[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.

[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.

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.

A Prediction Nomogram for Acute Kidney Injury in Very-Low-Birth-Weight Infants: A Retrospective Study.

Background and objective: Acute kidney injury (AKI) is recognized as an independent predictor for mortality in very-low-birth-weight (VLBW) infants and is reported to have a high incidence. In this study, we sought to identify the predictors for AKI in VLBW infants and thereby develop a prediction nomogram for the early detection and management of VLBW infants at high risk of developing AKI. Methods: We designed a retrospective study wherein we investigated the baseline hospitalization data of VLBW infants treated at our hospital between January 2012 and October 2018. Independent predictors of AKI in VLBW infants, as identified by multivariate logistic regression, were incorporated into a model. Hosmer-Lemeshow test was used to test the goodness of fit of the model, and a receiver operating characteristic (ROC) curve was plotted to assess the discriminative ability of the model. The model was internally validated using the 10-fold cross-validation method. A nomogram was plotted to predict the risk of AKI in VLBW infants on the basis of the results of multivariate logistic regression analysis. Results: We investigated the data of 604 VLBW infants, of which 144 (23.8%) developed AKI; in 111 (77.1%) of these infants, AKI occurred within 7 days of birth. Multivariate logistic regression analysis identified the following as predictive factors for AKI in VLBW infants: gestational age, red blood cell count within 3 days of birth, serum calcium concentration within 3 days of birth, maternal age of ≥35 years, and pulmonary arterial hypertension or myocardial injury. Furthermore, the nomogram was found to be effective in estimating the risk of AKI in VLBW infants, with an area under the curve (AUC) of 0.794 [95% confidence interval (CI): 0.754-0.834; P < 0.001]. Internal validation done by cross-validation showed that the average AUC was 0.788. Conclusion: The nomogram developed in this study was found to be sensitive and specific for the preoperative prediction of AKI in VLBW infants, as per the Kidney Disease: Improving Global Outcomes (KDIGO) criteria modified for neonates.

Efficacy and safety of fluconazole in prophylaxis of invasive fungal infections in very low birth weight infants: a Meta analysis / 中国当代儿科杂志

OBJECTIVE@#To assess the efficacy and safety of fluconazole in the prophylaxis of invasive fungal infection in very low birth weight (VLBW) infants.@*METHODS@#Databases including PubMed, Embase, the Cochrane Library, Wanfang Data, Weipu, and CNKI were searched for randomized controlled trials (RCTs) of prophylactic fluconazole in VLBW infants. Review Manager 5.3 software was used to perform a Meta analysis of the included studies.@*RESULTS@#A total of 12 RCTs were included, involving 1 679 VLBW infants. The Meta analysis showed that prophylactic fluconazole significantly reduced the incidence of invasive fungal infection (RR=0.44, 95%CI: 0.27-0.71, P0.05). No significant differences were found in the incidence of fluconazole resistance and complications between the fluconazole and control groups (P>0.05).@*CONCLUSIONS@#Prophylactic fluconazole can effectively and safely prevent invasive fungal infection in VLBW infants, even at a small dose.

[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.

[Role of caspase-1 activation in bilirubin-induced injury in cultured primary rat hippocampal neurons].

OBJECTIVE: To investigate the role of caspase-1 activation in bilirubin-induced neuronal injury and the protective effect of VX-765 against bilirubin-induced neurotoxicity in cultured primary rat hippocampal neurons. METHODS: Cultured primary rat hippocampal neurons were exposed to DMSO (control group), 50 µmol/L bilirubin, or 50 µmol/L bilirubin 1 h after 50 µmol/L VX-765 treatment. The expressions of NLRP3 and caspase-1 in the neurons were detected by Western blotting, and the relative cell survival and death rates were assessed with a modified MTT assay, lactate dehydrogenase assay and Typan blue staining. Interleukin-18 (IL-18) concentration in the culture supernatant was measured using enzyme-linked immunosorbent assay (ELISA). RESULTS: In cultured primary rat hippocampal neurons, bilirubin exposure for 3 and 6 h caused significant increases in the expressions of NLRP3 and activated caspase-1 compared with those in the control group (P<0.05). Pretreatment of the cells with VX-765 obviously suppressed bilirubin-induced activation of caspase-1 (P<0.05). The relative survival rate of the neurons was (84.02∓2.31)% in VX-765 intervention group, significantly higher than that in bilirubin group (P<0.05) but lower than that in the control group (P<0.05); LDH release rate in VX-765 intervention group was (10.78∓1.58)%, significantly lower than that in bilirubin group (P<0.05) but higher than that in the control group (P<0.05). The cell death rate in VX-765 intervention group was (5.58∓1.23)%, significantly lower than that in bilirubin group (P<0.05) but higher than that in the control group (P<0.05). CONCLUSION: In cultured primary rat hippocampal neurons, caspase-1 activation plays a role in bilirubin-induced neurotoxicity, and VX-765 treatment provides protection against bilirubin-induced neuronal injury by inhibiting caspase-1 activation.

[Effects of antibiotic stewardship on neonatal bloodstream infections].

OBJECTIVE: To investigate the effects of antibiotic stewardship on the pathogen and clinical outcome of neonatal bloodstream infections (BSIs). METHODS: A retrospective study was performed on neonates with BSIs who were admitted to the neonatal ward in the years of 2010 (pre-stewardship) and 2013 (post-stewardship) for pathogens, antibiotic resistance, antibiotic use, and clinical outcomes. RESULTS: The admission rate of BSIs (6.47% vs 2.78%) and the incidence of nosocomial BSIs (0.70% vs 0.30%) in 2013 were significantly higher than in 2010 (P<0.01). However, there were no signicant differences in the clinical outcomes between the years of 2010 and 2013 (P>0.05). The four most common pathogens isolated from blood cultures, Staphylococcus haemolyticus, Staphylococcus epidermidis, Klebsiella pneumoniae ssp pneumoniae and E.coli, were similar between the two years. There were no significant differences in the detection rates of extended spectrum ß-lactamase-positve Klebsiella pneumoniae ssp pneumoniae or E.coli between the two years. The detection rates of methicillin-resistant Staphylococcus/ß-lactamase-positive Staphylococcus haemolyticus and Staphylococcus epidermidis were similar between the two years (P>0.05). CONCLUSIONS: Since the implementation of antibiotic stewardship, there has been no marked variation in the common pathogens and their antibacterial resistance in neonatal BSIs. The antibiotic stewardship could promote the recovery of patients with BSIs.

[Efficacy of pulmonary surfactant therapy in neonates with meconium aspiration syndrome: a meta-analysis].

OBJECTIVE: The efficacy of pulmonary surfactant (PS) replacement therapy for meconium aspiration syndrome (MAS) remains controversial. This study aimed to evaluate the efficacy of PS therapy in neonates with MAS by a meta-analysis. METHODS: Randomized controlled trials (RCTs) on the treatment of MAS with PS were searched electronically in medical debases including PubMed, Science Citation Index, The Cochrane Central Register of Controlled Trials, Ovid, EBSCOhost, BIOSIS previews, Chinese BioMedical Literature Database, Wanfang Database and VIP Chinese Sci-Tech Periodical Database. The Cochrane Handbook 5.0.2 was employed to evaluate methodological quality. RevMan 5.0.25 software was used for the meta-analysis. RESULTS: Eight RCTs including 512 MAS neonates (257 cases in the PS treatment group and 255 cases in the control group) were enrolled in this meta-analysis. The meta-analysis showed that PS treatment reduced oxygenation index (MD=-2.59; 95%CI: -4.33, -0.86; P=0.003), increased arterial oxygen/alveolar oxygen ratio (MD=0.05; 95%CI: 0.05, 0.06; P<0.00001), shortened hospitalization days (MD=-4.94; 95%CI: -7.44, -2.44; P=0.0001) and decreased mortality rate (OR=0.47; 95%CI: 0.24, 0.93; P=0.03) significantly. There were no statistical differences in the durations of mechanical ventilation and oxygen therapy, and the incidences of air leak, pulmonary hemorrhage and intracranial hemorrhage between the PS treatment and control groups. CONCLUSIONS: Currently published evidence from RCTs suggests that PS replacement therapy is effective for MAS, however because of the limited quantity and quality of trials enrolled in the study, further evidence from RCTs is needed to prove the efficacy.