Implementation of a free cataract surgery program in rural China: a community-based randomized interventional study.

PURPOSE: To identify effective methods to increase the number of cataract surgeries in a rural setting in Pucheng County of Shaanxi Province, northwestern China. DESIGN: Community-based randomized interventional study. PARTICIPANTS: Four hundred thirty-two patients 50 years of age or older with operable cataract who had not undergone surgery 3 months after participation in a cataract outreach screening program. METHODS: Three hundred fifty-five (82.2%) patients eligible for surgery, but not scheduling it on their own, were contacted and were assigned randomly into 4 groups. Participants in group 1 (n = 86) were given informative reminders by telephone or in person by a trained facilitator about undergoing low-cost cataract surgery. Group 2 (n = 86) was offered free cataract surgery. Group 3 (n = 90) was offered free surgery and reimbursement of transportation expenses. Group 4 (n = 93) was provided with free rides from home to hospital in addition to the reminder and free surgery. MAIN OUTCOME MEASURES: Number of participants undergoing cataract surgery after interventions. RESULTS: In total, 94 patients (26.5%) underwent cataract surgery after interventions. In group 1, 13 patients (14.4%) underwent surgery, which was significantly lower than the number in group 2 (n = 25 [27.8%]; P = 0.027), group 3 (n = 28 [31.1%]; P = 0.012), and group 4 (n = 26 [28%]; P = 0.038). There were no significant differences between groups 2 and 3 (P = 0.768) or between groups 2 and 4 (P = 0.869). CONCLUSIONS: Provision of free cataract surgery was twice as effective as giving patients an informative reminder when it came to increasing the uptake of cataract surgery. However, offering reimbursement of transportation expenses or provision of free rides had minimal added impact on the response rate of participants to undergo cataract surgery.

Dissection of Cellular Communication between Human Primary Osteoblasts and Bone Marrow Mesenchymal Stem Cells in Osteoarthritis at Single-Cell Resolution.

Background and Objectives: Osteoblasts are derived from bone marrow mesenchymal stem cells (BMMSCs) and play important role in bone remodeling. While our previous studies have investigated the cell subtypes and heterogeneity in osteoblasts and BMMSCs separately, cell-to-cell communications between osteoblasts and BMMSCs in vivo in humans have not been characterized. The aim of this study was to investigate the cellular communication between human primary osteoblasts and bone marrow mesenchymal stem cells. Methods and Results: To investigate the cell-to-cell communications between osteoblasts and BMMSCs and identify new cell subtypes, we performed a systematic integration analysis with our single-cell RNA sequencing (scRNA-seq) transcriptomes data from BMMSCs and osteoblasts. We successfully identified a novel preosteoblasts subtype which highly expressed ATF3, CCL2, CXCL2 and IRF1. Biological functional annotations of the transcriptomes suggested that the novel preosteoblasts subtype may inhibit osteoblasts differentiation, maintain cells to a less differentiated status and recruit osteoclasts. Ligand-receptor interaction analysis showed strong interaction between mature osteoblasts and BMMSCs. Meanwhile, we found FZD1 was highly expressed in BMMSCs of osteogenic differentiation direction. WIF1 and SFRP4, which were highly expressed in mature osteoblasts were reported to inhibit osteogenic differentiation. We speculated that WIF1 and sFRP4 expressed in mature osteoblasts inhibited the binding of FZD1 to Wnt ligand in BMMSCs, thereby further inhibiting osteogenic differentiation of BMMSCs. Conclusions: Our study provided a more systematic and comprehensive understanding of the heterogeneity of osteogenic cells. At the single cell level, this study provided insights into the cell-to-cell communications between BMMSCs and osteoblasts and mature osteoblasts may mediate negative feedback regulation of osteogenesis process.

Imputation of Human Primary Osteoblast Single Cell RNA-Seq Data Identified Three Novel Osteoblastic Subtypes.

BACKGROUND: Recently, single-cell RNA sequencing (scRNA-seq) technology was increasingly used to study transcriptomics at a single-cell resolution, scRNA-seq analysis was complicated by the "dropout", where the data only captures a small fraction of the transcriptome. This phenomenon can lead to the fact that the actual expressed transcript may not be detected. We previously performed osteoblast subtypes classification and dissection on freshly isolated human osteoblasts. MATERIALS AND METHODS: Here, we used the scImpute method to impute the missing values of dropout genes from a scRNA-seq dataset generated on freshly isolated human osteoblasts. RESULTS: Based on the imputed gene expression patterns, we discovered three new osteoblast subtypes. Specifically, these newfound osteoblast subtypes are osteoblast progenitors, and two undetermined osteoblasts. Osteoblast progenitors showed significantly high expression of proliferation related genes (FOS, JUN, JUNB and JUND). Analysis of each subtype showed that in addition to bone formation, these undetermined osteoblasts may involve osteoclast and adipocyte differentiation and have the potential function of regulate immune activation. CONCLUSIONS: Our findings provided a new perspective for studying the osteoblast heterogeneity and potential biological functions of these freshly isolated human osteoblasts at the single-cell level, which provides further insight into osteoblasts subtypes under various (pathological) physiological conditions.