Objective:To observe and analyze the clinical phenotype and genetic characteristics of COL2A1 and COL11A1 de novo mutation (DNM) related Stickler syndrome type Ⅰ and Ⅱ patients. Methods:A family-based cohort study. From December 2023 to November 2024, 4 patients (all probands) with Stickler syndrome diagnosed by clinical and genetic testing in Department of Ophthalmology of People's Hospital of Ningxia Hui Autonomous Region and their parents (8 cases) were included in the study. The patients came from 4 unrelated families. A detailed medical history was taken, and the patients underwent best-corrected visual acuity (BCVA), refraction, and fundus color photography examinations. Systemic examinations included the oral and facial regions, skeletal, joints, and hearing. Peripheral venous blood samples were collected from the patients and their parents, and genomic DNA was extracted. Whole-exome sequencing was used to screen for pathogenic genes and their loci, which were then validated by Sanger sequencing and combined with segregation analysis in the families to identify candidate gene mutation sites. The candidate variants were assessed for pathogenicity according to the American College of Medical Genetics and Genomics (ACMG) criteria and guidelines for the classification of genetic variants. Additionally, cross-species conservation analysis was performed to determine the evolutionary conservation of wild-type amino acids, and protein three-dimensional modeling techniques were used to characterize the spatial conformational changes of the variant proteins and the alterations in their local hydrogen bond networks.Results:Among the 4 patients, there were 2 males and 2 females; their ages ranged from 3 to 12 years. There were 2 cases of Stickler syndrome type Ⅰ (proband of families 1 and 2) and 2 cases of type Ⅱ (proband of families 3 and 4). The diopters ranged from -8.00 to-18.00 D. BCVA ranged from no light perception to 0.6 -. There were 2 cases each of vitreous membrane-like and "bead-like" opacity. Three cases showed peripapillary atrophy arcs and leopard pattern changes in the retina; one case had bilateral retinal detachment with a large macular hole in the left eye, which had previously been treated with vitrectomy surgery. One case had bilateral sensorineural hearing loss. There were 3 cases of simple micrognathia; one case had a flat nasal bridge, short nose, midface depression, and micrognathia. Two cases had excessive elbow joint extension. The phenotypes of the parents of the 4 patients were normal. Genetic testing results revealed that the probands of families 1 and 2 carried COL2A1 gene c.85+1G>C (M1) splice site variant and c.3950_3951insA (p.M1317Ifs*48) (M2) frameshift variant, respectively; the probands of families 3 and 4 carried COL11A1 gene (NM_001854.4) c.2549 G>T (p.G850V) (M3) missense variant and c.3816+6T>C (M4) splice site variant, respectively. The parents did not carry the related gene variants. Among them, M2, M3, and M4 are newly reported DNM. According to the ACMG guidelines, they were all considered likely pathogenic. The cross-species conservation analysis results showed that the wild-type amino acid of the COL11A1 gene M3 missense variant was highly conserved across multiple different species. Protein local structure modeling analysis revealed that the COL2A1 gene M2 frameshift variant and the COL11A1 gene M3 missense variant significantly altered the tertiary structure conformation of the protein, leading to abnormal spatial arrangement and hydrogen bond network in the key functional domains Conclusion:The COL2A1 gene M1 splice site variant, M2 frameshift variant, and the COL11A1 gene M3 missense variant, M4 splice site variant are respectively the potential pathogenic genes for families 1, 2, and families 3, 4; leading to the onset of Stickler syndrome type Ⅰ in families 1 and 2, and type Ⅱ in families 3 and 4.

Objective:To investigate and analyze the relationship between genotype and phenotype in patients with early-onset high myopia (eoHM) associated with hereditary eye diseases.Methods:A family-based study was conducted among 30 families diagnosed with eoHM at Department of Ophthalmology of People's Hospital of Ningxia Hui Autonomous Region from January 2022 to June 2023. Seven families (23.3%, 7/30), all probands, and their 14 parents were included. These seven families were unrelated. Detailed patient and family histories were collected. All participants underwent comprehensive ophthalmic examinations, including best-corrected visual acuity, color vision testing, fundus color photography, optical coherence tomography, fluorescein fundus angiography, and fundus autofluorescence imaging. Full-field electroretinography was performed in four cases. Peripheral venous blood samples were collected from patients and their parents for whole-genome DNA extraction and whole-exome sequencing. Potential pathogenic variants were identified, and their pathogenicity was analyzed and confirmed by Sanger sequencing. The pathogenicity of newly discovered gene variants was evaluated according to the guidelines of the American College of Medical Genetics and Genomics (ACMG). Literature on previously reported eoHM associated with hereditary eye diseases was reviewed to analyze the relationship between variant genes and clinical phenotypes.Results:Among the seven families, three exhibited X-linked inheritance, two showed autosomal recessive inheritance, and two demonstrated autosomal dominant inheritance. All the patients were male. Among the seven patients, one case each was identified with congenital stationary night blindness (CSNB), Bornholm eye disease, X-linked retinitis pigmentosa (XL-RP), cone-rod dystrophy, Knobloch syndrome, familial exudative vitreoretinopathy (FEVR), and Stickler syndrome. Genetic testing revealed nine gene variants highly correlated with the observed phenotypes. The genetic testing results revealed that all patients were found to carry nine gene variants highly associated with the phenotype, including: a hemizygous missense variant NYX c.647A>T (p.N216I) (M1), an OPN1LW LIAVA haplotype variant (M2), a hemizygous frameshift variant RPGR c.3096_3097del (p.E1033RfsTer45) (M3), compound heterozygous variants TTLL5 c.1588_1589del (p.L531EfsTer24) and c.850G>C (p.D284H) (M4, M5), compound heterozygous variants COL18A1 c.2118dup (p.G707RfsTer23) and c.3523_3524del (p.L1175VfsTer72) (M6, M7), a heterozygous missense mutation FZD4 c.1499C>T (p.T500I) (M8), and a heterozygous frameshift variant COL11A2 c.966dup (p.T323HfsTer19) (M9). Among them, M2, M4, M5, M8 and M9 were newly discovered mutation sites, and M1, M3, M6 and M7 were known mutation sites. According to the classification standards and guidelines of genetic variation issued by ACMG, M2, M3, M4, M6, M7, and M9 were judged to be pathogenic variants, while M1, M5, and M8 were of unknown clinical significance. Through literature review, it was found that eoHM was more common among the clinical phenotypes of 4 types of hereditary retinal diseases, including CSNB, Stickler syndrome, FEVR and XL-RP. Conclusion:eoHM is intricately associated with inherited eye diseases and may serve as the earliest indicator of such conditions.

Objective:To observe and analyze the clinical phenotype and genetic characteristics of COL2A1 and COL11A1 de novo mutation (DNM) related Stickler syndrome type Ⅰ and Ⅱ patients. Methods:A family-based cohort study. From December 2023 to November 2024, 4 patients (all probands) with Stickler syndrome diagnosed by clinical and genetic testing in Department of Ophthalmology of People's Hospital of Ningxia Hui Autonomous Region and their parents (8 cases) were included in the study. The patients came from 4 unrelated families. A detailed medical history was taken, and the patients underwent best-corrected visual acuity (BCVA), refraction, and fundus color photography examinations. Systemic examinations included the oral and facial regions, skeletal, joints, and hearing. Peripheral venous blood samples were collected from the patients and their parents, and genomic DNA was extracted. Whole-exome sequencing was used to screen for pathogenic genes and their loci, which were then validated by Sanger sequencing and combined with segregation analysis in the families to identify candidate gene mutation sites. The candidate variants were assessed for pathogenicity according to the American College of Medical Genetics and Genomics (ACMG) criteria and guidelines for the classification of genetic variants. Additionally, cross-species conservation analysis was performed to determine the evolutionary conservation of wild-type amino acids, and protein three-dimensional modeling techniques were used to characterize the spatial conformational changes of the variant proteins and the alterations in their local hydrogen bond networks.Results:Among the 4 patients, there were 2 males and 2 females; their ages ranged from 3 to 12 years. There were 2 cases of Stickler syndrome type Ⅰ (proband of families 1 and 2) and 2 cases of type Ⅱ (proband of families 3 and 4). The diopters ranged from -8.00 to-18.00 D. BCVA ranged from no light perception to 0.6 -. There were 2 cases each of vitreous membrane-like and "bead-like" opacity. Three cases showed peripapillary atrophy arcs and leopard pattern changes in the retina; one case had bilateral retinal detachment with a large macular hole in the left eye, which had previously been treated with vitrectomy surgery. One case had bilateral sensorineural hearing loss. There were 3 cases of simple micrognathia; one case had a flat nasal bridge, short nose, midface depression, and micrognathia. Two cases had excessive elbow joint extension. The phenotypes of the parents of the 4 patients were normal. Genetic testing results revealed that the probands of families 1 and 2 carried COL2A1 gene c.85+1G>C (M1) splice site variant and c.3950_3951insA (p.M1317Ifs*48) (M2) frameshift variant, respectively; the probands of families 3 and 4 carried COL11A1 gene (NM_001854.4) c.2549 G>T (p.G850V) (M3) missense variant and c.3816+6T>C (M4) splice site variant, respectively. The parents did not carry the related gene variants. Among them, M2, M3, and M4 are newly reported DNM. According to the ACMG guidelines, they were all considered likely pathogenic. The cross-species conservation analysis results showed that the wild-type amino acid of the COL11A1 gene M3 missense variant was highly conserved across multiple different species. Protein local structure modeling analysis revealed that the COL2A1 gene M2 frameshift variant and the COL11A1 gene M3 missense variant significantly altered the tertiary structure conformation of the protein, leading to abnormal spatial arrangement and hydrogen bond network in the key functional domains Conclusion:The COL2A1 gene M1 splice site variant, M2 frameshift variant, and the COL11A1 gene M3 missense variant, M4 splice site variant are respectively the potential pathogenic genes for families 1, 2, and families 3, 4; leading to the onset of Stickler syndrome type Ⅰ in families 1 and 2, and type Ⅱ in families 3 and 4.

Objective:To investigate and analyze the relationship between genotype and phenotype in patients with early-onset high myopia (eoHM) associated with hereditary eye diseases.Methods:A family-based study was conducted among 30 families diagnosed with eoHM at Department of Ophthalmology of People's Hospital of Ningxia Hui Autonomous Region from January 2022 to June 2023. Seven families (23.3%, 7/30), all probands, and their 14 parents were included. These seven families were unrelated. Detailed patient and family histories were collected. All participants underwent comprehensive ophthalmic examinations, including best-corrected visual acuity, color vision testing, fundus color photography, optical coherence tomography, fluorescein fundus angiography, and fundus autofluorescence imaging. Full-field electroretinography was performed in four cases. Peripheral venous blood samples were collected from patients and their parents for whole-genome DNA extraction and whole-exome sequencing. Potential pathogenic variants were identified, and their pathogenicity was analyzed and confirmed by Sanger sequencing. The pathogenicity of newly discovered gene variants was evaluated according to the guidelines of the American College of Medical Genetics and Genomics (ACMG). Literature on previously reported eoHM associated with hereditary eye diseases was reviewed to analyze the relationship between variant genes and clinical phenotypes.Results:Among the seven families, three exhibited X-linked inheritance, two showed autosomal recessive inheritance, and two demonstrated autosomal dominant inheritance. All the patients were male. Among the seven patients, one case each was identified with congenital stationary night blindness (CSNB), Bornholm eye disease, X-linked retinitis pigmentosa (XL-RP), cone-rod dystrophy, Knobloch syndrome, familial exudative vitreoretinopathy (FEVR), and Stickler syndrome. Genetic testing revealed nine gene variants highly correlated with the observed phenotypes. The genetic testing results revealed that all patients were found to carry nine gene variants highly associated with the phenotype, including: a hemizygous missense variant NYX c.647A>T (p.N216I) (M1), an OPN1LW LIAVA haplotype variant (M2), a hemizygous frameshift variant RPGR c.3096_3097del (p.E1033RfsTer45) (M3), compound heterozygous variants TTLL5 c.1588_1589del (p.L531EfsTer24) and c.850G>C (p.D284H) (M4, M5), compound heterozygous variants COL18A1 c.2118dup (p.G707RfsTer23) and c.3523_3524del (p.L1175VfsTer72) (M6, M7), a heterozygous missense mutation FZD4 c.1499C>T (p.T500I) (M8), and a heterozygous frameshift variant COL11A2 c.966dup (p.T323HfsTer19) (M9). Among them, M2, M4, M5, M8 and M9 were newly discovered mutation sites, and M1, M3, M6 and M7 were known mutation sites. According to the classification standards and guidelines of genetic variation issued by ACMG, M2, M3, M4, M6, M7, and M9 were judged to be pathogenic variants, while M1, M5, and M8 were of unknown clinical significance. Through literature review, it was found that eoHM was more common among the clinical phenotypes of 4 types of hereditary retinal diseases, including CSNB, Stickler syndrome, FEVR and XL-RP. Conclusion:eoHM is intricately associated with inherited eye diseases and may serve as the earliest indicator of such conditions.

Objective:To analyze the risk factors associated with retinal detachment in patients with myopia, and to establish and validate the predictive column-line diagram model.Methods:A cross-sectional clinical study. From January 2020 to November 2021, 90 patients with myopia combined with retinal detachment who were diagnosed by ophthalmologic examination in the People's Hospital of Ningxia Hui Autonomous Region were included in the study (observation group). Ninety myopic patients with age- and gender-matched myopia who underwent ophthalmologic examination for myopia during the same period were selected as the control group. The clinical data of the two groups were analyzed, and the indicators with differences were subjected to univariate and multivariate logistic regression analyses. The results of the regression analyses were visualized by using R software to obtain the column charts, and the accuracy of the column charts was verified by the ROC curves of the subjects' work characteristics; the clinical efficacy of the column chart model was verified by the internal data.Results:Compared with the control group, patients in the observation group were older, had higher myopic refraction, had more visual fatigue, ocular trauma, and cataracts, had lower choroidal and retinal thickness, and had more history of ophthalmic surgery, and the differences were statistically significant ( P<0.05). The area under the ROC curve (AUC) for age, myopic refraction, retinal thickness, and choroidal thickness were 0.612, 0.613, 0.720, and 0.704, respectively; the optimal cutoff values were 43 years old, -3.5 D, 225 μm, and 144 μm. the ROC values were 0.612, 0.613, 0.720, and 0.704 for age (>43 years old), myopic refraction (>-3.5 D), visual fatigue (yes), ocular trauma (yes), cataracts (yes), retinal thickness (≤225 μm), and choroidal thickness (≤144 μm) were the risk factors affecting the development of retinal detachment in myopic patients ( P<0.05). The consistency index of the column chart model for predicting the risk of retinal detachment in patients with myopia was 0.731 (95% confidence interval 0.665-0.824); the risk threshold for predicting the development of retinal detachment in patients was >0.07. Conclusions:Age >43 years, myopic refraction >-3.5 D, presence of visual fatigue, ocular trauma, cataract, retinal thickness ≤225 μm, choroidal thickness ≤144 μm are the risk factors affecting the development of retinal detachment in myopic patients. The column-line diagram model constructed on the basis of the risk factors has good accuracy.

Objective To explore the effective strategies of clinical pathway construction in intensive care unit (ICU).Methods From January 2016 to July 2018,1 488 patients were discharged from ICU of Liuzhou Worker's Hospital of Guangxi Zhuang Autonomous Region.The pilot project of "postoperative monitoring of heart disease" with simpler route and less variation was selected first,and then the pilot project was promoted to "post-operative monitoring" after its success.The implementation of the clinical pathway was divided into three stages:the first stage,January 2016 to May 2017,for the pilot phase,a total of 87 patients were enrolled in the clinical pathway trial;the second stage,June 2017 to December 2017,surgical ICU "postoperative monitoring of heart disease" was put into the pathway 111 times;the third stage,January 2018 to July 2018,surgical ICU "postoperative monitoring of heart disease" was entered in the path 116 times;comprehensive ICU "postoperative care" was put into the path 96 times.After carefully analyzed the reasons and sum up the experience,internet+medical treatment (Liuzhou Worker's Hospital became the fifih deep partner of Tencent Inc in the internct+medical field,and carried out the plan and practice of "WeChat wisdom hospital 3.0" in 2017) was used,four aspects of connection,payment,security and ecological cooperation were upgraded,and the construction of 6 level of electronic medical record (EMR) was accelerated.At the same time,through diagnosis related groups system (DRGs),the concept of evidence-based medicine,quality management and continuous improvement as the leading factor,and combined with the construction status of hospital information system (HIS) and EMR system,step by step implementation and design of information management platform for clinical pathway were formulated.The completion rate of clinical pathway,average length of hospital stay,average cost,cure rate and improvement rate were the main observation parameters.Results In the first stage,none of the 87 patients who entered the clinical pathway completed the clinical pathway.In the second stage,the completion rate of surgical ICU clinical pathway was increased from 33.33％ in June 2017 to 94.44％ in December 2017,and up to 100％ in October 2017,and the average completion rate from January to July 2018 was 94.00％.The completion rate of ICU clinical pathway was increased from 81.82％ in January 2008 to 92.86％ in July 2008.There was a significant difference in the overall clinical pathway completion rate from 2016 to 2018 (x2 =204.300,P =0.000).After the effective implementation of clinical pathway in June 2017,the length of hospital stay of patients was significantly shortened as compared with that before implementation (days:2.96 ± 0.43 vs.6.66 ± 0.75,P ＜ 0.01),and the daily cost was significantly reduced (Yuan:3 550.92 ± 755.51 vs.6 171.48 ± 377.29,P ＜ 0.01).The average length of hospital stay was shortened by about 3.84 days (P ＜ 0.01),and the average daily cost was reduced by about 2 108.39 Yuan (P ＜ 0.01) after the implementation of clinical pathway by surgical ICU "postoperative monitoring of heart disease" as compared with those before implementation.The average length of hospital stay was shortened by about 2.98 days (P ＜ 0.01) and the average daily cost was reduced by 5 094.13 Yuan (P ＜ 0.01) after the implementation of clinical pathway by comprehensive ICU "post-operative monitoring" as compared with those before implementation.At the same time,the cure rate was increased from 1.16％ (7/603) to 42.26％ (105/227),and the improvement rate was decreased from 94.36％ (569/603) to 52.86％ (120/227,both P ＜ 0.01) after the implementation of surgical ICU clinical pathway,but there was no significant difference in the cure rate or the improvement rate after the implementation of comprehensive ICU [2.77％ (33/1 193) vs.2.22％ (2/90),79.21％ (945/1 193) vs.97.78％ (88/90),both P ＞ 0.05].Conclusions Application of clinical pathway to control ICU quality and guide diagnosis and treatment,more refined diagnosis and treatment schemes including clinical guidelines,average length of stay,average cost of hospitalization,cost-efficiency ratio and so on were completed,which confirmed that the improvement of clinical pathway management strategy originated from clinical were needed.Informatization,intellectualization,standardization and effective control of medical cost of clinical pathway could improve medical quality and accurate management.The integration of ICU clinical pathway construction and HIS could promote the development of digital hospitals.

Objective To observe the gene mutation and clinical phenotype of patients with retinitis pigmentosa (RP) and cone rod dystrophy (CORD).Methods Thirty-seven patients with RP and 6 patients with CORD and 95 family members were enrolled in the study.The patient's medical history and family history were collected.All the patients and family members received complete ophthalmic examinations to determine the phenotype,including best corrected visual acuity,slit lamp microscope,indirect ophthalmoscopy,color fundus photography,optical coherence tomography,full-field electroretinogram,and fluorescein fundus angiography.DNA was abstracted from patients and family members.Using target region capture sequencing combined with next-generation sequencing to screen the 232 candidate pathogenic mutations.Polymerase chain reaction and direct sequencing were used to confirm the pathogenic pathogenic mutations and Co-segregation is performed among members in the family to determine pathogenic mutation sites.The relationship between genotype and clinical phenotype of RP and CORD was analyzed.Results Of the 37 patients with RP,13 were from 6 families,including 4 families with autosomal dominant inheritance,2 families with autosomal recessive inheritance,and 3 in 6 families were detected pathogenic gene mutations.24 cases were scattered RP.Six patients with CORD were from four families,all of which were autosomal recessive.Of the 43 patients,21 patients were detected the pathogenic gene mutation,and the positive rate was 48.8％.Among them,15 patients with RP were detected 10 pathogenic gene mutations including USH2A,RP1,MYO7A,C8orf37,RPGR,SNRNP200,CRX,PRPF31,C2orf71,IMPDH1,and the clinical phenotype included 10 typical RP,2 cases of RPSP,3 cases of Usher syndrome type 2 and 6 cases of CORD patients were all detected pathogenic gene mutations,including 2 cases of ABCA4,2 mutations of RIMS 1 gene,1 case of CLN3 gene mutation,and 1 case of CRB 1 and RPGR double gene mutation.Conclusions RP and CORD are clinically diverse in genotype and clinically phenotypically similar.For patients with early RP and CORD,clinical phenotype combined with genetic analysis is required to determine the diagnosis of RP and CORD.