The draft genome sequence of blaCTX-M-270-carrying Kluyvera ascorbata isolated from human sputum.

Kluyvera ascorbata is recognized as an opportunistic pathogen of the Enterobacteriaceae family but remains less studied. We report the draft genome of a K. ascorbata clinical strain recovered from human sputum, comprising approximately 5.18 million bases and harboring an intrinsic gene encoding the extended-spectrum ß-lactamase CTX-M-270.

Competitive Transmission of Carbapenem-Resistant Klebsiella pneumoniae in a Newly Opened Intensive Care Unit.

We conducted a 6-month prospective study in a newly opened ICU for high-resolution tracking of carbapenem-resistant Klebsiella pneumoniae (CRKP) through environmental surveillance, patient screening, and genome sequencing. Among all ICU patients (n = 348) screened, 3.5% carried CRKP on admission and 16.3% acquired CRKP thereafter. CRKP was not detected in the environment until 10 weeks and was then isolated from 98 of 2,989 environmental samples (3.3%). The first CRKP isolate from rectal swabs (n = 37) and the first clinical isolate (n = 8) of each patient as well as the 98 isolates from environmental were subjected to whole-genome sequencing. The 143 CRKP isolates from patients and environment samples were assigned to four sequence types, with ST11 dominating (95.8%) and further divided into 14 clones, suggesting introduction of multiple clones. Subsequent CRKP transmission was complex and dynamic with 10 clones found in multiple patients and seven also detected in the environment. Two particular ST11 clones caused extensive (≥5 rooms) and persistent (≥10 weeks) environmental contamination. Both clones were associated with patients who carried CRKP throughout their prolonged ICU stay. Such "super-contaminators" are a priority for isolation and environmental surveillance. IMPORTANCE Carbapenem-resistant Klebsiella pneumoniae (CRKP) is a global challenge for human health. In health care settings, patients have frequent interactions with other patients and the environment, rendering challenges for untangling the introduction and transmission of CRKP. We conducted a prospective surveillance study in a newly opened ICU for high-resolution tracking of CRKP. Our study demonstrated the dynamic, complicated transmission of CRKP and has important findings that may help to curb its spread in health care settings. First, compliance with basic measures such as routine environment cleaning and postdischarge terminal cleaning is needed to minimize the environmental contamination-driven spread. Second, active screening could demonstrate the scale of the problem, and room transfer of patients with CRKP should be prohibited whenever possible. Third, the priority for single-room isolation should be given to patients with prolonged carriage of CRKP, especially in resource-limited settings. Good infection control practice lays a foundation for tackling multidrug-resistant organisms like CRKP.

NDM-5-producing carbapenem-resistant Klebsiella pneumoniae of sequence type 789 emerged as a threat for neonates: a multicentre, genome-based study.

Klebsiella pneumoniae is a major human pathogen. Carbapenems are the main agents of choice to treat severe K. pneumoniae infections, but carbapenem-resistant K. pneumoniae (CRKP) have emerged as a major global problem. Novel high-risk CRKP lineages are continuously emerging, but those associated with neonatal infections are under-researched. In this study, we identified a common CRKP lineage carrying the blaNDM-5 carbapenemase-encoding gene belonging to sequence type 789 (ST789) based on analysis of the genome sequences of 28 isolates, including 27 clinical isolates from neonates and 1 isolate from a sink recovered in 2019 from multiple hospitals in Chengdu, southwest China. Isolates of this lineage caused various infections (pneumonia, bloodstream infection and urinary tract infection) in neonates and had circulated in and been transmitted between neonatal intensive care units of multiple local hospitals for several years. Its emergence was likely due to clonal expansion after acquiring a blaNDM-5-carrying self-transmissible IncX3 plasmid. Genome clock analysis dated the emergence of this lineage to December 2016 (95% confidence interval, January 2015 to December 2017). The above findings highlight that CRKP lineages in neonates and adults may differ. This ST789 blaNDM-5-carrying CRKP lineage represents a new, emerging threat for neonates and warrants rigorous monitoring.

[Clinical Features and Prognosis of Patients with Hematological Disease Complicated with Mucor Infection].

OBJECTIVE: To investigate the clinical features, treatment and prognosis of patients with hematological diseases complicated with mucor infection. METHODS: The risk factors, clinical features, treatment regimen and prognosis of 18 hematological disease patients with mucor infection diagnosed by histopathology in our center from April 2014 to June 2020 were retrospectively analyzed. RESULTS: Thirteen males and five females, with an average age of 30 (13－54) years old, were diagnosed as mucor infection by histopathological examination at the site of infection, including 16 cases of mucor infection alone and 2 cases of mucor + aspergillus mixed infection. There were 12 cases with malignant hematological disease and 6 cases with severe aplastic anemia, all of whom with long-term agranulocytosis, and their clinical manifestations and imaging findings were not specific. The common sites of infection were sinuses and lungs, and some patients showed multiple systemic manifestations. The remission status of hematological diseases and recovery of immune function showed an impact on the prognosis. All the patients were treated with amphotericin B liposome combined with posaconazole, and 15 patients were treated with surgery combined with antifungal drugs, 9 of whom were effective and 6 were ineffective, while intravenous administration in 3 cases was ineffective. CONCLUSION: It is difficult to diagnose hematological disease complicated with mucor infection. After early diagnosis, prognosis can be improved by amelioration of primary state and combination of drugs and surgery.

Spread of Carbapenem-Resistant Klebsiella pneumoniae in an Intensive Care Unit: A Whole-Genome Sequence-Based Prospective Observational Study.

The aim of this study was to determine the contribution of the contamination of the health care environment in the acquisition of carbapenem-resistant Klebsiella pneumoniae (CRKP) in a CRKP-prevalent setting. We performed a 3-month prospective study in a 20-bed medical intensive care unit (ICU) by collecting rectal/oral swabs from patients within 3 days of ICU admission and weekly thereafter. We also comprehensively sampled the beds and rooms of patients and instruments for patient care every week. CRKP were detected, genome sequenced, and assigned to clones based on core genome analyses. The survival of four CRKP clones was determined under ICU conditions. Seventeen patients were in the ICU at the start of the study, and 99 were admitted afterwards. Six were positive patients, with four detected on initial screening and two during weekly monitoring. CRKP was detected from 76 of 3,699 (2.1%) environment samples, including from the immediate surroundings of 21 patients (five had CRKP from clinical samples and 16 did not). CRKP was not detected outside patient care areas. Among 49 CRKP sequenced isolates (nine from swabs, five from clinical samples, and 35 from environment) from 21 patients, 45 were ST11 and had blaKPC-2. These could be assigned to four clones, with either KL47 (n = 22) or KL64 (n = 23) capsular type. The two dominant clones survived >30 days under ICU conditions. In conclusion, environmental contamination of CRKP was extensive but usually transient. It had little impact on CRKP acquisition by ICU patients, highlighting the ability to control CRKP transmission through infection prevention efforts even in high-prevalence settings. IMPORTANCE Klebsiella pneumoniae can be an opportunistic pathogen with the oral cavity and gut the main origin. However, carbapenem-resistant Klebsiella pneumoniae (CRKP) can be found in patient surroundings and is a serious threat for human infections. Although the hospital environment, particularly sinks, has long been considered a potential reservoir of CRKP, the exact role of environmental contamination contributing to the acquisition and transmission of CRKP among patients remains largely unknown. To understand the link between environmental contamination in health care settings and colonization and infection of patients by CRKP, we performed a 3-month prospective study in a 20-bed medical ICU. Isolates were collected by active patient screening and were subsequently genome sequenced to describe the diversity of CRKP and the linkage of patients and environmental reservoirs. We found that the environmental contamination of CRKP was extensive, and CRKP clones were freely circulating in the ICU. Environmental contamination was not due to sharing the bed unit or sharing contaminated instruments but more likely resulted from the movement of health care workers. Very few patients acquired CRKP in the ICU, which is likely due to the fact that environmental contamination was usually transient when a routine cleaning protocol was complied. Although CRKP contamination in patient surroundings may be extensive, as long as routine environment cleaning protocols are appropriate and well implemented, the health care environment is unlikely to be a major source of CRKP colonization and infection in ICU patients. Reducing the high workload for ICU nurses may help minimize CRKP environmental contamination.

Handwashing Sink Contamination and Carbapenem-resistant Klebsiella Infection in the Intensive Care Unit: A Prospective Multicenter Study.

BACKGROUND: Handwashing sinks can become contaminated by carbapenem-resistant Klebsiella (CRK), including carbapenem-resistant Klebsiella pneumoniae (CRKP) and carbapenem-resistant Klebsiella oxytoca (CRKO), but whether they are major sources of CRK infections remains unknown. METHODS: We performed a prospective multicenter study in 16 intensive care units (ICUs) (9 general and 7 neonatal) at 11 hospitals. All sinks at these locations were sampled to screen CRK. All CRK clinical isolates recovered between 2 weeks before and 3 months after sampling in ICUs with CRK-positive sinks or other participating ICUs at the same hospital were collected. Whole-genome sequencing of all isolates was performed. Isolates of the same sequence type (ST) were assigned to clones by calling single-nucleotide polymorphisms. RESULTS: Among 158 sinks sampled, 6 CRKP and 6 CRKO were recovered from 12 sinks in 7 ICUs, corresponding to a 7.6% CRK contamination rate. Twenty-eight clinical isolates were collected, and all were CRKP. The 34 CRKP isolates belonged to 7 STs, including ST789 (n = 14, all had blaNDM-5); ST11 (n = 12, 5 belonged to KL64 and 7 to KL47, all had blaKPC-2); ST709 (n = 4, all had blaNDM-5); and ST16, ST20, ST1027, and ST2407 (n = 1 each). One particular ST789 clone caused an outbreak and contaminated a sink. ST11_KL47 sink isolates were likely the source of a cluster of clinical isolates. Two ST11_KL64 isolates belonged to a common clone but were from 2 hospitals. CONCLUSIONS: Contaminated sinks were not the major source of CRK in our local settings. ST789 blaNDM-5-carrying CRKP might represent an emerging lineage causing neonatal infections.

STEAP1 facilitates metastasis and epithelial-mesenchymal transition of lung adenocarcinoma via the JAK2/STAT3 signaling pathway.

Six-transmembrane epithelial antigen of prostate-1 (STEAP1) is a relatively newly identified gene target from prostate cancer, breast cancer, and gastric cancer. However, functions of STEAP1 in lung adenocarcinoma (LUAD) are still unknown. In the present study, we explored the molecular and cellular mechanisms of STEAP1 in LUAD. Western blot and Q-PCR were conducted to detect the protein and mRNA expressions respectively. The cell proliferation was tested by CCK8 assay. The effects of STEAP1 on the metastasis and epithelial-mesenchymal transition (EMT) of LUAD were evaluated by EdU assay, wound healing assay, and transwell migratory assay. H1650, H358, HCC827, H1299, H23, A549, H1693 were selected as human LUAD cell lines in the study. Results have shown that STEAP1 expression was up-regulated in LUAD cells compared with normal lung epithelial cells. Knockdowning of STEAP1 suppressed the proliferation, migration, and invasion of LUAD epithelial cells. Importantly, after comparing the proliferation, migration, and invasion of LUAD to the corresponding control groups treated in STAT3 inhibitor ADZ1480, we found that STEAP1 regulates EMT via Janus kinase 2/signal transducer and activator of transcription 3 (JAK2/STAT3) signaling pathway. In conclusion, STEAP1 can serve as a therapeutic target, and it may have important clinical implications for LUAD treatment.

Correlation analysis of levels of inflammatory cytokines and nitric oxide in peripheral blood with urine proteins and renal function in patients with gestational hypertension.

The aim of the study was to investigate correlations among inflammatory cytokines, nitric oxide (NO) level, urine protein, renal function and blood pressure in peripheral blood of patients with hypertensive disorder complicating pregnancy (HDCP). A total of 60 patients diagnosed with HDCP in the Obstetrics Department of Wuhan Children's Hospital, Tongji Medical College, Huazhong University of Science and Technology from May 2016 to April 2017 were selected. The patients were divided into the HDCP (n=20), mild pre-eclampsia (n=20) and severe pre-eclampsia (n=20) groups. Additionally, 20 healthy pregnant women were selected as the control group. General data of the patients were collected. NO, renal function and 24-h urine protein were measured. The systolic and diastolic blood pressure, C-reactive protein (CRP), tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) in the HDCP group was significantly higher than that in the control group. The CRP, TNF-α and IL-6 levels in the pre-eclampsia groups were higher than those in the gestational hypertension group (P<0.05). The NO level in peripheral blood of patients in the pre-eclampsia groups was lower than that in the gestational hypertension group (P<0.05). The levels of 24-h urine protein, homocysteine (Hcy), cystatin-C (Cys-C), serum creatinine (SCr), urea and ß2 microglobulin in the pre-eclampsia groups were higher than those in the gestational hypertension group (P<0.05). Gestational age and the levels of baseline blood pressure, inflammatory cytokines, 24-h urine protein and renal function have independent predictive value for the occurrence of HDCP (P<0.05). The results show that, 24-h urine protein, renal function and inflammatory cytokines are closely correlated with the occurrence of HDCP, which can reflect the severity and prognosis of the disease to a certain extent. In addition, it has important reference value for the assessment and treatment of the disease.

[Correlations of thyroid hormone with deceleration capacity of heart rate and heart rate variability in children with hyperthyroidism].

OBJECTIVE: To investigate deceleration capacity of heart rate (DC), acceleration capacity of heart rate (AC), and heart rate variability (HRV) in children with hyperthyroidism and the correlations of serum thyroid hormone levels with DC, AC, and HRV. METHODS: A total of 47 children with hyperthyroidism were enrolled as hyperthyroidism group and 50 healthy children were enrolled as control group. The subjects in the two groups underwent 24-hour ambulatory electrocardiography. The two groups were compared in terms of DC, AC, heart rate (HR), HRV parameters [standard deviation of normal-to-normal RR intervals (SDNN), standard deviation of average normal-to-normal RR intervals (SDANN), root mean square of successive differences between adjacent RR intervals (RMSSD), low-frequency power (LF), and high-frequency power (HF)]. The correlations of thyroid hormone indices [free triiodothyronine (FT3) and free thyroxin (FT4)] with DC, AC, and HRV were analyzed. RESULTS: Compared with the control group, the hyperthyroidism group had significantly lower DC, SDNN, SDANN, RMSSD, LF, and HF and significantly higher AC and HR (P<0.05). In the children with hyperthyroidism, serum FT3 and FT4 levels showed significant negative correlation with DC, SDNN, SDANN, RMSSD, LF, and HF and significant positive correlation with AC and HR (P<0.05). CONCLUSIONS: Children with hyperthyroidism have cardiac autonomic nerve dysfunction manifested as reduced vagal tone. Vagal tone decreases with the increasing serum thyroid hormone levels, suggesting an increased risk of cardiovascular disease.

[Effect of vitamin D deficiency on cardiac autonomic nerve function in obese pre-school children].

OBJECTIVE: To study the effect of vitamin D (VitD) deficiency on cardiac autonomic nerve function in obese pre-school children. METHODS: A total of 242 pre-school children with simple obesity were enrolled, and according to the serum 25-(OH) VitD level, they were divided into VitD deficiency group (76 children), VitD insufficiency group (83 children), and VitD sufficiency group (83 children). The three groups were compared in terms of deceleration capacity (DC) of heart rate, acceleration capacity (AC) of heart rate, and heart rate variability (HRV). The correlations of VitD level with DC, AC, and HRV were analyzed for the VitD insufficiency and VitD deficiency groups. RESULTS: The VitD deficiency group had the lowest DC, root mean square of successive differences between adjacent RR intervals (RMSSD), and low-frequency power (LF) and the highest AC (P<0.05). The VitD insufficiency group had significantly lower DC, RMSSD, and LF and significantly higher AC compared with the VitD sufficiency group (P<0.05). The VitD deficiency group had significantly lower standard deviation of normal-to-normal RR intervals (SDNN) and high-frequency power (HF) than the VitD sufficiency group (P<0.05). In the VitD deficiency group, VitD level was positively correlated with DC, SDNN, standard deviation of average normal-to-normal RR intervals, RMSSD , LF, and HF and was negatively correlated with AC (P<0.05). In the VitD insufficiency group, VitD level was negatively correlated with AC (P<0.05). CONCLUSIONS: Obese pre-school children with VitD insufficiency or deficiency have cardiac autonomic dysfunction, and cardiac vagal tone decreases with the reduction in VitD level.

[An analysis of cardiac autonomic nerve function in girls with idiopathic central precocious puberty].

OBJECTIVE: To investigate the cardiac autonomic nerve function in girls with idiopathic central precocious puberty (ICPP). METHODS: A total of 66 girls with ICPP were enrolled, among whom 36 were obese and 30 were not obese. A total of 68 age-matched healthy girls (normal controls) and 51 girls with simple obesity were enrolled as controls. All the subjects underwent 24-hour ambulatory electrocardiography, and deceleration capacity of heart rate (DC), acceleration capacity of heart rate (AC), and heart rate variability (HRV), and body mass index (BMI) were compared between groups. RESULTS: Compared with the normal control group, the ICPP group had significantly lower DC, standard deviation of normal-to-normal R-R intervals (SDNN), standard deviation of the average normal-to-normal intervals (SDANN), root mean square of successive differences (RMSSD), and high-frequency power (HF) and significantly higher AC and BMI. The ICPP group had significantly lower RMSSD and BMI than the simple obesity group (P<0.05). Compared with the ICPP girls without obesity, those with obesity had significantly lower DC, RMSSD, and HF and significantly higher AC and BMI (P<0.05). CONCLUSIONS: Cardiac autonomic dysfunction is seen in girls with ICPP, especially those with obesity, mainly presenting with reduced vagal tone.

[Cardiac autonomic nerve function in obese school-age children].

OBJECTIVE: To analyze the deceleration capacity (DC) of heart rate, acceleration capacity (AC) of heart rate, and heat rate variability (HRV) in obese school-age children, and to observe the correlations of BMI with DC, AC, and HRV in these children. METHODS: A total of 108 obese school-age children were selected, including 75 cases of ortholiposis and 33 cases of dyslipidemia. A total of 103 healthy school-age children were selected as control group. All the subjects underwent 24-hour ambulatory electrocardiography. The comparisons of DC, AC, and HRV were made between the obese and control groups, as well as between children with ortholiposis and dyslipidemia in the obese group. The correlations of BMI with DC, AC, and HRV were analyzed in the obese group. RESULTS: The obese group showed lower DC, standard deviation of normal-to-normal R-R intervals (SDNN), standard deviation of the average normal-to-normal intervals (SDANN), root mean square of successive differences (RMSSD), low-frequency power (LF), and high-frequency power (HF) than the control group. The AC of the obese group was significantly higher than that of the control group (P<0.05). In the obese group, children with dyslipidemia had significantly lower DC, SDNN, SDANN, RMSSD, LF, and HF, but significantly higher AC and BMI, as compared with those with ortholiposis (P<0.01). In the obese group, BMI was negatively correlated with DC, SDNN, SDANN, RMSSD, and HF (P<0.05), but positively correlated with AC (P<0.05). CONCLUSIONS: Obese school-age children have impaired autonomic nerve function, presenting with reduced vagal tone, which is particularly prominent in those with dyslipidemia. The more obese the children, the lower the vagal tone, which may increase the risks of cardiovascular diseases.

[Changes in ambulatory electrocardiographic findings after oral administration of low-dose propranolol in infants with hemangioma].

OBJECTIVE: To investigate the effects of oral administration of low-dose propranolol on heart rate variability (HRV), acceleration capacity (AC), deceleration capacity (DC), and cardiac conduction in the treatment of infantile hemangioma. METHODS: A total of 118 infants with hemangioma (≤1 year) were enrolled, and 24-hour ambulatory electrocardiography was performed before oral administration of low-dose propranolol and after one month of administration. The changes in time-domain indices [standard deviation of all normal sinus RR intervals (SDNN), standard deviation of all mean 5-minute RR intervals (SDANN), root mean squared successive difference (RMSSD), and percentage of successive normal sinus RR intervals >50 ms (PNN50)] and frequency-domain indices [low frequency (LF) and high frequency (HF)] for HRV, AC, and DC were observed, as well as abnormalities in cardiac conduction and other aspects after administration of propranolol. RESULTS: After administration of propranolol, the infants had significantly increased SDNN, RMSSD, LF, HF, and PNN50 (P<0.01), and significantly reduced AC, mean heart rate (HR) and minimum HR (P<0.01). The 24-hour ambulatory electrocardiographic findings showed a nonsignificantly higher abnormal rate after administration of propranolol. CONCLUSIONS: In the treatment of infantile hemangioma, propranolol can inhibit the activity of sympathetic nerve and block cardiac conduction, but without any serious adverse effect.

Ulinastatin- and thymosin α1-based immunomodulatory strategy for sepsis: A meta-analysis.

OBJECTIVE: This meta-analysis was performed to evaluate the efficacy of ulinastatin (UTI) and thymosin α1 (Tα1) based immunomodulatory strategy in sepsis patients. METHODS: A systematic search was made of MEDLINE, Cochrane, ISI Web of Science and SCOPUS databases. Randomized clinical trials on treatment of sepsis with the combination of ulinastatin and Tα1, compared with placebo, were reviewed. Studies were pooled to relative risk (RR) and weighted mean differences (WMD), with 95% confidence interval (CI). RESULTS: Six trials (enrolling 915 participants) met the inclusion criteria. Compared with placebo, the combination of ulinastatin and Tα1 presented significant effects on 28-day all-cause mortality (RR 0.67; 95% CI 0.57 to 0.80), 90-day all-cause mortality (RR 0.75; 95% CI 0.61 to 0.93), TNF-α (WMD -73.86ng/L; 95% CI -91.00 to -56.73ng/L), IL-6 (WMD -55.04ng/L; 95% CI -61.22 to -48.85ng/L), and duration of mechanical ventilation (WMD -2.26days; 95% CI -2.79 to -1.73days). CONCLUSIONS: Immunomodulatory therapy that combines ulinastatin and Tα1 significantly improves all-cause mortality, inflammatory mediators and duration of mechanical ventilation in subjects with sepsis.

[Infiltration of CD(4)(+)CD(25)(+) T cells into the allergic asthmatic airways caused by house dust mite antigen administration.].

OBJECTIVE: To investigate whether house dust mite (HDM) could induce CD(4)(+) CD(25)(+) T cells infiltration into asthmatic airways in patients vivo. METHODS: Ten subjects with asthma underwent initial bronchoscopy during which normal saline and HDM were administered to two sublobar segments separately. The second bronchoscopy were carried out and bronchoal lavage fluid from HDM-challenged sites and saline-challenged sites were separately taken 24 h later. The differential cell counts were determined, and the absolute number of each type was calculated. At the same time, CD(3)(+), CD(4)(+) and CD(4)(+) CD(25)(+) T cells were determined by flow-cytometric analysis. We compared cellular counts in airways without and after topical instillation of HDM. RESULTS: Eosinophile granulocyte cells of broncho-alveolar fluid in the HDM-challenged sites (1.4 +/- 0.1) x 10(6)/ml are more than it in control sites (0.3 +/- 0.1) x 10(6)/ml, P < 0.003. Lymphocyte cells of BALF in the HDM-challenged sites (2.2 +/- 0.3) x 10(6)/ml are more than it in control sites (0.3 +/- 0.1) x 10(6)/ml, P < 0.001; CD(4)(+) CD(25)(+)T cells of BALF in the HDM-challenged sites (784.0 +/- 281.3) cell/microl are more than it in control sites (7.7 +/- 3.6) cell/microl, P < 0.001. CONCLUSIONS: Our findings suggest that HDM is capable of inducing CD(4)(+) CD(25)(+) T cells recruitment into non-acute mild allergic asthmatic airways.