The advancement of computers and data explosion have ushered in the third wave of artificial intelligence(AI). AI is an interdisciplinary field that encompasses new ideas, new theories, and new technologies, etc. AI has brought convenience to ophthalmology application and promoted its intelligent, precise, and minimally invasive development. At present, AI has been widely applied in various fields of ophthalmology, especially in oculoplastic surgery. AI has made rapid progress in image detection, facial recognition, etc., and its performance and accuracy have even surpassed humans in some aspects. This article reviews the relevant research and applications of AI in oculoplastic surgery, including ptosis, single eyelid, pouch, eyelid mass, and exophthalmos, and discusses the challenges and opportunities faced by AI in oculoplastic surgery, and provides prospects for its future development, aiming to provide new ideas for the development of AI in oculoplastic surgery.

Objective:To investigate the molecular pathogenesis of a newly discovered gene mutation in a family with hereditary coagulation factor Ⅺ(FⅪ) deficiency.Methods:The proband was admitted to the First Affiliated Hospital of Wenzhou Medical University in September 2021 due to "calculus of intrahepatic duct". The patient had no symptoms of spontaneous bleeding.The clinical data and blood samples of the proband and her family members (10 persons in 3 generations) were collected.The activated partial thromboplastin time (APTT) and FⅪ activity (FⅪ:C) were performed by the one-stage clotting assay. FⅪ antigen (FⅪ:Ag) were detected by enzyme linked immunosorbent assay (ELISA). Genomic DNA extracted from peripheral blood cells of subjects was used as template to analyze F11 gene mutation by DNA direct sequencing. Bioinformatics software was used to analyze the effects of mutations on protein structure and function. Wild-type and mutant FⅪ protein expression vectors were constructed and transient transfected into HEK293T cells. The total RNA was extracted from positive transfected cells and then reversely transcribed into cDNA. The mRNA expression level of F11 gene in transfected cells was detected by real-time fluorescence quantitative PCR (qRT-PCR). The content of FⅪ:Ag and the expression of FⅪ protein in transfected cell lysates and culture supernatant were detected by ELISA and western blot.Results:The APTT of the proband was significantly prolonged to 107.9s (reference range 29.0-43.0s), while FⅪ:C and FⅪ:Ag were significantly decreased to 2% (reference range 84%-122%) and 5% (reference range 76%-127%), respectively. Gene sequencing analysis indicated that the proband had c.536C>T (p.Thr161Met) heterozygous missense mutation and c.1556G>A (p.Trp501Ter) heterozygous nonsense mutation in exon 6 and 13 of the F11 gene, respectively. Bioinformatics analysis showed that the amino acids at site 161 of FⅪ protein were threonine (Thr) in the matrix composed of five different species, indicating that Thr161 site was highly conserved among homologous genes in different species. p.Thr161Met heterozygous mutation affected the stability of local intermolecular structure of FⅪ protein. In vitro expression experiments of p.Thr161Met mutation showed that FⅪ protein had a normal synthesis in the cells but secretion dysfunction.Conclusions:c.536C>T (p.Thr161Met) heterozygous missense mutation and c.1556G>A (p.Trp501Ter) heterozygous nonsense mutation were mainly responsible for the decrease of FⅪ in this family. p.Thr161Met mutation was first reported in the world and did not affect the normal synthesis of FⅪ protein, but caused secretion dysfunction.

Objective:To explore the molecular pathogenesis of hereditary protein C (PC) deficiency due to a p. Gly86Asp variant of the PROC gene through in vitro expression experiment.Methods:Wild type and Gly86Asp mutant expression plasmids of PC were constructed and respectively transfected into HEK 293FT cells. Total RNA was extracted from the transfected cells, and the expression of PROC gene was determined by quantitative real-time PCR (qRT-PCR). PC antigen (PC: Ag) in the supernatant of cell culture and cell lysate was determined by enzyme-linked immunosorbent assay (ELISA), and the level of PC protein was detected by Western blotting. Results:qRT-PCR has detected no significant difference in the transcription level of wild-type and mutant-type PC. Compared with the wild type, the level of mutant PC: Ag in the supernatant and cell lysate were 81.3%±2.6% and 110.0%±2.8%, respectively. No difference was detected in the molecular weight between the wild-type and mutant-type PC by Western blotting. The PC content of mutant type was higher than wild-type in cell lysate, while the opposite was found with the cell culture supernatant.Conclusion:The impaired secretion by mutant PC may be the molecular mechanism of PC deficiency caused by the p.

OBJECTIVE: To explore the molecular basis for a Chinese pedigree affected with hereditary coagulation factor VII (FVII) deficiency. METHODS: The coding regions of F7 gene were amplified by PCR and sequenced. Suspected variants were confirmed by reverse sequencing and validated in other members from the pedigree. Pathogenicity of the variants was analyzed with multiple bioinformatic tools. RESULTS: Genetic analysis revealed that the proband has carried compound heterozygous c.985T>C (p.Ser329Pro) and c.1091G>A (p.Arg364Gln) variants in exon 8 of the F7 gene. Her mother, brother and son were heterozygous for c.985T>C (p.Ser329Pro), while her father was heterozygous for c.1091G>A (p.Arg364Gln). Phylogenetic analysis suggested that both p.Ser329 and p.Arg364 are highly conserved among homologous species. Online bioinformatic software predicted both variants to be deleterious. Protein model analysis suggested that the Pro329 side chain may form a new hydrogen bond with Leu333. The Pro benzene ring may clash with Glu325 in the p.Ser329Pro variant model. The p.Arg364Gln variant have two additional hydrogen bonds compared with wild type Arg364. Both variants may lead to alteration of the protein structure. CONCLUSION The p.Ser329Pro and p.Arg364Gln variants in exon 8 of the F7 gene probably account for the reduced FVII in this pedigree.

Objective:Recently, increasing number of lung cancer patients benefit from immune-checkpoint inhibitors (ICIs). However, the data of Chinese small cell lung cancer (SCLC) patients is limited. This study aims to analyze the response and survival data of ICIs treatment in SCLC and to explore the predictive biomarkers.Methods:Forty-seven SCLC patients who received ICIs treatment from Peking University Cancer Hospital from May 2017 to September 2019 was recruited. Clinical characteristics including sex, age, smoking status, ICIs strategy, PD-L1 expression and therapeutic efficacy were collected to explore the clinical predictive biomarkers for SCLC ICIs treatment.Results:Among the 47 patients, 18 (38.3%) cases were partial repose (PR), 11 (23.4%) were stable disease (SD), 18 (38.3%) were progressive disease (PD), and the objective response rate (ORR) was 38.3%, disease control rate (DCR) was 61.7%, the median progression-free survival (PFS) was 5.3 months. ICIs monotherapy accounts for 27.7%, the ORR was 15.4%, DCR was 53.8%, median PFS was 2.7 months. Combined therapy accounts for 72.3%, the ORR was 47.1%, DCR was 64.7%, median PFS was 5.4 months. Fourteen (29.8%) patients received ICIs as the first line treatment, their ORR was 85.7%, DCR was 100%, median PFS was 9.1 month. The ORR was not related to the age, sex, body mass index (BMI), smoking status and programmed death-ligand 1 (PD-L1) expression ( P>0.05). The ORRs were higher in patients underwent PD-L1 monotherapy ( P=0.001), combined therapy ( P=0.002) and received ICIs as the first line treatment ( P<0.001). Log-rank analysis indicated that the PFS of female patients were 12.0 months, significantly longer than 4.4 months of male patients in ICIs treatment ( P=0.038). Patients who received PD-L1 monotherapy, combined treatment, or ICIs as the first line treatment had longer PFS than their counterparts, though no statistical significant was observed ( P>0.05). Cox multivariate analysis showed that, the gender was not an independent predictor for PFS in ICIs treatment ( HR=3.777, 95% CI=0.974~30.891, P=0.054). Conclusions:Immunotherapy is an effective treatment strategy for SCLC. Patients who receive combined ICIs treatment, first line ICIs treatment and PD-L1 treatment may get greater benefits. PD-L1 expression cannot predict the response and PFS in SCLC ICIs treatment.

Objective:Recently, increasing number of lung cancer patients benefit from immune-checkpoint inhibitors (ICIs). However, the data of Chinese small cell lung cancer (SCLC) patients is limited. This study aims to analyze the response and survival data of ICIs treatment in SCLC and to explore the predictive biomarkers.Methods:Forty-seven SCLC patients who received ICIs treatment from Peking University Cancer Hospital from May 2017 to September 2019 was recruited. Clinical characteristics including sex, age, smoking status, ICIs strategy, PD-L1 expression and therapeutic efficacy were collected to explore the clinical predictive biomarkers for SCLC ICIs treatment.Results:Among the 47 patients, 18 (38.3%) cases were partial repose (PR), 11 (23.4%) were stable disease (SD), 18 (38.3%) were progressive disease (PD), and the objective response rate (ORR) was 38.3%, disease control rate (DCR) was 61.7%, the median progression-free survival (PFS) was 5.3 months. ICIs monotherapy accounts for 27.7%, the ORR was 15.4%, DCR was 53.8%, median PFS was 2.7 months. Combined therapy accounts for 72.3%, the ORR was 47.1%, DCR was 64.7%, median PFS was 5.4 months. Fourteen (29.8%) patients received ICIs as the first line treatment, their ORR was 85.7%, DCR was 100%, median PFS was 9.1 month. The ORR was not related to the age, sex, body mass index (BMI), smoking status and programmed death-ligand 1 (PD-L1) expression ( P>0.05). The ORRs were higher in patients underwent PD-L1 monotherapy ( P=0.001), combined therapy ( P=0.002) and received ICIs as the first line treatment ( P<0.001). Log-rank analysis indicated that the PFS of female patients were 12.0 months, significantly longer than 4.4 months of male patients in ICIs treatment ( P=0.038). Patients who received PD-L1 monotherapy, combined treatment, or ICIs as the first line treatment had longer PFS than their counterparts, though no statistical significant was observed ( P>0.05). Cox multivariate analysis showed that, the gender was not an independent predictor for PFS in ICIs treatment ( HR=3.777, 95% CI=0.974~30.891, P=0.054). Conclusions:Immunotherapy is an effective treatment strategy for SCLC. Patients who receive combined ICIs treatment, first line ICIs treatment and PD-L1 treatment may get greater benefits. PD-L1 expression cannot predict the response and PFS in SCLC ICIs treatment.

OBJECTIVE: To detect potential mutations of the coagulation factor Ⅶ (F7) gene in a pedigree affected with hereditary FⅦ deficiency and explore its molecular pathogenesis. METHODS: The FⅦ antigen (FⅦ:Ag) was analyzed by an enzyme-linked immunosorbent assay (ELISA) method. Prothrombin time (PT), FⅦ activity (FⅦ:C) and other coagulant parameters were quantified with an one-stage clotting assay. The F7 gene was amplified by PCR and sequenced. Mutational sites were confirmed by reverse sequencing. Impact of amino acid substitution was assessed using SIFT and PolyPhen-2 software. Structure of the mutant protein was analyzed using Swiss-pdb Viewer software based on the three-dimensional structure in the Protein Data Bank. RESULTS: The propositus had prolonged PT (36.3 s), with FⅦ:C and FⅦ:Ag significantly reduced to 2% and 44%, respectively. Her father, mother, younger sister and daughter had slightly prolonged PT and reduced FⅦ:C (86%-120%). The FⅦ:Ag of her father and younger sister were also reduced. DNA sequencing revealed that the propositus has carried compound heterozygous mutations (Lys341Glu and IVS6-1G>A) of the F7 gene. Her father and younger sister were heterozygous for the IVS6-1G>A mutation, while her mother and daughter were heterozygous for the Lys341Glu mutation. Bioinformatics analysis indicated that Lys341Glu mutation may affect the stability and function of the FⅦ protein. CONCLUSION The Lys341Glu and IVS6-1G>A mutations probably underlie the reduced activity of FⅦ in this pedigree.
Factor VII ; genetics ; Factor VII Deficiency ; genetics ; Female ; Genetic Testing ; Heterozygote ; Humans ; Male ; Mutation ; Pedigree

OBJECTIVE: To identify potential mutations of F11 gene in a pedigree affected with hereditary coagulation factor XI (FXI) deficiency and explore its molecular pathogenesis. METHODS: Prothrombin time (PT), activated partial thromboplastin time (APTT), fibrinogen (FIB), coagulation factor VIII activity (FVIIIC), coagulation factor IX activity (FIXC), coagulation factor XI activity (FXIC), coagulation factor XII activity (FXIIC) and lupus anticoagulation (LA) of the proband and eight family members were determined. FXI antigen (FXIAg) was determined by enzyme-linked immunosorbent assay (ELISA). For the proband, potential mutations in the exons, flanking introns and 5'-, 3'-untranslated regions of the F11 gene were screened by direct DNA sequencing. The results were confirmed by reverse sequencing. Suspected mutations were detected in other family members. ClustalX-2.1-win and four online bioinformatic tools (PolyPhen-2, PROVEAN, SIFT, and Mutation Taster) were used to study the conservation and possible impact of the mutations. The structure of the mutational sites was processed with Swiss-PdbViewer. RESULTS: The propositus had prolonged APTT (69.6 s), whose FXIC and FXIAg were reduced to 6.0% and 10.7%, respectively. Her mother, elder sister, one younger sister, little brother, daughter and son showed slightly prolonged APTT and moderate FXIC and FXIAg levels. Gene sequencing revealed that the propositus carried a heterozygous nonsense mutation c.738G>A (p.Trp228stop) in exon 7 and a heterozygous mutation c.1556G>C (p.Trp501Ser) in exon 13. Her mother, elder sister and daughter were heterozygous for the p.Trp228stop mutation, while one younger sister and little brother and son were heterozygous for p.Trp501Ser. Her husband and the youngest sister were of the wild type. Phylogenetic analysis suggested that Trp501 was highly conserved among all homologous species. The p.Trp501Ser was predicted to be "probably damaging","deleterious", "affect protein function" and "disease causing" corresponding to PolyPhen-2, PROVEAN, SIFT and Mutation Taster. Model analysis demonstrated that the non-polar Trp501 has two benzene rings, forming a hydrogen bond with Gln512 in the wild type. Once substituted by Ser501, the side chain may form another hydrogen bond with the benzene of His396. This may affect the normal space conformation and stability of FXI protein. CONCLUSION The compound heterozygous mutations of the F11 gene probably accounted for the low FXI concentration in this pedigree.
Factor XI ; genetics ; Factor XI Deficiency ; genetics ; Female ; Heterozygote ; Humans ; Male ; Mutation ; Pedigree ; Phylogeny

Objective: To detect potential mutations of the coagulation factor Ⅶ (F7) gene in a pedigree affected with hereditary FⅦ deficiency and explore its molecular pathogenesis. Methods: The FⅦ antigen (FⅦ∶Ag) was analyzed by an enzyme-linked immunosorbent assay (ELISA) method. Prothrombin time (PT), FⅦ activity (FⅦ∶C) and other coagulant parameters were quantified with an one-stage clotting assay. The F7 gene was amplified by PCR and sequenced. Mutational sites were confirmed by reverse sequencing. Impact of amino acid substitution was assessed using SIFT and PolyPhen-2 software. Structure of the mutant protein was analyzed using Swiss-pdb Viewer software based on the three-dimensional structure in the Protein Data Bank. Results: The propositus had prolonged PT (36.3 s), with FⅦ∶C and FⅦ∶Ag significantly reduced to 2% and 44%, respectively. Her father, mother, younger sister and daughter had slightly prolonged PT and reduced FⅦ∶C (86%-120%). The FⅦ∶Ag of her father and younger sister were also reduced. DNA sequencing revealed that the propositus has carried compound heterozygous mutations (Lys341Glu and IVS6-1G>A) of the F7 gene. Her father and younger sister were heterozygous for the IVS6-1G>A mutation, while her mother and daughter were heterozygous for the Lys341Glu mutation. Bioinformatics analysis indicated that Lys341Glu mutation may affect the stability and function of the FⅦ protein. Conclusion The Lys341Glu and IVS6-1G>A mutations probably underlie the reduced activity of FⅦ in this pedigree.

Objective To Analyze the expression profiles of LncRNAs and mRNAs in ovarian epithelial cancer cell lines by gene mi-croarray, and then provide experimental evidences for investigating the function of LncRNAs associated with ovarian cancer. Methods The differentially expressed LncRNAs and mRNAs in ovarian epithelial cancer cell lines, such as A2780, HO8910 and SKOV3, and ovarian epithelial cell line HOSEpiC were analyzed by gene microarray. The differentially expressed mRNAs were further performed the KEGG pathway enrichment analysis. The expression levels of six candidate LncRNAs, which had significant difference between the o-varian epithelial cancer cell line and the ovarian epithelial cell line, were further verified by qRT-PCR. Results There were 227 up-regulated LncRNAs and 483 down-regulated LncRNAs in A2780, HO8910 and SKOV3 cell lines. The differentially expressed mRNAs in A2780, HO8910 and SKOV3 cell lines were mainly enriched in the tumor-related pathways such as PI3K-AKT, mTOR and TNF-α( P<0.05) . The expression levels of PTPRG-AS1, CCNT2-AS1, XLOC 009869 and LINC01138 in ovarian epithelial cancer A2780, SKOV3 and OVCR3 cell lines were up-regulated (P<0.05), while those of RP11-252P19.2 and RP11-744I24.2 in ovarian epithelial cancer A2780, SKOV3, OVCR3 and 3AO cell lines were down-regulated ( P<0.05) . Conclusion The differentially expressed LncR-NAs and mRNAs in ovarian epithelial cancer cell lines may be obtained by gene microarray, and the differentially expressed mRNAs are associated with the tumor-related pathways such as PI3K-AKT, mTOR and TNF-α, which may provide new targets for the diagnosis and treatment of ovarian cancer.