Comparison of Posterior Fixation Strategies for Thoracolumbar Burst Fracture: A Finite Element Study.

The management of thoracolumbar (TL) burst fractures remained challenging. Due to the complex nature of the fractured vertebrae and the lack of clinical and biomechanical evidence, currently, there was still no guideline to select the optimal posterior fixation strategy for TL burst fracture. We utilized a T10-L3 TL finite element model to simulate L1 burst fracture and four surgical constructs with one- or two-level suprajacent and infrajacent instrumentation (U1L1, U1L2, U2L1, and U2L2). This study was aimed to compare the biomechanical properties and find an optimal fixation strategy for TL burst fracture in order to minimize motion in the fractured level without exerting significant burden in the construct. Our result showed that two-level infrajacent fixation (U1L2 and U2L2) resulted in greater global motion reduction ranging from 66.0 to 87.3% compared to 32.0 to 47.3% in one-level infrajacent fixation (U1L1 and U2L1). Flexion produced the largest pathological motion in the fractured level but the differences between the constructs were small, all within 0.26 deg. Comparisons in implant stress showed that U2L1 and U2L2 had an average 25.3 and 24.8% less von Mises stress in the pedicle screws compared to U1L1 and U1L2, respectively. The construct of U2L1 had better preservation of the physiological spinal motion while providing sufficient range of motion reduction at the fractured level. We suggested that U2L1 is a good alternative to the standard long-segment fixation with better preservation of physiological motion and without an increased risk of implant failure.

Integrative genomic analyses identify WDR12 as a novel oncogene involved in glioblastoma.

Glioblastoma (GBM) is the most malignant primary brain tumor in adults. Due to its invasive nature, it cannot be thoroughly eliminated. WD repeat domain 12 (WDR12) processes the 32S precursor rRNA but cannot affect the synthesis of the 45S/47S primary transcript. In this study, we found that WDR12 is highly expressed in GBM according to the analysis results of mRNA expression by The Cancer Genome Atlas database. The high expression level of WDR12 is dramatically related to shorter overall survival and reduced disease-free survival. Next, we knocked down WDR12 and found that knockdown of WDR12 promoted the apoptosis and inhibited the proliferation by cell biology experiments. Differential expression genes in gene-chip revealed that WDR12 knockdown mainly inhibited cell cycle. Finally, we also found that WDR12 is associated with PLK1 and EZH2 in cell proliferation of GBM. Resumptively, this report showed a possible evidence that WDR12 drove malignant behavior of GBM, whose expression may present a neoteric independent prognostic biomarker in GBM.

Covalent immobilization of recombinant Citrobacter koseri transaminase onto epoxy resins for consecutive asymmetric synthesis of L-phosphinothricin.

Transaminase responsible for alienating prochiral ketone compound is applicable to asymmetric synthesis of herbicide L-phosphinothricin (L-PPT). In this work, the covalent immobilization of recombinant transaminase from Citrobacter koseri (CkTA) was investigated on different epoxy resins. Using optimum ES-105 support, a higher immobilized activity was obtained via optimizing immobilization process in terms of enzyme loading, coupling time and initial PLP concentration. Crucially, due to blocking unreacted epoxy groups on support surface with amino acids, the reaction temperature of blocked immobilized biocatalyst was enhanced from 37 to 57 °C. Its thermostability at 57 °C was also found to be superior to that of free CkTA. The Km value was shifted from 36.75 mM of free CkTA to 39.87 mM of blocked immobilized biocatalyst, demonstrating that the affinity of enzyme to the substrate has not been apparently altered. Accordingly, the biocatalyst performed the consecutive synthesis of L-PPT for 11 cycles (yields>91%) with retaining more than 91.13% of the initial activity. The seemingly the highest reusability demonstrates this biocatalyst has prospective for reducing the costs of consecutive synthesis of L-PPT with high conversion.

Sumoylation Negatively Regulates CSR1-Dependent Prostate Cancer Cell Death.

BACKGROUND/AIMS: SUMOylation is a dynamic process and reversed by the activity of SUMO-specific proteases (SENPs) family. SENP1, a member of this family, is highly expressed and plays oncogenic roles in diverse cancers including prostate cancer. However, the SENP1-transgenic mice exhibit aberrant transformation of the mouse prostate gland but do not develop cancer. Cellular Stress Response 1 (CSR1) is a tumor suppressor gene and frequently deleted in prostate cancers. Overexpression of CSR1 in prostate cancer cells inhibits colony formation, anchorage-independent growth and induces cell death. METHODS: The relationship between CSR1 and SENP1 were determined by immunoprecipitation-based proteomics screen and verified by GST-pull down assay. In vivo SUMOylation assay was used to detect the direct effect of SENP1 in the regulation of CSR1. Clustered regularly interspaced short palindromic repeats (CRISPR)-based gene editing was used to generate Senp1-/- and CSR1-/- PC3 cells. FACS assay was used to determine the apoptosis ratio of cells after transfection. RESULTS: CSR1 is SUMOylated at K582 and rapid ubiquitinated and degradated in prostate cancer cells. SENP1 interacts with and deSUMOylates CSR1 to prevent its degradation and enhances CSR1-dependent prostate cancer cell death. CONCLUSION: Thus, our data indicates that CSR1 is a critical SUMOylated substrate of SENP1 that might partially explain the controversial roles of SENP1 in prostate cancer development.

CPEB4 interacts with Vimentin and involves in progressive features and poor prognosis of patients with astrocytic tumors.

Cytoplasmic polyadenylation element binding protein 4 (CPEB4) is a regulator of gene transcription and has been reported to be associated with biological malignancy in cancers. However, it is unclear whether CPEB4 has any clinical significance in patients with astrocytic tumors, and mechanisms that CPEB4 contribute to progression of astrocytic tumors remain largely unknown. Here, correlation between CPEB4 expression and prognosis of patients with astrocytic tumors were explored by using qPCR, WB and IHC, and X-tile, SPSS software. Cell lines U251 MG and A172 were used to study CPEB4's function and mechanisms. Co-immunoprecipitation, mass spectrometry, immunofluorescent assay, and western blot were performed to observe the interaction between CPEB4 and Vimentin. CPEB4 mRNA and protein levels were markedly elevated in 12/12 astrocytic tumors in comparison to paratumor. High expression of CPEB4 was significantly correlated with clinical progressive futures and work as an independent adverse prognostic factor for overall survival of patients with astrocytic tumors (relative risk 4.5, 95 % CI 2.1-11.2, p = 0.001). Moreover, knockdown of CPEB4 in astrocytic tumor cells inhibited their proliferation ability , clonogenicity, and invasiveness. Five candidate proteins, GRP78, Mortalin, Keratin, Vimentin, and ß-actin, were identified, and the interaction between CPEB4 and Vimentin was finally confirmed. Downregulation of CPEB4 could reduce the protein expression of Vimentin. Our studies first validated that CPEB4 interacts with Vimentin and indicated that high CPEB4 expression in astrocytic tumors correlates closely with a clinically aggressive future, and that CPEB4 might represent a valuable prognostic marker for patients with astrocytic tumors.

Prognostic significance of Nemo-like kinase expression in patients with hepatocellular carcinoma.

Nemo-like kinase (NLK) is an evolutionarily conserved serine/threonine protein kinase and belongs to the extracellular signal-regulated kinases/microtubule-associated protein kinase families (Erks/MAPKs). Previous studies have indicated that abnormal expressions of NLK played critical roles in various types of human cancers. Recent studies suggested that NLK expression was significantly upregulated in the hepatocellular carcinoma (HCC) specimens. However, the clinical significance of NLK expression in HCC remains largely unknown. In this study, we focused on the clinical significance of NLK in HCC and found that high expression of NLK was significantly associated with Edmondson-Steiner grade (P = 0.002), tumor size (P = 0.022), and no. of tumor nodules (P < 0.001), and NLK was positively correlated with proliferation marker Ki-67 (P < 0.01). Univariate analysis suggested that NLK expression was associated with poor prognosis (P < 0.001). Multivariate analysis indicated that NLK expression was an independent prognostic indicator for HCC (P = 0.0370). In conclusion, NLK overexpression is associated with poor overall survival in patients with HCC, it might be an independent poor prognostic marker for HCC.

[Position analysis of three recombinant proteins of Echinococcus granulosus protoscolex with two-dimensional electrophoresis].

OBJECTIVE: To obtain specific antibodies of the three recombinant antigens obtained previously, rEgZW-5, rEg14-3-3 and rEgP-29, for identifying the corresponding proteins in two-dimensional electrophoretogram of Echinococcus granulosus protoscolex. METHODS: The distribution of proteins from E. granulosus protoscoleces was judged by SDS-PAGE previously. Two-dimensional electrophoresis was used to separate proteins from E. granulosus protoscoleces, and the result was scanned and analyzed by the PDquest software to get the information about the quantity of proteins as well as their isoelectric point (IP) and relative molecular mass (MA,). Rabbits were immunized with the 3 recombinant antigens and antibodies were purified from antisera. Western blotting was used to identify the protein as marker in two-dimensional electrophoretogram of protoscolex. RESULTS: SDS-PAGE displayed that the proteins separated from Echinococcus granulosus protoscoleces mainly distributed in the M, region of 18,000-90,000. 240 proteins were obtained by two-dimensional electrophoresis with M, 15,790-117,050 and IP 4.0-9.5, and 85.8% (206/241) of the proteins showed the IP ranged from 5 to 9. Western blotting showed that the specific antibody of rEg14-3-3 identified the 14-3-3 protein in two-dimensional electrophoretogram of protoscolex with Mr 33 000 and IP 4.86, the specific antibody of rEgZW-5 identified the ZW-5 protein with Mr 23,000 and IP 4.98, and the specific antibody of rEg P-29 identified the P-29 protein with Mr 29,000 and IP 5.65. CONCLUSION: The antibodies against the three recombinant proteins from Echinococcus granulosus protoscoleces can identify corresponding proteins in the two-dimensional electrophoregrams.

The Correlation Between 18F-Fluorodeoxyglucose-Positron Emission Tomography/Computed Tomography Semiquantitative Parameters and the Clinical Features and Pathological Biological Indexes of Gastric Cancer.

Objective: This study explored the application value of the maximum standard uptake value (SUVmax) of 18F-fluorodeoxyglucose-positron emission tomography/computed tomography (18F-FDG PET/CT) in gastric cancer. Materials and Methods: Data of 164 patients with gastric cancer who had undergone18F-FDG PET/CT before a biopsy were collected, and the correlation of SUVmax with clinical stage, pathological differentiation degree, human epidermal growth factor receptor-2 (HER-2) status, and Ki-67 index of gastric cancer was analyzed. Results: The SUVmax of poorly differentiated adenocarcinoma was significantly higher than that of moderately differentiated adenocarcinoma and signet-ring cell carcinoma (p < 0.01), and SUVmax in the well-differentiated adenocarcinoma group was higher than that in the signet-ring cell carcinoma group (p < 0.01). The SUVmax in the HER-2 negative group was higher than that in the HER-2 positive group (p < 0.01). The SUVmax was higher in the Ki-67 high expression group than in the low expression group (p < 0.01), and there was a significant positive correlation between the two (p < 0.01). Conclusion: 18F-FDG PET/CT SUVmax can, to some extent, predict the degree of differentiation, HER-2 status, and Ki-67 index of gastric cancer patients.

The activation of GABAergic neurons in the hypothalamic tuberomammillary nucleus attenuates sevoflurane and propofol-induced anesthesia in mice.

Background: The histaminergic neurons in the hypothalamic tuberomammillary nucleus (TMN) have been suggested to play a vital role in maintaining a rising state. But the neuronal types of the TMN are in debate and the role of GABAergic neurons remains unclear. Methods: In the present study, we examined the role of TMN GABAergic neurons in general anesthesia using chemogenetics and optogenetics strategies to regulate the activity of TMN GABAergic neurons. Results: The results indicated that either chemogenetic or optogenetic activation of TMN GABAergic neurons in mice decreased the effect of sevoflurane and propofol anesthesia. In contrast, inhibition of the TMN GABAergic neurons facilitates the sevoflurane anesthesia effect. Conclusion: Our results suggest that the activity of TMN GABAergic neurons produces an anti-anesthesia effect in loss of consciousness and analgesia.

Effects of elevated CO2 concentration on cell structure and stress resistance physiology of Setaria italica under drought stress.

The frequency of drought will increase under further warming. The increase in atmospheric CO2 concentration, along with more frequent drought, will affect crop growth. We examined the changes of cell structure, photosynthetic physiology, antioxidant enzymes, osmotic regulatory substances, and yield of foxtail millet (Setaria ita-lica) leaves under different CO2 concentrations (ambient air CO2 concentration and ambient atmospheric CO2 concentration + 200 µmol·mol-1) and water treatment (soil moisture content maintained at 45%-55%, and 70%-80% of field capacity, representing mild drought and normal water condition, respectively). The results showed that elevated CO2 concentration increased the number of starch grains, the area of single starch grains, and the total area of starch grains in the chloroplast of millet mesophyll cells. Under mild drought condition, elevated CO2 concentration increased net photosynthetic rate of millet leaves at the booting stage by 37.9%, but did not affect water use efficiency at this stage. Elevated CO2 concentration increased net photosynthetic rate and water use efficiency of millet leaves under mild drought condition at the filling stage by 15.0% and 44.2%, respectively. Under mild drought condition, elevated CO2 concentration increased the content of peroxidase (POD) and soluble sugar in millet leaves at the booting stage by 39.3% and 8.0%, respectively, but decreased proline content by 31.5%. It increased the content of POD in millet leaves at the filling stage by 26.5% but decreased the content of MDA and proline by 37.2% and 39.3%, respectively. Under mild drought condition, elevated CO2 concentration significantly increased the number of grain spikes by 44.7% and yield by 52.3% in both years compared with normal water condition. The effect of elevated CO2 concentration on grain yield under mild drought conditions was higher than that under normal water condition. Under mild drought conditions, elevated CO2 concentration increased leaf thickness, vascular bundle sheath cross-sectional area, net photosynthetic rate, and water use efficiency of millet, improved the antioxidant oxidase activity, and changed the concentration of osmotic regulatory substances, alleviated the nega-tive effect of drought on foxtail millet, and finally increased the number of grains per ear and yield of foxtail millet. This study would provide a theoretical basis for millet production and sustainable agricultural development in arid areas under future climate change.

HMME-based PDT restores expression and function of transporter associated with antigen processing 1 (TAP1) and surface presentation of MHC class I antigen in human glioma.

Numerous studies have established that photodynamic therapy (PDT) can trigger tumor-specific immunity and cancer cell immunogenicity, both of which play a critical role in the long-term control of oncogenesis; however, the underlying mechanisms are largely unexplained. Deficiency of the transporter associated with antigen processing 1 (TAP1) has been observed in a variety of tumors, and the question has been raised whether the restoration of TAP1 could facilitate the activation of antitumor immunity. To elucidate the mechanisms underlying PDT-induced immunopotentiation, we examined the hypothesis that upregulating TAP1 via PDT may contribute to enhancement of antitumor immunity and cancer cell immunogenicity. In this study, we investigated the effects of PDT on the expression and function of TAP1 in glioma cells. We found that HMME-based PDT restored TAP1 expression in a rapid and transient manner. Furthermore, the newly synthesized TAP1 protein was capable of potentiating the activity of transporting antigen peptides. As a result, restoration of the expression and function of TAP1 translated into augmenting the presentation of surface MHC class I molecules. Overall, our data indicate that PDT enables glioma cells to recover both the expression of functional TAP1 and the presentation of surface MHC class I antigens, which are processes that may enhance antitumor immunity after PDT. These findings may have implications for PDT and provide new insights into the mechanisms underlying PDT-induced immunopotentiation.

Redesign of (R)-Omega-Transaminase and Its Application for Synthesizing Amino Acids with Bulky Side Chain.

ω-Transaminase (ω-TA) is an attractive biocatalyst for stereospecific preparation of amino acids and derivatives, but low catalytic efficiency and unfavorable substrate specificity hamper their industrial application. In this work, to obtain applicable (R)-ω-TA responsible for amination of α-keto acids substrates, the reactivities of eight previously synthesized ω-TAs toward pyruvate using (R)-α-methylbenzylamine ((R)-α-MBA) as amine donor were investigated, and Gibberella zeae TA (GzTA) with the highest (R)-TA activity and stereoselectivity was selected as starting scaffold for engineering. Site-directed mutagenesis around enzymatic active pocket and access tunnel identified three positive mutation sites, S214A, F113L, and V60A. Kinetic analysis synchronously with molecular docking revealed that these mutations afforded desirable alleviation of steric hindrance for pyruvate and α-MBA. Furthermore, the constructed single-, double-, and triple-mutant exhibited varying degrees of improved specificities toward bulkier α-keto acids. Using 2-oxo-2-phenylacetic acid (1d) as substrate, the conversion rate of triple-mutant F113L/V60A/S214A increased by 3.8-fold relative to that of wide-type GzTA. This study provided a practical engineering strategy for improving catalytic efficiency and substrate specificity of (R)-ω-TA. The obtained experience shed light on creating more industrial ω-TAs mutants that can accommodate structurally diverse substrates.

Precise diagnosis of three top cancers using dbGaP data.

The challenge of decoding information about complex diseases hidden in huge number of single nucleotide polymorphism (SNP) genotypes is undertaken based on five dbGaP studies. Current genome-wide association studies have successfully identified many high-risk SNPs associated with diseases, but precise diagnostic models for complex diseases by these or more other SNP genotypes are still unavailable in the literature. We report that lung cancer, breast cancer and prostate cancer as the first three top cancers worldwide can be predicted precisely via 240-370 SNPs with accuracy up to 99% according to leave-one-out and 10-fold cross-validation. Our findings (1) confirm an early guess of Dr. Mitchell H. Gail that about 300 SNPs are needed to improve risk forecasts for breast cancer, (2) reveal an incredible fact that SNP genotypes may contain almost all information that one wants to know, and (3) show a hopeful possibility that complex diseases can be precisely diagnosed by means of SNP genotypes without using phenotypical features. In short words, information hidden in SNP genotypes can be extracted in efficient ways to make precise diagnoses for complex diseases.

Asymmetric synthesis of l-phosphinothricin using thermostable alpha-transaminase mined from Citrobacter koseri.

α-Transaminase (α-TA) responsible for catalyzing the reversible transfer of amino groups between amine donors and amine acceptors, is applicable to enzymatic route for asymmetric synthesis of herbicide l-phosphinothricin (l-PPT). In the search for α-TAs with better catalysis performance, three α-TAs were discovered by genome mining approach using a known sequence encoding Escherichia coli tyrosine TA (TyrB) as probe. Through detailed comparison of their expression amount, activities and characteristics, Citrobacter koseri TA (CkTA) exhibited better activity and thermostability, which retain 65.9% of initial activity after incubation at 57 °C for 4 h. The Km and kcat/Km values of CkTA were 36.75 mM and 34.29 mM-1 min-1, respectively. In addition, recombinant CkTA cells were immobilized onto Celite 545 using tris(hydroxymethyl)phosphine as crosslinker. During five repetitive asymmetric synthesis of l-PPT from 20 g/L prostereogenic ketone using l-Glu as amine donor, all the yields of l-PPT reached up to 91.2% (＞99% ee). These characteristics made CkTA a valuable addition to the currently scarce α-TA library for stereospecific synthesis of l-PPT.

Liver retransplantation: a single-centre experience.

BACKGROUND: The curative effect of liver transplantation for patients with end-stage liver disease was encouraging in recent years and the 5-year patient survival rate can reach up to 70%. However, some patients might lose grafts due to a variety of reasons, including bile duct complications, vascular complications, primary non-function, graft rejection and disease recurrence etc. Liver retransplantation (re-LT) was the only available means for those patients whose initial grafts had failed, but the inferior outcomes of re-LT compared to primary liver transplantation (PLT) continue to be a major concern. This study aimed to analyze the indications for re-LT, optimal timing of re-LT, and strategies to improve the survival rate after re-LT. METHODS: From January 2001 to December 2006, we performed 738 liver transplants and 39 re-LT (5.3%) at our center. A retrospective analysis was performed to identify factors (indication for re-LT, preoperative score of model for end-stage liver disease (MELD), interval to re-LT from primary liver transplantation, methods of vascular and biliary reconstruction and common causes of death) associated with survival. RESULTS: Mean follow-up period was 1.8 years (1 to 5 years). Patients with MELD score less than 20 were better than those whose MELD score was > 20 and MELD score > 30 (1-year survival, 80.0% versus 50.0% and 3/5). The perioperative survival rate of patients who received re-LT at an interval of more than 30 days and less than 8 days after the initial transplantation was higher than those who received retransplantation between 8 to 30 days following the first operation (88.5% and 74.3% versus 50.0%). The main causes of death were infection (60.0%), multiple organ failure (20.0%), vascular complications (10.0%) and biliary fistula (10.0%) in perioperative period. The overall patient survival rate of 1-month, 6-month and 1-year was 80.0%, 76.7% and 66.7%, respectively. CONCLUSIONS: Our study suggested the favorable results after re-LT. The analysis also showed optimal timing of operation, refined surgical techniques, individualized immunosuppressive regimen and effective prophylaxis and treatment of perioperative infection play an important role in achieving a higher survival after re-LT.

Underlying mechanism of the photodynamic activity of hematoporphyrin­induced apoptosis in U87 glioma cells.

Photodynamic therapy (PDT) is a relatively novel type of tumor therapy method with low toxicity and limited side­effects. The aim of the present study was to investigate the underlying mechanism and potential microRNAs (miRNAs) involved in the treatment of glioma by PDT with hematoporphyrin, a clinical photosensitizer. The photodynamic activity of hematoporphyrin on the cell viability and apoptosis of gliomas was investigated by MTT, and flow cytometry and fluorescence microscopy, respectively. Alterations in singlet oxygen and mitochondrial membrane potential were detected. The differentially expressed miRNAs and proteins were evaluated by miRNA gene chip and apoptosis­associated protein chip, respectively. The results demonstrated that cell viability significantly decreased with hematoporphyrin concentration. PDT with hematoporphyrin significantly increased cell apoptosis at a later stage, induced the content of reactive oxygen species (ROS) and decreased the mitochondrial membrane potential, indicating that PDT with hematoporphyrin inhibited cell growth via induction of radical oxygen, decreased the mitochondrial membrane potential and induced apoptosis. The upregulated miRNAs, including hsa­miR­7641, hsa­miR­9500, hsa­miR­4459, hsa­miR­21­5p, hsa­miR­663a and hsa­miR­205­5p may be important in PDT­induced cell apoptosis in glioma. Transporter 1, ATP binding cassette subfamily B member­ and nuclear factor­κB­mediated apoptosis signaling pathways were the most significant pathways. Thus, the current study presents PDT as a potential therapeutic approach for the treatment of malignant glioma, and identified miRNAs for the molecular design and development of a third­generation photosensitizer (PS).

Downregulation of miR­205 is associated with glioblastoma cell migration, invasion, and the epithelial-mesenchymal transition, by targeting ZEB1 via the Akt/mTOR signaling pathway.

Glioblastoma (GBM) is the most common type of malignant brain tumor. In spite of recent advancements in surgical techniques, chemotherapy, and radiation therapy, patients with GBM often face a dire prognosis. MicroRNAs have been shown to modulate the aggressiveness of various cancers, and have emerged as possible therapeutic agents for the management of GBM. miR­205 is dysregulated in glioma and act as a prognostic indicator. However, the role of miR­205 in the development of GBM has not been elucidated. To better understand the pathogenesis of GBM, we examine the biological significance and molecular mechanisms of miR­205 in GBM cells. Zinc finger E-box binding homeobox 1 (ZEB1) has been shown to regulate the epithelial-mesenchymal transition (EMT), which is strongly associated with GBM malignancy. In the present study, we show miR­205 expression is reduced in GBM tissues and cell lines, and ZEB1 expression is inversely correlated with miR­205 expression. We also show ZEB1 is a downstream target of miR­205 and the Akt/mTOR signaling pathway is activated when miR­205 interacts with ZEB1. Increased activity of miR­205 in GBM cells significantly inhibits migration and invasion, and prevents EMT. Furthermore, overexpression of ZEB1 partially abolishes these inhibitory effects of miR­205. We show that miR­205 negatively regulates the expression of ZEB1 in GBM, inhibits cell migration and invasion, and prevents EMT, at least in part through the inhibition of the activation of the Akt/mTOR signaling pathway. Our results indicate miR­205 may be an efficacious therapeutic agent in the treatment of GBM.

MALAT1 is a prognostic factor in glioblastoma multiforme and induces chemoresistance to temozolomide through suppressing miR-203 and promoting thymidylate synthase expression.

Glioblastoma multiforme (GBM) is the most malignant brain tumor with limited therapeutic options. Temozolomide (TMZ) is a novel cytotoxic agent used as first-line chemotherapy for GBM, however, some individual cells can't be isolated for surgical resection and show treatment-resistance, thus inducing poor prognosis. By using the HiSeq sequencing and bioinformatics methods, we identified lncRNAs showing different expression levels in TMZ-resistant and non-resistant patients. RT-qPCR was then performed in tissues and serum samples, and lncRNA MALAT1 was finally identified to show considerable discriminating potential to identify responding patients from non-responding patients. Moreover, high serum MALAT1 expression was associated with poor chemoresponse and survival in GBM patients receiving TMZ treatment. Subsequently, the TMZ resistant cell lines were established, and the CCK8 assay showed that lncRNA MALAT1 knockdown significantly reversed TMZ resistance in GBM cells. The gain and loss-function experiments revealed that miR-203 was down-regulated by MALAT1 and this interaction has reciprocal effects. Besides, thymidylate synthase (TS) mRNA was identified as a direct target of miR-203. LncRNA MALAT1 inhibition re-sensitized TMZ resistant cells through up-regulating miR-203 and down-regulating TS expression. On the other hand, MALAT1 overexpression promoted resistance by suppressing miR-203 and promoting TS expression. In conclusion, our integrated approach demonstrates that enhanced expression of lncRNA MALAT1 confers a potent poor therapeutic efficacy and inhibition of MALAT1 levels could be a future direction to develop a novel therapeutic strategy to overcome TMZ resistance in GBM patients.

[One hepatic echinococcosis patient complicated with systemic sclerosis].

This article reports one hepatic echinococcosis patient complicated with systemic sclerosis. His clinical manifestations were the progressive fibrosis of the skin, sour regurgitation, and belching. The blood examination showed that eosinophils was reduced, and antinuclear antibody (ANA) was positive at 1:100 in cytoplasm particle type. He was given prednisone acetate 25 mg, q. d., aspirin 100 mg, q. d., centella triterpenes cream 12 mg t. i. d., esomeprazole 40 mg q. d., and domperidone 10 mg t. i. d. After one week, the Rodnan skin score reduced from 27 to 17. The liver hydatid cyst resection was performed, and the follow-up showed that his clinical manifestations improved and the Rodnan skin score reduced further.