[Abstract] The research on immune checkpoint has made breakthrough progress in recent years. The PD-1/PD-L1 signaling pathway is closely related to the immune escape mechanism, and their inhibitors have also made great success in lung cancer. From Checkmate017, Checkmate-057 to KEYNOTE-010 and OAK studies, PD-1/PD-L1 inhibitors have gradually established their position as standard treatment for the advanced NSCLC patients after chemotherapy failed. PD-1/PD-L1 inhibitors can be combined with other cancer treatment methods, including radiotherapy, chemotherapy, targeted therapy and other immunotherapies, whichhave synergistic effects in the treatment of lung cancer, thus improving the efficacy. Immune checkpoint inhibitors bring changes in the treatment patterns of lung cancer, but also to the traditional efficacy evaluation model,as wellas reaction to the treatment-related adverse. In addition, the development of immune check point inhibitors has effectively promoted the progress of precision medicine.

Objective To observe the efficacy of pars plana vitrectomy with internal limiting membrane (ILM) peeling and gas tamponade in the treatment of myopic macular retinoschisis (MF).Methods This is a retrospective case study.A total of 35 MF patients (36 eyes) were enrolled in this study.There were 5 males (5 eyes) and 30 females (31 eyes),with an average age of (60.13 ± 10.00) years.All patients were examined for best corrected visual acuity (BCVA),diopter,optical coherence tomography (OCT) and axial length.The patients were divided into a MF group (group A,10 eyes),MF with foveal detachment group (group B,12 eyes) and MF with lamellar macular hole group (group C,14 eyes) according to the OCT characteristics.There was no difference of age,gender,spherical equivalent refraction and axial length among 3 groups (F=0.020,0.624,0.009,0.195;P＞0.05).There were significant differences of the minimum resolution angle logarithm (logMAR) BCVA and central fovea thickness (CFT) (F=11.100,41.790;P＜ 0.05).All patients underwent pars plana vitrectomy with ILM peeling and gas tamponade.The follow-up was more than one year.The BCVA and macular structure at the final follow-up were analyzed.The efficacy between 3 forms of MF was compared.Results At the final follow-up,the BCVA was 0.40±0.44 and CFT was (213.35±97.58) μm,which were significantly improved compared with preoperative measurements (t=5.984,5.113;P＜0.001).MF was resolved in 33 eyes.In group A,B and C,the logMAR BCVA were 0.13 ± 0.10,0.73±0.33 and 0.38± 0.52,respectively;CFT was (222.40± 57.16),(212.50 ± 150.45),(206.67 ± 55.97) μm,respectively;MF was resolved in 10,11 and 12 eyes,respectively;complete ellipsoid was observe in 8,2 and 12 eyes.The logMAR BCVA (F=6.750,P=0.003) and the rate of complete ellipsoid (x2=18.590,P＜0.001) in group B was lower than group A and C,the differences were significant.There was no difference of CFT (F=0.068,P=0.935) and the rate of MF resolving (x2=1.558,P=0.459) among the three groups.One eye (1/14) in group C suffered from full layer macular hole.Conclusion Pars plana vitrectomy with ILM peeling and gas tamponade is effective in the treatment of myopic macular retinoschisis.The macular structures and BCVA are worst in eyes with foveal detachment.

Objective:To identify the genetic variation in a mucopolysaccharidosis type Ⅱ(MPS Ⅱ)family, and conduct a functional study of iduronate-2-sulfatase(IDS): c.323A>C.Methods:A five-generation MPS Ⅱ family of 83 individuals including 4 patients from northern China was collected. Urine mucopolysaccharide and Alder-Reilly body were tested to assist the clinical diagnosis of MPS Ⅱ. IDS enzyme activity was detected on core family members. By the whole exome sequencing of a MPS Ⅱ patient in this family and bioinformatics analysis, the variant was screened and further identified by PCR-Sanger sequencing. Finally, to validate the function of the variant in vitro, the wild-type IDS overexpression plasmid(pCMV-hIDS-WT)and the IDS overexpression plasmid carrying the mutation site(pCMV-hIDS-c.323A>C)were transfected into COS-7 cells and the IDS activity was detected. Results:The proband(Ⅳ3)and Ⅳ4 were diagnosed as MPS Ⅱ by urine mucopolysaccharide, Alder-Reilly body, and IDS enzyme activity tests. Ⅳ3, Ⅳ4, Ⅲ19, and Ⅲ32 were determined to carry IDS: c.323A>C missense variant through the whole-exome sequencing, and diagnosed as MPS Ⅱ. Meanwhile, Ⅱ2, Ⅱ4, Ⅱ8, Ⅱ12, Ⅱ14, Ⅲ5, Ⅲ7, Ⅳ14 in the MPS Ⅱ family carried IDS: c.323A>C missense variant, and were excluded as MPS Ⅱ. The in vitro experiment in COS-7 cells showed that the missense mutation led to a significant decrease in IDS enzyme activity. Conclusion:The variant IDS: c.323A>C: p.Y108S significantly decreases the activity of IDS enzyme in vivo and in vitro, and it is identified as a pathogenic variant for MPS Ⅱ.