Advances in the study of mitophagy-related receptor proteins / 生理学报

Cells selectively scavenge redundant or damaged mitochondria by mitophagy, which is an important mechanism of mitochondrial quality control. Recent studies have shown that mitophagy is mainly regulated by autophagy-related genes (Atgs) in yeast cells, while mitochondrial membrane associated proteins such as PTEN-induced putative kinase 1 (PINK1), NIX/BNIP3L, BNIP3, FUN14 domain containing 1 (FUNDC1), FKBP8/FKBP38, Bcl-2-like protein 13 (Bcl2L13), nucleotide binding domain and leucine-rich-repeat-containing proteins X1 (NLRX1), prohibitin 2 (PHB2) and lipids such as cardiolipin (CL) are the key mitophagic receptors in mammalian cells, which can selectively recognize damaged mitochondria, recruit them into isolation membranes by binding to microtubule-associated protein 1 light chain 3 (LC3) or γ-aminobutyric acid receptor-associated protein (GABARAP), and then fuse with lysosomes to eliminate the trapped mitochondria. This article reviews recent research progress of mitophagy-related receptor proteins.

Expression of Fascin-1 and β-catenin protein in colorectal adenocarcinoma and its relevance with K-ras gene mutations / 临床与实验病理学杂志

Purpose To examine the expression of Fascin-1 and β-catenin protein and K-ras gene mutation in colorectal adenocarcinoma, and to explore their role in progression of colorectal neoplasm and their relevance. Methods Fascin-1 and β-catenin were analyzed by use of immunohistochemistry En Vision two-step. K-ras gene mutation was detected by ARMS method.Relationship between overexpression of Fascin-1, the nuclear expression of β-catenin, and the mutations of K-ras gene and clinicopathologic parameters was analyzed, the correlation between them was also analyzed. Results In 112 colorectal adenocarcinoma samples, the overexpression rate of Fascin-1 protein was 27.7％ (31/112), significantly higher than non-neoplastic mucosa (P < 0.01). The high nuclear expression rate of β-catenin was 29.5％ (33/112) in adenocarcinoma and non-neoplastic mucosa respectively with a significant difference between two groups (P < 0.01). High expression rate of Fascin-1 protein and β-catenin were correlated significantly with lymph node metastasis (P = 0.022, P = 0.027), and TNM staging (P =0.042, P = 0.019) in colorectal adenocarcinoma. The overexpression of Fascin-1 protein was correlated with tumor location (P = 0.004). The mutation rate of K-ras gene was 34.8％ (39/112), which showed no correlation with age, gender, tumor size, grade of differentiation, lymph node metastasis and TNM staging (P> 0.05). There was a correlation between the overexpressison of Fascin-1 protein, the nuclear expression of β-catenin and the mutation of K-ras gene (rs= 0.252, rs= 0.258, P < 0.05). The overexpression of Fascin-1 protein positively correlated with the nuclear expression of β-catenin (rs= 0.213, P < 0.05). Conclusion Fascin-1 protein and β-catenin protein are involved in invasion and metastasis of colorectal cancer and are associated with K-ras gene mutation. K-ras may promote the overexpression of Fascin-1 by virtue of nuclear expression ofβ-catenin, which provided a new research direction on the treatment of K-ras gene mutated colorectal adenocarcinoma.

Clinical significance of distribution of ABO blood group in patients with deep sternal wound infection after cardiac surgery / 中国感染控制杂志

Objective To explore the clinical significance of distribution of ABO blood group in patients with deep sternal wound infection(DSWI)after cardiac surgery.Methods Clinical data of 84 patients with DSWI after cardiac surgery in the department of cardiothoracic surgery in General Hospital of China Aviation of China Medical University in 2012-2014 were analyzed retrospectively, according to ABO blood group, patients were divided into 4 groups:A blood group, B blood group, AB blood group, and O blood group, according to whether the blood group was A group, they were divided into A blood group and non-A blood group.Distribution of ABO blood group in DSWI patients was analyzed, risk factors, clinical manifestations, and etiological characteristics of DSWI patients with different ABO blood groups were compared.Results Among patients with DSWI, A blood group and non-A blood group were 33 cases(39.3％)and 51 cases(60.7％)respectively(B, O, and AB blood group were 16 cases[19.1％], 29 cases[34.5％], and 6 cases[7.1％]respectively);the proportion of A blood group in DSWI patients was higher than that of the healthy population, but the difference was not statistically significant(P=0.055). Distribution of baseline characteristics and incidences of various clinical manifestations among DSWI patients of different blood groups were not statistically significant(all P＞0.05).However, compared with non-A blood group or other ABO blood groups, DSWI patients with A blood group had higher incidence of elevated white blood cell count, difference was statistically significant(P＜0.05), positive detection rate of gram-positive bacteria in A blood group was also higher, difference was statistically significant(P＜0.05).In addition, only 3 strains of Pseudomonas aeruginosa was detected only in B blood group, while gram-negative bacteria were not detected in AB blood group. Conclusion ABO blood group may play a role in the pathogenesis of DSWI after cardiac surgery, which may be associated with a specific bacterial infection.

Expression of long non-coding RNA DGCR5 in gastric cancer and its clinical significance / 医学研究生学报

Objective Recent evidence points towards a close relationship between dysregulation of long non-coding RNA (lncRNA) and carcinogenesis and progression of various tumors including gastric cancer. The aim of this study was to investigate the expression of lncRNA DGCR5 in the gastric cancer tissue and plasma and its influence on the biological behavior of gastric cancer cells. Methods We collected tumorous and adjacent normal tissues from 96 gastric adenocarcinoma patients as well as plasma samples from 34 gastric cancer patients and another 34 healthy controls. We deter-mined the expression of DGCR5 by real-time fluorescent quantitative PCR,analyzed its correlation with the clinicopathological features of gastric cancer,observed the apoptosis, proliferation and invasiveness of the gastric cancer cells after overexpressing DGCR5, and detected the expressions of epithelial-mesenchymal transition (EMT)-associat-ed genes and proteins by Western blot. Results The expression of DGCR5 was significantly decreased in tumor tissue of the gastric canc-er patients as compared with that in the adjacent normal tissue,which was correlated with the advanced TNM stage and lymph node metastasis, and so was it in the plasma of the patients, which was also correlated with the TNM stage. The area under the ROC curve for the diagnosis of gastric cancer by the expression level of plasma DGCR5 was 0.722. Overexpressed DGCR5 induced significant apoptosis and inhibited the proliferation and invasion of gastric cancer cells,markedly promoted the expression of E-cadherin,and suppressed the expressions of N-cadherin,vimentin and Twist. Conclu-sion The expression of DGCR5 is significantly decreased in the tumor tissue and plasma of gastric cancer patients. The DGCR5 level in the plasma has a certain diagnostic value for gastric cancer. Overexpressed DGCR5 can reduce the proliferation and invasiveness of gastric cancer cells,increase their apoptosis,and inhibit EMT.

Study on intestinal absorption features of berberine hydrochloride phospholipid solid dispersions by rat single-pass perfusion model / 中草药

Objective: To compare intestinal absorption features of berberine hydrochloride phospholipid solid dispersions (BBH-PSD) by rat single-pass perfusion model, and to explore the mechanism of berberine bioavailability increasing mechanism by phospholipid solid dispersion technology. Methods: The single-pass perfusion model was established in rats, the concentration of berberine in intestinal perfusion was determined by HPLC, and phospholipid solid dispersion technology promoting intestinal absorption of berberine was investigated. Results: Compared with berberine, BBH-PSD could promote much more absorption of berberine in various intestinal segments, especially in jejunum, and the mechanism was related to improving permeability and strengthen simple diffusion of berberine. The Ka and Papp values of BBH and BBH-PSD in jejunum were obviously higher than BBH (P < 0.05); When the volumetic flow rate of BBH-PSD was 0.2, 0.4, and 0.8 mL/min, Ka and Papp were both higher than BBH (P < 0.05); The increasing mass concentration was not obvious to intestinal absorption of BBH, while the increasing mass concentration of BBH-PSD obviously increased the intestinal absorption of BBH (P < 0.05). Conclusion: Intestinal absorption characteristics of berberine phospholipid solid dispersion is beneficial to improve berberine oral bioavailability, and it can provide a scientific basis for the development of new dosage forms of berberine hydrochloride.

Expression of CHMP4A and TSPYL-2 in early esophageal cancer and their significance / 临床与实验病理学杂志

Purpose To investigate the role of CHMP4A and TSPYL-2 in early pathogenesis of esophageal cancer.Methods Through comparison of the four subtractive libraries,early esophageal squamous cell carcinoma genes CHMP4A and TSPYL-2 were chosen for further study.Through RT-PCR and immunohistochemistry methods,CHMP4A and TSPYL-2's expression was detected in esophageal squamous cell carcinoma tissue,cancerous tissue and normal esophageal mucosa.Results CHMP4A and TSPYL-2 expression between esophageal squamous cell carcinoma and normal esophageal epithelium tissue had significant differences (P ＜ 0.05),and the CHMP4A gene expression in esophageal mucosa,field cancerization areas,esophageal squamous cell carcinoma tissue increased,while TSPYL-2 gene expression in esophageal mucosa,field cancerization areas,esophageal squamous cell carcinoma tissue decreased,which were consistent with the protein expression of CHMP4A and TSPYL-2.Conclusion CHMP4A and TSPYL-2 genes are differentially expressed in esophageal squamous cell carcinoma,which can be used as alternative genetic markers for further research.

Gene chip technology used in the detection of HPV infection in esophageal cancer of Kazakh Chinese in Xinjiang Province / 华中科技大学学报（医学）（英德文版）

This study was aimed to screen human papillomavirus (HPV) types associated with esophageal squamous cell carcinoma of Kazakh in Xinjiang using the gene chip technique and study the clinical significance of this application. The DNAs were collected from esophageal squamous cell carcinoma tissues and healthy esophageal mucosa of Kazakh adults in Xinjiang, and amplified firstly using HPV MY09/11 and then using HPV G5+/6+ to screen positive HPV specimens. These positive specimens were further detected by the gene chip technique to screen highly pathogenic HPV types. After determination with nested PCR amplification with HPV MY09/11 and G5+/6+, the infection rate of HPV was 66.67% in the esophageal squamous cell carcinoma group and 12.12% in the healthy control group. By testing the positive HPV specimens from the esophageal squamous cell carcinoma group, the infection rate of HPV16 was 97.72% and the co-infection rate of HPV16 and HPV18 was 2.27%. HPV16 infection may be involved in the development of esophageal squamous cell carcinoma in Xinjiang Hazakh adults.

Gene chip technology used in the detection of HPV infection in esophageal cancer of Kazakh Chinese in Xinjiang Province / 华中科技大学学报（医学）（英德文版）

This study was aimed to screen human papillomavirus (HPV) types associated with esophageal squamous cell carcinoma of Kazakh in Xinjiang using the gene chip technique and study the clinical significance of this application. The DNAs were collected from esophageal squamous cell carcinoma tissues and healthy esophageal mucosa of Kazakh adults in Xinjiang, and amplified firstly using HPV MY09/11 and then using HPV G5+/6+ to screen positive HPV specimens. These positive specimens were further detected by the gene chip technique to screen highly pathogenic HPV types. After determination with nested PCR amplification with HPV MY09/11 and G5+/6+, the infection rate of HPV was 66.67% in the esophageal squamous cell carcinoma group and 12.12% in the healthy control group. By testing the positive HPV specimens from the esophageal squamous cell carcinoma group, the infection rate of HPV16 was 97.72% and the co-infection rate of HPV16 and HPV18 was 2.27%. HPV16 infection may be involved in the development of esophageal squamous cell carcinoma in Xinjiang Hazakh adults.

Resveratrol induces apoptosis and autophagy in T-cell acute lymphoblastic leukemia cells by inhibiting Akt/mTOR and activating p38-MAPK / 生物医学与环境科学（英文）

<p><b>OBJECTIVE</b>To explore the effects of resveratrol-induced apoptosis and autophagy in T-cell acute lymphoblastic leukemia (T-ALL) cells and potential molecular mechanisms.</p><p><b>METHODS</b>The anti-proliferation effect of resveratrol-induced, apoptosis and autophagy on T-ALL cells were detected by using MTT test, immunofluorescence, electronic microscope, and flow cytometry, respectively. Western blotting was performed for detecting changes of apoptosis-associated proteins, cell cycle regulatory proteins and state of activation of Akt, mTOR, p70S6K, 4E-BP1, and p38-MAPK.</p><p><b>RESULTS</b>Resveratrol inhibited the proliferation and induced apoptosis and autophagy in T-ALL cells in a dose and time-dependent manner. It also induced cell cycle arrest at G0/G1 phase via up regulating cyclin-dependent kinase (CDK) inhibitors p21 and p27 and down regulating cyclin A and cyclin D1. Western blotting revealed that resveratrol significantly decreased the expression of antiapoptotic proteins (Mcl-1 and Bcl-2) and increased the expression of proapoptotic proteins (Bax, Bim, and Bad), and induced cleaved-caspase-3 in a time-dependent manner. Significant increase in ratio of LC3-II/LC3-I and Beclin 1 was also detected. Furthermore, resveratrol induced significant dephosphorylation of Akt, mTOR, p70S6K, and 4E-BP1, but enhanced specific phosphorylation of p38-MAPK which could be blocked by SB203580. When autophagy was suppressed by 3-MA, apoptosis in T-ALL cells induced by resveratrol was enhanced.</p><p><b>CONCLUSION</b>Our findings have suggested that resveratrol induces cell cycle arrest, apoptosis, and autophagy in T-ALL cells through inhibiting Akt/mTOR/p70S6K/4E-BP1 and activating p38-MAPK signaling pathways. Autophagy might play a role as a self-defense mechanism in T-ALL cells treated by resveratrol. Therefore, the reasonable inhibition of autophagy in T-ALL cells may serve as a promising strategy for resveratrol induced apoptosis and can be used as adjuvant chemotherapy for T-ALL.</p>

Rapamycin sensitizes glucocorticoid resistant acute lymphoblastic leukemia CEM-C1 cells to dexamethasone induced apoptosis through both mTOR suppression and up-regulation and activation of glucocorticoid receptor / 生物医学与环境科学（英文）

<p><b>OBJECTIVE</b>To explore the role of glucocorticoid (GC) receptor (GR) in rapamycin's reversion of GC resistance in human GC-resistant T-acute lymphoblastic leukemia (ALL) CEM-C1 cells.</p><p><b>METHODS</b>CEM-C1 cells were cultured in vitro and treated with rapamycin at different concentrations with or without 1 μmol/L dexamethasone (Dex). 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) test was performed to assess cell proliferation. The cell cycle and cell apoptosis were analyzed by flow cytometry. The expression of GRα mRNA was determined by real-time quantitative RT-PCR. The expression of GR, p-70S6K, Mcl-1, and Bim proteins was detected by Western blot.</p><p><b>RESULTS</b>When incubated with rapamycin at different concentrations, CEM-C1 cells showed significant growth inhibition in a time- and concentration-dependent manner. The growth inhibition was synergistically increased when CEM-C1 cells were treated with rapamycin plus 1 μmol/L Dex. CEM-C1 cells treated with rapamycin alone showed no apparent apoptosis, and were arrested at G0/G1 phase. After the treatment with Dex plus rapamycin, CEM-C1 cells demonstrated apparent apoptosis and increased the cell cycle arrested at G0/G1 phase. Rapamycin combined with Dex up-regulated GRα, phosphorylated GR(p-GR), and pro-apoptotic protein Bim-EL in CEM-C1 cells, but inhibited the expression of p-p70S6K, a downstream target protein of mTOR (mammalian target of rapamycin).</p><p><b>CONCLUSION</b>After the treatment with rapamycin plus Dex, Dex resistant CEM-C1 cells induce growth inhibition and apoptosis. The underlying mechanism may involve inhibition of the mTOR signaling pathway and also be associated with up-regulation of GR expression and activation of GC-GR signaling pathway.</p>

Measurement of serum growth differentiation factor 15 concentration in children with hemophagocytic lympohistiocytosis and implications in the development of hyperferritinemia / 中华实用儿科临床杂志

Objective To measure the serum growth differentiation factor (GDF15) levels in children with hemophagocytic lympohistiocytosis (HLH),and to explore its possible implications in the development of hyperferritinemia in HLH.Methods Twenty-eight children with newly-diagnosed HLH and 20 age-and-sex matched healthy children were enrolled in this study as research subjects and controls respectively.Serum GDF15 levels were measured by Quantikine ELISA assay (product of R&D Company,USA) according to manufacturer's instructions.Serum ferritin concentration and other biochemical parameters were determined by conventional methods.Comparison of serum GDF15 levels between HLH group and healthy control group were made by nonparametric Mann-Whitney test.Correlations between serum GDF15 concentration and hemobiochemical parameters (Hb,serum ferritin,fibrinogen,blood lipids,and liver and renal function tests) were made via Spearman correlation analysis.Results Serum GDF15 concentration was significantly higher in HLH group than that in healthy control group,with median concentrations and ranges of 1710 ng/L,190-2400 ng/L,and 260 ng/L,104-649 ng/L,respectively (P ＜ 0.001).Serum GDF15 concentration was correlated neither to Hb concentration at diagnosis nor to lowest Hb concentration before HLH-directed chemotherapy.Nevertheless it was positively correlated to serum level of total bilirubin at diagnosis and highest concentration of triglycerates during disease course (x2 =0.475,0.465 ; P =0.011,0.019,respectively),and negatively correlated to lowest levels of fibrinogen and albumin at diagnosis (x2 =-0.423,-0.399 ;P =0.031,0.039,respectively).Serum GDF15 level was not correlated to underlying etiology and mortality rate of children with HLH.Conclusions GDF15 has been documented as an upstream negative regulator of hepcidin,the central iron regulatory hormone produced primarily by hepatocytes,and is massively produced by activated macrophages in an autocrine fashion to suppress further activation of macrophages.This research finding that serum GDF15 level is significantly elevated in children with HLH suggests that GDF 15 is intimately implicated in the modulation of iron homeostasis and the development of hyperferritinemia in HLH.

Myxoid adrenal cortical tumor: report of four cases / 中华医学杂志(英文版)

Myxoid adrenocortical neoplasms are rare. Surgical resection of the mass is the first-line therapy. Here we reported a total of four patients, aged 44–66 years, diagnosed with myxoid adrenocortical tumor. The clinical characteristics and immunohistochemical features of the tumor are discussed in the current literature.

TfR2 mRNA expression in bone marrow mononuclear cells of children with hyperplastic anemia and its implications / 中国实验血液学杂志

The aim of this study was to investigate the expression of transferrin receptor 2 (TfR2) mRNA in bone marrow mononuclear cells (BMMNC) of children with hyperplastic anemia (HA), to analyze the correlation of TfR2 mRNA expression level with Hb level, bone marrow erythroid hyperplasia, iron status in body and underlying diseases, and to evaluate the role of TfR2 in erythroid hemopoiesis and the useful value in diagnosis of HA. The experiment was divided into 2 groups: test group, in which 40 patients with HA were enrolled, and control group in which 10 patients without erythroid disorders and hematological malignancies confirmed by bone marrow examination were enrolled. The bone marrow samples of patients in mentioned above 2 groups were collected, the TfR2 mRNA expression in BMMNC of patients with HA was detected by fluorescence-quantitative PCR, the correlation of HA with bone marrow erythroid hyperplasia, iron status of body and underlying diseases was analyzed. The results showed that the relative level of TfR2 mRNA expression in HA patients was significantly higher than that in control patients. The TfR2 mRNA expression level negatively correlated with Hb level in peripheral blood (r = -0.715), while it positively correlated with ratio of bone marrow erythroblasts (r = 0.533). It is concluded that TfR2 mRNA expression in HA patients increases and closely correlates with hyperplasia status of bone marrow and anemia level in peripheral blood.

Effect of jieze no. 1 gel on vaginal levels of lactobacillus, glycogen and lactoferrin in mice / 中国中西医结合杂志

<p><b>OBJECTIVE</b>To evaluate the effect of Jieze No. 1 Gel (JZ1) on the inner environment of vagina through observing its influences on vaginal levels of lactobacillus, glycogen and lactoferrin in mice.</p><p><b>METHODS</b>One hundred female Kunming mice were randomized into 5 groups, the blank control (BC) group, the blank gel (BG) group, and the three JZ1 treated groups. They were treated via vagina with saline, matrix gel, high (2 mg/microL), middle (1 mg/microL) and low (0.5 mg/microL) dose JZ1 respectively in volume of 20 microL, 72 h after being subcutaneously injected with physiological estradiol benzoate (E2) 2 microg. The 24 h and 72 h living lactobacillus in vaginal lavage fluid cultures were counted, the content of glycogen and the expression of lactoferrin in vaginal tissue were measured.</p><p><b>RESULTS</b>No significant difference was found between the BC group and the three JZ1 treated groups in terms of lactobacillus-CFU, glycogen content and lactoferrin expression, and these indices detected at 24 h were not different to those detected at 72 h in the groups treated with various doses of JZ1 respectively (P > 0.05).</p><p><b>CONCLUSION</b>Once application of JZ1 shows no effect on levels of lactobacillus, glycogen, and lactoferrin expression in the vagina of mice.</p>

Effect of Jieze No.1 on cervicitis caused by ureaplasma urealyticum and on ureaplasma urealyticum in vitro / 中国结合医学杂志

<p><b>OBJECTIVE</b>To observe the clinical therapeutic effect of Jieze No. 1 ( I ) on cervicitis caused by ureaplasma urealyticum and its inhibitory effect on ureaplasma urealyticum (Uu) in vitro.</p><p><b>METHODS</b>A total of 393 patients suffering from cervicitis induced by ureaplasma urealyticum without other complications were randomly assigned to 3 groups, the combined treatment group: 140 patients treated with Chinese herbs Jieze No.1 by vaginal lavage, 30 min each time, once a day for 10 consecutive days and oral administration of Azithromycin, 1.0 g once every 72 h for three times; Jieze group: 115 patients were treated with Jieze No.1 alone by vaginal lavage, 30 min each time, once a day for 10 consecutive days; and the Azithromycin group: 138 patients were treated with oral administration of Azithromycin, 1.0 g once in 72 h for three times. All the patients were treated for 1 therapeutic course and condom were used for contraception during the treatment course. The Uu patients were examined again after 21 days of treatment. The therapeutic effect on cervicitis was observed. The experimental study of Jieze No. 1 on the Uu strain separated from the secretion of the urogenital tract was also observed. The minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) of the Uu were investigated.</p><p><b>RESULTS</b>The total effective rate of the combined group was 85.3%, showing a significant difference compared with the Jieze group (67.8%) and the Azithromycin group (60.3%, both P<0.01). There was no statistical significance between the latter two groups (P>0.05). The clearing rate of Uu in the combined group was 78.4%, that of the Jieze group was 60.9% and the Azithromycin group was 47.9%. The combined group also showed a significant difference in comparison with the other two groups (all P<0.01). Especially for the drug-resistant strain, the clearing rate of Uu reached 48.1% in the combined group, 42.1% in the Jieze group, and 16.1% in the Azithromycin group, respectively. The clearing rate of Uu for the drug-resistant strain in the former two groups had significant differences in comparison with the latter (P<0.01, P<0.05), while there was no significant difference between the former two (P>0.05). The range of MIC and MBC of Jieze No. 1 to the drug-resistant strain of Uu was 15.62-250.00 mg/mL. To the non-drug-resistant MIC and MBC strain, it was 15.62-125.00 mg/mL. For the drug-resistant strain, MIC(50) was < or = 31.25 mg/mL, MBC(50) was < or = 62.50 mg/mL, MIC(90) was < or = 125.00 mg/mL and MBC(90) was 250.00 mg/mL. For the non-drug-resistant strain, MIC(50) was < or = 31.25 mg/mL, MBC50 was< or = 62.50 mg/mL, MIC(90) was< or = 62.50 mg/mL and MBC(90) was < or = 125.00 mg/mL.</p><p><b>CONCLUSION</b>Jieze No.1 combined with Azithromycin can effectively treat cervicitis caused by Uu. The laboratory study confirms that Jieze No. 1 has an inhibitory effect on ureaplasma urealyticum strain. It has a remarkably effective therapeutic effects on drug-resistant strains, which is worthy of further research.</p>

Study on activation of AKT/mTOR pathway in anaplastic large cell lymphoma / 中华血液学杂志

<p><b>OBJECTIVE</b>To study the expression of anaplastic lymphoma kinase (ALK) and the phosphorylation status of AKT, mammalian target of rapamycin (mTOR), 4E-binding protein 1 (4E-BP1) and ribosomal protein S6 kinase (p70S6K) and their interrelationships and clinical pathological significance in anaplastic large cell lymphoma (ALCL) patients.</p><p><b>METHODS</b>Immunohistochemical and EnVision methods were used to detect the expression of ALK, p-AKT, p-mTOR, p-4E-BP1 and p-p70S6K.</p><p><b>RESULTS</b>Among the 81 ALCL patients, 51 (63.0%) expressed ALK, whereas the other 30 (37.0%) did not. Patients with ALK(+) ALCL had a better prognosis than those with ALK-ALCL (P < 0.05). Out of the 71 ALCL samples studied, p-AKT was detected in 54 (76.1%) samples and its phosphorylation was correlated with ALK expression (P < 0.05); p-mTOR was detected in 57 (80.3%) samples and its expression was correlated with both ALK and p-AKT (P < 0.05); p-4E-BP1 and p-p70S6K were detected in 64 (90.1%) and 66 (93.0%) samples respectively, and their expressions were related with p-mTOR (P < 0.05), but not with ALK or p-AKT (P > 0.05). COX Proportional Hazard Model analysis showed that both the expression of ALK and the B symptoms affected the prognosis (P < 0.05), moreover, the former had greater impact than the later.</p><p><b>CONCLUSION</b>Expressions of p-AKT, p-mTOR, p-4E-BP1 and p-p70S6K are detected in ALCL, while ALK(+) cases have higher incidence than those with ALK(-) cases. Phosphorylation of AKT and mTOR is correlated with ALK expression, suggesting that there is an activated pathway of AKT/mTOR in patients with ALK(+) ALCL, but the activation have no obvious prognostic significance.</p>

Blockage of mTOR signaling pathway by rapamycin contributes to inhibition of tumor cell proliferation in ALK-positive lymphoid cell strains / 中华血液学杂志

<p><b>OBJECTIVE</b>To investigate the relationship between mTOR signaling pathway and ALK-positive lymphoid cell lines.</p><p><b>METHODS</b>The expression of the downstream effector proteins of mTOR were analyzed by Western blot before and after Karpas299, BaF3/NPM-ALK and BaF3 cell lines treated with rapamycin. Effect of rapamycin on cell proliferation was detected by MTT assay. FACS was used to analyze apoptosis and cell cycles.</p><p><b>RESULTS</b>mTOR signaling phosphoproteins, p-p70S6K and p-4E-BP1 were highly expressed in ALK(+) Karpas299, BaF3/NPM-ALK and parental BaF3 cell lines, and they were dephosphorylated after 1 h withdrawal of IL-3 in BaF3 cells. After 48 h exposure to 10 nmol/L rapamycin, p-p70S6K and p-4E-BP1 proteins expression were decreased, and mainly for the former. The relative inhibitory rate to its control cells was 24.4% in Karpas299, 37.8% in BaF3/NPM-ALK and 61.6% in BaF3. The apoptotic ratio was increased from (11.97 +/- 0.11)% to (15.87 +/- 0.62)% in Karpas299 (P < 0.05), from (3.23 +/- 0.11)% to (7.67 +/- 0.49)% in BaF3 (P < 0.05) and from (1.90 +/- 0.47)% to (2.80 +/- 0.27)% in BaF3/NPM-ALK (P > 0.05). The fraction of G(1) phase cells increased from (37.63 +/- 1.91)% to (69.77 +/- 5.44)% in BaF3/NPM-ALK, from (31.13 +/- 2.51)% to (40.70 +/- 1.47)% in Karpas299 and (53.57 +/- 2.22)% to (63.70 +/- 1.20)% in BaF3 (P < 0.05).</p><p><b>CONCLUSION</b>NPM-ALK kinase can activate mTOR signaling pathway. Rapamycin can inhibit the proliferation of ALK(+) lymphoid cells by blocking mTOR signaling pathway and inducing cell cycling arrest at G(1) phase.</p>

Diffuse large B-cell lymphoma with expression of anaplastic lymphoma kinase protein: clinicopathologic and immunohistochemical study of 5 cases / 中华病理学杂志

<p><b>OBJECTIVE</b>To study the clinicopathologic features of diffuse large B-cell lymphoma (DLBCL) with expression of anaplastic lymphoma kinase (ALK) protein.</p><p><b>METHODS</b>Nine hundred and forty-five (945) cases of DLBCL (including 177 consultation cases) diagnosed according to the 2001 World Health Organization classification of tumors of hematopoietic and lymphoid tissues were enrolled into the study. Immunohistochemical study for anti-ALK-11 was performed using LSAB technique. The ALK-positive cases were further confirmed by immunohistochemical study using EnVision technique. Only ALK-positive cases by EnVision technique were further analyzed by immunostaining for antigens including CD20, CD3, CD30, EMA, granzyme-B, TIA-1 and PC. Immunoglobulin heavy chain gene rearrangement study was also performed and follow-up data collected.</p><p><b>RESULTS</b>There were altogether 5 (4 males and 1 female) cases of DLBCL showing expression of ALK protein. The age of the patients ranged from 34 to 72 years. All were primary nodal DLBCL. One case belonged to clinical stage I, 2 in stage II and 2 in stage III. The duration of follow up ranged from 4 to 32 months. Three patients subsequently died and the longest survival was 32 months. Morphologic subtypes included centroblastic 2, anaplastic 1, immunoblastic with plasmacytoid differentiation 1 and plasmablastic 1. Immunohistochemically, 4 cases were CD20 positive (including 2 centroblastic, 1 anaplastic and 1 immunoblastic cases). The plasmablastic case expressed kappa light chain and was negative for CD20. Rearrangement of immunoglobulin heavy chain gene was demonstrated in all 5 cases studied. As for ALK protein staining, a mixed membranous and cytoplasmic (1 immunoblastic case), granular cytoplasmic (2 centroblastic and 1 anaplastic cases) and mixed nuclear and cytoplasmic (1 plasmablastic case) patterns were observed.</p><p><b>CONCLUSIONS</b>Expression of ALK protein is a rare phenomenon in DLBCL and can be seen in centroblastic, anaplastic, immunoblastic and plasmablastic subtypes. It is often associated with aggressive clinical behavior and worse prognosis. A new pattern of ALK protein expression, mixed membranous and cytoplasmic, is reported.</p>

The Choice of Intra-esophageal Metallic Stent / 实用放射学杂志

Objective To further control the indications and to improve the effect of intra-esophageal metallic stents.Methods 83 metallic stents were be planted into esophageal through endoscopy and under X-ray TV guiding using two kinds of stent meterials in 72 cases with benign or maligant stenosis(esophageal,cardiac orifice).Results The operation of planting stents was successful in all patients and the effect of treatment of esophageal stenosis with stents covered by dacron kint membrane was best.The clinical symptoms and food intaking ablities of all patients were improved.Conclusion Home-made nitinol stents can be plant in treatment of malighent esophageal stenosis.It should be first choice for the patients without indications of surgery or after operation.

Compartive Analysis on CT Diagnosis and Surgical Finding of LDH / 实用放射学杂志

Objective To improve the level of CT in diagnosing LDH and to provide the proof for selecting method of clinical treatment in lumbar disc herniation (LDH). Methods 218 cases of LDH showed by CT and operative exploration were analysed retrospectively.Results The accurate rats of CT diagnosis of LDH were 95.4%. According to CT findings it may be divided into 5 types: Ⅰ was central type, Ⅱ was postero-lateral type, Ⅲ was forminal type, Ⅳ was extreme lateral type, was nucleus pulposus type. Conclusion CT plays an important role in diagnosis and selecting methods of clinical treatment of LDH; It is signficance to enhance the accurate rats of CT diagnosis and the effect of treatment by distinguish nucleus pulposus and fibrous scar tissue from CT finding of LDH.