Integrating systemic immune-inflammation index, fibrinogen, and T-SPOT.TB for precision distinction of active pulmonary tuberculosis in the era of mycobacterial disease research.

Background: The clinical challenge of differentiating suspected tuberculosis with positive T-SPOT.TB results persist. This study aims to investigate the utility of the Systemic Immune-Inflammation Index (SII), Fibrinogen, and T-SPOT.TB in distinguishing between active pulmonary tuberculosis (PTB) and non-tuberculous lung diseases. Methods: A retrospective analysis included 1,327 cases of active PTB with positive T-SPOT.TB results and 703 cases of non-tuberculous lung diseases from May 2016 to December 2020 at Meizhou People's Hospital. These were designated as the case group and the control group, respectively. The detection indicators of T-SPOT.TB: Early Secreted Antigenic Target 6 (ESAT-6), Culture Filtrate Protein 10 (CFP-10), as well as SII and Fibrinogen levels-were compared and analyzed for association and joint diagnostic value between the two groups. Results: The case group showed higher values of ESAT-6, CFP-10, SII, and Fibrinogen compared to the control group (all p < 0.001). In the case group, SII and Fibrinogen did not correlate with ESAT-6 and CFP-10 (∣rs∣ all < 0.3) but were positively correlated with C-reactive protein (CRP; rs all > 0.3). SII and Fibrinogen values in smear-positive pulmonary tuberculosis were higher than in smear-negative cases (all p < 0.05). The optimal diagnostic thresholds for ESAT-6, CFP-10, SII, and Fibrinogen in differentiating between active PTB and non-tuberculous lung diseases were 21.50 SFCs/106 PBMC, 22.50 SFCs/106 PBMC, 2128.32, and 5.02 g/L, respectively. Regression logistic analysis showed that ESAT-6 < 21.5 (OR: 1.637, 95% CI: 1.311-2.043, p < 0.001), CFP-10 < 22.5 (OR: 3.918, 95% CI: 3.138-4.892, p = 0.025), SII < 2128.32 (OR: 0.763, 95% CI: 0.603-0.967, p < 0.001), and FIB < 5.02 (OR: 2.287, 95% CI: 1.865-2.806, p < 0.001) were independent risk factors for active PTB. The specificity for ESAT-6 + CFP-10, ESAT-6 + CFP-10 + SII, ESAT-6 + CFP-10 + FIB, and ESAT-6 + CFP-10 + SII + FIB was 82.5%, 83.2%, 95.8%, and 80.1%, respectively, while sensitivity was 52.6%, 53.0%, 55.8%, and 44.7%, and positive predictive values were 85.0%, 85.6%, 84.1%, and 89.6%, respectively. Conclusion: SII and Fibrinogen are positively correlated with the degree of tuberculosis inflammation and the bacterial load of Mycobacterium tuberculosis. The combined detection of SII, Fibrinogen, and T-SPOT.TB is significant in distinguishing between active PTB with positive T-SPOT.TB results and non-tuberculous lung diseases.

Diagnostic significance of cerebrospinal fluid flow cytometry in Chinese children with B lineage acute lymphoblastic leukemia.

BACKGROUND: Central nervous system leukemia (CNSL) is one of the major causes of the poor prognosis of childhood leukemia. We aimed to compare the sensitivity of cytomorphology (CM) and flow cytometry (FCM) in diagnosing CNSL, emphasizing the importance of FCM in the diagnosis process. METHODS: One-hundred-sixty-five children with newly diagnosed B-cell Acute Lymphoblastic Leukemia (B-cell ALL) were included in this study. Cerebrospinal fluid (CSF) samples were taken for routine CSF analysis, CM analysis, and FCM examination. Computed tomography scans and/or magnetic resonance imaging were performed at diagnosis. Patients with CNS2, CNS3, and traumatic lumbar puncture (TLP) at diagnosis received two additional courses of triple intrathecal injections during induction treatment. We compared the sensitivity of FCM and CM in the diagnosis of children with CNSL. RESULTS: One hundred and twenty-eight (77.58%) CSF samples were negative by either CM or FCM (CM-/FCM-), four (2.42%) were positive by both CM and FCM (CM+/FCM+), and thirty-three (20%) displayed a single positive finding by FCM (CM-/FCM+) (p = 0.044). By adding two intrathecal injections in the induction treatment, ten children with TLP+ had no CNS relapse, like those with TLP-. However, compared to CNS1 and TLP, the event-free survival (EFS) did not significantly improve in patients with CNS2 and CNS3. Moreover, CNSL status was associated with worse 3-year EFS (p < 0.05). CONCLUSIONS: We have validated that FCM is more accurate in stratifying the status of the CNS compared to CM analysis. However, to improve the EFS rate of childhood leukemia, it is necessary to combine CM examination, FCM, and cranial imaging for the early diagnosis of CNSL.

RNA-binding protein RBM5 plays an essential role in acute myeloid leukemia by activating the oncogenic protein HOXA9.

BACKGROUND: The oncogenic protein HOXA9 plays a critical role in leukemia transformation and maintenance, and its aberrant expression is a hallmark of most aggressive acute leukemia. Although inhibiting the upstream regulators of HOXA9 has been proven as a significant therapeutic intervention, the comprehensive regulation network controlling HOXA9 expression in leukemia has not been systematically investigated. RESULTS: Here, we perform genome-wide CRISPR/Cas9 screening in the HOXA9-driven reporter acute leukemia cells. We identify a poorly characterized RNA-binding protein, RBM5, as the top candidate gene required to maintain leukemia cell fitness. RBM5 is highly overexpressed in acute myeloid leukemia (AML) patients compared to healthy individuals. RBM5 loss triggered by CRISPR knockout and shRNA knockdown significantly impairs leukemia maintenance in vitro and in vivo. Through domain CRISPR screening, we reveal that RBM5 functions through a noncanonical transcriptional regulation circuitry rather than RNA splicing, such an effect depending on DNA-binding domains. By integrative analysis and functional assays, we identify HOXA9 as the downstream target of RBM5. Ectopic expression of HOXA9 rescues impaired leukemia cell proliferation upon RBM5 loss. Importantly, acute protein degradation of RBM5 through auxin-inducible degron system immediately reduces HOXA9 transcription. CONCLUSIONS: We identify RBM5 as a new upstream regulator of HOXA9 and reveal its essential role in controlling the survival of AML. These functional and molecular mechanisms further support RBM5 as a promising therapeutic target for myeloid leukemia treatment.

Surveillance and Outcomes of Pediatric Hematopoietic Stem Cell Transplantation Recipients During the Recent COVID-19 Outbreak in China.

Background: The COVID-19 pandemic presents challenges for healthcare systems globally, especially in vulnerable populations such as pediatric hematopoietic stem cell transplant (HSCT) recipients. This study examines the clinical characteristics and outcomes of COVID-19 infection in pediatric HSCT recipients within one year post-HSCT. Methods: Retrospective analysis was conducted on data from 247 pediatric patients. None of them had received SARS-CoV-2 vaccination or had prior infection. SARS-CoV-2 infection was confirmed using RT-PCR testing. COVID-19 disease severity was categorized according to established guidelines. Demographic, clinical, laboratory, imaging and treatment data were collected. Results: The median age of the cohort was 7±3.7 years, with thalassemia major as the predominant underlying disease. Allogeneic HSCT was performed in the majority of cases, with haploidentical donors being the most common source of grafts. Nearly half of the patients developed COVID-19, with significantly higher infection rates observed in recipients over 100 days compared to recipients within 100 days post-HSCT (40.1% vs 21.7%, p<0.05, Fisher's Exact test). Fever (n=107, 43.2%) and cough (n=88, 35.6%) were the most common symptoms. While most patients had mild disease and did not require specific anti-viral treatment, a significant proportion required hospitalization (n=34, 13.8%). Various treatments were employed hospitalized patients, including Paxlovid (n=19, 55.9%), methylprednisolone (n=7, 20.6%), IL-6 antibody (n=2, 5.9%), mesenchymal stem cells (n=3, 8.8%), and exosomes nebulization therapy (n=2, 5.9%). Despite multidisciplinary approaches, one patient died from severe respiratory failure. However, overall survival of all patients remained high (99.53%; CI 96.72-99.93%), indicating favorable outcomes in pediatric HSCT recipients with COVID-19. Conclusion: This study provides insights into clinical features, therapeutic measures, and outcomes of pediatric HSCT recipients following COVID-19 infection in a large HSCT center in China. These findings contribute to our understanding of COVID-19 in this population and inform strategies to mitigate the impact the pandemic's impact on their care.

Green extraction of Milletia pinnata oil for the development, and characterization of pectin crosslinked carboxymethyl cellulose/guar gum herbal nano hydrogel.

Milletia pinnata oil and Nardostachys jatamansi are rich sources of bioactive compounds and have been utilized to formulate various herbal formulations, however, due to certain environmental conditions, pure extract form is prone to degradation. Therefore, in this, study, a green hydrodistillation technology was used to extract M. pinnata oil and N. jatamansi root for the further application in development of pectin crosslinked carboxymethyl cellulose/guar-gum nano hydrogel. Both oil and extract revealed the presence of spirojatamol and hexadecanoic acid methyl ester. Varied concentrations (w/w) of cross-linker and gelling agent were used to formulate oil emulsion extract gel (OEEG1, OEG1, OEEG2, OEG2, OEEG3, OEG3, OEEG4, OEG4, OEEG5, OEG5), in which OEEG2 and OEG2 were found to be stable. The hydrogel displayed an average droplet size of 186.7 nm and a zeta potential of -20.5 mV. Endo and exothermic peaks and the key functional groups including hydroxyl, amide II, and amide III groups confirmed thermal stability and molecular structure. The smooth surface confirmed structural uniformity. Bactericidal activity against both Gram-positive (25.41 ± 0.09 mm) and Gram-negative (27.25 ± 0.01 mm) bacteria and anti-inflammatory activity (49.25%-83.47%) makes nanohydrogel a potential option for treating various infections caused by pathogenic microorganisms. In conclusion, the use of green hydrodistillation technology can be used to extract the bioactive compounds that can be used in formulation of biocompatible and hydrophobic nanohydrogels. Their ability to absorb target-specific drugs makes them a potential option for treating various infections caused by pathogenic microorganisms.

Self-driven immune checkpoint blockade and spatiotemporal-sensitive immune response monitoring in acute myeloid leukemia using an all-in-one turn-on bionanoprobe.

Immune checkpoint (ICP) blockade (ICB) is one of the most promising immunotherapies for acute myeloid leukemia (AML). However, owing to their heterogeneity, AML cells may cause uncoordinated metabolic fluxes and heterogeneous immune responses, inducing the release of a spatiotemporally sensitive immune response marker. Timely and in situ detection of immune responses in ICB therapy is important for therapeutic strategy adjustment. Herein, we constructed an all-in-one nanoprobe for self-driving ICB and simultaneously detecting an immune response in the same AML cell in vivo, thus enabling accurate evaluation of heterogenetic immune responses in living AML mice without additional drug treatment or probe processes. The nature-inspire polydopamine (PDA) nanoparticles loaded with an ICP blocker were targeted to the leukocyte immunoglobulin like receptor B4 (a new ICP) of AML cells to induce the release of immune response marker granzyme B (GrB). The PDA nanoparticles were additionally paired with carbon-derived graphene quantum dots (GQDs) to construct a full-organic 'turn-on' bionanoprobe that can transfer fluorescence resonance energy for GrB detection. This multifunctional nanoprobe was validated for triggering ICB therapy and monitoring the changes of GrB levels in real-time both in vitro and in vivo. The organic nanoprobe showed excellent permeability and retention in tumor cells and high biocompatibility in vivo. This bionanoprobe orderly interacted with the upstream ICP molecules and downstream signal molecule GrB, thereby achieving in situ immune response signals within the therapeutic efficacy evaluation window.

Synthesis of Berberis aristate rhizome extract stabilized magnesium nanoparticles using green chemistry: rhizome characterization, in vitro antimicrobial and anti-inflammatory activity.

In the present study, magnesium nanoparticles (Mg NPs) were synthesized utilizing an aqueous extract of Berberis aristate rhizome and evaluated for antimicrobial and anti-inflammatory activity. Technofunctional properties of rhizome powder were evaluated and during thermal stability evaluation four stages of decomposition with a maximum delta Y value of 76.04 % was observed. Optimization of Mg NPs was carried out by employing eight different concentrations (C1-C8) and the C4 showed maximum absorbance at 330 nm confirming the NPs synthesis. The Mg NPs showed the particle size of 62 nm, zeta potential of -24.7 mV and hexagonal mprphology. Potential inhibition against S. aureus and E. coli (76.78 ± 0.05% and 74.62 ± 0.17%)and anti-inflammatory activity ranging from 42.43 ± 0.07-82.92 ± 0.04% was observed for Mg NPs. Therefore, green synthesis of Mg NPs is a promising approach for the development ofbiological active NPs to cure microbial infections.

A Retrospective Analysis of the Therapeutic Outcomes of 117 Neuroblastoma Patients Treated at a Single Pediatric Oncology Center in China.

OBJECTIVE: Recent therapeutic advances have greatly enhanced the survival rates of patients with neuroblastoma (NB). However, the outcomes of neuroblastoma patients in China, particularly those with high-risk (HR) NB, remain limited. METHOD: We retrospectively analyzed the clinical data and outcomes of NB patients who were treated at a tertiary pediatric cancer facility in China between January 2013 and October 2021. RESULTS: A total of 117 NB patients were recruited. Patients with very low-risk (VLR), low-risk (LR), intermediate-risk (IR), and HR-NB patients made up 4%, 27%, 15%, and 54% of total patient population, respectively. Patients diagnosed between 2013 and 2018 were treated according to the protocol of Sun Yat-Sen University Cancer Center and those diagnosed between 2019 and 2021 were treated according to the COG ANBL0531 or ANBL0532 protocol with or without autologous stem cell transplantation (ASCT). The 5-year EFS and OS of all risk groups of patients were 67.29% and 77.90%, respectively. EFS and OS were significantly decreased in patients with higher risk classifications (EFS: VLR/LR vs IR vs HR: 97.22% vs 67.28% vs 51.83%; ***P = .001; OS: VLR/LR vs IR vs HR: 97.06% vs 94.12% vs 64.38%; *P = .046). In HR-NB patients treated according to the COG protocol between 2019 and 2021, the 3-year OS of patients who received tandem ASCT was significantly greater than those who did not receive ASCT (93.33% % vs 47.41%; *P = .046; log-rank test). EFS was not significantly different between patients with and without ASCT (72.16% vs 60.32%). CONCLUSION: Our findings show that patients with lower risk classification have a positive prognosis for survival. The prognosis of patients with HR-NB remains in need of improvement. ASCT may enhance OS in HR-NB patients; however, protocol adjustment may be necessary to increase EFS in these patients.

Trends in Antibiotic Resistance Patterns and Burden of Escherichia Coli Infections in Young Children: A Retrospective Cross-Sectional Study in Shenzhen, China from 2014-2018.

Purpose: The emergence of multi-drug resistant ESBL-producing E. coli poses a global health problem. In this study, we aimed to investigate the prevalence of E. coli infections and their antibiotic susceptibility profiles in paediatric clinical cases in Shenzhen, China from Jan 1, 2014, to Jan 30, 2019, while also determining temporal trends, identifying ESBL-producing strains, and recommending potential empirical antibiotic therapy options. Methods: We isolated a total of 4148 E. coli from different specimens from a single paediatric healthcare centre. Additionally, we obtained relevant demographic data from the hospital's electronic health records. Subsequently, we performed antimicrobial susceptibility testing for 8 classes of antibiotics and assessed ESBL production. Results: Out of the 4148 isolates, 2645 were from males. The highest burden of E. coli was observed in the age group of 0-1 years, which gradually declined over the five-year study period. Antimicrobial susceptibility results indicated that 82% of E. coli isolates were highly resistant to ampicillin, followed by 52.36% resistant to cefazolin and 47.46% resistant to trimethoprim/sulfamethoxazole. Notably, a high prevalence of ESBL production (49.54%) was observed among the E. coli isolates, with 60% of them displaying a multi-drug resistance phenotype. However, it is worth mentioning that a majority of the isolates remained susceptible to ertapenem and imipenem. Our findings also highlighted a decrease in E. coli infections in Shenzhen, primarily among hospitalized patients in the 0-1 year age group. However, this decline was accompanied by a considerably high rate of ESBL production and increasing resistance to multiple antibiotics. Conclusion: Our study underscores the urgent need for effective strategies to combat multi-drug resistant ESBL-producing E. coli Infections.

Effects of the SNAP-25 Mnll variant on hippocampal functional connectivity in children with attention deficit/hyperactivity disorder.

Objectives: Attention-deficit/hyperactivity disorder (ADHD) is one of the most widespread and highly heritable neurodevelopmental disorders affecting children worldwide. Although synaptosomal-associated protein 25 (SNAP-25) is a possible gene hypothesized to be associated with working memory deficits in ADHD, little is known about its specific impact on the hippocampus. The goal of the current study was to determine how variations in ADHD's SNAP-25 Mnll polymorphism (rs3746544) affect hippocampal functional connectivity (FC). Methods: A total of 88 boys between the ages of 7 and 10 years were recruited for the study, including 60 patients with ADHD and 28 healthy controls (HCs). Data from resting-state functional magnetic resonance imaging (rs-fMRI) and clinical information were acquired and assessed. Two single nucleotide polymorphisms (SNP) in the SNAP-25 gene were genotyped, according to which the study's findings separated ADHD patients into two groups: TT homozygotes (TT = 35) and G-allele carriers (TG = 25). Results: Based on the rs-fMRI data, the FC of the right hippocampus and left frontal gyrus was evaluated using group-based comparisons. The corresponding sensitivities and specificities were assessed. Following comparisons between the patient groups, different hippocampal FCs were identified. When compared to TT patients, children with TG had a lower FC between the right precuneus and the right hippocampus, and a higher FC between the right hippocampus and the left middle frontal gyrus. Conclusion: The fundamental neurological pathways connecting the SNAP-25 Mnll polymorphism with ADHD via the FC of the hippocampus were newly revealed in this study. As a result, the hippocampal FC may further serve as an imaging biomarker for ADHD.

Genomic characterisation of multi-drug resistant Escherichia coli and Klebsiella pneumoniae co-harbouring mcr-1 and mcr-3 genes on a single plasmid from paediatric clinical cases.

OBJECTIVES: Emergence of the plasmid-born mobile colistin resistance (mcr) gene is a growing concern in healthcare. Therefore, this study aimed to genomically characterise multidrug-resistant Escherichia coli and Klebsiella pneumoniae co-harbouring the mcr-1 and mcr-3 genes in young children. METHODS: E. coli (n = 3) and K. pneumoniae (n = 2) were collected from abdominal secretions and blood, respectively. The isolates were screened using tryptone soy broth with 4 µL/mL polymyxin-B. Growing bacteria were identified using the VITEK-2 system, matrix-assisted laser desorption/ionisation time-of-flight, and 16s RNA sequencing, followed by antibiotic susceptibility testing. Metallo-ß-lactamase (MBL) and extended-spectrum ß-lactamase (ESBL) production was also detected. Afterwards, strains were subjected to molecular screening targeting mcr variants and ESBL/MBL-encoding genes. Conjugation, pulsed-field gel electrophoresis, Southern hybridisation, multilocus sequence typing, and phylogenic group detection were performed, along with plasmid-genome sequencing and bioinformatics analysis. RESULTS: E. coli isolates (EC-19-322, 323, and 331) and K. pneumoniae isolates (KP-19-225 and 226) harboured both mcr-1 and mcr-3 genes. These strains were also found to be resistant to more than three classes of antibiotics. The conjugation experiment revealed the presence of mcr-1 and mcr-3 on a single plasmid, and the transmission frequency was 10-2 to 10-3. Both strains were found to be able to produce ESBLs and MBL. E. coli EC-19-322 and 323 were identified as ST131(O25a:H41); SP-19-331, as ST1577 (O16:H30); and K. pneumoniae, as ST231 (K2). All E. coli strains belonged to phylogenetic group B2, and the results of pulsed-field gel electrophoresis supported the multilocus sequence typing findings. CONCLUSION: This study reported the co-occurrence of mcr-1 and mcr-3 genes on a single plasmid in pathogenic ESBL/MBL-producing E. coli and K. pneumoniae isolated from young children.

Resistance genomics and molecular epidemiology of high-risk clones of ESBL-producing Pseudomonas aeruginosa in young children.

Introduction: The emergence of multidrug-resistant Pseudomonas aeruginosa poses a global threat, but the distribution and resistance profiling are unclear, especially in young children. Infections due to P. aeruginosa are common, associated with high mortality, and increasingly ß-lactam drug resistant. Methods: We studied the molecular epidemiology and antibiotic resistance mechanisms in 294 clinicalisolates of P. aeruginosa from a pediatric hospital in China. Non-duplicate isolates were recovered from clinical cases and were identified using an API-20 kit followed by antimicrobial susceptibility testing using the VITEK®2 compact system (BioMerieux, France) and also by broth dilution method. In addition, a double-disc synergy test for the ESBL/E-test for MBL was performed. The presence of beta-lactamases, plasmid types, and sequence types was determined by PCR and sequencing. Results: Fifty-six percent (n = 164) of the isolates were resistant to piperacillin-tazobactam, followed by cefepime (40%; n = 117), ceftazidime (39%; n = 115), imipenem (36%; n = 106), meropenem (33%; n = 97), and ciprofloxacin (32%; n = 94). Forty-two percent (n = 126) of the isolates were positive for ESBL according to the double-disc synergy test. The blaCTX-M-15 cephalosporinase was observed in 32% (n = 40/126), while 26% (n = 33/126) werepositive for blaNDM-1 carbapenemase. Aminoglycoside resistance gene aac(3)IIIawas observed in 16% (n = 20/126), and glycylcyclines resistance gene tet(A) was observed in 12% (n = 15/126) of the isolates. A total of 23 sequence types were detected, including ST1963 (12%; n = 16), followed by ST381 (11%; n = 14), ST234 (10%; n = 13), ST145 (58%; n = 10), ST304 (57%; n = 9), ST663 (5%; n = 7), and a novel strain. In ESBL-producing P. aeruginosa, 12 different Incompatibility groups (Inc) were observed, the most common being IncFI, IncFIS, and IncA/C. The MOBP was the most common plasmid type, followed by MOBH, MOBF, and MOBQ. Discussion: Our data suggest that the spread of antibiotic resistance is likely due toclonal spread and dissemination of different clinical strains of P. aeruginosa harbouring different plasmids. This is a growing threat in hospitals particularly in young children which needs robust prevention strategies.

Outcomes and Risk Factor Analysis of Plastic Bronchitis Among 321 Children with Influenza Pneumonia After Bronchoscopy Examination.

Background: Plastic bronchitis (PB) is a rare and severe lung disease. It can be triggered by influenza virus infection, which is a common respiratory infection in children. Bronchoscopy can aid in the early detection and treatment of PB. However, the outcomes and risk for PB development in pediatric patients with influenza virus infection are not fully understood. Methods: Data from 321 children diagnosed with influenza virus pneumonia who underwent bronchoscopy examinations between 1st January, 2009 and 31st December, 2020 were retrospectively analyzed to assess the outcomes and risk factors associated with PB development. Results: This study included 97 girls and 224 boys with influenza virus pneumonia with a median age of 42 months. Among them, 36 patients (11.2%) were categorized as having PB based on bronchoscopy findings. PB patients had significantly longer fever durations (p=0.010) and higher risks of developing severe conditions including respiratory failure (p<0.001), acute respiratory distress syndrome (p<0.001), and air-leak syndrome (p<0.001) compared to non-PB patients. Conventional treatment including the use of neuraminidase inhibitors and antibiotics did not differ between the PB and non-PB patients, but PB patients required more anti-inflammatory treatment (p=0.019) and ventilator support (p<0.001). Combined univariate and multivariate analyses suggested that radiographic findings, including mediastinal emphysema (p=0.012) and lung consolidation (p=0.012), as well as increased levels of neutrophils (p=0.026), aspartate aminotransferase (p=0.004), and lactate dehydrogenase (p<0.001), were identified as risk factors for PB development in patients with influenza virus pneumonia. Although PB patients required more intensive care and had longer hospital stays, they all recovered well after treatment. Conclusion: Influenza virus infection is linked to PB development in children. Identifying risk factors and early intervention such as bronchoscopy can improve the prognosis of children with PB.

Molecular Epidemiology and Characterization of Multidrug-Resistant MRSA ST398 and ST239 in Himachal Pradesh, India.

Aim: Methicillin-resistant Staphylococcus aureus (MRSA) is a common cause of severe and difficult-to-treat infections in humans and animals. We aimed to identify the predominant lineages of methicillin-resistant S. aureus in Himachal Pradesh, India, to understand the genomic epidemiology along with the genotypic and phenotypic characteristics. Methods: We isolated 250 S. aureus from two district hospitals in Himachal Pradesh, India. Methicillin-Resistant S. aureus (MRSA) isolates were subjected to MLST, SCCmec typing, and resistance as well as virulence determinants were determined by PCR and sequencing. Bio-typing was also performed for source tracking. Results: A 17.6% (44/250) of isolates were classified as MRSA by both the MRSA detection kit and disc diffusion methods. Antimicrobial Susceptibility Testing of MRSA isolates (n = 44) showed high resistance to oxacillin (77.27%), erythromycin (77.27%), tetracycline (75%), cefoxitin (65.9%), and gentamicin (61.36%), while low resistance was observed for teicoplanin (36.36%), vancomycin and levofloxacin (31.81%) and fusidic acid (18.18%). All isolates were sensitive to linezolid, quinupristin-dulfopristin, dalbavancin, and cefazoline. The SCCmec-II was observed in 20.45% of isolates, SCCmec-I in 11.36%, SCCmec-III in 9%, SCCmec-IV in 40.9% and SCCmec-V in 18.18%. The mecA gene was present in all isolates (n = 44) and 50% also had the vanA gene. 35% of isolates had the lukS-PV/lukf-PV toxin gene and 11.36% had the co-existence of mecA, vanA, and lukS-PV/lukf-PV. The major strain was ST398 (39%) followed by ST239 (27%), ST217 (16%), ST121 (11%), and ST338 (7%). The MRSA isolates produced staphylokinase and ß-hemolysis but were negative for bovine plasma coagulation tests. In Conclusion: The predominant MRSA clones in Himachal Pradesh, India, were hospital-associated multi-drug resistant-MRSA ST239 with PVL and community-associated MRSA ST398.

Comparison of 14 respiratory pathogens among hospitalized children during and after the COVID-19 outbreak in Chaoshan area.

BACKGROUND: Since January 2020, measures has been adopted in the Chaoshan area to limit the spread of COVID-19. Restrictions were removed after August 2020. At the same time, children returned to school. We previously reported the changes of 14 main respiratory pathogens in hospitalized children before and during the COVID-19 outbreak in Chaoshan area. However, the changes of respiratory pathogen spectrum in hospitalized children after the epidemic are still unknown, which will be elucidated in this study. METHODS: There are 6201 children hospitalized with respiratory tract infection were enrolled in the study, which were divided into two groups: 2533 from outbreak group (1 January 2020-31 December 2020), and 3668 from post-outbreak group (1 January 2021-31 December 2021). Pharyngeal swab samples were collected. 14 respiratory tract pathogens were detected by liquid chip technology. RESULTS: The positive rate of pathogen detection is significantly lower in the outbreak group (65.42%, 1657/2533) than that in the post-outbreak group (70.39%, 2582/3668; χ2 = 17.15, P < 0.05). The Influenza A virus (FluA) detection rate was 1.9% (49) in 2020, but 0% (0) in 2021. The detection rates of Bordetella pertussis (BP) decreased from 1.4% (35) in 2020 to 0.5% (17) in 2021. In contrast, the detection rates of  Influenza B virus (FluB), Cytomegalovirus (CMV), Haemophilus influenzae (HI), Streptococcus pneumoniae (SP) increased from 0.3% (8), 24.7% (626), 2.0% (50) and 19.4% (491) in 2020 to 3.3% (121), 27.9% (1025), 4.6% (169), 22.8% (836) in 2021, respectively (P < 0.01). CONCLUSIONS: The detection rates of pathogens such as FluA, FluB, CMV, HI, SP, BP were statistically different between 2020 and 2021. From 2020 to 2021, the positive rates of Flu, CMV, HI and SP increased, while the positive rates of FluA and BP decreased. After the COVID-19 prevention and control measures are gradually relaxed, the positive rate of respiratory pathogens in children aged from 6 months to 6 years will increase.

Successful Treatment of Rare Pulmonary Coprinopsis cinerea Infection in a 17-Year-Old Female After Hematopoietic Stem Cell Transplantation: A Case Report.

Invasive fungal infections (IFIs) are among the most severe complications in recipients of hematopoietic stem cell transplantation (HSCT) recipients and in patients with hematological malignancies. An increasing number of uncommon fungal infections have been reported in this era of antifungal prophylaxis. Coprinopsis cinerea is a rare pathogen that causes opportunistic infections in the immunocompromised patients, including HSCT recipients and is associated with very high mortality rates. Herein, we present a successfully treated pediatric HSCT patient with breakthrough pulmonary IFI caused by Coprinopsis cinerea despite posaconazole, prophylaxis using multidisciplinary approaches.

A Rapid Antimicrobial Resistance Diagnostic Platform for Staphylococcus aureus Using Recombinase Polymerase Amplification.

Antimicrobial resistance (AMR) has posed a global threat to public health. The Staphylococcus aureus strains have especially developed AMR to practically all antimicrobial medications. There is an unmet need for rapid and accurate detection of the S. aureus AMR. In this study, we developed two versions of recombinase polymerase amplification (RPA), the fluorescent signal monitoring and lateral flow dipstick, for detecting the clinically relevant AMR genes retained by S. aureus isolates and simultaneously identifying such isolates at the species level. The sensitivity and specificity were validated with clinical samples. Our results showed that this RPA tool was able to detect antibiotic resistance for all the 54 collected S. aureus isolates with high sensitivity, specificity, and accuracy (all higher than 92%). Moreover, results of the RPA tool are 100% consistent with that of PCR. In sum, we successfully developed a rapid and accurate AMR diagnostic platform for S. aureus. The RPA might be used as an effective diagnostic test in clinical microbiology laboratories to improve the design and application of antibiotic therapy. IMPORTANCE Staphylococcus aureus is a species of Staphylococcus and belongs to Gram-positive. Meanwhile, S. aureus remains one of the most common nosocomial and community-acquired infections, causing blood flow, skin, soft tissue, and lower respiratory tract infections. The identification of the particular nuc gene and the other eight genes of drug-resistant S. aureus can reliably and quickly diagnose the illness, allowing doctors to prescribe treatment regimens sooner. The detection target in this work is a particular gene of S. aureus, and a POCT is built to simultaneously recognize S. aureus and analyze genes representing four common antibiotic families. We developed and assessed a rapid and on-site diagnostic platform for the specific and sensitive detection of S. aureus. This method allows the determination of S. aureus infection and 10 different AMR genes representing four different families of antibiotics within 40 min. It was easily adaptable in low-resource circumstances and professional-lacking circumstances. It should be supported in overcoming the continuous difficulty of drug-resistant S. aureus infections, which is a shortage of diagnostic tools that can swiftly detect infectious bacteria and numerous antibiotic resistance indicators.

Retracted: WNT974 Inhibits Proliferation, Induces Apoptosis, and Enhances Chemosensitivity to Doxorubicin in Lymphoma Cells by Inhibiting Wnt/b-Catenin Signaling.

This publication has been retracted by the Editor due to the identification of non-original figure images and manuscript content that raise concerns regarding the credibility and originality of the study and the manuscript. Reference: Senmin Chen, Xiuli Yuan, Huanli Xu, Meng Yi, Sixi Liu, Feiqiu Wen. WNT974 Inhibits Proliferation, Induces Apoptosis, and Enhances Chemosensitivity to Doxorubicin in Lymphoma Cells by Inhibiting Wnt/b-Catenin Signaling. Med Sci Monit, 2020; 26: e923799. DOI: 10.12659/MSM.923799.