Objective: To explore the key deubiquitinating enzymes that maintain the stemness of liver cancer stem cells and provide new ideas for targeted liver cancer therapy. Methods: The high-throughput CRISPR screening technology was used to screen the deubiquitinating enzymes that maintain the stemness of liver cancer stem cells. RT-qPCR and Western blot were used to analyze gene expression levels. Stemness of liver cancer cells was detected by spheroid-formation and soft agar colony formation assays. Tumor growth in nude mice was detected by subcutaneous tumor-bearing experiments. Bioinformatics and clinical samples were examined for the clinical significance of target genes. Results: MINDY1 was highly expressed in liver cancer stem cells. The expression of stem markers, the self-renewal ability of cells, and the growth of transplanted tumors were significantly reduced and inhibited after knocking out MINDY1, and its mechanism of action may be related to the regulation of the Wnt signaling pathway. The expression level of MINDY1 was higher in liver cancer tissues than that in adjacent tumors, which was closely related to tumor progression, and its high expression was an independent risk factor for a poor prognosis of liver cancer. Conclusion: The deubiquitinating enzyme MINDY1 promotes stemness in liver cancer cells and is one of the independent predictors of poor prognosis in liver cancer.

To establish and identify induced pluripotent stem cells (iPSCs) derived from patients with Aicardi-Goutières syndrome (AGS) with TREX1 gene 667G>A mutation, and obtain a specific induced pluripotent stem cell model for Aicardi-Goutières syndrome (AGS-iPSCs). A 3-year-old male child with Aicardi-Goutieres syndrome was admitted to Zhongshan People's Hospital in December 2020. After obtaining the informed consent of the patient's family members, 5 ml peripheral blood samples from the patient were collected, and mononuclear cells were isolated. Then,the peripheral blood mononuclear cells(PBMCs) were transduced with OCT3/4, SOX2, c-Myc and Klf4 by using Sendai virus, and PBMCs were reprogrammed into iPSCs. The pluripotency and differentiation ability of the cells were identified by cellular morphological analysis, real-time PCR, alkaline phosphatase staining (AP), immunofluorescence, teratoma formation experiments in mice. The results showed that the induced pluripotent stem cell line of Aicardi-Goutieres syndrome was successfully constructed and showed typical embryonic stem-like morphology after stable passage, RT-PCR showed mRNA expression of stem cell markers, AP staining was positive, OCT4, SOX2, NANOG, SSEA4, TRA-1-81 and TRA-1-60 pluripotency marker proteins were strongly expressed. In vivo teratoma formation experiments showed that iPSCs differentiate into the ectoderm (neural tube like tissue), mesoderm (vascular wall tissue) and endoderm (glandular tissue). Karyotype analysis also confirmed that iPSCs still maintained the original karyotype (46, XY). In conclusion, induced pluripotent stem cell line for Aicardi-Goutières syndrome was successfully established using Sendai virus, which provided an important model platform for studying the pathogenesis of the disease and for drug screening.

To summarize the clinicopathological features and prognosis of kidney injury after hematopoietic stem cell transplantation (HSCT), to provide basis for preventing its occurrence and development. By using a retrospective cohort study method, we collected the clinical and renal biopsy pathological data of all the patients who hospitalized in the Department of Nephrology of Peking University First Hospital from June 2011 to June 2021 with renal injury after HSCT and underwent renal biopsy, and prognosis was followed up by telephone. The clinical laboratory characteristics, renal pathology and prognosis, and their association were analyzed. The results showed that the most common clinical phenotype was chronic kidney disease (CKD,69.2%, 18/26), in this term 13/18 patients received stem cells from haploidentical donors, and 11/18 patients experienced with extrarenal graft-versus-host disease (GVHD). The most common pathologic phenotype was thrombotic microangiopathy (TMA, 61.5%, 16/26). Renal function returned to baseline level in 6 patients, and the kidney survival at 2 years and 5 years were 95.7% (22/23) and 87.5% (14/16), respectively. In conclusion, the clinical phenotype of renal injury after HSCT were mainly CKD, and the most common pathologic phenotype was TMA, the long-term prognosis was favourable.

Acute myeloid leukemia (AML) is a heterogeneous hematopoietic tumor originated from hematopoietic stem cells. FLT3 is an important receptor tyrosine kinase in cell signal transduction pathway and one of the common mutated genes in AML. AML patients with FLT3-ITD mutation have a poor prognosis and tendency to relapse. Therefore, early identification of FLT3 gene mutation and selection of appropriate treatment are particularly important. Currently, the small moleculetargeted drugs have been new treatment methods for AML patients with FLT3-ITD mutation, but accompanied drug resistance need to be solved. This paper reviews the mechanism of FLT3 mutation, the clinical significance of FLT3 mutation in AML, FLT3 inhibitors and drug resistance mechanism.

With the development of molecular biology techniques, the people's understanding of myelodysplastic syndromes (MDS) has greatly improved, a heterogeneous hematopoietic pre-malignant disorder of the stem cells. Gene mutations include RNA splicing, DNA methylation, chromosome modification, transcription factors, signal transduction kinases, RAS pathways, cohesion complexes, DNA repair, etc. Gene mutation is the determinant of diagnostic typing and therapeutic efficacy of MDS. The new concepts of CHIP and ICUS have aroused people's attention to the elderly patients with clonal hematopoiesis and non-clonal cytopenia but without MDS characteristics, who have the possibility of high-risk transformation to MDS and leukemia. In order to better understand the pathogenesis of MDS, the significance of gene mutations, CHIP and ICUS in the diagnosis and prognosis of MDS were reviewed in this paper.

To explore the clinical characteristics, treatment, and prognosis of patients with blastic plasmacytoid dendritic cell neoplasm(BPDCN).

To explore the chronic injury and its possible mechanism of ionizing radiation on multipotent hematopoietic progenitor cells (MPPs) by determining the related indicators of MPPs in bone marrow of mice post-radiation.

Objective To investigate the effects of miR-877-3p on migration and apoptotic T lymphocytes of bone mesenchymal stem cells (BMSCs). Methods The model of osteoporosis induced by bilateral ovariectomy (OVX) and sham operation was established. At 8 weeks after operation, the bone parameters of the two groups were detected by micro-CT. The levels of monocyte chemotactic protein 1(MCP-1) in BMSCs were detected by ELISA. BMSC in OVX group and sham group were co-cultured with T lymphocytes, respectively. The migration ability of T lymphocytes in the two groups was observed by TranswellTM assay with PKH26 staining and apoptosis of T lymphocytes were detected by flow cytometry. Reverse transcription PCR was used to detect the expression of miR-877-3p in BMSCs. miR-877-3p was overexpressed or down-regulated by cell transfection. The level of MCP-1 secreted by BMSCs in each group was detected by ELISA. The migration and apoptosis of T lymphocytes were detected by the above methods. Results The number of trabecular bone and bone mineral density in OVX group were lower than those in sham group. The levels of MCP-1 secretion, chemotactic and apoptotic T lymphocyte ability of BMSCs in OVX group were also lower than those in sham group. The expression level of miR-877-3p in BMSC in OVX group was higher than that in sham group. After overexpression of BMSC miR-877-3p, the levels of MCP-1 secreted from BMSCs, and apoptotic T lymphocytes decreased, while the results were opposite after down-regulation of miR-877-3p. Conclusion miR-877-3p may be one of the causes of osteoporosis by inhibiting MCP-1 secretion of BMSCs and the migration and apoptosis of T lymphocytes.

It has been well documented that exercise can improve bone metabolism, promote bone growth and development, and alleviate bone loss. MicroRNAs (miRNAs) are widely involved in the proliferation and differentiation of bone marrow mesenchymal stem cells, osteoblasts, osteoclasts and other bone tissue cells, and regulation of balance between bone formation and bone resorption by targeting osteogenic factors or bone resorption factors. Thus miRNAs play an important role in the regulation of bone metabolism. Recently, regulation of miRNAs are shown to be one of the ways by which exercise or mechanical stress promotes the positive balance of bone metabolism. Exercise induces changes of miRNAs expression in bone tissue and regulates the expression of related osteogenic factors or bone resorption factors, to further strengthen the osteogenic effect of exercise. This review summarizes relevant studies on the mechanism whereby exercise regulates bone metabolism via miRNAs, providing a theoretical basis for osteoporosis prevention and treatment with exercise.

To review the research progress of the feasibility of a new treatment method for atrophic rhinitis (ATR) based on tissue engineering technology (seed cells, scaffold materials, and growth factors), and provide new ideas for the treatment of ATR.

To summarize the research progress of stem cell transplantation in treating spinal cord injury (SCI) at different stages based on the pathophysiological mechanism of SCI.

To prepare customized porous silicone orbital implants using embedded 3D printing and assess the effect of surface modification on the properties of the implants.

To investigate the effect of Zuogui Jiangtang Jieyu Decoction (ZJJ) on Shh signaling and self-renewal of neural stem cells in the hippocampal dentate gyrus of diabetic rats with depression.

The scientific basis of acupuncture on mesenchymal stem cells (MSCs) for treating ischemic stroke (IS) is discussed. MSCs transplantation has great potential for the treatment of tissue damage caused by early stage inflammatory cascade reactions of IS, but its actual transformation is limited by various factors. How to improve the homing efficiency of MSCs is the primary issue to enhance its efficacy. As such, the possible mechanisms of acupuncture and MSCs transplantation in inhibiting inflammatory cascade reactions induced by IS are explored by reviewing literature, and a hypothesis that acupuncture could promote the secretion of stromal cell-derived factor-1α (SDF-1α) from ischemic foci to regulate SDF-1α/CXC chemokine receptor 4 (CXCR4) axis, thereby improving the homing efficiency of MSCs transplantation, exerting its neuroprotective function, and improving the bed transformation ability, is proposed.

Objective: To investigate the effect of SIX2 gene on the proliferation of bovine skeletal muscle satellite cells. Methods: Bovine skeletal muscle satellite cells were used as experimental materials, and the expression of SIX2 gene in bovine skeletal muscle satellite cells was detected by real-time quantitative PCR at 24 h, 48 h, and 72 h of proliferation. The SIX2 gene overexpression vector was constructed by homologous recombination. The SIX2 gene overexpression plasmid and the control empty plasmid were transfected into bovine skeletal muscle satellite cells, and each group had three complex Wells. The cell viability was detected by MTT assay at 24 h, 48 h and 72 h after transfection. At 48 h after transfection, the cell cycle was detected by flow cytometry, and the expressions of cell proliferation marker genes were detected by real-time quantitative PCR (qRT-PCR) and Western blot. Results: With the proliferation of bovine skeletal muscle satellite cells, the expression of SIX2 mRNA was increased. Compared with the control group, the expressions of SIX2 mRNA and protein in the SIX2 gene overexpression plasmid group were increased by 18 and 2.6 times, respectively (P＜0.01). The cell viability of the SIX2 gene overexpression plasmid group was increased (P＜0.01), the proportion of G1 cells was decreased by 24.6%, and the proportion of S phase and G2 phase cells was increased by 20.3% and 4.31%, respectively (P＜0.01). The mRNA and protein expressions of Pax7 gene were increased by 15.84 and 1.22 times, respectively, and the mRNA and protein expressions of proliferation marker genes PCNA and CCNB1 were increased by 4.82, 2.23,1.55 and 1.46 times, respectively (P＜0.01). Conclusion: Overexpression of SIX2 gene promotes the proliferation of bovine skeletal muscle satellite cells.

To explore whether the differentiation of vascular stem cells (VSC) into smooth muscle cells (SMC) in aortic dissection (AD) is dysregulated, and to verify the role of Notch3 pathway in this process.

To explore the therapeutic effect of transplantation of menstrual blood stem cells (MenSCs) in rats with thin endometrium.

Corneal organoids are cornea-like tissue structures that are developed from induced pluripotent stem cells or embryonic stem cells in vitro. They have similar anatomical characteristics and gene expression profiles to the human cornea. Although the culture of corneal organoids is difficult, expensive, and time-consuming, they can be tailored to reconstruct the physiological environment and the interaction between corneal cells in each layer, which suggests broad application prospects. In this article, we review the latest research progress and summarize the application of corneal organoids in the research of corneal development mechanisms, keratopathy pathogenesis, donor corneal transplantation, and corneal organoids-on-a-chip, in order to provide reference for further clinical corneal research concerning keratopathy models, drug screening, and personalized medicine.

Objective: To analyze the clinical features and treatment outcomes of eyes with contact lens-induced limbal stem cell deficiency (CL-iLSCD). Methods: This cross-sectional study involved patients diagnosed with CL-iLSCD at the Eye, Ear, Nose & Throat Hospital of Fudan University between October 2018 and September 2022. A total of 17 patients (25 eyes) with a mean age of (36.4±6.9) years were enrolled. Among them, 14 were females (82.4%). Corneal and limbal abnormalities, especially the range of epitheliopathy, were observed under a slit lamp biomicroscope with fluorescein staining. Anterior segment optical coherence tomography and in vivo laser scanning confocal microscopy were performed to obtain the central corneal epithelial thickness, density of basal epithelial cells and corneal nerve fiber length. The clinical features of CL-iLSCD, along with their treatment outcomes and related risk factors, were analyzed. Results: All patients wore soft contact lenses, with an average daily wearing time of (10.5±2.5) hours and a median wearing duration of 10 (4 to 30) years. Ocular symptoms, including decreased vision, ocular discomfort or pain, redness, and photophobia, were present in 22 eyes (88.0%). The most characteristic clinical sign of CL-iLSCD was comb-or whorl-pattern late fluorescein staining under cobalt blue light, which was most commonly seen at the superior limbus (25/25, 100.0%). Additionally, reductions in central corneal epithelial thickness, basal cell density, and corneal nerve fiber length were observed. A comprehensive score was assigned to each eye based on clinical findings and in vivo imaging biomarkers. LSCD was mild, moderate, and severe in 5, 11, and 8 eyes, respectively. A history of misdiagnosis was found in 20 eyes (80.0%). After discontinuing the use of contact lenses and receiving medical treatment, significant improvement was observed in all eyes, with 13 eyes fully recovered. Conclusions: The symptoms and clinical signs of CL-iLSCD can be subtle at the early stage. Discontinuing contact lens wear and medication are effective to treat CL-iLSCD.