Monitoring and Analysis of Chinese Chronic Myeloid Leukemia Patients Who Have Stopped Tyrosine Kinase Inhibitor Therapy

Discontinuation of tyrosine kinase inhibitor(TKI)therapy after achieving a persistent deep molecular response(DMR)is an urgently needed treatment goal for chronic myeloid leukemia(CML)patients and has been included in the National Comprehensive Cancer Network(NCCN)guidelines(version 2.2017)for CML.Indeed,various studies have confirmed the feasibility of discontinuing TKI therapy.In this study,we analyzed data from 45 CML patients who had discontinued TKI therapy.Univariate analysis was performed to predict factors that were potentially related to treatment-free remission(TFR)and identify the differences between early relapse and late relapse.Out of the 45 patients,20 exhibited molecular relapse after a median follow-up of 18 months(range,1-54 months),and the estimated TFR at 24 months was 40%.The univariate analysis revealed that a high Sokal score and interruptions or dose reductions during TKI treatment were the only baseline factors associated with poor outcomes.Our results indicate that TKI discontinuation could be successfully put into practice in China.

Effect of VEGF,P53 and telomerase on angiogenesis of gastric carcinoma tissue

Objective:To investigate the effect of vascular endothelial growth factor(VEGF),P53 and telomerase on angiogenesis in gastric carcinoma tissue.Methods:A total of 95 surgical resection samples of gastric cancer tissue after pathological diagnosis are collected to observe the VEGF,P53 and telomerase expression using immunohistochemical methods.Relationship between their expression and its influence on angiogenesis in gastric carcinoma tissue were analyzed.Results:Microvascular density(MVD)and the expression of VEGF,P53 and telomerase were positively correlated.Expression of VEGF and P53 protein were related to tumor type and lymph metastasis,and also a correlation was observed between P53 and VEGF.The telomerase expression had no correlation with VEGF,and P53.Conclusions:VEGF angiogenesis has a angiogenesis promoting effect on gastric cancer tissue development and plays an important role in tumor generation and metastasis.Mutant P53 promotes the tumor angiogenesis generation by adjusting VEGF.Telomerase has a certain role in promoting activity of angiogenesis through different way rather than P53.

Transplantation of human umbilical cord blood mesenchymal stem cells to treat a rat model of traumatic brain injury

In the present study, human umbilical cord blood mesenchymal stem cells were injected into a rat model of traumatic brain injury via the tail vein. Results showed that 5-bromodeoxyuridine-labeled cells aggregated around the injury site, surviving up to 4 weeks post-transplantation. In addition, transplantation-related death did not occur, and neurological functions significantly improved. Histological detection revealed attenuated pathological injury in rat brain tissues following human umbilical cord blood mesenchymal stem cell transplantation. In addition, the number of apoptotic cells decreased. Immunohistochemistry and in situ hybridization showed increased expression of brain-derived neurotrophic factor, nerve growth factor, basic fibroblast growth factor, and vascular endothelial growth factor, along with increased microvessel density in surrounding areas of brain injury. Results demonstrated migration of transplanted human umbilical cord blood mesenchymal stem cells into the lesioned boundary zone of rats, as well as increased angiogenesis and expression of related neurotrophic factors in the lesioned boundary zone.

TPX2 promotes migration and invasion of human breast cancer cells

Objective:To investigate the expression of targeting protein for Xenopus kinesin-like protein 2(TPX2) in breast cancer tissue and to explore its role in proliferation,migration and invasion of breast cancer cells.Methods:The mRNA and protein expressions of TPX2 in breast cancer tissue and cell lines were assessed by quantitative RT-PCR and Western blot.The effect of TPX2 with RNA interference on proliferation,invasion and migration of breast cancer cells was observed by MTT and Transwell assays.Results:Both mRNA and protein expressions of TPX2 were upregulated in breast cancer tissues compared to tumor-adjacent tissue.TPX2 expression was also upregulated in breast cancer cell lines,and the TPX2 interfered by small interfering RNA could inhibit the proliferation,invasion and migration of breast cancer cells by inhibiting matrix metalloproteinase-2 and matrix metalloproteinase-9.Conclusions:Significantly upregulated TPX2 expression is observed in breast cancer tissue and cells,and contributes to promote the proliferation,migration and invasion of breast cancer cells.

Identification of a Homozygous Missense Mutation in the TYR Gene in a Chinese Family with OCA1

Oculocutaneous albinism (OCA)is an autosomal recessive pigmentation abnormality,characterized by variable hair,skin,and ocular hypopigmentation.OCA1 is the most frequent subtype of OCA,caused by mutations in the tyrosinase gene (TYR). In this study,we investigated the genetic mutation of a Chinese family with a female OCA patient who came for genetic counseling before pregnancy.Complete physical examination was performed,and DNA from blood samples was collected from the family members.Mutations of TYR,OCA2,and SLC45A2 genes were examined in the proband, and verified in her parents by Sanger sequencing.Large deletion or duplication of TYR and OCA2 genes was detected by multiplex ligation-dependent probe amplification (MLPA).A homozygous TYR c.307T>C (p.Cys103Arg)missense mutation was identified in the proband,and both parents were heterozygous carriers.No large deletion or duplication was found in the proband.This mutation was absent in 1000G,ExAC,or HGMD database,and multiple lines of in silico tools supported a deleterious effect.These results suggest that TYR c.307T>C mutation might be responsible for OCA1,and our study further expands the mutation spectrum of OCA1 in the Chinese population.

Ruxolitinib add-on in corticosteroid-refractory graft-vs-host disease after allogeneic stem cell transplantation:Results from a retrospective study on 38 Chinese patients

BACKGROUND Graft-vs-host disease (GVHD) is a major cause of mortality after allogeneic hematopoietic stem cell transplantation.Some patients have steroid-refractory(SR) GVHD.AIM To evaluate the effect and safety of ruxolitinib add-on in the treatment of patients with SR acute (a) and chronic (c) GVHD.METHODS We retrospectively analyzed 38 patients administered ruxolitinib add-on to standard immunosuppressive therapy for SR-aGVHD or SR-cGVHD following allogeneic hematopoietic stem cell transplantation.Ruxolitinib was administered5-10 mg/d depending on disease severity,patient status,and the use of antifungal drugs.Overall response rate,time to best response,malignancy relapse rate,infection rate,and treatment-related adverse events were assessed.RESULTS The analysis included 10 patients with SR-aGVHD (gradeⅢ/Ⅳ,n=9) and 28patients with SR-cGVHD (moderate/severe,n=24).For the SR-aGVHD and SRcGVHD groups,respectively:Median number of previous GVHD therapies was 2(range:1-3) and 2 (1-4);median follow-up was 2.5 (1.5-4) and 5 (1.5-10) mo;median time to best response was 1 (0.5-2.5) and 3 (1-9.5) mo;and overall response rate was 100%(complete response:80%) and 82.1%(complete response:10.7%) with a response observed in all GVHD-affected organs.The malignancy relapse rates for the SR-aGVHD and SR-cGVHD groups were 10.0%and 10.7%,respectively.Reactivation rates for cytomegalovirus,Epstein-Barr virus,and varicella-zoster virus,respectively,were 30.0%,10.0%,and 0%for the SR-aGVHD group and 0%,14.3%,and 7.1%for the SR-cGVHD group.CONCLUSION Ruxolitinib add-on was effective and safe as salvage therapy for SR-GVHD.

The Performance of Chinese Private Firms in Coping with a Global Financial Crisis： Who Is Best Positioned？

把组织上的灵活性用作一个研究透镜，我们调查怎么私人公司，特别制造工程师协会，在中国应付 2008 金融危机。从由差别不在乎分析的私人公司(N=3,459 ) 的一件大样品的严峻的数据，我们发现没有，有工业多样化，地理扩大和政治连接的公司比那些在危机期间更好表现。这些结果被自己挑选问题少些影响(当突然的危机提供一个自然实验) 并且对 endogeneity 和几 nberg 举起， 2008 ) 。察觉的领导有效性，为研究人员的 job-satiportant 含意，企业主人，政策制造者和未来研究。

Erratum to:A novel GSH responsive poly(alpha-lipoic acid)nanocarrier bonding with the honokiol-DMXAA conjugate for combination therapy(vol 63,pg 307,2020)

In the version of the article originally published in the volume 63,issue 2,2020 of Sci China Mater(2020,63(2):307–315,https://doi.org/10.1007/s40843-019-1183-0),the affiliations of two of the authors(Zhaohui Tang and Xuesi Chen)were incompletely labeled.The corrected version of the authors’affiliations is as below.

A ROS-Stimulus-Responsive Nanocarrier Loading with Guanidine-Modified Hydroxycamptothecin Prodrug for Enhanced Anti-Tumor Efficacy

We report a reactive oxygen species(ROS)-stimulus-responsive phenylboronic acid pinacol ester nanocarrier,loaded with guanidine-modified 10-hydroxycamptothecin(HCPT)prodrug,to create a drug delivery-base nanomedicine.The prodrug was stuck tightly in the nanocarrier with over 99%drug-loading efficiency due to the superposition of hydrogen bonds from guanidine and carboxyl,hydrophobic interaction,π–πstacking interaction from phenylboronic acid pinacol ester,and the HCPT prodrug.The aqueous stability of the phenylboronic acid pinacol ester nanocarrier improved remarkably after drug loading because of the interaction between the prodrug and the nanocarrier.Thus,the nanomedicine could realize ROS-triggered disassembly at the tumor sites,release the cell-penetrating prodrug,and achieve improved cellular uptake than the HCPT alone.The results of in vivo antitumor determination demonstrated three-fold inhibition of tumor growth rate of the ROS-stimulus-responsive nanomedicine,compared with HCPT,and the side effects of the prodrug complex reduced significantly.Therefore,our approach offers a promising strategy for the enhancement of antitumor efficacy.

Restoration of Brain Acid Soluble Protein 1 Inhibits Proliferation and Migration of Thyroid Cancer Cells

Background： Brain acid soluble protein 1 （BASPI） is identified as a novel potential tumor suppressor in several cancers. However, its role in thyroid cancer has not been investigated yet. In the present study, the antitumor activities of BASP1 against the growth and migration of thyroid cancer cells were evaluated. Methods： BASP1 expression in thyroid cancer tissues and normal tissues were examined by immunohistochemical staining and the association between its expression and prognosis was analyzed, pcDNA-BASP 1 carrying full length of BASP1 cDNA was constructed to restore the expression of BASP1 in thyroid cancer cell lines （BHT- I 01 and KMH-2）. The cell proliferation in vitro and in vivo was evaluated by WST-1 assay and xenografl tumor models, respectively. Cell cycle distribution after transfection was analyzed using flow cytometry. Cell apoptosis after transfection was examined by annexin V/propidium iodide assay. The migration was examined using transwell assay. Results： BASP1 expression was abundant in normal tissues while it is significantly decreased in cancer tissues （P = 0.000）. pcDNA-BASP1 restored the expression of BASPI and significantly inhibited the growth of BHT-101 and KMH-2 cells as well as xenograft tumors in nude mice （P = 0.000）. pcDNA-BASPI induced G1 arrest and apoptosis in BHT-101 and KMH-2 cells. In addition, pcDNA-BASP1 significantly inhibited the cell migration. Conclusions： Downregulation of BASP1 expression may play a role in the tumorigenesis of thyroid cancer. Restoration of BASPI expression exerted extensive antitumor activities against growth and migration of thyroid cancer cells, which suggested that BASPI gene might act as a potential therapeutic agent for the treatment of thyroid cancer.

一种新型GSH响应性聚硫辛酸纳米载体键合和厚朴酚-DMXAA缀合物用于联合治疗（英文）

提高肿瘤治疗效果的关键在于增加药物肿瘤部位递送.为此,肿瘤微环境刺激响应性材料具有很大的潜力.本文通过将和厚朴酚和DMXAA缀合物键合到GSH响应性聚硫辛酸-聚乙二醇纳米载体上,制备出一种新型纳米药物.在肿瘤部位高谷胱甘肽水平时纳米药物解体,实现和厚朴酚与DMXAA在肿瘤部位的共同递送.通过和厚朴酚的近程攻击与DMXAA的远程杀伤,协同治疗乳腺癌.在小鼠4T1乳腺肿瘤模型中,该策略显示肿瘤抑制率高达93%,为肿瘤治疗提供了有价值的候选治疗方案.

Predicting the Loading Capability of mPEG-PDLLA to Hydrophobic Drugs Using Solubility Parameterst

Physical encapsulation of drugs into polymer micelles is a common method of loading hydrophobic drugs.Methoxy polyethylene glycol-poly(D,L.-lactide)(mPEG-PDLLA)is one of the most commonly used drug carrier.At present,whether a carrier is suitable for the loading of a certain drug is determined by drug loading experiments.This process costs a lot of time.Therefore,an efficient predicting method to avoid time-consuming tests is critical.In this study,we prepared mPEG5k-PDLLA5k and used it to load a series of drugs.Three parameters were used to test the miscibility of mPEG5k-PDLLA5k with drugs,including absolute difference in Hildebrand solubility parameters(|△δ|),Flory-Huggins interaction parameter(x)and the distance(D value)calculated from the two-dimensional solubility parameters.We found the two-dimensional solubility parameters obtained from JB2013 group contribution(GC)method was useful.By comparing the drug loading content(DLC)with the D value,we found that when the D value was less than 5.0(MJ/m3)1/2,the miscibility of drug and mPEGSk-PDLLASk was good and drug loading capability was high;when the D value was more than 8.0(MJ/m3)1/2,the drug was barely loaded.Thus,this work provided a rationale to qualitatively predict the loading capability of mPEGSk-PDLLA5k for hydrophobic drugs.