Whether inhibiting the activity of nuclear factor (NF)-κB potentiates cisplatin-induced apoptosis in non-small cell lung cell line A549 cells was investigated. The recombinant plasmid pcDNA3.1(+)/IκBα expressing IκBα was constructed. The in vitro cultured A549 cells were trans-fected with pcDNA3.1(+)/IκBα alone, or pcDNA3.1(+)/IκBα combined with cisplatin. The mitochondrial membrane potential (△ψm) was determined by rhodamine 123, the activity of caspase-3 was tested by colorimetric assay, and cell apoptosis was detected by flow cytometry with the annexin V/propidium iodide assay. The results showed that the activity of NF-κB in A549 cells was inhibited by transfecting pcDNA3.1(+)/IκBα. Transfection of pcDNA3.1(+)/IκBα alone did not promote apoptosis. Treatment of cisplatin alone had a little effect on cell apoptosis. Transfection of pcDNA3.1(+)/IκBα combined with cisplatin treatment significantly induced apoptosis of A549 cells. It was concluded that inhibiting the activity of NF-κB potentiated cisplatin-induced apoptosis of A549 cells.

Objective:To evaluate the efficacy and safety of linaclotide with polyethylene glycol in bowel preparation.Methods:From September 2021 to February 2022, 240 patients who visited the Department of Gastroenterology, Third People′s Hospital of Hubei Province, Jianghan University and underwent colonoscopy were selected. According to the random number table, in the ratio of 1 to 1, the patients were divided into the linaclotide with polyethylene glycol group and the simple polyethylene glycol group, with 120 cases in each group. The patients in the linaclotide with polyethylene glycol group took 580 μg linaclotide and 2 L polyethylene glycol electrolyte powder solution, and the patients in the simple polyethylene glycol group took 3 L polyethylene glycol electrolyte powder solution. The Boston bowel preparation scale(BBPS) score, the detection rate of polyps or adenomas, the insertion time of colonoscopy, the withdrawal time of colonoscopy, the time of the first defecation, the frequency of defecations, the success rate of cecal intubation, the occurrence of adverse effects and the satisfaction rate of patients were compared between the 2 groups. Independent sample t test and chi-square test were used for statistical analysis. Results:A total of 235 patients completed bowel preparation and accepted colonoscopy. There were no statistically significant differences in the BBPS score, the detection rate of polyps or adenomas, the insertion time of colonoscopy, the withdrawal time of colonoscopy, the success rate of cecal intubation and the frequency of defecations between the linaclotide with polyethylene glycol group and simple polyethylene glycol group(7.3±1.1 vs. 7.0±1.2; 58.1%, 68/117 vs. 60.2%, 71/118; 38.5%, 45/117 vs. 39.8%, 47/118; (4.2±1.9) min vs.(4.3±1.6) min; (5.9±2.7) min vs.(6.2±2.4) min; 100.0%, 117/117 vs. 100.0%, 118/118; 5.3±2.3 vs. 5.1±2.7; all P>0.05). The rate of adverse effects of the linaclotide with polyethylene glycol group was lower than that of simple polyethylene glycol group(25.6%, 30/117 vs. 39.8%, 47/118), the satisfaction rate of patients was higher than that of the simple polyethylene glycol group (93.2%, 109/117 vs. 76.3%, 90/118), and the differences were statistically significant( χ2=0.24 and 0.64, P=0.018 and 0.031). Conclusion:Compared with the 3 L polyethylene glycol regimen, 580 g linaclotide with 2 L polyethylene glycol regimen can achieve the same bowel preparation effect with higher safety and patient satisfaction, which is worthy of clinical application.

Objective:To explore the influence factors of neurodevelopmental disorders in children with SCN8A-related early-onset epilepsy through analyzing their clinical characteristics and following up their neurodeve-lopmental status. Methods:A retrospective analysis was carried out on 21 children (13 males and 8 females, the age ranged from 4 months to 8 years, average 31.6 months)with SCN8A-related early-onset epilepsy treated in Guangzhou Women and Children′s Medical Center and Kunming Children′s Hospital between January 2017 and February 2021.All patients underwent whole-exome sequencing and Sanger sequencing.The pathogenicity was estimated according to the American College of Medical Genetics and Genomics guidelines.The clinical data of all patients were also collected, including the age of onset of the disease, forms of seizures, seizure frequency, neurological development at onset, electroencephalogram (EEG) and brain magnetic resonance imaging (MRI). Besides, the patients were followed up to acquire the effect of sodium channel blockers after the onset of seizures, the process or improvement of neurodeve-lopment, EEG evaluation and neurodevelopmental outcomes.Patients were grouped based on data analysis results.The Fisher′s exact test was conducted to measure the effect of various factors on the neurodevelopmental process and outcome, and corresponding coe-fficients were calculated. Results:The average onset age of 21 patients was 0-9 months.The follow-up duration was 4 months-8 years.Three cases died.Sixteen cases (76.2%) had early infantile epileptic encephalopathy (EIEE), 5 cases (23.8%) had epilepsy without encephalopathy, and 1 case had benign infantile epilepsy.Fourteen cases (66.7%) belonged to drug resistant epilepsy.Only one child showed normal neurodevelopment.Eleven children showed delayed neurodevelopment, but improvement was observed.Nine children were retrogressed and stagnated in terms of neurodevelopment.Small age at onset ( Fisher=9.517, P=0.020, r=0.571), high seizure frequency ( Fisher=10.512, P=0.003, r=0.572), EEG background ( Fisher=10.512, P=0.003, r=0.572), epileptic discharges ( Fisher=8.288, P=0.008, r=0.542), and EEG changes before and after treatment ( Fisher=10.437, P=0.009, r=0.586) were important factors affecting the neurodevelopmental process.Neurodevelopmental outcome was normal in only 1 case, 1 child belonged to mild mental retardation (MR), 7 children belonged to moderate MR, 3 children belonged to severe MR, and 9 children belonged to profound MR.Statistical analysis indicated that the clinical phenotype ( Fisher=10.059, P=0.004, r=0.739) and drug resistance ( Fisher=13.706, P=0.001, r=0.640) were significantly correlated with neurodevelopmental outcomes.However, the forms of seizures, EEG findings at onset and mutation sites were not related to neurodevelopmental disorders. Conclusions:Most children with SCN8A-related early-onset epilepsy are accompanied with neurodevelopmental retardation of varying degrees.Epileptic encephalopathy and poor response to drug treatment will lead to severe neurodevelopmental disorders.

More than 100 genes located on the X chromosome have been found to be associated with X-linked intellectual disability (XLID) to date, and NEXMIF is a pathogenic gene for XLID. In addition to intellectual disability, patients with NEXMIF gene mutation can also have other neurological symptoms, such as epilepsy, abnormal behavior, and hypotonia, as well as abnormalities of other systems. Two children with intellectual disability and epilepsy caused by NEXMIF gene mutation were treated in the Department of Pediatrics, Xiangya Hospital, Central South University from March 8, 2017 to June 20, 2020. Patient 1, a 7 years and 8 months old girl, visited our department because of the delayed psychomotor development. Physical examination revealed strabismus (right eye), hyperactivity, and loss of concentration. Intelligence test showed a developmental quotient of 43.6. Electroencephalogram showed abnormal discharge, and cranial imaging appeared normal. Whole exome sequencing revealed a de novo heterozygous mutation, c.2189delC (p.S730Lfs*17) in the NEXMIF gene (NM_001008537). During the follow-up period, the patient developed epileptic seizures, mainly manifested as generalized and absent seizures. She took the medicine of levetiracetam and lamotrigine, and the seizures were under control. Patient 2, a 6-months old boy, visited our department due to developmental regression and seizures. He showed poor reactions to light and sound, and was not able to raise head without aid. Hypotonia was also noticed. The electroencephalogram showed intermittent hyperarrhythmia, and spasms were monitored. He was given topiramate and adrenocorticotrophic hormone (ACTH). Whole exome sequencing detected a de novo c.592C>T (Q198X) mutation in NEXMIF gene. During the follow-up period, the seizures were reduced with vigabatrin. He had no obvious progress in the psychomotor development, and presented strabismus. There were 91 cases reported abroad, 1 case reported in China, and 2 patients were included in this study. A total of 85 variants in NEXMIF gene were found, involving 83 variants reported in PubMed and HGMD, and the 2 new variants presented in our patients. The patients with variants in NEXMIF gene all had mild to severe intellectual disability. Behavioral abnormalities, epilepsy, hypotonia, and other neurological symptoms are frequently presented. The phenotype of male partially overlaps with that of female. Male patients often have more severe intellectual disability, impaired language, and autistic features, while female patients often have refractory epilepsy. Most of the variants reported so far were loss-of-function resulted in the reduced protein expression of NEXMIF. The degree of NEXMIF loss appears to correlate with the severity of the phenotype.
Child ; Epilepsy/genetics* ; Female ; Humans ; Intellectual Disability/genetics* ; Male ; Muscle Hypotonia/complications* ; Mutation ; Phenotype ; Seizures/genetics* ; Strabismus/complications*