Two cases of Kawasaki disease: Clinical characteristics and onset of fever and gastrointestinal symptoms.

BACKGROUND: Kawasaki disease (KD) is a prevalent form of systemic vasculitis that can damage various organs and systems in children. Typical KD is not difficult to diagnose in clinical practice. In recent years, it has been shown that an increasing number of children do not satisfy the diagnostic criteria for typical KD. This condition is known as incomplete KD (IKD). It is challenging to promptly diagnose and treat such children in clinical practice. CASE DESCRIPTION: A 10-year-old girl was admitted to the hospital due to fever and abdominal pain. She presented with shock symptoms. An enhanced abdominal computed tomography scan revealed intestinal pneumatosis, effusion, and gallbladder enlargement, indicating intestinal obstruction. Due to the poor outcome following an emergency laparoscopic cholecystectomy, IKD was suspected. A 3-month-old male pediatric patient was admitted to the hospital due to a fever. Patchy, congestive rashes formed on the patient's body as KD progressed. IKD was suspected based on the clinical signs of fever, rash, and hyperemia of the lips. The two patients were then treated with human immunoglobulin and aspirin treatment. The prognosis for the two children was favorable following prompt treatment. CONCLUSION: Due to the fact that IKD is frequently misdiagnosed, it is vital to (1) improve the patient prognosis for the early identification of children with KD with prolonged fever and anti-infection failure as the initial manifestation and (2) perform timely diagnosis and comprehensive treatment.

Clinical features and diagnostic value of metagenomic next -generation sequencing in five cases of non-HIV related Pneumocystis jirovecii pneumonia in children.

Background: Pneumocystis jirovecii (PJ) is an opportunistic pathogenic fungus, and PJ pneumonia (PJP) is a commonly problem in HIV-positive patients. While PJP is not caused by HIV, it generally advances rapidly and can quickly lead to severe respiratory failure. To improve pediatricians' understanding of the condition and aid early accurate diagnoses and therapy, we examined the clinical characteristics of five instances of non-HIV related PJP (NH-PJP) in children and the efficacy of metagenomic next-generation sequencing (mNGS) in its diagnosis. Methods: From January 2020 to June 2022, five children with NH-PJP were admitted to the PICU of the First Affiliated Hospital of Zhengzhou University. We retrospectively summarize the clinical presentation, previous histories, routine laboratory findings, treatment, outcome of regression, and results of mNGS in these five children. Results: Five male children between the ages of 11 months and 14 years had an acute onset on NH-PJP, three of the children had chest tightness after activity, shortness of breath and paroxysmal dry cough, - and two had high fever and dry cough. All five of the children had several flocculent high-density pictures in both lungs at the beginning of the disease, and lung auscultation revealed coarse breath sounds in both lungs, one of which was accompanied by a modest quantity of dry rales. PJ nuclear sequences were found in one patient and four patients' blood and alveolar lavage fluid. All five children were treated with Trimethoprim-sulfamethoxazole (TMP-SMX) in combination with Caspofungin and corresponding symptomatic treatment. Four patients were cured and one patient died. Conclusion: Children commonly encounter an initial exposure to NH-PJP, which manifests as a high fever, dry cough, chest discomfort, dyspnea that worsens over time, fast disease progression, and a high death rate. The clinical presentation of children with PJ infection should be taken into consideration along with the results for diagnose. mNGS has higher sensitivity and a shorter detection period compared to identification of PJP.

Metagenomic next-generation sequencing may assist diagnosis of cat-scratch disease.

Bartonella henselae, the pathogen that causes cat-scratch disease (CSD), is relatively rare in the clinic. CSD usually causes mild clinical manifestations, which self-heal in a matter of weeks. However, in immunocompromised patients, CSD may cause systemic disorders that can lead to critical illness. Due to the diversity of symptom signs and the lack of a golden standard for diagnosis, identifying atypical CSD in a timely manner presents a challenge. Metagenomic next-generation sequencing (mNGS), is a promising technology that has been widely used in the detection of pathogens in clinical infectious diseases in recent years. mNGS can detect multiple pathogens quickly and accurately from any given source. Here, we present a case of atypical CSD, which was diagnosed using mNGS. The patient manifested a fever of unknown infectious origin, and routine antibiotic treatment was ineffective. mNGS was employed to test the patient's peripheral blood, which led to the detection of B. henselae. This was rarely seen in previous CSD reports. We surmised that the patient presented with atypical CSD and thus a targeted therapy was recommended. Crucially, the patient recovered rapidly. Based on this case study findings, we recommend that CSD should be included in the differential diagnosis for fever of unknown origin and that mNGS may be helpful in the diagnosis of CSD.

Genetic Characterization of Enterobacter hormaechei Co-Harboring bla NDM-1 and mcr-9 Causing Upper Respiratory Tract Infection.

Purpose: With the spread of multiple drug-resistant bacteria, bla NDM-1 and mcr-9 have been detected in various bacteria worldwide. However, the simultaneous detection of bla NDM-1 and mcr-9 in Enterobacter hormaechei has been rarely reported. This study identified an E. hormaechei strain carrying both bla NDM-1 and mcr-9. We investigated the genetic characteristics of these two resistance genes in detail, elucidating various potential mechanisms by which they may be transmitted. Methods: Bacterial genomic features and possible origins were assessed by whole-genome sequencing (WGS) with Illumina and PacBio platforms and phylogenetic analysis. Subsequent investigations were performed, including antimicrobial susceptibility testing and multilocus sequence typing (MLST). Results: We isolated an E. hormaechei strain DY1901 carrying both bla NDM-1 and mcr-9 from the sputum sample. Susceptibility testing showed that the isolate was multidrug-resistant. Multiple antibiotic resistance genes and virulence genes are widely distributed in DY1901. S1-PFGE, Southern blotting, and plasmid replicon typing showed that DY1901 carried four plasmids. The plasmid carrying mcr-9 was 259Kb in size and belonged to IncHI2, while the plasmid carrying bla NDM-1 was 45Kb in length and belonged to IncX3. Conclusion: The E. hormaechei strain isolated in this study has a broad antibiotic resistance spectrum, posing a challenge to clinical treatment. Plasmids carrying mcr-9 are fusion plasmids, and those taking NDM are widely disseminated in China, suggesting that we should conduct routine genomic surveillance on such plasmids to curb the spread of drug-resistant bacteria in the region.

Overlapping infection of Nocardia farcinica and Aspergillus fumigatus in a child with X-linked chronic granulomatous disease: a case report.

BACKGROUND: Chronic granulomatous disease (CGD) is a rare inherited primary immunodeficiency syndrome, manifested as recurrent infections and inflammatory complications. Although prophylactic treatment with antibiotics and antifungals improved the outcome of CGD patients, infections remain the major cause of mortality. CASE PRESENTATION: A boy aged 3 years and 8 months was admitted to hospital complaining of lip swelling with fever for half a month and neck abscess for 11 days. After a thorough examination, severe pneumonia, respiratory failure, oral and maxillofacial space infection, and perianal abscess were confirmed. However, his condition didn't improve after initial comprehensive therapy. Subsequently, overlapping infections of Nocardia farcinica and Aspergillus fumigatus were identified by metagenomic next-generation sequencing. He was treated with imipenem, linezolid, and voriconazole intravenously, plus taking oral compound sulfamethoxazole. Later, his condition improved. Through whole-exome sequencing, the child was ultimately diagnosed as X-linked chronic granulomatous disease (X-CGD) caused by CYBB gene mutation. Allogeneic hematopoietic stem cell transplantation was the potential sanative approach but there were no available human leukocyte antigen compatible donors for the child. The family requested to transfer to a superior hospital for further treatment. Two months later, we followed up the child's family. Unfortunately, the child had expired due to severe infection. CONCLUSION: To our knowledge, this is the first case of overlapping infection of Nocardia farcinica and Aspergillus fumigatus identified by metagenomic next-generation sequencing in a child with X-CGD from China. For infectious pathogens that are hard to diagnosis by traditional detection methods, metagenomic next-generation sequencing is recommended as an adminicle or indispensable approach for microbial identification. Patients with X-CGD have poor prognosis, early diagnosis and intervention of X-CGD may reduce the mortality.

Ginsenoside Rb1 Alleviates Lipopolysaccharide-Induced Inflammatory Injury by Downregulating miR-222 in WI-38 Cells.

Pneumonia is a serious respiratory tract infection disease in children, which threatens to the health or life of children patients. Ginsenoside Rb1 (Rb1) is a principle active ingredient extracted from the root of Panax notoginseng (Burk.) F.H. Chen with anti-inflammatory effect. Our study aimed to determine the effects and molecular mechanisms of Rb1 on lipopolysaccharide (LPS)-induced inflammatory injury of lung fibroblasts WI-38 cells. Cell viability and apoptosis were evaluated by CCK-8 and flow cytometry, respectively. The production of inflammatory cytokines were measured by ELISA and RT-qPCR. miR-222 expression was examined by RT-qPCR. The expression levels of the nuclear factor-kappa B (NF-κB) p65 and phosphorylated p65 were detected by western blot. We found that LPS stimulation induced WI-38 cell inflammatory injury by inhibiting cell viability, and inducing apoptosis and inflammatory cytokine production, while treatment with Rb1 significantly attenuated LPS-induced inflammatory injury in WI-38 cells. Additionally, Rb1 decreased LPS-induced upregulation of miR-222 and activation of the NF-κB pathway in WI-38 cells. Overexpression of miR-222 abolished the inhibitory effects of Rb1 on LPS-induced viability reduction, apoptosis, inflammatory cytokine production and activation of the NF-κB pathway. In conclusion, Rb1 alleviated LPS-induced inflammatory injury in WI-38 cells via downregulating miR-222 and inactivation of the NF-kB pathway.

Silencing of long non-coding RNA DLX6-AS1 weakens neuroblastoma progression by the miR-513c-5p/PLK4 axis.

Emerging evidence has demonstrated the crucial roles of long noncoding RNAs in human cancers, including neuroblastoma (NB). DLX6 antisense RNA 1 (DLX6-AS1) has been identified as an oncogenic driver in NB. However, the mechanisms of DLX6-AS1 in NB progression are not fully understood. Our data showed that DLX6-AS1 was significantly overexpressed in NB tissues and cells. Moreover, DLX6-AS1 silencing repressed NB cell viability, colony formation, migration, and invasion, and promoted cell cycle arrest and apoptosis in vitro, as well as decreased tumor growth in vivo. Mechanistically, DLX6-AS1 operated as a miR-513c-5p sponge. MiR-513c-5p mediated the regulation of DLX6-AS1 on NB cell malignant progression in vitro. PLK4 was a target of miR-513c-5p- and DLX6-AS1-controlled PLK4 expression via sponging miR-513c-5p. Furthermore, the suppressive effect of miR-513c-5p overexpression on NB cell malignant progression in vitro was reversed by PLK4 upregulation. Our findings identified a novel regulatory mechanism, the DLX6-AS1/miR-513c-5p/PLK4 axis, in NB progression, highlighting a strong rationale for developing DLX6-AS1 as a new target for NB management.

Two new compounds from the roots of Scrophularia ningpoensis and their anti-inflammatory activities.

Aiming to investigate the bioactive constituents with anti-inflammatory activity from the roots of Scrophularia ningpoensis, two new compounds (1 and 3) were isolated from the extract of the roots of the plant. Their structures were elucidated on the basis of spectral analyses (UV, IR, NMR, and MS spectroscopy), as well as experimental and calculated electronic circular dichroism (ECD) analyses. All of the isolates were tested for their anti-inflammatory properties in terms of suppressing the production of NO in lipopolysaccharide-induced BV2 cells. Compound 2 exhibited stronger anti-inflammatory effects (77.65%) than the positive control curcumin (69.75%) at 10 µM.

[Mechanism of Smad 3 signaling pathway and connective tissue growth factor in the inhibition of form deprivation myopia by pirenzepine].

OBJECTIVE: To observe the inhibitive effect of pirenzepine on form deprivation myopia in guinea pigs and to explore the mechanism of Smad3 signaling pathway and connective tissue growth factor (CTGF) in the inhibition of myopia by pirenzepine. METHODS: Forty 1-week-old guinea pigs of either sex were randomly divided into 4 groups: a control group (Group I), a form deprivation group (Group II), a pirenzepine ophthalmic solution group (Group III), and a sodium chloride ophthalmic solution group (Group IV). Translucent blinders were used in the right eyes of Group II, III and IV. The left eyes were not given any treatment as the normal control group. Covered eyes of Group III and IV were given 3% pirenzepine ophthalmic solution and 0.1% azone ophthalmic solution respectively twice every day. Six weeks later, refraction and axial length were measured at the end of the experiment, and immunohistochemistry and Western blot were used to analyze the expression levels of Smad3 and CTGF in the sclera of all 4 groups. RESULTS: There was no significant difference between Group III and I in relative refraction and changes of axial length (P>0.05). The difference of Group II and IV compared with Group I was statistically significant (P<0.05). The number of Smad3 and CTGF positive cells in the sclera between Group III and I was not significantly different (P>0.05), while the difference in Group II, IV and I was significant (P<0.05). Western blot showed that the expression levels of Smad3 and CTGF in Group II and IV were much lower than those in Group I (P<0.05), but not evident in Group III and I (P>0.05). CONCLUSION: Pirenzepine ophthalmic solution can inhibit the development of form deprivation myopia. Pirenzepine may affect Smad3 signaling pathway in the sclera by inhibiting the development of form deprivation myopia.