Single-frequency orbital angular momentum switchable modes from a microchip laser.

We demonstrate the direct generation of single-frequency switchable orbital angular momentum (OAM) modes in a 1 µm wavelength range using a Nd:YVO4 microchip laser. The 808 nm laser diode pump beam is shaped into annular through an axicon associated with a lens. By adjusting the diameter and power of the annular pump beam, various OAM modes with different mode volumes can oscillate inside the Nd:YVO4 microchip. Moreover, a single-frequency output is also available due to the short cavity of the microchip. In the proof-of-principle experiment, single-frequency twofold multiplexed OAM modes | ± 1> and | ± 2> are generated, with experimentally measured fidelity higher than 96%. This work presents a compact and versatile single-frequency OAM source and will inspire multiple advanced scenarios ranging from classical to quantum photonics.

Resilience and adaptation: a mixed-methods exploration of COVID-19's influence on neonatal residency education in China.

BACKGROUND: This study aimed to assess the impact of the pandemic of the coronavirus disease 2019 (COVID-19) on neonatology residency training in a tertiary children's hospital in Chongqing, located in southwest China. Specifically, the study encompassed the effects on residents' education, lived experiences, well-being, and the quality of neonatal care delivered. As higher educational institutions adapt to the post-COVID-19 era after the pandemic disruption, it is imperative that educational designers/academics learn from their experiences and challenges in curriculum design and delivery, ensuring quality and relevance in education. METHODS: This study employed a mixed-methods approach to investigate the influence of the COVID-19 pandemic on neonatology residency training at a tertiary children's hospital in Chongqing. The first phase surveyed residents' perceptions and experiences of their clinical education and well-being during the crisis. The second phase compared the quality of neonatal care between the pre-pandemic and pandemic periods. RESULTS: The survey of 123 neonatology residents examines the effects of COVID-19 on their learning, training, and mental health. The survey showed that most residents adapted well to the situation. Still, some faced challenges in their clinical education and experiences, such as reduced clinical exposure and opportunities to see rare diseases and conditions. A retrospective analysis of clinical data revealed that 7,151 neonates were admitted to the neonatology department during the study period. There was a 27.6% decrease in neonatal admissions during COVID-19, with more premature births and transfers. Residents conducted fewer clinical procedures but managed more complex cases. During COVID, hospital stays and costs were higher, but antibiotic use was lower. Although the case-mix index (CMI) score increased during the pandemic (1.25 vs. 1.18, p < 0.05), there was no significant difference in the rates of readmission within 7 days or poor prognosis. CONCLUSIONS: Despite reduced clinical exposure, the quality of neonatal care was maintained through innovative training methods that enhanced comprehensive residency programs. The study suggested that neonatology residency education remained effective and resilient during the crisis. Exceptional health professional education is vital to train qualified physicians and enhance healthcare systems for future challenges.

[Impact of chaperone-mediated autophagy on bilirubin-induced damage of mouse microglial cells]. / åˆ†å­ä¼´ä¾£ä»‹å¯¼çš„è‡ªå™¬å¯¹èƒ†çº¢ç´ è¯±å¯¼çš„å°é¼ å°èƒ¶è´¨ç»†èƒžæŸä¼¤çš„å½±å“.

OBJECTIVES: To investigate the effect of chaperone-mediated autophagy (CMA) on the damage of mouse microglial BV2 cells induce by unconjugated bilirubin (UCB). METHODS: The BV2 cell experiments were divided into two parts. (1) For the CMA activation experiment: control group (treated with an equal volume of dimethyl sulfoxide), QX77 group (treated with 20 µmol/L QX77 for 24 hours), UCB group (treated with 40 µmol/L UCB for 24 hours), and UCB+QX77 group (treated with both 20 µmol/L QX77 and 40 µmol/L UCB for 24 hours). (2) For the cell transfection experiment: LAMP2A silencing control group (treated with an equal volume of dimethyl sulfoxide), LAMP2A silencing control+UCB group (treated with 40 µmol/L UCB for 24 hours), LAMP2A silencing group (treated with an equal volume of dimethyl sulfoxide), and LAMP2A silencing+UCB group (treated with 40 µmol/L UCB for 24 hours). The cell viability was assessed using the modified MTT method. The expression levels of p65, nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3), and cysteinyl aspartate specific proteinase-1 (caspase-1) were detected by Western blot. The relative mRNA expression levels of the inflammatory cytokines interleukin (IL)-1ß, IL-6, and tumor necrosis factor-α (TNF-α) were determined by real-time quantitative polymerase chain reaction. Levels of IL-6 and TNF-α in the cell culture supernatant were measured using ELISA. The co-localization of heat shock cognate protein 70 with p65 and NLRP3 was detected by immunofluorescence. RESULTS: Compared to the UCB group, the cell viability in the UCB+QX77 group increased, and the expression levels of inflammation-related proteins p65, NLRP3, and caspase-1, as well as the mRNA relative expression levels of IL-1ß, IL-6, and TNF-α and levels of IL-6 and TNF-α decreased (P<0.05). Compared to the control group, there was co-localization of heat shock cognate protein 70 with p65 and NLRP3 in both the UCB and UCB+QX77 groups. After silencing the LAMP2A gene, compared to the LAMP2A silencing control+UCB group, the LAMP2A silencing+UCB group showed increased expression levels of inflammation-related proteins p65, NLRP3, and caspase-1, as well as increased mRNA relative expression levels of IL-1ß, IL-6, and TNF-α and levels of IL-6 and TNF-α (P<0.05). CONCLUSIONS: CMA is inhibited in UCB-induced BV2 cell damage, and activating CMA may reduce p65 and NLRP3 protein levels, suppress inflammatory responses, and counteract bilirubin neurotoxicity.

Diversity of σ66-Specific Promoters Contributes to Regulation of Developmental Gene Expression in Chlamydia trachomatis.

Promoter recognition by the RNA polymerase (RNAP) holoenzyme is a key step in gene regulation. In Chlamydia trachomatis, a medically important obligate intracellular bacterium, σ66 allows the RNAP to initiate promoter-specific transcription throughout the chlamydial developmental cycle. Here, we investigated the intrinsic properties of σ66-specific promoters with emphasis on their role in the developmental gene expression of C. trachomatis. First, we examined whether promoters that contain a 5'-T(-15)G(-14)-3' (TG) motif upstream from the -10 element appear more often than others in genes that are preferentially expressed during the early, middle, or late stages of the C. trachomatis developmental cycle. We then determined the critical genetic elements that are required for transcription initiation in vitro. We also assessed the activity of promoters in the presence of Scc4, which can directly interact with σ66RNAP. Finally, we evaluated the promoter-specific dynamics during C. trachomatis infection using a reporter assay. These results reveal that the TG motif is an important determinant in certain early or late promoters. The TG promoters that have the -35 element are recognized by σ66RNAP and Scc4 differently from those lacking the -35 element. Based on these properties, the σ66-specific promoters can fall into three classes. Architectural diversity, behavioral plasticity, and the specific interplays between promoters and the σ66RNAP likely contribute to developmental gene transcription in C. trachomatis. IMPORTANCE Meticulous promoter elucidation is required to understand the foundations of transcription initiation. However, knowledge of promoter-specific transcription remains limited in C. trachomatis. This work underscores the structural and functional plasticity of σ66-specific promoters that are regulated by σ66RNAP, as well as their importance in the developmental gene regulation of C. trachomatis.

Bilirubin impacts microglial autophagy via the Akt-mTOR signaling pathway.

Bilirubin encephalopathy is a severe complication of neonatal hyperbilirubinemia. With elevation of serum unconjugated bilirubin (UCB) levels, UCB crosses the blood-brain barrier and possibly leads to neurological dysfunction. Neuroinflammation is recognized as a prominent pathological feature in bilirubin encephalopathy. Recent studies have suggested that autophagy plays a crucial role in the inflammatory response. However, the potential effect of microglial autophagy in the pathogenesis of bilirubin encephalopathy remains uncertain. The in vitro findings verified that in primary cultured microglia, UCB significantly reduced the ratio of LC3B-II to LC3B-I and downregulated the expression of ATG5, Beclin-1, and ATG7, while increasing the expression of p62/SQSTM1. The results showed that UCB could decrease the number of mCherry-EGFP-LC3 positive puncta, even when chloroquine (CQ) was applied to block the microglial autophagy flux. Mechanistically, UCB was found to upregulate the expression of TLR4 and increase the phosphorylation levels of Akt and mammalian target of rapamycin (mTOR). Promoting microglial autophagy by treatment with Rapamycin (RAPA), an mTOR inhibitor, decreased the levels of NOD-like receptor protein 3 (NLRP3) inflammasome components and IL-1ß, rescued microglial overactivation, and improved neurological functions. These data indicated that UCB could impact microglial autophagy via the Akt-mTOR signaling pathway and synergistically promote neuroinflammatory responses. Enhancing autophagy might disrupt the assembly of NLRP3 inflammasome, attenuate UCB-induced neuroinflammation, and improve the prognosis of model rats with bilirubin encephalopathy. In conclusion, this study implies that regulating microglial autophagy might be a promising therapeutic strategy for bilirubin encephalopathy.

Bilirubin Induces A1-Like Reactivity of Astrocyte.

Astrocytes play an important role in the pathogenesis of bilirubin neurotoxicity, and activated astrocytes might be potential mediators of neuroinflammation processes contributing to neuronal cell death and tissue injury. Recent studies have reported that activated microglia induce two types of reactive astrocytes. A1 astrocytes could cause neuronal death and synaptic damage, as well as impaired phagocytosis. Therefore, the purpose of this study was to investigate whether unconjugated bilirubin (UCB)-induced A1-like astrocytes take on a neuroinflammation type and the underlying regulatory mechanisms. In this study, primary cortical astrocytes were treated with UCB in vitro. We detected the expression of complement component 3 (C3), S100 calcium binding protein A10 (S100A10), nuclear factor kappa B (NF-κB), NLR family pyrin domain containing 3 (NLRP3), activated caspase-1, gasdermin D N-terminal (GSDMD-N), PSD95, synaptophysin (SYP), the transcription levels of interleukin (IL)-1ß and IL-18, and the survival rate of astrocytes after UCB treatment. The results showed that an increase in C3 was accompanied by a decrease in S100A10, and that A1-like astrocytes were functionally expressed after UCB stimulation. Meanwhile, the NF-κB and caspase-1 pathways were activated after UCB stimulation. After adding the NF-κB-specific inhibitor trans-activator of transcriptional-NEMO-binding domain (TAT-NBD) and caspase-1 specific inhibitor VX-765, the survival rate of astrocytes and neurons increased, whereas the protein expression of C3, NF-κB, NLRP3, activated caspase-1, and GSDMD-N decreased, and the mRNA levels of IL-1ß and IL-18 reduced. Thus, we concluded that UCB stimulates the activation of A1-like astrocytes. Inhibition of NF-κB and caspase-1 alleviated A1-like astrocytes and exerted anti-inflammatory protective effects.

Evaluation of antibiotic stewardship among near-term and term infants admitted to a neonatal unit.

To evaluate the safety and effectiveness of evidence-based antibiotic stewardship in a neonatal unit in China. The study period consisted of two phases, one retrospective (the baseline period, January to December 2018, and the transition period, January 2019 to August 2020) and one prospective intervention period (September 2020 to August 2021). During the prospective period, evidence-based antibiotic stewardship was applied to neonates with suspected infections, pneumonia, and culture-negative sepsis. The antibiotic stewardship included the observation form of neonatal infections, antibiotic therapy of no more than 48 h for suspected infections, and 5 days for pneumonia and culture-negative sepsis. The change in antibiotic use measured by days of therapy per 1000 patient-days between the baseline and intervention period was analyzed. Safety outcomes included reinitiation of antibiotics within 14 days, length of stay, occurrence of late-onset sepsis and necrotizing enterocolitis (Bell stage ≥ II), multidrug-resistant organism infections, and mortality. A total of 7705 neonates were enrolled during the baseline (n = 4804) and the intervention periods (n = 2901). The total antibiotic usage during the baseline period was 771 days of therapy per 1000 patient-days, while that was 525 days of therapy per 1000 patient-days during the intervention period, indicating a 32% decrease in antibiotic consumption. No significant difference in safety outcomes was observed between the baseline and intervention period (P > 0.05), whereas the length of stay was longer during the intervention period (P < 0.001). CONCLUSION: The evidence-based antibiotic stewardship can safely and effectively reduce antibiotic use and shorten the duration of therapy in the neonatal unit. WHAT IS KNOWN: • Overuse of antibiotics has been associated with adverse events in neonates, including necrotizing enterocolitis, multidrug-resistant organism infections, and death. • More clinical effectiveness evidence is needed to support antibiotic stewardship of neonates in China. WHAT IS NEW: • Using prospective audit, targeted stewardship interventions, this study shows that a 32% reduction in overall antibiotic consumption was achieved safely. • Implementation of evidence-based neonatal antibiotic stewardship, including the observation form of neonatal infections, antibiotic therapy of no more than 48 h for suspected infections, and 5 days for pneumonia and culture-negative sepsis, is safe and effective among newborns in a developing country.

Global, regional, and national burden of neonatal sepsis and other neonatal infections, 1990-2019: findings from the Global Burden of Disease Study 2019.

To provide an overview of the global, regional, and national incidence and mortality of neonatal sepsis and other neonatal infections (NS) and their change trends from 1990 to 2019, based on the data from the 2019 Global Burden of Disease study. This was a retrospective demographic analysis based on aggregated data. Annual incident cases, deaths, age-standardized incidence rate (ASIR), age-standardized mortality rate (ASMR) and their percentage changes of NS during 1990-2019 were collected from the 2019 Global Burden of Disease study. Globally, the incident cases of NS increased by 12.79% (from 5.59 million in 1990 to 6.31 million in 2019), and the deaths decreased by 12.93% (from 0.26 million in 1990 to 0.23 million in 2019). In the globe, the ASIR of NS per 100,000 population increased by 14.35% (from 85.21 in 1990 to 97.43 in 2019), and the ASMR decreased by 11.91% (from 3.97 in 1990 to 3.5 in 2019). CONCLUSION: Increasing trends in incidence and decreasing trends in mortality of NS were observed worldwide from 1990 to 2019. More robust epidemiological research and effective health strategies are urgently needed to reduce the disease burden of neonatal sepsis worldwide. WHAT IS KNOWN: • Neonatal sepsis has significant impacts on neonatal health, but estimates on the global burden and trends of neonatal sepsis are scarce and existing findings vary considerably. WHAT IS NEW: • Globally, there were 6.31 million incident cases of neonatal sepsis and 0.23 million deaths due to neonatal sepsis. • Increasing trends in incidence and decreasing trends in mortality of neonatal sepsis were observed worldwide from 1990 to 2019, with the highest absolute burden in sub-Saharan Africa and Asia.

[Global disease burden of neonatal jaundice from 1990 to 2019]. / 1990­2019å¹´å ¨çƒæ–°ç”Ÿå„¿é»„ç–¸ç–¾ç— è´Ÿæ‹ åˆ†æž.

OBJECTIVES: To examine the global, regional, and national disease burden of neonatal jaundice. METHODS: The 2019 Global Burden of Disease database was searched to collect incident cases/incidence and deaths/mortality of neonatal jaundice, as well as global socio-demographic index (SDI) and universal health coverage index (UHCI). The epidemiological trend of neonatal jaundice from 1990 to 2019 was analyzed. The correlations between incidence/mortality of neonatal jaundice and SDI and UHCI were evaluated. RESULTS: From 601 681 in 1990 to 626 005 in 2019, with a 4.04% increase in global incident cases of neonatal jaundice. The overall age-standardized incidence rate exhibited an increase [estimated annual percent change=0.13 (95%CI: 0.03 to 0.23)] during this period. Additionally, deaths due to neonatal jaundice decreased by 58.83%, from 128 119 in 1990 to 52 742 in 2019. The overall age-standardized mortality rate showed a decrease [estimated annual percent change=-2.78 (95%CI: -3.00 to -2.57)] over the same period. Countries with lower SDI, such as India, Pakistan, and Nigeria, reported a higher proportion of neonatal morbidity and mortality. In 2019, a negative correlation was observed between estimated annual percent change in age-standardized mortality rate and SDI (ρ=-0.320, P<0.05) or UHCI (ρ=-0.252, P<0.05). CONCLUSIONS: The global incidence of neonatal jaundice is on the rise, while the mortality rate is declining. The burden of neonatal jaundice is influenced by social development, economic factors, and the level of medical care.

Guideline for the management of pediatric off-label use of drugs in China (2021).

BACKGROUND: The "Law on Doctors of the People's Republic of China," which was officially implemented on March 1, 2022, emphasizes the requirements for rational drug use and the necessity for appropriate management of off-label drug use. The safety and ethical considerations related to off-label drug use are different in children than in adults. There is so far no management guideline for pediatric off-label use of drugs in China, and the applicability of foreign guidelines is limited. Establishing a localized evidence-based management guideline for pediatric off-label use of drugs to support the national legislation and clinical practice is of critical importance. METHODS: We established a guideline working group, including experts from a broad range of disciplines and developed recommendations following the guidance of the World Health Organization Handbook and the Chinese Medical Association. The following themes were identified by questionnaires and expert interviews to be of great concern in the management of off-label drug use in children: general principles and characteristics of management of pediatric off-label drug use; establishment of expert committees; evidence evaluation; risk-benefit assessment; informed consent; monitoring and assessment of the risk; and monitoring and patient education. Two rounds of Delphi surveys were organized to determine the final recommendations of this guideline. We graded the recommendations based on the body of evidence, referring to the evaluation tool of the Evidence-based management (EBMgt) and the Oxford Center for Evidence-Based Medicine: Level of Evidence (March 2009). RESULTS: We developed the first guideline for the management of pediatric off-label use of drugs in China. CONCLUSIONS: The guideline is to offer guidance for pediatricians, pharmacists, medical managers, policymakers, and primary care physicians on how to manage off-label drug use in pediatrics and to provide recommendations for Chinese healthcare policy in the future.

Serum troponin I: a potential biomarker of hypoxic-ischemic encephalopathy in term newborns.

OBJECTIVE: This study was intended to evaluate the predictive values of serum procalcitonin (PCT), lactate, creatine kinase (CK-MB), and troponin I on the diagnosis and staging of neonatal hypoxic-ischemic encephalopathy (HIE). MATERIALS AND METHODS: We retrospectively retrieved data from electronic medical records at our children's hospital, and we included all term newborns admitted between December 2018 and June 2020 with features of perinatal asphyxia. Receiver operating characteristic (ROC) curve and area under the curve (AUC) were used to measure and evaluate the predictive values of biomarkers. p values < 0.05 were set as statistical significance. RESULTS: A total of 201 neonates were included. They were grouped as control (n = 40), mild HIE (n = 105), moderate HIE (n = 36), and severe HIE (n = 20). Serum lactate, PCT, CK-MB, and troponin I levels in severe hypoxic-ischemic brain injury group were significantly higher than those in mild to moderate hypoxic-ischemic brain injury group and control group (p < 0.05). Based on ROC and AUC analysis, troponin I showed highest predictive ability with AUC of 0.904, and sensitivity and specificity of 95.00% and 87.50% respectively. CONCLUSION: Serum troponin I has a good predictive value for neonatal hypoxic-ischemic encephalopathy after perinatal asphyxia.

Effect of prophylactic use of hydrolyzed protein formula on gastrointestinal diseases and physical growth in preterm infants: a Meta analysis. / é¢„é˜²æ€§ä½¿ç”¨æ°´è§£è›‹ç™½é æ–¹å¥¶å¯¹æ—©äº§å„¿èƒƒè‚ é“ç–¾ç— åŠä½“æ ¼ç”Ÿé•¿å½±å“çš„Meta分析.

OBJECTIVES: To systematically evaluate the effect of prophylactic use of hydrolyzed protein formula on gastrointestinal diseases and physical development in preterm infants. METHODS: A computerized search was performed in the databases including China National Knowledge Infrastructure, Wanfang Data, Weipu, PubMed, Embase, and the Cochrane Library to identify randomized controlled trials of the effect of prophylactic use of hydrolyzed protein formula on gastrointestinal diseases and physical growth in preterm infants. RevMan 5.3 software was used to perform a Meta analysis for the included studies. RESULTS: A total of 7 randomized controlled studies were included. The results of Meta analysis showed that compared with the whole protein formula, the prophylactic use of hydrolyzed protein formula could reduce the risk of neonatal necrotizing enterocolitis (RR=0.40, P=0.04) and feeding intolerance (RR=0.40, P=0.005), and had no significant effect on the growth of weight, length and head circumference (P>0.05). CONCLUSIONS: Compared with the whole protein formula, the prophylactic use of hydrolyzed protein formula in preterm infants may reduce the occurrence of necrotizing enterocolitis and feeding intolerance, and can meet the nutrient requirement of physical development. However, the evidence is limited, and the results of this study cannot support the routine prophylactic use of hydrolyzed protein formula in preterm infants.

[Sepsis risk calculator-guided antibiotic management in neonates with suspected early-onset sepsis].

OBJECTIVE: To evaluate the efficacy of sepsis risk calculator (SRC) in guiding antibiotic use in neonates with suspected early-onset sepsis (EOS). METHODS: A total of 284 neonates with a gestational age of ≥ 35 weeks were enrolled as the control group, who were hospitalized in the Children's Hospital of Chongqing Medical University from March to July, 2019 and were suspected of EOS. Their clinical data were retrospectively collected and the use of antibiotics was analyzed based on SRC. A total of 170 neonates with a gestational age of ≥ 35 weeks were enrolled as the study group, who were admitted to the hospital from July to November, 2020 and were suspected of EOS. SRC was used prospectively for risk scoring to assist the decision making of clinical antibiotic management. The two groups were compared in terms of the rate of use of antibiotics, blood culture test rate, clinical outcome, and adherence to the use of SRC. RESULTS: Compared with the control group, the study group had a significantly higher SRC score at birth and on admission (P < 0.05). The rate of use of antibiotics in the study group was significantly lower than that in the control group[84.7% (144/170) vs 91.5% (260/284), 6.8% decrease; P < 0.05]. The blood culture test rate in the study group was also significantly lower than that in the control group (85.3% vs 91.9%, P < 0.05). There was no significant difference between the two groups in the incidence rate of adverse outcomes and the final diagnosis of EOS (P > 0.05). CONCLUSIONS: The use of SRC reduces the rate of empirical use of antibiotics in neonates with suspected EOS and does not increase the risk of adverse outcomes, and therefore, it holds promise for clinical application.

[Role of pyroptosis in bilirubin-induced microglial injury].

OBJECTIVE: To study whether pyroptosis is involved in the bilirubin-induced injury of primary cultured rat cortical microglial cells. METHODS: Primary cultured rat cortical microglial cells were randomly administered with 30 µmol/L bilirubin (bilirubin group), 30 µmol/L bilirubin following 30 µmol/L VX-765 pretreatment (VX-765+bilirubin group), or an equal volume of dimethyl sulfoxide (control group). Modified MTT assay was used to measure the viability of microglial cells. Western blot was used to measure the expression of the pyroptosis-related proteins Caspase-1 and gasdermin D (GSDMD). Lactate dehydrogenase (LDH)-release assay was used to evaluate the cytotoxicity of microglial cells. EtBr/EthD2 with different molecular weights (394 Da/1 293 Da) was used to measure the size of plasma membrane pores. ELISA was used to measure the level of the inflammatory factor interleukin-1ß (IL-1ß) in culture supernatant. RESULTS: After bilirubin stimulation, the viability of microglial cells decreased and LDH release increased, both in a time-dependent manner. Compared with the control group, the bilirubin group had a significantly higher positive rate of small-molecule EtBr passing through the cell membrane (P<0.001), while there was no significant difference in the pass rate of large-molecule EthD2 between groups (P>0.05). The expression of activated Caspase-1 significantly increased at 0.5 hour after bilirubin stimulation (P<0.05), and that of activated GSDMD significantly increased at 6 hours after bilirubin stimulation (P<0.05). The release of IL-1ß significantly increased at 6 hours after bilirubin stimulation and reached the peak at 24 hours (P<0.001). Compared with the bilirubin group, the VX-765+bilirubin group had a significant increase in cell viability (P<0.05) and significant reductions in the expression of activated GSDMD, the pass rate of EtBr, and the release of LDH and IL-1ß (P<0.05). CONCLUSIONS: Pyroptosis is involved in bilirubin-induced injury of primary cultured microglial cells.

[C-reactive protein-guided antibiotic treatment strategy for neonates with suspected early-onset sepsis].

OBJECTIVE: To evaluate the efficacy and safety of C-reactive protein (CRP)-guided antibiotic treatment strategy for neonates with suspected early-onset sepsis (EOS). METHODS: A total of 428 neonates, with a gestational age of >35 weeks, who were admitted to the Children's Hospital of Chongqing Medical University from February to July, 2019 and were suspected of EOS were enrolled as the observation group. The effect of antibiotic treatment was prospectively observed, and if clinical symptoms were improved and CRP was <10 mg/L in two consecutive tests, discontinuation of antibiotics was considered. A total of 328 neonates (gestational age of >35 weeks) who were admitted to this hospital from February to July, 2018 and were suspected of EOS were enrolled as the control group, and the use of antibiotics was analyzed retrospectively. The two groups were compared in terms of duration of antibiotic treatment, length of hospital stay, incidence rate of repeated infection and clinical outcome. RESULTS: Compared with the control group, the observation group had significantly shorter duration of antibiotic treatment and length of hospital stay (P<0.05). There were no significant differences in the incidence rate of repeated infection and clinical outcome between the two groups (P>0.05). CONCLUSIONS: For neonates with a gestational age of >35 weeks and a suspected diagnosis of EOS, CRP-guided antibiotic treatment strategy can shorten duration of antibiotic treatment and length of hospital stay and does not increase the incidence rate of repeated infection. Therefore, it holds promise for clinical application.

Caspase-1 involves in bilirubin-induced injury of cultured rat cortical neurons.

BACKGROUND: Bilirubin encephalopathy, the most serious complication of hyperbilirubinemia during the neonatal period, with high mortality and morbidity, often causes irreversible neurological damage. Currently, caspase-1, a member of the cysteinyl aspartate-specific protease caspase family, is regarded as a key mediator of inflammatory processes, attracting widespread attention. The purpose of this study was to investigate whether caspase-1 is involved in bilirubin-induced neuronal injury. METHODS: VX-765, a highly potent and selective inhibitor of caspase-1, was used to investigate the effects of unconjugated bilirubin (UCB) on rat cortical neurons, including cell viability, morphological changes in the cell membrane, and nuclear factor-kappa B (NF-κB) activation. RESULTS: Neurons treated with UCB showed increased caspase-1 activity without the secretion of interleukin (IL)-1ß and IL-18, and caspase-1 was significantly inhibited by pretreatment with VX-765. The cell viability of the VX-765-pretreated neurons was improved, and cell membrane rupture was prevented, as detected by lactate dehydrogenase release and ethidium bromide uptake. Moreover, NF-κB activation by UCB exposure, was attenuated by VX-765 pretreatment. CONCLUSION: Bilirubin-induced neuronal injury involves the activation of caspase-1 and NF-κB, leading to membrane leakage, independently of IL-1ß and IL-18.

Potency of Solithromycin against Fast- and Slow-Growing Chlamydial Organisms.

Evidence is provided that solithromycin is a bactericidal against not only fast-growing chlamydial organisms but also those slowed by gamma interferon (IFN-γ) in vitro At sublethal concentrations, Sol impedes homotypic fusion of Chlamydia-containing vacuoles and reduces secretion of the type III secretion (T3S) effector IncA. Sol may therefore represent a potential new clinical treatment for Chlamydia infections. Selective perturbation of the T3S system suggests a novel mode of antibacterial action for Sol that warrants further investigation.

Unconjugated bilirubin induces pyroptosis in cultured rat cortical astrocytes.

BACKGROUND: Bilirubin-induced neurological dysfunction (BIND), a severe complication of extreme neonatal hyperbilirubinemia, could develop into permanent neurodevelopmental impairments. Several studies have demonstrated that inflammation and nerve cell death play important roles in bilirubin-induced neurotoxicity; however, the underlying mechanism remains unidentified. METHODS: The present study was intended to investigate whether pyroptosis, a highly inflammatory form of programmed cell death, participated in the bilirubin-mediated toxicity on cultured rat cortical astrocytes. Further, VX-765, a potent and selective competitive drug, was used to inhibit the activation of caspase-1. The effects of VX-765 on astrocytes treated with bilirubin, including the cell viability, morphological changes of the cell membrane and nucleus, and the production of pro-inflammation cytokines, were observed. RESULTS: Stimulation of the astrocytes with unconjugated bilirubin (UCB) at the conditions mimicking those of jaundiced newborns significantly increased the activation of caspase-1. Further, caspase-1 activation was inhibited by treatment with VX-765. Compared with UCB-treated astrocytes, the relative cell viability of VX-765-pretreated astrocytes was improved; meanwhile, the formation of plasma membrane pores was prevented, as measured by lactate dehydrogenase release, trypan blue staining, and ethidium bromide (EtBr) uptake. Moreover, DNA fragmentation was partly attenuated and the release of IL-1ß and IL-18 was apparently decreased. CONCLUSION: Pyroptosis is involved in the process of UCB-induced rat cortical astrocytes' injury in vitro and may be the missing link of cell death and inflammatory response exacerbating UCB-related neurotoxicity. More importantly, the depression of caspase-1 activation, the core link of pyroptosis, attenuated UCB-induced cellular dysfunction and cytokine release, which might shed light on a new therapeutic approach to BIND.

[Application of the Evidence-based Practice for Improving Quality method in neonatal intensive care units].

The Evidence-based Practice for Improving Quality (EPIQ) method was proposed by Canadian Neonatal Network for high quality health care. The method is characterized by evidence-based, targeted, collaborative and continuous concept. At present it is applied in neonatal intensive care units (NICUs). This review article focuses on the application of the method in NICUs.

[Comparison and Discussion of National/Military Standards Related to Flow Measurement of Medical Injection Pump].

Medical injection pump is a commonly used clinical equipment with high risk. Accurate detection of flow is an important aspect to ensure its reliable operation. In this paper, we carefully studied and analyzed the flow detection methods of three standards being used in medical injection pump detection in our country. The three standards were compared from the aspects of standard device, flow test point selection, length of test time and accuracy judgment. The advantages and disadvantages of these standards were analyzed and suggestions for improvement were put forward.