Single-cell analyses reveal evolution mimicry during the specification of breast cancer subtype.

Background: The stem or progenitor antecedents confer developmental plasticity and unique cell identities to cancer cells via genetic and epigenetic programs. A comprehensive characterization and mapping of the cell-of-origin of breast cancer using novel technologies to unveil novel subtype-specific therapeutic targets is still absent. Methods: We integrated 195,144 high-quality cells from normal breast tissues and 406,501 high-quality cells from primary breast cancer samples to create a large-scale single-cell atlas of human normal and cancerous breasts. Potential heterogeneous origin of malignant cells was explored by contrasting cancer cells against reference normal epithelial cells. Multi-omics analyses and both in vitro and in vivo experiments were performed to screen and validate potential subtype-specific treatment targets. Novel biomarkers of identified immune and stromal cell subpopulations were validated by immunohistochemistry in our cohort. Results: Tumor stratification based on cancer cell-of-origin patterns correlated with clinical outcomes, genomic aberrations and diverse microenvironment constitutions. We found that the luminal progenitor (LP) subtype was robustly associated with poor prognosis, genomic instability and dysfunctional immune microenvironment. However, the LP subtype patients were sensitive to neoadjuvant chemotherapy (NAC), PARP inhibitors (PARPi) and immunotherapy. The LP subtype-specific target PLK1 was investigated by both in vitro and in vivo experiments. Besides, large-scale single-cell profiling of breast cancer inspired us to identify a range of clinically relevant immune and stromal cell subpopulations, including subsets of innate lymphoid cells (ILCs), macrophages and endothelial cells. Conclusion: The present single-cell study revealed the cellular repertoire and cell-of-origin patterns of breast cancer. Combining single-cell and bulk transcriptome data, we elucidated the evolution mimicry from normal to malignant subtypes and expounded the LP subtype with vital clinical implications. Novel immune and stromal cell subpopulations of breast cancer identified in our study could be potential therapeutic targets. Taken together, Our findings lay the foundation for the precise prognostic and therapeutic stratification of breast cancer.

A human-specific insertion promotes cell proliferation and migration by enhancing TBC1D8B expression.

Human-specific insertions play important roles in human phenotypes and diseases. Here we reported a 446-bp insertion (Insert-446) in intron 11 of the TBC1D8B gene, located on chromosome X, and traced its origin to a portion of intron 6 of the EBF1 gene on chromosome 5. Interestingly, Insert-446 was present in the human Neanderthal and Denisovans genomes, and was fixed in humans after human-chimpanzee divergence. We have demonstrated that Insert-446 acts as an enhancer through binding transcript factors that promotes a higher expression of human TBC1D8B gene as compared with orthologs in macaques. In addition, over-expression TBC1D8B promoted cell proliferation and migration through "a dual finger" catalytic mechanism (Arg538 and Gln573) in the TBC domain in vitro and knockdown of TBC1D8B attenuated tumorigenesis in vivo. Knockout of Insert-446 prevented cell proliferation and migration in cancer and normal cells. Our results reveal that the human-specific Insert-446 promotes cell proliferation and migration by upregulating the expression of TBC1D8B gene. These findings provide a significant insight into the effects of human-specific insertions on evolution.

Genomic alterations affecting tumor-infiltrating lymphocytes and PD-L1 expression patterns in triple-negative breast cancer.

BACKGROUND: Tumor-infiltrating lymphocytes (TILs) and programmed cell death 1 ligand 1 (PD-L1) remain imperfect in predicting clinical outcomes of triple-negative breast cancer because outcomes do not always correlate with the expression of these biomarkers. Genomic and transcriptomic alterations that may contribute to the expression of these biomarkers remain incompletely uncovered. METHODS: We evaluated PD-L1 immunohistochemistry scores (SP142 and 28-8 assays) and TILs in our triple-negative breast cancer multiomics dataset and 2 immunotherapy clinical trial cohorts. Then, we analyzed genomic and transcriptomic alterations correlated with TILs, PD-L1 expression, and patient outcomes. RESULTS: Despite TILs serving as a decent predictor for triple-negative breast cancer clinical outcomes, exceptions remained. Our study revealed that several genomic alterations were correlated with unexpected events. In particular, PD-L1 expression may cause a paradoxical relationship between TILs and prognosis in certain patients. Consequently, we classified triple-negative breast cancers into 4 groups based on PD-L1 and TIL levels. The TIL-negative PD-L1-positive and TIL-positive PD-L1-negative groups were not typical "hot" tumors; both were associated with worse prognoses and lower immunotherapy efficacy than TIL-positive PD-L1-positive tumors. Copy number variation of PD-L1 and oncogenic signaling activation were correlated with PD-L1 expression in the TIL-negative PD-L1-positive group, whereas GSK3B-induced degradation may cause undetectable PD-L1 expression in the TIL-positive PD-L1-negative group. These factors have the potential to affect the predictive function of both PD-L1 and TILs. CONCLUSIONS: Several genomic and transcriptomic alterations may cause paradoxical effects among TILs, PD-L1 expression, and prognosis in triple-negative breast cancer. Investigating and targeting these factors will advance precision immunotherapy for patients with this disease.

Clinical and pathological features and differential diagnosis of fibro-osseous tumors and dysplasias / 中华口腔医学杂志

Fibro-osseous lesions is a class of diseases with obvious similarities in clinical manifestations and pathological features, which has been attracting the attention of clinicians and pathologists. The latest WHO 2022 Classification (5th edition) included six of these diseases (cemento-osseous dysplasia, segmental odontomaxillary dysplasia, fibrous dysplasia, juvenile trabecular ossifying fibroma, psammomatoid ossifying fibroma and familial gigantiform cementoma) in the " fibro-osseous tumours and dysplasias ", and put forward new ideas on the diagnosis and treatment of these diseases. According to the latest WHO 2022 Classification (5th edition), the clinical and pathological features, diagnosis and differential diagnosis of these six diseases were described.

Research progress of tunneling nanotube in bone biology / 中华口腔医学杂志

Tunneling nanotube (TNT) is a newly discovered communication mode between animal cells in recent years, which have important physiological and pathological significance. However, the role of TNT in bone biology is still unclear. At present, there are many reports about tunneling nanotubes in bone marrow mesenchymal stem cells, osteoclast precursor cells, osteoblasts and immune cells. This review describes the research advances of TNT and its research progress in bone biology. It looks forward to the research direction of TNT in oral and maxillofacial bone development and bone biology, to provide new strategies for the maintenance of bone homeostasis and the treatment of bone diseases.

An applied research on precise sustentacular screw placement based on anatomical division of the anterior lateral wall of calcaneus and the sustentaculum tali / 中华创伤骨科杂志

Objective:To evaluate our novel path based on anatomical division of the anterior lateral wall of calcaneus and the sustentaculum tali for precise sustentacular screw placement in the surgical treatment of calcaneal fractures of Sanders types Ⅱ and Ⅲ.Methods:The anterior lateral wall of the calcaneus was divided into the anterior-superior zone S 1, the anterior-inferior zone S 2, the posterior-superior zone S 3 and the posterior-inferior zone S 4 for demarcation of the screw insertion points by our method of Four Zones, and into the front, middle and rear sections by our method of Three Sections for demarcation of the screw target points. The specimens were scanned by CT and modeled by Mimics. On the 3D virtual model of the calcaneus, one screw was placed from each zone of the anterior lateral wall of the calcaneus to the sustentaculum tali body. The screw placement target for S 1 and S 2 was the medial intersection point P 1 of the front and middle sections of the sustentaculum tali, and that for S 3 and S 4 was the medial intersection point P 2 of the middle and rear sections of the sustentaculum tali. It was observed whether the screws were placed in the bone channel. A total of 72 patients were included who had been admitted to Department of Orthopaedics, Suqian Hospital Affiliated to Xuzhou Medical University for calcaneal fractures of Sanders types Ⅱ and Ⅲ from January 2017 to January 2021. They were divided into an anatomical division group and a 3D printing group according to their screw placement method for the sustentaculum tali. In the anatomical division group of 32 patients subjected to screw placement based on our anatomical division, there were 25 males and 7 females, aged from 24 to 60 years; in the 3D printing group of 40 patients subjected to screw placement assisted by 3D printing, there were 31 males and 9 females, aged from 25 to 58 years. The disparities between the parameters of sustentacular screw placement and the actual values were compared in the anatomical division group, and the total number of screws, screws on average, distribution of screws, and accuracy of screw placement were compared between the 2 groups. Results:All the screws which were virtually placed in the specimens of the calcaneus from S 1 and S 2 to P 1 and from S 3 and S 4 to P 2 passed through the bony channel, with no perforation into the tarsal sinus. There was no significant difference in the general date between the anatomical division group and the 3D printing group, showing they were comparable ( P > 0.05). In the anatomical division group, a total of 52 screws were placed to the sustentaculum tali with an average of (1.63 ± 0.48) screws per patient, and 2 screws were placed in 20 patients, yielding an accuracy rate of screw placement of 92.3% (48/52). There were no statistically significant differences between the parameters and the actual values of screw placement in the anatomical division group ( P > 0.05). In the 3D printing group, a total of 63 screws were placed to the sustentaculum tali with an average of (1.58 ± 0.49) screws per patient, and 2 screws were placed in 23 patients, yielding an accuracy rate of screw placement of 93.7% (59/63). There were no significant differences in the above comparisons between the anatomical division group and the 3D printing group ( P > 0.05). Conclusion:In the surgical treatment of calcaneal fractures of Sanders types Ⅱ and Ⅲ, the sustentacular screw placement based on our anatomical division of the anterior lateral wall of the calcaneus and the sustentaculum tali can lead to similar clinical accuracy as 3D printing-assisted screw placement does.

Breast cancer animal models and applications.

Breast cancer is the most common malignancy in women. Basic and translational breast cancer research relies heavily on experimental animal models. Ideally, such models for breast cancer should have commonality with human breast cancer in terms of tumor etiology, biological behavior, pathology, and response to therapeutics. This review introduces current progress in different breast cancer experimental animal models and analyzes their characteristics, advantages, disadvantages, and potential applications. Finally, we propose future research directions for breast cancer animal models.

A new Schiff base copper(II) complex induces cancer cell growth inhibition and apoptosis by multiple mechanisms.

A new Schiff base copper(II) complex [N,N'-bis(2'-hydroxyphenylacetone)-o-ethanediamine] copper (II) (M1) has been synthesized and characterized by single X-ray crystallography. The cytotoxicity of complex M1 was evaluated against HeLa, LoVo, A549, A549/cis cancer cell lines, and the normal cell lines LO2 and HUVEC, by MTT (3-(4,5-dimethylthiazoyl-2-yl)2,5-diphenyltetrazoliumbromide) assays. The IC50 (50% inhibition concentrations) is in the range of 5.13-11.68 µM, which is somewhat lower than cisplatin on the basis of platinum molar concentration. Furthermore, anticancer mechanistic studies showed that the complex M1 inhibited cell proliferation by blocking DNA synthesis and then acted on nuclear division of HeLa cells over time. Moreover, M1 increased intracellular ROS (Reactive oxygen species) levels in a dose-dependent manner. Western blot analysis indicated M1 dramatically decrease c-Myc transcription factor and KLF5 (Krüppel-like factor 5) protein expression levels in HeLa. M1 did not inhibit proteasomal activity. Finally, M1 induced DNA damages and activated the DNA damage repair pathways.

UCH-L1-mediated Down-regulation of Estrogen Receptor α Contributes to Insensitivity to Endocrine Therapy for Breast Cancer.

Purpose: To determine the role of UCH-L1 in regulating ERα expression, and to evaluate whether therapeutic targeting of UCH-L1 can enhance the efficacy of anti-estrogen therapy against breast cancer with loss or reduction of ERα. Methods: Expressions of UCH-L1 and ERα were examined in breast cancer cells and patient specimens. The associations between UCH-L1 and ERα, therapeutic response and prognosis in breast cancer patients were analyzed using multiple databases. The molecular pathways by which UCH-L1 regulates ERα were analyzed using immunoblotting, qRT-PCR, immunoprecipitation, ubiquitination, luciferase and ChIP assays. The effects of UCH-L1 inhibition on the efficacy of tamoxifen in ERα (-) breast cancer cells were tested both in vivo and in vitro. Results: UCH-L1 expression was conversely correlated with ERα status in breast cancer, and the negative regulatory effect of UCH-L1 on ERα was mediated by the deubiquitinase-mediated stability of EGFR, which suppresses ERα transcription. High expression of UCH-L1 was associated with poor therapeutic response and prognosis in patients with breast cancer. Up-regulation of ERα caused by UCH-L1 inhibition could significantly enhance the efficacy of tamoxifen and fulvestrant in ERα (-) breast cancer both in vivo and in vitro. Conclusions: Our results reveal an important role of UCH-L1 in modulating ERα status and demonstrate the involvement of UCH-L1-EGFR signaling pathway, suggesting that UCH-L1 may serve as a novel adjuvant target for treatment of hormone therapy-insensitive breast cancers. Targeting UCH-L1 to sensitize ER negative breast cancer to anti-estrogen therapy might represent a new therapeutic strategy that warrants further exploration.

Treatment of intra-articular calcaneal fractures with precise screw placement into sustentaculum tali based on virtual and simulation techniques / 中华创伤骨科杂志

Objective:To evaluate the clinical application of virtual and simulation techniques to aid pre-operative design for precise screw placement into the sustentaculum tali in the treatment of intra-articular calcaneal fractures.Methods:From January 2016 to January 2019, 68 patients were treated at Department of Orthopaedics, Suqian Hospital Affiliated to Xuzhou Medical University for intra-articular calcaneal fractures of Sanders types Ⅱ-Ⅳ. According to different designs of screw placement into the sustentaculum tali, they were assigned into a control group (38 cases and 42 feet) and an observation group (30 cases and 33 feet). There were 24 males and 14 females with an age of 39.3 years±8.8 years in the control group. There were 17 males and 13 females with an age of 42.0 years ± 7.6 years in the observation group. The control group was given a routine placement design based on the X-ray and MSCT scanning images of the injured feet. In the observation group, a Mimics model was first constructed using the X-ray and MSCT scanning images of the normal or less injured feet for further virtual screw placement into the sustentaculum tali on a 3D printed model. The disparity was investigated between the parameters designed and the actual values in both groups. The 2 groups were compared in terms of average placements, screw distribution, placement accuracy, placement time and Maryland scores of foot function one year after operation.Results:There were no significant differences in the preoperative general data between the 2 groups, showing comparability ( P>0.05). The design parameters and actual values in the control group were respectively as follows: 17.7°±3.2° versus 15.1°±5.9° in upward oblique angle, 20.3°±2.1° versus 16.2°±6.8° in backward oblique angle, and 47.9 mm ± 3.8 mm versus 45.4 mm ± 4.2 mm in length of screw path, showing significant differences ( P< 0.05). The design parameters and actual values in the observation group were as follows: 16.5°±3.5° versus 17.1°±3.9° in upward oblique angle, 20.9°±4.3° and 19.6°±3.8° in backward oblique angle, and 48.1 mm ± 3.1 mm versus 47.3 mm ± 3.8 mm in length of screw path, showing insignificant differences ( P>0.05). The average screw placements into the sustenta culum tali in the observation group (1.6±0.5) were significantly more than those in the control group (1.2±0.4). Compared with the control group, the observation group had a higher rate of placement of 2 screws[60.6 % (20/23) versus 16.7% (7/42)], higher accuracy of placement [94.3% (50/53) versus 77.6% (38/49)], less placement time for each screw (9.6 mm±3.9 min versus 13.2 mm±4.7 mm), less placement time for each foot (15.6 mm±4.8 min versus 20.5 mm±3.8 mm), and higher Maryland scores at one year after operation (94.2±6.5 versus 89.7±6.9). All the above comparisons were statistically significant ( P<0.05). Conclusions:Application of virtual and simulation techniques to aid pre-operative design for precise screw placement into the sustentaculum tali can improve the outcomes of intra-articular calcaneal fractures, because it increases the number of screws placed, enhances quality of screw placement, shortens operation time, and thus facilitates functional recovery of the injured foot.

Polarity of ameloblasts and odontoblasts and their related regulators / 华西口腔医学杂志

The polarity of ameloblasts and odontoblasts is crucial for their differentiation and function. Polarity-related molecules play an important role in this process. This review summarizes the process of polarity formation of ameloblasts and odontoblasts and their related regulators.

Expressions of cell polarity related proteins CDC42and PAR3 during tooth germ development in mice / 吉林大学学报(医学版)

Objective:To study the expressions of cell polarity related proteins CDC42 and PAR3 during tooth germ development in the mice,and to discuss their possible roles during tooth development in the mice.Methods:The whole heads were obtained from the mouse embryo on the days 13.5,14.5,16.5 and 18.5 (E13.5,E14.5,E16.5 and E18.5) and the mice on the postnatal days 1 (PN1) and 5 (PN5).The tissues were fixed in paraformaldehyde,decalcified,dehydrated,embedded in paraffin,and sectioned.The histology of tooth germ was observed by HE staining.The expressions of CDC42 and PAR3 during tooth germ development were detected by immunohistochemistry staining.Results:The HE staining results showed that E13.5,E14.5,E16.5 and E18.5were the bud stage,the cap stage,the early and the late bell stage of tooth germ development,respectively;the tooth germ of PN1 mice showed the matured odontoblasts and ameloblasts;the tooth germ of PN5 mice showed the completed tooth crown development.The immunohistochemistry staining results showed that CDC42 expressed in the tooth germ of the mice at E13.5,E14.5 and E16.5;the CDC42 expression at E 18.5 was reduced compared with E13.5,E14.5 and E16.5;CDC42 mainly expressed in the odontoblasts and ameloblasts of the tooth germ of the mice at PN1 and PN5;PAR3 weakly expressed in the tooth germ of the mice at E13.5 and E14.5,and it was increased at E16.5 and E18.5.At PN1 and PN5,the expressions of PAR3 were decreased compared with E18.5.Conclusion:CDC42 and PAR3 partieipat in the mouse tooth development;during the early stage of tooth germ development,they may be involved in the proliferation and migration of mouse dental germ;during the late stage,CD42 and PAR3 may be involved in the differentiation of the odontoblasts and the ameloblasts,especially in the establishment and maintenance of cell polarity.

The role of bone morphogenetic protein signaling pathway in tooth root development / 华西口腔医学杂志

The bone morphogenetic protein (BMP) family is an important factor in the regulation of cell ular life activities and in the development of almost all tissues. BMP-mediated signaling plays an important role in tooth root development, which is a part of tooth development. Epithelial and mesenchymal interactions are involved in tooth root development, but the BMP signaling pathway has a different effect on tooth root development in epithelial and mesenchymal. This review summarizes the advances of BMP signaling in tooth root development.

Mifepristone derivative FZU-00,033 suppresses triple-negative breast cancer cell viability via down-regula-ting KLF5 expression / 医学研究生学报

Objective Mifepristone (MIF) can inhibit triple-negative breast cancer cell (TNBC) survival at high concentra-tions. The purpose of the present study is to study the effect of mifepristone derivatives on triple-negative breast cancer cell (TNBC) survival at low concentrations. Methods SUM149PT and HCC1937 triple negative breast cancer cells were used in the study; the experiment was set in four groups: DMSO group,MIF group(10 μmol/L MIF),5 μmol/L FZU-00,033 group and 10 μmol/L FZU-00,033 group. They were treated with 24,48,72 h,and cell viability was measured by SRB. KLF5 overexpression HCC1937 cell line was used in the study; the experiment was set in four groups: PCDH-DMSO group(PCDH vector,DMSO),PCDH-FZU-00,033 group (PCDH vector,10 μmol/L FZU-00,033),KLF5-DMSO group(overexpress KLF5,DMSO),KLF5-FZU-00,033 group(overexpress KLF5,10 μmol/L FZU-00,033). Cell apoptosis was investigated by detecting PARP cleavage using Western blot. In order to investi-gate how FZU-00,033 reduced cell viability,we detected KLF5 protein expression after drug treatment. On the basic of the original PC-DH-DMSO group,PCDH-FZU-00,033 group,KLF5-DMSO group and KLF5-FZU-00,033 group,5 μmol/L PCDH-FZU-00,033 group (PCDH vector,5 μmol/L FZU-00,033),5 μmol/L KLF5-FZU-00,033 group(overexpress KLF5,5 μmol/L FZU-00,033). Western blot was used to detect the effect of FZU-00,033 in KLF5 overexpression cell line. Results Compared with DMSO group,5 μmol/L FZU-00,033 group,10 μmol/L FZU-00,033 group and MIF group decreasd TNBC cell viability more efficiently at 24,48,72h (P<0.01); the cell survival rate of DMSO group,5 μmol/L FZU-00,033 group,10 μmol/L FZU-00,033 group and MIF group was [(100±4)%,(17±2)%,(5±1)%,(58±1)%] respectively in SUM149PT cell line and was [(100±7)%,(39±1)%,(30±1)%,(62±1)%] respectively in HCC1937 cell line. Compared with MIF group,5 μmol/L FZU-00,033 group and 10 μmol/L FZU-00,033 group decreasd TNBC cell viability more efficiently at 24,48,72 h (P<0.01). Compared with DMSO group,5 μmol/L FZU-00,033 group,10 μmol/L FZU-00,033 group and MIF group suppressed KLF5 expression more potently and increased cell apoptosis. Com-pared with 10 μmol/L MIF group,5 μmol/L FZU-00,033 group and 10 μmol/L FZU-00,033 group significantly increased apoptosis. Compared with PCDH-DMSO group,10 μmol/L PCDH-FZU-00,033 group decreasd TNBC cell viability more efficiently at 48,72 h and cell survial rate was [(100±6)% vs (39±2)%,P<0.05] and [(100±3)% vs (21±1)%,P<0.05] respectively. Compared with KLF5-DMSO group,10 μmol/L KLF5-FZU-00,033 group decreasd TNBC cell viability more efficiently at 48,72h and cell survial rate was [(100±1)% vs (47±1)%,P<0.05] and [(100±1)% vs (27±1)%,P<0.05] respectively; Meanwhile,Compared with 10 μmol/L PCDH-FZU-00,033 group,10 μmol/L KLF5-FZU-00,033 group increased TNBC cell viability more efficiently at 48,72 h (P<0.05). Compared with PCDH-DMSO group,5 μmol/L PCDH-FZU-00,033 group and 10 μmol/L PCDH-FZU-00,033 group in-creased cell apoptosis; Compared with KLF5-DMSO group,5 μmol/L KLF5-FZU-00,033 group and 10 μmol/L KLF5-FZU-00,033 group increased cell apoptosis. Conclusion Novel mifepristone derivative FZU-00,033 suppressed TNBC cell viability partially through suppressing KLF5 expression.

The regulatory mechanisms and functional roles of the Hippo signaling pathway in breast cancer.

Hippo signaling pathway has attracted broad attention due to its essential roles in controlling organ size and tumorigenesis. TAZ/YAP, two core downstream molecules of the Hippo signaling pathway in mammals, are tightly regulated by a wide range of extracellular and intrinsic signals in both Hippo signaling pathway-dependent and -independent manners. Besides their roles in the development and function of normal mammary glands, TAZ/YAP display remarkable potency and relevance to multiple aspects of human breast carcinogenesis, including cellular proliferation, differentiation, apoptosis, migration, invasion, epithelial-mesenchymal transition and stemness. In this review, we summarize the regulators of TAZ/YAP, discuss the significant contribution of the Hippo signaling pathway to human breast cancers and highlight their potential therapeutic roles.

Tree shrew (Tupaia belangeri) as a novel laboratory disease animal model.

The tree shrew (Tupaia belangeri) is a promising laboratory animal that possesses a closer genetic relationship to primates than to rodents. In addition, advantages such as small size, easy breeding, and rapid reproduction make the tree shrew an ideal subject for the study of human disease. Numerous tree shrew disease models have been generated in biological and medical studies in recent years. Here we summarize current tree shrew disease models, including models of infectious diseases, cancers, depressive disorders, drug addiction, myopia, metabolic diseases, and immune-related diseases. With the success of tree shrew transgenic technology, this species will be increasingly used in biological and medical studies in the future.

Carcinoma ex pleomorphic adenoma composed of three malignant components in parotid gland:A case report and literature review / 吉林大学学报(医学版)

Objective:To investigate the diagnosis and prognosis of one patient with carcinoma ex pleomorphic adenoma (CXPA)composed of three malignant components in parotid gland,and to raise the clinicians'awareness of the disease.Methods:A patient was presented to hospital because of the mass in left parotid gland region for more than 30 years and the accompanied pain lasted for one month.After color ultrasonography,the left parotid gland tumor resection was performed. Results: The operation was successful. The postoperative pathological diagnosis results comfirmed as CXPA,it was composed of three malignant components,including non-specific adenocarcinoma,ductal carcinoma,and myoepithelial carcinoma.Conclusion:CXPA composed of three malignant components at the same time are extremely rare.CXPA is difficult to diagnose and its prognosis is poor.The clinicians are supposed to improve the understanding of CXPA.

Effect of granulocyte-macrophage colony-stimulating factor gargle in control of the oral mucositis after allogeneic hematopoietic stem cell transplantation / 中国实用护理杂志

Objective To identify the efficacy of granulocyte-macrophage colony-stimulating factor (GM-CSF) gargle in patients who had oral mucositis after allogeneic hematopoietic stem cell transplantation. Methods A total of 134 patients were enrolled in this study from 2014 to 2015. They were randomly divided into two groups:the experimental group (n=65) and the control group (n=69). Both groups received preventive measures for oral mucositis. But once oral mucositis occurred, the control group continued with the routine nursing measure, while the experimental group added GM-CSF gargle based on previous routine nursing measure. The effective rate and healing time were compared between two groups. Results The effective rate of the experimental group (81.54%, 53/65) was significantly higher than that of the control group (24.64%,17/69) (χ2=43.434, P=0.000). The median healing time in the experimental group was 4.5 days, shorter than 9.0 days in the control group (Z=-5.379, P< 0.01). Conclusions GM-CSF gargle can control the oral mucositis after allogeneic hematopoietic stem cell transplantation.

The big bang of genome editing technology: development and application of the CRISPR/Cas9 system in disease animal models.

Targeted genome editing technology has been widely used in biomedical studies. The CRISPR-associated RNA-guided endonuclease Cas9 has become a versatile genome editing tool. The CRISPR/Cas9 system is useful for studying gene function through efficient knock-out, knock-in or chromatin modification of the targeted gene loci in various cell types and organisms. It can be applied in a number of fields, such as genetic breeding, disease treatment and gene functional investigation. In this review, we introduce the most recent developments and applications, the challenges, and future directions of Cas9 in generating disease animal model. Derived from the CRISPR adaptive immune system of bacteria, the development trend of Cas9 will inevitably fuel the vital applications from basic research to biotechnology and bio-medicine.