The treatment of macrolide-resistant Mycoplasma pneumoniae pneumonia in children.

WHAT IS KNOWN AND OBJECTIVE: In recent years, the resistance of Mycoplasma pneumoniae to macrolide antibiotics has increased significantly. The health systems are facing significant challenges in carrying out the diagnosis and treatment of refractory Mycoplasma pneumoniae pneumonia in children. Levofloxacin is suitable for treating infectious diseases in various systems but limited in children due to arthropathy issues in weight-bearing joints. This study aimed to evaluate the efficacy and safety of levofloxacin in children with macrolide-resistant Mycoplasma pneumoniae pneumonia. METHODS: We retrospectively enrolled six confirmed cases of refractory Mycoplasma pneumoniae pneumonia who were admitted in the paediatric respiratory ward of Shandong provincial hospital Affiliated to Shandong first Medical University between 1st January 2020 and 29th February 2020. Levofloxacin was given to the patients through the intravenous or oral route as per the following dosages :<5 years, 8-10 mg/kg q12 h; >5 years, 8-10 mg/kg, qd for 10 days. The clinical data were collected and analysed. RESULTS AND DISCUSSION: The average age of the enrolled cases was six years and nine months (range, four years, and seven months to eleven years and seven months). All cases were found to be drug-resistant and were treated with azithromycin combined with antibacterial drugs. Levofloxacin was used in the patient's refractory to macrolide antibiotics. The temperature of five cases returned to normal 1-2 days after treatment with levofloxacin, and the imaging of the four cases showed expected improvements. The gastrointestinal symptoms, neurological manifestations, joint symptoms, blood parameters, liver and kidney functions, and exercise conditions of the children were closely monitored. The follow-up time of the patients ranged from one week to five months. No drug-related adverse reactions were observed in patients during treatment or during follow-up. WHAT IS NEW AND CONCLUSION: The clinical symptoms and imaging significantly improved after treatment with levofloxacin, and no drug-related adverse reactions were observed. Levofloxacin proved to be an effective and safe drug in the treatment of children with macrolide-resistant mycoplasma pneumonia. This study will provide a reference for evaluating the efficacy and safety of levofloxacin in the paediatric population.

Genome-wide association study identifies NRG1 as a susceptibility locus for Hirschsprung's disease.

Hirschsprung's disease (HSCR), or aganglionic megacolon, is a congenital disorder characterized by the absence of enteric ganglia in variable portions of the distal intestine. RET is a well-established susceptibility locus, although existing evidence strongly suggests additional loci contributing to sporadic HSCR. To identify these additional genetic loci, we carried out a genome-wide association study using the Affymetrix 500K marker set. We successfully genotyped 293,836 SNPs in 181 Chinese subjects with sporadic HSCR and 346 ethnically matched control subjects. The SNPs most associated with HSCR were genotyped in an independent set of 190 HSCR and 510 control subjects. Aside from SNPs in RET, the strongest overall associations in plausible candidate genes were found for 2 SNPs located in intron 1 of the neuregulin1 gene (NRG1) on 8p12, with rs16879552 and rs7835688 yielding odds ratios of 1.68 [CI(95%):(1.40, 2.00), P = 1.80 x 10(-8)] and 1.98 [CI(95%):(1.59, 2.47), P = 1.12 x 10(-9)], respectively, for the heterozygous risk genotypes under an additive model. There was also a significant interaction between RET and NRG1 (P = 0.0095), increasing the odds ratio 2.3-fold to 19.53 for the RET rs2435357 risk genotype (TT) in the presence of the NRG1 rs7835688 heterozygote, indicating that NRG1 is a modifier of HSRC penetrance. Our highly significant association findings are backed-up by the important role of NRG1 as regulator of the development of the enteric ganglia precursors. The identification of NRG1 as an additional HSCR susceptibility locus not only opens unique fields of investigation into the mechanisms underlying the HSCR pathology, but also the mechanisms by which a discrete number of loci interact with each other to cause disease.

Cognitive P300-evoked potentials in school-age children after surgical or transcatheter intervention for ventricular septal defect.

BACKGROUND: Some studies have suggested that neurological development may be adversely affected in children with severe coronary heart disease who have undergone long periods of deep hypothermic cardiopulmonary bypass (CPB). Reports of cognitive function in VSD patients in whom surgical repair required only a relatively brief period of CPB are rare. Also, CPB is unnecessary for VSD patients undergoing transcatheter closure. The aim of this study was to assess the cognitive function in patients with ventricular septal defect. METHODS: A total of 29 patients treated with surgery, and 35 treated with transcatheter closure and their age- and sex-matched best friends completed the cognitive P300 auditory-evoked potentials test and the intelligence test. RESULTS: The patients and their best friends had normal intelligence quotient; however, the patients had longer P300 peak latencies in cranial frontal lobe and cranial vertex leads (329.2 ± 24.8 and 335.1 ± 20.0 ms) than the healthy controls did (319.1 ± 20.6 and 313 ± 18.2 ms) (P < 0.05). Patients who underwent surgery had longer P300 peak latency in the cranial frontal lobe and cranial vertex leads than did those with transcatheter closure and controls. When cardiopulmonary bypass and aortic clamping were used, the duration was associated with P300 peak latency for patients (P < 0.05). CONCLUSION: VSD patients, especially those undergoing surgery, showed poor cognitive function, which may be associated with duration of cardiopulmonary bypass or aortic-clamping.

[Mutation analysis of keratin 5 and keratin 14 genes in a family with epidermolysis bullosa simplex with mottled pigmentation].

OBJECTIVE: To identify keratin 5 (K5) and keratin 14 (K14) gene mutations in a family affected with epidermolysis bullosa simplex with mottled pigmentation. METHODS: Genomic DNA was extracted from peripheral blood samples obtained from eleven patients from the family and controls. All the exons of K5 and K14 genes were amplified using polymerase chain reaction (PCR) and directly sequenced. RESULTS: By DNA sequence analysis, a missense mutation in K5 gene (c.237C>T) was detected. The same mutation was not found in non-affected members from the family and normal controls. CONCLUSION: Mutation in K5 gene (c.237C>T) may be responsible for the development of disease in this family.

LPS-induced up-regulation of TGF-beta receptor 1 is associated with TNF-alpha expression in human monocyte-derived macrophages.

The immunosuppressive activity of TGF-beta-mediated signaling is well documented, but in contrast, its ability to promote proinflammatory responses is less clear. In this study, we report that blockade of TGF-beta signaling by a specific inhibitor of the TGF-beta receptor I [activin receptor-like kinase 5 (ALK5)] SB431542 significantly reduces the production of TNF-alpha, a key proinflammatory cytokine, by LPS-stimulated human monocyte-derived macrophages. ALK5 protein was only detectable after LPS stimulation, and the failure of treatment with SB431542 to alter TNF-alpha mRNA expression indicates that regulation is post-transcriptional. The additive effect of blocking TGF-beta and p38 MAPK signaling on reducing TNF-alpha but not IL-6 production suggests that there is selectivity in pathway signaling. SB431542 had similar inhibitory effects on TNF-alpha production by human monocytes and endothelial cells as well as macrophages. Furthermore, treatment with SB431542 reduced plasma TNF-alpha levels and tissue damage and thereby, prevented the lethal effects of LPS in a mouse model of septic shock. Our data demonstrate a direct effect of TGF-beta signaling via ALK5 on the regulation of TNF-alpha synthesis.

[Effect of Nitrification on N2O Emissions and Their Environmental Factors in Saline-alkali Wetlands].

Wetlands are important sources and sinks for N2O. Exploring the role of N2O emissions in saline-alkali wetlands has great significance in understanding the nitrification mechanism of N2O production and assessing the role of saline-alkali wetlands in the greenhouse effect. The present study examined the N2O fluxes and environmental factors of a typical Zhalong reed wetland during the growing season. The results suggested that the N2O fluxes tended to decrease in volatility, with the highest value in mid-July. The mean flux of N2O was (37.49±15.75) µg·(m2·h)-1, indicating that the typical Zhalong reed wetland was a source of N2O. The N2O fluxes exhibited a significantly positive correlation with soil temperature at different depths (P<0.05), and the impact of the upper soil temperature on N2O flux was higher than that of deep soil. In the flooding period, the relationship between N2O fluxes and water table depth was negatively correlated (P<0.05). Meanwhile, the TOC and TN contents were lower, and the N2O flux was significantly positively correlated with the NH4+-N content in the 0-40 cm soil layer (P<0.05), but it was not related to NO3--N content. Nitrification was stronger than denitrification. There was a significant positive correlation between ammonia-oxidizing bacterial activity and soil temperature in 0-20 cm layer (P<0.01). Additionally, the activity of ammonia-oxidizing bacteria also presented significantly positive linear correlation with the N2O fluxes (P<0.001), which indicated that the release of N2O in saline-alkali wetlands was greatly affected by nitrification.

A highly specific BODIPY-based fluorescent probe for the detection of hypochlorous acid.

A fluorescent probe, HKOCl-1, has been successfully developed for the detection of hypochlorous acid on the basis of a specific reaction with p-methoxyphenol. The formation of HOCl has been successfully detected not only in an abiotic system but also in an enzymatic system (myeloperoxidase/H2O2/Cl(-) system) and in living macrophage cells upon stimulation. This new probe might be used as an efficient tool for probing the roles HOCl plays in biological systems.

BODIPY-based fluorescent probe for peroxynitrite detection and imaging in living cells.

A fluorescent probe, HKGreen-2, has been developed based on a specific reaction between ketone and peroxynitrite (ONOO(-)). This probe is highly sensitive and selective for the detection of peroxynitrite not only in abiotic but also in biological systems. With this probe, we successfully detected peroxynitrite generated in murine macrophage cells activated by phorbol 12-myristate 13-acetate (PMA), interferon-gamma (IFN-gamma), and lipopolysaccharide (LPS). This new probe will be a useful tool for studying the roles of peroxynitrite in biological processes.

Hypoxia modulates lipopolysaccharide induced TNF-alpha expression in murine macrophages.

The pro-inflammatory activity of Tumor necrosis factor-alpha (TNF-alpha) together with tissue hypoxia determine the clinical outcome in sepsis and septic shock. p38 MAPKinase is the primary intracellular signaling pathway that regulates lipopolysaccharide (LPS)-induced TNF-alpha biosynthesis, however, the effect of hypoxia on LPS mediated activation of p38 is not known. Here we report that SB203580, a specific p38 MAPK inhibitor, which completely abolished LPS-induced TNF-alpha expression by the mouse macrophage cell RAW264.7 in normoxic conditions, lost the inhibitory effect in hypoxic conditions. Hypoxia did not modulate expression of p38 MAPK, but increased that of p-MK2, a downstream target of p38 MAPK. In LPS induced endotoxemia mice model SB203580 had no inhibitory effect on the serum levels of TNF-alpha. Furthermore, hypoxia inducible factor-1alpha (HIF-1alpha) was detected in vivo after LPS administration but its expression was not affected by SB203580. Our data indicate that LPS induced p38 MAPK activation was enhanced by hypoxia and consequently increased TNF-alpha secretion. Furthermore, the induction of HIF-1alpha in mice with endotoxemia suggested a synergistic effect on p38 mediated TNF-alpha expression. These findings provide new insights on the pathophysiological effects of hypoxia in sepsis and septic shock.

Immune tolerance to cardiac myosin induced by anti-CD4 monoclonal antibody in autoimmune myocarditis rats.

Autoimmune myocarditis is a T-cell-mediated autoimmune disease. CD4-positive T cells are believed to be the most important for the initiation and mediation of the disease. This study was aimed at evaluating whether anti-CD4 monoclonal antibody could induce immune tolerance to porcine cardiac myosin and whether the immune tolerance could protect rats with autoimmune myocarditis from myocardial injury. Lewis rats were immunized with porcine cardiac myosin to induce experimental autoimmune myocarditis. Immune tolerance was induced by injections of anti-CD4 monoclonal antibody on days -2, -1, 0, and 1. Results showed that cardiac function of antibody-treated rats was significantly increased compared with untreated rats 18 days postimmunization examined by transthoracic echocardiography. Typical cardiac histopathological changes were observed obviously in untreated group but not in antibody-treated group. Lymphocytes obtained from antibody-treated group had no proliferative response to porcine cardiac myosin examined by lymphocyte proliferation assay. Serological examination showed that rats immunized with cardiac myosin could produce high levels of anti-cardiac myosin antibody. The administration of anti-CD4 monoclonal antibody significantly prevented the increase of them. Serum levels of Th1 cytokines were significantly down-regulated by antibody administration, while the production of Th2 cytokines were up-regulated or unaffected evaluated by enzyme-linked immunosorbent assay. It concluded that immune tolerance to porcine cardiac myosin could be induced by anti-CD4 monoclonal antibody in vivo, and cardiac dysfunction and myocardial injury could be prevented by induction of immune tolerance.

Clinical and experimental study of therapeutic effect of Weixibaonizhuan pills on gastric precancerous lesions.

AIM:To observe the therapeutic effect of Wei-xibaonizhuan pills on gastric precancerous lesions.METHODS: Thirty patients with gastric precancerous lesions were treated with Weixibaonizhuan pills for 3 months. Of the 36 cases, 13 (36.1%) were mild atrophic gastritis, 14 (38.9%) moderate atrophic gastritis and 9 (25.0%) severe atrophic gastritis; among them 22 (61.1%) and 27 cases (75.0%) were accompanied with intestinal metaplasia (IM) and dysplasia (DYS) respectively. Of the 36 patients, 20 were men and 16 women, aged from 30-60 years and those aged 30-59 years accounted for 61.1%. The course of disease ranged from 3 months to 21 years, and 20 (55.6%) of them had a course of 5-10 years. The clinical manifestations were fullness of the abdomen (31 cases),abdominalgia (27 cases), anorexia (30 cases), gas eructation (26 cases), acid regurgitation (6 cases) and loose stool (9 cases). When treatment ended, the improvement of patients' clinical symptoms, atrophy of gastric mucosa, IM and DYS were analysed.RESULTS: After 3 months' treatment with Wei-xibaonizhuan pills,7 cases recovered, 11 cases were much improved, 13 cases showed some improvement, and 5 cases were ineffective; the total rate of symptomatic improvement was 86.1%. Of the 13 cases with mild atrophic gastritis, 11 cases changed into superficial gastritis, and 2 cases had no changes. Of the 14 cases of moderate atrophic gastritis, 4 cases changed into superficial gastritis, 7 cases changed into mild atrophic gastritis, and 3 cases had no changes. Five of 9 cases of severe atrophic gastritis were reduced to moderate atrophic gastritis, and 4 cases had no changes. The total effective rate was 77.8% in chronic atrophic gastritis. Of the 9 cases with mild IM, IM disappeared in 6 cases and 3 showed no change. Of the 10 cases with moderate IM, it disappeared in 2 cases, 5 cases changed to ild IM, and 3 cases had no change. One of the 4 cases of severe IM changed to moderate IM and 3 had no change. The total effective rate was 63.6% in IM. Of the 16 cases of mild DYS, 11 cases showed disappearance of DYS and 5 had no change. In 9 cases of moderate DYS, 2 showed disappearance, 5 changed to mild DYS and 2 had no change. Two cases of severe DYS, both showed no change. The total effective rate was 66.7% in DYS. Before treatment, the I, II, III and IV degree positive expressions of CEA were present in 13, 12, 9 and 2 cases, respectively, whereas after treatment, the positive expressions were present in 25, 7, 3 and 1, respectively. Before treatment, the I, II, III and IV degree positive expressions of PCNA were present in 16, 11, 10 and 4 respectively, but after treatment, they were present in 21, 9, 5 and 1 respectively. In short, the positive expressions of CEA and PCNA of gastric mucosa were significantly decreased after treatment (P < 0.01).CONCLUSION: Weixibaonizhuan pill has a therapeutic effect in gastric precancerous lesions.