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Whether screening can attenuate the influence of genetic risk and environmental risk factors for colorectal cancer (CRC) mortality risk remains unknown. Our study is to investigate the association of the screening history, genetic risk and environmental risk factors with CRC incidence and mortality risks using UK Biobank data. Screening history was associated with lower CRC incidence (hazard ratio [HR]: 0.63, 95% confidence interval [CI]: 0.58-0.69) and mortality risk (HR: 0.56, 95% CI: 0.49-0.63). Compared to the HRs of participants with a low genetic risk, low environmental risk and no screening history, the HRs of participants with a high genetic risk, high environmental risk and no screening history were 3.42 (95% CI: 2.76-4.24) for CRC incidence and 3.36 (95% CI: 2.48-4.56) for CRC mortality. In contrast, the HRs of participants with a high genetic risk and no screening history, but a low environmental risk, were 1.92 (95% CI: 1.55-2.36) for CRC incidence and 1.88 (95% CI: 1.39-2.53) for CRC mortality. Furthermore, the HRs of participants with a high genetic risk and a low environmental risk, but a screening history were 1.62 (95% CI: 1.15-2.28) for CRC incidence and 1.77 (95% CI: 1.08-2.89) for CRC mortality. Participants benefited more substantially from screenings for CRC mortality than for CRC incidence risk. A higher environmental risk was associated with higher risk of CRC incidence and mortality within each category of genetic risk. These findings emphasize the importance of CRC screening and identifying environmental factors to reduce CRC incidence and mortality risks.

Introduction: Premature infants are exceptionally vulnerable to nutrition-related diseases, and the utilization of standardized feeding guidelines may reduce nutritional practice variation, which can promote growth. Nutritional risk screening is the first step for standardized nutrition advice. However, risk screening tools specific for following up preterm infants are scarce. Hence, our study aimed to develop and evaluate a standardized Nutritional Risk Screening Tool for Preterm Infants (NRSP subscale 1) from birth to corrected age four months old . Methods: This study was a two-phase (the development phase and evaluation phase) study. Initially, we used the Delphi expert consultation method to create NRSP subscale 1. Then, a professional panel interviewed the participated preterm infants using the screening tool, measured anthropometric parameters, and conducted an intellectual development test on the interview day and remeasured anthropometric parameters 2 weeks or 1 month after the first interview. In the development phase, we cross-tabulated the responses to the screening tool with the classifications of z-scores of the body weight, length, or head circumference to identify significant predictors of underweight, stunting, or microcephaly. We then combined significant predictors to produce models for predicting underweight, stunting, or microcephaly by multivariate logistic regression analysis. In the evaluation phase, the area under the curve (AUC), sensitivity, specificity, and correlation coefficient by Spearman’s correlation analysis (rs) between the risk classifications by NRSP subscale 1 and the classifications of the z-scores of the body weight, length, or head circumference were calculated to assess the validity of the screening tool. Intellectual development levels between high and low nutritional risk infants were statistically compared. Results: A total of 219 and 244 preterm infants were included to two phases, respectively. AUC was 0.936 (95% CI: 0.860–1.000, p < 0.001), sensitivity was 0.667, specificity was 0.941, rs = 0.407 (p < 0.001); AUC was 0.794 (95% CI: 0.638–0.951, p = 0.002), sensitivity was 0.500, specificity was 0.953, rs = 0.339 (p < 0.001); AUC was 0.831 (95% CI: 0.737–0.925, p = 0.001), sensitivity was 0.889, specificity was 0.643, rs = 0.215 (p = 0.001) in predicting underweight, stunting, and microcephaly on the interview day, respectively. AUC was 0.905 (95% CI: 0.826–0.984, p = 0.006), sensitivity was 0.500, specificity was 0.905, rs = 0.504 (p < 0.001); AUC was 0.738 (95% CI: 0.515–0.960, p = 0.034), sensitivity was 0.429, specificity was 0.848, rs = 0.382 (p < 0.001); AUC was 0.664 (95% CI: 0.472–0.856, p = 0.071), sensitivity was 0.455, specificity was 0.809, rs = 0.169 (p = 0.037) in predicting underweight, stunting, and microcephaly 2 weeks or 1 month after the first interview, respectively. Gross motor development quotients (DQs) (95.85 [32.87] vs. 86.29 [17.19], p = 0.022), fine motor DQs (115.77 [46.03] vs. 102.12 [20.27], p = 0.010), and verbal DQs (110.73 [35.27] vs. 100.63 [21.28], p = 0.042) were higher in low nutritional risk infants than high-risk ones. Conclusion: NRSP subscale 1 was acceptable and reliable in predicting underweight, but the validity in predicting stunting or microcephaly was slightly mild. Further investigations are required to authenticate NRSP subscale 1’s effectiveness.

Regular use of non-steroidal anti-inflammatory drugs (NSAIDs) was associated with the lower risk of colorectal cancer (CRC). However, whether regular use of NSAIDs could attenuate the effect of genetic risk and environmental risk factors on CRC is unknown. We aimed to evaluate the association of NSAID use, genetic risk, and environmental risk factors with CRC. Using data from a UK Biobank, a Cox proportional hazards model was performed to estimate the risk of CRC according to NSAID use, polygenic risk score, and environmental risk factors. Regular use of NSAIDs was associated with a 36.0% lower risk of CRC. No statistically significant interaction was observed between NSAID use and the genetic risk score (p = 0.190), and between NSAID use and the environmental risk score (p = 0.740). However, regular NSAID use was still associated with lower CRC incidence among subjects with either high environmental risk or high genetic risk. Furthermore, the genetic and environmental risk of CRC were additives. These findings appear to support the chemopreventive effect of regular NSAID use. Furthermore, controlling of modifiable environmental risk factors can reduce the CRC risk, especially among individuals with a moderate or high genetic risk of CRC.

Gestational diabetes mellitus (GDM) has become a global health concern as the main result of its contribution to the high risk of adverse pregnancy outcomes for both the mother and fetus. However, there is absence of an ideal and widely acceptable therapy. Nuciferine has previously been shown to exert beneficial effects in various metabolic diseases. This study aimed to investigate the potential therapeutic efficacy of nuciferine on GDM in C57BL/6J mice induced by a high-fat diet (HFD), which has not been reported before. The results showed that nuciferine improved glucose intolerance, reduced lipid accumulation and increased the glycogen content within hepatocytes, and decreased placental lipid and glycogen deposition, thus ameliorating glycolipid disorders in GDM mice. Additionally, nuciferine protected against histological degeneration of metabolism-associated critical organs including the liver, pancreas, and abdominal adipose tissue. Most interestingly, nuciferine could correct intestinal dysbacteriosis in GDM mice, as evidenced by the elevation of probiotic abundances consisting of Akkermansia, Lactobacillus, and Bifidobacterium, which were all negatively correlated with serum and liver triglyceride (TG) and positively associated with hepatic glycogen, and the reduction of conditional pathogen abundances including Escherichia-Shigella and Staphylococcus, and the latter was positively related to serum and liver TG and negatively linked with liver glycogen. Collectively, these findings suggest that nuciferine as a food-borne strategy played important roles in the management of GDM.

Background Retinoic acid-related orphan receptor alpha (RORA) has been reported to be suppressed in autistic patients and is associated with autism spectrum disorders (ASD), although the potential role and mechanism of RORA on gastrointestinal (GI) symptoms in ASD patients is still not reported. In this study, we aim to investigate the contribution of RORA to GI symptoms through a maternal diabetes-mediated autism-like mouse model. Results Male offspring of diabetic dams were treated with either superoxide dismutase (SOD) mimetic MnTBAP or RORA agonist SR1078, or were crossbred with intestine epithelial cells (IEC)-specific RORA knockout (RORA−/−) mouse. Gene expression, oxidative stress and inflammation were measured in brain tissues, peripheral blood mononuclear cells (PBMC) and IEC, and GI symptoms were evaluated. Our results showed that SOD mimetic MnTBAP completely, while RORA agonist SR1078 partly, reversed maternal diabetes-mediated oxidative stress and inflammation in the brain, PBMC and IEC, as well as GI symptoms, including intestine permeability and altered gut microbiota compositions. IEC-specific RORA deficiency either mimicked or worsened maternal diabetes-mediated GI symptoms as well as oxidative stress and inflammation in IEC, while there was little effect on maternal diabetes-mediated autism-like behaviors. Conclusions We conclude that RORA suppression contributes to maternal diabetes-mediated GI symptoms in autism-like mouse offspring, this study provides a potential therapeutical target for maternal diabetes-mediated GI symptoms in offspring through RORA activation.

Anemia is associated with neurodevelopmental delays and brain injury in infants and toddlers, but whether early anemia has a similar effect in neonatal preterm infants is largely unknown. Thus, this study aimed to determine the relationship of early anemia with neurodevelopment and brain injury in very-low-birth-weight (VLBW) preterm infants within the neonatal period. A prospective cohort study including 110 VLBW preterm infants was conducted in Southern China from 2016 to 2018. All participants were followed from birth to 1 month corrected age. Early anemia is defined as hemoglobin of ≤145 g/L within the first week after birth. The non-anemic group (control group, N = 55) was 1:1 matched with the early anemia group (N = 55) according to birth weight and gestational age. Neurodevelopment at 1 month corrected age and brain injury within 1 month corrected age were measured by neonatal behavioral neurological assessments (NBNA) and cranial ultrasound, respectively. Compared to the control group, the early anemia group had a lower score in behavioral ability in the NBNA test [11 (10–12) vs. 10 (9.5–11), p = 0.033]. Early anemia was negatively associated with the NBNA total score (β= −0.680, 95% CI: −1.300, −0.059), especially with the behavioral ability score (β= −0.504, 95% CI: −0.941, −0.067) after adjusting for the confounders. However, no association between early anemia and brain injury was observed. In conclusion, in VLBW preterm infants, early anemia is negatively correlated with neurodevelopment, especially with behavioral ability.

Rolandic epilepsy (RE) is among the most common focal epilepsies in childhood. For the majority of patients with RE and atypical RE (ARE), the etiology remains elusive. We thus screened patients with RE/ARE in order to detect disease-causing variants.. A trios-based whole-exome sequencing approach was performed in a cohort of 28 patients with RE/ARE. Clinical data and EEGs were reviewed. Variants were validated by Sanger sequencing. Two compound heterozygous missense variants p.Val272Ile/p.Asn3028Ser and p.Ala3657Val/p.Met4419Val of ADGRV1 were identified in two unrelated familial cases of RE/ARE. All the variants were in the calcium exchanger β domain and were suggested to be damaging by at least one web-based prediction tool. These variants are not present or are present at a very low minor allele frequency in the gnomAD database. Previously, biallelic ADGRV1 variants (p.Gly2756Arg and p.Glu4410Lys) have been observed in RE, consistent with the observation in this study and supporting the association between ADGRV1 variants and RE. Additionally, a de novo mutation, p.Asp668Asn, in GRIN2B was identified in a sporadic case of ARE, and a missense variant, p.Asn1551Ser, in RyR2 was identified in a family with RE with incomplete penetrance. These genes are all calcium homeostasis associated genes, suggesting the potential effect of calcium homeostasis in RE/ARE. The results from the present study suggest that the genes ADGRV1, GRIN2B, and RyR2 are associated with RE/ARE. These data link defects in neuronal intracellular calcium homeostasis to RE/ARE pathogenesis implicating that these defects plays an important role in the development of these conditions.

NPHS2 mutations are responsible for autosomal recessive familial steroid-resistant nephrotic syndrome (SRNS) with minor glomerular abnormalities or focal segmental glomerulosclerosis (FSGS), which is characterized by early childhood onset and rapid progression to chronic renal insufficiency. This gene mutation is also responsible for an adolescent onset form of autosomal recessive familial FSGS with heavy proteinuria. Many infants with late steroid-resistant nephrotic syndrome (late SRNS) are prone to an implicated clinical and therapeutic course. The etiopathogenesis and the long-term prognosis of late SRNS remain obscure. Considering the similar steroid resistance between late and initial SRNS, analysis of NPHS2 variation was performed in 70 sporadic Chinese infants with late SRNS and 70 controls in the present study to investigate the possible role of NPHS2 gene in late SRNS. The variation analysis revealed three polymorphisms (288C T heterozygous in exon 2, 954T C heterozygous and homozygous, and 1038A G heterozygous in exon 8) in 22 out of 70 patients studied. In conclusion, NPHS2 gene mutations are not a major cause of chronic renal insufficiency caused by late SRNS in Chinese southern infants.