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Objective To explore the clinical characteristics and prognosis of children and adolescents over 10 years of age with acute lymphoblastic leukemia (ALL). Methods A total of 86 newly diagnosed ALL children and adolescents over 10 years of age (62 cases of B-ALL and 24 cases of T-ALL) were enrolled. Clinical characteristics, therapeutic effect and prognostic factors were retrospectively analyzed. Event-free survival (EFS) and overall survival (OS) rates were estimated by the Kaplan-Meier method. Prognostic factors were evaluated by COX regression analysis. Results Of 86 patients, 62 were in medium risk, and 24 in high risk. At diagnosis, 53 patients (62%) had hepatomegaly, 50 patients (58%) had splenomegaly, and 46 patients (54%) had lymphoadenopathy. Twenty-nine patients (34%) showed high leukocyte counts (≥ 50×109/L) at diagnosis. The karyotype analysis was performed on 78 patients. The percentage of hyperdiploidy was 19% (15 cases), and that of hypodiploidy was 5% (4 cases). Eleven patients (14%) had abnormalities of chromosome structure. Of them, one patient was Philadelphia chromosome-positive, and another patient had the t (1; 19) chromosomal translocation. Three patients (4%) were positive for TEL/AML1, 3 (4%) were positive for E2A/PBX1, 6 were positive for BCR/ABL (7%), and 4 (5%) were positive for SIL/TAL1. During 4 weeks of induction therapy, 85 patients (99%) achieved complete remission (CR). In 86 patients, the 5-year anticipated EFS and OS were (64±6)% and (75±5)% respectively. The 5-year EFS and OS in the medium risk group were significantly higher than those in the high risk group (P < 0.05). The 5-year EFS in B-ALL patients was significantly higher than that in T-ALL patients (P < 0.05). COX multivariate analysis showed that white blood counts at diagnosis and minimal residual disease (MRD) after induction therapy were independent prognostic factors. Conclusions Children and adolescents with ALL over 10 years of age often have clinical characteristics of unfavorable prognosis. White blood counts at diagnosis and MRD after induction therapy may be important factors for the long-term prognosis.
Objective To study the expression of β-integrin family members in children with T-cell acute lymphoblastic leukemia (T-ALL) and their significance. Methods Quantitative real-time PCR analyses were performed to assess the expression levels of β-integrin family members in bone marrow samples from 22 children with newly-diagnosed T-ALL and 21 controls (16 children with non-malignant hematologic disease and 5 healthy donors with bone marrow transplantation). Jurkat cells were treated with integrin inhibitor arginine-glycine-aspartate (Arg-Gly-Asp, RGD) peptide. The cell viability and apoptosis rate were determined by CCK8 assay and flow cytometry respectively. Results The mRNA levels of integrins β2, β3, and β5 were significantly lower in children with T-ALL than in controls (P < 0.05). In T-ALL patients, high integrin β3 expression was associated with lower white blood cell counts (< 100×109/L), minimal residual disease (MRD) positivity, and day 33 bone marrow negative remission (P < 0.05). In T-ALL patients, higher integrin β5 expression was associated with relapse of T-ALL (P < 0.05). Based on survival curve analysis, higher integrin β3 expression was related to lower event-free survival and overall survival rates. RGD peptide treatment inhibited the proliferation of Jurkat cells and increased their apoptosis rate (P < 0.05). Conclusions β-Integrin may play a role in the occurrence and development of T-ALL by affecting cell proliferation and apoptosis. The expression of integrin β5 is closely related to the risk of relapse of T-ALL. The expression of integrin β3 is closely related the treatment response and prognosis of T-ALL.
Objective To investigate the clinical features and prognosis of children with Langerhans cell histiocytosis (LCH). Methods A retrospective analysis was performed for the clinical data of 34 children with newly diagnosed LCH. Results The 34 children had a median age of 14.5 months (range:22 d to 60 months). Of all 34 children, 23 were aged 0-2 years and 11 were aged > 2 years. There were 17 children in the high-risk group and 17 in the low-risk group. Thirty children received chemotherapy, and the 6-week and 12-month overall response rates were 67% (20/30) and 87% (26/30), respectively. The 3-year overall survival (OS) rate was 86%±6% and the 3-year event-free survival (EFS) rate was 64%±9%. Compared with the low-risk group, the high-risk group had significantly lower 6-week chemotherapy response rate (47% vs 87%; P < 0.05), 3-year OS rate (72%±12% vs 100%; P < 0.05), and 3-year EFS rate (46%±13% vs 82%±9%; P < 0.05). There was no significant difference in the 12-month chemotherapy response rate between the high-risk and low-risk groups (80% vs 93; P > 0.05). The high-risk group had a recurrence rate of 27% and a mortality rate of 27%. There were no recurrence or deaths in the low-risk group. Conclusions Children with LCH have a high overall survival rate, but the high-risk patient has a low 6-week response rate of induction chemotherapy and poor long-term prognosis.
Objective To investigate the fat emulsion tolerance in preterm infants of different gestational ages in the early stage after birth. Methods A total of 98 preterm infants were enrolled and divided into extremely preterm infant group (n=17), early preterm infant group (n=48), and moderate-to-late preterm infant group (n=33). According to the dose of fat emulsion, they were further divided into low-and high-dose subgroups. The umbilical cord blood and dried blood filter papers within 3 days after birth were collected. Tandem mass spectrometry was used to measure the content of short-, medium-, and long-chain acylcarnitines. Results The extremely preterm infant and early preterm infant groups had a significantly lower content of long-chain acylcarnitines in the umbilical cord blood and dried blood filter papers within 3 days after birth than the moderate-to-late preterm infant group (P < 0.05), and the content was positively correlated with gestational age (P < 0.01). On the second day after birth, the low-dose fat emulsion subgroup had a significantly higher content of short-, medium-, and long-chain acylcarnitines than the high-dose fat emulsion subgroup among the extremely preterm infants (P < 0.05). In the early preterm infant and moderate-to-late preterm infant groups, there were no significant differences in the content of short-, medium-, and long-chain acylcarnitines between the low-and high-dose fat emulsion subgroups within 3 days after birth. Conclusions Compared with moderate-to-late preterm infants, extremely preterm infants and early preterm infants have a lower capacity to metabolize long-chain fatty acids within 3 days after birth. Early preterm infants and moderate-to-late preterm infants may tolerate high-dose fat emulsion in the early stage after birth, but extremely preterm infants may have an insufficient capacity to metabolize high-dose fat emulsion.
Objective To study the clinical effect and safety of early postnatal application of glucocorticoids in the prevention of bronchopulmonary dysplasia (BPD) in preterm infants. Methods The databases including PubMed, Cochrane Library, Embase, CNKI, Wanfang Data, and VIP were comprehensively searched for articles on early postnatal application of glucocorticoids in the prevention of BPD in preterm infants published up to June 2016. Review Manager 5.3 was used for the Meta analysis of 16 randomized controlled trials (RCTs) that met the inclusion criteria. Results A total of 2 962 participants were enrolled in the 16 RCTs, with 1 486 patients in the trial group and 1 476 in the control group. The Meta analysis showed that early postnatal application of glucocorticoids reduced the incidence rate of BPD at a corrected gestational age of 36 weeks (OR=0.73, 95%CI:0.61-0.87, P=0.0004), but there was an increase in the risk of hyperglycemia (OR=1.61, 95%CI:1.24-2.09, P=0.0003), hypertension (OR=1.63, 95%CI:1.11-2.38, P=0.01), and intestinal perforation (OR=1.51, 95%CI:1.12-2.04, P=0.007). Conclusions At present, it is not recommended to use glucocorticoids to prevent BPD in preterm infants. Its advantages and disadvantages need further studies, with special focuses on the adverse effects of hyperglycemia, hypertension, and intestinal perforation.
Objective To investigate the status of pubertal development in children born with assisted reproductive technology (ART). Methods A retrospective analysis was performed on the pubertal development data of children born with ART in Peking University Third Hospital from 1994 to 2003 (ART group). The data in the cross-sectional study "Reports on the Physical Fitness and Health Research of Chinese School Students in 2010" were used as a control. The age at menarche and the age at spermarche were compared between the two groups. The status of pubertal development in the overweight and obese children in the ART group was evaluated to investigate the correlation between pubertal development and body mass index (BMI). Results A total of 200 children born with ART were enrolled in this study, and 72 of them (41 males and 31 females) completed the survey (response rate=36.0%). In the ART group, the mean age at spermarche and the mean age at menarche were 13.9 years (95%CI:13.7-14.3 years) and 12.2 years (95%CI:11.8-12.6 years), respectively. There were no significant differences in the age at spermarche and the age at menarche between the ART and control groups (P > 0.05). In the ART group, there were no significant differences in the age at spermarche and the age at menarche between the overweight and obese children and the normal weight children (P > 0.05). There were also no significant differences in overweight rate and obesity rate between the children in the ART group and the adolescents in Beijing (P > 0.05). In the ART group, there was no significant correlation between the age at spermarche or menarche and BMI (P > 0.05). Conclusions No delayed or precocious puberty is observed in children born with ART. This is consistent with the normal control data. And there is no significant correlation between pubertal development and BMI in children born with ART.
Objective To explore the differences of NKX2.5 and TBX5 gene mutations between in vitro fertilization (IVF) children with congenital heart disease (CHD) and naturally conceived children with CHD. Methods Blood samples from 68 IVF children with CHD and 98 naturally conceived children with CHD were collected. The mutations in coding regions 1 and 2 of the NKX2.5 gene, and coding regions 4, 5, and 8 of the TBX5 gene were examined by polymerase chain reaction (PCR) and DNA sequencing. Results An A-to-G mutation at nucleotide 63 (c.63A > G) in coding region 1 of the NKX2.5 gene was found in both IVF and naturally conceived children with CHD. There were no significant differences in genotype and allele frequencies at c.63A > G locus of the NKX2.5 gene between the two groups. No mutations were detected in coding region 2 of the NKX2.5 gene and coding regions 4, 5 and 8 of the TBX5 gene. Conclusions There is no difference in NKX2.5 and TBX5 gene mutations between IVF and naturally conceived children with CHD. Therefore, it is presumed that assisted reproductive technology may not lead to mutations in the NKX2.5 and TBX5 genes.
Objective To evaluate the clinical features, laboratory findings, diagnosis and treatment, and prognosis of children with systemic lupus erythematosus (SLE) accompanied by pulmonary hypertension (PH). Methods The clinical symptoms, laboratory findings, echocardiographic features, SLE disease activity index, and treatment outcome of 15 hospitalized children with SLE accompanied by PH were retrospectively analyzed. Results Among the 15 patients, the median interval from diagnosis of SLE to diagnosis of PH was 0.1 year (range:0-6.5 years). Aside from PH-related symptoms, Raynaud's phenomenon was observed in 6 (40%) of the 15 patients. There was no significant difference in SLE disease activity (evaluated by complements 3 and 4 levels, erythrocyte sedimentation rate, and positive rate of anti-double-stranded DNA) between patients with mild-to-moderate PH and those with severe PH (P < 0.05). As for treatment, 13 patients received immunosuppressive therapy with glucocorticoids, and among them 2 patients received PH-targeted therapy. During a median follow-up of 8.0 years (range:0.5-18.1 years) since the diagnosis of PH, 2 deaths were noted with class III or IV cardiac function (World Health Organization), while the other patients were in a stable condition. Conclusions Raynaud's phenomenon is a common clinical manifestation in children with SLE accompanied by pulmonary hypertension (PH). PH severity is not significantly associated with SLE disease activity, and thus greater focus should be placed upon early screening of pulmonary arterial pressure in SLE patients. Early diagnosis and early treatment can improve the prognosis of children with SLE.
Objective To observe the changes in electrocardiographic parameters in children with complete left bundle branch block (CLBBB) after the transcatheter closure of simple ventricular septal defect (VSD). Methods A total of 21 children with CLBBB early after transcatheter closure of perimembranous VSD were recruited. Another 21 children without any type of arrhythmia after transcatheter closure of perimembranous VSD were enrolled as the control group. The sex, age, and the size of occluder were matched between the two groups. The changes in the following indices were compared between the two groups:left ventricular voltage, QT interval, corrected QT interval (QTc), QT dispersion (QTd), corrected QT dispersion (QTcd), JT dispersion (JTd), and corrected JT dispersion (JTcd) on the electrocardiogram before transcatheter closure and at 1, 3, 5, 30 days after transcatheter closure. Results Left ventricular voltage and JTcd changed with operation time in the CLBBB and control groups (P < 0.05). There were interaction effects between time and grouping in the changes in left ventricular voltage and QTd (P < 0.05). There was a significant difference in JTcd between the CLBBB and control groups (P < 0.05). There was also a significant difference in left ventricular voltage between the CLBBB and control groups at 3 and 5 days after the transcatheter closure (P < 0.05). Conclusions There are significant differences in electrocardiographic left ventricular voltage and JTcd between VSD children with and without CLBBB early after transcatheter closure. JTcd might be useful in predicting the development of CLBBB early after transcatheter closure of VSD.
Objective To evaluate the efficacy and safety of cyclophosphamide as a second-line drug in the treatment of children with anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis. Methods Six children with anti-NMDAR encephalitis, who showed poor response to steroids and intravenous immunoglobulin, were given cyclophosphamide as a second-line immunotherapy. Follow-up was performed to evaluate the efficacy and safety of cyclophosphamide. Results After first-line immunotherapy for 1-4 weeks, the six patients had reduced psychiatric symptoms, seizures, and involuntary movements; three patients had an improved level of consciousness and were able to make simple conversations. However, all the patients still showed slow response, as well as cortical dysfunction symptoms such as aphasia, alexia, agraphia, acalculia, apraxia, and movement disorders. The six patients continued to receive cyclophosphamide as a sequential therapy. They were able to answer simple questions 7 days after treatment. Three school-aged patients were able to make simple calculation, had greatly improved reading and writing ability, and almost recovered self-care ability 2-3 weeks later. The cognitive function of the six patients was almost restored to the level before the onset of disease, and their living ability returned to normal 2-3 months later. During the treatment period, there were no adverse reactions or abnormal results of routine blood test and liver and kidney function tests. Conclusions Children with anti-NMDAR encephalitis should be given appropriate immunotherapy as soon as possible. Cyclophosphamide as a sequential therapy has good efficacy and safety.
Objective To investigate the clinical effects of sequential therapy, triple therapy, sequential therapy combined with Lactobacillus, and triple therapy combined with Lactobacillus in the eradication of Helicobacter pylori (H.pylori) infection in children. Methods A total of 416 children with H.pylori infection were randomly assigned to sequential group (102 children), triple group (100 children), sequential-Lactobacillus group (109 children), and triple-Lactobacillus group (105 children). The clinical outcome, H.pylori eradication rate, cost-effect ratio, and incidence of adverse events were compared between the four groups. Results The sequential-Lactobacillus and triple-Lactobacillus groups had significantly better clinical outcomes than the sequential group and the triple group (P < 0.05). The sequential-Lactobacillus group had the highest marked response rate, followed by the triple-Lactobacillus group. The triple group had the lowest marked response rate. The sequential-Lactobacillus group also had the highest H.pylori eradication rate, followed by the triple-Lactobacillus group. The triple group had the lowest H.pylori eradication rate (P < 0.05). The sequential group had the lowest cost-effect ratio, followed by the sequential-Lactobacillus group. The triple group had the highest cost-effect ratio (P < 0.01). The sequential-Lactobacillus group had the lowest incidence rate of adverse events, followed by the triple-Lactobacillus group. The triple group had the highest incidence rate. Conclusions Sequential therapy combined with Lactobacillus seems to be the best regimen for the eradication of H.pylori infection in children.
Objective To investigate the expression of IFN-λ1 in respiratory epithelial cells of children with respiratory syncytial virus (RSV) infection and its relationship with RSV load. Methods The nasopharyngeal swabs were collected from the children who were hospitalized with respiratory tract infection from June 2015 to June 2016. A direct immunofluorescence assay was used to detect the antigens of seven common respiratory viruses (including RSV) in the nasopharyngeal swabs. A total of 120 children who were only RSV positive were selected as the RSV infection group. A total of 50 children who had negative results in the detection of all viral antigens were selected as the healthy control group. Fluorescence quantitative real-time PCR was used to determine the RSV load and the expression of IFN-λ1 mRNA in the nasopharyngeal swabs of children in the two groups. Results The expression of IFN-λ1 in the RSV infection group was significantly higher than that in the healthy control group (P < 0.05). The expression of IFN-λ1 was positively correlated with RSV load (r=0.56, P < 0.05). Conclusions RSV can induce the expression of IFN-λ1 in respiratory epithelial cells, suggesting that IFN-λ1 may play an important role in anti-RSV infection.
Objective To investigate the quality of life of children with atopic dermatitis (AD) and their families, and to assess the changes in quality of life after treatment. Methods The Infants' Dermatitis Quality of Life Index (IDQOL), Children's Dermatology Life Quality Index (CDLQI), and Dermatitis Family Impact (DFI) questionnaires were used to evaluate quality of life in 109 children with AD and 55 normal children. The Severity Scoring of Atopic Dermatitis (SCORAD) was used to evaluate disease severity. The children were given external application of glucocorticoids according to the SCORAD index, and the clinical outcome and changes in quality of life were observed after 3 months of treatment. Results The three items in both IDQOL and CDLQI questionnaires with higher scores were itching/scratching, mood problems, and sleeping disturbance in the AD patients. Sleeping disturbance, fatigue and mood problems were the three items in the DFI questionnaire with higher scores. There was a positive correlation between IDQOL/CDLQI score and SCORAD index (r=0.358, 0.386 respectively; P < 0.05). In the younger group (1-4 years), there was a positive correlation between DFI score and SCORAD index (r=0.297; P < 0.05). After treatment the severity of AD and quality of life in the children and their families (P < 0.05) were significantly improved. Conclusions AD has an adverse effect on quality of life in children with AD and their families. Topical glucocorticoids may control the symptoms of AD and improve the quality of life in children and their families.
Objective To investigate the efficacy of 2-month course of sleeping position correction in the treatment of positional plagiocephaly in infants aged < 8 months. Methods A total of 73 infants with positional plagiocephaly between January 2015 and June 2016 were divided into treatment group (n=46) and control group (n=27) according to parents' wishes. The treatment group received sleeping position correction, while the control group received sleep curve mattress. The oblique diameters A and B in the two groups were measured and the cranial vault asymmetry (CVA) was calculated before and after treatment. The severity of positional plagiocephaly based on CVA was compared between the two groups before and after treatment. The Gesell Developmental Scale was used to determine the developmental quotients (DQs) in the motor, adaptive, language, and social domains in the two groups before and after treatment. Results Before treatment, there were no significant differences in oblique diameters A and B, CVA, and DQs in the four specific domains between the two groups (P > 0.05). After 2 months of treatment, the treatment group had a significantly greater oblique diameter B and a significantly smaller CVA than the control group (P < 0.05); there were no significant differences in DQs in the four specific domains between the two groups (P > 0.05). After treatment, both groups had significant improvements in oblique diameters A and B, CVA, and DQs in the motor and adaptive domains (P < 0.01); moreover, the treatment group showed a significant improvement in the DQs in the social domain (P < 0.01). There was no significant difference in the severity of positional plagiocephaly between the two groups before and after treatment (P > 0.05). Conclusions For infants with positional plagiocephaly, sleeping position correction has better efficacy and is more convenient and economical than the sleep curve mattress, so it holds promise for clinical application.
Objective To investigate the change in the expression of tight junction protein ZO-1 in intestinal epithelial cells (Caco-2 cells) and the protective effect of eicosapentaenoic acid (EPA) after adherent-invasive Escherichia coli (E.coli) LF82 infection. Methods The Caco-2 cell line was used to establish an in vitro model of tight junction of intestinal epithelial cells. Caco-2 cells were divided into EPA treatment groups (0, 25, 50, 100, and 200 μmol/L EPA) and EPA (0, 25, 50, 100, and 200 μmol/L EPA)+E.coli LF82 treatment (0, 6, and 12 hours) groups. A microscope was used to observe the morphological characteristics of the cells. MTT assay was used to determine the cell growth curve. The activity of alkaline phosphatase (ALP) at both sides of the cell membrane was compared to evaluate the Caco-2 cell model. MTT assay and flow cytometry were used to investigate the effects of different concentrations of EPA on the survival rate and apoptosis rate of Caco-2 cells. RT-qPCR was used to measure the mRNA expression of ZO-1 in Caco-2 cells after EPA and/or E.coli LF82 treatment. ELISA was used to measure the change in the level of tumor necrosis factor-α (TNF-α) in culture supernatant. Results After EPA treatment (25 and 50 μmol/L), the proliferation of Caco-2 cells was induced in a dose-dependent manner. The survival rates of the cells were significantly higher than those in the control group (P < 0.05). The EPA treatment (100 and 200 μmol/L) groups had a significant inhibitory effect on the proliferation of Caco-2 cells in a dose-dependent manner. The survival rates of the cells were significantly lower than those in the control group (P < 0.05). The EPA treatment (100 and 200 μmol/L) groups had a significant increase in cell apoptosis rate compared with the control group (P < 0.05). The 6-and 12-hour E.coli LF82 treatment groups had decreasing mRNA expression of ZO-1 in Caco-2 cells over the time of treatment and had significantly lower mRNA expression of ZO-1 than the untreated group (P < 0.05). The Caco-2 cells treated with E.coli LF82 and 25 or 50 μmol/L EPA for 6 or 12 hours showed an increase in the mRNA expression of ZO-1 with the increasing concentration of EPA, as well as significantly higher mRNA expression of ZO-1 than the Caco-2 cells treated with E.coli LF82 alone (P < 0.05). The Caco-2 cells treated with E.coli LF82 alone for 6 or 12 hours had increasing secretion of TNF-α over the time of treatment and had significantly higher secretion than the untreated Caco-2 cells (P < 0.05). The Caco-2 cells treated with E.coli LF82 and 25 or 50 μmol/L EPA for 6 or 12 hours showed a reduction in the secretion of TNF-α with the increasing concentration of EPA and had significantly lower secretion than the Caco-2 cells treated with E.coli LF82 alone (P < 0.05). Conclusions EPA can effectively prevent the destruction of tight junction of intestinal epithelial cells induced by E.coli LF82 infection and inhibit the secretion of inflammatory factors. Therefore, it has a certain protective effect on intestinal mucosal barrier.
Objective To investigate the effects of vasoactive intestinal peptide (VIP) on the airway inflammation and its regulatory effect on Th17/Treg imbalance in asthmatic mice. Methods A total of 30 BALB/c mice were equally and randomly divided into three groups:control, asthma, and VIP. An acute asthmatic mouse model was established by sensitization and challenge with ovalbumin (OVA). The control group received normal saline instead of OVA. Before the challenge with OVA, the VIP group was administered VIP (20 μg/mL) by aerosol inhalation for 30 minutes. The bronchoalveolar lavage fluid (BALF) and the lung tissue were collected from mice. The pathological changes in the lung tissue were observed by hematoxylin and eosin staining. The levels of Th17/Treg-related cytokines in BALF were measured by enzyme-linked immunosorbent assay. The expression of retinoid-related orphan receptor gamma t (RORγt) and forkhead box P3 (Foxp3) were measured by real-time fluorescence quantitative PCR and immunohistochemistry. Results The histopathological results showed that the VIP group had milder symptoms of airway inflammation than the asthma group. The level of IL-17 in BALF in the asthma group was significantly higher than that in the control group and the VIP group (P < 0.01), but the level of IL-17 in the control group was significantly lower than that in the VIP group (P < 0.01). The level of IL-10 in BALF in the asthma group was significantly lower than that in the control group and the VIP group (P < 0.01, but the level of IL-10 in the VIP group was significantly higher than that in the control group (P < 0.01). The asthma group showed significantly higher expression levels of RORγt mRNA and protein in the lung tissue and significantly lower expression levels of Foxp3 mRNA and protein than the control group (P < 0.01). The VIP group had significantly lower expression levels of RORγt mRNA and protein in the lung tissue and significantly higher expression levels of Foxp3 mRNA and protein than the asthma group (P < 0.05). Conclusions The Th17/Treg imbalance may be closely related to the airway inflammation in asthmatic mice. VIP can improve airway inflammation by regulating the Th17/Treg imbalance in asthmatic mice.
Objective To observe the effects of recombinant fusion protein interleukin (IL)-18 on the expression of immune-inflammatory factors in the mice infected with Staphylococcus aureus (SA), and to investigate the mechanism of action of IL-18 in defense of SA infection in vivo. Methods A total of 40 specific pathogen-free female BLAB/c mice were randomly divided into four groups:control, SA infection, immunized, and intervention. A mouse model of SA infection was established by nasal inoculation with SA liquid. The immunized group and the intervention group were intranasally given IL-18 before SA modeling, and then the SA infection group and the intervention group received the nasal inoculation with SA liquid; the control group was treated with phosphate buffered saline instead. The levels of IL-4, interferon (IFN)-γ, tumor necrosis factor (TNF), granulocyte colony-stimulating factor (G-CSF), IgM in the serum and bronchoalveolar lavage fluid (BALF) of mice were measured by enzyme-linked immunosorbent assay. The expression of macrophage inflammatory protein (MIP)-1α mRNA and MIP-2β mRNA in the lung tissue of mice were determined by real-time fluorescent quantitative PCR. Results Compared with the control group, the SA infection group and the immunized group had significantly higher levels of IL-4, G-CSF, and IgM in the serum and BALF and expression of MIP-1α mRNA and MIP-2β mRNA in the lung tissue (P < 0.05); the SA infection group had a significantly lower level of IFN-γ and a significantly higher level of TNF in the serum and BALF (P < 0.05); the immunized group had a significantly higher level of IFN-γ in the serum and BALF (P < 0.05). Compared with the SA infection group, the intervention group had significantly higher levels of IL-4, IFN-γ, G-CSF, and IgM in the serum and BALF and expression of MIP-1α mRNA in the lung tissue. In contrast, the intervention group showed a significantly lower level of TNF in the serum and BALF and expression of MIP-2β mRNA in the lung tissue (P < 0.05). All the above indicators in the intervention group were significantly higher than those in the control group (P < 0.05), except the serum level of IFN-γ. Conclusions In the mice infected with SA, the recombinant fusion protein IL-18 by mucosal immunity can affect inflammatory factors in the serum and BALF and the expression of MIP-1α mRNA and MIP-2β mRNA in the lung tissue to promote the anti-infective immune response and enhance the ability to clear pathogens.
Objective To investigate the effects of microRNA-145 (miR-145) on epithelial-mesenchymal transition (EMT) of TGF-β1-induced human renal proximal tubular epithelial (HK-2) cells. Methods The gene sequence of miR-145 was synthesized and cloned into pCMV-myc to construct recombinant plasmid pCMV-miR-145. HK-2 cells were divided into four groups:control (untreated), TGF-β1 (treated with TGF-β1), blank+TGF-β1 (treated with TGF-β1 after HK-2 cells transfected with blank plasmid) and miR-145+TGF-β1 (treated with TGF-β1 after HK-2 cells transfected with pCMV-miR-145 recombinant plasmid). Expression of miR-145 was detected by real-time PCR (RT-PCR). TGF-β1, Smad3, Smad2/3, p-Smad2/3, α-SMA, FN and type I collagen (Col I) protein levels were detected by Western blot. Concentrations of fibronectin (FN) and Col I in cell culture supernatants were measured using ELISA. Results pCMV-miR-145 recombinant plasmid was successfully transfected into HK-2 cells. Compared with the control group, the miR-145+TGF-β1 group showed a significant up-regulation in the expression level of miR-145 (P < 0.01). However, the TGF-β1 and blank+TGF-β1 groups showed a significant down-regulation in the expression level of miR-145 compared with that in the control and miR-145+TGF-β1 groups (P < 0.01). Compared with the TGF-β1 and blank+TGF-β1 groups, the miR-145+TGF-β1 group showed significantly reduced levels of the signal proteins TGF-β1, Smad3, Smad2/3 and p-Smad2/3 (P < 0.05), as well as significantly reduced levels of the biomarkers α-SMA, FN and Col I (P < 0.05). Meanwhile, concentrations of FN and Col I in cell culture supernatants also decreased (P < 0.05). Conclusions miR-145 modulates the EMT of HK-2 cells treated with TGF-β1, possibly by inhibition of the activation of TGF-β-dependent Smad signaling pathway.
All-trans retinoic acid (ATRA) is a vitamin A derivative and plays an important role in the regulation of cell aggregation, differentiation, apoptosis, proliferation, and inflammatory response. In recent years, some progress has been made in the role of ATRA in renal diseases, especially its protective effect on podocytes. This article reviews the research advances in podocyte injury, characteristics of ATRA, podocyte differentiation and regeneration induced by ATRA, and the protective effect of ATRA against proliferation, deposition of fibers, and apoptosis.
Mitophagy is a process during which the cell selectively removes the mitochondria via the mechanism of autophagy. It is crucial to the functional completeness of the whole mitochondrial network and determines cell survival and death. On the one hand, the damaged mitochondria releases pro-apoptotic factors which induce cell apoptosis; on the other hand, the damaged mitochondria eliminates itself via autophagy, which helps to maintain cell viability. Mitophagy is of vital importance for the development and function of the nervous system. Neural cells rely on autophagy to control protein quality and eliminate the damaged mitochondria, and under normal circumstances, mitophagy can protect the neural cells. Mutations in genes related to mitophagy may cause the development and progression of neurodegenerative diseases. An understanding of the role of mitophagy in nervous system diseases may provide new theoretical bases for clinical treatment. This article reviews the research advances in the relationship between mitophagy and different types of nervous system diseases.