficiency, heart-spleen paired deficiency, qi-yin paired deficiency, phlegm-damp, and blood stasis, and finally into yin-yang deficiency of the heart, spleen and kidneys, combined with phlegm-damp and blood stasis.
Adult ; Erectile Dysfunction ; diagnosis ; drug therapy ; etiology ; Humans ; Male ; Medicine, Chinese Traditional ; Middle Aged
4.Study on the genotoxicity of exhausts of diesel engine with ethanol-diesel blending fuel.
Ke-ming LIU ; Chun-hua WANG ; Lei ZHOU ; Ming-yue ZHANG ; Chong-lin SONG ; Guo-liang FAN ; Peng LIU
Chinese Journal of Industrial Hygiene and Occupational Diseases 2005;23(1):42-44
OBJECTIVETo study the genotoxicity of components of diesel engine exhausts with ethanol-diesel blending fuel. To provide scientific arguments to find more economical and less polluted fuels.
METHODSAmes test, comet assay and GC-MS technique were used to test the genotoxicity and 16 kinds of PAHs on diesel engine exhausts with different proportions of ethanol (E0, E5, E10, E20).
RESULTSBoth Ames test and comet assay were positive. It shows that diesel engine exhausts can lead to mutation and DNA damage, especially in pure diesel oil. But the content of 16 kinds of PAHs and DNA damage level decreased in exhausts of E5. With the increase of ethanol proportion in diesel oil, the content of 16 kinds of PAHs and DNA damage level increased.
CONCLUSIONCompared with pure diesel oil and high proportion of ethanol fuel, E5 can reduce the genotoxicity and the brake specific exhausts of PAHs.
Air Pollutants ; toxicity ; Air Pollution ; Carbon Monoxide ; Comet Assay ; DNA Damage ; Ethanol ; toxicity ; Gasoline ; toxicity ; Mutagenicity Tests ; Particulate Matter ; Vehicle Emissions ; toxicity
5.Study of therapeutic effect and mechanism of Sihuang powder treating acute synovitis in experimental rabbit induced by papain injection.
Quan WU ; Qi-Yun LI ; Xu-Guang ZHOU ; Chun-Hai KE
China Journal of Orthopaedics and Traumatology 2008;21(1):42-45
OBJECTIVETo prove the therapeutic effects of Sihuang powder (composed by four traditional Chinese herbs: root of baikal skullcap, bark of amur corktree, root of sorrel rhubarb, fruit of cape jasmine, which were mixed with wild Chrysanthemum flower solution)in treating acute synovitis in experimental rabbit knee osteoarthritic models induced by papain injection and to explore its mechanism.
METHODSThirty-two New-Zealand white rabbits were divided into 6 groups: blank group, model group, Sihuang powder with high dosage group (2 g/kg), Sihuang powder with low dosage group (1 g/kg), Yingtaiqing group and wild Chrysanthemum flower group. The latter four groups were treated respectively with low and high dose Sihuang powder synovium and cartilage were tested concentrations of nitrogen monoxide (NO) and IL-1 level and then were prepared for pathologic and histologic observation 10 days later. Cartilage pathologic changes were record and synovium pathologic changes were valued by means of Mankin's value system.
RESULTSThe NO concentration of synovium in Sihuang powder with high dosage group was lower than that of model group, and there was significantly differences between the two groups (P < 0.01). The IL-1 level of synovium was failed after treated with Sihuang powder with high dosage (P < 0.05). Sihuang powder with low dosage and Yingtaiqing also could restrain IL-1's release (P < 0.05). In Mankin's value system, Sihuang powder with high dosage almost eliminated inflammatory cells infiltrating in synovium, which was seldom found in other groups. The value of Sihuang powder with high dosage group was the lowest in treatment groups (P < 0.005). Sihuang powder with low dosage group and wild Chrysanthemum flower group also decreased the degree of inflammatory in synovium (P < 0.05).
CONCLUSIONSihuang powder can reduce the concentration of NO and IL-1 and improve inflammatory cell infiltrate in lining cells of synovium. Moreover, it can alleviate swelling and pain of joint, improve joint movement and postpone degeneration of the cartilage.
Acute Disease ; Animals ; Drugs, Chinese Herbal ; therapeutic use ; Female ; Interleukin-1 ; analysis ; Nitric Oxide ; analysis ; Osteoarthritis ; drug therapy ; pathology ; Papain ; toxicity ; Powders ; Rabbits ; Synovitis ; chemically induced ; drug therapy ; pathology
6.Determination of the serum antibody in pneumonic plague patients
Qing, ZHOU ; Li-qiong, SU ; Bei, LI ; Peng, SU ; Ke-chun, ZHENG ; Die-xin, WEI ; Zhi-zhong, SONG
Chinese Journal of Endemiology 2009;28(4):361-364
Objective To analyze the species of the antibody and immune responsibility in pneumonic plague patients in order to pave the way to screen the new sub-unit of the vaccine to provide the experimental basis. Methods Using the virulence-related protein microarray containing 149 proteins of Yersinia pestis (Y.pestis), the species of the antibody and immune responsibility were analyzed in serum of two pneumonic plague patients in six months after onset. Results Eighty-eight gene coded proteins were detected out the related antibodies except YPMT1.23c, YPMT1.86, YPO0406 and YPO1071 in patient 1. Forty-three antibodies from gene coded protein were analyzed, other forty-nine had not been identified in patient 2. Thirty-nine antibodies were detected in both patients. The proteins YPMT1.81c, YPMT1.84, YPCD1.31c, rw10, YPCD1.28, YPCD1.58, YPMT1.62c, YPO3247-related antibodies increased significantly by 109.96,176.4 ;20.64,17.73 ;16.50,7.16 ;23.51,7.65 ;46.00,25.61 ;4.50,8.24 ;5.98,5.08 ;23.98,4.76 folds, respectively. Conclusions The study on the antibody in pneumonic plague patients helps us to select the potential vaccine candidates, which reveals that eight proteins are the immunity diagnosis targets and the research key of sub-unit vaccine.
7.Prophylaxis and treatment of chronic graft versus host disease.
Ke HUANG ; Yang LI ; Shao-liang HUANG ; Jian-pei FANG ; Dun-hua ZHOU ; Chun CHEN
Chinese Journal of Pediatrics 2005;43(3):174-177
OBJECTIVEChronic graft versus host disease (cGVHD) is the most common late complication after allogeneic hematopoietic stem cell transplantation (allo-HSCT) and it represents the major cause of mortality in long-term survivors. Over the past decade, although conventional therapy has achieved complete responses in approximately 50% of patients, the prophylaxis and treatment of cGVHD are still not satisfactory. In the late years, utilization of new immunosuppressant such as tacrolimus (FK506), mycophenolate mofetil (MMF) on cGVHD improved the curative effects. This study tried to analyze the results of combination of methylprednisolone (MP), MMF and FK506 or cyclosporine A (CSA) as immunosuppressive therapies for cGVHD and to explore the effective regimen for children.
METHODSForty-five patients received allo-HSCT. Among them 32 received UCBT and 13 received PBSCT. The conditional regimen mainly consisted of busalphan, cyclophosphamide, antihuman thymocyte globulin, fludarabin, melphalan, thiotepa and total lymph node irradiation. Prophylaxis of GVHD consisted of CSA, MP and MMF. Patients with cGVHD received a regimen with combination of MP, MMF and FK506 or CSA.
RESULTSSeventeen out of 32 patients who received UCBT were engrafted. while 9 out of 13 patients who received PBSCT were engrafted. Nine cases of the 30 engrafted patients developed cGVHD (morbidity 30%). Among the 17 patients who received UCBT, 3 developed cGVHD (18%). Among the 13 patients who received PBSCT, 6 developed cGVHD (46%). Six cGVHD continued from aGVHD (6/9). One patient was given CSA plus MMF, and 8 were given three-drug regimen with MP, MMF and FK506. The overall response rate was 100%. Two patients died of CMV-IP or septicemia (mortality 20%). Seven (78%) patients survived (event free survival, EFS) longer than 3 years. The side effects included hepatotoxicity, nephrotoxicity, hypertension, articular capsulitis and arrhythmia. The main complication and the major causes of death were infection.
CONCLUSIONThe incidence of cGVHD is low in children. The incidence of cGVHD after PBSCT is higher than that after UCBT. aGVHD is a highly dangerous factor. Combined therapy of MP plus MMF and FK506 or CSA is safe and effective for the treatment of cGVHD in children.
Child ; Child, Preschool ; Chronic Disease ; Drug Therapy, Combination ; Female ; Graft vs Host Disease ; drug therapy ; epidemiology ; prevention & control ; Hematopoietic Stem Cell Transplantation ; adverse effects ; Humans ; Incidence ; Male ; Methylprednisolone ; administration & dosage ; Mycophenolic Acid ; administration & dosage ; analogs & derivatives ; Tacrolimus ; administration & dosage
8.Acute toxicity and immunoprotection of recombinant apxI toxin of Actinobacillus pleuropneumoniae in mice.
Ke-Xia YAN ; Jian-Jie LIU ; Rui ZHOU ; Bin WU ; Wei-Hong LIU ; Huan-Chun CHEN
Chinese Journal of Biotechnology 2006;22(1):65-70
Acute toxicity and immunoprotection of Actinobacillus pleuropneumoniae (APP) ApxI toxin recombinant proteins (include crude inclusion bodies and refolded recombinant protein) were evaluated in mice, and compared with the natural ApxI extracted from culture supernatant of APP serotype 10. In the acute toxicity experiment, the three proteins were intraperitoneally injected into Kunming mice in a dose of 200microg per mouse. The body and organ weight, heamatological and biochemical indexes were examined at 24h, 7 days and 14 days post administration. There was no death after the intraperitoneal administration of the three proteins, and no significant change was found in the body weight, organ indexes, heamatological and biochemical indexes. To study their immunoprotection, the three proteins were emulsified with Freund's adjuvant respectively and vaccinated the mice twice with a 2-week of interval. Two weeks after the second vaccination, the mice were challenged intraperitoneally with a lethal dose of APP serotype 10 (1.09 x 10(8) cfu), and serums were examined by an ApxI-specific ELISA. The results revealed that the recombinant protein had a good immunogenicity and could induce protection immune reaction.
Actinobacillus Infections
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prevention & control
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Actinobacillus pleuropneumoniae
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genetics
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immunology
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metabolism
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Animals
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Bacterial Proteins
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genetics
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immunology
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Bacterial Vaccines
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genetics
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immunology
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Cloning, Molecular
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Escherichia coli
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genetics
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metabolism
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Female
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Hemolysin Proteins
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genetics
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immunology
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Immunization
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Male
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Mice
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Random Allocation
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Recombinant Proteins
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genetics
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immunology
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Toxicity Tests, Acute
9.Evaluation of the effect of chronic virus infection on laboratory tests results in patients with osteoarticular tuberculosis.
Yun LIU ; Hui YANG ; Ke MA ; Ai-wu WU ; Ming-Xia ZHANG ; Qun-Yi DENG ; Bo-Ping ZHOU ; Xin-Chun CHEN
Chinese Journal of Experimental and Clinical Virology 2012;26(6):450-452
OBJECTIVETo evaluate the effect of chronic virus infection on laboratory tests results in patients with osteoarticular tuberculosis.
METHODSA total of 121 patients with osteoarticular tuberculosis, who were hospitalized in Shenzhen Third People's Hospital during June 2008 to June 2012, were recruited for analysis. Clinical laboratory tests results were collected for comparison between patients with or without chronic co-infection with virus.
RESULTSAmong the 121 patients, thirty patients were co-infected with hepatitis B virus (HBV), two were with Human immunodeficiency virus (HIV), and one was co-infected with HBV, HIV and hepatitis C virus (HCV). Compared to patients with osteoarticular tuberculosis without HBV/HCV/HIV infection, patients with chronic HBV/HCV/HIV virus infection had similar positive rate of laboratory tests including tissue smear acid-fast bacilli (AFB) staining, tissue Mycobacterium tuberculosis (Mtb) culture, tissue Mtb DNA detection, serological test of antibodies against Mtb, and Mtb. antigen-specific interferon-gamma release assay. Similar results were also found for erythrocyte sedimentation rate, C-reative protein level and liver function including Alanine aminotransferase and Aspartate Aminotransferase.
CONCLUSIONChronic infection with HBV/HCV in patients with have no obvious effect on clinical laboratory tests related to tuberculosis.
Adult ; Female ; HIV ; genetics ; isolation & purification ; physiology ; HIV Infections ; complications ; virology ; Hepacivirus ; genetics ; isolation & purification ; physiology ; Hepatitis B virus ; genetics ; isolation & purification ; physiology ; Hepatitis B, Chronic ; complications ; virology ; Hepatitis C ; complications ; virology ; Humans ; Male ; Middle Aged ; Mycobacterium tuberculosis ; genetics ; isolation & purification ; physiology ; Tuberculosis, Osteoarticular ; etiology ; microbiology ; virology
10.Clinical on molecular basis of atrial fibrosis in patients with atrial fibrillation investigation.
Dan KE ; Chun-xuan XU ; Ya-zhou LIN ; Jian-cheng ZHANG ; Lin CHEN ; Li-fang LIN ; Xi-zhong HU
Chinese Journal of Cardiology 2005;33(5):459-463
OBJECTIVETo determine the molecular mechanisms involved in atrial fibrosis which occurs in patients with atrial fibrillation (AF) and to investigate their effects on the initiation and maintenance of AF.
METHODSThe right atrial tissue samples were taken from 73 patients with rheumatic heart disease who underwent heart valve replacement surgery. 34 patients had no history of AF (sinus rhythm group), 9 patients had paroxysmal AF and 30 patients had persistent AF. The mRNA content of collagen type I, collagen type III, MMP-2, TIMP-1, TIMP-2, TIMP-3 and TIMP-4 was measured by semi-quantitative reverse transcription-polymerase chain reaction (RT-PCR) and normalized to beta-actin or GAPDH.
RESULTSCompared to sinus rhythm group, the mRNA of collagen type I and MMP-2 increased significantly in the persistent AF group (all, P < 0.01), followed by the paroxysmal AF group (all, P < 0.05). The mRNA of collagen type III was slightly higher in both AF groups than in the sinus rhythm group, but the differences were not statistically significant (P > 0.05). The mRNA of TIMP-1, TIMP-2 and TIMP-3 was down-regulated in the persistent AF group (all, P < 0.01, respectively), however, the trends of reduction did not reach statistical significance in the paroxysmal AF group (P > 0.05). The mRNA of TIMP-4 remained compatible in each group. The mRNA of collagen type I was significantly correlated with left atrial dimension (r = 0.336, P = 0.004) and AF duration (r = 0.339, P = 0.003). The mRNA of MMP-2 was significantly correlated with the mRNA of TIMP-2 (r = -0.326, P = 0.006), the mRNA of collagen type I (r = 0.322, P = 0.006), left atrial dimension (r = 0.300, P = 0.011) and AF duration (r = 0.300, P = 0.010).
CONCLUSIONThe increased level of collagen type I associated with selective downregulation of TIMP-2 and upregulation of MMP-2 gene expression in atrium could be one of the molecular mechanisms of atrial fibrosis during atrial fibrillation, which correlates with the initiation and maintenance of AF.
Adolescent ; Adult ; Atrial Fibrillation ; metabolism ; pathology ; Collagen Type I ; genetics ; Female ; Fibrosis ; Humans ; Male ; Matrix Metalloproteinase 2 ; genetics ; Middle Aged ; Myocardium ; pathology ; RNA, Messenger ; analysis ; Tissue Inhibitor of Metalloproteinase-2 ; genetics ; Tissue Inhibitor of Metalloproteinases ; genetics