Publications by authors named "Xiuhua Chen"

68 Publications

The clinical characteristics and prognosis of Chinese acute myeloid leukemia patients with CSF3R mutations.

Int J Lab Hematol 2021 Nov 24. Epub 2021 Nov 24.

Shanxi Medical University, Taiyuan, China.

Introduction: The colony-stimulating factor 3 receptor (CSF3R) controls the proliferation of myeloid progenitors and differentiation into neutrophils. However, the clinical features and prognostic significance of CSF3R mutations in primary acute myeloid leukemia (AML) patients are still unclear.

Methods: 158 newly diagnosed AML patients were retrospectively evaluated in our study. Amplicon-based next-generation sequencing (NGS) and multiplex-nested reverse-transcription polymerase chain reaction (RT-PCR) were used to investigate the 34 genes and 43 fusion genes associated with leukemia. In addition, clinical features, mutation incidence, and survival outcomes were compared between patients with CSF3R mutation and patients with wild-type CSF3R.

Results: In our study, CSF3R mutations were found in 7.6% (12/158) cases. The membrane-proximal amino acid substitution T618I (58.3%) was the most frequent mutation. CSF3R mutations were associated with higher WBC counts (P = .035). CEBPA mutation, TET2 mutation, and RUNX1-RUNX1T1 translocation were the most common co-mutations of CSF3R. The CSF3R gene was mutually exclusive with signal transduction genes (P = .029), while positively associated with TET2 mutations (P = .014). CSF3R mutations had no effect on CR1 (P = .935), R (P = .625) and OS (P = .1172). Patients with CSF3R mutations had a worse DFS (P = .0352) than those with wild-type CSF3R. Multivariate survival analysis showed that CSF3R mutation was an independent risk factor for DFS of primary AML patients (HR=2.048, 95%CI: 1.006-4.170, P = .048).

Conclusion: AML patients with CSF3R mutations had unique clinical features and gene co-mutation spectrum. CSF3R mutation was an independent risk factor for DFS and could be a potential prognostic marker and therapeutic target for Chinese primary AML patients.
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http://dx.doi.org/10.1111/ijlh.13762DOI Listing
November 2021

GATA2 rs2335052 and GATA2 rs78245253 single-nucleotide polymorphisms in Chinese patients with acute myelocytic leukemia.

Int J Lab Hematol 2021 Dec 9;43(6):1491-1500. Epub 2021 Aug 9.

Institute of Hematology, the Second Hospital of Shanxi Medical University, Taiyuan, China.

Introduction: GATA binding protein 2 (GATA2) gene, involved in progression of hematologic malignancies and various solid tumors, is a susceptibility gene for inherited acute myeloid leukemia (AML). However, the influence of its single-nucleotide polymorphisms (SNPs) on AML remains unknown.

Methods: We used allele-specific PCR to genotype GATA2 rs2335052 and rs78245253 in 159 newly diagnosed AML (non-M3) patients and 300 healthy volunteers, and all of participants came from China. And 34 common hematological tumor gene mutations in 159 AML patients were detected by next-generation sequencing. Kaplan-Meier survival analysis and Cox proportional hazard regression were used to analyze the association between the two SNPs and the prognosis of AML.

Results: We found GATA2 rs2335052 C/T genotype, rs2335052 T/T genotype and rs78245253 G/C genotype in 51.6%, 13.8% and 11.3% AML patients. Our results demonstrated that GATA2 rs2335052 and rs78245253 were associated with certain laboratory features in AML patients, which had no effect on the pathogeny, chemotherapy response and recurrence of patients. Nevertheless, Kaplan-Meier survival analysis showed that, compared with rs78245253 G/G genotype, rs78245253 G/C genotype was significantly related to a decrease in overall survival (OS) (P = .020). Additionally, multivariate cox regression analysis showed that GATA2 rs78245253 was an independent risk factor for OS of AML patients in China.

Conclusion: GATA2 rs78245253 was an independent predictor for prognosis of AML patients in China and may be used as a potential indicator to predict the survival of AML patients in China. Further studies are needed to validate these findings and clarify the underlying mechanism.
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http://dx.doi.org/10.1111/ijlh.13649DOI Listing
December 2021

Recycling of photovoltaic silicon waste for high-performance porous silicon/silver/carbon/graphite anode.

Waste Manag 2021 Aug 24;132:56-63. Epub 2021 Jul 24.

School of Photovoltaic and Renewable Energy Engineering (SPREE), University of New South Wales, Sydney 2052, Australia.

The rapid development photovoltaic industry has generated a huge amount of waste ultra-fine silicon cutting powder. The management and value-added recovery of silicon cutting waste is highly important for both environmental remediation and economic efficiency. In this work, silicon waste was used as a cost-effective raw material for the preparation of silicon/graphite anode for lithium-ion batteries. First, porous Si embedded with Ag particles (pSi/Ag) was produced by silver-assisted chemical etching (Ag-ACE). Then, pSi/Ag was loaded on a micron-sized graphite matrix (pSi/Ag/G), and organic carbon (C) produced by the pyrolysis of polyvinylpyrrolidone (PVP) acted as a link to closely connect pSi/Ag and graphite to form the pSi/Ag/C/G composite. The incorporated Ag particles and the porous structure improve electron transfer and mitigate the volume expansion effect of silicon. The novel design and structure of the anode can maintain the integrity of the electrode during cycling, and thus strongly improve cycling stability. The prepared pSi/Ag/C/G composite exhibited a large initial discharge capacity of 2353 mAh/g at 0.5 A/g and good initial coulombic efficiency of 83%, delivering a high capacity of 972 mAh/g at 1 A/g after 200 cycles. This work confirmed the possibility of the preparation of lithium battery silicon-carbon anode from silicon waste and provides a promising new avenue for value-added utilization of silicon cutting waste materials.
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http://dx.doi.org/10.1016/j.wasman.2021.07.014DOI Listing
August 2021

The clinical characteristics and prognosis of cytogenetically normal AML with single mutations of CEBPA.

Int J Lab Hematol 2021 Dec 3;43(6):1424-1431. Epub 2021 Jul 3.

Institute of Hematology, The Second Hospital of Shanxi Medical University, Taiyuan, China.

Introduction: CEBPA mutation is a common mutation in normal karyotype AML. CEBPAdm AML has been recognized as a separate entity, but there is still controversy to the prognosis of CEBPAsm patients.

Methods: A total of 151 newly diagnosed cytogenetically normal AML patients treated at the Second Hospital Center of Shanxi Medical University from February 2017 to December 2019 were the subjects of the study. According to the number of mutations in the CEBPA gene, the patients were divided into three groups, CEBPAsm, CEBPAdm, and CEBPAwt patients. The clinical characteristics, gene mutations, response, and prognosis were retrospectively compared among the three groups.

Results: CEBPAsm patients had lower hemoglobin values compared to CEBPAdm (P = .049). There was no statistical difference between the CEBPAsm cases and the CEBPAdm cases in the mutation types and the distribution of mutation regions (P > .050). Compared with CEBPAdm, cases with CEBPAsm were more likely associated with multiple other gene mutations (P = .023). Patients with CEBPAdm had a higher CR, ORR, and OS than those CEBPAwt (P < .050). CEBPAsm patients had a similar OS with CEBPAdm and CEBPAwt patients (P = .281). These CEBPAsm patients with VAF<30% had lower OS than the patients with VAF≥30%. FLT3-ITD mutations could reduce CEBPAsm patients' OS (P = .019).

Conclusion: Our data first highlighted the impact of CEBPAsm VAF on OS, and the results showed the lower the VAF was, the shorter the OS tended to. The VAF of CEBPAsm could provide specific significance in some extent for the prognosis of patients.
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http://dx.doi.org/10.1111/ijlh.13612DOI Listing
December 2021

A lineage switch from NPM1-mutant acute myeloid leukemia to acute T-cell lymphoblastic leukemia with KMT2D and ARID2 mutant.

Int J Lab Hematol 2021 08 21;43(4):O230-O233. Epub 2021 Apr 21.

The Haematology Department, The Second Hospital of Shanxi Medical University, Taiyuan, Shanxi, China.

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http://dx.doi.org/10.1111/ijlh.13534DOI Listing
August 2021

Application of Nano-Insulin Pump in Children with Diabetic Ketoacidosis.

J Nanosci Nanotechnol 2021 10;21(10):5051-5056

Department of Pediatrics, The First Affiliated Hospital of Jiamusi University, Jiamusi 154000, Heilongjiang, PR China.

Type 1 diabetes is an insulin-dependent type of diabetes that is most common among children. Due to absolute deficiency of insulin in patients, diabetic ketoacidosis (DKA) can easily ensue. Insulin pump can simulate the physiological secretion of islet, but increases the risk of pain and infection in children due to its traumatic effect. This study aimed to analyze the application effect of nano-insulin pump in children with DKA. Children with DKA admitted to our hospital from May 2018 to May 2020 were included in this study and, according to the random number table method, they were divided into two groups, with each group containing 36 cases. The first group received traditional insulin pump infusion (IP), while the second group received nano-insulin pump infusion (NIP). It was found that the reduction of FBG and PBG in NIP group was greater than that in IP group. The recovery time of urine ketone, blood ketone, glucose, venous pH, and other clinical indicators in the NIP group were all lower than those in the IP group ( < 0.05). The length of hospital stay, insulin dosage, incidence of hypoglycemia, and infusion site infection rate in the NIP group were all lower than those in the IP group (P <0.05). The findings indicate that the application of nano-insulin pump in children with DKA had a significant effect and could quickly and obviously correct the levels of blood glucose and ketone body in children.
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http://dx.doi.org/10.1166/jnn.2021.19356DOI Listing
October 2021

[email protected]/Nano-Ag composite derived from silicon cutting waste as high-performance anode material for Li-ion batteries.

J Hazard Mater 2021 Jul 22;414:125480. Epub 2021 Feb 22.

Nanomaterials Centre, School of Chemical Engineering and Australian Institute for Bioengineering and Nanotechnology, The University of Queensland, Brisbane 4072, Australia. Electronic address:

Integration of photovoltaic (PV) power generation and energy storage has been widely believed to be the ultimate solution for future energy demands. Herein, an ingenious method was reported to make full use of photovoltaic silicon cutting waste (SiCW) natural characters fabricating [email protected]/Nano-Ag composite as anode material for high-performance lithium-ion batteries. The sheet-like structure with nano/micropores and native SiOx layer addressed the volume expansion issues of Si material. Ag nanoparticles greatly enhanced electrical conductivity of composite and promoted Li/e transport. Synergistic effect of the designed [email protected]/Nano-Ag composite contributed outstanding cyclic performance with reversible capacity of 1409mAhg after 500 cycles. Notably, full LIBs with [email protected]/Nano-Ag anode and commercial Li[NiCoMn]O (NCM622) cathode delivered stable capacity of 137.5mAhg at current density of 200 mA g, accompanying with a high energy density of 438 Wh kg. Furthermore, electrochemical Li storage behavior of this [email protected]/Nano-Ag electrode was studied, and reaction mechanism and crystal structure evolution during cycles were also revealed by in-situ XRD analysis. The synthesis method is facile and cost-effective, which paves a novel way towards high-performance Si-based anodes and promising markets for both solar photovoltaic and lithium-ion battery industries.
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http://dx.doi.org/10.1016/j.jhazmat.2021.125480DOI Listing
July 2021

Functional analysis of atypical mutations in exons 13 and 15 of JAK2 gene in myeloproliferative neoplasms.

Int J Lab Hematol 2021 06 27;43(3):e110-e113. Epub 2020 Nov 27.

Institute of Hematology, The Second Hospital of Shanxi Medical University, Taiyuan, China.

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http://dx.doi.org/10.1111/ijlh.13398DOI Listing
June 2021

Efficacy of Bloodletting Therapy in Patients with Chronic Idiopathic Urticaria: A Randomized Control Trial.

Evid Based Complement Alternat Med 2020 30;2020:6598708. Epub 2020 Oct 30.

Dermatology Department, The Second Clinical College of Guangzhou University of Chinese Medicine, Guangzhou 510120, China.

Objective: To assess the efficacy of bloodletting therapy (acupoint pricking and cupping) in patients with chronic idiopathic urticaria (CIU) in a randomized, control, parallel-group trial.

Methods: A total of 174 patients with CIU enrolled from March 2018 to October 2019 were randomized into three groups: group A treated with bloodletting therapy and ebastine, group B treated with placebo treatment (acupoint pseudopricking and cupping) and ebastine, and group C treated with ebastine only. The intention-to-treat analysis was conducted, and the primary outcome was the effective rate of UAS7 score being reduced to 7 or below after treatment phase.

Results: The effective rates at the end of treatment phase were different among the three groups ( < 0.05), which were 73.7% in group A, 45.6% in group B, and 42.9% in group C. Multiple analysis indicated differences between groups A and B ( < 0.0125) and groups A and C ( < 0.0125) and no difference between groups B and C ( > 0.0125). No severe bloodletting therapy-related adverse events were observed.

Conclusions: In this study on patients with CIU, one month of bloodletting therapy combined with ebastine is clinically beneficial compared with placebo treatment combined with ebastine and treatment with ebastine only. Thus, bloodletting therapy can be an effective complementary treatment in CIU. This trial is registered with ChiCTR1800015294.
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http://dx.doi.org/10.1155/2020/6598708DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7647761PMC
October 2020

expression enhances low-temperature stress resistance in tomato plants.

PeerJ 2020 7;8:e10059. Epub 2020 Oct 7.

College of Plant Science and Technology, Beijing University of Agriculture, Beijing, China.

Herein, we identified the tomato gene as a MYB family transcription factor of the R2R3-MYB subfamily. We additionally determined that the promoter region contains photoresponsive, abiotic stress-responsive, and hormone-responsive regulatory elements, and we detected higher expression in the reproductive organs of tomato than that in vegetative organs, with the expression being highest in ripe fruits and in roots. expression was also shown to be cold-inducible. The protein encoded by localized to the nucleus wherein it was found to mediate the transcriptional activation of target genes through its C-terminal domain. Overexpression of in tomato plants conferred enhanced tolerance to cold stress. Under such cold stress conditions, we found that proline levels in the leaves of overexpressing transgenic plants were higher than those in WT plants. In addition, overexpression was associated with the enhanced expression of cold response genes including and . We also found that the overexpression of further enhanced the cold-induced upregulation of and Taken together, these results suggest that may be involved in the C-repeat binding transcription factor (CBF) and proline synthesis pathways, thereby improving tomato plant cold resistance.
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http://dx.doi.org/10.7717/peerj.10059DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7547593PMC
October 2020

Monitoring Treatment-Free Remission by Droplet Digital PCR in CML Patients with Deep Molecular Response to Tyrosine Kinase Inhibitor: An Analysis Based on Real-World Data.

Ann Clin Lab Sci 2020 Sep;50(5):591-599

Department of Hematology, the Second Hospital of Shanxi Medical University, Taiyuan, China

Treatment-free remission (TFR) is emerging as a new therapy goal for chronic myeloid leukemia (CML) patients in the tyrosine kinase inhibitors (TKI) era. Data indicates the unfavorable success rate of TFR. This study aimed to compare and evaluate the clinical value of dd-PCR in predicting relapse in CML patients entering TFR. Using dd-PCR and RT-qPCR technology, dynamic BCR/ABL transcripts were detected in 13 CML patients who discontinued TKI treatment after sustaining undetectable BCR-ABL levels for a median time of 25 months. The results showed that in 13 patients, only 2 cases (22.2%) of 9 patients who executed planned discontinuation achieved TFR within 12 months. In the first 6 months, the detection rate of BCR/ABL transcripts by dd-PCR was higher than that by RT-qPCR and the two methods kept a positive correlation (r=0.9651, =0.0349). Meanwhile, the time of detectable BCR/ABL by dd-PCR were significantly shorter (<0.05), which was an average of 2.98 months earlier than RT-qPCR. The total TKI therapy and MR4.5 duration time related with TFR were longer in patients with intermediate or high Sokal risk scores (<0.05). The dd-PCR could be more sensitive than RT-qPCR for monitoring BCR/ABL transcripts of CML patients with deep molecular response to TKI. The technique can be used as a preferred method to detect the transcripts in the first 6 months after TKI cessation.
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September 2020

High-Performance Porous Silicon/Nanosilver Anodes from Industrial Low-Grade Silicon for Lithium-Ion Batteries.

ACS Appl Mater Interfaces 2020 Oct 14;12(43):49080-49089. Epub 2020 Oct 14.

Nanomaterials Centre, Australian Institute for Bioengineering and Nanotechnology and School of Chemical Engineering, The University of Queensland, St. Lucia, Queensland, 4072, Australia.

Silicon (Si) has been considered as one of the most promising candidates for the next-generation lithium-ion battery (LIB) anode materials owing to its huge theoretical specific capacity of 4200 mA h g. However, the practical application of Si anodes in commercial LIBs is facing challenges because of the lack of scalable and cost-effective methods to prepare Si-based anode materials with proper microstructure and competitive electrochemical performances. Herein, we report a facile and scalable method to produce multidimensional porous silicon embedded with a nanosilver particle (pSi/Ag) composite from commercially available low-cost metallurgical-grade silicon (MG-Si) powder. The unique hybrid structure contributes to fast electronic transport and relieves volume change of silicon during the charge-discharge process. The pSi/Ag composite exhibits a large initial discharge capacity (3095 mA h g at a high current of 1 A g), an excellent cycling performance (1930 mA h g at 1 A g after 50 cycles), and outstanding rate capacities (up to 1778 mA h g at a higher current of 2 A g). After the samples are modified by reduced graphene oxide, the capacities of the pSi/[email protected] composite electrode can still be maintained over 1000 mA h g after 200 cycles. This study provides a simple and effective strategy for production of high-performance anode materials.
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http://dx.doi.org/10.1021/acsami.0c14157DOI Listing
October 2020

Rice immune sensor XA21 differentially enhances plant growth and survival under distinct levels of drought.

Sci Rep 2020 10 9;10(1):16938. Epub 2020 Oct 9.

Department of Plant Pathology, University of Florida, Gainesville, FL, 32611, USA.

Drought is a complex stress that limits plant growth and crop production worldwide. The mechanisms by which plants coordinately respond to distinct levels of water deficits (e.g., mild, moderate or severe drought) remain elusive. Here we demonstrate that the rice immune sensor XA21 promotes survival of rice seedlings during dehydration stress. XA21 expression increases deposition of lignin and cellulose in the xylem vessels and their surrounding cells. Inhibition of aquaporin water channels by mercuric chloride eliminates XA21-mediated dehydration survival, suggesting that XA21 enables plant survival during drought, probably by protecting xylem functionality. In contrast to prevailing observations of stress tolerance genes, XA21 is also capable of enhancing rice growth during moderate drought. Thus, XA21 acts as a mediator for stress protection and plant growth under water-limiting conditions.
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http://dx.doi.org/10.1038/s41598-020-73128-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7547014PMC
October 2020

Identification of Two Novel Truncated Transcripts of Janus Kinase 2 Gene.

Ann Clin Lab Sci 2020 Jul;50(4):497-503

Institute of Hematology, the Second Hospital of Shanxi Medical University

Jak2 is a nonreceptor tyrosine kinase that plays a critical role in signal transduction through an abundance of receptors, such as erythropoietin receptor. In this paper, we report two previously unknown transcripts of Jak2 gene. One transcript deletes the 77nt of 3' end exon 10 of the Jak2 gene, resulting in a frameshift that introduces a stop codon in the downstream exon and produces a truncated protein of 421 amino acids if translated. The other transcript skips the entire exon 10, leading to a premature stop codon in the adjacent exon 11, producing a truncated protein of 414 amino acids if translated. Therefore, the physiological significance of the expression of two novel transcripts in healthy volunteers and patients with myeloproliferative neoplasms, acute leukemia, and chronic myeloid leukemia needs to be investigated further.
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July 2020

Disulfiram/cytarabine eradicates a subset of acute myeloid leukemia stem cells with high aldehyde dehydrogenase expression.

Leuk Res 2020 Mar 19;92:106351. Epub 2020 Mar 19.

Institute of Hematology, The Second Hospital of Shanxi Medical University, Taiyuan, China. Electronic address:

Most patients with acute myeloid leukemia (AML) achieve complete remission (CR) after induction chemotherapy, however, in some patients, the disease subsequently relapses and may lead to death. Leukemia stem cells (LSC) have been identified as the main cause for recurrence. Increased aldehyde dehydrogenase (ALDH) activity in a variety of cancer stem cells prevents effective action of chemotherapeutic drugs. In this study, we found that approximately 50.7% of AML patients had ALDH, and the presence of ALDH stem cells was associated with poor cytogenetic prognosis. Lentiviral vector transduced ALDH leukemia cell lines are insensitive to the conventional chemotherapy drug cytarabine, and inhibition of ALDH activity by disulfiram (DSF) can increase the sensitivity of ALDH leukemia cells to cytarabine. Unlike traditional chemotherapy drugs, DSF is not toxic to healthy umbilical cord blood stem cells. An ALDH leukemia cell xenograft model was established using immunodeficient mice to mimic the disease environment, and DSF and cytarabine were found to eliminate the ALDH leukemia cells in transplanted mice while not affecting the healthy blood cells of mice. These findings suggest that DSF may have therapeutic potential by inhibiting ALDH activity and thereby increasing chemosensitivity.
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http://dx.doi.org/10.1016/j.leukres.2020.106351DOI Listing
March 2020

Opportunities and Challenges of the Human Microbiome in Ovarian Cancer.

Front Oncol 2020 18;10:163. Epub 2020 Feb 18.

Central Laboratory of the Eastern Division, The First Hospital of Jilin University, Changchun, China.

Ovarian cancer is the most lethal malignancy among gynecological cancers worldwide. Most ovarian cancer patients are diagnosed at an advanced stage because of non-specific clinical symptoms. The human microbiome plays a crucial role in maintaining the normal physiological and pathological state of the body. With the development of technologies such as DNA and 16S rRNA sequencing, an increasing number of findings on the role of microbiome in cancers are being reported. Microbiome abnormalities are increasingly associated with diseases, including cancer development, and response to therapies. Some studies have shown the relationship between microbiome changes and ovarian cancer. However, the mechanisms underlying this relationship are not yet fully understood. Here, we summarize the key findings in this regard by focusing on estrogen metabolism and host recognition receptors in microorganisms and changes in the gut or pelvic microbiome in patients with ovarian cancer. We further discuss the potential of using the microbiome as a novel biomarker for cancers. We also highlight the possibility to use microorganisms as a treatment modality to enhance the immune system, activate anti-tumor response, mediate chemotherapy resistance, and ameliorate the adverse effects of the treatment.
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http://dx.doi.org/10.3389/fonc.2020.00163DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7040031PMC
February 2020

Effective removal of Cr(VI) from aqueous solution based on APTES modified nanoporous silicon prepared from kerf loss silicon waste.

Environ Sci Pollut Res Int 2020 Apr 17;27(10):10899-10909. Epub 2020 Jan 17.

Institution of Materials Science and Engineering, Yunnan University, Kunming, 650091, China.

Recently, the recycling of kerf loss silicon waste has trigged much attention due to the rapid growth of PV market. In this study, 3-aminopropylethoxysilane (APTES)-functionalized nanoporous silicon (NPSi) hybrid materials were prepared by nanosilver-assisted chemical etching (Ag-ACE) of kerf loss silicon waste derived from diamond-wire saw cutting silicon ingot process. The resulting APTES-NPSi indicated high-effective adsorption ability of Cr(VI) from aqueous solution, which was highly pH dependent, and the maximum adsorption capacity reached up to 103.75 mg/g after 60 min at room temperature. The adsorption kinetics and adsorption isotherms were in good agreement with pseudo-second-order model and Langmuir isotherm. Additionally, the Cr(VI) up-take mechanism was carefully investigated and ascribed to the Cr(VI) adsorption on the protonated anime groups by chemical chelating reaction in which the Cr(VI) was reduced to Cr(III). It was worth mentioning that the APTES-NPSi maintained excellent adsorption capacity after five successive regenerated cycles. Therefore, the work would pave the way for recycling of silicon cutting waste and the potential of Cr(VI) removal from aqueous solution based on the modified NPSi.
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http://dx.doi.org/10.1007/s11356-019-07427-6DOI Listing
April 2020

Coagulopathy in cytogenetically and molecularly distinct acute leukemias at diagnosis: Comprehensive study.

Blood Cells Mol Dis 2020 03 30;81:102393. Epub 2019 Nov 30.

Department of Hematology, the Second Hospital of Shanxi Medical University, Taiyuan, Shanxi, China. Electronic address:

We analyzed the characteristics of coagulopathy in cytogenetically and molecularly distinct acute leukemias. We retrospectively analyzed 211 adult patients with de novo non-acute promyelocytic leukemia (APL) and acute myeloid leukemia (AML), and 105 newly diagnosed patients with B-cell acute lymphoblastic leukemia (B-ALL). Disseminated intravascular coagulation (DIC) occurrence was assessed according the International Society of Thrombosis and Haemostasis (ISTH) criteria. Further, we analyzed the associations of the cytogenetics and mutations with DIC development and coagulation profile. Significant differences were observed between APL and non-APL AML (P = 0.001), APL and B-ALL (P = 0.002), and non-APL AML and B-ALL (P = 0.009) in the distribution of ISTH DIC scores of the acute leukemia patients that met the criteria for diagnosis of DIC. Except for the elevated leukocyte count, a normal karyotype with NPM1 mutations or/and FLT3-ITD mutations was independently associated with the development of DIC in non-APL AML, characterized by significant PT prolongation and significantly elevated D-Dimers. The P210 transcript strongly predicted hypofibrinogenemia in B-ALL in the final multivariate model, but Philadelphia chromosome negatively affected elevated D-dimers. In conclusion, DIC occurrence and the coagulation profile were associated with the cytogenetics and mutations in acute leukemia.
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http://dx.doi.org/10.1016/j.bcmd.2019.102393DOI Listing
March 2020

Inhibition of the Nrf2-TrxR Axis Sensitizes the Drug-Resistant Chronic Myelogenous Leukemia Cell Line K562/G01 to Imatinib Treatments.

Biomed Res Int 2019 18;2019:6502793. Epub 2019 Nov 18.

Department of Hematology, 2nd Hospital of Shanxi Medical University, Taiyuan, Shanxi 030001, China.

Nuclear factor erythroid 2-related factor 2 (Nrf2) is involved in tumor drug resistance, but its role in imatinib resistance of chronic myeloid leukemia (CML) remains elusive. We aimed to investigate the effects of Nrf2 on drug sensitivity, thioredoxin reductase (TrxR) expression, reactive oxygen species (ROS) production, and apoptosis induction in imatinib-resistant CML K562/G01 cells and explored their potential mechanisms. Stable K562/G01 cells with knockdown of Nrf2 were established by infection of siRNA-expressing lentivirus. The mRNA and protein expression levels of Nrf2 and TrxR were determined by real-time quantitative polymerase chain reaction and western blot, respectively. ROS generation and apoptosis were assayed by flow cytometry, while drug sensitivity was measured by the Cell Counting Kit-8 assay. Imatinib-resistant K562/G01 cells had higher levels of Nrf2 expression than the parental K562 cells at both mRNA and protein levels. Expression levels of Nrf2 and TrxR were positively correlated in K562/G01 cells. Knockdown of Nrf2 in K562/G01 cells enhanced the intracellular ROS level, suppressed cell proliferation, and increased apoptosis in response to imatinib treatments. Nrf2 expression contributes to the imatinib resistance of K562/G01 cells and is positively correlated with TrxR expression. Targeted inhibition of the Nrf2-TrxR axis represents a potential therapeutic approach for imatinib-resistant CML.
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http://dx.doi.org/10.1155/2019/6502793DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6885806PMC
April 2020

Effective removal of Cd(II) from aqueous solution based on multifunctional nanoporous silicon derived from solar kerf loss waste.

J Hazard Mater 2020 03 10;385:121522. Epub 2019 Nov 10.

State Key Laboratory of Complex Nonferrous Metal Resources Clean Utilization/Silicon Metallurgy and Silicon Material Engineering Research Center of Universities in Yunnan Province, Kunming University of Science and Technology, Kunming 650093, China.

Recycling of kerf-loss slurry waste has become a meaningful and urgent issue in recent years. In this study, a novel hybrid material was prepared by Ag-assisted chemical etching kerf loss silicon waste and subsequently functionalized by a facile three-step graft process of 3-aminopropyltrimethoxy-silane, maleic anhydride, and ethylenediamine, named as EDA-MAH-APTES-NPSi, which could work as an effective adsorbent for removal of Cd(Ⅱ) from aqueous solution. The effect of initial pH, absorption duration, and metal ion concentrations on absorption performance were investigated. The adsorption equilibrium achieved after 120 min, the maximum adsorption capacity reached up to 210.01 mg/g and pH was at 5.5. The adsorption kinetic was fitted in the pseudo-second-order model and the Freundlich equation provided an accurate description for adsorption behavior. The XPS and FT-IR analysis manifested that Cd(Ⅱ) removal might be ascribed to the adsorption on the surface organic functional group by chemical chelating reaction and the ion exchange reaction. The EDA-MAH-APTES-NPSi maintained excellent adsorption capacity which decreased approximately 15.3 % (from 40.5-34.3 mg/g) after five successive regenerated cycles. The work confirms the potential of Cd(Ⅱ) removal from aqueous solution based on the modified NPSi and opens up a new way for recycling silicon cutting waste.
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http://dx.doi.org/10.1016/j.jhazmat.2019.121522DOI Listing
March 2020

Clonal Analysis of a Patient with Polycythemia Vera and Coexisting Chronic Lymphocytic Leukaemia.

Ann Clin Lab Sci 2019 Sep;49(5):671-674

Institute of Hematology, the Second Hospital of Shanxi Medical University, China

More than 100 cases harboring both myeloproliferative neoplasms (MPN) and chronic lymphocytic leukaemia (CLL) have been reported, suggesting that the two diseases can coexist in one patient. However, the mechanism by which this phenomenon is caused remains unclear. In this study, one patient with polycythemia vera (PV) and CLL is examined. Identifications of the and mutations were obtained via targeted next generation sequencing. Furthermore, B lymphocytes and neutrophils were separated from peripheral blood. This led to the discovery that occurs in neutrophil's compartment, with mutations emerging in B lymphocytes. These results indicate that PV and CLL are independent clonal diseases in this case, rather than phenotypes derived from one clone.
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September 2019

Analysis of gene mutation characteristics in patients with chronic neutrophilic leukaemia.

Hematology 2019 Dec;24(1):538-543

a Institute of Hematology , the Second Hospital of Shanxi Medical University , Taiyuan , People's Republic of China.

This study aims to investigate the gene mutation characteristics of chronic neutrophilic leukaemia (CNL). This study retrospectively analyses the molecular biological characteristics, laboratory characteristics and clinical data of four patients with CNL that were admitted in the second Hospital of Shanxi Medical University from May 2014 to October 2016. On the basis of the molecular biological data of 22 patients with CNL and 4 patients with CNL, we further analysed the characteristics of CNL molecular mutation. Two out of the four patients with CNL were carriers of () mutation, among which two were carriers of mutation combined with mutation and mutation, and two were only carriers of mutation. According to the molecular biological data of 22 patients with CNL, 20 patients were positive for mutation. Two patients were positive for mutation. A total of 10 patients were positive for mutation which was correlated with the gene mutation ( = 0.03). A total of 13 patients were positive for mutation. No patients carried mutations in ASXL2 and MPL genes. mutation is the main tumorigenic mutation in CNL, in which mutation is the main mutation, and an extremely small number of CNL patients may be caused by mutation. and are the most common concomitant mutations in CNL with mutation, and and mutations may have a certain correlation.
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http://dx.doi.org/10.1080/16078454.2019.1642554DOI Listing
December 2019

Two activating mutations of MPL in triple-negative myeloproliferative neoplasms.

Cancer Med 2019 Sep 11;8(11):5254-5263. Epub 2019 Jul 11.

Institute of Hematology, The Second Hospital of Shanxi Medical University, Taiyuan, China.

MPLW515K or W515L mutation plays an important role in the pathogenesis of myeloproliferative neoplasms (MPNs) through signaling molecules of the cytokine receptor axis. Besides MPLW515K or W515L, more than 30 atypical MPL mutations have been reported in patients who are negative for JAK2V617F, MPLW515K/L, and CALR mutations. Here, we aimed to identify the disease-causing mutations in the triple-negative case of ET. We described two MPL mutations in patients diagnosed with ET by target sequencing the hotspot mutation region of MPL gene. The MPLA497-L498ins4 is an insertion mutation detected recurrently in ET patients, and the MPLW515RQ516E is a novel double-point mutation found in an ET patient. Functional studies of MPLA497-L498ins4 and MPLW515RQ516E revealed that they are gain-of-function mutations. Mutants of MPLA497-L498ins4 and MPLW515RQ516E promoted autonomous proliferation on Ba/F3 cells in the absence of IL-3. Autonomous activation of TPO-R without ligand TPO was observed in MPLA497-L498ins4 and MPLW515RQ516E mutants. Lower percentage of cells in G1 phase and higher percentage of cells in S phase of two atypical MPL mutants were detected after culturing without any cytokines. These two atypical MPL mutations also presented increase in phosphorylation of signaling proteins including JAK2/STAT, PI3K/AKT, and MAPK/RAS. In summary, the MPLA497-L498ins4 and MPLW515RQ516E are gain-of-function mutations which may be novel driving factors participating in the pathogenesis of triple-negative MPN.
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http://dx.doi.org/10.1002/cam4.2387DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6718619PMC
September 2019

Epidemiological and clinical differences between sexes and pathogens in a three-year surveillance of acute infectious gastroenteritis in Shanghai.

Sci Rep 2019 07 10;9(1):9993. Epub 2019 Jul 10.

The Center for Disease Control and Prevention of Minhang District, Minhang District, 965 Zhongyi Avenue, Shanghai, 201101, P.R. China.

Acute infectious gastroenteritis cases in Shanghai, reported over three years, were analyzed. Pathogens were identified in 1031 patients; of these, 725 and 306 were bacterial and viral cases, respectively. Vibrio parahemolyticus and Salmonella were the dominant bacteria, and Caliciviridae and Reoviridae were the dominant viral families in the local area. The acute gastroenteritis epidemic peaks appeared in August and January, which represented the active peak periods of bacteria and viruses, respectively. Logistic regression analyses with sex stratification showed that abdominal pain, fever and ingestion of unsafe food at restaurants were independent factors more frequently associated with bacterial gastroenteritis irrespective of sex; red cell-positive fecal matter was associated with bacterial gastroenteritis with an odds ratio (OR) of 3.28 only in males; and white blood cell count was associated with bacterial gastroenteritis with an OR of 1.02 only in females. Pathogen stratification showed that age, vomiting and red cell-positive fecal matter were associated with males with ORs of 0.99, 0.61 and 1.71, respectively, in bacterial gastroenteritis; and the migrant ratio was higher in males with an OR of 2.29 only in viral gastroenteritis. In conclusion, although bacterial and viral gastroenteritis shared many features, epidemiological and clinical factors differed between sexes and pathogens.
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http://dx.doi.org/10.1038/s41598-019-46480-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6620335PMC
July 2019

The novel PI3K inhibitor S1 synergizes with sorafenib in non-small cell lung cancer cells involving the Akt-S6 signaling.

Invest New Drugs 2019 10 19;37(5):828-836. Epub 2018 Nov 19.

China State Key Laboratory of New Drug & Pharmaceutical Process, Center for Pharmacological Evaluation and Research, Shanghai Institute of Pharmaceutical Industry, 1111 Rd. Zhongshanbeiyi, Hongkou, Shanghai, 200437, China.

Non-small cell lung cancer (NSCLC) has been the major cause of cancer-related deaths worldwide. Targeted therapy has been available as an additive strategy for NSCLC patients, but the inevitable resistance to mono-targeted agents has largely hampered its usage in the clinic. We have previously designed and synthesized a novel small molecule compound S1, 2-methoxy-3-phenylsulfonamino-5-(quinazolin-6-yl) benzamides and demonstrated its inhibition of PI3K and mTOR as well as the anti-tumor potential. In the present study, we have identified that S1 alone or combined with the multi-kinase inhibitor sorafenib can inhibit the in vitro cell proliferation of NSCLC cells (A549, NCI-H157 and 95D cells) and tumor growth in the A549 xenograft model. S1 alone produced inhibitory effects on the colony formation, cell migration and invasion and angiogenesis, with more pronounced inhibition when used with sorafenib. We further revealed that S1 mainly inhibited the Akt/S6 phosphorylation while sorafenib mostly decreased the phosphorylation of ERK. Together, the novel PI3K/mTOR inhibitor S1 per se exhibits strong anti-tumor effects in NSCLC cells and A549 xenograft, effects possibly via its inhibition of cell proliferation, invasion and migration and angiogenesis. The combination of S1 and sorafenib exerts potentiated anti-tumor effects, in which the underlying mechanisms may involve their differential modulation of the phosphorylation of Akt and S6 in the PI3K/Akt/mTOR cascades and ERK phosphorylation in the Raf/MEK/ERK pathways. The combination of S1 and sorafenib could be used as an additive approach in treating NSCLC in the clinic.
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http://dx.doi.org/10.1007/s10637-018-0698-2DOI Listing
October 2019

TET2 rs2454206, TET2 rs12498609 and ASXL1 rs3746609 single nucleotide polymorphisms in patients with myelodysplastic syndromes.

Blood Cells Mol Dis 2019 02 7;74:44-50. Epub 2018 Nov 7.

Department of Hematology, The Second Hospital of Shanxi Medical University,382 Wuyi St, Taiyuan, Shanxi, China. Electronic address:

To study the association between TET2rs2454206, TET2rs12498609 and ASXL1rs3746609 and Myelodysplastic syndromes (MDS), a total of 90 MDS patients and 143 healthy volunteers were included. The clinical data, bone marrow samples of patients and peripheral blood samples of volunteers were obtained. We found TET2rs2454206 G/A genotype, TET2rs12498609 G/C genotype and ASXL1rs3746609 A/G genotype in 13.3%, 11.1%, 10.1% MDS patients and in 42.7%, 22.4%, 23.8% healthy volunteers (P < 0.001; P = 0.029; P = 0.009, respectively). TET2 rs2454206 G/A genotype was associated with higher serum LDH level in MDS (P = 0.025). Patients with TET2rs12498609 G/C genotype were characterized with higher frequency of mutated SRSF2 gene (P = 0.042) and lower occurrence rate of anemia (P = 0.026) than those with C/C genotype. ASXL1rs3746609 A/G genotype linked with higher thrombocyte counts (P = 0.02) and percent of total T lymphocyte (P = 0.029), whereas with lower percent of NK cell (P = 0.032) and B lymphocyte (P = 0.007). None of these three SNPs had impact on the overall survival and disease progression to AML. We concluded that People with TET rs2454206 G/A genotype, TET2rs12498609 G/C genotype or ASXL1rs3746609 A/G genotype were related to lower prevalence of MDS. All of the three SNPs were associated with certain laboratory features in MDS patients.
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http://dx.doi.org/10.1016/j.bcmd.2018.11.002DOI Listing
February 2019

The CD9 CD11b HLA-DR immunophenotype can be used to diagnose acute promyelocytic leukemia.

Int J Lab Hematol 2019 Apr 13;41(2):168-175. Epub 2018 Oct 13.

The Haematology Department, The Second Hospital of Shanxi Medical University, Taiyuan City, Shanxi Province, China.

Objective: To investigate the immunophenotypic characteristics of acute promyelocytic leukemia (APL) and explore the sensitivity and specificity of various antibody combinations for the timely and accurate diagnosis APL.

Methods: A retrospective analysis was performed using morphological, immunological, genetic, and molecular biological data from 92 patients diagnosed with APL and 190 controls diagnosed with non-APL acute myeloid leukemia.

Results: For APL diagnosis, the CD9/CD11b/human leukocyte antigen (HLA)-DR antibody combination had 85% sensitivity and 95% specificity, AUC = 0.85. However, the sensitivity and specificity were 39% and 92%, AUC = 0.65, respectively, for the HLA-DR/CD34/CD117 combination, and 80% and 80%, AUC = 0.80, respectively for the CD11b/HLA-DR combination. Significant differences were observed between the different antibody combinations.

Conclusions: The CD9/CD11b/HLA-DR antibody combination displays high sensitivity and specificity and can be used to diagnose APL.
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http://dx.doi.org/10.1111/ijlh.12929DOI Listing
April 2019

Virus-induced gene silencing (VIGS) for functional analysis of MYB80 gene involved in Solanum lycopersicum cold tolerance.

Protoplasma 2019 Mar 5;256(2):409-418. Epub 2018 Sep 5.

Beijing Key Laboratory of New Technology in Agricultural Application, Plant Science and Technology College, Beijing University of Agriculture, Beijing, 102206, China.

Virus-induced gene silencing (VIGS) is a method for transiently silencing genes in dicot and monocot plants. To evaluate the effects of chilling injury on activity of the MYB80 gene in Solanum lycopersicum, an investigation was conducted by VIGS using TRV-GFP (a modified TRV vector) to silence the target gene. During the chilling treatment (4/12 °C, 8/16-h dark/light photoperiod, with 60% humidity), the leaves were collected to analyze the malondialdehyde (MDA) content, soluble sugar content, free proline levels, and relative electric conductivity (REC). Leaves collected 2 weeks after chilling treatment were used to detect the in situ accumulation of superoxide radical (O). Additionally, we collected leaves at selected time points for semi-quantitative reverse transcription-PCR (RT-PCR) analysis. Eventually, 20 days after chilling treatment, all plants were evaluated at 4 °C for 7 days to assess the chilling injury index. The results validated that the MYB80 gene was related to cold tolerance of tomato plants, and that silencing of the MYB80 gene reduced the cold resistance ability.
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http://dx.doi.org/10.1007/s00709-018-1302-5DOI Listing
March 2019

Clinical significance of droplet digital PCR quantitative monitoring of KIT gene mutation levels in core binding factor leukemia.

Int J Lab Hematol 2018 Dec 8;40(6):e124-e126. Epub 2018 Jul 8.

Department of Hematology, The Second Hospital of Shanxi Medical University, Taiyuan, Shanxi, China.

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http://dx.doi.org/10.1111/ijlh.12883DOI Listing
December 2018

Synthetic Polymer Affinity Ligand for Bacillus thuringiensis ( Bt) Cry1Ab/Ac Protein: The Use of Biomimicry Based on the Bt Protein-Insect Receptor Binding Mechanism.

J Am Chem Soc 2018 06 24;140(22):6853-6864. Epub 2018 May 24.

Department of Chemistry , University of California-Irvine , Irvine , California 92697 , United States.

We report a novel strategy for creating abiotic Bacillus thuringiensis ( Bt) protein affinity ligands by biomimicry of the recognition process that takes place between Bt Cry1Ab/Ac proteins and insect receptor cadherin-like Bt-R proteins. Guided by this strategy, a library of synthetic polymer nanoparticles (NPs) was prepared and screened for binding to three epitopes FRGSAQGIEGS, RRPFNIGINNQQ and FRSGFSNSSVSIIR located in loop α8, loop 2 and loop 3 of domain II of Bt Cry1Ab/Ac proteins. A negatively charged and hydrophilic nanoparticle (NP12) was found to have high affinity to one of the epitopes, RRPFNIGINNQQ. This same NP also had specific binding ability to both Bt Cry1Ab and Bt Cry1Ac, proteins that share the same epitope, but very low affinity to Bt Cry2A, Bt Cry1C and Bt Cry1F closely related proteins that lack epitope homology. To locate possible NP- Bt Cry1Ab/Ac interaction sites, NP12 was used as a competitive inhibitor to block the binding of NITIHITDTNNK, a specific recognition site in insect receptor Bt-R, to RRPFNIGINNQQ. The inhibition by NP12 reached as high as 84%, indicating that NP12 binds to Bt Cry1Ab/Ac proteins mainly via RRPFNIGINNQQ. This epitope region was then utilized as a "target" or "bait" for the separation and concentration of Bt Cry1Ac protein from the extract of transgenic Bt cotton leaves by NP12. This strategy, based on the antigen-receptor recognition mechanism, can be extended to other biotoxins and pathogen proteins when designing biomimic alternatives to natural protein affinity ligands.
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http://dx.doi.org/10.1021/jacs.8b01710DOI Listing
June 2018
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