Objective:To investigate the clinical features and pathogenesis of a child with Stargardt disease caused by variants of ABCA4 gene. Methods:A child presented at Shenzhen Eye Hospital between September 5, 2020, and April 3, 2023 was selected as the study subject. Clinical data of the child were collected. Whole exome sequencing was performed on peripheral blood samples from the child and his parents. Candidate variants were validated by Sanger sequencing and bioinformatic analysis. This study was approved by the Medical Ethics Committee of Shenzhen Eye Hospital (Ethics No.: 2022KYPJ072).Results:The child was a 10-year-old male presenting with uncorrected visual acuity of 0.1 in both eyes without improvement with refractive correction. Fundus photography showed diffusely distributed yellow-white flecks in the macular region. FAF revealing central hypofluorescence surrounded by a hyperfluorescent ring, and OCT demonstrating significant foveal thinning (right eye: 45 μm; left eye: 50 μm) with ellipsoid zone disruption. Whole exome sequencing and Sanger sequencing revealed that the child has harbored compound heterozygous variants of the ABCA4 gene, namely c. 2384G>T (p.Gly795Val) and c. 2903G>A (p.Arg968Glu), which were inherited from his phenotypically normal parents and consistent with an autosomal recessive inheritance. This specific combination of the variants was previously unreported. According to the guidelines from the American College of Medical Genetics and Genomics (ACMG) guidelines, both variants were classified as likely pathogenic (PM2_Supporting+ PM3+ PP3+ PP4; PM1+ PM2_Supporting+ PP3+ PP4). Conclusion:The novel compound heterozygous variants of the ABCA4 gene probably underlay the genetic etiology of Stargardt disease type 1 in this child. Above finding has expanded the mutational spectrum of the ABCA4 gene among the Chinese population and provided further evidence for understanding the genetic heterogeneity and genotype-phenotype correlation of the Stargardt disease.

OBJECTIVE: To investigate the clinical features and pathogenesis of a child with Stargardt disease caused by variants of ABCA4 gene. METHODS: A child presented at Shenzhen Eye Hospital between September 5, 2020, and April 3, 2023 was selected as the study subject. Clinical data of the child were collected. Whole exome sequencing was performed on peripheral blood samples from the child and his parents. Candidate variants were validated by Sanger sequencing and bioinformatic analysis. This study was approved by the Medical Ethics Committee of Shenzhen Eye Hospital (Ethics No.: 2022KYPJ072). RESULTS: The child was a 10-year-old male presenting with uncorrected visual acuity of 0.1 in both eyes without improvement with refractive correction. Fundus photography showed diffusely distributed yellow-white flecks in the macular region. FAF revealing central hypofluorescence surrounded by a hyperfluorescent ring, and OCT demonstrating significant foveal thinning (right eye: 45 μm; left eye: 50 μm) with ellipsoid zone disruption. Whole exome sequencing and Sanger sequencing revealed that the child has harbored compound heterozygous variants of the ABCA4 gene, namely c.2384G>T (p.Gly795Val) and c.2903G>A (p.Arg968Glu), which were inherited from his phenotypically normal parents and consistent with an autosomal recessive inheritance. This specific combination of the variants was previously unreported. According to the guidelines from the American College of Medical Genetics and Genomics (ACMG) guidelines, both variants were classified as likely pathogenic (PM2_Supporting+PM3+PP3+PP4; PM1+PM2_Supporting+PP3+PP4). CONCLUSION The novel compound heterozygous variants of the ABCA4 gene probably underlay the genetic etiology of Stargardt disease type 1 in this child. Above finding has expanded the mutational spectrum of the ABCA4 gene among the Chinese population and provided further evidence for understanding the genetic heterogeneity and genotype-phenotype correlation of the Stargardt disease.
Humans ; Male ; Child ; ATP-Binding Cassette Transporters/genetics* ; Stargardt Disease/genetics* ; Heterozygote ; Mutation ; Exome Sequencing ; Macular Degeneration/congenital*

AIM:To investigate the mechanism by which muscle segment homeobox 2(Msx2)regulates the differentiation of outer enamel epithelial cells in the enamel organ.METHODS:Tissue paraffin sections were prepared and subjected to hematoxylin-eosin(HE)staining to analyze the effect of Msx2 deficiency on the differentiation status of epithelial cells in the enamel organ at the morphological level.At the ultrastructural level,alterations in cell structure were analyzed.The intermediate steps mediating cell differentiation were identified.Transcriptome sequencing analysis was performed to validate the molecular mechanisms underlying the observed phenomena.RESULTS:Msx2 deficiency was innovatively found to induce severe squamous epithelial hyperplasia in outer enamel epithelial cells of enamel organ,accompanied by dynamic restructuring of the cell cytoskeleton and alterations in cell adhesion at the ultrastructure level.As a transcriptional repressor,the loss of Msx2 expression results in significant increases(P＜0.05 or P＜0.01)in the mRNA expression levels of integrin β2(Itgβ2),ItgαM,Itgα4,Rac family small GTPase 2(Rac2),Rac/Cdc42 guanine nucleo-tide exchange factor 6(Arhgef6)and protein tyrosine phosphatase receptor type C(Ptprc).CONCLUSION:Msx2 regu-lates cytoskeleton structure and cell-cell interaction through the Rho GTPases signaling pathway,thereby influencing the differentiation state of outer enamel epithelial cells.This study reveals the mechanism through which Msx2 regulates the differentiation of outer enamel epithelial cells,providing a theoretical foundation for the prevention and treatment of enam-el-related clinical dental diseases.

Objective:To evaluate the effectiveness of yttrium aluminum garnet (Nd∶YAG) laser vitreolysis in the treatment of symptomatic vitreous opacity.Methods:An observational case series study was performed.Forty-four eyes of 44 patients diagnosed as physiological vitreous opacity in Shenzhen Eye Hospital from June 2021 to September 2022 and treated with Nd∶YAG laser vitreolysis were enrolled.Before treatment and 2 months after last treatment, best corrected visual acuity (BCVA) evaluated with standard logarithmic visual acuity chart, floater areas calculated through infrared fundus photography, and objective scattering index (OSI) obtained by the Optical Quality Analysis System (OQAS) were recorded.The occurrence of complications during the follow-up period was recorded.The differences in each indicator were compared, and a simple linear regression model was used to analyze the relationship between floater area and OSI.This study adhered to the Declaration of Helsinki and was approved by the Medical Ethics Committee of Shenzhen Eye Hospital (No.2021-6-3).Patients were informed of the study methods and purposes.Written informed consent was obtained from each subject.Results:There was no significant difference in BCVA before and after Nd∶YAG laser vitreolysis ( t=-0.478, P=0.635).The floater area before laser treatment was (3.043±1.942)mm 2, which was significantly larger than (1.074±0.735)mm 2 after laser treatment ( t=0.769, P<0.001).The OSI before laser treatment was 1.976±0.975, which was significantly greater than 1.560±0.796 after laser treatment ( t=0.730, P<0.001).The results of linear regression analysis showed that the OSI=1.45+ 0.16× floater area ( F=5.681, P=0.020).No patient had visual acuity loss or intraocular pressure increase and no traumatic cataract or retinal damage occurred. Conclusions:After laser treatment, the floater area decreased, the OSI decreased, and the visual quality of patients improved.The OSI from OQAS Ⅱ and floater area can be used as quantitative evaluation indicators to objectively evaluate the effectiveness of Nd∶YAG laser vitreolysis.

Objective:To evaluate the effectiveness of yttrium aluminum garnet (Nd∶YAG) laser vitreolysis in the treatment of symptomatic vitreous opacity.Methods:An observational case series study was performed.Forty-four eyes of 44 patients diagnosed as physiological vitreous opacity in Shenzhen Eye Hospital from June 2021 to September 2022 and treated with Nd∶YAG laser vitreolysis were enrolled.Before treatment and 2 months after last treatment, best corrected visual acuity (BCVA) evaluated with standard logarithmic visual acuity chart, floater areas calculated through infrared fundus photography, and objective scattering index (OSI) obtained by the Optical Quality Analysis System (OQAS) were recorded.The occurrence of complications during the follow-up period was recorded.The differences in each indicator were compared, and a simple linear regression model was used to analyze the relationship between floater area and OSI.This study adhered to the Declaration of Helsinki and was approved by the Medical Ethics Committee of Shenzhen Eye Hospital (No.2021-6-3).Patients were informed of the study methods and purposes.Written informed consent was obtained from each subject.Results:There was no significant difference in BCVA before and after Nd∶YAG laser vitreolysis ( t=-0.478, P=0.635).The floater area before laser treatment was (3.043±1.942)mm 2, which was significantly larger than (1.074±0.735)mm 2 after laser treatment ( t=0.769, P<0.001).The OSI before laser treatment was 1.976±0.975, which was significantly greater than 1.560±0.796 after laser treatment ( t=0.730, P<0.001).The results of linear regression analysis showed that the OSI=1.45+ 0.16× floater area ( F=5.681, P=0.020).No patient had visual acuity loss or intraocular pressure increase and no traumatic cataract or retinal damage occurred. Conclusions:After laser treatment, the floater area decreased, the OSI decreased, and the visual quality of patients improved.The OSI from OQAS Ⅱ and floater area can be used as quantitative evaluation indicators to objectively evaluate the effectiveness of Nd∶YAG laser vitreolysis.

AIM:To investigate the mechanism by which muscle segment homeobox 2(Msx2)regulates the differentiation of outer enamel epithelial cells in the enamel organ.METHODS:Tissue paraffin sections were prepared and subjected to hematoxylin-eosin(HE)staining to analyze the effect of Msx2 deficiency on the differentiation status of epithelial cells in the enamel organ at the morphological level.At the ultrastructural level,alterations in cell structure were analyzed.The intermediate steps mediating cell differentiation were identified.Transcriptome sequencing analysis was performed to validate the molecular mechanisms underlying the observed phenomena.RESULTS:Msx2 deficiency was innovatively found to induce severe squamous epithelial hyperplasia in outer enamel epithelial cells of enamel organ,accompanied by dynamic restructuring of the cell cytoskeleton and alterations in cell adhesion at the ultrastructure level.As a transcriptional repressor,the loss of Msx2 expression results in significant increases(P＜0.05 or P＜0.01)in the mRNA expression levels of integrin β2(Itgβ2),ItgαM,Itgα4,Rac family small GTPase 2(Rac2),Rac/Cdc42 guanine nucleo-tide exchange factor 6(Arhgef6)and protein tyrosine phosphatase receptor type C(Ptprc).CONCLUSION:Msx2 regu-lates cytoskeleton structure and cell-cell interaction through the Rho GTPases signaling pathway,thereby influencing the differentiation state of outer enamel epithelial cells.This study reveals the mechanism through which Msx2 regulates the differentiation of outer enamel epithelial cells,providing a theoretical foundation for the prevention and treatment of enam-el-related clinical dental diseases.

Objective:To investigate the clinical features and pathogenesis of a child with Stargardt disease caused by variants of ABCA4 gene. Methods:A child presented at Shenzhen Eye Hospital between September 5, 2020, and April 3, 2023 was selected as the study subject. Clinical data of the child were collected. Whole exome sequencing was performed on peripheral blood samples from the child and his parents. Candidate variants were validated by Sanger sequencing and bioinformatic analysis. This study was approved by the Medical Ethics Committee of Shenzhen Eye Hospital (Ethics No.: 2022KYPJ072).Results:The child was a 10-year-old male presenting with uncorrected visual acuity of 0.1 in both eyes without improvement with refractive correction. Fundus photography showed diffusely distributed yellow-white flecks in the macular region. FAF revealing central hypofluorescence surrounded by a hyperfluorescent ring, and OCT demonstrating significant foveal thinning (right eye: 45 μm; left eye: 50 μm) with ellipsoid zone disruption. Whole exome sequencing and Sanger sequencing revealed that the child has harbored compound heterozygous variants of the ABCA4 gene, namely c. 2384G>T (p.Gly795Val) and c. 2903G>A (p.Arg968Glu), which were inherited from his phenotypically normal parents and consistent with an autosomal recessive inheritance. This specific combination of the variants was previously unreported. According to the guidelines from the American College of Medical Genetics and Genomics (ACMG) guidelines, both variants were classified as likely pathogenic (PM2_Supporting+ PM3+ PP3+ PP4; PM1+ PM2_Supporting+ PP3+ PP4). Conclusion:The novel compound heterozygous variants of the ABCA4 gene probably underlay the genetic etiology of Stargardt disease type 1 in this child. Above finding has expanded the mutational spectrum of the ABCA4 gene among the Chinese population and provided further evidence for understanding the genetic heterogeneity and genotype-phenotype correlation of the Stargardt disease.

Objective To investigate the effect of thalidomide combined with infliximab (IFX) in treatment of refractory inflammatory bowel disease (IBD) and its effects on insulin-like growth factor-1 (IGF-1) and transforming growth factor-β1 (TGF-β1). Methods A total of 120 patients with refractory IBD were randomly divided into experimental group and control group, with 60 cases in each group. The two groups were given conventional treatment (mesalazine), the control group was given IFX, and the experimental group was given IFX combined with thalidomide, continuous treatment for two months. The efficacy, intestinal flora disturbance rate, adverse reactions, Crohn's disease activity index (CDAI), Lewis score, serum IGF-1, TGF-β1 levels and nutritional status indexes[albumin (ALB), transferrin (Tf)]before and after treatment for 1 month and 2 months of the two groups were compared. Results The total effective rate of the experimental group was significantly higher than that of the control group (P < 0.05). After one month and two months of treatment, CDAI and Lewis scores of the experimental group were significantly lower than those of the control group (P < 0.05); the serum levels of IGF-1, TGF-β1 as well as ALB and Tf in the experimental group were significantly higher than those in the control group (P < 0.05). The improvement of intestinal flora disturbance rate in the experimental group was significantly better than that in the control group (P < 0.05). There was no significant difference in the incidence of oral and nasal mucosa dryness, throat discomfort, nausea and vomiting between two groups (P>0.05). Conclusion In the treatment of refractory IBD patients, thalidomide combined with IFX can regulate serum IGF-1 and TGF-β1 levels, effectively relieve clinical manifestations, inhibit inflammatory activities, and improve nutritional status and intestinal flora disorders of patients, and it has high safety.

Objective To explore the chain mediating effect of interpersonal promotion and calling on work autonomy and work engagement of medical staff.Methods From June to July 2023,a total of 310 medical staff from 5 tertiary public hos-pitals in Hangzhou were selected by convenience sampling.The questionnaire included work autonomy scale,interpersonal promo-tion scale,calling scale and work engagement scale for accurate and effective investigation,and data analysis was conducted using SPSS2 6.0 and AMOS 26.0.Results A total of 310 questionnaires were distributed and 257 were recovered with a recovery rate of 82.90％.There were statistically significant differences in work engagement among medical staff with different ages,marital status,working time,titles and positions(all P＜0.05).Calling partially mediated the effect of work autonomy on work engage-ment(95％CI[0.090,0.291],P＜0.001),and interpersonal promotion and calling played a partially chain mediating role be-tween work autonomy and work engagement(95％CI[0.016,0.103],P＜0.001).Conclusion Interpersonal promotion and calling play a partially chain mediating role between work autonomy and work engagement of medical staff.Work autonomy of medical staff not only has an indirect effect on work engagement through the mediating role of calling,but also enhances calling through interpersonal promotion and ultimately affects work engagement.

Objective To build a comprehensive evaluation system for the operating benefit of clinical departments in cancer hospitals,so as to provide data support for the fine operation management of hospitals.Methods Literature review and semi-structured interview were used to form the index pool.Two rounds of Delphi expert consultation were used to determine the index of the evaluation system,and the analytic hierarchy process was used to determine the index weight.Finally,the weighted TOPSIS was used for empirical case analysis.Results The positive coefficient in the two rounds of Delphi expert consultation were 82.6％and 100％,the authority coefficient was 0.808,and the coordination coefficient was between 0 and 1.All indexes at all levels passed the consistency test.Finally,a comprehensive evaluation system consisting of 4 dimensions,19 indexes in surgery,16 indicators in radiotherapy and 16 indicators in internal medicine was constructed.Indicators at all levels were tested for consistency,resulting in the construction of a comprehensive evaluation system consisting of 4 dimensions,19 indicators for surgery and 16 indicators each for radiotherapy and internal medicine departments.Conclusion The comprehensive evaluation system of operating benefit of clinical departments in cancer hospitals can help hospitals and departments to find out the shortcomings of operation,build the path of operating benefit improvement,and realize the connotation improvement and high-quality development of hospitals.