Epidemiologic characteristics and the change of surgical methods of pterygium and pseudopterygium from 2013 to 2019 in China: A retrospective analysis.

Introduction: Pterygium is a common multifactorial external eye disease, which causes various ocular symptoms and negatively affects appearance. The aim of this study was to analyze the epidemiological characteristics and the change of surgical methods of pterygium and pseudopterygium in China from 2013 to 2019. Materials and methods: This study was a hospital-based nationwide retrospective study to estimate the epidemiologic characteristics and the change of surgical methods of pterygium and pseudopteygium in China from 2013 to 2019. The data was extracted from the Hospital Quality Monitoring System (HQMS) database. The diagnosis was based on the tenth revision of the International Classification of Diseases (ICD-10) code. Results: Our study included 1,007,800 pterygium and 2,681 pseudopteygium inpatients. From 2013 to 2019, the proportion of pterygium and pseudopterygium patients who underwent surgery, among all ophthalmology inpatients, increased from 3.3% in 2013 to 7.84% in 2019. The male-female ratio of surgically treated pterygium and pseudopterygium is 1:1.8 and 1.6:1 respectively. Among all age groups, the hospitalized pterygium patients who received surgery were mainly 60-69 years old, accounting for 36.53%. The pseudopterygium patients who received surgery were mostly 50-59 years old, accounting for 24.02%. Among the 31 provinces of mainland China, Yunnan Province has the highest proportion of pterygium patients treated surgically (6.40%), while Shanghai has the highest proportion of pseudopterygium patients treated surgically (12.98%). The most common occupation of participants in the study was farmer, accounting for 47.62% and 28.53%, respectively. During the study period, the application of autologous stem cell transplantation increased year by year, and became the first choice for pterygium and pseudopterygium surgery. Discussion: This study was the first to describe the epidemiological characteristics and surgical methods of hospitalized pterygium and pseudopterygium patients in China. This study provides important information for better diagnosis, treatment and prevention of pterygium and pseudopterygium.

Global spectrum of USH2A mutation in inherited retinal dystrophies: Prompt message for development of base editing therapy.

Purpose: Mutation in the USH2A gene is the most common cause of inherited retinal dystrophy (IRD), including non-syndromic retinitis pigmentosa (RP) and Usher syndrome II (USH2). Gene editing and therapy targeting USH2A, especially the hotspot region, would benefit a large proportion of IRD patients. In this study, we comprehensively analyzed the genetic spectrum of the USH2A gene, aiming to identify global hot spot mutations in USH2A-related IRDs and differences in hot spot regions across continents. Materials and methods: A retrospective USH2A-related IRD study was conducted, including our IRD cohort, and reported USH2A studies worldwide. Results: A total of 3,972 mutated USH2A alleles of approximately 1,935 patients were collected from 33 cohort studies worldwide, containing 102 alleles of 51 patients in our IRD cohort. Mutations in exon 13 were the most common, reaching 18.4% globally and a higher frequency of 22% in America, 19.2% in Europe, and a lower 12% in East Asia. Pathogenic mutations that affected 10 of the 72 exons of USH2A, exon 2, exon 13, exon 41-43, exon 50, exon 54, exon 57, exon 61, and exon 63 in total were responsible for half of global USH2A mutant alleles. With base editors including adenine base editor (ABE), cytidine base editor (CBE), and glycosylase base editor (GBE), 76.3% of single nucleotide variations (SNVs) and 58% of all mutations in USH2A are correctable. Meantime, four novel pathogenic mutations were revealed in our IRD cohort, p. (Val1130Cysfs*72), p. (Ala2139fs*14), p. (Gly4139Arg), and p. (Val4166Cysfs*7). Conclusion: In this study, we revealed four novel mutations, expanding the spectrum of USH2A mutations, and importantly presented global hotspot exons and mutations of USH2A as well as the proportion of SNVs that can be restored by different base editors, providing a perspective for exploring high-efficiency and broader-reaching gene editing and gene therapies.

Transplantation of GMP-grade human iPSC-derived retinal pigment epithelial cells in rodent model: the first pre-clinical study for safety and efficacy in China.

BACKGROUND: Age-related macular degeneration (AMD) is the leading cause of blindness in the elderly due in large part to age-dependent atrophy of retinal pigment epithelium (RPE) cells. RPE cells form a monolayer located between the choroid and the outer segments of photoreceptors, playing multifarious roles in maintenance of visual function. Allogeneically induced pluripotent stem cell-derived RPE (iPSC-RPE or iRPE) has become a potential approach for providing an abundant source of donors for clinical cell products. Transplantation of iRPE has been proven effective in rescuing impaired retinas in Royal College of Surgeons (RCS) rats after approximately 5 to 6 weeks. Here, we explore the long-term (19 weeks) safety and efficacy of human iRPE cell transplantation in pre-clinical animal models. METHODS: The expression of human RPE-specific markers in iRPE cells was determined using immunofluorescence staining. For the proliferative test, Ki-67 expression was also verified by immunofluorescence and flow cytometric analysis. Then, iRPE cells were transplanted into the subretinal space of immune-deficient NOD/SCID/IL-2Rgcnull (NSG) mice to assess their safety. To evaluate whether the transplanted cells could survive and rescue visual function, we performed color fundus photography, focal electroretinogram and immunostaining after delivering iRPE cells into the subretinal space of RCS rats. RESULTS: Human iRPE cells expressed native RPE-specific markers, such as microphthalmia-associated transcription factor (MiTF), retinal pigment epithelium-specific 65-kDa protein (RPE65) and tight-junction associated structural protein (ZO-1), and their proliferative capacity (Ki-67 expression) was poor after 25 days of induction. A tumorigenicity test revealed no tumor formation or abnormal proliferation in the immunodeficient mice after subretinal injection of 5×105 iRPE cells. The transplanted iRPE cells survived for at least 19 weeks and maintained visual function for 15 weeks. CONCLUSIONS: In the present study, we provided further evidence for the use of human iRPE transplantation to treat retinal degenerative disease in pre-clinical animal models. Therefore, we consider human iRPE cells a promising source of cell replacement therapy for AMD.

Low doses of paclitaxel enhance liver metastasis of breast cancer cells in the mouse model.

UNLABELLED: Paclitaxel is the most commonly used chemotherapeutic agent in breast cancer treatment. In addition to its well-known cytotoxic effects, recent studies have shown that paclitaxel has tumor-supportive activities. Importantly, paclitaxel levels are not maintained at the effective concentration through one treatment cycle; rather, the concentration decreases during the cycle as a result of drug metabolism. Therefore, a comprehensive understanding of paclitaxel's effects requires insight into the dose-specific activities of paclitaxel and their influence on cancer cells and the host microenvironment. Here we report that a low dose of paclitaxel enhances metastasis of breast cancer cells to the liver in mouse models. We used microarray analysis to investigate gene expression patterns in invasive breast cancer cells treated with low or clinically relevant high doses of paclitaxel. We also investigated the effects of low doses of paclitaxel on cell migration, invasion and metastasis in vitro and in vivo. The results showed that low doses of paclitaxel promoted inflammation and initiated the epithelial-mesenchymal transition, which enhanced tumor cell migration and invasion in vitro. These effects could be reversed by inhibiting NF-κB. Furthermore, low doses of paclitaxel promoted liver metastasis in mouse xenografts, which correlated with changes in estrogen metabolism in the host liver. Collectively, these findings reveal the paradoxical and dose-dependent effects of paclitaxel on breast cancer cell activity, and suggest that increased consideration be given to potential adverse effects associated with low concentrations of paclitaxel during treatment. DATABASE: Gene expression microarray data are available in the GEO database under accession number GSE82048.

Recombinant human PDCD5 protein enhances chemosensitivity of breast cancer in vitro and in vivo.

Resistance to paclitaxel is common for treatment of breast cancer. Programmed cell death 5 (PDCD5) accelerates apoptosis in different cell types in response to various stimuli; moreover PDCD5 has been shown to be down-regulated in many tumors. In this study, protein levels of PDCD5 were found to be up-regulated in paclitaxel-treated MDA-MB-231 breast cancer cells. MTT, CCK-8, and clonogenic assays have shown that recombinant human PDCD5 (rhPDCD5) alone could not produce an obvious growth inhibition. However, upon paclitaxel triggering apoptosis, rhPDCD5 protein potentiated chemotherapeutic drugs-induced growth arrest in MDA-MB-231, SK-BR-3, and ZR-75-1 breast cancer cells. In vivo, we use a human breast cancer xenograft model to study. We found that rhPDCD5 dramatically improves the antitumor effects of paclitaxel treatment by intraperitoneal administration. These data suggest that rhPDCD5 has the potential to use as a therapeutic agent to enhance the paclitaxel sensitivity of breast cancer cells.

Evaluation of the novel gene Rabl3 in the regulation of proliferation and motility in human cancer cells.

Rab is a large subfamily of small GTPases which play an important role in multiple processes relating to cellular transportation and modulation of the cytoskeleton. Novel gene Rab-like 3 (Rabl3), which we originally reported as a new member belonging to this subfamily, may participate in other processes in human cancer cell lines based on our research. In order to investigate the function of Rabl3 and the basic mechanism which regulates cancer cell survival and motility, we constructed the Rabl3-pcDNA3.1 fusion plasmid, also, the specific siRNA against Rabl3 was used. We detected cellular viability and motility changes in Rabl3 overexpressed or si-Rabl3 transfected cancer cell lines. Overexpression of Rabl3 resulted in the enhancement of cell proliferation, inhibition of apoptosis and paclitaxel resistance in human cancer cell lines. Rabl3 also promoted cell motility activity. Next, we silenced Rabl3 in order to determine its exact physiological function. We found that processes which are associated with tumor formation and metastasis were inhibited. These included an increased incidence of apoptosis, abrogated cellular proliferation and mobility. Furthermore, western blot analysis revealed that the function of Rabl3 was closely associated with focal adhesion kinase (FAK) phosphorylation, both in HeLa and MDA-MB-231 cell lines at the sites of Tyr 397/576/577. Our results suggested that Rabl3 may be a novel oncogene which regulates the oncological behavior of human cancer cells. As a consequence, Rabl3 can be considered as a novel candidate in the control of tumorigenesis and as a new target for anti-tumor treatment.