Objective:To observe and analyze the ocular clinical features and pathogenic genes of horizontal gaze palsy with progressive scoliosis (HGPPS).Methods:A pedigree study was conducted.Two families with HGPPS diagnosed by ophthalmology examination at Henan Children's Hospital from November 2023 to April 2024 were included, with 3 people from two generations in each family.Medical history and family history of the subjects were inquired.Vision acuity, diopter, anterior segment, intraocular pressure, wide-angle laser scanning ophthalmoscopy, optical coherence tomography, visual evoked potential (VEP), electroretinogram (ERG), ocular B-ultrasound, full spine AP+ lateral view, orbit+ skull+ cervical spine+ thoracic spine+ lumbosacral spine MRI plain scan were performed on the subjects.Whole genomic DNA was extracted from 2 ml of peripheral venous blood collected from the subjects, and gene sequencing was performed using whole exome sequencing (WES) technology.Suspicious pathogenic variant loci were verified by Sanger sequencing, and the pathogenicity of gene variant loci was analyzed according to the ACMG standards and guidelines for the interpretation of sequence variants.This study followed the Declaration of Helsinki.The study protocol was reviewed and approved by the Ethics Committee of Henan Children's Hospital (No.2024-KY-0024).All subjects and guardians signed informed consent forms and were informed of relevant matters before genetic testing.Results:The proband from family 1 was male, 3 years and 2 months old.At the age of 6 months, he was found to have head tilted to the left with a right scoliosis of the spine centered on T11-12 and no obvious abnormalities on VEP and ERG examinations.The proband from family 2 was male, 3 years and 4 months old, with a left scoliosis of the spine centered on T12.Both probands developed horizontal fixation paralysis, unable to rotate eye outward, slightly limited inward rotation, left eye hypertropia, mild horizontal nystagmus, normal vertical eye movement, backward development of major movements, and normal vision, anterior segment and fundus.MRI examination showed that the medulla oblongata was butterfly shaped, and a brainstem fissure could be seen in the center of the medulla oblongata.The genetic testing showed that the proband from family 1 had compound heterozygous variations c. 1054delC/p.Gln352Serfs *90 (M1) in exon 7 and c. 1219G>T/p.Gly407Cys (M2) in exon 8 of ROBO3 gene.The father of the proband carried M1 and the mother of the proband carried M2.The proband from family 2 had compound heterozygous variations c. 1888C>T/p.R630X (M3) in exon 12 and c. 2684C>A/p.A895E (M4) in exon 17 of ROBO3 gene.M1 and M3 were possible pathogenic, and M2 and M4 were of unknown clinical significance, and prediction software predicted M2 and M4 were harmful variations. Conclusions:The main clinical features of two HGPPS pedigree are horizontal fixation paralysis and progressive scoliosis, accompanied by nystagmus and strabismus.MRI shows brainstem fissure in the central medullary area.Four variants are novel variants, which increases the variation spectrum of ROBO3 gene.

Objective:To observe and analyze the ocular clinical features and pathogenic genes of horizontal gaze palsy with progressive scoliosis (HGPPS).Methods:A pedigree study was conducted.Two families with HGPPS diagnosed by ophthalmology examination at Henan Children's Hospital from November 2023 to April 2024 were included, with 3 people from two generations in each family.Medical history and family history of the subjects were inquired.Vision acuity, diopter, anterior segment, intraocular pressure, wide-angle laser scanning ophthalmoscopy, optical coherence tomography, visual evoked potential (VEP), electroretinogram (ERG), ocular B-ultrasound, full spine AP+ lateral view, orbit+ skull+ cervical spine+ thoracic spine+ lumbosacral spine MRI plain scan were performed on the subjects.Whole genomic DNA was extracted from 2 ml of peripheral venous blood collected from the subjects, and gene sequencing was performed using whole exome sequencing (WES) technology.Suspicious pathogenic variant loci were verified by Sanger sequencing, and the pathogenicity of gene variant loci was analyzed according to the ACMG standards and guidelines for the interpretation of sequence variants.This study followed the Declaration of Helsinki.The study protocol was reviewed and approved by the Ethics Committee of Henan Children's Hospital (No.2024-KY-0024).All subjects and guardians signed informed consent forms and were informed of relevant matters before genetic testing.Results:The proband from family 1 was male, 3 years and 2 months old.At the age of 6 months, he was found to have head tilted to the left with a right scoliosis of the spine centered on T11-12 and no obvious abnormalities on VEP and ERG examinations.The proband from family 2 was male, 3 years and 4 months old, with a left scoliosis of the spine centered on T12.Both probands developed horizontal fixation paralysis, unable to rotate eye outward, slightly limited inward rotation, left eye hypertropia, mild horizontal nystagmus, normal vertical eye movement, backward development of major movements, and normal vision, anterior segment and fundus.MRI examination showed that the medulla oblongata was butterfly shaped, and a brainstem fissure could be seen in the center of the medulla oblongata.The genetic testing showed that the proband from family 1 had compound heterozygous variations c. 1054delC/p.Gln352Serfs *90 (M1) in exon 7 and c. 1219G>T/p.Gly407Cys (M2) in exon 8 of ROBO3 gene.The father of the proband carried M1 and the mother of the proband carried M2.The proband from family 2 had compound heterozygous variations c. 1888C>T/p.R630X (M3) in exon 12 and c. 2684C>A/p.A895E (M4) in exon 17 of ROBO3 gene.M1 and M3 were possible pathogenic, and M2 and M4 were of unknown clinical significance, and prediction software predicted M2 and M4 were harmful variations. Conclusions:The main clinical features of two HGPPS pedigree are horizontal fixation paralysis and progressive scoliosis, accompanied by nystagmus and strabismus.MRI shows brainstem fissure in the central medullary area.Four variants are novel variants, which increases the variation spectrum of ROBO3 gene.

Objective:To construct a risk prediction model for early post-injury respiratory failure in patients with traumatic cervical spinal cord injury (TCSCI) and validate its efficacy.Methods:A retrospective cohort study was conducted to analyze the clinical data of 393 TCSCI patients admitted to Zhengzhou Central Hospital Affiliated to Zhengzhou University from January 2020 to October 2024, including 294 males and 99 females, aged 18-82 years [59(45, 72)years]. Among them, 76 patients had respiratory failure (19.3%). The patients were randomly divided into the training set ( n=275) and validation set ( n=118) at a ratio of 7∶3. According to the presence of respiratory failure within one week after admission, 275 patients in the training set were divided into respiratory failure group ( n=53) and non-respiratory failure group ( n=222). The demographic data, injury characteristics, laboratory test results, and imaging findings of the patients were collected. Risk factors were determined through univariate analysis and multivariate Logistic regression analysis and a nomogram prediction model was constructed. The area under the receiver operating characteristic (ROC) curve (AUC) and Hosmer-Lemeshow test were used to evaluate the discrimination and calibration of the model. Decision curve analysis (DCA) was plotted to evaluate the clinical effectiveness of the prediction model. Results:The results of the univariate analysis showed that there were significant differences in history of respiratory diseases, causes of injury, Glasgow coma scale (GCS), American Spinal Injury Association (ASIA) classification, ASIA-motor score (AMS), injury severity score (ISS), clinical pulmonary infection score (CPIS), hypoproteinemia and cervical vertebra fracture and dislocation between the respiratory failure group and non-respiratory failure group in the training set ( P<0.05). The results of multivariate Logistic regression analysis indicated that GCS, ASIA classification, CPIS, and hypoproteinemia were independent risk factors for early post-injury respiratory failure in TCSCI patients ( P<0.05). Based on the above four variables, a Logistic regression equation was constructed: Logit( P)=2.361-0.675×ASIA classification+0.419×CPIS-0.358×GCS+0.854×hypoproteinemia. In the prediction model established based on this equation, the AUC was 0.96 (95% CI 0.94, 0.99) in the training set and 0.89 (95% CI 0.82, 0.96) in the validation set. In the calibration curves of the training set and validation set, the prediction curve and reference curve were approximately overlapping, with the average absolute errors of 0.04 and 0.03. DCA results demonstrated that both the training and validation sets exhibited positive net benefits when threshold probabilities fell within ranges of 0%-78% and 0%-87%, respectively. Conclusion:The risk prediction model for early post-injury respiratory failure in TCSCI patients based on GCS, ASIA classification, CPIS and hypoproteinemia has good predictive efficacy and clinical practicability.

Objective:To construct a risk prediction model for early post-injury respiratory failure in patients with traumatic cervical spinal cord injury (TCSCI) and validate its efficacy.Methods:A retrospective cohort study was conducted to analyze the clinical data of 393 TCSCI patients admitted to Zhengzhou Central Hospital Affiliated to Zhengzhou University from January 2020 to October 2024, including 294 males and 99 females, aged 18-82 years [59(45, 72)years]. Among them, 76 patients had respiratory failure (19.3%). The patients were randomly divided into the training set ( n=275) and validation set ( n=118) at a ratio of 7∶3. According to the presence of respiratory failure within one week after admission, 275 patients in the training set were divided into respiratory failure group ( n=53) and non-respiratory failure group ( n=222). The demographic data, injury characteristics, laboratory test results, and imaging findings of the patients were collected. Risk factors were determined through univariate analysis and multivariate Logistic regression analysis and a nomogram prediction model was constructed. The area under the receiver operating characteristic (ROC) curve (AUC) and Hosmer-Lemeshow test were used to evaluate the discrimination and calibration of the model. Decision curve analysis (DCA) was plotted to evaluate the clinical effectiveness of the prediction model. Results:The results of the univariate analysis showed that there were significant differences in history of respiratory diseases, causes of injury, Glasgow coma scale (GCS), American Spinal Injury Association (ASIA) classification, ASIA-motor score (AMS), injury severity score (ISS), clinical pulmonary infection score (CPIS), hypoproteinemia and cervical vertebra fracture and dislocation between the respiratory failure group and non-respiratory failure group in the training set ( P<0.05). The results of multivariate Logistic regression analysis indicated that GCS, ASIA classification, CPIS, and hypoproteinemia were independent risk factors for early post-injury respiratory failure in TCSCI patients ( P<0.05). Based on the above four variables, a Logistic regression equation was constructed: Logit( P)=2.361-0.675×ASIA classification+0.419×CPIS-0.358×GCS+0.854×hypoproteinemia. In the prediction model established based on this equation, the AUC was 0.96 (95% CI 0.94, 0.99) in the training set and 0.89 (95% CI 0.82, 0.96) in the validation set. In the calibration curves of the training set and validation set, the prediction curve and reference curve were approximately overlapping, with the average absolute errors of 0.04 and 0.03. DCA results demonstrated that both the training and validation sets exhibited positive net benefits when threshold probabilities fell within ranges of 0%-78% and 0%-87%, respectively. Conclusion:The risk prediction model for early post-injury respiratory failure in TCSCI patients based on GCS, ASIA classification, CPIS and hypoproteinemia has good predictive efficacy and clinical practicability.

The purpose of this study is to develop glipizide push-pull osmotic pump (PPOP) tablets by using a formulation design expert system and an artificial neural network (ANN). Firstly, the expert system for the formulation design of osmotic pump of poor water-soluble drug was employed to design the formulation of glipizide PPOP, taking the dissolution test results of Glucotrol XL as the goal. Then glipizide PPOP was prepared according to the designed formulations and the in vitro dissolution was carried out. And in vivo evaluation was carried out between the samples which were similar to Glucotrol XL and the Glucotrol XL in Beagle dogs. The range of the factors of formulation and procedure, which could influence the drug release, was optimized using artificial neural network. Finally, the design space was found. It was found that the target formulation which was similar to Glucotrol XL in dissolution test could be obtained in a short period by using the expert system. The samples which were similar to Glucotrol XL were bio-equivalent to the Glucotrol XL in Beagle dogs. The design space of the key parameter coating weight gain was 9.5%-12.0%. It could be concluded that a well controlled product of glipizide PPOP was developed since the dissolution test standard of our product was more strict than that of Glucotrol XL.
Animals ; Area Under Curve ; Delayed-Action Preparations ; Dogs ; Drug Compounding ; methods ; Drug Delivery Systems ; Drug Design ; Expert Systems ; Female ; Glipizide ; administration & dosage ; chemistry ; pharmacokinetics ; Hypoglycemic Agents ; administration & dosage ; chemistry ; pharmacokinetics ; Male ; Neural Networks (Computer) ; Osmosis ; Polyethylene Glycols ; chemistry ; Random Allocation ; Sodium Chloride ; chemistry ; Solubility ; Tablets