Epidemiology, microbiology and antibiotic treatment of bacterial and fungal meningitis among very preterm infants in China: a cross-sectional study.

OBJECTIVE: Neonatal meningitis significantly contributes to neonatal morbidity and mortality, yet large-scale epidemiological data in developing countries, particularly among very preterm infants (VPIs), remain sparse. This study aimed to describe the epidemiology of meningitis among VPIs in China. DESIGN: Cross-sectional study using the Chinese Neonatal Network database from 2019 to 2021. SETTING: 79 tertiary neonatal intensive care units in China. PATIENTS: Infants with gestational age <32 weeks or birth weight <1500 g. MAIN OUTCOME MEASURES: Incidence, pathogen distribution, antimicrobial use and outcomes of bacterial and fungal meningitis. RESULTS: Of 31 915 VPIs admitted, 122 (0.38%) infants were diagnosed with culture-confirmed meningitis, with 14 (11.5%) being early-onset (≤6 days of age) and 108 (88.5%) being late-onset (>6 days of age). The overall in-hospital mortality was 18.0% (22/122). A total of 127 pathogens were identified, among which 63.8% (81/127) were Gram-negative bacteria, 24.4% (31/127) were Gram-positive bacteria and 11.8% (15/127) were fungi. In terms of empirical therapy (on the day of the first lumbar puncture), the most commonly used antibiotic was meropenem (54.9%, 67/122). For definitive therapy (on the sixth day following the first lumbar puncture, 86 cases with available antibiotic data), meropenem (60.3%, 35/58) and vancomycin (57.1%, 16/28) were the most used antibiotics for Gram-negative and Gram-positive bacterial meningitis, respectively. 44% of infants with Gram-positive bacterial meningitis and 52% with Gram-negative bacterial meningitis received antibiotics for more than 3 weeks. CONCLUSION: 0.38% of VPIs in Chinese neonatal intensive care units were diagnosed with meningitis, experiencing significant mortality and inappropriate antibiotic therapy. Gram-negative bacteria were the predominant pathogens, with fungi emerging as a significant cause.

An Antiferromagnetic Neuromorphic Memory Based on Perpendicularly Magnetized CoO.

Antiferromagnets (AFMs) are ideal materials to boost neuromorphic computing toward the ultrahigh speed and ultracompact integration regime. However, developing a suitable AFM neuromorphic memory remains an aspirational but challenging goal. In this work, we construct such a memory based on the CoO/Pt heterostructure, in which the collinear insulating AFM CoO shows a strong perpendicular anisotropy facilitating its electrical readout and writing. Utilizing the unique nonlinear response and bipolar fading memory properties of the device, we demonstrate a multidimensional reservoir computing beyond the traditional binary paradigm. These results are expected to pave the way toward next-generation fast and massive neuromorphic computing.

Methodologic considerations in estimating racial disparity of mortality among very preterm infants.

This review explores methodological considerations in estimating racial disparities in mortality among very preterm infants (VPIs). Significant methodological variations are evident across studies, potentially affecting the estimated mortality rates of VPIs across racial groups and influencing the perceived direction and magnitude of racial disparities. Key methodological approaches include the birth-based approach versus the fetuses-at-risk approach, with each offering distinct insights depending on the specific research questions posed. Cohort selection and the decision for crude versus adjusted comparison are also critical elements that shape the outcomes and interpretations of these studies. This review underscores the importance of careful methodological planning and highlights that no single approach is definitively superior; rather, each has its strengths and limitations depending on the research objectives. The findings suggest that adjusting the methodological approach to align with specific research questions and contexts is essential for accurately assessing and addressing racial disparities in neonatal mortality. IMPACT: Elucidates the impact of methodological choices on perceived racial disparities in neonatal mortality. Offers a comprehensive comparison of birth-based vs. fetuses-at-risk approaches in the context of racial disparity research. Provides guidance on the cohort selection and adjustment criteria critical for interpreting studies on racial disparities in very preterm infant mortality.

Diagnostic and screening potential of plasma exosome miR­99b­5p and its combination with other miRNAs for colorectal cancer.

Extracellular vesicles (EVs) secreted by tumor cells have been documented to hold viable biomarker potential. Therefore, the present study evaluated the potential clinical value of EV-microRNAs (miRNAs or miRs) in the plasma exosomes of patients with colorectal cancer (CRC) for the early diagnosis and screening of CRC. In total, 95 plasma samples were collected at The Third Affiliated Hospital of Guangzhou Medical University (Guangzhou, China) between 2017 and 2019. Specifically, 68 samples were from patients with CRC and 27 were from healthy control (HC) donors. High-throughput sequencing was used to detect the expression of miRNAs in the isolated plasma EVs, which was subsequently verified by reverse transcription-quantitative PCR. Receiver operating characteristic (ROC) curves were used to analyze the diagnostic potential of single and combined miRNAs for CRC. Bioinformatics analysis was employed to predict the target genes of candidate miRNAs. Compared with those in the HC group, the CRC group expressed higher levels of miR-99b-5p and miR-409-3p, especially during the early stages of CRC. Clinicopathological analysis confirmed the higher expression levels of miR-99b-5p during the early stages, as well as higher expression levels in the colon compared with those in the rectum. ROC curve analysis revealed that the area under the curve (AUC) of miR-99b-5p for the diagnosis of early CRC was 73.5% (P=0.007). The early diagnostic capability of miR-99b-5p combined with miR-409-3p for CRC was evaluated, and the AUC was found to be 74.1% (P=0.006). In addition, the AUC of the combination of miR-99b-5p, miR-409-3p and carcinoembryonic antigen was 81.2% (P<0.001), indicating that this three-parameter combination displayed higher diagnostic power compared with any single miRNA for early CRC screening. The results from the present study suggest that the expression of miR-99b-5p in plasma exosomes is significantly upregulated in CRC, which holds potential for the early diagnosis of this cancer type. Such potential can be enhanced further by combining it with other miRNAs. Therefore, the present study provides a comprehensive but preliminary insight for the viability of miR-99b-5p (alone or combined with other miRNAs) for CRC diagnosis, which requires further exploration in the future.

Mortality and extrauterine growth restriction of necrotizing enterocolitis in very preterm infants with heart disease: a multi-center cohort study.

Congenital heart disease (CHD) and patent ductus arteriosus (PDA) are risk factors of necrotizing enterocolitis (NEC) in infants. However, it is unclear whether the prognosis of NEC is different between very preterm infants (VPIs) with and without heart diseases. This was an observational cohort study that enrolled VPIs (born between 24+0 and 31+6 weeks) admitted to 79 tertiary neonatal intensive care units (NICU) in the Chinese Neonatal Network (CHNN) between 2019 and 2021. The exposure was CHD or isolated PDA, and VPIs with NEC were divided into three groups: complicated with CHD, with isolated PDA, and without heart diseases. The primary outcomes were NEC-related adverse outcomes (death or extrauterine growth restriction (EUGR)). Logistic regression models were used to adjust potential confounders and calculate the odds ratios (ORs) and 95% confidential intervals (CIs) for each outcome. A total of 1335 VPIs with NEC were enrolled in this study, including 65 VPIs with CHD and 406 VPIs with isolated PDA. The VPIs with heart diseases had smaller gestational ages and lower body weights at birth, more antenatal steroids use, and requiring inotrope prior to the onset of NEC. While suffering from NEC, there was no significant increased risks in NEC-related death in VPIs with either CHD (adjusted OR [aOR]: 1.10; 95% CI: 0.41-2.50) or isolated PDA (aOR: 1.25; 95% CI 0.82-1.87), and increased risks in EUGR were identified in either survival VPIs with CHD (aOR: 2.35; 95% CI: 1.31-4.20) or isolated PDA (aOR: 1.53; 95% CI: 1.16-2.01) in survivors. The composite outcome (death or EUGR) was also more often observed in VPIs with either CHD (aOR: 2.07; 95% confidence interval [CI]: 1.20-3.60) or isolated PDA (aOR: 1.51; 95% CI: 1.17-1.94) than that without heart diseases. VPIs with either CHD or isolated PDA were associated with significantly prolonged duration of fasting, extended time to achieve full enteral feeding, and longer ventilation duration and hospitalization duration. Similar characteristics were also seen in VPIs with isolated PDA, with the exception that VPIs with CHD are more likely to undergo surgical intervention and maintain a prolonged fast after NEC.     Conclusion: In VPIs with NEC, CHD and isolated PDA are associated with an increased risk in worse outcomes. We recommend that VPIs with cardiac NEC be managed with aggressive treatment and nutrition strategies to prevent EUGR. What is Known: • CHD and PDA are risk factors for NEC in infants, which can lead to adverse outcomes such as death and EUGR. • NEC in infants with heart disease differs clinically from that in infants without heart disease and should be recognized as a separate disease process. What is New: • CHD and isolated PDA are associated with increased risks of EUGR in VPIs with NEC. • Risk factors associated with VPIs with cardiac NEC suggested these patients should be managed with aggressive treatment and nutrition strategies to adverse outcomes.

Early Antibiotic Exposure and Bronchopulmonary Dysplasia in Very Preterm Infants at Low Risk of Early-Onset Sepsis.

Importance: The overutilization of antibiotics in very preterm infants (VPIs) at low risk of early-onset sepsis (EOS) is associated with increased mortality and morbidities. Nevertheless, the association of early antibiotic exposure with bronchopulmonary dysplasia (BPD) remains equivocal. Objective: To evaluate the association of varying durations and types of early antibiotic exposure with the incidence of BPD in VPIs at low risk of EOS. Design, Setting, and Participants: This national multicenter cohort study utilized data from the Chinese Neonatal Network (CHNN) which prospectively collected data from January 1, 2019, to December 31, 2021. VPIs less than 32 weeks' gestational age or with birth weight less than 1500 g at low risk of EOS, defined as those born via cesarean delivery, without labor or rupture of membranes, and no clinical evidence of chorioamnionitis, were included. Data analysis was conducted from October 2022 to December 2023. Exposure: Early antibiotic exposure was defined as the total number of calendar days antibiotics were administered within the first week of life, which were further categorized as no exposure, 1 to 4 days of exposure, and 5 to 7 days of exposure. Main Outcomes and Measures: The primary outcome was the composite of moderate to severe BPD or mortality at 36 weeks' post menstrual age (PMA). Logistic regression was employed to assess factors associated with BPD or mortality using 2 different models. Results: Of the 27 176 VPIs included in the CHNN during the study period (14 874 male [54.7%] and 12 302 female [45.3%]), 6510 (23.9%; 3373 male [51.8%] and 3137 female [48.2.%]) were categorized as low risk for EOS. Among them, 1324 (20.3%) had no antibiotic exposure, 1134 (17.4%) received 1 to 4 days of antibiotics treatment, and 4052 (62.2%) received 5 to 7 days of antibiotics treatment. Of the 5186 VPIs who received antibiotics, 4098 (79.0%) received broad-spectrum antibiotics, 888 (17.1%) received narrow-spectrum antibiotics, and 200 (3.9%) received antifungals or other antibiotics. Prolonged exposure (5-7 days) was associated with increased likelihood of moderate to severe BPD or death (adjusted odds ratio [aOR], 1.23; 95% CI, 1.01-1.50). The use of broad-spectrum antibiotics (1-7 days) was also associated with a higher risk of moderate to severe BPD or death (aOR, 1.27; 95% CI, 1.04-1.55). Conclusions and Relevance: In this cohort study of VPIs at low risk for EOS, exposure to prolonged or broad-spectrum antibiotics was associated with increased risk of developing moderate to severe BPD or mortality. These findings suggest that VPIs exposed to prolonged or broad-spectrum antibiotics early in life should be monitored for adverse outcomes.

Association of Antenatal Corticosteroids with Neonatal Outcomes among Very Preterm Infants Born to Mothers with Clinical Chorioamnionitis: A Multicenter Cohort Study.

The objective of this study was to assess the relationship of ACS with neonatal outcomes among very preterm infants born to mothers with clinical chorioamnionitis in China. This was a multicenter retrospective cohort study. Study participants included infants born at <32 weeks' gestation with clinical chorioamnionitis and registered in the Chinese Neonatal Network from 1 January 2019 to 31 December 2020. Infants were divided into two groups: any amount of ACS or no administration of ACS. Multivariable generalized linear models using generalized estimating equations were used to assess the association between ACS and neonatal outcomes among the study population. We identified 2193 infants eligible for this study; 1966 (89.6%) infants had received ACS therapy, and 227 (10.4%) had not received any ACS therapy. Among very preterm infants born to mothers with clinical chorioamnionitis, any ACS usage was significantly associated with decreased risks of early death (aRR 0.56, 95% CI 0.32, 0.99) and severe ROP (aRR 0.51, 95% CI 0.28, 0.93) after adjustment for maternal hypertension, gestational age at birth, Caesarean section, being inborn, and administration of systemic antibiotics to the mother within 24 h before birth. In addition, out of the 2193 infants, the placentas of 1931 infants underwent pathological examination with recorded results. Subsequently, 1490 of these cases (77.2%) were diagnosed with histological chorioamnionitis. In 1490 cases of histologic chorioamnionitis, any ACS usage was significantly related to decreased risks of overall mortality (aRR 0.52, 95% CI 0.31, 0.87), severe ROP (aRR 0.47, 95% CI 0.25, 0.97), and respiratory distress syndrome (aRR 0.52, 95% CI 0.31, 0.87). We concluded that any ACS was associated with reduced risks for neonatal early death and severe ROP among very preterm infants born to mothers with clinical chorioamnionitis.

RBC transfusion and necrotizing enterocolitis in very preterm infants: a multicenter observational study.

The causal relationship between Packed red blood cell (RBC) transfusion and necrotizing enterocolitis (NEC) remains uncertain. This study aims to provide an exploration of transfusion and NEC in very preterm infants. Using data from the Chinese Neonatal Network cohort study between 2019 and 2021, the analysis focused on very preterm infants (with a birth weight of < 1500 g or a gestational age of < 32 weeks) who developed NEC after receiving transfusions. The time interval between the prior transfusion and NEC was analyzed. An uneven distribution of the time interval implies an association of transfusion and NEC. Additionally, multivariable logistic analysis was conducted to detect the prognosis of defined transfusion-associated NEC(TANEC). Of the 16,494 infants received RBC transfusions, NEC was noted in 1281 (7.7%) cases, including 409 occurred after transfusion. Notably, 36.4% (149/409) of post-transfusion NEC occurred within 2 days after transfusion. The time interval distribution showed a non-normal pattern (Shapiro-Wilk test, W = 0.513, P < 0.001), indicating a possible link between transfusion and NEC. TANEC was defined as NEC occurred within 2 days after transfusion. Infants with TANEC had a higher incidence of death (adjusted OR 1.69; 95% CI 1.08 to 2.64), severe bronchopulmonary dysplasia (adjusted OR 2.03; 95% CI 1.41 to 2.91) and late-onset sepsis (adjusted OR 2.06; 95% CI 1.37 to 3.09) compared with infants without NEC after transfusion. Unevenly high number of NEC cases after RBC transfusions implies transfusion is associated with NEC. TANEC is associated with a poor prognosis. Further research is warranted to enhance our understanding of TANEC.

The performance of the practices associated with the occurrence of severe intraventricular hemorrhage in the very premature infants: data analysis from the Chinese neonatal network.

BACKGROUND: The occurrence of severe intraventricular hemorrhage (sIVH) was high in the very preterm infants (VPIs) in China. The management strategies significantly contributed to the occurrence of sIVH in VPIs. However, the status of the perinatal strategies associated with sIVH for VPIs was rarely described across the multiple neonatal intensive care units (NICUs) in China. We aim to investigate the characteristics of the perinatal strategies associated with sIVH for VPIs across the multiple NICUs in China. METHODS: This was a retrospective analysis of data from a prospective cohort of Chinese Neonatal Network (CHNN) dataset, enrolling infants born at 24+0-31+6 from 2019 to 2021. Eleven perinatal practices performed within the first 3 days of life were investigated including antenatal corticosteroids use, antenatal magnesium sulphate therapy, intubation at birth, placental transfusion, need for advanced resuscitation, initial inhaled gas of 100% FiO2 in delivery room, initial invasive respiratory support, surfactant and caffeine administration, early enteral feeding, and inotropes use. The performances of these practices across the multiple NICUs were investigated using the standard deviations of differences between expected probabilities and observations. The occurrence of sIVH were compared among the NICUs. RESULTS: A total of 24,226 infants from 55 NICUs with a mean (SD) gestational age of 29.5 (1.76) and mean (SD) birthweight of 1.31(0.32) were included. sIVH was detected in 5.1% of VPIs. The rate of the antenatal corticosteroids, MgSO4 therapy, and caffeine was 80.0%, 56.4%, and 31.5%, respectively. We observed significant relationships between sIVH and intubation at birth (AOR 1.52, 95% CI 1.13 to 1.75) and initial invasive respiratory support (AOR 2.47, 95% CI 2.15 to 2.83). The lower occurrence of sIVH (4.8%) was observed corresponding with the highest utility of standard antenatal care, the lowest utility of invasive practices, and early enteral feeding administration. CONCLUSIONS: The current evidence-based practices were not performed in each VPI as expected among the studied Chinese NICUs. The higher utility of the invasive practices could be related to the occurrence of sIVH.

Spontaneous intestinal perforation among very preterm infants in China: a multicenter cohort study.

Background: Spontaneous intestinal perforation (SIP) is one of the most serious surgical bowel conditions affecting preterm infants. There are limited data on the mortality and morbidities of very preterm infants [VPIs, <32 weeks' gestational age (GA)] with SIP in China. The study aimed to describe the prevalence, treatment, and outcomes of SIP among VPIs in China. Methods: This retrospective cohort study included all infants born at 24+0-31+6 weeks GA from January 1, 2019, to December 31, 2020, and admitted within seven days after birth to the neonatal intensive care units in the Chinese Neonatal Network. The primary outcome was survival without major morbidities. The association between SIP and neonatal outcomes was evaluated using multivariate logistic regression controlling for possible confounders. Results: Out of the 15,814 enrolled infants, 150 (1.0%) developed SIP with a median onset age of four (IQR 2-6) days. Infants with GA 24+0-25+6 weeks had the highest incidence of SIP (13/532, 2.4%), followed by those with GA 26+0-27+6 weeks (22/2,005, 1.1%), 28+0-29+6 weeks (44/5,269, 0.8%) and 30+0-31+6 weeks (71/8,008, 0.9%). Ten SIP cases were lost to follow-up with unknown survival status and 41 (29.3%) of the remaining 140 infants with SIP died during hospitalization. Only 29.3% of infants with SIP survived without major morbidities, significantly lower than those without SIP (59.2%; P<0.01). Multivariate analysis revealed SIP was associated with a higher risk of overall death (adjusted OR 3.36; 95% CI: 1.85 to 6.08), late-onset sepsis (adjusted OR 2.10; 95% CI: 1.02 to 4.31), and bronchopulmonary dysplasia (adjusted OR 2.49; 95% CI: 1.44 to 4.30). Among all infants with SIP, 28 (18.7%) did not receive any surgical intervention. Laparotomy was provided to 113 (92.6%) of the remaining 122 infants, solely (84/122, 68.9%) or following peritoneal drainage (29/122, 23.8%), while nine (7.4%) infants underwent peritoneal drainage only. Conclusions: Around 1% of VPIs in China developed SIP, associated with increased risk of mortality and morbidities. Over 90% of VPIs with SIP underwent laparotomy as initial or subsequent surgical treatment. Effective and evidence-based strategies are needed for the prevention and management of SIP.

Association between Neonatal Outcomes and Admission Hypothermia among Very Preterm Infants in Chinese Neonatal Intensive Care Units: A Multicenter Cohort Study.

OBJECTIVE: We aimed to investigate the relationship between admission hypothermia and outcomes among very preterm infants (VPIs) in neonatal intensive care units (NICUs) in China. We also investigated the frequency of hypothermia in VPIs in China and the variation in hypothermia across Chinese Neonatal Network (CHNN) sites. STUDY DESIGN: This retrospective cohort study enrolled infants with 240/7 to 316/7 weeks of gestation with an admission body temperature ≤37.5 °C who were admitted to CHNN-participating NICUs between January 1 and December 31, 2019. RESULTS: A total of 5,913 VPIs were included in this study, of which 4,075 (68.9%) had hypothermia (<36.5 °C) at admission. The incidence of admission hypothermia varied widely across CHNN sites (9-100%). Lower gestational age (GA), lower birth weight, antenatal steroid administration, multiple births, small for GA, Apgar scores <7 at the 5th minute, and intensive resuscitation were significantly associated with admission hypothermia. Compared with infants with normothermia (36.5-37.5 °C), the adjusted odds ratios (ORs) for composite outcome among infants with admission hypothermia <35.5 °C increased to 1.47 (95% confidence interval [CI], 1.15-1.88). The adjusted ORs for mortality among infants with admission hypothermia (36.0-36.4 and <35.5 °C) increased to 1.41 (95% CI, 1.09-1.83) and 1.93 (95% CI, 1.31-2.85), respectively. Admission hypothermia was associated with a higher likelihood of bronchopulmonary dysplasia, but was not associated with necrotizing enterocolitis ≥stage II, severe intraventricular hemorrhage, cystic periventricular leukomalacia, severe retinopathy of prematurity, or sepsis. CONCLUSION: Admission hypothermia remains a common problem for VPIs in a large cohort in China and is associated with adverse outcomes. Continuous quality improvement of admission hypothermia in the future may result in a substantial improvement in the outcomes of VPIs in China. KEY POINTS: · Admission hypothermia is common in VPIs.. · The incidence of admission hypothermia in VPIs remains high in China.. · Admission hypothermia is associated with adverse outcomes in VPIs..

Metformin normalizes mitochondrial function to delay astrocyte senescence in a mouse model of Parkinson's disease through Mfn2-cGAS signaling.

BACKGROUND: Senescent astrocytes play crucial roles in age-associated neurodegenerative diseases, including Parkinson's disease (PD). Metformin, a drug widely used for treating diabetes, exerts longevity effects and neuroprotective activities. However, its effect on astrocyte senescence in PD remains to be defined. METHODS: Long culture-induced replicative senescence model and 1-methyl-4-phenylpyridinium/α-synuclein aggregate-induced premature senescence model, and a mouse model of PD were used to investigate the effect of metformin on astrocyte senescence in vivo and in vitro. Immunofluorescence staining and flow cytometric analyses were performed to evaluate the mitochondrial function. We stereotactically injected AAV carrying GFAP-promoter-cGAS-shRNA to mouse substantia nigra pars compacta regions to specifically reduce astrocytic cGAS expression to clarify the potential molecular mechanism by which metformin inhibited the astrocyte senescence in PD. RESULTS: We showed that metformin inhibited the astrocyte senescence in vitro and in PD mice. Mechanistically, metformin normalized mitochondrial function to reduce mitochondrial DNA release through mitofusin 2 (Mfn2), leading to inactivation of cGAS-STING, which delayed astrocyte senescence and prevented neurodegeneration. Mfn2 overexpression in astrocytes reversed the inhibitory role of metformin in cGAS-STING activation and astrocyte senescence. More importantly, metformin ameliorated dopamine neuron injury and behavioral deficits in mice by reducing the accumulation of senescent astrocytes via inhibition of astrocytic cGAS activation. Deletion of astrocytic cGAS abolished the suppressive effects of metformin on astrocyte senescence and neurodegeneration. CONCLUSIONS: This work reveals that metformin delays astrocyte senescence via inhibiting astrocytic Mfn2-cGAS activation and suggest that metformin is a promising therapeutic agent for age-associated neurodegenerative diseases.

Application of machine learning in the study of cobalt-based oxide catalysts for antibiotic degradation: An innovative reverse synthesis strategy.

This study addresses antibiotic pollution in global water bodies by integrating machine learning and optimization algorithms to develop a novel reverse synthesis strategy for inorganic catalysts. We meticulously analyzed data from 96 studies, ensuring quality through preprocessing steps. Employing the AdaBoost model, we achieved 90.57% accuracy in classification and an R²value of 0.93 in regression, showcasing strong predictive power. A key innovation is the Sparrow Search Algorithm (SSA), which optimizes catalyst selection and experimental setup tailored to specific antibiotics. Empirical experiments validated SSA's efficacy, with degradation rates of 94% for Levofloxacin and 97% for Norfloxacin, aligning closely with predictions within a 2% margin of error. This research advances theoretical understanding and offers practical applications in material science and environmental engineering, significantly enhancing catalyst design efficiency and accuracy through the fusion of advanced machine learning techniques and optimization algorithms.

Characteristics of red blood cell transfusion among very preterm infants in China.

BACKGROUND AND OBJECTIVES: National-level data on the incidence of red blood cell (RBC) transfusions and outcomes among very preterm infants (VPIs) are lacking in China. This study aims to describe the use and variation of RBC transfusion among VPIs in China. MATERIALS AND METHODS: This cohort study was conducted among 70 tertiary hospitals participating in the Chinese Neonatal Network (CHNN) from 2019 to 2020 across China. All VPIs admitted to the CHNN neonatal intensive care units (NICUs) were included. RESULTS: A total of 13,447 VPIs were enrolled, of whom 7026 (52.2%) received ≥1 RBC transfusions. The mean number of transfusions per infant was 2 (interquartile range [IQR] 1-4 times) and the median age at first transfusion was 15 days (IQR 3-27 days). The transfusion rate was higher in critically ill infants compared with non-critically ill infants (70.5% vs. 39.3%). The transfusion rate varied widely (13.5%-95.0%) between different NICUs. The prevalence of death, severe intra-ventricular haemorrhage, necrotizing enterocolitis (NEC) or spontaneous intestinal perforation (SIP), sepsis, bronchopulmonary dysplasia (BPD), severe retinopathy of prematurity (ROP) and cystic periventricular leukomalacia (cPVL) was significantly higher in the transfused group. Among non-critically ill infants, RBC transfusion was independently associated with BPD, severe ROP and cPVL. CONCLUSION: Our study, providing the first baseline data on RBC transfusions among VPIs in China, shows an alarmingly high RBC transfusion rate with significant site variations. There is an urgent need for national guidelines on RBC transfusions for VPIs in China.

Pathogen-specific alterations in intestinal microbiota precede urinary tract infections in preterm infants: a longitudinal case-control study.

Urinary tract infections (UTIs) are among the most common late-onset infections in preterm infants, characterized by nonspecific symptoms and a pathogenic spectrum that diverges from that of term infants and older children, which present unique diagnostic and therapeutic challenges. Existing data on the role of gut microbiota in UTI pathogenesis in this demographic are limited. This study aims to investigate alterations in gut microbiota and fecal calprotectin levels and their association with the development of UTIs in hospitalized preterm infants. A longitudinal case-control study was conducted involving preterm infants admitted between January 2018 and October 2020. Fecal samples were collected weekly and analyzed for microbial profiles and calprotectin levels. Propensity score matching, accounting for key perinatal factors including age and antibiotic use, was utilized to match samples from UTI-diagnosed infants to those from non-UTI counterparts. Among the 151 preterm infants studied, 53 were diagnosed with a UTI, predominantly caused by Enterobacteriaceae (79.3%) and Enterococcaceae (19.0%). Infants with UTIs showed a significantly higher abundance of these families compared to non-UTI infants, for both Gram-negative and positive pathogens, respectively. Notably, there was a significant pre-UTI increase in the abundance of pathogen-specific taxa in infants later diagnosed with UTIs, offering high predictive value for early detection. Shotgun metagenomic sequencing further confirmed the dominance of specific pathogenic species pre-UTI and revealed altered virulence factor profiles associated with Klebsiella aerogenes and Escherichia coli infections. Additionally, a decline in fecal calprotectin levels was observed preceding UTI onset, particularly in cases involving Enterobacteriaceae. The observed pathogen-specific alterations in the gut microbiota preceding UTI onset offer novel insight into the UTI pathogenesis and promising early biomarkers for UTIs in preterm infants, potentially enhancing the timely management of this common infection. However, further validation in larger cohorts is essential to confirm these findings.

Vagus nerve stimulation as a promising neuroprotection for ischemic stroke via α7nAchR-dependent inactivation of microglial NLRP3 inflammasome.

Ischemic stroke is a major cause of disability and death worldwide, and its management requires urgent attention. Previous studies have shown that vagus nerve stimulation (VNS) exerts neuroprotection in ischemic stroke by inhibiting neuroinflammation and apoptosis. In this study, we evaluated the timing for VNS intervention in ischemic stroke, and the underlying mechanisms  of VNS-induced neuroprotection. Mice were subjected to transient middle cerebral artery occlusion (tMCAO) for 60 min. The left vagus nerve at cervical level was exposed and attached to an electrode connected to a low-frequency electrical stimulator. Vagus nerve stimulation (VNS) was given for 60 min before, during and after tMCAO (Pre-VNS, Dur-VNS, Post-VNS). Neurological function was assessed 24 h after reperfusion. We found that all the three VNS significantly protected against the tMCAO-induced injury evidenced by improved neurological function and reduced infarct volume. Moreover, the Pre-VNS was the most effective against the ischemic injury. We found that tMCAO activated microglia in the ischemic core and penumbra regions of the brain, followed by the NLRP3 inflammasome activation-induced neuroinflammation, which finally triggered neuronal death. VNS treatment preserved α7nAChR expression in the penumbra regions, inhibited NLRP3 inflammasome activation and ensuing neuroinflammation, rescuing cerebral neurons. The role of α7nAChR in microglial NLRP3 inflammasome activation in ischemic stroke was further validated using genetic manipulations, including Chrna7 knockout mice and microglial Chrna7 overexpression mice, as well as pharmacological interventions using the α7nAChR inhibitor methyllycaconitine and agonist PNU-282987. Collectively, this study demonstrates the potential of VNS as a safe and effective strategy to treat ischemic stroke, and presents a new approach targeting microglial NLRP3 inflammasome, which might be therapeutic for other inflammation-related diseases.

UDRSNet: An unsupervised deformable registration module based on image structure similarity.

BACKGROUND: Image registration is a challenging problem in many clinical tasks, but deep learning has made significant progress in this area over the past few years. Real-time and robust registration has been made possible by supervised transformation estimation. However, the quality of registrations using this framework depends on the quality of ground truth labels such as displacement field. PURPOSE: To propose a simple and reliable method for registering medical images based on image structure similarity in a completely unsupervised manner. METHODS: We proposed a deep cascade unsupervised deformable registration approach to align images without reliable clinical data labels. Our basic network was composed of a displacement estimation module (ResUnet) and a deformation module (spatial transformer layers). We adopted l 2 $l_2$ -norm to regularize the deformation field instead of the traditional l 1 $l_1$ -norm regularization. Additionally, we utilized structural similarity (ssim) estimation during the training stage to enhance the structural consistency between the deformed images and the reference images. RESULTS: Experiments results indicated that by incorporating ssim loss, our cascaded methods not only achieved higher dice score of 0.9873, ssim score of 0.9559, normalized cross-correlation (NCC) score of 0.9950, and lower relative sum of squared difference (SSD) error of 0.0313 on CT images, but also outperformed the comparative methods on ultrasound dataset. The statistical t $t$ -test results also proved that these improvements of our method have statistical significance. CONCLUSIONS: In this study, the promising results based on diverse evaluation metrics have demonstrated that our model is simple and effective in deformable image registration (DIR). The generalization ability of the model was also verified through experiments on liver CT images and cardiac ultrasound images.

[A case of neonatal Netherton syndrome]. / 新生儿Netherton综合征1例.

A male infant, aged 6 days, was admitted to the hospital due to respiratory distress and systemic desquamative rash after birth. The infant presented with erythema and desquamative rash, respiratory failure, recurrent infections, chronic diarrhea, hypernatremic dehydration, and growth retardation. Comprehensive treatment, including anti-infection therapy, intravenous immunoglobulin administration, and skin care, resulted in improvement of the rash, but recurrent infections persisted. Second-generation sequencing revealed a homozygous mutation in the SPINK5 gene, consistent with the pathogenic variation of Netherton syndrome. The family opted for palliative care, and the infant died at the age of 2 months after discharge. This report documents a case of Netherton syndrome caused by the SPINK5 gene mutation in the neonatal period, and highlights multidisciplinary diagnosis and therapy for this condition.

Synergistic effects of achieving perinatal interventions on bronchopulmonary dysplasia in preterm infants.

To investigate the effect of perinatal interventions on the risk of severe BPD (sBPD) and death in extremely preterm infants (EPIs) and their synergistic effects. This was a secondary analysis of the prospective cohort Chinese Neonatal Network (CHNN). Infants with a birth weight of 500 to 1250 g or 24-28 weeks completed gestational age were recruited. The impacts and the synergistic effects of six evidence-based perinatal interventions on the primary outcomes of sBPD and death were assessed by univariate and multivariable logistic regression modeling. Totally, 6568 EPIs were finally enrolled. Antenatal corticosteroid (adjusted OR, aOR, 0.74; 95%CI, 0.65-083), birth in centers with tertiary NICU (aOR, 0.64; 95%CI, 0.57-0.72), preventing intubation in the delivery room (aOR, 0.65; 95%CI, 0.58-0.73), early caffeine therapy (aOR, 0.59; 95%CI, 0.52-0.66), and early extubating (aOR, 0.42; 95%CI 0.37-0.47), were strongly associated with a lower risk of sBPD and death while early surfactant administration was associated with a lower risk of death (aOR, 0.84; 95%CI, 0.72, 0.98). Compared with achieving 0/1 perinatal interventions, achieving more than one intervention was associated with decreased rates (46.6% in 0/1 groups while 38.5%, 29.6%, 22.2%, 16.2%, and 11.7% in 2/3/4/5/6-intervention groups respectively) and reduced risks of sBPD/death with aORs of 0.76(0.60, 0.96), 0.55(0.43, 0.69), 0.38(0.30, 0.48), 0.28(0.22, 0.36), and 0.20(0.15, 0.27) in 2, 3, 4, 5, and 6 intervention groups respectively. Subgroup analyses showed consistent results. CONCLUSION: Six perinatal interventions can effectively reduce the risk of sBPD and death in a synergistic form. WHAT IS KNOWN: • Bronchopulmonary dysplasia (BPD) is a multifactorial chronic lung disease associated with prematurity. The effective management of BPD requires a comprehensive set of interventions. However, the extent to which these interventions can mitigate the risk of severe outcomes, such as severe BPD or mortality, or if they possess synergistic effects remains unknown. WHAT IS NEW: • The implementation of various perinatal interventions, such as prenatal steroids, birth in centers with tertiary NICU, early non-Invasive respiratory support, surfactant administration within 2 hours after birth, early caffeine initiation within 3 days, and early extubation within 7 days after birth has shown promising results in the prevention of severe bronchopulmonary dysplasia (BPD) or mortality in extremely preterm infants. Moreover, these interventions have demonstrated synergistic effects when implemented in combination.

In vitro inhalation bioaccessibility and health risk assessment of difenoconazole in the atmosphere.

BACKGROUND: Assessment of the risk of pesticide inhalation in populations around farmland is necessary because inhalation is one of the ways in which pesticides can risk human health. This study aimed to identify the inhalation risk of difenoconazole on humans by using dose-response and exposure assessments. RESULTS: In the field simulation application, respiratory exposure in populations around farmland ranged from 71 to 430 ng/m3 . Using response surface methodology, the maximum bioaccessibility of difenoconazole in three simulated lung fluids was 35.33% in Gamble's solution (GS), 34.12% in artificial lysosomal fluid (ALF), and 42.06% in simulated interstitial lung fluid (SLF). Taking the proliferation activity of the A549 cell model as the endpoint, the benchmark dose limit and benchmark dose of difenoconazole on A549 cells were 16.36 and 5.60 mg/kg, respectively. The margin of exposure to difenoconazole in GS, ALF and SLF were, respectively, 8.66 × 105 to 5.28 × 106 , 8.97 × 105 to 5.47 × 106 and 7.28 × 105 to 4.44 × 106 . CONCLUSION: The risk assessment results indicate that under all circumstances, applying difenoconazole is safe for populations around farmland. However, a fan-shaped nozzle, suspension concentrate and greater inhalation height increase the risk of inhalation. © 2023 Society of Chemical Industry.