Objective To investigate the effect of HOX transcriptional antisense RNA (HOTAIR) targeted regulating miR-424 expression on the biological behavior of ovarian cancer cells. Methods Sixty ovarian cancer samples from patients with ovarian cancer and randomly matched 60 benign ovarian tumor tissues were collected during January to June 2018 in the Third Affiliated Hospital of Zunyi Medical University. q-PCR was used to detect the expression of HOX transcript antisense RNA (HOTAIR) in ovarian cancer and adjacent tissues, and analyze the survival rate of ovarian cancer patients with different HOTAIR expression levels, analyze the relationship between the expression level of HOTAIR and the clinicopathological parameters of ovarian cancer patients. A2780 ovarian cancer cells were transfected with small interfering RNA (siRNA) to construct siRNA-HOTAIR (si-HOTAIR) cells as the experimental group, and A2780 ovarian cancer cells transfected with siRNA-NC (si-NC) cells were used as the control group. Dual fluorescence was used to detect the interaction between HOTAIR and miR-424 by the enzyme reporter gene,A2780 cells were used in scratch test to detect the change in the migration ability of ovarian cancer cells after inhibiting HOTAIR,Transwell invasion test was used to detect the change in the invasive ability of ovarian cancer cells after inhibiting HOTAIR, and Flow cytometry was performed to analyze the changes of ovarian cancer cell apoptosis after inhibiting HOTAIR. The nude mouse subcutaneous tumor formation experiment was used to detect the effect of inhibiting HOTAIR on the tumor size and volume of ovarian cancer cells. Results qPCR results showed that the expression of HOTAIR increased significantly in ovarian cancer tissues than in benign ovarian tumor tissues [(58.64±6.32) vs. (6.35±0.02), P<0.05]. The long term survival rate was lower in patients with high expression level of HOTAIR than in patients with low expression level of HOTAIR. Dual-Luciferase reporter gene system showed that HOTAIR can specifically bind to the 3'-UTR of miR-424 [(0.42±0.08) vs. (1.06±0.11), P<0.05]. Scratch test and Transwell invasion test showed that, compared with control group, inhibiting the expression of HOTAIR can inhibit the migration behavior [(21.21±3.08) μm vs. (92.34±8.65) μm, P<0.05] and invasion behavior of ovarian cancer cells in experimental group(28.63%±5.59% vs. 275.36%±21.62%, P<0.05). The results of flow cytometry showed that inhibiting the expression of HOTAIR can enhance the apoptosis of ovarian cancer cells in experimental group (30.2%±2.12% vs. 7.31%±2.01%, t=10.64, P<0.05). In vivo tumor formation experiments in nude mice showed that, compared with control group, the tumor volume and weight of tumor-bearing mice correspondingly decreased [(0.85±0.06) cm³ vs. (3.05±0.28) cm³, t=13.41, P<0.05; (1.12±0.08) g vs. (2.91±0.19) g,t=11.64, P<0.05] after inhibiting HOTAIR expression. Conclusion lncRNA HOTAIR can target miR-424 to regulate the apoptosis, migration and invasion of ovarian cancer cells.

Objective To construct a complete chemical culture system based on small molecule compounds and study its role in promoting the reversal of senescence of mesenchymal stem cells (MSCs). Methods MSCs were transmitted to 20 generations (P20) continuously. The model of the replicative aging cells (P20-MSCs) was established, then divided into aging model group and small molecule treatment group, and the fifth generation of umbilical cord MSCs (P5-MSCs) was set as control group. The aging model group and control group were cultured in the whole chemical culture system for 7 days, and small molecular treatment group was cultured in the whole chemical culture system containing valproate and Repsox for 7 days. β-galactosidase staining was used to detect cell senescence, immunofluorescence staining was used to detect the protein expression levels of Ki-67, OCT4, Nanog,P16, and P21; RT-qPCR to detect the mRNA expression levels of OCT4, Nanog, P16 and P21. Flow cytometry was used to detect the anti-apoptotic ability of cells. Migration experiments, Transwell invasion experiments and clone formation experiments to detect small molecules effects on migration, invasion and self-cloning functions of senescent MSCs. Results The cell bodies of senescent mesenchymal stem cells were enlarged and presented dendritic processes. After incubation in the full chemical culture system, the cells return to a spindle shape or irregular triangle similar to young MSCs. SA-β-gal staining results showed that compared with aging model group, the positive rate of galactosidase in cells treated with small molecules was significantly reduced, and the difference was statistically significant (45.00%±1.23% vs. 84.80%±1.50%, P<0.001). The immunofluorescence results showed that compared with aging model group, the proportion of positive cells expressing Ki-67, OCT4 and Nanog increased (Ki-67: 89.00%±1.50%vs. 25.00%±2.00%, P<0.001; OCT4: 88.40%±0.80% vs. 25.40%±1.20%, P<0.001; Nanog: 76.30%±1.70% vs. 10.50%±0.60%,P<0.001), the proportion of positive cells expressing P16, P21 decreased (P16: 64.00%±3.20% vs. 98.00%±1.50%, P<0.05; P21:45.00%±1.10% vs. 82.00%±2.00%, P<0.05) in small molecule treatment group. RT-qPCR results showed that compared with aging model group, small molecule compounds could up-regulate the mRNA expression levels of OCT4 and Nanog in aging MSCs(P<0.001), down-regulate the mRNA expression levels of P16 and P21 (P<0.05). Compared with aging model group, the abilities of anti-apoptosis (21.60%±1.20% vs. 31.40%±0.80%), migration (49.30%±3.30% vs. 30.60%±4.40%), invasion [(90.00±12.00)cells vs. (34.00±9.00) cells] and self-cloning abilities [(144.00±10.00) cells vs. (68.00±7.00) cells] in small molecule treatment group were significantly increased, and the differences were statistically significant (P<0.05 or P<0.01). Conclusion The constructed small molecule full chemical culture system can inhibit and partially reverse the aging process of long-term cultured MSCs in vitro.

Breast cancer is the most common malignant tumor in the world. Endocrine therapy is an important treatment for HR positive breast cancer, and its drugs are mainly divided into premenopausal estrogen receptor antagonists and postmenopausal aromatase inhibitors, but drug resistance has become a major challenge in endocrine therapy for breast cancer. This article reviews the drug resistance mechanism and the latest research results of endocrine therapy in premenopausal and postmenopausal breast cancer from the aspects of gene regulation, estrogen and coregulatory cofactor, growth factor signal pathway, cell cycle regulation,autophagy and apoptosis, non-coding RNA regulation, immune surveillance, etc., in order to provide a new basis for clinical solution of endocrine therapy resistance in breast cancer.

Hypertension is a common complication of patient with chronic kidney diseases (CKD), and an important risk factor for the development of CKD. Therefore, controlling hypertension is one of the keys to block the progression of CKD. Since the release of 2012 edition "KDIGO clinical practice guideline for management of blood pressure (BP) in patient with chronic kidney disease", new clinical trials has been constantly emerging. Based on this, KDIGO has released a 2021 updated guide. The new guideline covers standardized BP measurements, lifestyle interventions without dialysis, BP management and medication recommendations, and for special CKD population, including kidney transplant patients and children, the corresponding BP management and medication recommendations are recommended. Compared with the previous guideline, standardized BP measurements in the clinic is a new addition. Furthermore, one of the most noteworthy is that the target BP of CKD patients without dialysis is systolic pressure <120 mmHg, which further demonstrates the benefits of intensive hypotensive therapy, but the recommendation level is only 2B. This article launches interpretation for the above several aspects in this new consensus.

Objective To explore the short-term efficacy and safety of golimumab (GLM) for treatment of refractory non-infectious uveitis. Methods Nonrandomized retrospective case series. Forty-six patients in Department of Ophthalmology Beijing Chaoyang Hospital from October 2018 to December 2019 with different types of uveitis that were resistant to treatment with previous immunosuppressors were included in this study. All the patients were treated with GLM (50 mg every four weeks) during at least 3 months. Clinical evaluation and treatment-related side effects were assessed in all included patients. Results At the end of follow up, ocular inflammation was controlled or relieved in 34 patients, the response rate was 73.91%.There was a statistically significant improvement in mean best corrected visual acuity (0.22 vs. 0.26, P=0.002). GLM therapy achieved complete control of inflammation in 9 patients (19.57%). GLM was continuously used in 17 patients (36.96%) without inflammation recurrence, including single GLM treatment in 14 patients, and combination with conventional immunosuppressors in 3 patients. The types of conventional immunosuppressors [M(Q₁, Q₃)] decreased from 2(2, 3) to 1(1, 2) (P<0.001) after GLM treatment. The dosage of prednisone decreased from 38 mg/d [(30, 45) mg/d] at baseline to 8 mg/d [(5, 15) mg/d](P<0.001). The systemic adverse effects associated with GLM therapy were observed in 4 patients, including bacterial pneumonia in 1 patient, anaphylactic reaction in 2 patients, and transaminase elevation in 1 patient. Conclusion GLM can effectively reduce the recurrence of non-infectious refractory uveitis, improve patients' vision, and reduce the combined use of glucocorticoid and immunosuppressors.

Objective To explore the correlation between the components of immune cell subsets in tumor microenvironment of colorectal cancer and the progression of colorectal cancer disease, and to explore the differential regulatory effects of different CD4⁺ T cell subsets on the progression of colorectal cancer. Methods Using the single cell transcriptome sequencing data of colorectal cancer patients in GEO database, CIBERSORTx algorithm was used to assess the immune cell subsets score from the transcriptome sequencing data of colorectal cancer patients in The Cancer Genome Atlas (TCGA) database. The obtained immune cell subsets scores were combined with clinical data to analyze the correlation between metastasis and prognosis. Subsets related genes were calculated based on immune cell subsets scores, and functional enrichment scores performed by using DAVID analysis platform were used to compare the different regulatory function of immune cell subsets in colorectal cancer. Lasso algorithm/regression was used to screen immune cell subsets and Cox analysis was used to construct a risk prognosis model. Results The abundance of CD4-TCF7 was significantly increased in metastatic patients of colorectal cancer compared with non-metastatic patients (P<0.01), the abundance of CD4-CTLA4, CD8-LEF1, PLASMAB-IgG, and MACRO-IL1B decreased in metastatic patients(P<0.05). In the survival analysis, 15 of the 38 immune cell subsets were significantly associated with over survival based on the AUC curve (P<0.05). After analyzing the regulatory functions of CD4⁺ T cell subsets in colorectal cancer cells, we find the CD4-GNLY,CD4-ANXA1 and CD4-CXCR6 with more powerful regulation on the colorectal cancer angiogenesis related pathways compared to others, CD4-IL23R preferentially enriched in energy metabolism related pathways, CD4-GZMK compared to other subsets uniquely enriched in hypoxia stress related pathways, CD4-ANXA1, CD4-TCF7 and CD4-CTLA4 compared to other subsets preferentially enriched in the cell proliferation related pathways, CD4-ANXA1, CD4-TCF7, CD4-CTLA4, and CD4-CXCL13 preferentially enriched in the pathways of cell adhesion and cell migration compared to other subsets. Conclusions There are differences in the regulation of colorectal cancer cell function by immune cell subsets. The composition of immune cell subsets in colorectal cancer immune microenvironment affects the survival and prognosis of patients.

Renal cancer, as a common urinary system tumor, its occurrence and development involve a series of genetic events including changes in the level of epigenetics. Its etiology is complex and highly heterogeneous. Renal cell carcinoma is the chief type of kidney cancer, while the clear cell renal cell carcinoma (CCRCC) is the most common subtype of renal cell carcinoma.Recently, exon sequencing revealed that the mutation rate of polybromo-1 (PBRM1) gene in CCRCC can be as high as 40%. BAF180 protein, which is encoded by PBRM1 gene, is one of the specific subunits of the chromatin remodeling complex PBAF (polybromo-associated BRG1-associated factor), a type of SWItch/sucrose nonfermentable (SWI/SNF) complexes. It not only participates in the formation of PBAF complex, but also mediates the binding of the complex to specific DNA regions, thus affecting the gene transcription and translation processes, so indicates that PBRM1 plays an important role in the occurrence and development of renal cell carcinoma. The research status, molecular mechanism and clinical transformation of the major cancer related genes in CCRCC,especially the tumor suppressor gene PBRM1, were reviewed in present paper, in order to provide reference for the basic and clinical transformation research of SWI/SNF in renal cell carcinoma and other related tumors.

4D printing, which distorts smart materials under specific stimulation, is emerging as a kind of modern fabrication technology. Underpinned by computer science and materialogy, 4D printing combines a wide range of disciplines including physics, bioengineering, medicine with manufacturing industry, and creates three-dimensional solid objects by adding smart materials layer by layer. Compared with 3D printing, 4D printing is functional demand-oriented, and the geometric structure formed by intelligent materials folds, bends, expands or shrinks under specific stimuli such as temperature and water, thus realizing the change of the performance of the object itself, such as hardness, stiffness, permeability and so on. 4D printing would serve as a new way of digital intelligent manufacturing, which emphasizes the need to consider the dynamic tissue healing and regeneration processes within human body. In addition, it can effectively realize the self-repair of the tissue and complete the bionics from structure to function, so it more truly simulates the dynamic evolution of human micro-environment. In this review, we collect the latest cases of 4D printing in biomedicines at home and abroad and then the potential advantages and challenges of 4D printing in practical application will be analyzed. Finally, we propose future directions and perspectives to further promote intelligentized 4D bioprinting technology in imitating architectures and function of native human tissues.

A variety of mechanisms help tumor escape from the recognition and killing by the body immune system. In recent years, the adenosine pathway has been found to play an important role in tumor immune evasion. Adenosine is produced from extracellular adenosine triphosphate (ATP) in the presence of two ectonucleotidases (CD39 and CD73), and exerts specific functions through binding to its receptors [mainly adenosine A2A receptor (A2AR)]. Studies have suggested that the adenosine pathway can be over-activated in the tumor micro-environment, and thus promoting tumor development and progression by generating the immuno-suppressive signals. This review talked about the role of the adenosine pathway in regulating tumor immunity and its potential clinical application value. At the same time, the latest research evidence of adenosine-pathway-related targeted drugs is evaluated and summarized to provide a comprehensive reference for understanding the significance of the adenosine pathway in cancer management.

Periodontitis is a typical osteoimmune disorder characterized by inflammatory absorption of alveolar bone, and is the main cause for loose and fall off teeth in adults. Bacterial antigens stimulate the osteoclasts and aggravate periodontal inflammation, so it is of great significance for treatment of periodontitis to control inflammation and block the resorption of alveolar bone. Milk fat globule epidermal growth factor 8 (MFG-E8), as a lipophilic glycoprotein on the cell membrane, is expressed in multiple organs and histiocytes and participates in the bone immune response. MFG-E8 is involved in the development of osteoinflammatory diseases including periodontitis, so can be used as a new marker for the diagnosis of periodontal disease, and also has the potential of targeted therapy for periodontitis with the aggravation of osteoinflammatory diseases, the decreased expression of MFG-E8, reduction of osteoclasts formation and inhibition of alveolar bone resorption. MFG-E8 may be committed to early diagnosis and intervention to control the disease in order to reduce the economic burden of patients and improve the quality of life, and may become a hot spot for the treatment of periodontitis and other osteoinflammatory diseases in the future. Therefore, the research progress of MFG-E8-mediated osteoimmunology in periodontitis has reviewed in present paper to provide new ideas for clinical diagnosis and treatment of periodontitis.