Objective:To identify two pathogenic gene mutations in two families with Alstr?m syndrome (ALMS).Methods:A retrospective clinical study. Two patients and five family members from two Han families of ALMS diagnosed at Henan Eye Hospital from August 2020 to December 2021 were enrolled in this study. All participants underwent comprehensive ophthalmic examinations including best corrected visual acuity (BCVA), color test, slit-lamp, fundus biomicroscopy with slit lamp, fundus color photography, optical coherence tomography (OCT) and full-field electroretinography (ff-ERG) after the detailed history of the patient was taken. Five millilitres peripheral venous blood of each subject was collected, and the whole genome DNA was extracted. The pathogenic genes and mutation sites were identified using whole exome sequencing and the identified mutations were verified by Sanger sequencing. Mutation sites were analyzed via bioinformatics softwares.Results:Family one included one victim and two members and family two included one victim and three members. Proband in the first family was a four-year old boy whose chief complaint was poor vision along with photophobia since born, while proband in the second family was a 12-year old girl whose chief complaint was the same. The boy proband could not distinguish color, and both the anterior segment and fundus were normal. Ellipsoid zone of the boy was unclear in both eyes in OCT, and though rod system function decreased mildly-moderately in both eyes, the cone system function decreased severely in ff-ERG. The girl could not distinguish color as well, and the anterior segment was normal, though obvious pigmentary change could be seen in both retinas. The integrity of outer retinal bands was unclear in both eyes in OCT, and both cone and rod systems function decreased severely in both eyes in ff-ERG. Gene tests and bioinformatics analyze showed c.468dupT and c.10819C>T of ALMS1 gene in family one were novel mutations and c.10819C>T in family one and c.10831_10832del in family two were pathogenic mutations. Conclusions:M1, M2 and M3, M4 may be pathogenic gene variants in family 1 and family 2, respectively. The compound heterozygous mutation, c.468dupT and c.10819C>T of ALMS1 gene was a novel mutation.

Objective:To determine the pathogenic gene mutation in a family with incomplete congenital quiescent night blindness (CSNB) of Schubert-Bornschein type.Methods:A retrospective clinical study. In February 2021, one patient and his parents and elder brother from a Han Chinese incomplete CSNB of Schubert-Bornschein type family diagnosed by clinical and genetic examination at Henan Provincial People's Hospital were included in the study. The patient’s medical history, family history were inquired; best corrected visual acuity (BCVA), color vision, fundus color photography, full-field electroretinogram (ERG), and frequency domain optical coherence tomography (OCT) were examined in detail. Five ml of the subject’s peripheral venous blood was collected and the whole genome DNA was extracted. The genomic DNA of the subject was library constructed, and all-exon probes were polymerized for capture. The suspected pathogenic mutation site was verified by Sanger, and the pathogenicity of the gene mutation site was determined by parallel bioinformatics analysis.Results:The BCVA of both eyes of the proband (Ⅱ2) was 0.4; the color vision test could not recognize the red color. Fundus examination showed no obvious abnormalities. The retina thickness in the macular area of both eyes was slightly thinned. ERG examination of the whole field showed that the amplitude of ERG b wave was significantly reduced under the stimulation of binocular dark adaptation 3.0 and showed a negative waveform. The mother of the proband (Ⅰ2) had normal BCVA, color vision, fundus color photography, and frequency domain OCT examination. The full-field ERG examination showed that the amplitude of each eye reaction was slightly reduced, and the amplitude of the dark adaptation shock potential was significantly reduced. Genetic testing showed that the proband (Ⅱ2) had a c.1761dupC hemizygous mutation in exon 14 of the voltage-dependent calcium channel α1F subunit gene ( CACNA1F gene). The results of protein sequence homology analysis showed that the site was highly conserved in multiple species; the results of bioinformatics analysis showed that the CACNA1F gene c.1761dupC (pY588fs) subsequently had a frameshift mutation and became a stop at position 10. Codons appear translational termination in the conserved regions of the protein. According to the standards and guidelines of the American College of Medical Genetics and Genomics, the mutation was judged to be a possible pathogenic variant. The mother of the proband (Ⅰ2) was a carrier of this site mutation. The clinical and genetic test results of the father and elder brother of the proband were not abnormal. Conclusion:CACNA1F gene c.1761dupC is the pathogenic mutation site of the Schubert-Bornschein type incomplete CSNB family.

Sedation therapy is an important part of the safety and comfort management of critically ill children.The accurate selection of a sedation assessment tool can help nurses effectively assess the level of sedation and guide clinical care.This review summarized the existing six commonly used sedation assessment scales in pediatric intensive care unit, such as the Ramsay Sedation Scale, Richmond Agitation-Sedation Scale and Comfort Scale and related sedation concepts.Our study aims to provide a reference for choosing a sedation assessment scale suitable for critically ill children and standardizing sedation nursing practice.

To investigate the effects of neuronal histamine on spatial memory acquisition impairment in rats with pentylenetetrazole-kindling epilepsy, and to explore its mechanisms.A subconvulsive dose of pentylenetetrazole (35 mg/kg) was intraperitoneally injected in rats every 48 h to induce chemical kindling until fully kindled. Morris water maze was used to measure the spatial memory acquisition of the rats one week after fully pentylenetetrazole-kindled, and the histamine contents in different brain areas were measured spectrofluorometrically. Different dosages of hitidine (the precursor of histamine), pyrilamine (H1 receptor antagonist), and zolantidine (H2 receptor antagonist) were intraperitoneally injected, and their effects on spatial memory acquisition of the rats were observed.Compared with control group, escape latencies were significantly prolonged on Morris water maze training day 2 and day 3 in pentylenetetrazole-kindling epilepsy rats (all<0.05); and the histamine contents in hippocampus, thalamus and hypothalamus were decreased significantly (all<0.05). Escape latencies were markedly shortened on day 3 by intraperitoneally injected with histidine 500 mg/kg, and on day 2 and day 3 by intraperitoneally injected with histidine 1000 mg/kg in pentylenetetrazole-kindling epilepsy rats (all<0.05). The protection of histidine was reversed by zolantidine (10 and 20 mg/kg), but not by pyrilamine.Neuronal histamine can improve the spatial memory acquisition impairment in rats with pentylenetetrazole-kindling epilepsy, and the activation of H2 receptors is possibly involved in the protective effects of histamine.
Animals ; Benzothiazoles ; pharmacology ; Brain Chemistry ; drug effects ; Epilepsy ; chemically induced ; complications ; Hippocampus ; chemistry ; Histamine H1 Antagonists ; pharmacology ; Histamine H2 Antagonists ; pharmacology ; Histidine ; pharmacology ; Hypothalamus ; chemistry ; Kindling, Neurologic ; physiology ; Memory Disorders ; drug therapy ; etiology ; Pentylenetetrazole ; Phenoxypropanolamines ; pharmacology ; Piperidines ; pharmacology ; Pyrilamine ; pharmacology ; Rats ; Rats, Sprague-Dawley ; Receptors, Histamine H2 ; drug effects ; physiology ; Spatial Memory ; drug effects ; Spectrometry, Fluorescence ; Thalamus ; chemistry

Targeted temperature management mainly affects the progression of sepsis by inhibiting inflammatory response, protecting mitochondrial function and reducing metabolism, which can improve survival, the prognosis and outcome of sepsis to some extent.Targeted temperature management has a positive impact on the occurrence and development of sepsis, which may be an adjuvant treatment method of sepsis.This review summarized the mechanism studies on the impact of targeted temperature management on sepsis in recent years, and summarized the existing problems, so as to provide reference for carrying out practical research on targeted temperature management for patients with sepsis.