BACKGROUND: In China, lung cancer remains the cancer with the highest incidence and mortality rate. Among early-stage lung adenocarcinomas (LUAD), the micropapillary (MPP) component is prevalent and typically exhibits high aggressiveness, significantly correlating with early metastasis, lymphatic infiltration, and reduced five-year survival rates. Therefore, the study is to explore the similarities and differences between MPP and non-micropapillary (non-MPP) components in malignant pulmonary nodules characterized by GGOs in early-stage LUAD, identify unique mutational features of the MPP component and analyze the relationship between the ZNF469 gene, a member of the zinc-finger protein family, and the prognosis of early-stage LUAD, as well as its correlation with immune infiltration. METHODS: A total of 31 malignant pulmonary nodules of LUAD were collected and dissected into paired MPP and non-MPP components using microdissection. Whole-exome sequencing (WES) was performed on the components of early-stage malignant pulmonary nodules. Mutational signatures analysis was conducted using R packages such as maftools, Nonnegative Matrix Factorization (NMF), and Sigminer to unveil the genomic mutational characteristics unique to MPP components in invasive LUAD compared to other tumor tissues. Furthermore, we explored the expression of the ZNF469 gene in LUAD using The Cancer Genome Atlas (TCGA) database to investigate its potential association with the prognosis. We also investigated gene interaction networks and signaling pathways related to ZNF469 in LUAD using the GeneMANIA database and conducted Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis. Lastly, we analyzed the correlation between ZNF469 gene expression and levels of immune cell infiltration in LUAD using the TIMER and TISIDB databases. RESULTS: MPP components exhibited a higher number of genomic variations, particularly the 13th COSMIC (Catalogue of Somatic Mutations in Cancer) mutational signature characterized by the activity of the cytidine deaminase APOBEC family, which was unique to MPP components compared to non-MPP components in tumor tissues. This suggests the potential involvement of APOBEC in the progression of MPP components in early-stage LUAD. Additionally, MPP samples with high similarity to APOBEC signature displayed a higher tumor mutational burden (TMB), indicating that these patients may be more likely to benefit from immunotherapy. The expression of ZNF469 was significantly upregulated in LUAD compared to normal tissue, and was associated with poor prognosis in LUAD patients (P<0.05). Gene interaction network analysis and GO/KEGG enrichment analysis revealed that COL6A1, COL1A1, COL1A2, TGFB2, MMP2, COL8A2 and C2CD4C interacted with ZNF469 and were mainly involved in encoding collagen proteins and participating in the constitution of extracellular matrix. ZNF469 expression was positively correlated with immune cell infiltration in LUAD (P<0.05). CONCLUSIONS The study has unveiled distinctive mutational signatures in the MPP components of early-stage invasive LUAD in the Asian population. Furthermore, we have identified that the elevated expression of mutated ZNF469 impacts the prognosis and immune infiltration in LUAD, suggesting its potential as a diagnostic and prognostic biomarker in LUAD.
Humans ; Lung Neoplasms/genetics* ; Adenocarcinoma of Lung/genetics* ; China ; Prognosis ; Transcription Factors

With the growth of the global economy , changes in climate and ecological environments, and increased mobility of humans and animals, the transmission risk of vector-borne tropical diseases continues to rise. To address this challenge, strengthening surveillance of vector-borne tropical diseases is urgent. This consensus brought together 29 renowned experts in related professional fields from 26 institutions in China, who, through analyzing the epidemic trend and hazard situation of vector-borne tropical diseases and summarizing the working experiences of experts, have firstly reached following consensus: the burden of vector-borne tropical diseases is heavy with great threats to human health; China has achieved remarkable results in prevention and control of vector-borne tropical diseases , but still needs to strengthen the surveillance and response actively. Secondly, a unanimous consensus has been reached on the aspects of surveillance definition, objectives, contents, and methods of vector-borne tropical diseases. Thirdly, detail requirements have been agreed including: strengthening the concept of early surveillance and forecast, standarding the function, evaluation steps, and construction requirements of surveillance system for vector-borne tropical diseases. Fourthly, key tasks were put forward that need to be investigated and strengthened in the future. This expert consensus provides a standardized reference for the construction of the surveillance pathway and surveillance system for vector-borne tropical diseases in China.

bstract: Objective To elucidate the distribution characteristics of mosquito species and the population genetic diversity of important mosquito species in the Wuyi Mountain Nature Reserve, with the aim of providing a scientific basis for the prevention and control of mosquito-borne diseases in the region. Methods Within Wuyi Mountain Nature Reserve 2022- 2023, 16 sampling sites were selected, where larvae were collected using the pipette method and adult mosquitoes were collected using the mosquito trap lamp method. Mosquito species identification was accomplished by integrating morphological characteristics and molecular identification techniques based on CO Ⅰ and CO Ⅱ gene sequences. Software tools such as ClustalX, DnaSP v5.0, and Network v4.6.1.0 were utilized to analyze the genetic differentiation (Fst), gene flow (Nm) among populations of Aedes japonicus, Aedes albopictus and Armigeres subalbatus. Results The mosquito specimens collected from the Wuyi Mountain Nature Reserve were identified as 30 species belonging to 8 genera within the Culicidae family. Among them, there were 10 species of Aedes, 13 species of Culex, 1 species each of Armigeres, Orthopodomyia, Uranotaenia, Tripyeroides, and Anopheles, and 2 species of Toxorhynchites. Analysis of the genetic structure of important mosquito populations showed that the haplotype diversity index (Hd) of Ae. japonicus was 0.994 7, with a generally moderate degree of differentiation between populations and a higher degree of genetic differentiation between populations 6 and 12; Aedeslbopictus had a haplotype diversity index of 0.634 0, with significant genetic differentiation between populations 1 and 2 compared to other groups; Armigeres subalbatus had a haplotype diversity index of 0.703 3, with substantial genetic differentiation and limited gene flow between population 2 and populations 3, 4, 6, and 7. Conclusions The mosquito species are rich in Wuyi Mountain Nature Reserve. A comprehensive survey of the composition and distribution of mosquito populations was carried out, and the characteristics of the population genetic structure of the important species of Ae. japonicus, Ae. Albopictus, and Ar. subalbatus populations were analyzed, providing valuable scientific data reference for local mosquito-borne ecological research and disease prevention and control.

Objective:To investigate the risk factors of bronchopulmonary dysplasia (BPD) in very low birth weight (VLBW) infants with gestational age ≤32 weeks within 28 days after birth and to establish and validate the nomogram model for BPD prediction.Methods:We retrospectively chose VLBW infants with gestational age ≤32 weeks who survived to postmenstrual age (PMA) 36 weeks and were admitted to the neonatal intensive care unit of Peking University Third Hospital from January 2016 to April 2020 as the training cohort. BPD was diagnosed in accordance with the 2018 criteria. The clinical data of these infants were collected, and the risk factors of BPD were analyzed by Chi-square test, Mann-Whitney U test, and multivariate logistic regression, and a nomogram model was established. The area under the curve (AUC) of the receiver operating characteristic (ROC) curve was used to assess the predictive performance. Decision curve analysis (DCA) was constructed for differentiation evaluation, and the calibration chart and Hosmer-Lemeshow goodness of fit test were used for the calibration evaluation. Bootstrap was used for internal validation. VLBW infants with gestational age ≤32 weeks survived to PMA 36 weeks and admitted to Hebei Chengde Maternal and Child Health Hospital from October 2017 to February 2022 were included as the validation cohort. ROC curve and calibration plot were conducted in the validation cohort for external validation. Results:Of the 467 premature infants included in the training cohort, 104 were in the BPD group; of the 101 patients in the external validation cohort, 16 were in the BPD group. Multivariate logistic regression analysis showed that low birth weight ( OR=0.03, 95% CI: 0.01-0.13), nosocomial pneumonia ( OR=2.40, 95% CI: 1.41-4.09), late-onset sepsis ( OR=2.18, 95% CI: 1.18-4.02), and prolonged duration of endotracheal intubation ( OR=1.61, 95% CI: 1.26-2.04) were risk factors for BPD in these groups of infants (all P<0.05). According to the multivariate logistic regression analysis results, a nomogram model for predicting BPD risk was established. The AUC of the training cohort was 0.827 (95% CI: 0.783-0.872), and the ideal cut-off value for predicted probability was 0.206, with a sensitivity of 0.788 (95% CI: 0.697-0.862) and specificity of 0.744 (95% CI: 0.696-0.788). The AUC of the validation cohort was 0.951 (95% CI:0.904-0.999). Taking the prediction probability of 0.206 as the high-risk threshold, the sensitivity and specificity corresponding to this value were 0.812 (95% CI: 0.537-0.950) and 0.882 (95% CI: 0.790-0.939). The Hosmer-Lemeshow goodness-of-fit test in the training and validation cohort showed a good fit ( P>0.05). DCA results showed a high net benefit of clinical intervention in very preterm infants when the threshold probability was 5%~80% for the training cohort. Conclusion:Low birth weight, nosocomial pneumonia, late-onset sepsis, and prolonged tracheal intubation duration are risk factors for BPD. The established nomogram model has a certain value in predicting the risk of BPD in VLBW less than 32 weeks.

This article elaborates the key points of the updated recommendations and the latest evidence of the important steps in China neonatal resuscitation guideline (revised in 2021), aiming to help clinicians better understand the guideline and guide training to achieve a standardized and efficient resuscitation and further to improve neonatal outcomes.

Correct neonatal resuscitation is the primary way to reduce perinatal mortality and neurological sequelae, and adequate preparation is essential. This article introduces the details for preparing neonatal resuscitation (including antenatal consultation) and ways to optimize the practice, aiming to improve the success rate of neonatal resuscitation.

Objective:To analyze the factors influencing pH value in umbilical arterial blood gas (UABG) analysis in preterm infants.Methods:A retrospective study was conducted on live singleton preterm infants ( n=573) who received UABG analysis in Peking University Third Hospital from January 2017 to February 2019. Analysis of variance, independent sample t-test, Spearman's or Pearson's correlation analysis, or linear regression analysis was used to analyze the influencing factors. Results:There was no significant difference in UABG pH value between preterm infants of different gestational ages (F=1.74, P=0.077). Spearman's correlation analysis found no correlation between gestational age and UABG pH value in premature infants ( r=0.003, P=0.940), and neither did Pearson's correlation between birth weight and pH value ( r=0.025, P=0.548). UABG pH value in preterm infants was linearly correlated with vaginal delivery ( t=－5.72, P<0.001), gestational hypertension ( t=－3.99, P<0.001) and placental abruption ( t=－4.52, P<0.001). Conclusions:Preterm infants at different gestational ages show a similar pH value in UABG. For those born to mothers with gestational hypertension or placental abruption, when vaginal delivery is pending, close monitoring and full preparation for resuscitation are necessary.

Objective:To investigate the application of umbilical vein catheterization in neonates.Methods:The patients who underwent umbilical vein catheterization from November 2007 to September 2019 in neonatal intensive care unit (NICU) at Peking University Third Hospital were selected consecutively.Clinical data were collected retrospectively to investigate the application time of umbilical vein catheterization in neonates, the incidence of catheter-related bloodstream infection, pathogenic bacteria and the causes of extubation.Results:A total of 835 newborns were enrolled, including 435 males (52.1%) and 400 females (47.9%). The average gestational age was (30.6±2.4) weeks.The median birth weight was 1 310(1 080, 1 520)g.The average indwelling time of umbilical vein catheterization was (4.850±1.893) days.Catheter related bloodstream infection occurred in ten (1.2%) neonates.The main pathogens were Staphylococcus epidermidis, Staphylococcus wallichi, Staphylococcus haemolyticus and Enterococcus faecium.A total of 770 (92.2%) newborns were extubated in a planned manner, and 65 (7.8%) were unplanned extubation.The top three causes of unplanned extubation were umbilical wheel swelling, clinical diagnosis of sepsis, catheter-related bloodstream infection and tube blockage.Conclusion:Umbilical vein catheterization is simple, high success rate, safe and can be used in NICU for a short time.If possible, abdominal B-ultrasound and echocardiography should be monitored and catheter related complications should be noted.

Objective:To explore the feasibility and application effect of Mini-CEX in pediatric clinical practice.Methods:Residents who received standardized residency training in pediatrics department of Peking University Third Hospital from March 2016 to September 2017 were selected as research objects. The clinical ability of the residents were evaluated by application of the Mini-CEX structured form. Its effectiveness as a training guide and assessment method was also evaluated. SPSS 25.0 was used for t test. Results:The Mini-CEX scale was refined according to the characteristics of pediatrics. In this study, a total of 36 residents participated in the evaluation and 110 cases were completed by introducing Mini-CEX structured form in 7 examinations. Compared with 2016, the Mini-CEX scores of the residents in the 2017 showed different degrees of improvement in information gathering [(7.4±0.9) vs. (7.7±0.7)], clinical examination [(7.5±1.1) vs. (7.6±0.9)], clinical judgment [(7.5±0.9) vs. (7.6±0.9)], organizational effectiveness [(7.4±0.9) vs. (7.7±0.9)], and overall clinical competency [(7.5±0.9) vs. (7.7±0.9)], without significant differences ( P > 0.05). A total of 17 residents completed the assessments more than or equal to 3 times. Compared with 2016, the mean scores of the 17 individuals' Mini-CEX scales in 2017 were significantly improved in terms of information gathering, organizational effectiveness, and overall clinical competency. Conclusion:The results have shown that the Mini-CEX scale is simple and easy to operate, it maybe helpful to improve the clinical ability of pediatric residents, and it can be used as a method to evaluate the clinical ability of pediatric residents.

Objective:To investigate the status and influencing factors of enteral nutrition support in late preterm infants (34-36 +6 gestational weeks) treated in different grades of hospitals in Beijing. Methods:This was a prospective study involving late preterm infants treated in 25 hospitals in Beijing from October 2015 to October 2017. Data about nutritional management and nutrition-related complications were recorded. Exclusive breastfeeding status of the infants by gestational age(GA) and hospital levels was analyzed. The achievement of full enteral feeding and the potential influencing factors were also analyzed. t-test, Mann-Whitney U test, analysis of variance (ANOVA), Kruskal-Wallis test and Chi-square test were used for statistical analysis. Logistic regression and Cox regression analysis were used in multivariate analysis. Results:(1) A total of 1 463 late preterm infants with GA of 35.6±0.8 (ranging from 34.9 to 36.1) weeks was enrolled in this study. Compared with the infants with GA of 35-35 +6 and 36-36 +6 weeks, those born at 34-34 +6 gestational weeks had longer hospital stay [10 (8-13) vs 8 (7-10) and 7 (6-9) d, both P<0.05], greater loss of minimum weight [4.3% (2.6%-6.3%) vs 3.8% (2.0%-5.6%) and 3.3% (1.9%-5.5%), both P<0.05], higher incidence of apnea [5.3% (20/369) vs 2.1% (12/566) and 1.3% (7/528), both P<0.05] and respiratory distress syndrome (RDS) [7.1% (28/369) vs 3.0% (17/566) and 3.2% (17/528), both P<0.05], and lower percentage of failure to regain birth weight at discharge [32.5% (120/369) vs 38.7% (219/566) and 47.9% (253/528), both P<0.05]. Only the incidence of premature rupture of membranes among all maternal complications during pregnancy had statistical difference between 34-34 +6, 35-35 +6 and 36-36 +6 GA groups [6.2% (23/369) vs 12.7% (72/566) and 11.9% (63/528), χ2=10.244, P=0.007]. (2) The rate of enteral feeding increment in hospital was 13.7 (10.5-17.3) ml/(kg·d) and 46.0% (673/1 463) of the infants were fed formula. The exclusive breastfeeding rate increased from 4.5% (66/1 463) during hospitalization to 14.4% (211/1 463) at discharge. The breastfeeding rate at discharge varied widely among the 25 hospitals ( χ2=327.893, P<0.001) ranging from 32% to 0. (3) Logistic regression analysis demonstrated that gestational diabetes mellitus ( OR=2.426, 95% CI: 1.075-5.437, P=0.033) and premature rupture of membranes ( OR=8.726, 95% CI: 1.193-63.802, P=0.033) were the prenatal risk factors influencing the exclusive breastfeeding in late preterm infants. Enteral nutrition achieving 150 ml/(kg·d) and 120 kcal/(kg·d) (1 kcal=4.184 kJ) were noted for 28.4% (416/1 463) and 19.2% (281/1 463) of the late preterm infants at discharge, respectively. Cox regression analysis showed that hospital grades ( HR=1.470, 95% CI: 1.030-2.098, P=0.034), the length of hospital stay ( HR=1.162, 95% CI: 1.097-1.231, P<0.001), birth weight ( HR=0.946, 95% CI: 0.898-0.995, P=0.003), exclusive breastfeeding ( HR=2.354, 95% CI:1.031-5.374, P=0.042), feeding intolerance ( HR=3.677, 95% CI: 1.201-11.253, P=0.023), parenteral nutrition ( HR=1.900, 95% CI: 1.379-2.616, P<0.001), and the rate of enteral feeding advancement ( HR=1.426, 95% CI: 1.369-1.484, P<0.001) were independent factors associated with full enteral feeding at discharge. Conclusions:Exclusive breastfeeding rate in late preterm infants is low and enteral nutrition support varies greatly in different hospitals. The rate of enteral feeding increment is slow for hospitalized late preterm infants and most fail to achieve full enteral feeding at discharge. Gestational diabetes mellitus and premature rupture of membranes are prenatal risk factors affecting breastfeeding of late preterm infants. Those with low birth weight, exclusive breastfeeding in hospital, feeding intolerance, parenteral nutrition support, longer hospital stay or rapid enteral feeding advancement are more likely to achieve full enteral feeding at discharge.