Cryomicroneedle delivery of nanogold-engineered Rhodospirillum rubrum for photochemical transformation and tumor optical biotherapy.

Tumor metabolite regulation is intricately linked to cancer progression. Because lactate is a characteristic metabolite of the tumor microenvironment (TME), it supports tumor progression and drives immunosuppression. In this study, we presented a strategy for antitumor therapy by developing a nanogold-engineered Rhodospirillum rubrum (R.r-Au) that consumed lactate and produced hydrogen for optical biotherapy. We leveraged a cryogenic micromolding approach to construct a transdermal therapeutic cryomicroneedles (CryoMNs) patch integrated with R.r-Au to efficiently deliver living bacterial drugs. Our long-term storage studies revealed that the viability of R.r-Au in CryoMNs remained above 90%. We found that the CryoMNs patch was mechanically strong and could be inserted into mouse skin. In addition, it rapidly dissolved after administering bacterial drugs and did not produce by-products. Under laser irradiation, R.r-Au effectively enhanced electron transfer through Au NPs actuation into the photosynthetic system of R. rubrum and enlarged lactate consumption and hydrogen production, thus leading to an improved tumor immune activation. Our study demonstrated the potential of CryoMNs-R.r-Au patch as a minimally invasive in situ delivery approach for living bacterial drugs. This research opens up new avenues for nanoengineering bacteria to transform tumor metabolites into effective substances for tumor optical biotherapy.

A prediction model for the efficacy of continuous positive airway pressure on bronchiolitis.

Objectives: Prediction of the efficacy of continuous positive airway pressure (CPAP) on bronchiolitis is necessary for timely treatment. This study aims to establish a nomogram for efficacy of CPAP on bronchiolitis, and compares accuracy with Pediatric Risk of Mortality III (PRISM III), Brighton Pediatric Early Warning Score (Brighton PEWS) and Pediatric Critical Illness Score (PCIS). Methods: From February 2014 to December 2020, data on children diagnosed with bronchiolitis and treated with CPAP in Chongqing was collected. The nomogram was evaluated by using multivariate logistic regression analysis. We compared the predictive value of model with PRISM III, PEWS and PCIS. Results: A total of 510 children were included. The nomogram prediction model including fever, APTT, white blood cells, serum potassium concentration, lactic acid, immunodeficiency, atelectasis, lung consolidation, congenital airway dysplasia and congenital heart disease was established. The AUC of the nomogram was 0.919 in the training set and 0.947 in the validating set. The model fitted well, as evidenced by the calibration curve and Hosmer-Lemeshow goodness-of-fit test. We discovered that the nomogram significantly performed better than PRISM III, PCIS and PEWS. Conclusions: A nomogram including ten factors for predicting the efficacy of CPAP on bronchiolitis was established. It had higher performance than the PRISM III, PCIS, and PEWS in terms of clinical benefits.

Hypoxia-alleviated sonodynamic therapy based on a hybrid protein oxygen carrier to enhance tumor inhibition.

Sonodynamic therapy (SDT) is a highly attractive therapy due to its advantages of being non-invasive and having good penetration depth, but tumor hypoxia extremely restricts its therapeutic effect. Here, a novel oxygen-enhanced hybrid protein nanosonosensitizer system (MnPcS@HPO) is designed using human serum albumin (HSA) and hemoglobin (Hb) through disulfide reconfiguration, followed by encapsulating Mn-phthalocyanine (MnPcS), aiming to develop O2 self-supplementing nanoparticles (NPs) for enhanced SDT. Benefitting from the O2-carrying ability of Hb and the tumor-targeting property of HSA, the MnPcS@HPO NPs are able to target tumor sites and alleviate hypoxia. Meanwhile, as a sonosensitizer, MnPcS is excited under US irradiation and activates dioxygen to generate abundant singlet oxygen (1O2), resulting in oxidative damage of tumor cells. Guided by photoacoustic and magnetic resonance dual-modal imaging, the MnPcS@HPO NPs alleviate tumor hypoxia and achieve good SDT efficiency for suppressing tumor growth. This work presents a novel insight into enhanced SDT antitumor activity through natural protein-mediated tumor microenvironment improvement.

Biomarker-based score for predicting in-hospital mortality of children admitted to the intensive care unit.

This study aims to establish a new scoring system based on biomarkers for predicting in-hospital mortality of children admitted to the pediatric intensive care unit (PICU). The biomarkers were chosen using the least absolute shrinkage and selection operator (LASSO)-logistic regression in this observational case-control study. The performance of the new predictive model was evaluated by the area under the receiver operating characteristic curve (AUC). Calibration plot was established to validate the new score accompanied by the Hosmer-Lemeshow test. There were 8818 patients included in this study. Finally, six predictors were included in the LASSO-regression model. Albumin <40 g/L, lactate dehydrogenase >452 U/L, lactate >3.2 mmol/L, urea >5.6 mmol/L, arterial PH <7.3 and glucose >6.9 mmol/L were treated as risk factors for higher mortality. The new score ranged from 1 to 6 among all the included patients. In the training set, the AUC of the probability of in-hospital mortality for the new predictive model was 0.81 (95% CI 0.79 to 0.84), which is larger than for the Pediatric Critical Illness Score (PCIS) (0.69, 95% CI 0.66 to 0.72). Similarly, in the validating set, the AUC of the probability of in-hospital mortality was larger for the new score (0.80, 95% CI 0.77 to 0.84) than for PCIS (0.67, 95% CI 0.63 to 0.72). The calibration plot and Hosmer-Lemeshow test showed excellent calibration. The calculated ORs showed a trend that higher scores indicated higher risk of death (p value for trend <0.001). In summary, this study develops and validates a totally biomarker-based new score to predict in-hospital mortality for pediatric patients admitted to PICU. More attention and more positive care and treatment should be given to children with a higher score.

The Effects and Safety of Continuous Positive Airway Pressure in Children with Bronchiolitis: A Systematic Review and Meta-Analysis.

OBJECTIVES: To evaluate the effects and safety of continuous positive airway pressure (CPAP) for initial respiratory management of bronchiolitis. METHODS: PubMed, EMBASE, Cochrane Library, CNKI, Wanfang data and CQ VIP were searched until 17 June 2020. Randomized controlled trials (RCTs) which investigated the effect of CPAP for bronchiolitis were included. RESULTS: Twenty-seven RCTs met the eligibility criteria. In the comparison of CPAP versus standard oxygen therapy, CPAP can reduce the length of stay (LOS) in hospital, respiratory rate (RR), PaCO2, heart rate, mechanical ventilation and increase PaO2, but the SpO2 and PH were not improved. In the comparison of CPAP versus high-flow nasal cannula, CPAP can reduce treatment failure, but the PICU LOS, Incidence of intubation, RR, Modified Woods Clinical Asthma Score were not decreased. Treatment failure may be less in helmet comparing with the mask though there was no quantitative analysis. CONCLUSION: CPAP for the initial respiratory management significantly benefit children with bronchiolitis, the delivery of CPAP by helmet may be a better choice. More high-quality research is needed to confirm the conclusion.

Associations of hand washing frequency with the incidence of illness: a systematic review and meta-analysis.

BACKGROUND: Hand hygiene is one of the ways to prevent the spread of diseases. Our aim was to explore the relationship between hand washing frequency and the impact on disease, and give recommendations on the number of times to wash hands. METHODS: We searched seven electronic databases from their inception to April 11, 2020, and reference lists of related reviews for all studies on hand washing frequency and disease prevention. The Review Manager 5.3. software was used to conduct a meta-analysis. We assessed the risk of bias of included studies, and quality of evidence of the main findings. RESULTS: A total of eight studies were included. The results of the meta-analysis showed that there was no statistical significance between the effect of disease prevention and washing more than 4 times/day compared to not [odds ratio (OR) =0.61, 95% confidence interval (CI): 0.37 to 1.01]. The results of a case-control study showed that compared with hand washing ≤4 times/day, hand washing 5-10 times/day (OR =0.75, 95% CI: 0.63 to 0.91) and hand washing >10 times/day (OR =0.65, 95% CI 0.53 to 0.80) could reduce the risk of disease infection. There was no statistical significance advantage to hand washing more than 10 times/day compared to 5-10 times/day (OR =0.86, 95% CI: 0.70 to 1.06). Comparing hand washing ≤10 times/day with hand washing >10 times/day, increased hand washing was a protective factor against infection (OR =0.59, 95% CI: 0.36 to 0.97). CONCLUSIONS: The more frequently hands were washed, the lower risk of disease. So far however, there is no high-quality evidence indicating the best range of hand washing frequency for disease prevention.

Diagnostic accuracy of time to first positivity of blood cultures for predicting severe clinical outcomes in children with pneumonia-related bacteremia.

Early recognition of severe clinical outcomes in children with pneumonia-related bacteremia is vitally important because of the high mortality. This study aims to explore risk factors for severe clinical outcomes in children with pneumonia-related bacteremia and evaluate the value of time to first positive blood cultures (TTFP) in predicting prognosis. Children with pneumonia-related bacteremia in Children's Hospital of Chongqing Medical University were included (January 2013-May 2019), respectively. TTFP and clinical parameters were collected and analyzed. The area under the curve (AUC)-receiver operating characteristic was used to evaluate the discrimination ability of TTFP. Multivariate logistic regression tests were performed to evaluate the association between TTFP and severe clinical outcomes. A total of 242 children with pneumonia-related bacteremia were included. The least absolute shrinkage and selection operator (LASSO) regression analysis identified TTFP, serum albumin (ALB) and lactic dehydrogenase (LDH) as predictors of in-hospital mortality. Multivariate logistic regression analysis showed that shorter TTFP (OR 0.94; 95% CI 0.89 to 0.97; p<0.01), lower ALB level (OR 0.93; 95% CI 0.89 to 0.98; p<0.01) and higher LDH level (OR 1.001; 95% CI 1.000 to 1.001; p<0.01) were risk factors for in-hospital mortality in children with pneumonia-related bacteremia. AUC of TTFP for predicting in-hospital mortality was 0.748 (95% CI 0.668 to 0.829). Shorter TTFP (≤16 hours) was associated with in-hospital mortality and septic shock. TTFP plays an important role in predicting severe clinical outcomes in children with pneumonia-related bacteremia.