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Objective:To summarize the clinical characteristics, diagnosis and treatment of caspase recruitment domain-containing protein 9 (CARD9) gene deficiency associated invasive candidiasis, and report a novel mutation in CARD9 gene.Methods:The clinical characteristics, laboratory tests, treatment and the outcome of follow-up in a boy with invasive candidiasis were described. The boy′s main clinical manifestations were central nervous system infection and retroperitoneal mass. Whole-exome sequencing was performed and Sanger sequencing was verified to identify the CARD9 gene mutations in the patient and his parents. A literature search for “CARD9”and “invasive candidiasis”was conducted in PubMed, Wanfang and CNKI databases from their establishment to May 2020.Results:A 10-year-old boy suffered onset symptom of chronic diarrhea, which lasted for two months. The symptom was followed by progressive neurological symptoms such as headache, vomiting, seizures and disorder of consciousness. His unusual medical history was absent. Candida albicans were cultured several times in cerebrospinal fluid and blood, and yeast-like fungi were found in the stool high power field of vision. Cerebral magnetic resonance imaging indicated obstructive hydrocephalus and abdominal CT scan showed retroperitoneal mass and thickening of the intestinal wall. The whole-exome sequencing analyses of blood samples from the boy and his parents were performed. The results showed that there was a homozygous mutation of c.952-12_956delinsAG in the CARD9 gene, which was an unreported pathogenic mutation. This was confirmed by Sanger sequencing. There was no significant relief from intravenous combined antifungal medications. After lateral ventricular drainage surgery and injection of amphotericin B into the lateral ventricle, improvement of clinical symptoms and cerebral spinal fluid abnormalities was observed after nine weeks, and the retroperitoneal mass shrank. At follow-up after four-month oral combined antifungal medications, the child had no complaint except fatigue. However, cerebral spinal fluid analysis showed increased protein level and decreased glucose. Persistent hydrocephalus and periventricular white matter abnormal signals were revealed on the brain magnetic resonance imaging and the smaller retroperitoneal mass than before on the abdominal CT scan. In addition to this case, totally 21 cases with CARD9 gene deficiency associated invasive candidiasis have been reported worldwide, most of which featured central nervous system infections.Conclusions:CARD9 gene deficiency is an autosomal recessive primary immunodeficiency that confers human susceptibility to fungal disease. The associated invasive candidiasis often affects the central nervous system and makes the patient severely ill. Adequate systemic antifungal therapies should be given, and patients with hydrocephalus need surgical treatment. A novel mutation is reported that expands the variant diversity of CARD9 gene. For patients with unexplained invasive candidiasis, including those without a history of previous recurrent infection, genetic testing is recommended for primary immunodeficiency including CARD9 gene deficiency.
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Objective:To observe and compare the therapeutic effect of metoprolol by routine increasing dose method and rapid titration method on acute myocardial infarction (AMI).Methods:A total of 60 inpatients,who were di-agnosed with AMI within 24h and without contraindications for metoprolol,were randomly divided into two groups:routine therapy group (received metoprolol using routine methods,the dose was added in seven days)and rapid ti-tration group (metoprolol was added in three days using titration).The dosage maintained with 190 mg/d after both groups reaching the target dose of 190mg/d;then therapeutic effects were observed in both groups.Results: ①There were no re-myocardial infarction,rehospitalization caused by heart failure and sudden death etc.in both groups;② Patients received echocardiography in outpatients after three months.Compared with routine increasing dose group,there was significant reduction in left ventricular end-diastolic diameter [LVEDd,(55.00±7.56)mm vs.(50.00± 5.81)mm]and significant rise in left ventricular ejection fraction [LVEF,(49.13 ± 10.18)% vs. (57.84±10.34)%]in rapid titration group,P <0.01 both.Conclusion:Rapid titration method could make the pa-tients rapidly reach the targeted dose of metoprolol and inhibit renin release earlier,block the renin-angiotensin sys-tem,and improve myocardial remodeling and cardiac function.
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Objective Our study was performed to design a drug-sustained capsular tension ring (CTR) to evaluate its potentiality on prevention of PCO in the swine capsular bag model in vitro.Methods Following the continuous capsule curvilinear capsulorhexis ( CCCC),Phacomulsification with capsular tension ring implantation was pedormed.CTR-supported swine capsular bag models were prepared and divided into two groups,group CTR ( n =13 ) implanted with the original CTR without any modification and group CTR-PLGA-MG132 ( n =13) implanted with the CTR covered with PLGA and MG132.The CTRsupported capsular bags were cultured in vitro for up to 3 weeks.The area of lens epithelial cells (LEC) coverage over the posterior capsule surface was quantified every day under microscope.The capsules were treated for histological examination.The change of fibronectin was assessed by ELISA assay kit.Results After 2 ～ 3 days,outgrowth of LEC across the posterior capsule was observed,and the posterior capsule was totally covered by a confluent monolayer of cell after (9.06 ± 1.61 ) days in group CTR.Capsular wrinkles became increasingly apparent as time progressed.An increase in capsular thickness was also observed.In contrast,there was less LEC deposition in group CTR-PLGA-MG132.Histological examination showed LEC layers were closely arranged on the posterior capsular surface in group CTR.In group CTR-PLGA-MG132,there was comparatively looser cell arrangement.Compared with group CTR,the mean fibronectin level of posterior capsule by week 3 in group CTR-PLGA-MG132 was 25.14 μg/ml and 106.09 μg/ml respectively.Statistical analysis showed a significant difference ( P ＜ 0.01 ).Conclusions LEC migration,proliferation,and synthesis of EMT markers were inhibited in Group CTR-PLGA-MG132,compared with Group CTR.Drug-sustained capsular tension rings can effectively inhibit the migration,proliferation of LEC and the change of EMT ( epithelial-to-mesenchymal transition) in swine capsular bag models.Drug-sustained capsular tension rings might be a potential therapy to prevent the posterior capsular opacification in the future.
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ObjectiveTo compare the effects on left ventricular remodeling of bone marrow mononuclear cells transplantation one week and three months after acute myocardial infarction.MethodsAcute myocardial infarction models were successfully established in 15 swine,which were randomly divided into three groups:placebo group,early transplantation group and late trasplantation group.One week after model had been established,early transplantation group underwent bone marrow mononuclear cells transplantation,and then so did the late trasplantation group three months after acute myocardial infarction.B-ultrasound and single photon emission computed tomography (SPECT) examinations were performed to assess the left ventricular end diastolic dimension( LVd),left ventricular end diastolic volume(EDV) and left ventricular ejection fraction(EF) before and one week,three months,six months after acute myocardial infarction.ResultsThe LVd of late transplantation group [ (54.20:t:3.70) mm] was lower than placebo group [ (63.20 ±5.63)mm],but higher than early transplantation group [ (47.40 ± 1.14)mm].The EDV of late transplantation group [ ( 163.00 ±6.96)ml] was lower than placebo group [ (209.40 ± 18.69)ml],but higher than early transplantation group [ ( 135.40 ± 4.93 ) ml ].The EF of late transplantation group (0.25 ±0.02) was higher than placebo group (0.19 ±0.02),but lower than early transplantation group (0.37 ±0.02).ConclusionsBone marrow mononuclear cells transplantation can alleviate progressing ventricular remodeling,even it is performed three month after acute myocardial infarction,but its therapeutic effects are inferior to early transplantation's.
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Objective To investigate the effect of proteasome inhibitor MG132 on the proliferation of human lens epithelial cells SRA01/04. Methods The SRA01/04 cells were treated with MG132 by different concentrations (0, 0. 1, 0. 5, 1. 0, 2. 5, 5.0, 10. 0μmol/L) for 36 hours. The cell viability in all groups was determined using methylthiazoltetrazolium (MTT) test. The effect of MG132 on the apoptosis and regulation of cell cycle about SRA01/04 cells were detected by flow cytometry (FCM). The SRA01/04 cells treated with MG132 were observed after Annexin V/FITC-PI staining by fluorescence microscope. Results The inhibitory effect of MG132 on SRA01/04 cells proliferation was enhanced with the increase of MG132 concentration. The 50% inhibiting concentration ( IC50 ) of MG132 was 2. 50μmol/L after SRA01/04 cells were treated with MG132 for 36 hours. The apoptosis index of the cells treated by MG132 at 2. 5μmol/L and 5 μmol/L for 36 hours was 6. 55 ± 0. 35% and 13.75 ± 3.18%, and 0. 75 ± 0. 21% for 5.0μmol/L for 36 hours in control group. After cells were treated with MG132 for 48h, the percentages of cells at G0/G1 phase were (42. 57 ± 0. 64) %, (73.42 ± 3.10) %, ( 80. 95 ± 3.83 ) % 0, 2. 5,5.0 μmol/Lgroups respectively, and those at S phase were (49. 44±1.36)%, ( 17. 40 ± 1.50)%, ( 19. 57 ± 1.29)%.Annexin V/FITC-PI staining was used, and MG132 was found to result to apoptosis. Conclusions MG132 could inhibit the proliferation of SRA01/04 cells by the effect of inducing apoptosis and regulation of cell cycle. The proteasome inhibitor-might play a key role in the prevention of posterior capsular opacification.
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Objective To investigate the effects of bone marrow stem cells autologous transplantation on left ventricular remodeling after acute myocardial infarction. Methods Acute myocardial infarction models were successfully established in 10 swines, which were ran-dom divided into two groups, placebo group and trasplantation group. One week after operation, bone marrow stem cells autologous transplan-tation was performed, and control group was administrated with placebo. B-ultrasound and emission computed tomography aexaminations were performed to assess the left ventrieular end diastolic dimension, left ventricular tip wall thickness, left ventricular end diastolic volume and left ventricula ejection fraction before operation, one week, three months after acute myocardial infarction. Results Compared with that of control group, three months after acute myocardial infarction, transplantation group witnessed smaller left ventricular end diastolic dimension, thicker left ventricular tip wall, smaller left ventricular end diastolic volume and higher left ventricular ejection fraction. Conclusions Bone marrow autologous transplantation after acute myocardial infarction can alleviate left ventricular remodeling.
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AIM: To identify the differences of gene expression between human age-related cataract and clear lenses. METHODS: The RNA were extracted from human age related cataract and clear lens epithelial cells, labeled with cy3/cy5 as probes, then were hybridized to cDNA chip containing 8 064 genes. The differential expressions of the genes were screened. Furthermore, a primary classification of these genes function was given. The expression levels of the identified genes were further evaluated by real time polymerase chain reaction. RESULTS: 286 genes expression were observed to increase and 438 genes expression were observed to decrease in cataractous lens epithelial cells as compared with normal lens. According to functional analysis, the changed genes in cataract lens are associated with lens structural components, cytoskeleton, cell cycle, apoptosis and stress responses. CONCLUSION: These data suggest that there are differences in gene expression between cataract and clear human lens epithelial cells. The majority of genes changed in cataract exhibited decreased expression. Processes associated with the down-regulated genes may reflect the inability of the lens to maintain its homeostasis and transparency.