Highly multiplex PCR assays by coupling the 5'-flap endonuclease activity of Taq DNA polymerase and molecular beacon reporters.

Real-time PCR is the most utilized nucleic acid testing tool in clinical settings. However, the number of targets detectable per reaction are restricted by current modes. Here, we describe a single-step, multiplex approach capable of detecting dozens of targets per reaction in a real-time PCR thermal cycler. The approach, termed MeltArray, utilizes the 5'-flap endonuclease activity of Taq DNA polymerase to cleave a mediator probe into a mediator primer that can bind to a molecular beacon reporter, which allows for the extension of multiple mediator primers to produce a series of fluorescent hybrids of different melting temperatures unique to each target. Using multiple molecular beacon reporters labeled with different fluorophores, the overall number of targets is equal to the number of the reporters multiplied by that of mediator primers per reporter. The use of MeltArray was explored in various scenarios, including in a 20-plex assay that detects human Y chromosome microdeletions, a 62-plex assay that determines Escherichia coli serovars, a 24-plex assay that simultaneously identifies and quantitates respiratory pathogens, and a minisequencing assay that identifies KRAS mutations, and all of these different assays were validated with clinical samples. MeltArray approach should find widespread use in clinical settings owing to its combined merits of multiplicity, versatility, simplicity, and accessibility.

C188-9 reduces patient-specific primary breast cancer cells proliferation at the low, clinic-relevant concentration.

OBJECTIVES: STAT3 is a transcriptional activator of breast cancer oncogenes, suggesting that it could be a potential therapeutic target for breast cancer. Therefore, this study investigated the potential application of C188-9, a STAT3 signal pathway inhibitor, in the treatment of breast cancer through a novel pre-clinical platform with patient-specific primary cells (PSPCs). METHODS: PSPCs were isolated from breast cancer samples obtained via biopsy or surgery from fifteen patient donors with their full acknowledgements. PSPCs were treated with C188-9 or other chemotherapeutic agents, and then analyzed with cell viability assay. Western blot assay and real-time quantitative PCR were also used to determine the expression and activity of STAT3 signaling pathway of corresponding PSPCs. RESULTS: C188-9 treatment at normal (experimental) concentration had valid inhibition on PSPCs proliferation. Meanwhile, treatment at a low (clinic-relevant) concentration of C188-9 for an extended period reduced cell viability of PSPCs still more than some of other traditional chemotherapy drugs. In addition, C188-9 decreased expression level of pSTAT3 in PSPCs from some, but not all patient samples. The treatment of C188-9 reduced cell viability of the breast cancer samples through inhibiting the STAT3 to C-myc signaling pathway. CONCLUSIONS: In this study, we tested a novel drug C188-9 at a low, clinic-relevant concentration, together with several traditional chemotherapy agents. PSPCs from ten out of fifteen patient donors were sensitive to C188-9, while some of traditional chemotherapy agents failed. This finding suggested that C188-9 could have treatment effects only on those ten PSPC patient donors, indicating the future personalized utilization of PSPCs.

The efficacy and safety of continuous blood purification in neonates with septic shock and acute kidney injury: a two-center retrospective study.

To investigate the efficacy and safety of continuous blood purification (CBP) in neonates with septic shock and acute kidney injury (AKI). This retrospective study was conducted at two tertiary care children's hospitals between January 2015 and May 2022. A total of 26 neonates with septic shock and AKI were included in this study, with a mortality rate of 50%. Fourteen neonates (53.8%) received continuous veno-venous hemodiafiltration, and 12 (46.2%) received continuous veno-venous hemofiltration. Compared with the indices before CBP, urine output increased 12 h after CBP initiation (P = 0.003) and serum creatinine decreased (P = 0.019). After 24 h of CBP, blood urea nitrogen had decreased (P = 0.006) and mean arterial pressure had increased (P = 0.007). At the end of CBP, the vasoactive-inotropic score and blood lactate were decreased (P = 0.035 and 0.038, respectively) and PH was increased (P = 0.015). Thrombocytopenia was the most common complication of CBP.  Conclusion: CBP can efficiently maintain hemodynamic stability, improve renal function, and has good safety in neonates with septic shock and AKI. However, the mortality rate remains high, and whether CBP improves the prognosis of neonates with septic shock and AKI remains unclear. What is Known: • Over 50% of children with septic shock have severe AKI, of which 21.6% required CBP. • The clinical application of CBP in septic shock has attracted increasing attention. What is New: • CBP can efficiently maintain hemodynamic stability, improve renal function, and has good safety in neonates with septic shock and AKI. • The mortality rate in neonates with septic shock and AKI receiving CBP remains high.

Genetic architecture in neonatal intensive care unit patients with congenital heart defects: a retrospective study from the China Neonatal Genomes Project.

BACKGROUND: Congenital heart defects (CHDs) are the most common type of birth defects. The genetic aetiology of CHD is complex and incompletely understood. The overall distribution of genetic causes in patients with CHD from neonatal intensive care units (NICUs) needs to be studied. METHODS: CHD cases were extracted from the China Neonatal Genomes Project (2016-2021). Next-generation sequencing results and medical records were retrospectively evaluated to note the frequency of genetic diagnosis and the respective patient outcomes. RESULTS: In total, 1795 patients were included. The human phenotype ontology term of atrial septal defect, patent ductus arteriosus and ventricular septal defect account for a large portion of the CHD subtype. Co-occurring extracardiac anomalies were observed in 35.1% of patients. 269 of the cases received genetic diagnoses that could explain the phenotype of CHDs, including 172 copy number variations and 97 pathogenic variants. The detection rate of trio-whole-exome sequencing was higher than clinical exome sequencing (21.8% vs 14.5%, p<0.05). Further follow-up analysis showed the genetic diagnostic rate was higher in the deceased group than in the surviving group (29.0% vs 11.9%, p<0.05). CONCLUSION: This is the largest cohort study to explore the genetic spectrum of patients with CHD in the NICU in China. Our findings may benefit future work on improving genetic screening and counselling for NICU patients with CHD.

A real-world study on the treatment of extremely preterm infants: a multi-center study in southwest area of Fujian Province in China.

BACKGROUND: Due to regional and cultural differences, the current status of extremely preterm infants(EPIs) treatment across different areas of mainland China remains unclear. This study investigated the survival rate and incidence of major diseases among EPIs in the southwest area of Fujian province. METHOD: This retrospective and multicenter study collected perinatal data from EPIs with gestational ages between 22-27+ 6w and born in the southwest area of Fujian province. The study population was divided into 6 groups based on gestational age at delivery. The primary outcome was the survival status at ordered hospital discharge or correct gestational age of 40 weeks, and the secondary outcome was the incidence of major diseases. The study analyzed the actual survival status of EPIs in the area. RESULT: A total of 2004 preterm infants with gestational ages of 22-27+ 6 weeks were enrolled in this study. Among them, 1535 cases (76.6%) were born in the delivery room but did not survive, 469 cases (23.4%) were transferred to the neonatal department for treatment, 101 cases (5.0%) received partial treatment, and 368 cases (18.4%) received complete treatment. The overall all-cause mortality rate was 84.4% (1691/2004). The survival rate and survival rate without major serious disease for EPIs who received complete treatment were 85.1% (313/368) and 31.5% (116/318), respectively. The survival rates for gestational ages 22-22+ 6w, 23-23+ 6w, 24-24+ 6w, 25-25+ 6w, 26-26+ 6w, and 27-27+ 6w were 0%, 0%, 59.1% (13/22), 83% (39/47), 88.8% (87/98), and 89.7% (174/198), respectively. The survival rates without major serious disease were 0%, 0%, 9.1% (2/22), 19.1% (9/47), 27.6% (27/98), and 40.2% (78/194), respectively. CONCLUSION: The all-cause mortality of EPIs in the southwest area of Fujian Province remains high, with a significant number of infants were given up after birth in the delivery room being the main influencing factor. The survival rate of EPIs who received complete treatment at 25-27 weeks in the NICU was similar to that in developed countries. However, the survival rate without major serious disease was significantly lower compared to high-income countries.

The role of nutrition in analysis of risk factors and short-term outcomes for late-onset necrotizing enterocolitis among very preterm infants: a nationwide, multicenter study in China.

BACKGROUND: Necrotizing enterocolitis (NEC) is a serious gastrointestinal disease, primarily affects preterm newborns and occurs after 7 days of life (late-onset NEC, LO-NEC). Unfortunately, over the past several decades, not much progress has been made in its treatment or prevention. This study aimed to analyze the risk factors for LO-NEC, and the impact of LO-NEC on short-term outcomes in very preterm infants (VPIs) with a focus on nutrition and different onset times. METHOD: Clinical data of VPIs were retrospectively collected from 28 hospitals in seven different regions of China from September 2019 to December 2020. A total of 2509 enrolled VPIs were divided into 2 groups: the LO-NEC group and non-LO-NEC group. The LO-NEC group was divided into 2 subgroups based on the onset time: LO-NEC occurring between 8 ~ 14d group and LO-NEC occurring after 14d group. Clinical characteristics, nutritional status, and the short-term clinical outcomes were analyzed and compared among these groups. RESULTS: Compared with the non-LO-NEC group, the LO-NEC group had a higher proportion of anemia, blood transfusion, and invasive mechanical ventilation (IMV) treatments before NEC; the LO-NEC group infants had a longer fasting time, required longer duration to achieve the target total caloric intake (110 kcal/kg) and regain birthweight, and showed slower weight growth velocity; the cumulative dose of the medium-chain and long-chain triglyceride (MCT/LCT) emulsion intake in the first week after birth was higher and breastfeeding rate was lower. Additionally, similar results including a higher proportion of IMV, lower breastfeeding rate, more MCT/LCT emulsion intake, slower growth velocity were also found in the LO-NEC group occurring between 8 ~ 14d when compared to the LO-NEC group occurring after 14 d (all (P < 0.05). After adjustment for the confounding factors, high proportion of breastfeeding were identified as protective factors and long fasting time before NEC were identified as risk factors for LO-NEC; early feeding were identified as protective factors and low gestational age, grade III ~ IV neonatal respiratory distress syndrome (NRDS), high accumulation of the MCT/LCT emulsion in the first week were identified as risk factors for LO-NEC occurring between 8 ~ 14d. Logistic regression analysis showed that LO-NEC was a risk factor for late-onset sepsis, parenteral nutrition-associated cholestasis, metabolic bone disease of prematurity, and extrauterine growth retardation. CONCLUSION: Actively preventing premature birth, standardizing the treatment of grade III ~ IV NRDS, and optimizing enteral and parenteral nutrition strategies may help reduce the risk of LO-NEC, especially those occurring between 8 ~ 14d, which may further ameliorate the short-term clinical outcome of VPIs. TRIAL REGISTRATION: ChiCTR1900023418 (26/05/2019).

COLEC10 Induces Endoplasmic Reticulum Stress by Occupying GRP78 and Inhibits Hepatocellular Carcinoma.

Collectin subfamily member 10 (COLEC10), a C-type lectin mainly expressed in the liver, is involved in the development of hepatocellular carcinoma (HCC). However, its underlying molecular mechanism in HCC progression remains unknown. In this study, reduced COLEC10 expression in tumor tissues was validated using various HCC cohorts and was associated with poor patient prognosis. COLEC10 overexpression attenuated HCC cell growth and migration abilities in vitro and in vivo. We identified that COLEC10 was a novel interactor of 78-kDa glucose-regulated protein (GRP78), a master modulator of the unfolded protein response in the endoplasmic reticulum (ER). COLEC10 overexpression potentiated ER stress in HCC cells, as demonstrated by elevated expression levels of phosphorylated protein kinase RNA-like ER kinase, phosphorylated inositol-requiring protein 1α, activating transcription factor 4, DNA damage-inducible transcript 3, and X-box-binding protein 1s. The ER in COLEC10-overexpressing cells also showed a dilated and fragmented pattern. Mechanistically, COLEC10 overexpression increases GRP78 occupancy through direct binding by the C-terminal carbohydrate recognition domain in the ER, which released and activated the ER stress transducers protein kinase RNA-like ER kinase and phosphorylated inositol-requiring protein 1α, triggering the unfolded protein response activity. COLEC10-overexpressing HCC cells generated a relatively high reactive oxygen species level and switched to apoptotic cell death under sorafenib-treated conditions. Our study provides the first novel view that COLEC10 inhibits HCC progression by regulating GRP78-mediated ER stress signaling and may serve as a promising therapeutic and prognostic biomarker.

Genetic spectrums and clinical profiles of critically ill neonates with congenital auricular deformity in the China Neonatal Genomes Project.

Congenital auricular deformity (CAD) is a complex phenotype that may occur as a single malformation or part of a congenital syndrome. The genetic architecture and utility of next-generation sequencing (NGS) in a sizable cross-sectional study of critically ill neonates with CAD have not yet been systematically investigated. This cross-sectional study investigated the genetic spectrum in critically ill neonates with CADs. Critically ill neonates with CADs (n = 251) were enrolled between August 8, 2016 and October 1, 2022. All neonates underwent NGS. The outcomes were molecular diagnostic yield, spectrum of genetic events, and clinical findings. Genetic findings were obtained in 107 neonates (42.6%), of which 67.3% (72/107) had pathogenic/likely pathogenic/variants of uncertain significance (P/LP/VUS) gene variations and 32.7% (35/107) had P/LP/VUS copy number variations (CNVs). The diagnostic rates of clinical exome sequencing were similar to those of exome sequencing. The logistic regression model revealed that CAD neonates with craniofacial abnormalities (OR = 4.15, 95% CI 2.29-7.53) or cardiovascular malformation (OR = 2.09, 95% CI 1.14-3.84) are more likely to be attributed to genetic causes. Follow-up analysis revealed that, compared to those in the undiagnosed group, the number of neonates whose care was withdrawn or who died was higher in the genetically diagnosed group (P < 0.05). This study identified a high incidence of genetic causes in critically ill neonates with CADs, with a combination of single-nucleotide variations and CNVs among the genetic causes of CAD. These findings highlight potential of NGS in the genetic testing of critically ill neonates with CADs.

Changes in endemic patterns of respiratory syncytial virus infection in pediatric patients under the pressure of nonpharmaceutical interventions for COVID-19 in Beijing, China.

A series of nonpharmaceutical interventions (NPIs) was launched in Beijing, China, on January 24, 2020, to control coronavirus disease 2019. To reveal the roles of NPIs on the respiratory syncytial virus (RSV), respiratory specimens collected from children with acute respiratory tract infection between July 2017 and Dec 2021 in Beijing were screened by capillary electrophoresis-based multiplex PCR (CEMP) assay. Specimens positive for RSV were subjected to a polymerase chain reaction (PCR) and genotyped by G gene sequencing and phylogenetic analysis using iqtree v1.6.12. The parallel and fixed (paraFix) mutations were analyzed with the R package sitePath. Clinical data were compared using SPSS 22.0 software. Before NPIs launched, each RSV endemic season started from October/November to February/March of the next year in Beijing. After that, the RSV positive rate abruptly dropped from 31.93% in January to 4.39% in February 2020; then, a dormant state with RSV positive rates ≤1% from March to September, a nearly dormant state in October (2.85%) and November (2.98%) and a delayed endemic season in 2020, and abnormal RSV positive rates remaining at approximately 10% in summer until September 2021 were detected. Finally, an endemic RSV season returned in October 2021. There was a game between Subtypes A and B, and RSV-A replaced RSV-B in July 2021 to become the dominant subtype. Six RSV-A and eight RSV-B paraFix mutations were identified on G. The percentage of severe pneumonia patients decreased to 40.51% after NPIs launched. NPIs launched in Beijing seriously interfered with the endemic season of RSV.

One-Pot Synthesis of Diverse 1,4-[60]Fullerephenols via Three-Component Umpolung Cascade Coupling of Phenols, C60 , and Nucleophiles.

A three-component umpolung cascade coupling reaction of phenols, C60 , and different nucleophiles which includes H2 O, alcohols, triphenylamines and carbazoles was developed. Furthermore, one-pot 1,4-bisphenol coupling on C60 has been realized by this method. This practical protocol features high chemo- and regioselectivity, wide substrate range, easy operation and low cost, thus providing a robust method for the one-pot synthesis of various unsymmetrical 1,4-[60]fullerephenols.

The changed endemic pattern of human adenovirus from species B to C among pediatric patients under the pressure of non-pharmaceutical interventions against COVID-19 in Beijing, China.

BACKGROUND: Under the pressure of non-pharmaceutical interventions (NPIs) targeting severe acute respiratory syndrome coronavirus 2, the prevalence of human adenovirus (HAdV) was monitored before and after NPIs launched on Jan 24, 2020 in pediatric patients in Beijing, China. METHODS: Respiratory samples collected from children hospitalized with acute respiratory infections from Jan 2015 to Dec 2021 were screened by direct immunofluorescence test or capillary electrophoresis-based multiplex PCR assay. The hexon, penton base, and fiber genes were amplified from HAdV positive specimens, then sequenced. For HAdV typing, phylogenetic trees were built by MEGA X. Then clinical data of HAdV positive cases were collected. All data were evaluated using SPSS Statistics 22.0 software. RESULTS: A total of 16,097 children were enrolled and 466 (2.89%, 466/16,097) were HAdV-positive. The positive rates of HAdV varied, ranging from 4.39% (151/3,438) in 2018 to1.25% (26/2,081) in 2021, dropped from 3.19% (428/13,408) to 1.41% (38/2,689) from before to after NPIs launched (P < 0.001). There were 350 cases typed into nine types of species B, C, or E and 34 recorded as undetermined. Among them, HAdV-B3 (51.56%, 198/384) was the most prevalent types from 2015 to 2017, and HAdV-B7 (29.17%, 112/384) co-circulated with HAdV-B3 from 2018 to 2019. After NPIs launched, HAdV-B3 and B7 decreased sharply with HAdV-B7 undetected in 2021, while HAdV-C1 became the dominant one and the undetermined were more. CONCLUSIONS: The endemic pattern of HAdV changed in Beijing because of the NPIs launched for COVID-19. Especially, the dominant types changed from HAdV-B to HAdV-C.

Coordination-Driven Heterochiral Self-Assembly: Construction of Cd(II) Coordination Polymers with Sorption Behaviors for Iodine and Dyes.

A racemic bispyridyl ligand (L) was synthesized via a Schiff base condensation reaction. Four Cd(II) complexes, {[CdL2Cl2]·2DMF}n (1), [CdLI2]n (2), {[CdL2Br2]·4H2O}n (3), and {[CdL2(H2O)2](NO3)2·2CH3OH·8H2O}n (4), were synthesized and further characterized based on this ligand. Single-crystal structures show that the coordination-driven assembly of the bispyridyl ligand with Cd(II) salts bearing different counteranions can lead to multidimensional coordination polymers via a heterochiral self-discrimination process. Complex 1 exists as a one-dimensional (1D) looped chain polymer, and complex 2 exists as a 1D zigzag chain polymer. Complex 3 is a 2D grid coordination polymer, and complex 4 exists as a 3D framework polymer. Furthermore, the iodine sorption capacities of the four complexes were investigated in the solution of n-hexane and water as well as in the iodine steam. The dye sorption behaviors were investigated in water, which showed that complex 2 exhibited good adsorption for crystal violet (CV), while complex 4 had good adsorption capability toward direct yellow 4 (DY).

Five Porous Complexes Constructed from a Racemic Ligand: Synthesis, Chiral Self-Assembly, Iodine Adsorption, and Desorption Properties.

Herein, a chiral bispyridyl ligand (L) was designed and synthesized using a Schiff base condensation reaction, followed by a 1,3-H shift. Five complexes, [Zn2L2(OAc)4] (1), {[CdLCl2(DMF)]·4H2O}n (2), [Cd2L2I4]·4H2O (3), {[CdL2(H2O)2](NO3)2·2CH3OH}n (4), and [Hg2L2Cl4]·2DMF (5), were synthesized and characterized upon its reaction with Zn(II), Cd(II), or Hg(II) ions, respectively. X-ray crystallography shows that the organic compound exists as a racemic ligand with equal amounts of its R- and S-isomers, and all of the synthesized complexes exhibit heterochiral self-assembly via a chiral self-discrimination process. Complexes 1, 3, and 5 exist as centrosymmetric binuclear metallamacrocycles, while complexes 2 and 4 exist as 1D looped-chain coordination polymers. Inspired by the assembled structures of the five complexes, I2 adsorption/desorption measurements for the complexes were carried out. The results show that complexes 1 and 5 exhibit good adsorption capacities toward I2 in n-hexane and in water, respectively.

Interleukin 10 inhibits oxidative stress-induced autophagosome formation in hepatic stellate cells by activating the mTOR-STAT3 pathway.

Autophagy is involved in the activation of hepatic stellate cells (HSCs) and liver fibrosis. Previous studies have shown that interleukin 10 (IL-10) has a marked therapeutic effect against liver fibrosis. However, few studies have evaluated the effect of IL-10 on autophagy in HSCs and fibrotic livers. The aim of this study was to assess the effect of IL-10 on the autophagy of HSCs in vitro and in vivo and then to explore the underlying pathway. In vitro, The results revealed that IL-10 had inhibitory effects on hydrogen peroxide (H2O2)-induced autophagy, as evidenced by the decreased LC3II/I ratio and Beclin1 expression, increased p62 expression, reduced numbers of autophagosomes, and blocked autophagy initiation in HSCs. Mechanistically, IL-10 significantly promoted the phosphorylation of the signal transducer and activator of transcription 3(STAT3) and mammalian target of rapamycin (mTOR), leading to the activation of STAT3 and mTOR, which in turn inhibited autophagy. In vivo, the increased expression of IL-10 in fibrotic livers inhibited significantly liver fibrosis and decreased the autophagic activity in fibrotic livers and HSCs. Overall, our results indicate that IL-10 suppressed H2O2-induced autophagy in HSCs by activating the STAT3-mTOR signaling pathway. Present study provides a new theoretical basis for the anti-fibrotic effects of IL-10.

Real-life effects, complications, and outcomes in 39 critically ill neonates receiving continuous kidney replacement therapy.

BACKGROUND: Continuous kidney replacement therapy (CKRT) has been expanded from simple kidney replacement therapy to the field of critical illness in children. However, CKRT is rarely used in critically ill neonates in the neonatal intensive care unit (NICU). This study aimed to describe patients' clinical characteristics at admission and CKRT initiation, CKRT effects, short-term outcomes, and predictors of death in critically ill neonates. METHODS: A 7-year single-center retrospective study in a tertiary NICU. RESULTS: Thirty-nine critically ill neonates received CKRT between May 2015 and April 2022 with a mortality rate of 35.9%. The most common primary diagnosis was neonatal sepsis in 15 cases (38.5%). Continuous veno-venous hemodiafiltration and continuous veno-venous hemofiltration were applied in 43.6% and 56.4% of neonates, respectively. The duration of CKRT was 44 (18, 72) h. Thirty-one patients (79.5%) had complications due to CKRT-related adverse events, and the most common complication was thrombocytopenia. Approximately 12 h after the CKRT initiation, urine volume, mean arterial pressure, and pH were increased, and serum creatinine, blood urea nitrogen, and blood lactate were decreased. In the multivariate logistic regression analysis, neonatal critical illness score [odds ratio 0.886 (0.786 ~ 0.998), P = 0.046] was an independent risk factor for death in critically ill neonates who received CKRT. CONCLUSIONS: CKRT can be an effective and feasible technique in critically ill neonates, but the overall mortality and CKRT-related complications are relatively high. Furthermore, the probability of death is greater among neonates with greater severity of illness at CKRT initiation. A higher resolution version of the Graphical abstract is available as Supplementary information.

Analysis of risk factors for death in 59 cases of critically ill neonates receiving continuous renal replacement therapy: a two-centered retrospective study.

To investigate the risk factors for death in critically ill neonates receiving continuous renal replacement therapy (CRRT). This retrospective study analyzed the clinical data of critically ill neonates receiving CRRT at two tertiary hospitals from January 2015 to December 2021. A multi-factor logistic regression analysis was performed, and the predictive value of relevant risk factors on death was verified by receiver operating characteristic (ROC) curve. A total of 59 cases of critically ill neonates were included in this study, with a mortality of 37.3%. The most common primary disease in these cases was neonatal sepsis, followed by neonatal asphyxia, and inborn errors of metabolism (IEM). Univariate analysis showed that the risk factors related to death included primary diseases; the number of organs involved in multiple organ dysfunction syndrome (MODS), neonatal critical illness scores (NCIS), and indications of CRRT; the blood lactate, blood glucose, hemoglobin, and platelet before CRRT initiation; and the incidence of bleeding or thrombosis during CRRT. Multi-factor logistic regression analysis showed that risk factors for death in critically ill neonates receiving CRRT included the occurrence of neonatal sepsis, the number of organs involved in MODS, and the NCIS. ROC curve analysis showed that the number of organs involved in MODS and NCIS had a good predictive value for death in critically ill neonates receiving CRRT, with the areas under the curve (AUC) being 0.700 and 0.810, respectively. CONCLUSION: Neonatal sepsis, the number of organs involved in MODS, and NCIS were independent risk factors for death in critically ill neonates receiving CRRT. Moreover, the number of organs involved in MODS and NCIS could effectively predict death in critically ill neonates receiving CRRT. WHAT IS KNOWN: • The population to which CRRT is applicable is gradually expanding from critically ill children to critically ill neonates. • The mortality of critically ill neonates receiving CRRT remains high. WHAT IS NEW: • The most common primary disease in critically ill neonates receiving CRRT was neonatal sepsis, followed by neonatal asphyxia and inborn errors of metabolism (IEM). • The number of organs involved in MODS and NCIS could effectively predict death in critically ill neonates receiving CRRT.

Perinatal characteristics and neonatal outcomes of singletons and twins in Chinese very preterm infants: a cohort study.

BACKGROUND: The prevalence of preterm birth has been rising, and there is a paucity of nationwide data on the perinatal characteristics and neonatal outcomes of twin deliveries of very preterm infants (VPIs) in China. This study compared the perinatal characteristics and outcomes of singletons and twins admitted to neonatal intensive care units (NICUs) in China. METHODS: The study population comprised all infants born before 32 weeks in the Chinese Neonatal Network (CHNN) between January 2019 and December 2019. Three-level and population-average generalized estimating equation (GEE)/alternating logistic regression (ALR) models were used to determine the association of twins with neonatal morbidities and the use of NICU resources. RESULTS: During the study period, there were 6634 (71.2%) singletons and 2680 (28.8%) twins, with mean birth weights of 1333.70 g and 1294.63 g, respectively. Twins were significantly more likely to be delivered by caesarean section (p < 0.01), have antenatal steroid usage (p = 0.048), have been conceived by assisted reproductive technology (ART) (p < 0.01), have a higher prevalence of maternal diabetes (p < 0.01) and be inborn (p < 0.01) than singletons. In addition, twins had a lower prevalence of small for gestational age, maternal hypertension, and primigravida mothers than singletons (all p < 0.01). After adjusting for potential confounders, twins had higher mortality rates (adjusted odds ratio [AOR] 1.28, 95% confidence interval [CI] 1.10-1.49), higher incidences of short-term composite outcomes (AOR 1.28, 95% CI 1.09-1.50), respiratory distress syndrome (RDS) (AOR 1.30, 95% CI 1.12-1.50), and bronchopulmonary dysplasia (BPD) (AOR 1.10, 95% CI 1.01-1.21), more surfactant usage (AOR 1.22, 95% CI 1.05-1.41) and prolonged hospital stays (adjusted mean ratio 1.03, 95% CI 1.00-1.06), compared to singletons. CONCLUSION: Our work suggests that twins have a greater risk of mortality, a higher incidence of RDS and BPD, more surfactant usage, and longer NICU stays than singletons among VPIs in China.

Clinical and metabolic characteristics of endometrial lesions in polycystic ovary syndrome at reproductive age.

BACKGROUND: We aimed to explore the clinical and metabolic characteristics in polycystic ovary syndrome (PCOS) patients with different endometrial lesions. METHODS: 234 PCOS patients who underwent hysteroscopy and endometrial biopsy were categorized into four groups: (1) normal endometrium (control group, n = 98), (2) endometrial polyp (EP group, n = 92), (3) endometrial hyperplasia (EH group, n = 33), (4) endometrial cancer (EC group, n = 11). Serum sex hormone levels, 75 g oral glucose tolerance test, insulin release test, fasting plasma lipid, complete blood count and coagulation parameters were measured and analyzed. RESULTS: Body mass index and triglyceride level of the EH group were higher while average menstrual cycle length was longer in comparison with the control and EP group. Sex hormone-binding globulin (SHBG) and high density lipoprotein were lower in the EH group than that in the control group. 36% of the patients in the EH group suggested obesity, higher than the other three groups. Using multivariant regression analysis, patients with free androgen index > 5 had higher risk of EH (OR 5.70; 95% CI 1.05-31.01), while metformin appeared to be a protective factor for EH (OR 0.12; 95% CI 0.02-0.80). Metformin and hormones (oral contraceptives or progestogen) were shown to be protective factors for EP (OR 0.09; 95% CI 0.02-0.42; OR 0.10; 95% CI 0.02-0.56). Hormones therapy appeared to be a protective factor for EC (OR 0.05; 95% CI 0.01-0.39). CONCLUSION: Obesity, prolonged menstrual cycle, decreased SHBG, and dyslipidemia are risk factors for EH in patients with PCOS. Oral contraceptives, progestogen and metformin are recommended for prevention and treatment of endometrial lesions in PCOS patients.

The impact of SARS-COV-2 infection on menstruation.

BACKGROUND: Recent study has demonstrated that the GnRH system in patients with post-COVID syndrome may be influenced by SARS-CoV-2. However, the impact of COVID-19 infection on women's menstruation is still unknown. OBJECTIVE: We aimed to investigate the the relationship between coronavirus disease 2019 (COVID-19) and menstruation in premenopausal women. METHODS: This was a retrospective cohort study. Pre-menopausal women were invited to participate in the online questionnaire on wechat. Participants were divided into four groups according to whether they were infected with severe acute respiratory syndrome coronavirus-2 (SARS-COV-2) and whether they had menstrual changes during the pandemic. Sociodemographic characteristics, history of COVID-19, menstruation and menstrual changes of the participants were collected. Statistical analyses were performed using SPSS, version 25.0 (SPSS Inc., Chicago, IL, USA). RESULTS: A total of 1946 women were included in the study. 1800 participants had been or were currently infected with SARS-COV-2, and 146 people had not been infected. Among 1800 patients with COVID-19, 666 (37.0%) had changes in menstruation, and 1134 (63.0%) did not, which was significantly higher than the uninfected participants (c2 = 12.161, P = 0.000). The proportion of participants with menstrual cycle changes (450/67.6%) is larger than that of uninfected participants (c2 = 6.904, P = 0.009). COVID-19 vaccination was associated with lower odds of menstrual cycle change (OR, 0.855; 95% CI, 0.750-0.976). Participants who reported chest pain (OR, 1.750, 95% CI, 1.209-2.533) and dyspnea (OR, 1.446; 95% CI, 1.052-1.988) during infection had greater odds of changes to their menstrual cycle compared with the participants who did not. CONCLUSIONS: The association between the COVID-19 and increased prevalence of menstrual cycle irregularity. COVID-19 vaccination is a protective factor in the long term, and participants with chest pain and dyspnea are more likely to develop AUB.

Etiological and clinical characteristics of severe pneumonia in pediatric intensive care unit (PICU).

OBJECTIVE: To analyze the etiological distribution characteristics of pediatric patients with severe pneumonia admitted to the Pediatric Intensive Care Unit (PICU), in order to provide a reference for the rational use of clinical antimicrobial drugs. METHODS: A retrospective analysis of pediatric patients admitted to PICU with a diagnosis of severe pneumonia from January 2018 to December 2021 was performed and statistical analysis of pathogenic characteristics was performed. RESULTS: A total of 649 pathogens were detected in 515 children, with a positive detection rate of 77.48%. Bacteria were detected at the highest rate (40.52%), followed by viruses (34.35%), atypical pathogens (19.72%) and fungal (4.31%). Gram-positive infections were dominated by Staphylococcus aureus (39.56%) and Streptococcus pneumoniae (32.97%), and Gram-negative infections were dominated by Acinetobacter Bahmani (16.28%) and Haemophilus influenzae (15.12%), followed by Klebsiella pneumoniae (13.95%) and Pseudomonas aeruginosa (12.21%). Viral infections were dominated by respiratory syncytial virus (25.65%) and EB virus (20.43%), fungal infections were dominated by Candida albicans (50.0%). The proportion of children infected with single pathogen (49.62%) was comparable to that of those with mixed infections (50.38%). There were statistically significant differences in the distribution of children with single pathogen infection by gender (P < 0.05). The age distribution of children with single bacterial, single viral and single fungal infections was statistically different (P < 0.05). There was no significant difference in the distribution of onset season in children with single pathogen infections (P > 0.05), but the number of children with single viral infections was significantly higher in winter and spring than that in summer and autumn, and the difference was statistically significant (P < 0.05). A mixture of 2 pathogens (77.61%) accounted for the majority of mixed infections, there were statistical differences in the distribution of bacterial + viral infection in terms of gender, age, and onset season (P < 0.05), children with viral + mycoplasma infection in terms of gender and age (P < 0.05), and children with viral + fungal infection in terms of gender (P < 0.05), and children with bacterial + mycoplasma infection in terms of age and onset season (P < 0.05). Among the children infected with 3 pathogens, there were statistically significant differences in the distribution of bacterial + viral + fungal and viral + mycoplasma + fungal infections in terms of gender (P < 0.05), and children with bacterial + viral + mycoplasma infection in terms of age (P < 0.05), while there was no significant difference in the distribution of onset season (P > 0.05). There were no significant differences in the distribution of children infected with 4 pathogens in terms of gender, age and onset season (P > 0.05). CONCLUSION: The pathogens of pediatric patients with severe pneumonia in PICU commonly involves bacteria and viruses. As the age of children grows, the detection rate of bacteria shows a decreasing trend, and the pathogenic spectrum gradually changes from bacteria to mycoplasma and viruses, and the number of mixed infections gradually increase. Rational selection of antimicrobial drugs needs to consider pathogenic characteristics of different age, gender, and onset season in clinical practice.