Evolution of the Correlated Genomic Variation Landscape Across a Divergence Continuum in the Genus Castanopsis.

The heterogeneous landscape of genomic variation has been well documented in population genomic studies. However, disentangling the intricate interplay of evolutionary forces influencing the genetic variation landscape over time remains challenging. In this study, we assembled a chromosome-level genome for Castanopsis eyrei and sequenced the whole genomes of 276 individuals from 12 Castanopsis species, spanning a broad divergence continuum. We found highly correlated genomic variation landscapes across these species. Furthermore, variations in genetic diversity and differentiation along the genome were strongly associated with recombination rates and gene density. These results suggest that long-term linked selection and conserved genomic features have contributed to the formation of a common genomic variation landscape. By examining how correlations between population summary statistics change throughout the species divergence continuum, we determined that background selection alone does not fully explain the observed patterns of genomic variation; the effects of recurrent selective sweeps must be considered. We further revealed that extensive gene flow has significantly influenced patterns of genomic variation in Castanopsis species. The estimated admixture proportion correlated positively with recombination rate and negatively with gene density, supporting a scenario of selection against gene flow. Additionally, putative introgression regions exhibited strong signals of positive selection, an enrichment of functional genes, and reduced genetic burdens, indicating that adaptive introgression has played a role in shaping the genomes of hybridizing species. This study provides insights into how different evolutionary forces have interacted in driving the evolution of the genomic variation landscape.

First Report on the Trophic Transfer and Priority List of Liquid Crystal Monomers in the Pearl River Estuary.

Liquid crystal monomers (LCMs) are emerging organic pollutants due to their potential persistence, toxicity, and bioaccumulation. This study first characterized the levels and compositions of 19 LCMs in organisms in the Pearl River Estuary (PRE), estimated their bioaccumulation and trophic transfer potential, and identified priority contaminants. LCMs were generally accumulated in organisms from sediment, and the LCM concentrations in all organisms ranged from 32.35 to 1367 ng/g lipid weight. The main LCMs in organisms were biphenyls and analogues (BAs) (76.6%), followed by cyanobiphenyls and analogues (CBAs) (15.1%), and the least were fluorinated biphenyls and analogues (FBAs) (11.2%). The most abundant LCM monomers of BAs, FBAs, and CBAs in LCMs in organisms were 1-(4-propylcyclohexyl)-4-vinylcyclohexane (15.1%), 1-ethoxy-2,3-difluoro-4-(4-(4-propylcyclohexyl) cyclohexyl) benzene (EDPBB, 10.1%), and 4'-propoxy-4-biphenylcarbonitrile (5.1%), respectively. The niche studies indicated that the PRE food web was composed of terrestrial-based diet and marine food chains. Most LCMs exhibited biodilution in the terrestrial-based diet and marine food chains, except for EDPBB and 4,4'-bis(4-propylcyclohexyl) biphenyl (BPCHB). The hydrophobicity, position of fluorine substitution of LCMs, and biological habits may be important factors affecting the bioaccumulation and trophic transfer of LCMs. BPCHB, 1-(prop-1-enyl)-4-(4-propylcyclohexyl) cyclohexane, and EDPBB were characterized as priority contaminants. This study first reports the trophic transfer processes and mechanisms of LCMs and the biomonitoring in PRE.

Design Considerations for Virtual Reality Intervention for People with Intellectual and Developmental Disabilities: A Systematic Review.

OBJECTIVES: This systematic review aims to explore virtual reality (VR) applications for rehabilitation purposes among people with intellectual and developmental disabilities (IDD), identify their effects on rehabilitation outcomes, explore themes to consider in VR intervention design, and provide guidance for designers and researchers in creating therapeutic environments using VR technology. BACKGROUND: VR has gained increasing attention in healthcare settings to assist in achieving rehabilitation goals for people with IDD. VR is particularly advantageous since it simulates the real world while providing controllable, safe, and versatile environments. It is necessary to expand the current body of knowledge on VR intervention's outcomes by synthesizing further information on VR application characteristics as well as identifying design considerations regarding feasibility, usability, safety, and other aspects that will benefit future VR intervention design and research. METHODS: The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) framed the current review. Multiple databases were searched to identify studies published between 2001 and 2023. The review qualitatively organized VR environment design considerations according to three themes: feasibility, usability, and safety. RESULTS: This review included 27 articles and included 868 participants. The overall findings indicated that VR interventions are promising in enhancing rehabilitation outcomes among people with IDD, such as physical, cognitive, emotional, and functional independence domains. CONCLUSION: This review provides design recommendations to create effective, usable, and safe VR interventions for individuals with IDD. The suggested design implications should be applied with the awareness that VR is a relatively emerging technology with rapidly evolving features.

Mesenchymal Stromal Cells Increase the Natural Killer Resistance of Circulating Tumor Cells via Intercellular Signaling of cGAS-STING-IFNß-HLA.

Circulating tumor cells (CTCs) shed from primary tumors must overcome the cytotoxicity of immune cells, particularly natural killer (NK) cells, to cause metastasis. The tumor microenvironment (TME) protects tumor cells from the cytotoxicity of immune cells, which is partially executed by cancer-associated mesenchymal stromal cells (MSCs). However, the mechanisms by which MSCs influence the NK resistance of CTCs remain poorly understood. This study demonstrates that MSCs enhance the NK resistance of cancer cells in a gap junction-dependent manner, thereby promoting the survival and metastatic seeding of CTCs in immunocompromised mice. Tumor cells crosstalk with MSCs through an intercellular cGAS-cGAMP-STING signaling loop, leading to increased production of interferon-ß (IFNß) by MSCs. IFNß reversely enhances the type I IFN (IFN-I) signaling in tumor cells and hence the expression of human leukocyte antigen class I (HLA-I) on the cell surface, protecting the tumor cells from NK cytotoxicity. Disruption of this loop reverses NK sensitivity in tumor cells and decreases tumor metastasis. Moreover, there are positive correlations between IFN-I signaling, HLA-I expression, and NK tolerance in human tumor samples. Thus, the NK-resistant signaling loop between tumor cells and MSCs may serve as a novel therapeutic target.

Microscopic Electric Rotary Grinding of Plaques Combined with Graft Repair in the Management of Peyronie's Disease.

Peyronie's Disease (PD) is clinically characterized by the development of localized fibrous plaques, primarily on the tunica albuginea, especially on the dorsal area of the penis. These plaques are the hallmark feature of this condition, resulting in penile curvature, deformity, and painful erections for affected individuals. Although various nonsurgical treatment options exist, their overall effectiveness is limited. As a result, surgical intervention has become the ultimate choice for patients with severe penile curvature deformities and associated erectile dysfunction. Our research team has successfully employed a combined approach involving microscopic electric rotary grinding of the fibrous plaques and the use of tunica vaginalis or bovine pericardium as graft materials for the repairing of the defects of tunica albuginea in the treatment of PD. This approach has consistently yielded highly satisfactory results regarding the restoration of penile shape, with excellent cosmetic results and significantly improved sexual satisfaction. This protocol aims to present a comprehensive surgical management strategy utilizing electric rotary grinding of the plaques and repairing the defects of tunica albuginea by using the tunica vaginalis, which represents an optimal surgical strategy for treating PD.

Trophic Transfer of Halogenated Organic Pollutants in a Wetland Food Web: Insights from Compound-Specific Nitrogen Isotope of Amino Acids and Food Source Analysis.

A trophic position (TP) model (TPmix model) that simultaneously considered trophic discrimination factor and ßGlu/Phe variations was developed in this study and was first applied to investigate the trophic transfer of halogenated organic pollutants (HOPs) in wetland food webs. The TPmix model characterized the structure of the wetland food web more accurately and significantly improved the reliability of TMF compared to the TPbulk, TPAAs, and TPsimmr models, which were calculated based on the methods of stable nitrogen isotope analysis of bulk, traditional AAs-N-CSIA, and weighted ßGlu/Phe, respectively. Food source analysis revealed three interlocking food webs (kingfisher, crab, and frogs) in this wetland. The highest HOP biomagnification capacities (TMFmix) were found in the kingfisher food web (0.24-82.0), followed by the frog (0.08-34.0) and crab (0.56-11.7) food webs. The parabolic trends of TMFmix across combinations of log KOW in the frog food web were distinct from those of aquatic food webs (kingfisher and crab), which may be related to differences in food web composition and HOP bioaccumulation behaviors between aquatic and terrestrial organisms. This study provides a new tool to accurately study the trophic transfer of contaminants in wetlands and terrestrial food webs with diverse species and complex feeding relationships.

A chromosome-scale genome assembly of Castanopsis hystrix provides new insights into the evolution and adaptation of Fagaceae species.

Fagaceae species dominate forests and shrublands throughout the Northern Hemisphere, and have been used as models to investigate the processes and mechanisms of adaptation and speciation. Compared with the well-studied genus Quercus, genomic data is limited for the tropical-subtropical genus Castanopsis. Castanopsis hystrix is an ecologically and economically valuable species with a wide distribution in the evergreen broad-leaved forests of tropical-subtropical Asia. Here, we present a high-quality chromosome-scale reference genome of C. hystrix, obtained using a combination of Illumina and PacBio HiFi reads with Hi-C technology. The assembled genome size is 882.6 Mb with a contig N50 of 40.9 Mb and a BUSCO estimate of 99.5%, which are higher than those of recently published Fagaceae species. Genome annotation identified 37,750 protein-coding genes, of which 97.91% were functionally annotated. Repeat sequences constituted 50.95% of the genome and LTRs were the most abundant repetitive elements. Comparative genomic analysis revealed high genome synteny between C. hystrix and other Fagaceae species, despite the long divergence time between them. Considerable gene family expansion and contraction were detected in Castanopsis species. These expanded genes were involved in multiple important biological processes and molecular functions, which may have contributed to the adaptation of the genus to a tropical-subtropical climate. In summary, the genome assembly of C. hystrix provides important genomic resources for Fagaceae genomic research communities, and improves understanding of the adaptation and evolution of forest trees.

Definitive Endodermal Cells Supply an in vitro Source of Mesenchymal Stem/Stromal Cells.

Mesenchymal stem/Stromal cells (MSCs) have great therapeutic potentials, and they have been isolated from various tissues and organs including definitive endoderm (DE) organs, such as the lung, liver and intestine. MSCs have been induced from human pluripotent stem cells (hPSCs) through multiple embryonic lineages, including the mesoderm, neural crest, and extraembryonic cells. However, it remains unclear whether hPSCs could give rise to MSCs in vitro through the endodermal lineage. Here, we report that hPSC-derived, SOX17+ definitive endoderm progenitors can further differentiate to cells expressing classic MSC markers, which we name definitive endoderm-derived MSCs (DE-MSCs). Single cell RNA sequencing demonstrates the stepwise emergence of DE-MSCs, while endoderm-specific gene expression can be elevated by signaling modulation. DE-MSCs display multipotency and immunomodulatory activity in vitro and possess therapeutic effects in a mouse ulcerative colitis model. This study reveals that, in addition to the other germ layers, the definitive endoderm can also contribute to MSCs and DE-MSCs could be a cell source for regenerative medicine.

Systematic Review on Environmental Design for Adaptive and Problem Behaviors of People With Intellectual and Developmental Disabilities.

OBJECTIVES: The presented systematic review explores the empirical studies regarding environmental design strategies that support adaptive behaviors while improving problem behaviors of people with intellectual and developmental disabilities (IDD). BACKGROUND: People with IDD perceive and interact with their environment differently from people without disabilities. Design research has not always considered these differences, and environmental design solutions are not commonly found. METHODS: The review process followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses protocols. The study reports the findings from the systematic review of 32 peer-reviewed studies published in EBSCO, ERIC, ProQuest, PsycINFO, MEDLINE CINAHL, Consumer Health Complete (EBSCOhost), and Psychology and Behavioral Sciences Collection between 1990 and 2020. In addition, quality assessment tools appraised the study's quality. RESULTS: The review identified 26 design strategies. Five themes qualitatively organized these environmental attributes: coherence, affordance, control, stimulation, and restoration. CONCLUSION: The evidence indicates that adequately designed physical environments can support the adaptive behaviors of people with IDD while alleviating behavioral problems. Design features not supported by strong empirical evidence should be further addressed in future studies.

Case report: Pathological and genetic features of pancreatic undifferentiated carcinoma with osteoclast-like giant cells.

Objectives: Pancreatic undifferentiated carcinoma accounts for 2%-7% of pancreatic carcinomas. We aimed to investigate the pathological and genetic characteristics of pancreatic undifferentiated carcinoma with osteoclast-like giant cells and the key points of treatment. Methods: The clinical data and follow-up results of four patients diagnosed with pancreatic undifferentiated carcinoma with osteoclast-like giant cells between May 2015 and May 2020 at the First Affiliated Hospital of Xi'an Jiaotong University were retrospectively analyzed. Results: Chief complaints included "pain and discomfort in the upper abdomen" (2/4), "nausea and vomiting" (1/4) or no symptoms (1/4). Preoperative mildly elevated tumor markers included carcinoembryonic antigen (1/4) and CA19-9 (1/4). The tumors were located in the tail of the pancreas in three patients and the head and neck in one patient. Tumor metastasis was found in pancreatic adipose tissue in two patients and lymph node metastasis in one patient, with microscopic heterogeneous mononuclear cells and scattered osteoclast-like giant cells of various sizes. One patient (1/4) had a mucinous cystic tumor of the pancreas, and two patients (2/4) had adenocarcinoma of the pancreatic duct. Only one patient received postoperative gemcitabine combined with albumin-bound paclitaxel chemotherapy. Conclusion: Currently, treatment guidelines are lacking for PUC-OGC, and prognosis varies markedly. More cases must be reported to clarify its origination. The long-term follow-up of diagnosed patients and genetic mutation testing can also contribute to improving treatment and prognosis of this disease.

Genomic vulnerability to climate change in Quercus acutissima, a dominant tree species in East Asian deciduous forests.

Understanding the evolutionary processes that shape the landscape of genetic variation and influence the response of species to future climate change is critical for biodiversity conservation. Here, we sampled 27 populations across the distribution range of a dominant forest tree, Quercus acutissima, in East Asia, and applied genome-wide analyses to track the evolutionary history and predict the fate of populations under future climate. We found two genetic groups (East and West) in Q. acutissima that diverged during Pliocene. We also found a heterogeneous landscape of genomic variation in this species, which may have been shaped by population demography and linked selections. Using genotype-environment association analyses, we identified climate-associated SNPs in a diverse set of genes and functional categories, indicating a model of polygenic adaptation in Q. acutissima. We further estimated three genetic offset metrics to quantify genomic vulnerability of this species to climate change due to the complex interplay between local adaptation and migration. We found that marginal populations are under higher risk of local extinction because of future climate change, and may not be able to track suitable habitats to maintain the gene-environment relationships observed under the current climate. We also detected higher reverse genetic offsets in northern China, indicating that genetic variation currently present in the whole range of Q. acutissima may not adapt to future climate conditions in this area. Overall, this study illustrates how evolutionary processes have shaped the landscape of genomic variation, and provides a comprehensive genome-wide view of climate maladaptation in Q. acutissima.

Corrigendum: Serum cytokine levels for predicting immune-related adverse events and the clinical response in lung cancer treated with immunotherapy.

[This corrects the article DOI: 10.3389/fonc.2022.923531.].

Serum cytokine levels for predicting immune-related adverse events and the clinical response in lung cancer treated with immunotherapy.

Background: At present, immunotherapy has become an important treatment for lung cancer. With the widespread use of immune checkpoint inhibitors (ICIs), we must be strict with the emergence of immune related adverse events (irAEs). There are also some patients who do not respond to immunotherapy. However, there was no biomarkers to predict the safety and efficacy of immunotherapy. The selection of immunotherapy beneficiaries contributes to improving the efficacy and safety of lung cancer treatment. Method: The electronic medical records of 221 lung cancer patients with complete clinical data who received immunotherapy from the First Affiliated Hospital of Xi 'an Jiaotong University from November 2020 to October 2021 were collected and followed up. IBM SPSS Statistic 26.0 and R 4.1.2 software were used for statistical analysis and mapping. Results: 1. A total of 221 lung cancer patients receiving immunotherapy were included in the study. Higher baseline levels of IL-1ß (7.88 vs 16.16pg/mL, P=0.041) and IL-2 (1.28 vs 2.48pg/mL, P=0.001) were significantly associated with irAEs. Higher levels of IL-5 (2.64 vs 5.68pg/mL, P=0.013), IFN-α (1.70 vs 3.56pg/mL, P=0.004) and IFN-γ (6.14 vs 21.31pg/mL, P=0.022) after the first cycle therapy were associated with irAEs. There was no statistical significance between cytokines and irAEs after the second cycle therapy. Higher IL-5 levels in peripheral blood (9.50 vs 3.57pg/mL, P=0.032) were associated with the occurrence of irAEs after the third cycle therapy. 2.The efficacy of immunotherapy was assessed in 142 lung cancer patients. There was no statistical significance between baseline cytokine levels and clinical benefit. After the first cycle therapy, the level of serum cytokines had no statistical significance with the occurrence of immunotherapy clinical benefit. Lower serum levels of IL-10 (2.66 vs 1.26pg/mL, P=0.016) and IL-17 (8.47 vs 2.81pg/mL, P=0.015) were associated with clinical benefit after the second cycle therapy. Lower serum levels of IL-6 (10.19 vs 41.07pg/mL, P=0.013) and IL-8 (8.01 vs 17.22pg/mL, P=0.039) were associated with clinical benefit of immunotherapy after the third cycle therapy. Conclusion: 1. Baseline IL-1ß and IL-2 levels in peripheral blood were associated with the occurrence of irAEs in lung cancer patients. The levels of IL-5, IFN-α and IFN-γ during treatment were associated with irAEs. 2. Baseline cytokine levels in peripheral blood were not associated with immunotherapy efficacy. The levels of IL-6, IL-8, IL-10, and IL-17 levels during treatment were associated with immunotherapy efficacy.

Globally Relaxed Selection and Local Adaptation in Boechera stricta.

The strength of selection varies among populations and across the genome, but the determinants of efficacy of selection remain unclear. In this study, we used whole-genome sequencing data from 467 Boechera stricta accessions to quantify the strength of selection and characterize the pattern of local adaptation. We found low genetic diversity on 0-fold degenerate sites and conserved non-coding sites, indicating functional constraints on these regions. The estimated distribution of fitness effects and the proportion of fixed substitutions suggest relaxed negative and positive selection in B. stricta. Among the four population groups, the NOR and WES groups have smaller effective population size (Ne), higher proportions of effectively neutral sites, and lower rates of adaptive evolution compared with UTA and COL groups, reflecting the effect of Ne on the efficacy of natural selection. We also found weaker selection on GC-biased sites compared with GC-conservative (unbiased) sites, suggested that GC-biased gene conversion has affected the strength of selection in B. stricta. We found mixed evidence for the role of the recombination rate on the efficacy of selection. The positive and negative selection was stronger in high-recombination regions compared with low-recombination regions in COL but not in other groups. By scanning the genome, we found different subsets of selected genes suggesting differential adaptation among B. stricta groups. These results show that differences in effective population size, nucleotide composition, and recombination rate are important determinants of the efficacy of selection. This study enriches our understanding of the roles of natural selection and local adaptation in shaping genomic variation.

Phylogenomic analyses highlight innovation and introgression in the continental radiations of Fagaceae across the Northern Hemisphere.

Northern Hemisphere forests changed drastically in the early Eocene with the diversification of the oak family (Fagaceae). Cooling climates over the next 20 million years fostered the spread of temperate biomes that became increasingly dominated by oaks and their chestnut relatives. Here we use phylogenomic analyses of nuclear and plastid genomes to investigate the timing and pattern of major macroevolutionary events and ancient genome-wide signatures of hybridization across Fagaceae. Innovation related to seed dispersal is implicated in triggering waves of continental radiations beginning with the rapid diversification of major lineages and resulting in unparalleled transformation of forest dynamics within 15 million years following the K-Pg extinction. We detect introgression at multiple time scales, including ancient events predating the origination of genus-level diversity. As oak lineages moved into newly available temperate habitats in the early Miocene, secondary contact between previously isolated species occurred. This resulted in adaptive introgression, which may have further amplified the diversification of white oaks across Eurasia.

Linked selection shapes the landscape of genomic variation in three oak species.

Natural selection shapes genome-wide patterns of diversity within species and divergence between species. However, quantifying the efficacy of selection and elucidating the relative importance of different types of selection in shaping genomic variation remain challenging. We sequenced whole genomes of 101 individuals of three closely related oak species to track the divergence history, and to dissect the impacts of selective sweeps and background selection on patterns of genomic variation. We estimated that the three species diverged around the late Neogene and experienced a bottleneck during the Pleistocene. We detected genomic regions with elevated relative differentiation ('FST -islands'). Population genetic inferences from the site frequency spectrum and ancestral recombination graph indicated that FST -islands were formed by selective sweeps. We also found extensive positive selection; the fixation of adaptive mutations and reduction neutral diversity around substitutions generated a signature of selective sweeps. Prevalent negative selection and background selection have reduced genetic diversity in both genic and intergenic regions, and contributed substantially to the baseline variation in genetic diversity. Our results demonstrate the importance of linked selection in shaping genomic variation, and illustrate how the extent and strength of different selection models vary across the genome.

Research on Applications of Transurethral Plasmakinetic Enucleation of the Prostate in Elderly Patients Aged ≥80 Years.

Objective: To evaluate the safety and efficacy of transurethral plasmakinetic enucleation of the prostate (PKERP) vs. transurethral resection of the prostate (TURP) in elderly patients aged ≥80 years with benign prostate hyperplasia. Materials and Methods: We conducted a retrospective analysis of the PKERP (n = 123) and TURP (n = 143) in patients aged ≥80 years at urology department of The Third Xiangya Hospital of Central South University from January 2016 to October 2019. Then the preoperative, intraoperative, and postoperative data of different indicators were compared between the two groups. The follow-up was done at 3 months, 1 year after surgical treatment. Results: No significant differences were observed between the two groups for the baseline characteristics, including age, prostate volume, prostate-specific antigen (PSA) level, concurrent disease, maximum urinary flow rate (MFR), international prostate symptoms score (IPSS), and quality of life (QoL) score. The operative time, hemoglobin decrease, and postoperative flushing time were significantly lower in the PKERP group compared with the TURP group. However, no significant differences were observed between both groups for postoperative hospital stay, incidence of transurethral resection syndrome (TURS), prostatic capsular perforation, and genuine urinary incontinence. The follow-up results showed that the MFR of the PKERP group was significantly higher than the TURP group at 1 year after surgery. Conclusion: Compared with TURP, PKERP is a safe and efficacious method for treating patients aged ≥80 years with benign prostate hyperplasia, and it may improve long-term urination symptoms.

A Comprehensive Pan-Cancer Analysis of RBM8A Based on Data Mining.

BACKGROUND: As a member of the exon junction complex (EJC), RNA-binding motif protein 8A (RBM8A) plays a crucial role in the maintenance of mRNA and multiple activities of an organism. Immunotherapy has been proven to be a staple type of cancer treatment. However, the role of RBM8A and immunity across cancer types is unclear. OBJECTIVE: This study aims to visualize the expression, prognosis, mutations, and coexpressed gene results of RBM8A across cancer types and to explore the link between RBM8A expression and immunity. METHODS: In this study, data were collected from multiple online databases. We analyzed the data using the HPA, UALCAN Database, COSMIC, cBioPortal, Cancer Regulome tools, Kaplan-Meier Plotter, and TIMER website. RESULTS: For the expression of RBM8A in normal tissues, higher expression of RBM8A was observed in immune-related cells than in nonimmune organs. The expression level of RBM8A was related to tumor type. Missense mutations in RBM8A were found in most tumors and affected the prognosis of carcinomas with coexpressed genes. RBM8A was strongly associated with immune-infiltrating cells and immune checkpoint inhibitors, especially in LIHC. CONCLUSIONS: RBM8A is a gene worth exploring and may be a unique immune target in the future.

[Advances in gene therapy for ß-thalassemia and hemophilia based on the CRISPR/Cas9 technology].

Thalassemia and hemophilia are common inherited blood disorders caused by genetic abnormalities. These diseases are difficult to cure and can be inherited to the next generation, causing severe family and social burden. The emergence of gene therapy provides a new treatment for genetic diseases. However, since its first clinical trial in 1990, the development of gene therapy has not been as optimistic in the past three decades as one could hope. The development of gene-editing technology, particularly the third generation gene-editing technology CRISPR/Cas9 (clustered regularly interspaced short palindromic repeats/CRISPR-associated protein 9), has given hope in such therapeutic approach for having advantages in high editing efficiency, simple operation, and low cost. Gene editing-mediated gene therapy has thus received increasing attention from the biomedical community. It has shown promises for the treatment of inherited blood disorders, such as thalassemia and hemophilia. This paper reviews the fundamental research progress of gene therapy for ß-thalassemia and hemophilia based on CRISPR/Cas9 technology in the past six years. It also summarizes the CRISPR/Cas9-based clinical trials of gene therapy. The problems and possible solutions to this technology for gene therapy are also discussed, thereby providing a reference for the research on gene therapy of inherited blood disorders based on CRISPR/Cas9 technology.