Expression profile of microRNA secreted by rat condylar chondrocytes under tensile stress / 中华口腔医学杂志

Objective: To preliminarily explore the mechanism of tensile stress regulating endochondral osteogenesis of condyle by analyzing the expression profiles of significantly different microRNAs (miRNAs) in exosomes of rat mandibular condylar chondrocytes (MCC) under quiescent and cyclic tensile strain (CTS) conditions. Methods: Rat condylar chondrocytes were cultured under static and CTS conditions respectively (10 SD rats, male, 2 weeks old), and exosomes were extracted. The two groups of exosomes were named as control group and CTS group respectively. The differential expression miRNAs were screened by high-throughput sequencing. Bioinformatics analysis and prediction of target genes related to osteogenesis were performed by TargetScan and miRanda website. Results: The exosomes of rat condylar chondrocytes cultured under tensile stress showed a "double concave disc" monolayer membrane structure, the expression of CD9 and CD81 were positive, and the particle size distribution accorded with the characteristics of exosomes, which was consistent with that of static cultured rat condylar chondrocytes. A total of 85 miRNAs with significantly different expression were detected by high-throughput sequencing (P<0.05). The main biological processes and molecular functions of differential miRNAs were biological processes and protein binding, respectively. Kyoto Encyclopedia of Genes and Genomes (KEGG) database pathway enrichment analysis showed that there was significant enrichment in mammalian target of rapamycin (mTOR) signal pathway. The candidate target genes of miR-199a-5p include bone morphogenetic protein 3 (BMP3), endothelin converting enzyme 1, and miR-186-5p may target Smad8 and BMP3 to exert osteogenesis-related functions. Conclusions: Compared with static state, tensile stress stimulation can change the expression of miRNAs such as miR-199a-5p, miR-186-5p in the exocrine body of rat condylar chondrocytes, which can be considered as a mean to regulate the application potential of the exosomes.

Melatonin-Mediated Inhibitory Effect on Hyperimmune Status of Acquired Aplastic Anemia / 中国实验血液学杂志

OBJECTIVE@#To evaluate the expression level of melatonin and its effects on immune function in aplastic anemia (AA) patients.@*METHODS@#The enzyme-linked immunosorbent assay (ELISA) was used to detect the plasma levels of melatonin in AA patients, and the correlation between melatonin levels and laboratory indexs was analyzed. The activation, proliferation, and apoptosis of T cells from AA patients were analyzed by flow cytometry with or without melatonin in vitro.@*RESULTS@#The plasma levels of melatonin in AA patients were significantly lower compared with healthy controls (HC) (12.23 pg/ml vs 20.04 pg/ml, P < 0.01), while the plasma melatonin levels of AA patients in remission group after immunosuppressive therapy (IST) were significantly higher than those in non-remission group (29.16 pg/ml vs 11.73 pg/ml, P =0.04). Moreover, the melatonin levels were positively correlated with platelets (r =0.49), the absolute reticulocyte count (r =0.45), and the percentage of neutrophils (r =0.43). Meanwhile, there was a negative correlation between melatonin levels and the percentages of lymphocytes (r =-0.45). The expressions of CD25 and CD69 in both CD4+ and CD8+ T cells from AA patients were remarkably inhibited by melatonin in vitro (all P < 0.05). When cultured with melatonin, the proliferation rates of both CD4+ and CD8+ T cells from AA patients were markedly suppressed (P =0.01 andP < 0.01).@*CONCLUSION@#The plasma levels of melatonin were decreased in AA patients, which might play an important role in the mechanism of immunological abnormalities. The hyperimmune status of AA patients could be partially ameliorated by melatonin in vitro.

Signaling Mechanism for Modulation by GLP-1 and Exendin-4 of GABA Receptors on Rat Retinal Ganglion Cells / 神经科学通报·英文版

Glucagon-like peptide-1 (GLP-1) is expressed in retinal neurons, but its role in the retina is largely unknown. Here, we demonstrated that GLP-1 or the GLP-1 receptor (GLP-1R; a G protein-coupled receptor) agonist exendin-4 suppressed γ-aminobutyric acid receptor (GABAR)-mediated currents through GLP-1Rs in isolated rat retinal ganglion cells (GCs). Pre-incubation with the stimulatory G protein (Gs) inhibitor NF 449 abolished the exendin-4 effect. The exendin-4-induced suppression was mimicked by perfusion with 8-Br-cAMP (a cAMP analog), but was eliminated by the protein kinase A (PKA) inhibitor Rp-cAMP/KT-5720. The exendin-4 effect was accompanied by an increase in [Ca2+]i of GCs through the IP3-sensitive pathway and was blocked in Ca2+-free solution. Furthermore, when the activity of calmodulin (CaM) and CaM-dependent protein kinase II (CaMKII) was inhibited, the exendin-4 effect was eliminated. Consistent with this, exendin-4 suppressed GABAR-mediated light-evoked inhibitory postsynaptic currents in GCs in rat retinal slices. These results suggest that exendin-4-induced suppression may be mediated by a distinct Gs/cAMP-PKA/IP3/Ca2+/CaM/CaMKII signaling pathway, following the activation of GLP-1Rs.

Pinocembrin Promotes OPC Differentiation and Remyelination via the mTOR Signaling Pathway / 神经科学通报·英文版

The exacerbation of progressive multiple sclerosis (MS) is closely associated with obstruction of the differentiation of oligodendrocyte progenitor cells (OPCs). To discover novel therapeutic compounds for enhancing remyelination by endogenous OPCs, we screened for myelin basic protein expression using cultured rat OPCs and a library of small-molecule compounds. One of the most effective drugs was pinocembrin, which remarkably promoted OPC differentiation and maturation without affecting cell proliferation and survival. Based on these in vitro effects, we further assessed the therapeutic effects of pinocembrin in animal models of demyelinating diseases. We demonstrated that pinocembrin significantly ameliorated the progression of experimental autoimmune encephalomyelitis (EAE) and enhanced the repair of demyelination in lysolectin-induced lesions. Further studies indicated that pinocembrin increased the phosphorylation level of mammalian target of rapamycin (mTOR). Taken together, our results demonstrated that pinocembrin promotes OPC differentiation and remyelination through the phosphorylated mTOR pathway, and suggest a novel therapeutic prospect for this natural flavonoid product in treating demyelinating diseases.

Pinocembrin Promotes OPC Differentiation and Remyelination via the mTOR Signaling Pathway / 神经科学通报·英文版

The exacerbation of progressive multiple sclerosis (MS) is closely associated with obstruction of the differentiation of oligodendrocyte progenitor cells (OPCs). To discover novel therapeutic compounds for enhancing remyelination by endogenous OPCs, we screened for myelin basic protein expression using cultured rat OPCs and a library of small-molecule compounds. One of the most effective drugs was pinocembrin, which remarkably promoted OPC differentiation and maturation without affecting cell proliferation and survival. Based on these in vitro effects, we further assessed the therapeutic effects of pinocembrin in animal models of demyelinating diseases. We demonstrated that pinocembrin significantly ameliorated the progression of experimental autoimmune encephalomyelitis (EAE) and enhanced the repair of demyelination in lysolectin-induced lesions. Further studies indicated that pinocembrin increased the phosphorylation level of mammalian target of rapamycin (mTOR). Taken together, our results demonstrated that pinocembrin promotes OPC differentiation and remyelination through the phosphorylated mTOR pathway, and suggest a novel therapeutic prospect for this natural flavonoid product in treating demyelinating diseases.

Sepsis risk calculator-guided antibiotic management in neonates with suspected early-onset sepsis / 中国当代儿科杂志

OBJECTIVE@#To evaluate the efficacy of sepsis risk calculator (SRC) in guiding antibiotic use in neonates with suspected early-onset sepsis (EOS).@*METHODS@#A total of 284 neonates with a gestational age of ≥ 35 weeks were enrolled as the control group, who were hospitalized in the Children's Hospital of Chongqing Medical University from March to July, 2019 and were suspected of EOS. Their clinical data were retrospectively collected and the use of antibiotics was analyzed based on SRC. A total of 170 neonates with a gestational age of ≥ 35 weeks were enrolled as the study group, who were admitted to the hospital from July to November, 2020 and were suspected of EOS. SRC was used prospectively for risk scoring to assist the decision making of clinical antibiotic management. The two groups were compared in terms of the rate of use of antibiotics, blood culture test rate, clinical outcome, and adherence to the use of SRC.@*RESULTS@#Compared with the control group, the study group had a significantly higher SRC score at birth and on admission (@*CONCLUSIONS@#The use of SRC reduces the rate of empirical use of antibiotics in neonates with suspected EOS and does not increase the risk of adverse outcomes, and therefore, it holds promise for clinical application.

Histomorphological Identification of Nandina domestica / 中国实验方剂学杂志

Objective::Histomorphological study of the Nandinae Radix, Nandinae Caulis, Nandinae Folium, Nandinae Fructus were conducted to provide the basis for the identification of its authenticity and falsehood. Method::The origin and macroscopic identification were used to describe the plant morphology and the appearance characteristics of all medicinal parts. The microscopic characteristics of the medicinal parts, such as roots, stems, leaves, flowers, fruits, were observed and photographed by paraffin section and powder preparation techniques. Result::It was found that the morphological characteristics of the original plant were consistent with the descriptions in herbaceous books. There was no pith on the cross-section of roots. In the transverse section of stems, there were intermittent circular fiber bundles in the cortex and a cap-shaped fibrous bundle in the inner part of the xylem. In the transverse section of the leaves, the palisade tissue was wider and the fiber bundles around the main vascular bundles formed a ring. In the transverse section of petiole, the fiber bundles were arranged intermittently into rings. In the transverse section of fruit, multi-layered sclereids formed a ring in the mesocarp. The powder characteristics of root and stem mainly contained crystalliferous sclereids. There were crystal sheath fibers and stomatal infinitive in the leaf powder, and pollen grains in the flower powder, with 3-hole grooves, obvious reticulate engraving pattern in the outer wall and more reticulate cells. There were a large number of branched sclereids and calcium oxalate square crystals in the fruit powder. Conclusion::The above-mentioned morphological and microscopic features have identification significance, and provide scientific basis for the authenticity identification, the quality standard and the utilization of resources of Nandina domestica.

Shikimic Acid Promotes Oligodendrocyte Precursor Cell Differentiation and Accelerates Remyelination in Mice / 神经科学通报·英文版

The obstacle to successful remyelination in demyelinating diseases, such as multiple sclerosis, mainly lies in the inability of oligodendrocyte precursor cells (OPCs) to differentiate, since OPCs and oligodendrocyte-lineage cells that are unable to fully differentiate are found in the areas of demyelination. Thus, promoting the differentiation of OPCs is vital for the treatment of demyelinating diseases. Shikimic acid (SA) is mainly derived from star anise, and is reported to have anti-influenza, anti-oxidation, and anti-tumor effects. In the present study, we found that SA significantly promoted the differentiation of cultured rat OPCs without affecting their proliferation and apoptosis. In mice, SA exerted therapeutic effects on experimental autoimmune encephalomyelitis (EAE), such as alleviating clinical EAE scores, inhibiting inflammation, and reducing demyelination in the CNS. SA also promoted the differentiation of OPCs as well as their remyelination after lysolecithin-induced demyelination. Furthermore, we showed that the promotion effect of SA on OPC differentiation was associated with the up-regulation of phosphorylated mTOR. Taken together, our results demonstrated that SA could act as a potential drug candidate for the treatment of demyelinating diseases.

Clonal evolution and clinical significance of trisomy 8 in acquired bone marrow failure / 中华血液学杂志

Objective: To analyze clonal evolution and clinical significance of trisomy 8 in patients with acquired bone marrow failure. Methods: The clinical data of 63 patients with acquired bone marrow failure accompanied with isolated trisomy 8 (+8) from June 2011 to September 2018 were analyzed retrospectively, the clonal evolution patterns and relationship with immmunosuppressive therapy were summarized. Results: Totally 24 male and 39 female patients were enrolled, including 39 patients with aplastic anemia (AA) and 24 patients with relatively low-risk myelodysplastic syndrome (MDS) . Mean size of+8 clone in MDS patients[65% (15%-100%) ]was higher than that of AA patients[25% (4.8%-100%) , z=3.48, P=0.001]. The patients were was divided into three groups (<30%, 30%-<50%,and ≥50%) according to the proportion of+8 clone. There was significant difference among the three groups between AA[<30%:55.6% (20/36) ; 30-50%: 22.2% (8/36) ; ≥50%22.2% (8/36) ]and MDS patients[<30%:19.0% (4/21) ; 30%-<50%:19.0% (4/21) ; ≥50%61.9% (13/21) ] (P=0.007) . The proportion of AA patients with+8 clone <30% was significantly higher than that of MDS patients (P=0.002) ; and the proportion of AA patients with+8 clone ≥50%was significantly lower than that of MDS patients (P=0.002) . The median age of AA and MDS patients was respectively 28 (7-61) years old and 48.5 (16-72) years old. Moreover, there was no correlation between age and+8 clone size in AA or MDS (r(s)=0.109, P=0.125; r(s)=-0.022, P=0.924, respectively) . There was statistical difference in total iron binding capacity, transferrin and erythropoietin between high and low clone group of AA patients (P=0.016, P=0.046, P=0.012, respectively) , but no significant difference in MDS patients. The immunosuppressive therapy (IST) efficacy of AA and MDS patients was respectively 66.7% and 43.8% (P=0.125) . Comparing with initial clone size (27.3%) , the +8 clone size (45%) of AA patients was increased 1-2 year after IST, but no statistical difference (z=0.83, P=0.272) . Consistently, there was no significant change between initial clone size (72.5%) and 1-2 year clone size (70.5%) after IST in MDS patients. There was no significant difference in IST efficient rate between +8 clone size expansion and decline group of in AA patients at 0.5-<1, 1-2 and>2 years after IST. We found four dynamic evolution patterns of +8 clone, which were clone persistence (45%) , clone disappearance (30%) , clone emergence (10%) and clone recurrence (15%) . Conclusions: AA patients had a low clone burden, while MDS patients had a high burden of +8 clone. The +8 clone of AA patients didn't significantly expanded after IST, and the changes of +8 clone also had no effect on IST response.

Differential Expression Profiles of MicroRNAs between de novo and Complete Response Severe Aplastic Anemia / 中国实验血液学杂志

<p><b>OBJECTIVE</b>To detect the expression of miRNA in de novo and complete response SAA patients and predict the targets of the miRNAs.</p><p><b>METHODS</b>The expression profiles of miRNA from bone marrow mononuclear cells of the SAA patients with de novo and CR were detected by miRNA microarray.</p><p><b>RESULTS</b>Totally 35 up-regulated and 37 down-regulated miRNA were identified in CR SAA patients in comparison with de novo SAA patients. Furthermore, by predicting the targets of the differentlly expressed miRNA, it was found that some targets associated with T cell receptor signaling pathway and cell adhesion molecules.</p><p><b>CONCLUSION</b>Some miRNA may be involved in the pathogenesis of SAA.</p>

Myt1L Promotes Differentiation of Oligodendrocyte Precursor Cells and is Necessary for Remyelination After Lysolecithin-Induced Demyelination / 神经科学通报·英文版

The differentiation and maturation of oligodendrocyte precursor cells (OPCs) is essential for myelination and remyelination in the CNS. The failure of OPCs to achieve terminal differentiation in demyelinating lesions often results in unsuccessful remyelination in a variety of human demyelinating diseases. However, the molecular mechanisms controlling OPC differentiation under pathological conditions remain largely unknown. Myt1L (myelin transcription factor 1-like), mainly expressed in neurons, has been associated with intellectual disability, schizophrenia, and depression. In the present study, we found that Myt1L was expressed in oligodendrocyte lineage cells during myelination and remyelination. The expression level of Myt1L in neuron/glia antigen 2-positive (NG2) OPCs was significantly higher than that in mature CC1 oligodendrocytes. In primary cultured OPCs, overexpression of Myt1L promoted, while knockdown inhibited OPC differentiation. Moreover, Myt1L was potently involved in promoting remyelination after lysolecithin-induced demyelination in vivo. ChIP assays showed that Myt1L bound to the promoter of Olig1 and transcriptionally regulated Olig1 expression. Taken together, our findings demonstrate that Myt1L is an essential regulator of OPC differentiation, thereby supporting Myt1L as a potential therapeutic target for demyelinating diseases.

Comparison of hemolytic characteristics among paroxysmal nocturnal hemoglobinuria, autoimmune hemolytic anemia and hereditary spherocytosis / 中华血液学杂志

Objective: To determine the valuable hemolytic characteristics in differential diagnosis of paroxysmal nocturnal hemoglobinuria (PNH), autoimmune hemolytic anemia (AIHA) and hereditary spherocytosis (HS). Method: The clinical and hemolytic characteristics of 108 PNH patients, 127 AIHA patients and 172 HS patients diagnosed from January 1998 to April 2017 were compared. Results: ①Reticulocyte percentage (Ret%) of PNH patients [6.70% (0.14%-22.82%)] was significantly lower than that of AIHA [14.00%(0.10%-55.95%), P<0.001] and HS patients [11.83%(0.60%-57.39%), P<0.001]. The Ret% in PNH patients were significantly lower than those in AIHA and HS patients at the same levels of anemia, except for in mild anemia between PNH and AIHA patients. However, when comparing the Ret% between AIHA and HS patients, there was significant difference only in mild anemia [7.63%(1.87%-29.20%)% vs 11.20%(3.31%-22.44%), z=-2.165, P=0.030]. ②The level of TBIL in HS patients was significantly higher than that in AIHA and PNH patients [79.3 (11.2-244.0) μmol/L vs 57.6 (7.6-265.0) μmol/L, z=5.469, P<0.001; 79.3(11.2-244.0) μmol/L vs 26.2(4.6-217.7) μmol/L, z=-2.165, P<0.001], and the proportion of HS patients with TBIL more than 4 times the upper limit of normal (ULN) (64.1%) was significantly higher than that of AIHA (37.7%, χ(2)=19.896, P<0.001) and PNH patients (4.6%, P<0.001). ③The LDH level of PNH patients was significantly higher than that of AIHA and HS [1 500 (216-5 144) U/L vs 487 (29-3 516) U/L, z=-9.556, P<0.001; 1 500 (216-5 144) U/L vs 252 (132-663) U/L, z=-11.518, P<0.001], and the proportion of PNH patients with LDH more than 1 000 U/L (79.1%) was significantly higher than that of AIHA patients (13.0%, χ(2)=93.748, P<0.001) and HS patients (0, P<0.001). ④Splenomegaly occurred in 43.5% of PNH patients, including 16.0% with severe splenomegaly. In contrast, the occurrence of splenomegaly was 98.6% in AIHA patients and 100.0% in HS patients (P<0.001), and 63.0% of AIHA patients (P<0.001) and 90.4% of HS patients (P<0.001) were with severe splenomegaly. ⑤The prevalence of cholelithiasis in HS patients was up to 43.1%, significantly higher than that in AIHA patients (10.5%, P<0.001) and PNH patients (2.9%, P<0.001). Conclusion: The comprehensive assessment of the five hemolytic characteristics is simplified, practical and efficient, with great clinical significance, providing specific indicators for differential diagnosis and efficient approach for making further work-up.

Conventional and Contrast-enhanced Ultrasound Features of Adenoid Cystic Carcinoma in Major Salivary Gland / 中华医学超声杂志（电子版）

Objective To investigate the characterization of adenoid cystic carcinoma (ACC) in major salivary glandby conventional and contrast-enhanced ultrasound (CEUS).Methods The conventional and contrast-enhanced ultrasound images of 17 ACC in major salivary gland with pathological confirmation were retrospectively reviewed.Results 12 (70.6％) cases in 17 were found in submandibular,while 5 cases (29.4％) were in parotid.All the patients complained a mass,52.9％ had cheek pain,and 17.6％ had hadfacial nerve or lingual nerve paralysis;these symptoms had been present from 3 to 240 months (mean duration was 42.9± 62.1 months).14 cases (82.4％) were primary focuses,and 3 cases (17.6％) were recurrences with recurrence time from 36 to 132 months (mean recurrence time was 70.7±43.2 months).All lesions were hypoechoic with irregular shape,and only 17.6％ had a homogeneous echotexture,64.7％ heterogeneous.64.7％ of all tumors were well-defined.On CDFI,blood flow signal hadn't detected in 23.5％ patients,and 64.7％ hadintermediate (+ and + +) grades of vascularity.Only 11.8％ had the highest grade of vascularity (+ + +).The CEUS images of ACC in major salivary showed slow fill-in,centripetal,higher enhancement,inhomogeneous enhancement,poorly defined margins and after enhancing the size unchanged.No enhancement orlow enhancement area were common in the AC.Facial nerve invasion can be seen in all cases,including 3 cases (17.6％) of lingual nerve invasion,4 cases (23.5％) of blood vessel invasion;4 cases (23.5％) of striated muscle infiltration;1 case with mandibular involvement;1 case (5.9％) with cervical lymph node metastasis.94.1％ of ACC in major salivary gland were cribriform patterns,and 5.9％ were solid pattems.Conclusions ACC in major salivary gland are more likely to happen in the submandibular gland,which has especially high tendency of facial nerve invasion and cheek pain.Conventional Ultrasound and CEUS imaging characteristics can be used to differentiate ACC firom other tumors in major salivary gland,which would help clinicians to diagnose.The clinical course is characterized by very late recurrences;consequently,longer following-up with ultrasound is proposed.

Progress in metabolism and function of myelin lipids / 生理学报

Myelin is a highly specialized membrane structure, wrapping around the axons. It is essential for the protection of axons, insulation and maintenance of the saltatory conduction of the action potential. Myelin membrane is rich in lipids, however, the lipid composition varies significantly from other biological membranes. Since myelination requires extraordinarily high level of lipid synthesis, the integrity of myelin is susceptible to numerous lipid metabolism disorders. Studies on transgenic mice targeting key molecules of various lipid biosynthesis pathways have elucidated the lipid metabolism and functions of myelin. Besides, myelinating glial cells have a remarkable capacity to take up extracellular lipids, which also contributes to myelination. Therefore, understanding the metabolism and functions of myelin lipids will help us to understand the role of lipids in myelin damage-related diseases and provide novel strategies for the treatment of demyelinating diseases. In this paper, some progresses in metabolism and functions of myelin lipids are reviewed.

Long-term Follow-up of Patients with Hepatitis-Associated Aplastic Anemia / 中国实验血液学杂志

<p><b>OBJECTIVE</b>To explore the clinical characteristic, therapeutic efficacy and prognosis of patients with hepatitis-associated aplasitc anemia (HAAA).</p><p><b>METHODS</b>the clinical data and labrotatory examination results of 30 cases of HAAA were analyzed retrospectively, the 6-month response ratio and overall survival (OS) were assessed.</p><p><b>RESULTS</b>HAAA most commonly occured in males, with the occurence rate of males and females was 4:1, the median onset age was 16 (4-43) years old, HAAA oriented focus on sever aplastic anemia (SAA)(4 cases,13%) and very sever aplastic anemia (VSAA)(22 cases,73%). Aplastic anemia (AA) could be seen on occurence of hepatitis (accompanied aplastic anemia) (7 cases,23%), or after the onset of hepatits (delayed aplastic anemia) (23 cases,77%), but more often occured in the latter. Statistical analysis showed that when compared with the patients of delayed aplastic anemia, patients accompanied aplastic anemia possesses lower levels of glutamic-pyruvic transaminase(ALT), aspertate aminotransferase (AST) and total bilirubin (TBIL)(P=0.042,0.012,0.001), and possessed a more obvious lymphoid cell disorder when AA occured, with more lower peripheral blood CD19B cells proportion (P=0.046) and more obvious imbalance of CD4/CD8ratio, but the difference was no statistical significant (P=0538). Factors affecting the 6-month respose were the severity of AA (P=0.044), the peak level of bilirubin of hepatitis (P=0.006) and the propotion of mature monocyte in bone marrow (P=0.034). The long-term follow-up showed that the 2-year OS of HAAA was 64.3±9.2%, the 6-month curative efficacy significantly affect the prognosis (P<0.001).</p><p><b>CONCLUSION</b>HAAA more often occur in young male, HAAA is mainly SAA and VSAA and mostly non-A-C hepatitis associated aplastic anemia, patients usually have a high incidence of early infection. Patients acompanied with aplastic anemia possess more obvious immunological derangement; the treatment efficacy for HAAA is poor, patients who haven't obtained 6-month response indicate a sinister prognosis, allogeneic hematopoietic stem cell transplantion is a better choice for these patients.</p>

Clinical Characteristics and Gene Mutations of Gilbert Syndrome Complicated with Myeloproliferative Neoplasm / 中国实验血液学杂志

<p><b>OBJECTIVE</b>To investigate the clinical characteristics and gene mutations of patients with Gilbert syndrome complicated with myeloproliferative neoplasms (MPN).</p><p><b>METHODS</b>Peripheral blood samples from 1 patient with Gilbert syndrome complicated with MPN and his son were collected to analyse all exon mutations of UGT1A1 gene.</p><p><b>RESULTS</b>The patient with leukocytosis, thrombocythemia, mild anemia and positive JAK2/V617F mutation was initially diagnosed as MPN. The hyperbilirubinemia suggested concurrent disease. Further gene evaluation disclosed a insertion mutation in the (TA)TAA box, and a missense mutation(G→A) at 211 bp of exon 1, corresponding to the deficiency in the bilirubin-conjugating enzyme uridine-diphosphoglucuronosyl transferase1A1 (UGT1A1). His son only carried some polymorphism mutation without manifestation of this disease.</p><p><b>CONCLUSION</b>It is a first report case of MPN complicated with Gilbert syndrome that can highlight the differential diagnosis for hyperbilirubinemia.</p>

Application of contrast-enhanced ultrasound in differential diagnosis of pleomorphic adenoma and carcinoma expleomorphic adenoma / 中华超声影像学杂志

Objective To assess the contrast-enhanced ultrasound (CEUS) characteristics of pleomorphic adenoma (PA) and carcinoma ex pleomorphic adenoma (CXPA).Methods A retrospective analyse was made from the contrast-enhanced ultrasonic features of 42 PA and 8 CXPA.The features included tumor size,echotexture,boundary,shape and blood flow richness on conventional US imaging and rise time (RT),time to peak (TP),peak intensity(PI),time from peak to one half(HT),mean transit time (MTT),and area under the curve(AUC) on contrast-enhanced ultrasound.Results All of PA and CXPA were hypoechoic,but there was no difference between them in shape and blood flow richness (P ＞0.05).37.5％ CXPA has hetergeneous echotexture with the presence of anechoic area,but it appeared in only 4.8％ PA(P ＜0.05).The following findings were observed from a perfusion kinetics of CEUS in all of PA and CXPA:slow in,centripetal,heterogeneous enhancement,with no enhancement area.Well-defined margins were presented in 42 PA and in 7 CXPA(P ＜0.05).Their time-intensity curves showed RT,TP,HT and MTT in CXPA group were obviously higher than those in the PA group(P ＜0.05).However there was no statistical difference in PI and AUC between both groups (P ＞ 0.05).Conclusions Conventional US and CEUS perfusion patten provide limited diagnostic information for distinguishing PA from CXPA.CXPA could be diagnosed by ill defined margins,more internal anechoic area and poorly defined margins.But CEUS quantitative analysis can significantly promote the differentiation.

Value of combining PCT, BNP, D-dimer and PCIS score in predicting the prognosis of severe pediatric pneu-monia / 临床儿科杂志

Objective To evaluate the value of combining PCT, BNP, D-Dimer and PCIS score in predicting the prognosis of pediatric severe pneumonia in the early stage. Methods 80 cases of children with severe pneumonia were selected, 49 cases were boys , 31 cases were girls, with a median age of 7.5 months (1 month to 156 months). According to the final outcome, the cases are divided into treatment group and poor prognosis group. The score of PCIS, PCT, BNP and D-dimer within 24 hours after admission were recorded. According to the indicators, ROC curve was drawn independently and integrated with the four indicators,and the corresponding areas under ROC curve (AUC) were calculated to compare the accuracy of the assessment. Results The AUC of PCIS, PCT, BNP and D-dimer were between 0.7 and 0.9. The ROC curve integrated the four indicators showed the AUC were 0.932, which improved sensitivity and specificity. Conclusions The integration of PCIS, PCT, BNP and D-Dimer could improve the accuracy of prediction in the prognosis of severe pediatric pneumonia.

Effect of integrinβ1 on multidrug resistance in gastric cancer SGC-7901 cells / 中国病理生理杂志

AIM:To study the effect of integrin β1 on multidrug resistance in gastric cancer and its possible mechanisms .METHODS:The expression of integrin β1 at mRNA and protein levels in the SGC-7901 cells and SGC-7901/DDP cells was determined by qPCR and Western blot .The expression of integrin β1 in the SGC-7901/DDP cells was silenced by antisense oligodeoxynucleotide .The cell viability was detected by the CCK-8 assay, the cell apoptosis were ana-lyzed by flow cytometry, and the protein levels of integrin β1, Bcl-2/Bax, cleaved caspase-3/caspase-3, cytochrome C ( Cyt-C) and p-AKT/AKT were determined by Western blot .RESULTS:The expression of integrin β1 at both mRNA and protein levels was significantly upregulated in SGC-7901/DDP cells.The expression of integrin β1 was increased in SGC-7901 cells treated with chemotherapeutic agents such as cisplatin , paclitaxel and 5-fluorouracil .Knockdown of integrin β1 induced apoptosis of SGC-7901/DDP cells with an increased sensitivity to the chemotherapeutic agents .Meanwhile , knock-down of integrin β1 downregulated the protein levels of Bcl-2/Bax, p-AKTSer473 and p-AKTThr308 , while promoted the release of Cyt-C and upregulated the protein level of cleaved caspase-3.CONCLUSION:Knockdown of integrin β1 increases the sensitivity of SGC-7901/DDP cells to the chemotherapeutic agents , and promotes the cell apoptosis via mitochondrial apop-tosis pathway .The mechanism may be related to the attenuation of AKT pathway by inhibiting phosphorylations of AKT at Ser473 and Thr308.

Clinical Analysis of 70 Adult Patients with Paroxysmal Nocturnal Hemoglobinuria / 中国实验血液学杂志

<p><b>OBJECTIVE</b>To investigate the clinical characteristics of Chinese patients with paroxysmal nocturnal hemoglobinuria (PNH).</p><p><b>METHODS</b>The clinical data of 70 adult PNH cases in our hospital from January 2000 to December 2009 were analyzed retrospectively, and the clinical manifestation, laboratory examination, treatment, complications and prognostic factors influencing survival rate were assessed.</p><p><b>RESULTS</b>The nosopoietic median age of 70 cases(41 male cases and 29 female cases) was 37 (18-73) years old. The clinical manifestation included fatigue (87.1%), hemogolobinuria (44.3%), infection (22.9%), bleeding (37.1%), and abdominal pain (2.9%). FHb (free hemoglobin) in 56 patients (80%) was <50 mg/L. Hp (haptoglobin) in 54 patients (77.1%) was <0.5 g/L, and LDH in 49 patients (70.0%) was <220 U/L. The overall 10 year-survival rate after diagnosis was 72.2% estimated by Kaplan-Meier. The complications in this study were as follow: recurrent abdominal pain crisis (2.9%), infections (30.0%), thrombotic events (8.6%), evolution to MDS/AML (5.7%), calculus (11.4%) and death (17.1%). Both univariate and multivariate analyses identified risk factors affecting survival, including development of thrombotic events, progression to myelodysplastic syndrome or acute myelogenous leukemia (MDS/AML) and recurrent infections.</p><p><b>CONCLUSION</b>This larger number of cases for the first time allowed us to carry out a detailed analysis of prognostic factors for this rare disease. Evaluation of PNH prognostic factors may provide a basis to assess the current and future therapies of this disease.</p>