Patient-derived pathogenic microbe deposition enhances exposure risk in pediatric clinics.

Healthcare-associated infections (HAIs) pose significant risks to pediatric patients in outpatient settings. To prevent HAIs, understanding the sources and transmission routes of pathogenic microorganisms is crucial. This study aimed to identify the sources of opportunistic bacterial pathogens (OBPs) in pediatric outpatient settings and determine their transmission routes. Furthermore, assessing the public health risks associated with the core OBPs is important. We collected 310 samples from various sites in pediatric outpatient areas and quantified the bacteria using qPCR and CFU counting. We also performed 16S rRNA gene and single-bacterial whole-genome sequencing to profile the transmission routes and antibiotic resistance characteristics of OBPs. We observed significant variations in microbial diversity and composition among sampling sites in pediatric outpatient settings, with active communication of the microbiota between linked areas. We found that the primary source of OBPs in multi-person contact areas was the hand surface, particularly in pediatric patients. Five core OBPs, Staphylococcus epidermidis, Acinetobacter baumannii, Pseudomonas aeruginosa, Streptococcus mitis, and Streptococcus oralis, were mainly derived from pediatric patients and spread into the environment. These OBPs accumulated at multi-person contact sites, resulting in high microbial diversity in these areas. Transmission tests confirmed the challenging spread of these pathogens, with S. epidermidis transferring from the patient's hand to the environment, leading to an increased abundance and emergence of related strains. More importantly, S. epidermidis isolated from pediatric patients carried more antibiotic-resistance genes. In addition, two strains of multidrug-resistant A. baumannii were isolated from both a child and a parent, confirming the transmission of the five core OBPs centered around pediatric patients and multi-person contact areas. Our results demonstrate that pediatric patients serve as a significant source of OBPs in pediatric outpatient settings. OBPs carried by pediatric patients pose a high public health risk. To effectively control HAIs, increasing hand hygiene measures in pediatric patients and enhancing the frequency of disinfection in multi-person contact areas remains crucial. By targeting these preventive measures, the spread of OBPs can be reduced, thereby mitigating the risk of HAIs in pediatric outpatient settings.

Efficacy and safety of Chinese medicine injections in combination with docetaxel and cisplatin for non-small cell lung cancer: a network meta-analysis.

Background: Non-small cell lung cancer (NSCLC) poses a serious threat to human health. Several clinical studies have reported the benefits of Chinese herbal injections (CHIs) in combination with docetaxel and cisplatin (DP). This multidimensional network meta-analysis aimed to investigate the preferred regimen of CHIs in combination with DP for the treatment of NSCLC. Methods: Multiple databases were searched to identify randomized controlled trials (RCTs) of CHIs for NSCLC from the database inception to 30 April 2023. Studies that met the inclusion criteria and exhibited good methodological quality were included. Data analysis was conducted using Stata 15.0 and R 4.2.1 software. An odds ratio (OR) was used as the effect size, and the surface under the cumulative ranking curve (SCURA) was employed to rank the evaluated treatments. Results: The network meta-analysis included 85 eligible RCTs, encompassing 6,580 patients and 11 CHIs. Astragalus Injection combined with DP was identified as the most effective regimen for improving the response rate (SUCRAs: 90.25%). Brucea Javanica Oil Milk Injection combined with DP proved most effective in ameliorating the quality of life (SUCRAs: 76.89%). Shenfu Injection combined with DP emerged as the most effective for enhancing CD3+ and CD4+ (SUCRAs: 93.75%, 88.50%). Kanglaite Injection combined with DP exhibited the best efficacy in improving CD8+ (SUCRAs: 88.96%). Brucea Javanica Oil Milk Injection combined with DP was the most potent regimen for enhancing CD4+/CD8+ (SUCRAs: 93.13%). Conclusion: CHIs in combination with DP outperformed DP alone in NSCLC patients. Astragalus Injection plus DP, Brucea Javanica Oil Milk Injection plus DP, Shenfu Injection plus DP, Kanglaite Injection plus DP, and Brucea Javanica Oil Milk Injection plus DP were significantly effective. However, further multicenter and well-designed RCTs are required to validate our findings.

The Mobility of Eurasian Avian-like M2 Is Determined by Residue E79 Which Is Essential for Pathogenicity of 2009 Pandemic H1N1 Influenza Virus in Mice.

In 2009, a novel H1N1 influenza virus caused the first influenza pandemic of the 21st century. Studies have shown that the influenza M gene played important roles in the pathogenicity and transmissibility of the 2009 H1N1 pandemic ((H1N1)pdm09), whilst the underlying mechanism remains unclear. The influenza M gene encodes two proteins, matrix protein 1 and matrix protein 2, which play important roles in viral replication and assembly. In this study, it is found that the M2 protein of the (H1N1)pdm09 virus showed a lower mobility rate than the North America triple-reassortant influenza M2 protein in Polyacrylamide Gel Electrophoresis (PAGE). The site-directed mutations of the amino acids of (H1N1)pdm09 M2 revealed that E79 is responsible for the mobility rate change. Further animal studies showed that the (H1N1)pdm09 containing a single M2-E79K was significantly attenuated compared with the wild-type virus in mice and induced lower proinflammatory cytokines and IFNs in mouse lungs. Further in vitro studies indicated that this mutation also affected NLRP3 inflammasome activation. To reveal the reason why they have different mobility rates, a circular dichroism spectra assay was employed and showed that the two M2 proteins displayed different secondary structures. Overall, our findings suggest that M2 E79 is important for the virus replication and pathogenicity of (H1N1)pdm09 through NLRP3 inflammasome and proinflammatory response.

Bacterial quorum sensing orchestrates longitudinal interactions to shape microbiota assembly.

BACKGROUND: The mechanism of microbiota assembly is one of the main problems in microbiome research, which is also the primary theoretical basis for precise manipulation of microbial communities. Bacterial quorum sensing (QS), as the most common means for bacteria to exchange information and interactions, is characterized by universality, specificity, and regulatory power, which therefore may influence the assembly processes of human microbiota. However, the regulating role of QS in microbiota assembly is rarely reported. In this study, we developed an optimized in vitro oral biofilm microbiota assembling (OBMA) model to simulate the time-series assembly of oral biofilm microbiota (OBM), by which to excavate the QS network and its regulating power in the process. RESULTS: By using the optimized OBMA model, we were able to restore the assembly process of OBM and generate time-series OBM metagenomes of each day. We discovered a total of 2291 QS protein homologues related to 21 QS pathways. Most of these pathways were newly reported and sequentially enriched during OBM assembling. These QS pathways formed a comprehensive longitudinal QS network that included successively enriched QS hubs, such as Streptococcus, Veillonella-Megasphaera group, and Prevotella-Fusobacteria group, for information delivery. Bidirectional cross-talk among the QS hubs was found to play critical role in the directional turnover of microbiota structure, which in turn, influenced the assembly process. Subsequent QS-interfering experiments accurately predicted and experimentally verified the directional shaping power of the longitudinal QS network in the assembly process. As a result, the QS-interfered OBM exhibited delayed and fragile maturity with prolonged membership of Streptococcus and impeded membership of Prevotella and Fusobacterium. CONCLUSION: Our results revealed an unprecedented longitudinal QS network during OBM assembly and experimentally verified its power in predicting and manipulating the assembling process. Our work provides a new perspective to uncover underlying mechanism in natural complex microbiota assembling and a theoretical basis for ultimately precisely manipulating human microbiota through intervention in the QS network. Video Abstract.

Eurasian Avian-like M1 Plays More Important Role than M2 in Pathogenicity of 2009 Pandemic H1N1 Influenza Virus in Mice.

Reassortant variant viruses generated between 2009 H1N1 pandemic influenza virus [A(H1N1)pdm09] and endemic swine influenza viruses posed a potential risk to humans. Surprisingly, genetic analysis showed that almost all of these variant viruses contained the M segment from A(H1N1)pdm09, which originated from Eurasian avian-like swine influenza viruses. Studies have shown that the A(H1N1)pdm09 M gene is critical for the transmissibility and pathogenicity of the variant viruses. However, the M gene encodes two proteins, M1 and M2, and which of those plays a more important role in virus pathogenicity remains unknown. In this study, the M1 and M2 genes of A(H1N1)pdm09 were replaced with those of endemic H3N2 swine influenza virus, respectively. The chimeric viruses were rescued and evaluated in vitro and in mice. Both M1 and M2 of H3N2 affected the virus replication in vitro. In mice, the introduction of H3N2 M1 attenuated the chimeric virus, where all the mice survived from the infection, compared with the wild type virus that caused 100 % mortality. However, the chimeric virus containing H3N2 M2 was still virulent to mice, and caused 16.6% mortality, as well as similar body weight loss to the wild type virus infected group. Compared with the wild type virus, the chimeric virus containing H3N2 M1 induced lower levels of inflammatory cytokines and higher levels of anti-inflammatory cytokines, whereas the chimeric virus containing H3N2 M2 induced substantial pro-inflammatory responses, but higher levels of anti-inflammatory cytokines. The study demonstrated that Eurasian avian-like M1 played a more important role than M2 in the pathogenicity of A(H1N1)pdm09 in mice.

Measuring Subthalamic Nucleus Volume of Parkinson's Patients and Evaluating Its Relationship with Clinical Scales at Pre- and Postdeep Brain Stimulation Treatment: A Magnetic Resonance Imaging Study.

This study investigated potential imaging biomarkers for predicting the efficacy of deep brain stimulation (DBS) of the subthalamic nucleus (STN) in patients with Parkinson's disease (PD). A total of 59 PD patients and 50 healthy control subjects underwent high-resolution 3-dimensional T1-weighted brain magnetic resonance imaging. Bilateral STN volumes were compared between the 2 groups, and a correlation analysis was performed to assess the relationship between bilateral STN volumes or intracranial volume (ICV) and pre- or postoperative clinical scale scores. The results showed that the left STN volume differed significantly between PD patients and controls. In patients, the left STN volume was negatively correlated with pre- and postoperative quality of life scores and positively correlated with Mini-mental State Examination (MMSE) and Montreal Cognitive Assessment scores; ICV was also positively correlated with the MMSE score. These findings indicate that changes in the left STN volume are a useful biomarker for evaluating the clinical outcome of PD patients following DBS.

Prognostic Value of Coronary CT Angiography-Derived Fractional Flow Reserve in Non-obstructive Coronary Artery Disease: A Prospective Multicenter Observational Study.

Coronary artery disease (CAD) is a major contributor to morbidity and mortality worldwide. Myocardial ischemia may occur in patients with normal or non-obstructive CAD on invasive coronary angiography (ICA). The comprehensive evaluation of coronary CT angiography (CCTA) integrated with fractional flow reserve derived from CCTA (CT-FFR) to CAD may be essential to improve the outcomes of patients with non-obstructive CAD. China CT-FFR Study-2 (ChiCTR2000031410) is a large-scale prospective, observational study in 29 medical centers in China. The primary purpose is to uncover the relationship between the CCTA findings (including CT-FFR) and the outcome of patients with non-obstructive CAD. At least 10,000 patients with non-obstructive CAD but without previous revascularization will be enrolled. A 5-year follow-up will be performed. The primary endpoint is the occurrence of major adverse cardiovascular events (MACE), including all-cause mortality, non-fatal myocardial infarct, unplanned revascularization, and hospitalization for unstable angina. Clinical characteristics, laboratory and imaging examination results will be collected to analyze their prognostic value.

The predictive value of energy spectral CT parameters for assessing Ki-67 expression of lung cancer.

BACKGROUND: To investigate the predictive value of energy spectral CT parameters for Ki-67 expression in lung cancer. METHODS: In this retrospective analysis, 27 primary lung cancer patients confirmed by pathological examination were enrolled between December 2018 and February 2019. All patients underwent baseline arterial phase (AP) and venous phase (VP) energy spectral CT scanning followed by surgery in our institution. The iodine concentration (IC), normalized iodine concentration (NIC) and the slope of 40-80 keV energy spectrum curve (λHU) were derived from dual-energy virtual imaging on a Siemens postprocessed workstation. Immunohistochemical examination was performed to analyze Ki-67 expression. The ROC curves were used for predicting the performance of energy spectral parameters for Ki-67 expression. RESULTS: The tumors appeared larger in Ki-67 high expression group than the low expression group (P=0.046). The energy spectral parameters were higher in venous phase when compared to arterial phase, but only the venous phase NIC (vpNIC) was significantly different from that of the arterial phase NIC (apNIC) (P<0.01). There are significant differences in high and low Ki-67 expression groups for vpNIC and venous λHU (vpλHU), (P=0.033 and 0.037 for vpNIC and vpλHU, respectively). vpNIC ROC analysis showed borderline P value (P=0.056) with an AUC, sensitivity (SE), specificity (SP) and cut-off value (0.717, 92.86, 61.54 and ≤0.347), respectively. The AUC, SE, SP and cut-off value of vpλHU were 0.698, 92.86, 53.85 and ≤2.407, respectively. CONCLUSIONS: The energy spectral parameters (NIC and λHU) of venous phase might be used for predicting Ki-67 stratification. The venous phase energy spectral parameters were higher than the arterial phase. Furthermore, low expression Ki-67 group showed association with higher IC, NIC and λHU than high expression group.

Electrocardiography-gated dual-source computed tomography in the detection of atrial septal aneurysm.

The aim of the current study was to investigate the atrial septal aneurysm (ASA) incidence rate and describe its morphologic features by dual-source computed tomography (DSCT). A total of 8,626 patients (4,284 men and 4,342 women) who underwent DSCT examinations were enrolled. The presence of ASA was defined as the protrusion of the complete or partial interatrial septum with a maximum vertical distance (MVD) from the atrial septum plane of >10 mm during a cardiac cycle and a diameter of the aneurysm base of >15 mm. The MVD and direction of the protrusion, as well as other abnormalities, were recorded. The ASA patients were classified by both gender and directions of protrusion into four groups, including the right atrium (RA) and left atrium (LA) groups in males and females, respectively. Values across groups were compared using the independent-sample t-test and differences in qualitative variables were assessed with the χ2 test. Of the 8,626 patients, 51 (0.6%) were diagnosed with ASA (mean age, 62±10 years), including 23 (0.5%) males and 28 (0.6%) females. There were no significant differences in the age (t=-1.37, P>0.05) and incidence rate (χ2=0.43, P>0.05) between the male and female groups. However, there were significant differences in the mean ages (t=-2.20, P<0.05) and the gender proportions (χ2=7.39, P<0.05) of patients in the RA and LA groups. In the two male groups, no significant differences were observed in the diameters of the ASA bases and MVD in the RA and LA groups. In the female groups, the differences in the MVD of protrusion in RA and LA groups were non-significant, whereas the diameters of the base of ASA demonstrated significant differences (t=2.27, P<0.05). In conclusion, the ASA incidence rate was 0.6%, and electrocardiography-gated DSCT scan served as an alternative diagnostic technique for the detection of ASA. It is essential for radiologists to recognize this clinical entity and to minimize misdiagnoses and missed diagnoses.

Comparison of 3.0T MRI with 3D LAVA sequence and digital subtraction angiography for the assessment of accessory hepatic veins in Budd-Chiari syndrome.

PURPOSE: To compare 3D liver acceleration volume acquisition (LAVA) and digital subtraction angiography (DSA) for evaluating the presence of accessory hepatic veins (AHV) in Budd-Chiari syndrome (BCS). MATERIALS AND METHODS: This was a retrospective study in 228 patients with BCS who underwent 3.0T magnetic resonance imaging (MRI) with the 3D LAVA sequence. Two reviewers noted AHV: openings located in the inferior vena cava (IVC), caliber, and the angle of entering into the IVC. MRI results were compared to DSA. Kappa statistics were calculated to quantify intrareader variability in detecting AHVs. RESULTS: On MRI, 63 patients demonstrated no AHV on LAVA images, 70 had one AHV, 62 had two AHVs, 26 patients had three AHVs, six patients had four AHVs, and one patient had five AHVs (P < 0.05 vs. DSA). The mean caliber of the AHVs was 8.3 ± 4.0 mm compared to 9.9 ± 3.2 for DSA (P < 0.001). Among the 301 AHVs, there were 140 with acute angles (46.5%), 71 with right angles (23.6%), and 90 with obtuse angles (29.8%). The prevalence of AHVs on DSA was 54.8% (125/228), while MRI demonstrated 301 AHVs in 165 patients, for a prevalence of 72.4% (165/228) compared to 54.8% for DSA (P = 0.001). The two methods were concordant in only 116/228 (50.9%) patients. The kappa coefficient demonstrated good intrareader consistency for all documented MRI findings of AHVs (κ = 0.626 for caliber and κ = 0.65 for angles). CONCLUSION: More AHVs were visible on MRI LAVA sequences than on conventional DSA. LEVEL OF EVIDENCE: 4 J. Magn. Reson. Imaging 2017;45:401-409.

[Reduced-dose mode with low-voltage and low contrast agent in coronary artery CT angiography-a preliminary study].

OBJECTIVE: To evaluate image quality of low-voltage coronary artery computed tomographic (CT) angiography with low contrast agent in comparison with image quality. METHODS: Forty-five patients underwent coronary artery computed tomographic (CT) angiography. They were randomly assigned to 3 groups, group A (n = 15) were scanned in 120 kVp with 350 mgI/ml iodinated contrast agent mode, group B (n = 15) were scanned in 100 kVp with 350 mgI/ml iodinated contrast agent mode, group C (n = 15) were scanned in 100 kVp with 270 mgI/ml iodinated contrast agent mode. Then measured CT attenuation value of three main branches (RCA, LAD and CX) of coronary artery, And compare the SNR, CNR, the effective radiation dose(ED) and iodine intake. The Kappa test were used to quantify inter- and intra-reader agreement in detecting quality of the images under different scanning solutions. RESULTS: Three groups of coronary artery CT image quality was no statistically significant differences (all P values >0.05), Good inter- and intra-reader agreement ( k = 0.754, P < 0.05) for the detection of noise in all the patients. There was significant difference in the CT attenuation of RCA, LAD and CX among the 3 groups (P < 0.05), the CT attenuation was the highest in group B, the CT value of RCA, LAD and CX were 537 ± 90, 505 ± 90, 484 ± 75 HU, respectively.the CT attenuation was the lowest in group C, the CT value of RCA, LAD and CX were 357 ± 126, 360 ± 95, 378 ± 121 HU, respectively. There was no significant difference in the SNR and CNR among the 3 groups (P > 0.05). There was significant difference in the ED among the 3 groups (P < 0.05). The ED value of the group A was bigger than the value of the group B and C. There was no significant difference between the group B and C. Compared the group A and B, the iodine intake of the group C had fallen by 23%. CONCLUSIONS: The coronary artery CT angiography using 100 kVp with 270 mgI/ml iodinated contrast agent provide similar objective or subjective image quality compared with the (350 mgI/ml) and the 100 kVp (350 mgI/ml), thus enabling effective dose and iodine intake reduction without loss of diagnostic information.

[Clinical value of multi-detector computed tomography source image on detecting extracoronary abnormalities].

OBJECTIVE: To assess the clinical value of multi-detector computed tomography (MDCT) source image on detecting extracoronary abnormalities in a large cohort of patients with suspected coronary artery disease (CAD). METHOD: MDCT source images from 3240 consecutive patients (mean 64.5 years) with suspected CAD were reviewed retrospectively by 2 readers.Extra-coronary findings were classified according to involved organ and level of clinical significance.Following organs were examined:lungs, upper abdomen, spine, chest wall, mediastinum and vascularatures. Clinical relevance of extracoronary findings was considered as either "significant" or "non-significant"."Significant" findings were subclassified as score 1:findings necessitating immediate therapeutic actions, or score 2:findings with uncertain clinical or prognostic relevance, requiring clinical awareness, follow-up or further investigations (non-urgent)."Non-significant" findings were assigned to score 3:findings without clinical implication. The irrelevant incidental findings (e.g. spinal degenerative changes, aortic calcification) were not analyzed. RESULTS: Extracoronary findings was evidenced in 330 patients with 424 abnormalities, 20.3% (67/330) patients had multiple lesions, 16.5% lesions were located in the lungs, 13.2% lesions found in the upper abdomen, 56.8% (241/424) lesions evidenced in the mediastinum,0.9% (4/424) lesions seen in the spine and chest wall, 13.9% (53/424) lesions were related to other vascular disease. Pleural effusion accounts for 5.5% of the mediastinum lesions.Incidence of heart cavity enlargement, heart valve disease, pericardial effusion/calcification, atrial/ventricular perfusion defects, myocardial disease, congenital heart disease, ventricular aneurysm was 14.7% (56/380), 15.5% (59/380), 10.8% (41/380), 3.9% (15/380), 0.8% (3/380), 1.6% (6/380), and 1.8% (7/380) respectively. The clinical significance score 1-3 was 8.5% (36/424) , 81.1% (344/424) , and 10.4% (44/424) respectively.Incidence of detected extracoronary findings was the highest by bone window and the lowest by lung window.Incidence of extracoronary findings was not related to CAD (χ2 = 81.76, C = 0.155, P > 0.05).Inter-reader agreement on extracoronary findings was excellent (Kappa = 0.934, P > 0.05). CONCLUSION: Our data show that it is of clinical value to observe and report extracoronary findings with source image of cardiac MDCT.

Dual-source computed tomography for evaluating coronary stenosis and left ventricular function.

This study aimed to evaluate the correlation between coronary stenosis and left ventricular function using dual-source computed tomography (DSCT). DSCT coronary angiography (CAG) was performed on 66 patients with coronary disease and 36 healthy volunteers. The degree of coronary stenosis, end-diastolic volume (EDV), end-systolic volume (ESV), stroke volume (SV), ejection fraction (EF) and myocardial mass (MM) were measured for the left ventricle. These values were compared with the results obtained by echocardiography (ECHO) and selective CAG, which were both adopted as controls. The diagnoses of coronary stenosis based on DSCT CAG and those based on selective CAG were not significantly different (P>0.05). Similarly, the values of EDV, ESV, SV or EV measured by DSCT CAG were not significantly different from thoses obtained by ECHO (P>0.05). However, significant differences were observed in the ESV, EF and SV of the severe stenosis group compared with the moderate and mild stenosis groups (both P<0.05). The values of EDV and MM significantly varied between the mild, moderate and severe stenosis groups (P<0.05). DSCT CAG is a highly accurate and highly reproducible method for evaluating the preliminary changes in cardiac function based on the variations of coronary stenosis. Significant changes were detected in the EDV and MM of the moderate stenosis group and in all parameters of the severe stenosis group.