Knockdown of Long Noncoding RNAs of Maternally Expressed 3 Alleviates Hyperoxia-Induced Lung Injury via Inhibiting Thioredoxin-Interacting Protein-Mediated Pyroptosis by Binding to miR-18a.

Long-term hyperoxia exposure may cause lung damage with characteristic inflammation. Long noncoding RNA of maternally expressed 3 (MEG3) is up-regulated in lung tissues exposed to hyperoxia; however, the underlying mechanism is unclear. Hyperoxia-induced cells and mouse models were used to study these mechanisms. Molecular assays were used to detect cell viability, cytotoxicity, and expression of miR-18a, MEG3, and inflammatory cytokines. The interaction among MEG3, miR-18a, and thioredoxin-interacting protein (TXNIP) was verified; and pyroptosis-related proteins were analyzed. The in vivo model was established by exposing MEG3 knockdown mice to hyperoxia. Hematoxylin and eosin staining was used to assess pathologic alterations of lung tissues. Hyperoxia suppressed cell viability, induced cell damage, and exacerbated the secretion of IL-1ß and IL-18. Hyperoxia inhibited miR-18a, with increased expression of MEG3, TXNIP, and nonobese diabetic-like receptor family pyrin domain containing 3 (NLRP3). MEG3 aggravated TXNIP expression by binding to miR-18a. Knockdown of MEG3 rescued hyperoxia-induced pyroptosis by up-regulating miR-18a. Furthermore, knockdown of MEG3 inhibited NLRP3 inflammasome activity and caspase-1 signaling by miR-18a. In vivo knockdown of MEG3 and overexpression of miR-18a relieved hyperoxia-induced lung injury via restraining NLRP3 inflammasome-mediated pyroptosis, whereas miR-18a inhibition reversed these effects. In conclusion, knockdown of MEG3 inhibits pyroptosis to alleviate hyperoxia lung injury by suppressing NLRP3 inflammasome and caspase-1 signaling via regulating miR-18a-TXNIP axis.

[Risk factors for cow's milk protein allergy in infants: a multicenter survey].

OBJECTIVE: To investigate the risk factors for cow's milk protein allergy (CMPA) among infants through a multicenter clinical study. METHODS: A total of 1 829 infants, aged 1-12 months, who attended the outpatient service of the pediatric department in six hospitals in Shenzhen, China from June 2016 to May 2017 were enrolled as subjects. A questionnaire survey was performed to screen out suspected cases of CMPA. Food avoidance and oral food challenge tests were used to make a confirmed diagnosis of CMPA CMPA. A multivariate logistic regression analysis was used to investigate the risk factors for CMPA. RESULTS: Among the 1 829 infants, 82 (4.48%) were diagnosed with CMPA. The multivariate logistic regression analysis showed that maternal food allergy (OR=4.91, 95%CI: 2.24-10.76, P<0.05), antibiotic exposure during pregnancy (OR=3.18, 95%CI: 1.32-7.65, P<0.05), and the introduction of complementary food at an age of <4 months (OR=3.55, 95%CI: 1.52-8.27, P<0.05) were risk factors for CMPA, while exclusive breastfeeding (OR=0.21, 95%CI: 0.08-0.58, P<0.05) and the introduction of complementary food at an age of >6 months (OR=0.38, 95%CI: 0.17-0.86, P<0.05) were protective factors. CONCLUSIONS: The introduction of complementary food at an age of <4 months, maternal food allergy, and antibiotic exposure during pregnancy are risk factors for CMPA in infants.

[Clinical features of cow's milk protein allergy in infants presenting mainly with gastrointestinal symptoms: an analysis of 280 cases].

OBJECTIVE: To investigate the epidemiological and clinical features of cow's milk protein allergy (CMPA) in infants presenting mainly with gastrointestinal symptoms. METHODS: A retrospective analysis was performed for the clinical data of 280 hospitalized infants, who were diagnosed with CMPA presenting mainly with gastrointestinal symptoms. RESULTS: Among the 280 infants, 203 infants(72.5%) were aged of less than 6 months. Major manifestations included diarrhea in 171 infants (61.1%), hematochezia in 149 infants (53.2%), vomiting in 71 infants (25.4%), eczema in 57 infants (20.4%), malnutrition in 42 infants (15%) and constipation in 13 infants (4.6%). Of the 280 infants, 258 (92.1%) had mild-to-moderate CMPA and 22 (7.9%) had severe CMPA. Compared with the mild-to-moderate CMPA group, the severe CMPA group had a significantly higher incidence rate of malnutrition (50.0% vs 12.0%) and a significantly lower incidence rate of hematochezia (22.7% vs 55.8%). The breastfeeding CMPA group had significantly lower incidence rates of malnutrition (10.3% vs 24.6%) and severe CMPA (4.4% vs 18.0%) than the artificial feeding CMPA group, and the artificial feeding CMPA group had a significantly lower incidence rate of hematochezia than the breastfeeding and mixed feeding CMPA groups (37.7% vs 56.6%/59.0%). CONCLUSIONS: CMPA presenting mainly with gastrointestinal symptoms is more common in infants aged of less than 6 months. Diarrhea and hematochezia are the most common manifestations at the time of onset. Most infants have mild-to-moderate allergy. Compared with breastfeeding, artificial feeding is more likely to cause malnutrition and severe CMPA.

Nexrutine inhibits cancer cell growth as a consequence of mitochondrial damage and mitophagy.

BACKGROUND/AIMS: Nexrutine is an herbal extract of Phellodendron amurense and has been used as nutrient supplement in China as well as America. Potential protection effect of Nexrutine has been reported. METHODS: To investigate the mechanism of Nexrutine, we used the HeLa, U2OS and HCT116 as a model. Based on the acidification of cell culture media, we examined the lactate, mitochondria damage as well as mitophagy status by corresponding assay. RESULTS: Our data suggest that Nexrutine alters the cellular glucose metabolism to promote lactate production. This effect is caused by mitochondrial damage, not an alteration to lactate dehydrogenase activity. As a result of the mitochondrial damage, cell proliferation was inhibited and was associated with an elevation in p21/p27 proteins, which are both important cell cycle inhibitors. As another consequence of the mitochondrial damage, mitophagy was highly activated in Nexrutine-treated cells in a dose-dependent manner. When the autophagy pathway was blocked by siRNAs against BECN1 or ATG7, the growth inhibition caused by Nexrutine was reversed. CONCLUSION: Our study revealed that autophagy plays an important role in the inhibition of cancer cell proliferation by Nexrutine.

[Prognostic analysis of children with Henoch-Schonlein purpura treated by Helicobacter pylori eradication therapy].

OBJECTIVE: To investigate the effect of Helicobacter pylori (Hp) eradication therapy on prognosis in children with Henoch-Schonlein purpura (HSP). METHODS: A total of 153 children with HSP were divided into Hp infection treatment group (n=22), Hp infection control group (n=21), and Hp infection-negative group (n=110). The Hp infection treatment group received one-week triple therapy for Hp eradication in addition to conventional treatment, while the Hp infection control group and Hp infection-negative group received conventional treatment. All patients were followed up for prognostic evaluation. RESULTS: The response rates of the Hp infection treatment, control, and negative groups were 86% (19/22), 90% (19/21) and 85% (94/110), respectively (P>0.05). The recurrence rates of HSP in the Hp infection treatment, control, and negative groups were 14% (3/22), 24% (5/21) and 31% (34/110), respectively (P>0.05). The incidence of Henoch-Schonlein purpura nephritis (HSPN) in the Hp infection-negative group (36%, 40/110) and control group (33%, 7/21) was significantly higher than that in the Hp infection treatment group (5%, 1/22) (P<0.05 for both), but no significant difference in the incidence of HSPN was found between the control and negative groups (P>0.05). CONCLUSIONS: One-week triple therapy for Hp eradication may be useful to reduce the incidence of HSPN in children with HSP infected with Hp.

Gut microbiome biomarkers in adolescent obesity: a regional study.

Purpose: This study aimed to characterize the gut microbiota in obese adolescents from Shenzhen (China), and evaluate influence of gender on BMI-related differences in the gut microbiome. Methods: Evaluation of physical examination, blood pressure measurement, serological assay and body composition were conducted in 205 adolescent subjects at Shenzhen. Fecal microbiome composition was profiled via high-throughput sequencing of the V3-V4 regions of the 16S rRNA gene. A Random Forest (RF) classifier model was built to distinguish the BMI categories based on the gut bacterial composition. Results: Fifty-six taxa consisting mainly of Firmicutes were identified that having significant associations with BMI; 2 OTUs belonging to Ruminococcaceae and 1 belonging to Lachnospiraceae had relatively strong positive correlations with body fate rate, waistline and most of serum biochemical properties. Based on the 56 BMI-associated OTUs, the RF model showed a robust classification accuracy (AUC 0.96) for predicting the obese phenotype. Gender-specific differences in the gut microbiome composition was obtained, and a lower relative abundance of Odoribacter genus was particularly found in obese boys. Functional analysis revealed a deficiency in bacterial gene contents related to peroxisome and PPAR signaling pathway in the obese subjects for both genders. Conclusions: This study reveals unique features of gut microbiome in terms of microbial composition and metabolic functions in obese adolescents, and provides a baseline for reference and comparison studies. Supplementary Information: The online version contains supplementary material available at 10.1007/s13755-023-00236-9.

Study of Mental Health Status of the Resident Physicians in China During the COVID-19 Pandemic.

Objective: Investigating the mental health status of Chinese resident physicians during the 2019 new coronavirus outbreak. Methods: A cluster sampling method was adopted to collect all China-wide resident physicians during the epidemic period as the research subjects. The Symptom Checklist-90 self-rating scale was used to assess mental health using WeChat electronic questionnaires. Results: In total, 511 electronic questionnaires were recovered, all of which were valid. The negative psychological detection rate was 93.9% (480/511). Among the symptoms on the self-rating scale, more than half of the Chinese resident physicians had mild to moderate symptoms of mental unhealthiness, and a few had asymptomatic or severe unhealthy mental states. In particular, the detection rate of abnormality was 88.3% (451/511), obsessive-compulsive symptoms was 90.4% (462/511), the sensitive interpersonal relationship was 90.6% (463/511), depression abnormality was 90.8% (464)/511), anxiety abnormality was 88.3% (451/511), hostility abnormality was 85.3% (436/511), terror abnormality was 84.9% (434/511), paranoia abnormality was 86.9% (444/511), psychotic abnormalities was 89.0% (455/511), and abnormal sleeping and eating status was 90.8% (464/511). The scores of various psychological symptoms of pediatric resident physicians were significantly lower than those of non-pediatrics (p < 0.05). Conclusion: The new coronavirus epidemic has a greater impact on the mental health of Chinese resident physicians.

Phylogenetic Comparison and Splicing Analysis of the U1 snRNP-specific Protein U1C in Eukaryotes.

As a pivotal regulator of 5' splice site recognition, U1 small nuclear ribonucleoprotein (U1 snRNP)-specific protein C (U1C) regulates pre-mRNA splicing by interacting with other components of the U1 snRNP complex. Previous studies have shown that U1 snRNP and its components are linked to a variety of diseases, including cancer. However, the phylogenetic relationships and expression profiles of U1C have not been studied systematically. To this end, we identified a total of 110 animal U1C genes and compared them to homologues from yeast and plants. Bioinformatics analysis shows that the structure and function of U1C proteins is relatively conserved and is found in multiple copies in a few members of the U1C gene family. Furthermore, the expression patterns reveal that U1Cs have potential roles in cancer progression and human development. In summary, our study presents a comprehensive overview of the animal U1C gene family, which can provide fundamental data and potential cues for further research in deciphering the molecular function of this splicing regulator.

Phylogenetic comparison and splice site conservation of eukaryotic U1 snRNP-specific U1-70K gene family.

Eukaryotic cells can expand their coding ability by using their splicing machinery, spliceosome, to process precursor mRNA (pre-mRNA) into mature messenger RNA. The mega-macromolecular spliceosome contains multiple subcomplexes, referred to as small nuclear ribonucleoproteins (snRNPs). Among these, U1 snRNP and its central component, U1-70K, are crucial for splice site recognition during early spliceosome assembly. The human U1-70K has been linked to several types of human autoimmune and neurodegenerative diseases. However, its phylogenetic relationship has been seldom reported. To this end, we carried out a systemic analysis of 95 animal U1-70K genes and compare these proteins to their yeast and plant counterparts. Analysis of their gene and protein structures, expression patterns and splicing conservation suggest that animal U1-70Ks are conserved in their molecular function, and may play essential role in cancers and juvenile development. In particular, animal U1-70Ks display unique characteristics of single copy number and a splicing isoform with truncated C-terminal, suggesting the specific role of these U1-70Ks in animal kingdom. In summary, our results provide phylogenetic overview of U1-70K gene family in vertebrates. In silico analyses conducted in this work will act as a reference for future functional studies of this crucial U1 splicing factor in animal kingdom.

Prevention program for the COVID-19 in a children's digestive endoscopy center.

The pneumonia caused by the coronavirus disease-2019 (COVID-19) outbreak in Wuhan, China constitutes a public health emergency of international concern. The gastrointestinal symptoms of vomiting, diarrhea and abdominal pain and the detection of COVID-19 nucleic acid from fecal specimens in a small number of patients suggest the possibility of transmission via the gastrointestinal tract. People of all ages are vulnerable to this virus, including children. Digestive endoscopy is an invasive procedure during which children cannot wear masks; therefore, they have higher risks of exposure to COVID-19, and the digestive endoscopy center is a relatively high-risk area for COVID-19 infection. Based on these factors and in combination with related policies and regulations, a prevention and control program for the COVID-19 pneumonia in a children's digestive endoscopy center was established to prevent the COVID-19 nosocomial infection.

Accuracy of multi-echo Dixon sequence in quantification of hepatic steatosis in Chinese children and adolescents.

BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) is currently the outstanding cause of chronic liver disease in children and adolescents, especially in overweight and obese groups. Liver biopsy is the reference standard to diagnose NAFLD but invasive, thus it is not the best choice in clinical diagnosis and follow-up. Magnetic resonance (MR) is widely used in clinical trials to noninvasively quantify liver fat content in adults and children in foreign countries. While currently, it is rarely used in Chinese children and adolescents. We postulated that quantifying hepatic steatosis by MR could be extended to children and adolescents in China. AIM: To investigate the accuracy of MR imaging (MRI) in quantifying liver fat with MR spectroscopy (MRS) as a reference. A secondary goal was to assess the prevalence of NAFLD in overweight and obese Chinese children and adolescents. METHODS: There were 86 children and adolescents enrolled in this study, including 65 overweight and obese children and 21 healthy children. The participants underwent MRI and MRS. MRI and MRS were performed using multi-echo Dixon and HISTO sequences, respectively, to calculate hepatic proton density fat fraction (PDFF). Hepatic steatosis was diagnosed using MRS-PDFF > 5% as the threshold. Spearman's analysis was used to evaluate the correlation between MRI and MRS. The agreement between these two methods was assessed by Bland-Altman analysis. RESULTS: The MRI-PDFF in the MRS region of interest and the entire liver was 9.9% ± 10.3% with a range of 0.3%-39.9%, and 10.6% ± 9.4% with a range of 1.9%-38.9%, respectively. The MRS-PDFF was 9.1% ± 10.0%, with a range of 0.5%-37.8%. The incidence of hepatic steatosis detected by MRS-PDFF was 46.5% (40/86) of all participants, all of whom belonged to the overweight and obese group. Spearman's analysis indicated an excellent correlation between multi-echo Dixon and MRS (r > 0.9, P < 0.01). Bland-Altman analysis also demonstrated a good agreement between these two methods. CONCLUSION: Multi-echo Dixon shows an excellent correlation and agreement with MRS in quantifying liver fat content and could be a potential tool to detect hepatic steatosis in Chinese children and adolescents.

Chemical Modulation of Alternative Splicing for Molecular-Target Identification by Potential Genetic Control in Agrochemical Research.

Alternative splicing (AS), the process of removing introns from pre-mRNA and the rearrangement of exons to produce several types of mature transcripts, is a remarkable step preceding protein synthesis. In particular, it has now been conclusively shown that up to ∼95% of genes are alternatively spliced to generate a complex and diverse proteome in eukaryotic organisms. Consequently, AS is one of the determinants of the functional repertoire of cells. Many studies have revealed that AS in plants can be regulated by cell type, developmental stage, environmental stress, and the circadian clock. Moreover, increasing amounts of evidence reveal that chemical compounds can affect various steps during splicing to induce major effects on plant physiology. Hence, the chemical modulation of AS can serve as a good strategy for molecular-target identification in attempts to potentially control plant genetics. However, the kind of mechanisms involved in the chemical modulation of AS that can be used in agrochemical research remain largely unknown. This review introduces recent studies describing the specific roles AS plays in plant adaptation to environmental stressors and in the regulation of development. We also discuss recent advances in small molecules that induce alterations of AS and the possibility of using this strategy in agrochemical-target identification, giving a new direction for potential genetic control in agrochemical research.

Infant cholestasis patient with a novel missense mutation in the AKR1D1 gene successfully treated by early adequate supplementation with chenodeoxycholic acid: A case report and review of the literature.

Steroid 5ß-reductase [aldo-keto reductase family 1 member D1 (AKR1D1)] is essential for bile acid biosynthesis. Bile acid deficiency caused by genetic defects in AKR1D1 leads to life-threatening neonatal hepatitis and cholestasis. There is still limited experience regarding the treatment of this disease. We describe an infant who presented with hyperbilirubinemia and coagulopathy but normal bile acid and γ-glutamyltransferase. Gene analysis was performed using genomic DNA from peripheral lymphocytes from the patient, his parents, and his elder brother. The patient was compound heterozygous for c.919C>T in exon 8 and exhibited a loss of heterozygosity of the AKR1D1 gene, which led to an amino acid substitution of arginine by cysteine at amino acid position 307 (p.R307C). Based on these mutations, the patient was confirmed to have primary 5ß-reductase deficiency. Ursodeoxycholic acid (UDCA) treatment did not have any effect on the patient. However, when we changed to chenodeoxycholic acid (CDCA) treatment, his symptoms and laboratory tests gradually improved. It is therefore crucial to supplement with an adequate dose of CDCA early to improve clinical symptoms and to normalize laboratory tests.

[Roles of bile and gastrin in the pathogenesis of childhood gastroesophageal reflux disease].

OBJECTIVE: To explore the incidence of acid and bile reflux in children with gastroesophageal reflux disease (GERD) and to study the roles of bile and gastrin in the pathogenesis of childhood GERD. METHODS: Forty-two cases of GERD were divided into two groups according to endoscopic findings: reflux esophagitis (RE) and non-erosive reflux disease (NERD). The patients underwent 24-hr ambulatory esophageal pH and bilirubin monitoring. The serum concentration of gastrin was detected by radioimmunoassay. Thirteen children without gastroesophageal reflux symptoms, digestive tract disease and severe systemic organic disease served as the Control group. RESULTS: Of the 42 cases of GERD, 24 cases were confirmed with RE, with esophageal mucosal lesions, and 18 were NERD without esophageal mucosal lesions by endoscopy. Both acid and bile reflux parameters, including the percentage of total time with pH < 4 and bilirubin absorbance >/= 0.14, the total number of reflux episodes and the number of bile reflux episodes lasting longer than 5 minutes, were significantly higher in the GERD patients than those in the Control group (P < 0.05). The time of esophageal acid exposure (pH < 4) and the percentage of total time with bilirubin absorbance >/= 0.14 increased significantly in the RE group compared with in the NERD group (P < 0.05). Sixteen RE patients had a mixed reflux of bile and acid (66.7%) but only 6 NERD patients (33.3%) had (P < 0.01). The serum concentration of gastrin in the RE group (125.12 +/- 45.06 pg/mL) and the NERD group (98.22 +/- 27.92 pg/mL) was significantly higher than that of the Control group (74.22 +/- 20.34 pg/mL) (P < 0.01, P < 0.05 respectively). A significant difference was noted in the serum concentration of gastrin between the RE and the NERD groups (P < 0.05). CONCLUSIONS: Mixed reflux of bile and acid are common in children with GERD. Bile reflux may play a role in the development of GERD. Gastrin parasecretion may participate in the development of GERD. Gastrin and bile reflux may have synergistic effects on the development of childhood GERD.