Short and long-term outcome of selective reduction by fetoscopy-guided bipolar cord coagulation in monochronic twin pregnancies.

OBJECTIVE: To assess the short and long-term outcome of selective reduction by fetoscopy-guided bipolar cord coagulation in monochronic twin pregnancies. METHODS: Retrospective analysis of a consecutive cohort of all monochorionic twin pregnancies treated with fetoscopy-guided bipolar cord coagulation between December 2015 and December 2022 in a single center in China. RESULTS: A total of 43 monochronic twin pregnancies undergoing fetoscopy-guided bipolar cord coagulation were analyzed. There were 5 intrauterine deaths with an 88.4% (38/43) survival rate overall. The preterm premature rupture of the membranes rate was 13.2% and the preterm birth before 37 and 32 weeks was 42.1% and 13.1% respectively. An uptrend in survival rate (78.9% vs 95.8%, p=0.086) and a downtrend of procedure time (30 vs 16.5minutes, p=0.036) were observed over time (period 1 from Dec.2015 to Dec.2019 verses period 2 from Jan. 2020 to Dec. 2022). Long-term outcome was assessed in 94.6% (35/37) of survivors and 91.4% (32/35) had normal neurodevelopmental outcome. CONCLUSION: Fetoscopy-guided bipolar cord coagulation for fetal reduction in complicated monochorionic twin pregnancies could achieve a favorable short and long-term outcome, especially in experienced hands.

A novel variant in the SLCO2A1 gene in a Chinese patient with chronic gastroenteropathy and primary hypertrophic osteoarthropathy.

BACKGROUND: Chronic enteropathy associated with SLCO2A1 gene (CEAS) results from loss-of-function variants in SLCO2A1, which encodes the prostaglandin transporter (PGT). CEAS follows an autosomal recessive inheritance pattern. To date, approximate 30 pathogenic variants have been reported in CEAS. METHODS: We performed whole exome sequencing (WES) to screen for potential pathogenic variants in a patient suspected of having CEAS, and confirmed a variant in SLCO2A1 using Sanger sequencing. We established an in vitro minigene model to compare splicing between wild type (WT) and mutant transcripts. Quantitative polymerase chain reaction (qPCR) was used to evaluate SLCO2A1 transcription in the stomach and colon tissues from the patient and a healthy control (HC). The transcripts were further cloned and sequenced. RESULTS: The patient had a novel, homozygous, recessive c.929A > G variant in exon 7 of SLCO2A1, which has not been previously reported in CEAS or PHO. This variant altered splicing, resulting in an exon 7-truncated transcript lacking 16 bases. No normal transcript was detected in the patient's stomach or colon tissue. qPCR also showed significantly decreased SLCO2A1 transcription compared to HC. CONCLUSION: A previously unreported variant caused defective SLCO2A1 splicing and reduced mRNA levels in a patient with CEAS and PHO. This research enhances understanding of CEAS and PHO pathophysiology and aids genetic counseling and diagnosis.

Effect of administration routes of oxytocin on hemoglobin in neonates with delayed umbilical cord clamping: a multi-centre randomized controlled clinical trial.

PURPOSE: To evaluate the effect of intravenous infusion versus intramyometrial injection of oxytocin on hemoglobin levels in neonates with delayed umbilical cord clamping during cesarean section. METHODS: The multi-centre randomized controlled trial was performed at three hospitals from February to June 2023. Women with term singleton gestations scheduled for cesarean delivery were allocated to receive an intravenous infusion of 10 units of oxytocin or a myometrial injection of 10 units of oxytocin during the surgery. The primary outcome was neonatal hemoglobin at 48 to 96 h after birth. Secondary outcomes were side-effects of oxytocin, postpartum haemorrhage, phototherapy for jaundice, feeding at 1 month, maternal and neonatal morbidity and re-admissions. RESULTS: A total of 360 women were randomized (180 women in each group). The mean neonatal hemoglobin did not show a significant difference between the intravenous infusion group (194.3 ± 21.7 g/L) and the intramyometrial groups (195.2 ± 24.3 g/L) (p = 0.715). Secondary neonatal outcomes, involving phototherapy for jaundice, feeding at 1 month and neonatal intensive care unit admission were similar between the two groups. The maternal outcomes did not differ significantly between the two groups, except for a 200 mL higher intraoperative infusion volume observed in the intravenous group compared to the intramyometrial group. CONCLUSION: Among women undergoing elective cesarean delivery of term singleton pregnancies, there was no significant difference in neonatal hemoglobin at 48 to 96 h after birth between infants with delayed cord clamping, whether the oxytocin was administrated by intravenous infusion or intramyometrial injection. TRIAL REGISTRATION: Chinese Clinical trial registry: ChiCTR2300067953 (1 February 2023).

Clinical and genetic characteristics of Chinese patients diagnosed with chronic enteropathy associated with SLCO2A1 gene.

BACKGROUND AND AIMS: Chronic enteropathy associated with SLCO2A1 gene is a rare intestinal disease caused by loss-of-function SLCO2A1 mutations, with clinical and genetic characteristics remaining largely unknown, especially in Chinese patients. This study aims to reveal clinical and genetic features of Chinese CEAS patients, highlighting the previously unreported or unemphasized characteristics. METHODS: We enrolled 12 Chinese patients with chronic enteropathy associated with SLCO2A1 gene admitted to Peking Union Medical College Hospital from January 2018 to December 2022. Clinical and genetic data of these patients were collected and analyzed. RESULTS: 58.3% of patients were male, who also had primary hypertrophic osteoarthropathy, whereas female patients did not have primary hypertrophic osteoarthropathy. Apart from common symptoms associated with anemia and hypoalbuminemia, abdominal pain, ileus, diarrhea, and hematochezia were present. 4 of the 5 female patients had early-onset amenorrhea, though the causal relationship remained to be clarified. Endoscopy and computed tomography enterography revealed that lesions can occur in any part of the digestive tract, most commonly in the ileum. Pathology showed multiple superficial ulcers with adjacent vascular dilatation, and loss of SLCO2A1 expression, particularly in gastrointestinal vascular endothelial cells. Genetic analysis confirmed SLCO2A1 mutations in all patients and identified 11 new SLCO2A1 variants for CEAS. CONCLUSIONS: This study reports new clinical, pathological, and genetic findings in 12 Chinese patients with chronic enteropathy associated with SLCO2A1 gene. This study provides insights into the pathogenesis of this disease. However, studies with larger sample sizes and more in-depth mechanism research are still required.

Birth weight discordance and adverse neonatal outcomes in appropriately grown premature twins.

Objective: This study aimed to analyze the clinical characteristics of birth weight discordant twins (BWDT) who were premature and appropriate-for-gestational-age or large-for-gestational-age. Additionally, it assessed the impact of birth weight discordance on the prognosis of appropriately grown premature twins, and investigated the effect of maternal factors on neonatal outcomes. Study design: This retrospective cohort study included twins who were born alive after preterm labor at the Nanjing Drum Tower Hospital from January 2018 to December 2021, along with their mothers. Twins were arranged into discordant and concordant groups according to intertwin birth weight discordance, followed by the analysis of the clinical characteristics of mothers and the prognosis of neonates. Results: A total of 585 mothers and 1170 neonates were included, with 47 mothers and 94 neonates in the discordant group. The incidence of birth weight discordance was 8.0% (94/1,170) in appropriately grown premature twins. The incidence of complications (43.2% vs. 21.8%) and transfer to the neonatal intensive care unit (NICU) (53.2% vs. 29.2%) was higher in the discordant group than in the concordant group (p < 0.05). Furthermore, the incidence of infectious diseases (36.7% vs. 19.4%), necrotizing enterocolitis (7.6% vs. 1.6%), and oxygen therapy rate (22.8% vs. 12.8%) were statistically significantly higher in the discordant group than in the concordant group (p < 0.05). Conclusion: Birth weight discordance remains a high-risk factor for complications and transfer to the NICU in appropriately grown premature twins. It is important to pay attention to birth weight discordance when the outcomes of twins are assessed.

Lawsonia intracellularis flagellin protein LfliC stimulates NF-κB and MAPK signaling pathways independently of TLR5 interaction.

Lawsonia intracellularis, a Gram-negative obligate intracellular bacterium and etiologic agent of porcine proliferative enteropathy, was observed to have a long, single, and unipolar flagellum. Bacterial flagellar filament comprises thousands of copies of the protein flagellin (FliC), and has been reported to be recognized by Toll-like receptor (TLR5) to activate the NF-κB and MAPK signaling pathways, thereby inducing the expression of proinflammatory genes. Recently, two L. intracellularis flagellin proteins, LfliC and LFliC, were reported to be involved in bacterial-host interaction and immune response. Here, to further explore the role of LfliC in proinflammatory response, we purified LfliC, and found that its exposure could activate NF-κB signaling pathway in both HEK293T and IPI-FX cells, as well as activate MAPK p38 and ERK1/2 in HEK293T cells but not in IPI-FX cells. However, our yeast two-hybrid and co-immunoprecipitation assay results revealed that LfliC has no interaction with the porcine TLR5 ECD domain though it harbors the conserved D1-like motif required for the interaction. Moreover, LfliC was identified as a substrate of the virulence-associated type III secretion system (T3SS) by using the heterologous Y. enterocolitica system. Transient expression of LfliC also activated the NF-κB and MAPK signaling pathway in HEK293T cells. Collectively, our results suggest that both the exposure and expression of L. intracellularis LfliC can induce the NF-κB and MAPK signaling pathway in mammalian cells. Our findings may provide important implications and resources for the development of diagnostic tools or vaccines and dissection of the pathogenesis of L. intracellularis.

Efficient treatment of palladium from wastewater by acrolein cross-linked chitosan hydrogels: Adsorption, kinetics, and mechanisms.

Herein we present a study on the preparation and properties of a hydrogel adsorbent for treatment of wasted palladium souring from actial petrochemical industrial wastewater. Chitosan was used as the raw material and acrolein as the cross-linking agent for the hydrogel (A/CS). The adsorption behaviors of the hydrogel for Pd(II) ions were characterized and analyzed. The effect of pH, temperature, adsorption kinetics, and thermodynamics were investigated. Langmuir models were employed to describe the adsorption isotherms, while the pseudo-second-order equation was applied to describe the adsorption kinetics. The experimental results demonstrated that the adsorption was a monolayer chemical adsorption, and the adsorption capacity was found to reach 505.05 mg/g under optimal conditions. In addition, FT-IR and XPS analyses, combined with MS calculations confirmed that chelation and electrostatic attraction were dominated in the adsorption process. Overall, the development of this hydrogel adsorbent will provide a practical approach to the treatment of industrial wastewater containing palladium and have great potential for practical applications.

Molecular insights into the mechanisms of a leaf color mutant in Anoectochilus roxburghii by gene mapping and transcriptome profiling based on PacBio Sequel II.

Plants with partial or complete loss of chlorophylls and other pigments are frequently occurring in nature but not commonly found. In the present study, we characterize a leaf color mutant 'arly01' with an albino stripe in the middle of the leaf, which is an uncommon ornamental trait in Anoectochilus roxburghii. The albino "mutant" middle portion and green "normal" leaf parts were observed by transmission electron microscopy (TEM), and their pigment contents were determined. The mutant portion exhibited underdevelopment of plastids and had reduced chlorophyll and other pigment (carotenoid, anthocyanin, and flavonoid) content compared to the normal portion. Meanwhile, comparative transcript analysis and metabolic pathways mapping showed that a total of 599 differentially expressed genes were mapped to 78 KEGG pathways, most of which were down-regulated in the mutant portion. The five most affected metabolic pathways were determined to be oxidative phosphorylation, photosynthesis system, carbon fixation & starch and sucrose metabolism, porphyrin and chlorophyll metabolism, and flavonoid biosynthesis. Our findings suggested that the mutant 'arly01' was a partial albinism of A. roxburghii, characterized by the underdevelopment of chloroplasts, low contents of photosynthetic and other color pigments, and a number of down-regulated genes and metabolites. With the emergence of ornamental A. roxburghii in southern China, 'arly01' could become a popular cultivar due to its unique aesthetics.

Non-apoptotic programmed cell deaths in diabetic pulmonary dysfunction: the new side of advanced glycation end products.

Diabetes mellitus (DM) is a chronic metabolic disorder that affects multiple organs and systems, including the pulmonary system. Pulmonary dysfunction in DM patients has been observed and studied for years, but the underlying mechanisms have not been fully understood. In addition to traditional mechanisms such as the production and accumulation of advanced glycation end products (AGEs), angiopathy, tissue glycation, oxidative stress, and systemic inflammation, recent studies have focused on programmed cell deaths (PCDs), especially the non-apoptotic ones, in diabetic pulmonary dysfunction. Non-apoptotic PCDs (NAPCDs) including autophagic cell death, necroptosis, pyroptosis, ferroptosis, and copper-induced cell death have been found to have certain correlations with diabetes and relevant complications. The AGE-AGE receptor (RAGE) axis not only plays an important role in the traditional pathogenesis of diabetes lung disease but also plays an important role in non-apoptotic cell death. In this review, we summarize novel studies about the roles of non-apoptotic PCDs in diabetic pulmonary dysfunction and focus on their interactions with the AGE-RAGE axis.

Characterization of translocon proteins in the type III secretion system of Lawsonia intracellularis.

Lawsonia intracellularis, the etiologic agent of proliferative enteropathy (PE), is an obligate intracellular Gram-negative bacterium possessing a type III secretion system (T3SS), which enables the pathogen to translocate effector proteins into targeted host cells to modulate their functions. T3SS is a syringe-like apparatus consisting of a base, an extracellular needle, a tip, and a translocon. The translocon proteins assembled by two hydrophobic membrane proteins can form pores in the host-cell membrane, and therefore play an essential role in the function of T3SS. To date, little is known about the T3SS and translocon proteins of L. intracellularis. In this study, we first analyzed the conservation of the T3S apparatus between L. intracellularis and Yersinia, and characterized the putative T3S hydrophobic major translocon protein LI1158 and minor translocon protein LI1159 in the L. intracellularis genome. Then, by using Yersinia pseudotuberculosis as a surrogate system, we found that the full-length LI1158 and LI1159 proteins, but not the putative class II chaperone LI1157, were secreted in a - Ca2+ and T3SS-dependent manner and the secretion signal was located at the N terminus (aa 1-40). Furthermore, yeast-two hybrid experiments revealed that LI1158 and LI1159 could self-interact, and LI1159 could interact with LI1157. However, unlike CPn0809 and YopB, which are the major hydrophobic translocon proteins of the T3SS of C. pneumoniae and Yersinia, respectively, full-length LI1158 was non-toxic to both yeast and Escherichia coli cells, but full-length LI1159 showed certain toxicity to E. coli cells. Taken together, despite some differences from the findings in other bacteria, our results demonstrate that LI1158 and LI1159 may be the translocon proteins of L. intracellularis T3SS, and probably play important roles in the translocation of effector proteins at the early pathogen infection stage.

Maternal and Neonatal Outcomes of Twin Pregnant Women With Anemia.

The aim of this study was to investigate the prevalence of anemia in twin pregnancies and the influence of anemia on maternal and neonatal outcomes. This retrospective study included twin pregnant women who delivered in a tertiary hospital in China from January 2018 to December 2018. Patients were divided by WHO criteria (hemoglobin <11.0 g/dL): the anemic and nonanemic groups. Patients with anemia were further classified as recovered or unrecovered subgroup after oral iron therapy. Maternal and neonatal outcomes in women carrying twins were compared using Student's t test and the chi-squared test or the Fisher exact test. Univariable and multivariable logistic regression models were used to determine the association of maternal and neonatal characteristics with anemia. Linear regression analysis was used to estimate mean birth weight and gestational week. The prevalence of anemia was 42.6% (182/427) in twin pregnancies. The anemic group had higher rates of low 1-minute Apgar score (4.4% vs. 1.8%, p = .028), perinatal death (1.9% vs. 0.2%, p = .012) and neonatal intensive care unit (NICU) admission (27.2% vs. 20.2%, p = .017; adjusted OR, 1.478; 95% CI [1.07, 2.044]). The recovered subgroup had lower NICU admission rate (13.5% vs. 30.3%, p = .006; OR, 0.388; 95% CI [0.186, 0.809]), higher gestational week and birth weight (ß, 0.954 week; 95% CI [0.114, 1.794] and ß, 171.01 g; 95% CI [9.894, 332.126] respectively). The prevalence of anemia in twin gestation is high. Anemia is associated with adverse neonatal outcomes, and correction of anemia significantly improved the pregnancy outcomes.

Impact of Air Pollution on Atopic Dermatitis: A Comprehensive Review.

Air pollution is associated with multiple health problems worldwide, contributing to increased morbidity and mortality. Atopic dermatitis (AD) is a common allergic disease, and increasing evidence has revealed a role of air pollution in the development of atopic dermatitis. Air pollutants are derived from several sources, including harmful gases such as nitrogen dioxide (NO2), sulfur dioxide (SO2), and carbon monoxide (CO), as well as particulate matter (PM) of various sizes, and bioaerosols. Possible mechanisms linking air pollution to atopic dermatitis include damage to the skin barrier through oxidative stress, increased water loss, physicochemical injury, and an effect on skin microflora. Furthermore, oxidative stress triggers immune dysregulation, leading to enhanced sensitization to allergens. There have been multiple studies focusing on the association between various types of air pollutants and atopic dermatitis. Since there are many confounders in the current research, such as climate, synergistic effects of mixed pollutants, and diversity of study population, it is not surprising that inconsistencies exist between different studies regarding AD and air pollution. Still, it is generally accepted that air pollution is a risk factor for AD. Future studies should focus on how air pollution leads to AD as well as effective intervention measures.

Gut microbiome and mycobiome in inflammatory bowel disease patients with Clostridioides difficile infection.

Background: Clostridium difficile infection (CDI) is common in patients with inflammatory bowel disease (IBD) and has been reported as a risk factor for poor outcome. However, gut microbiome and mycobiome of IBD patients with CDI have been barely investigated. This study aimed to assess the gut microbiome and mycobiome in IBD patients with CDI. Methods: We collected fecal samples from patients with active IBD and concomitant CDI (IBD-CDI group, n=25), patients with active IBD and no CDI (IBD-only group, n=51), and healthy subjects (HC, n=40). Patients' characteristics including demographic data, disease severity, and medication history were collected. Metagenomic sequencing, taxonomic and functional analysis were carried out in the samples. Results: We found that the bacterial alpha diversity of the IBD-CDI group was decreased. The bacterial and fungal beta diversity variations between IBD patients and HC were significant, regardless of CDI status. But the IBD-CDI group did not significantly cluster separately from the IBD-only group. Several bacterial taxa, including Enterococcus faecium, Ruminococcus gnavus, and Clostridium innocuum were overrepresented in the IBD-CDI group. Furthermore, IBD patients with CDI were distinguished by several fungal taxa, including overrepresentation of Saccharomyces cerevisiae. We also identified functional differences in IBD patients with CDI include enrichment of peptidoglycan biosynthesis. The network analysis indicated specific interactions between microbial markers in IBD-CDI patients. Conclusion: IBD patients with CDI had pronounced microbial dysbiosis. Gut micro-ecological changes in IBD patients with CDI might provide insight into the pathological process and potential strategies for diagnosis and treatment in this subset of patients.

Minimal adverse outcomes of postnatal cytomegalovirus infection in term or moderate and late preterm infants.

Objective: The aim of study was to investigate at what extent breastfeeding and vaginal delivery can increase mother-to-child transmission of cytomegalovirus (CMV) and to observe the clinical outcomes of postnatal infection in term or moderate and late preterm infants. Methods: In this retrospective study of prospectively collected clinical data and serum samples, during 2012-2015, 380 women with CMV IgG positive/IgM negative and their 384 infants (4 twin pairs) with gestational age ≥32 weeks were included. CMV IgG and IgM were measured with enzyme-linked immunosorbent assay. Results: Of 384 infants followed up at 10.2 ± 2.3 months age, 177 (46.1%) were defined with CMV infection based on the presence of higher CMV IgG levels than in their mothers. The infection rate in 190 breastfed infants was higher than in 194 formula-fed infants (62.6% vs. 29.9%, P < 0.001). Vaginally delivered infants (172) had higher CMV infection rate than 212 infants delivered by caesarean section (55.2% vs. 38.7%, P = 0.001). Compared with formula feeding and caesarean section, breastfeeding and vaginal delivery increased postnatal CMV infection respectively (OR = 3.801, 95% CI 2.474-5.840, P < 0.001; OR = 1.818, 95% CI 1.182-2.796, P = 0.007). Nevertheless, compared to uninfected infants, CMV-infected infants had comparable height and body weight and showed no adverse effect on the liver enzymes. Conclusion: Breastfeeding and vaginal delivery can increase postnatal CMV infection; however, the infection does not influence the growth of the term infants or preterm infants with gestational age ≥32 weeks. Thus, breastfeeding should be encouraged in these infants regardless of maternal CMV IgG status.

Elevated Placental microRNA-155 Is a Biomarker of a Preeclamptic Subtype.

BACKGROUND: Preeclampsia is a complicated syndrome with marked heterogeneity. The biomarker-based classification for this syndrome is more constructive to the targeted prevention and treatment of preeclampsia. It has been reported that preeclamptic patients had elevated microRNA-155 (miR-155) in placentas or circulation. Here, we investigated the characteristics of patients with high placental miR-155 (pl-miR-155). METHODS: Based on the 95th percentile (P95) of pl-miR-155 in controls, preeclamptic patients were divided into high miR-155 group (≥P95) and normal miR-155 group (

Adverse Events of Immune Checkpoint Inhibitor-Based Therapies for Unresectable Hepatocellular Carcinoma in Prospective Clinical Trials: A Systematic Review and Meta-Analysis.

Background: The aim of the study was to investigate the incidence and spectrum of adverse events in unresectable hepatocellular carcinoma (HCC) patients treated with immune checkpoint inhibitors (ICIs) or ICI-based combinations. Summary: The study protocol was prospectively registered on PROSPERO (CRD42022319255). We searched PubMed, EMBASE, and the Cochrane Library for published clinical trials from database inception to April 22, 2022. Studies that included at least one group of unresectable HCC patients treated with ICIs or ICI-based combinations and reported the incidence or spectrum of treatment-related adverse events (trAEs) or immune-related adverse events (irAEs) were eligible. The incidence and spectra of all-grade and grade ≥3 trAEs were the primary outcomes. The profiles of irAEs, the incidence of trAEs leading to treatment discontinuation, and treatment-related mortalities were additional outcomes. We applied random-effects models to pool the incidence and spectra of adverse events. Subgroup analyses and meta-regression were performed. The literature search identified 2,464 records. Twenty studies (4,146 participants with HCC) met the eligibility criteria. The pooled incidences of all-grade trAEs, grade ≥3 trAEs, all-grade irAEs, and grade ≥3 irAEs were 80.1% (95% CI: 73.8-85.2), 35.4% (95% CI: 27.2-44.6), 31.1% (95% CI: 21.0-43.5), and 6.6% (95% CI: 3.6-11.8), respectively. ICIs plus oral targeted agents (all-grade OR = 17.07, 95% CI: 6.05-48.16, p < 0.001; grade ≥3 OR = 9.35, 95% CI: 4.53-19.29, p < 0.001) and ICIs plus intravenous targeted agents (all-grade OR = 4.91, 95% CI: 1.80-13.42, p = 0.003; grade ≥3 OR = 4.21, 95% CI: 1.42-12.48, p = 0.012) were associated with increased trAEs compared with monotherapy. The all-grade trAEs with the highest pooled incidences were reactive capillary endothelial proliferation (49.2%, 95% CI: 26.3-72.3), neutropenia (34.6%, 95% CI: 17.1-57.5), and proteinuria (32.8%, 95% CI: 19.8-49.2). The grade ≥3 trAEs with the highest pooled incidences were hypertension (11.1%, 95% CI: 4.0-29.0), neutropenia (10.5%, 95% CI: 7.0-15.4), and increased aspartate aminotransferase (7.7%, 95% CI: 6.3-9.4). The pooled incidence of trAEs leading to treatment discontinuation was 8.0% (95% CI: 6.0-10.5), and the overall incidence of treatment-related mortalities was 1.1%. Key Messages: This study comprehensively summarized the incidence and spectrum of trAEs in unresectable HCC patients receiving ICIs or ICI-based combinations in clinical trials. The results from this study will provide a useful reference to guide clinical practice.

Development and validation of novel models for the prediction of intravenous corticosteroid resistance in acute severe ulcerative colitis using logistic regression and machine learning.

Background: The early prediction of intravenous corticosteroid (IVCS) resistance in acute severe ulcerative colitis (ASUC) patients remains an unresolved challenge. This study aims to construct and validate a model that accurately predicts IVCS resistance. Methods: A retrospective cohort was established, with consecutive inclusion of patients who met the diagnosis criteria of ASUC and received IVCS during index hospitalization in Peking Union Medical College Hospital between March 2012 and January 2020. The primary outcome was IVCS resistance. Classification models, including logistic regression and machine learning-based models, were constructed. External validation was conducted in an independent cohort from Shengjing Hospital of China Medical University. Results: A total of 129 patients were included in the derivation cohort. During index hospitalization, 102 (79.1%) patients responded to IVCS and 27 (20.9%) failed; 18 (14.0%) patients underwent colectomy in 3 months; 6 received cyclosporin as rescue therapy, and 2 eventually escalated to colectomy; 5 succeeded with infliximab as rescue therapy. The Ulcerative Colitis Endoscopic Index of Severity (UCEIS) and C-reactive protein (CRP) level at Day 3 are independent predictors of IVCS resistance. The areas under the receiver-operating characteristic curves (AUROCs) of the logistic regression, decision tree, random forest, and extreme-gradient boosting models were 0.873 (95% confidence interval [CI], 0.704-1.000), 0.648 (95% CI, 0.463-0.833), 0.650 (95% CI, 0.441-0.859), and 0.604 (95% CI, 0.416-0.792), respectively. The logistic regression model achieved the highest AUROC value of 0.703 (95% CI, 0.473-0.934) in the external validation. Conclusions: In patients with ASUC, UCEIS and CRP levels at Day 3 of IVCS treatment appeared to allow the prompt prediction of likely IVCS resistance. We found no evidence of better performance of machine learning-based models in IVCS resistance prediction in ASUC. A nomogram based on the logistic regression model might aid in the management of ASUC patients.

Efficacy of the hepatitis B vaccine alone in the prevention of hepatitis B perinatal transmission in infants born to hepatitis B e antigen-negative carrier mothers.

Background: Vertical mother-to-child transmission (MTCT) of the hepatitis B virus (HBV) remains an important issue. Timely administration of hepatitis B immunoglobulin (HBIG) and of the HBV vaccine is effective in preventing MTCT in infants born to HBV-infected mothers. However, HBIG is often not easily available in low-income countries or regions. Methods: We compared in a retrospective cohort study the HBV vaccine efficacy alone and in combination with HBIG in preventing vertical MTCT in infants born to HBeAg-negative carrier mothers in Jiangsu province, China. Based on the administration of the HBV vaccine and HBIG shortly after birth, children were divided into two groups: Group 1, administration of the HBV vaccine alone, and Group 2, concurrent use of HBIG and of the HBV vaccine. Results: A total of 620 infants born to HBeAg-negative carrier mothers were enrolled into this study. Group 1 included 195 children who had received the HBV vaccine alone after birth, and Group 2, 425 children who had received both HBIG and the HBV vaccine. Children were followed up to the age of 68 and 42 months, respectively. MTCT of HBV occurred in 0% (0/195) in Group 1 (HBV vaccine alone) and 0% (0/425) in Group 2 (HBV vaccine and HBIG) (p = 1.00). Conclusion: In this retrospective cohort study, we found that HBV vaccination alone shortly after birth was effective in preventing MTCT of HBV in infants born to HBeAg-negative carrier mothers.

Novel ADAMTS13 mutation in a family with three recurrent neonatal deaths: a case report and literature review.

Background: Upshaw-Schulman syndrome (USS) is rare, autosomal recessive, hereditary thrombotic thrombocytopenic purpura (TTP) caused by variants in a disintegrin-like and metalloprotease with thrombospondin type 1 motif (ADAMTS13). USS has a heterogeneous clinical course, and most symptoms overlap with other diseases. Early diagnosis may have important implications for the patients. We found novel ADAMTS13 mutation and explored the clinical features and prognosis of newborn-onset USS to increase awareness of the disease. Case Description: The same, non-consanguineous couple had three unexplained neonatal deaths. The symptoms of the three infants were mainly severe jaundice, anemia and thrombocytopenia after birth, which was consistent with the reported USS symptoms of neonates and died rapidly suddenly in the during rescue efforts. By using whole-exome sequencing (WES) for the study family, we found a novel heterozygous compound in ADAMTS13 (c.1187 (exon10) G>A (p.C396Y)/c.1595 (exon14) G>T (p.C532F)) that was carried by the three newborns originating from father and mother respectively. We reviewed nine published studies of newborn-onset USS and compared our cases for clinical symptoms and laboratory testing. All nine published cases were diagnosed by ADAMTS13 activity; in seven cases gene mutation analysis was performed and eight cases were still alive at the time of publication. Conclusions: The case has added clinicians' awareness of the diagnosis and treatment of USS. A novel rare mutation in ADAMTS13 broadens the spectrum of genetic causes of this rare disorder and expands the phenotypic spectrum.

Lawsonia intracellularis LI0666 is a new EPIYA effector exported by the Yersinia enterocolitica type III secretion system.

Lawsonia intracellularis is the causative agent of proliferative enteropathy. While it harbors genes encoding the entire apparatus required for the type III secretion system (T3SS) and the expression of some of these components has been detected during experimental infection, the identification of L. intracellularis T3SS substrates (effector proteins) has been hampered. The Yersinia T3SS and yeast growth inhibition assays are two important heterologous systems used for the characterization of effector proteins. Bacterial EPIYA effectors are a distinct class of bacterial effectors defined by the presence of EPIYA or the EPIYA-related motif. When delivered into host cells via a T3SS or type IV secretion system, these effectors undergo tyrosine phosphorylation of the EPIYA motif, which enables them to manipulate host cell signaling by promiscuously interacting with multiple SH2 domain-containing proteins. A previous study showed that L. intracellularis LI0666 contains two EPIYA motifs and speculated that this protein could be a T3SS effector. In this study, we show that LI0666 is secreted by Yersinia in a T3SS-dependent manner and inhibits yeast growth. LI0666 is phosphorylated at tyrosine residues in porcine intestinal epithelial cells and in human epithelial cells. Like the archetypal EPIYA effector CagA, the EPIYA-containing region is not required for LI0666 association with yeast and mammalian cell membranes. Our results indicate that LI0666 is an authentic bacterial EPIYA effector. Identification of the tyrosine kinases that are responsible for LI0666 phosphorylation and the SH2 domain-containing host proteins that LI0666 interacts with will help to explore the molecular mechanisms of LI0666 in disease development.