Identification of circulating biomarkers for differentiating patients with papillary thyroid cancers from benign thyroid tumors.

BACKGROUND: This study aimed to identify the potential circulating biomarkers of protein, mRNAs, and long non-coding RNAs (lncRNAs) to differentiate the papillary thyroid cancers from benign thyroid tumors. METHODS: The study population of 100 patients was classified into identification (10 patients with papillary thyroid cancers and 10 patients with benign thyroid tumors) and validation groups (45 patients with papillary thyroid cancers and 35 patients with benign thyroid tumors). The Sengenics Immunome Protein Array-combined data mining approach using the Open Targets Platform was used to identify the putative protein biomarkers, and their expression validated using the enzyme-linked immunosorbent assay. Next-generation sequencing by Illumina HiSeq was used for the detection of dysregulated mRNAs and lncRNAs. The website Timer v2.0 helped identify the putative mRNA biomarkers, which were significantly over-expressed in papillary thyroid cancers than in adjacent normal thyroid tissue. The mRNA and lncRNA biomarker expression was validated by a real-time polymerase chain reaction. RESULTS: Although putative protein and mRNA biomarkers have been identified, their serum expression could not be confirmed in the validation cohorts. In addition, seven lncRNAs (TCONS_00516490, TCONS_00336559, TCONS_00311568, TCONS_00321917, TCONS_00336522, TCONS_00282483, and TCONS_00494326) were identified and validated as significantly downregulated in patients with papillary thyroid cancers compared to those with benign thyroid tumors. These seven lncRNAs showed moderate accuracy based on the area under the curve (AUC = 0.736) of receiver operating characteristic in predicting the occurrence of papillary thyroid cancers. CONCLUSIONS: We identified seven downregulated circulating lncRNAs with the potential for predicting the occurrence of papillary thyroid cancers.

Fluoroquinolone resistance in Haemophilus influenzae from nursing home residents in Taiwan: correlation of MICs and mutations in QRDRs.

AIMS: To study the association between number and positions of mutations with MICs of fluoroquinolone non-susceptible Haemophilus influenzae. METHODS AND RESULTS: More than 40% of 48 H. influenzae isolated from nursing home residents were not susceptible to fluoroquinolone. Amino acid changes in the quinolone resistance determining regions, and correlation with MICs and inhibition zone diameters were analysed. All isolates with reduced susceptibility to fluoroquinolones (MIC ≥0·125 µg ml-1 ) had at least one mutation in gyrA at position 84 and were resistant to nalidixic acid. Compared to isolates with reduced susceptibility, resistant isolates were associated with mutations in gyrA at positions 88 and 134, and in parC at position 88 (P < 0·001). Inhibition zone diameter for nalidixic acid disk ≥23 mm may detect susceptible isolates. CONCLUSIONS: Reduced susceptibility to fluoroquinolones was associated with mutations at position 84 in gyrA. A further increase in fluoroquinolone MIC was associated with mutations in gyrA at positions 88 and 134, and parC at position 88. SIGNIFICANCE AND IMPACT OF THE STUDY: Due to limited resistant H. influenzae strains, prior studies on association between positions of mutations and fluoroquinolone MICs were inconclusive. The comparison of mutations between isolates with susceptibility, reduced susceptibility and high resistance supported the importance of the present study.

Distinct prognostic roles of HSPB1 expression in non-small cell lung cancer.

Lung cancer is the leading cause of cancer morbidity and mortality around world. Heat shock protein beta-1 (HSPB1) expression is aberrantly increased in non-small cell lung cancer (NSCLC) patients. However, the roles of HSPB1 expression in the prognosis of NSCLC are still elusive. In this study, we investigated the prognostic roles of HSPB1 in NSCLC by using "The Kaplan-Meier plotter" (KM plotter) database. Our data indicated that HSPB1 mRNA low expression was correlated to better overall survival (OS) for all NSCLC patients, hazard ratio (HR) 1.41 (1.24-1.61), p=1.1e-7, and better OS in lung adenocarcinoma (LUAD) patients, HR 1.81 (1.42-2.32), p=1.5e-06, but not in lung squamous cell carcinoma (LUSC) patients, HR 1.21 (0.94-1.55), p=0.14. In addition, mRNA low expression of HSPB1 is also significantly associated with better OS of NSCLC patients in different smoking status, in different chemotherapy status, in clinical stage I et II, as well as patients with successful surgery treatment. Our results indicated that HSPB1 expression may have distinct prognostic values in NSCLC patients, and may provide an effective clinical strategy to accurately predict the prognosis of NSCLC patients.

[Clinical significance of combined detection of urine NTX and serum ICTP for breast cancer patients with bone metastases].

OBJECTIVE: To study the clinical significance and prognostic value of combined detection of urinary N-terminal telopeptide of type Ⅰ collagen (NTx) and serum C-terminal telopeptide of type Ⅰ collagen (ICTP) in breast cancer patients with bone metastases. METHODS: Serum and urine samples from 68 women with advanced breast cancer who received the treatment in Jilin Cancer Hospital between October 2012 and October 2008 were collected before and 2 months after treatment. Among them, 35 patients had bone metastases (group A), including 12 cases with single bone metastasis and 23 cases with multiple bone metastases. 33 out of the 68 patients had other organ metastases (group B). 30 healthy females were included as the control group (group C). The levels of urine NTX and serum ICTP were measured by ELISA. RESULTS: The levels of NTx and ICTP of group A were significantly higher than those of groups B and C [NTx: (7.17±1.11) nmol/L vs. (2.08±0.22) nmol/L and (2.09±0.24) nmol/L, respectively, (P<0.05); ICTP: (7.75±1.14) ng/ml vs. (2.15±0.34) ng/ml and (2.22±0.31) ng/ml, respectively, (P<0.05)], while no significant difference was found between the groups B and C. Compared with the patients with single bone metastasis, the patients with ≥2 bone metastases had significantly higher NTx and ICTP levels [NTx: (7.69±0.93) nmol/L vs. (6.16±0.62) nmol/L, P<0.05; ICTP: (8.21±1.00) ng/ml) vs. (6.88±0.81) ng/ml (P<0.05)]. At two months after treatment, 40.0%(14/35) of patients with bone metastasis had partial remission (PR), 42.9%(15/35) of patients had stable disease (SD), and 6 patients with progressive disease (PD). Both urinary NTx and serum ICTP of the patients with PR and SD were significantly decreased compared with those before treatment (P<0.05). 10 cases of patients (28.6%) with bone metastases had skeletal-related events (SREs) during the treatment, including one PR patient (1/14, 7.1%), 5 SD patients (5/15, 33.3%) and 4 PD patients (4/6, 66.7%). CONCLUSION: The combined detection of urinary NTx and serum ICTP is of important significance for early diagnosis and efficacy evaluation and to control skeletal-related adverse events in breast cancer patients with bone metastases.

[Comparison of clinical outcomes of patients with non-small cell lung cancer harboring different types of epidermal growth factor receptor sensitive mutations after first-line EGFR-TKI treatment].

OBJECTIVE: To analyze whether there are differences in the efficacy and clinical outcomes to first-line tyrosine kinase inhibitors (TKI) therapy in Chinese patients with metastatic non-small-cell lung cancer (NSCLC) harboring different subtypes of epidermal growth factor receptor (EGFR) mutations. METHODS: A retrospective analysis was made on the clinical data of stage ⅢB or Ⅳ NSCLC patients who were diagnosed by histology and received EGFR mutation test, in order to confirm if there is any difference between the therapeutic effects of TKIs as first-line therapy and the prognosis. RESULTS: A total of 165 patients harboring EGFR exon 19 deletion (19del, n=71), exon 21 L858R mutation (L858R, n=80) or uncommon sensitive mutation (n=14) were treated with EGFR-TKIs for first-line treatment. The comparison among different groups of common types of sensitive mutations revealed that the objective response rate (ORR) of group 19del and group L858R were 57.8% and 45.0%, respectively (P=0.113). The disease control rate (DCR) was 93.0% and 93.8%, respectively (P=0.158). However, the ORR and DCR of uncommon sensitive mutation were 35.7% and 78.6%, which were significantly lower than that of the group 19del (P=0.035) and group L858R (P=0.020). The median progression-free survival (PFS) of group 19del, group L858R and uncommon sensitive mutation were 14.0 months, 7.8 months and 5.1 months, respectively (P=0.001). The median PFS of the group 19del was significantly longer than that of the group L858R (P=0.009). The median overall survival (OS) of these three groups had significant difference (22.8, 15.2 and 10.0 months) (P=0.048). But those of group 19del and group L858R were similar (P=0.152). The multivariate analysis indicated that ECOG-PS (P=0.030), cigarette smoking (P=0.013) and EGFR mutation types (P=0.034) are independent prognostic factors of OS. CONCLUSIONS: For Chinese NSCLC patients with different types of sensitive mutation, there are differences between their efficacy and prognosis of EGFR-TKIs as first-line treatment. The PFS of group 19del is obviously longer than that of other types of sensitive mutations, but have no significant differences in OS. The PFS and OS of patients with common types of sensitive mutation are better than those with uncommon sensitive mutation.

Application of a theoretical framework to foster a cardiac-diabetes self-management programme.

AIM: This paper analyses and illustrates the application of Bandura's self-efficacy construct to an innovative self-management programme for patients with both type 2 diabetes and coronary heart disease. BACKGROUND: Using theory as a framework for any health intervention provides a solid and valid foundation for aspects of planning and delivering such an intervention; however, it is reported that many health behaviour intervention programmes are not based upon theory and are consequently limited in their applicability to different populations. The cardiac-diabetes self-management programme has been specifically developed for patients with dual conditions with the strategies for delivering the programme based upon Bandura's self-efficacy theory. This patient group is at greater risk of negative health outcomes than that with a single chronic condition and therefore requires appropriate intervention programmes with solid theoretical foundations that can address the complexity of care required. SOURCES OF EVIDENCE: The cardiac-diabetes self-management programme has been developed incorporating theory, evidence and practical strategies. DISCUSSION: This paper provides explicit knowledge of the theoretical basis and components of a cardiac-diabetes self-management programme. Such detail enhances the ability to replicate or adopt the intervention in similar or differing populations and/or cultural contexts as it provides in-depth understanding of each element within the intervention. CONCLUSION: Knowledge of the concepts alone is not sufficient to deliver a successful health programme. Supporting patients to master skills of self-care is essential in order for patients to successfully manage two complex, chronic illnesses. IMPLICATIONS FOR NURSING PRACTICE OR HEALTH POLICY: Valuable information has been provided to close the theory-practice gap for more consistent health outcomes, engaging with patients for promoting holistic care within organizational and cultural contexts.

Pneumonia caused by Aeromonas species in Taiwan, 2004-2011.

We investigated the clinical characteristics of patients with pneumonia caused by Aeromonas species. Patients with pneumonia caused by Aeromonas species during the period 2004 to 2011 were identified from a computerized database of a regional hospital in southern Taiwan. The medical records of these patients were retrospectively reviewed. Of the 84 patients with pneumonia due to Aeromonas species, possible Aeromonas pneumonia was diagnosed in 58 patients, probable Aeromonas pneumonia was diagnosed in 18 patients, and pneumonia due to Aeromonas was conclusively diagnosed in 8 patients. Most of the cases of Aeromonas pneumonia developed in men and in patients of advanced age. A. hydrophila (n = 50, 59.5 %) was the most common pathogen, followed by A. caviae (n = 24, 28.6 %), A. veronii biovar sobria (n = 7, 8.3 %), and A. veronii biovar veronii (n = 3, 3.6 %). Cancer (n = 37, 44.0 %) was the most common underlying disease, followed by diabetes mellitus (n = 27, 32.1 %). Drowning-associated pneumonia developed in 6 (7.1 %) patients. Of 47 patients who were admitted to the intensive care ward, 42 patients developed acute respiratory failure and 24 of those patients died. The overall in-hospital mortality rate was significantly associated with liver cirrhosis, cancer, initial presentation of shock, and usage of mechanical ventilation. In conclusion, Aeromonas species should be considered as one of the causative pathogens of severe pneumonia, especially in immunocompromised patients, and should be recognized as a cause of drowning-associated pneumonia. Cirrhosis, cancer, and shock as the initial presenting symptom are associated with poor outcome.

Reentrance of interface superconductivity in a high-Tc cuprate heterostructure.

Increasing the carrier density in a Mott insulator by chemical doping gives rise to a generic superconducting dome in high temperature superconductors. An intriguing question is whether a second superconducting dome may exist at higher dopings. Here we heavily overdope La2-xSrxCuO4 (0.45 ≤ x ≤ 1.0) and discover an unprecedented reentrance of interface superconductivity in La2-xSrxCuO4 /La2CuO4 heterostructures. As x increases, the superconductivity is weakened and completely fades away at x = 0.8; but it revives at higher doping and fully recovers at x = 1.0. This is shown to be correlated with the suppression of the interfacial charge transfer around x = 0.8 and the weak-to-strong localization crossover in the La2-xSrxCuO4 layer. We further construct a theoretical model to account for the sophisticated relation between charge localization and interfacial charge transfer. Our work advances both the search for and control of new superconducting heterostructures.

Extended X-ray absorption fine structure of dynamically-compressed copper up to 1 terapascal.

Large laser facilities have recently enabled material characterization at the pressures of Earth and Super-Earth cores. However, the temperature of the compressed materials has been largely unknown, or solely relied on models and simulations, due to lack of diagnostics under these challenging conditions. Here, we report on temperature, density, pressure, and local structure of copper determined from extended x-ray absorption fine structure and velocimetry up to 1 Terapascal. These results nearly double the highest pressure at which extended x-ray absorption fine structure has been reported in any material. In this work, the copper temperature is unexpectedly found to be much higher than predicted when adjacent to diamond layer(s), demonstrating the important influence of the sample environment on the thermal state of materials; this effect may introduce additional temperature uncertainties in some previous experiments using diamond and provides new guidance for future experimental design.

Negative argininosuccinate synthetase expression in melanoma tumours may predict clinical benefit from arginine-depleting therapy with pegylated arginine deiminase.

BACKGROUND: Arginine-depleting therapy with pegylated arginine deiminase (ADI-PEG20) was reported to have activity in advanced melanoma in early phase I-II trial, and clinical trials are currently underway in other cancers. However, the optimal patient population who benefit from this treatment is unknown. METHODS: Advanced melanoma patients with accessible tumours had biopsy performed before the start of treatment with ADI-PEG20 and at the time of progression or relapse when amenable to determine whether argininosuccinate synthetase (ASS) expression in tumour was predictive of response to ADI-PEG20. RESULTS: Twenty-seven of thirty-eight patients treated had melanoma tumours assessable for ASS staining before treatment. Clinical benefit rate (CBR) and longer time to progression were associated with negative expression of tumour ASS. Only 1 of 10 patients with ASS-positive tumours (ASS+) had stable disease, whereas 4 of 17 (24%) had partial response and 5 had stable disease, when ASS expression was negative (ASS-), giving CBR rates of 52.9 vs 10%, P=0.041. Two responding patients with negative ASS expression before therapy had rebiopsy after tumour progression and the ASS expression became positive. The survival of ASS- patients receiving at least four doses at 320 IU m(-2) was significantly better than the ASS+ group at 26.5 vs 8.5 months, P=0.024. CONCLUSION: ADI-PEG20 is safe and the drug is only efficacious in melanoma patients whose tumour has negative ASS expression. Argininosuccinate synthetase tumour positivity is associated with drug resistance and tumour progression.

Phase-specific cone beam computed tomography reduces reconstructed volume loss of moving phantom.

PURPOSE: The accurate volumetric calculation of moving targets/organs is required to use cone-beam computed tomography (CBCT) for replanning purposes. This study was aimed to correct the reconstructed volume losses of moving phantoms by phase-specific CBCT. MATERIALS AND METHODS: Planning fan-beam CT (FBCT) of five hepatobiliary/gastrointestinal/pancreatic cancer patients were acquired under active breathing control and compared with free-breathing CBCT for kidney volumes. Three different-sized ball phantoms were scanned by FBCT and CBCT. Images were imported to a planning system to compare the reconstructed volumes. The phantoms were moved longitudinally on an oscillator with different amplitudes/frequencies. The phase-specific projections of CBCT for moving phantoms were selected for volume reconstruction. RESULTS: The differences in reconstructed volumes of static small, medium, large phantoms between FBCT and CBCT were - 6.7%, - 2.3%, and - 2.0%, respectively. With amplitudes of 7.5-20 mm and frequencies of 8-16 oscillations/min, volume losses on CBCT were comparable with FBCT in large moving phantoms (range 9.1-27.2%). Amplitudes were more subject to volume losses than frequencies. On phase-specific CBCT, volume losses were reduced to 2.3-6.5% by reconstruction using 2-3 projections at end/midoscillation phase. CONCLUSION: Amplitude had more impact than frequency on volume losses of moving phantoms on CBCT. Phase-specific CBCT reduced volume losses.

Epidemiology, disease spectrum and economic burden of non-typhoidal Salmonella infections in Taiwan, 2006-2008.

The purpose of this study was to understand the seasonal, geographical and clinical characteristics of Taiwanese patients hospitalized for non-typhoidal Salmonella (NTS) infections and their economic burden. Hospital data obtained from the Taiwan National Health Insurance (NHI) database between 2006 and 2008 were analysed. Infants had the highest annual incidence of 525 cases/100 000 person-years. Elderly patients aged >70 years had the highest in-hospital mortality rate (2·6%). Most (82·6%) gastroenteritis occurred in children aged <10 years. Septicaemia, pneumonia, arthritis and osteomyelitis occurred mainly in patients aged >50 years. A median medical cost for NTS-associated hospitalizations was higher for patients with septicaemia than for those with gastroenteritis. Seasonal variation of NTS-associated hospitalizations was correlated with temperature in different areas of Taiwan. In summary, infants had a high incidence of NTS-associated hospitalizations. However, the elderly had a higher in-hospital mortality rate and more invasive NTS infections than children.

Non-typhoidal Salmonella bacteraemia in elderly patients: an increased risk for endovascular infections, osteomyelitis and mortality.

Non-typhoidal Salmonella (NTS) is a common pathogen causing foodborne infections, bacteraemia, and extra-intestinal focal infections (EFIs) in humans. The study compares the clinical characteristics of elderly patients with NTS bacteraemia with those of young adults. Of 272 adults with NTS bacteraemia identified in this study, 162 (59·6%) were aged ⩾55 years. EFIs were observed in 36% of the 162 patients. The most common EFIs in the elderly patients (⩾55 years) was mycotic aneurysm, followed by pulmonary infections and bone/joint infections. Elderly patients more often had chronic heart, lung, renal and malignant diseases, had more EFIs, and a higher 30-day mortality rate. Independent factors of 30-day mortality in elderly patients were solid-organ tumour [adjusted odds ratio (aOR) 4·4, P=0·003], mycotic aneurysm (aOR 3·7, P=0·023) and shock (aOR 12·1, P<0·0001). HIV infection, autoimmune diseases, and receipt of immunosuppressive therapy were more often observed in young patients.

Peer supporters for cardiac patients with diabetes: a randomized controlled trial.

AIMS: To determine whether incorporation of patient peer supporters in a Cardiac-Diabetes Self-Management Program (Peer-CDSMP) led to greater improvement in self-efficacy, knowledge and self-management behaviour in the intervention group compared to a control group. BACKGROUND: Promoting improved self-management for those with diabetes and a cardiac condition is enhanced by raising motivation and providing a model. Peer support from former patients who are able to successfully manage similar conditions could enhance patient motivation to achieve better health outcomes and provide a model of how such management can be achieved. While studies on peer support have demonstrated the potential of peers in promoting self-management, none have examined the impact on patients with two co-morbidities. METHODS: A randomized controlled trial was used to develop and evaluate the effectiveness of the Peer-CDSMP from August 2009 to December 2010. Thirty cardiac patients with type 2 diabetes were recruited. The study commenced in an acute hospital, follow-up at participants' homes in Brisbane, Australia. RESULTS: While both the control and intervention groups had improved self-care behaviour, self-efficacy and knowledge, the improvement in knowledge was significantly greater for the intervention group. CONCLUSIONS: Significant improvement in knowledge was achieved for the intervention group. Absence of significant improvements in self-efficacy and self-care behaviour represents an inconclusive effect; further studies with larger sample sizes are recommended.

Effect analysis of sacral canal therapy combined with Fufang Wulingzhi Tangjiang in the treatment of residual root pain after lumbar surgery.

OBJECTIVE: To observe the clinical effect of a combination of traditional Chinese and western medicine (sacral canal therapy combined with compound Fufang Wulingzhi Tangjiang) in the treatment of residual root pain after lumbar surgery. PATIENTS AND METHODS: From January 2019 to December 2020, 538 patients with residual root pain due to lumbar degenerative diseases were treated in our hospital [open decompression discectomy (ODD), Percutaneous Endoscopic Lumbar Discectomy (PELD) or Transforminal Lumbar Interbody Fusion (TLIF)]. They were randomly divided into control group (basic treatment + celecoxib), observation group 1 (basic treatment + compound Fufang Wulingzhi Tangjiang), observation group 2 (basic treatment + sacral canal therapy) and observation group 3 (basic treatment + sacral canal therapy + Fufang Wulingzhi Tangjiang). Follow-up 3-12 months. The therapeutic effect, VAS score, JOA score, treatment cost, complications, serum interleukin-6 (IL-6), interleukin-1 (IL-1) and tumor necrosis factor-a (TNF-α) were recorded and compared before treatment, 1 week after treatment, 2 weeks after treatment, 1 month after treatment, and the last follow-up. RESULTS: The treatment effect, VAS score, JOA, and treatment cost in the observation group were better than those in the control group (p < 0.05). There were significant differences in the above-mentioned indexes between the observation group 3 and the control group, observation group 1, and observation group 2 (p < 0 01). Inflammatory factors (IL-6, IL1, TNF-α) in the observation group were lower than those in the control group (p < 0 05). Inflammatory factors in observation group 3 were significantly lower than those in the control group, observation group 1, and observation group 2 (p < 0 01). CONCLUSIONS: Sacral canal injection combined with Fufang Wulingzhi Tangjiang can be effective in the treatment of postoperative root pain of lumbar degenerative diseases, which can reduce inflammatory factors such as IL-6, IL-1ß and TNF-α. It has the advantages of quick effect, short treatment time, low cost, high safety, in line with the concept of ERAS, easily accepted by patients and their families, and worthy of further popularizing and applying in clinic.

[A multicenter study on childhood Hodgkin lymphoma treated with HL-2013 regimen in China].

Objective: To evaluate the efficacy of the Hodgkin lymphoma (HL)-2013 regimen in the treatment of children with HL, and to investigate the prognostic factors of childhood HL. Methods: Clinical data of 145 children (aged ≤18 years) with newly diagnosed HL, treated with HL-2013 regimen in 8 tertiary referral centers for childhood cancer from August 2011 to April 2021 were analyzed retrospectively. All the diagnosis were confirmed by histopathological morphology and immunohistochemical examination. The clinical characteristics and treatment outcomes were summarized, and the patients were divided into different groups according to clinical characteristics. Kaplan-Meier method was used for survival analysis, and the comparison of survival rates between groups was performed with Log-rank test. Results: Of the 145 cases, there were 115 males and 30 females, the age at diagnosis was 7.9 (5.8, 10.6) years. Cervical lymph node enlargement (114 cases, 78.6%) was the common symptom of the disease, and 57 patients (39.3%) were accompanied by large masses. The most common pathological classification was mixed cell type (93 cases, 64.1%). According to the Ann Arbor staging system, there were 9 cases of stage Ⅰ, 62 cases of stage Ⅱ, 45 cases of stage Ⅲ, 29 cases of stage Ⅳ. According to the risk stratification: there were 14 cases of low-risk group, 76 cases of medium-risk group and 55 cases of high-risk group. Of all patients, 68 cases (46.9%) achieved an early complete remission (CR) after 2 courses of chemotherapy, and the CR rate was 93.8% (136/145) after first-line treatment. Disease recurrence or progression occurred in 22 cases (15.2%). Of all patients, 125 cases survived, 6 cases died and 14 cases were lost to follow-up. Among the survived cases, 123 cases were continuously at CR state,and the follow-up time was 55 (40, 76) months. The 5-year overall survival (OS) and event free survival (EFS) rates were (95.3±1.9)% and (84.2±3.0)% for the entire group, respectively. 5-year OS and EFS rates for patients with stage Ⅲ-Ⅳ were both lower than those for patients with stage Ⅰ-Ⅱ (χ2=6.28 and 7.58, both P<0.05), the 5-year OS and EFS rates for patients in high-risk group were both lower than those for patients in low-risk and medium-risk group (χ2=10.93, 7.79, both P<0.05). The 5-year OS rates for the patient with early CR and without early CR were 100.0% and (90.9±3.6)% (χ2=5.77, P=0.016). EFS rates for the patient with early CR (68 cases) and without early CR (77 cases) were (93.8±3.0)% and (75.8±5.0)% (χ2=8.78, P=0.003). Conclusions: HL-2013 regimen is significantly effective in the treatment of pediatric HL. However, the patients in high-risk group and those without early CR are prone to disease recurrence or progression. Stage Ⅲ-Ⅳ and without early CR were associated with worse prognosis.

In vivo evolution of an emerging zoonotic bacterial pathogen in an immunocompromised human host.

Zoonotic transfer of animal pathogens to human hosts can generate novel agents, but the genetic events following such host jumps are not well studied. Here we characterize the mechanisms driving adaptive evolution of the emerging zoonotic pathogen Bordetella hinzii in a patient with interleukin-12 receptor ß1 deficiency. Genomic sequencing of 24 B. hinzii isolates cultured from blood and stool over 45 months revealed a clonal lineage that had undergone extensive within-host genetic and phenotypic diversification. Twenty of 24 isolates shared an E9G substitution in the DNA polymerase III ε-subunit active site, resulting in a proofreading deficiency. Within this proofreading-deficient clade, multiple lineages with mutations in DNA repair genes and altered mutational spectra emerged and dominated clinical cultures for more than 12 months. Multiple enzymes of the tricarboxylic acid cycle and gluconeogenesis pathways were repeatedly mutated, suggesting rapid metabolic adaptation to the human environment. Furthermore, an excess of G:C > T:A transversions suggested that oxidative stress shaped genetic diversification during adaptation. We propose that inactivation of DNA proofreading activity in combination with prolonged, but sub-lethal, oxidative attack resulting from the underlying host immunodeficiency facilitated rapid genomic adaptation. These findings suggest a fundamental role for host immune phenotype in shaping pathogen evolution following zoonotic infection.

LncRNA NEAT1 promotes the progression of sepsis-induced myocardial cell injury by sponging miR-144-3p.

OBJECTIVE: Sepsis is a systemic inflammatory response that can lead to the dysfunction of many organs, including the cardiac one. Long noncoding RNAs (lncRNAs) have been shown to be involved in multiple organ injuries induced by sepsis. However, the regulatory effect of nuclear enriched abundant transcript 1 (NEAT1) on sepsis-induced myocardial injury remains to be explored. MATERIALS AND METHODS: The sepsis models of myocardial cell injury were constructed using lipopolysaccharide (LPS). Cell counting kit-8 (CCK-8) assay was used to detect cell viability. Flow cytometry was performed to assess cell apoptosis. Moreover, the levels of apoptosis-related and nuclear factor-kappa B (NF-κB) signaling pathway-related proteins were evaluated by Western blot (WB) analysis. Besides, the contents of inflammatory cytokines were tested by enzyme-linked immunosorbent assay (ELISA). The expression levels of NEAT1 and microRNA-144-3p (miR-144-3p) were determined by quantitative Real Time-Polymerase Chain Reaction (qRT-PCR). In addition, Dual-Luciferase reporter and RNA immunoprecipitation (RIP) assays were used to verify the interaction between NEAT1 and miR-144-3p. RESULTS: LPS could induce myocardial cell injury to construct sepsis models. NEAT1 was upregulated in LPS-treated myocardial cells, and its knockdown promoted viability, suppressed apoptosis, and relieved inflammatory response in LPS-induced myocardial cell injury. MiR-144-3p was downregulated in LPS-treated myocardial cells, and the effect of its overexpression on LPS-induced myocardial cell injury was similar to the effect of NEAT1 knockdown. Besides, miR-144-3p could be sponged by NEAT1, and its inhibitor could reverse the effect of NEAT1 knockdown on LPS-induced myocardial cell injury. Moreover, NEAT1 and miR-144-3p could regulate the activity of NF-κB signaling pathway. CONCLUSIONS: LncRNA NEAT1 could interact with miR-144-3p to regulate sepsis-induced myocardial cell injury through the NF-κB signaling pathway, which might provide a new theoretical basis for the study on the effect of sepsis treatment.