Effects of 2-dodecyl-6-methoxycyclohexa-2,5-diene-l ,4-dione on resisting hepatic fibrosis induced by CC14 in rats and its mechanisms via TGF-pi/Smads signaling pathway / 中国药理学通报

Aim To investigate the effects of 2-dode-cyl-6-methoxycyclohexa-2 , 5-diene-l, 4-dione ( DM-DD) on resisting hepatic fibrosis induced by carbon tetrachloride ( CC14 ) in rats and the underlying mechanisms , with a specific focus on the TGF-pi/Smads signaling pathway. Methods The hepatic fibrosis model was replicated using 50% CC14. Various parameters, including levels of aspartate transferase ( AST) , ala-nine transferase ( ALT ) , albumin/globulin ( A/G ) , total protein (TP) , total bilirubin (T-BIL) , hyaluron-ic acid ( HA ) , laminin ( LN ) , collagen type Ж ( Col Ж) , and collagen type IV(ColIV) in the blood, were measured. Liver tissue lesions and fiber formation were observed using HE and Masson staining. The expression levels of a smooth muscle actin (a-SMA) , collagen type I ( Col I ) , transformed growth factor (TGF-pi), Smad2, and Smad7 proteins were assessed using immunohistochemistry. a-SMA, Coll, TGF-pi, and Smad7 mRNA levels in liver tissue were measured by RT-PCR. Additionally, the expression levels of TGF-pi, Smad4, and Smad7 proteins in liver tissue were determined by Western blot. Results In comparison to the normal control group, the model group exhibited significantly elevated levels of AST, ALT, TP, T-BIL, HA, LN, Col Ш and Col IV in serum. But A/G level notably decreased. Successful modeling was confirmed by the presence of extensive fiber formations observed through HE and Massonstaining in liver tissue. The DMDD administration group demonstrated a notable decrease levels of AST, ALT, TP, T-BIL, HA, LN, Col III, and CollV, but A/G was significantly elevated when compared to the model group. Furthermore, a-SMA, Coll, TGF-f31, Smad2 and Smad4 mRNA and protein levels in the DMDD administration group were significantly reduced, while Smad7 significantly declined. HE and Masson staining results reflected a marked reduction in fibrous hyper-plasia. Conclusion DMDD exhibits a protective effect against CCl4-induced hepatic fibrosis, and its mechanism appears to be associated with the TGF-fJl/ Smads signaling pathway.

Effect of processing method on chemical constituents of Rehmanniae Radix: based on UHPLC-LTQ-Orbitrap MS / 中国中药杂志

This study aims to explore the chemical composition of Rehmanniae Radix braised with mild fire and compare the effect of processing method on the chemical composition of Rehmanniae Radix. To be specific, ultra-high performance liquid chromatography with linear ion trap-orbitrap mass spectrometry(UHPLC-LTQ-Orbitrap MS) was used to screen the chemical constituents of Rehmanniae Radix. The chemical constituents were identified based on the relative molecular weight and fragment ions, literature information, and Human Metabolome Database(HMDB). The ion peak area ratio of each component before and after processing was used as the index for the variation. SIMCA was employed to establish principal component analysis(PCA) and orthogonal partial least squares discriminant analysis(OPLS-DA) models of different processed products. According to the PCA plot, OPLS-DA plot, and VIP value, the differential components before and after the processing were screened out. The changes of the content of differential components with the processing method were analyzed. A total of 66 chemical components were identified: 57 of raw Rehmanniae Radix, 55 of steamed Rehmanniae Radix, 55 of wine-stewed Rehmanniae Radix, 51 of repeatedly steamed and sundried Rehmanniae Radix Praeparata, 62 of traditional bran-braised Rehmanniae Radix, and 63 of electric pot-braised Rehmanniae Radix. Among them, the 9 flavonoids of braised Rehmanniae Radix were from Citri Reticulatae Pericarpium. PCA suggested significant differences in the chemical composition of Rehmanniae Radix Praeparata prepared with different processing methods. OPLS-DA screened out 32 chemical components with VIP value >1 as the main differential components. Among the differential components, 9 were unique to braised Rehmanniae Radix(traditional bran-braised, electric pot-braised) and the degradation rate of the rest in braised(traditional bran-braised, electric pot-braised) or repeatedly steamed and sundried Rehmanniae Radix was higher than that in the steamed or wine-stewed products. The results indicated the chemical species and component content of Rehmanniae Radix changed significantly after the processing. The 32 components, such as rehmapicrogenin, martynoside, jionoside D, aeginetic acid, hesperidin, and naringin, were the most important compounds to distinguish different processed products of Rehmanniae Radix. The flavonoids introduced by Citri Reticulatae Pericarpium as excipient may be the important material basis for the effectiveness of braised Rehmanniae Radix compared with other processed products.

Effect of Notch1 on extracellular matrix deposition in the renal tubulointerstitium of diabetes / 生理学报

The aim of the present study was to observe the effects of Notch1 and autophagy on extracellular matrix deposition in renal tubulointerstitium of diabetes and to explore the mechanism. The mice were randomly divided into normal control group (db/m mice) and diabetes group (db/db mice). After 12 weeks of feeding, the mice were sacrificed and the corresponding biochemical indexes were measured. Rat renal tubular epithelial cells NRK52E were cultured under normal glucose (NG) and high glucose (HG) respectively, and the expression of Notch1 and LC3 proteins were detected by Western blotting. Autophagosomes in NRK52E cells with overexpressed and knockdown Notch1 under NG and HG conditions were observed by confocal microscope, and the expression changes of Notch1, Collagen-I and III protein were detected by immunofluorescence. The results showed that the Notch1 and Collagen-III expressions were increased (P < 0.01) and the LC3 expression was decreased (P < 0.05) in db/db mice compared with db/m mice. In vitro, the Notch1 was increased (P < 0.01) and the LC3 expression was decreased significantly (P < 0.01) in NRK52E cells of HG group compared with NG group. There was no significant change of Notch1 and LC3 expression between the mannitol (MA) group and the NG group. Autophagy was decreased and extracellular matrix deposition was aggravated when Notch1 was overexpressed. In contrast, autophagy was increased and extracellular matrix deposition was relieved by knockdown of Notch1 under HG conditions. In conclusion, Notch1 protein expression was increased and autophagy was reduced in renal tissue of diabetes and renal tubular epithelial cells under HG. The extracellular matrix deposition in the renal tubulointerstitium was relieved by regulating autophagy after the knockdown of Notch1.

Clinical application of combined infratemporal fossa approaches for internal carotid artery in petrous bone reconstruction for large lateral skull base tumors / 中华耳鼻咽喉头颈外科杂志

Objective: By summarizing the technical points and therapeutic outcomes of combing infratemporal fossa approach (IFA) and internal carotid artery (ICA) reconstruction for the colossal skull base tumor invading ICA in petrous bone, the clinical application value was discussed. Methods: Five patients (2 males, 3 females,aging from 27 to 55 years old) who received surgeries between July 2015 and May 2017 for lateral skull base pathology involved petrous ICA using technique combined IFA and pre-reconstruction, were reviewed. Results: Among the five patients, three were paraganglioma of head and neck, one was carotid aneurysms, and one was recurrent adenoid cystic carcinoma (ACC). The median tumor size in the largest cross-section was 60 mm × 51 mm (range, 28 mm × 22 mm-72 mm × 58 mm). Complete excision was achieved with IFA and ICA reconstruction. The median blood loss volume was 1 000 ml (range, 600-2 500 ml). Four cases showed no new long-term neurologic sequelae, while one showed hemiplegia due to graft vessel occlusion. Except for the one with ACC having facial nerve cut, others achieved good facial nerve function of HB grade Ⅰ to Ⅱ during 3 to 12 months, follow-up. No tumor recurrence was observed over the median duration of follow-up for above 36 months (range, 36-58 months). Conclusion: For lesions involved superior part of ICA, which is unable to separate from ICA, IFA and ICA reconstruction can achieve complete excision.

Preparation and evaluation of schisandrin B-loaded F127 modified lipid-polymer nanoparticles for inhibition of breast cancer lung metastasis / 中国中药杂志

In the current study, schisandrin B(SchB)-loaded F127 modified lipid-polymer hybrid nanoparticles(SchB-F-LPNs) were developed to improve the inhibition of breast cancer lung metastasis. Modified nanoprecipitation method was used to prepare SchB-F-LPNs. The nanoparticles were spherical in shape with shell-core structure by TEM observation. SchB-F-LPNs showed a mean particle size of(234.60±6.11) nm with zeta potential of(-5.88±0.49) mV. XRD results indicated that SchB existed in the nanoparticles in an amorphous state. The apparent permeability coefficient through porcine mucus of F-LPNs was 1.43-fold of that of LPNs as shown in the in vitro mucus penetration study. The pharmacokinetics study showed that the C_(max) of SchB was(369.06±146.94) μg·L~(-1),(1 121.34±91.65) μg·L~(-1) and(2 951.91±360.53) μg·L~(-1) respectively in SchB suspensions group, SchB-LPNs group and SchB-F-LPNs group after oral administration in rats. With SchB suspensions as the reference formulation, the relative bioavailability of SchB-F-LPNs was 568.60%. SchB-F-LPNs inhibited the morphological change during transforming growth factor-β1(TGF-β1)-induced epithelial-mesenchymal transition. In addition, SchB-F-LPNs significantly decreased the number of metastatic pulmonary nodules in 4 T1 tumor-bearing mice, suggesting that SchB-F-LPNs may inhibit the metastasis of breast cancer. These results reveal the promising potential of SchB-F-LPNs in treatment of breast cancer lung metastasis.

Cloning of New Antigen Gene MLAA-34 Promoter and Identification of Core Region in Acute Monocytic Leukemia / 中国实验血液学杂志

OBJECTIVE@#To clone the promoter sequence of acute monocytic leukemia new antigen gene.MLAA-34 and identify its promoter core region.@*METHODS@#The full-length fragment of MLAA-34 gene promoter region was amplified by PCR, then was ligated into pGL3-Basic vector, and the recombinant plasmid was cloned. Constructed a series of MLAA-34 gene promoter 5' flanking region truncated plasmid. These recombinant plasmids were transfected into U937 and HEK293 cells, and the dual luciferase reporter gene was used to detect the promoter activity of each fragment to determine the minimum active region. Transcription factor binding sites were analyzed by bioinformatics methods.@*RESULTS@#The recombinant plasmid containing MLAA-34 promoter sequence and its truncated plasmid were successfully constructed, and the promoter activity was significantly increased as compared with the empty vector (P＜0.001). The minimal active region of MLAA-34 located between 402 bp and 200 bp. It contained multiple transcription factor binding sites such as E2F1, MZF-1, SP1, USF2 and STAT3.@*CONCLUSION@#The promoter of luciferase reporter gene has been successfully constructed with different deletion fragments of MLAA-34, and its core promoter region may contain multiple transcription factor sequence.

Factors affecting prognosis of bronchiolitis in children and management after hospitalization / 中国实用儿科杂志

Bronchiolitis is a common lower respiratory tract infection in infants. Its incidence is high in young children,which seriously affects children's health. A variety of factors can affect the prognosis of bronchiolitis. Giving preventive and therapeutic measures can affect its prognosis,and reduce the occurrence of wheezing in some children.

Removal of giant intraocular foreign body with the assistance of silicone oil tamponade in 23G vitrectomy / 国际眼科杂志(Guoji Yanke Zazhi)

AIM:To evaluate the outcomes and safety of minimally invasive 23G pars plana vitrectomy(PPV) combined with silicone oil tamponade for the removal of giant intraocular foreign body (IOFB).METHODS:A total of 12 cases diagnosed with giant IOFB were included in this retrospective study in which 11 eyes of 11 males and 1 eye of 1 female were treated in Changsha Aier Eye Hospital between February 2012 and March 2015.Among these patients,the preoperative best corrected visual acuity varied from light perception to 0.1 with retinal detachment identified in all 12 eyes.All patients underwent 23G minimally invasive PPV.After the vitreous was removed and the damaged retina was repaired,silicone oil was filled,and then the scleral incision was extended to remove the giant IOFB.Lens extraction and intraocular lens implantation were performed in some patients when necessary.Silicone oil was removed 6mo later.RESULTS:The giant IOFB was removed successfully just with 1 attempt in each of 12 eyes,and no IOFB fell and reinjured the retina or damaged the cornea during the procedure.All retinas were reattached and no endophthalmitis was observed in any patients postoperatively.The silicone oil was removed successfully after 6mo,and by then the visual acuity was improved in all cases.Sixty-seven percent of patients became free of blindness and 25％ free of visual disability.CONCLUSION:Removing giant IOFB through 23G PPV assisted with silicone oil tamponade is safe and effective.

Contrast Researches of Liver Biopsy and Ultrasound in the Diagnosis of Fatty Liver / 昆明医科大学学报

Objective To evaluate the significance of liver biopsy and B ultrasonograpgy in the diagnosis of fatty liver. Methods The results of 62 patients with liver steatosis diagnosed by liver puncture biopsy but not by B-ultrasonograpgy were contrastively analyzed and combined with liver function, blood lipids, blood glucose, and body mass index. Results The 62 cases which were not diagnosed as fatty liver by B-ultrasonograpgy were proved to be 5％-33％liver steatosis after liver puncture biopsy. Among the 62 cases, 23 cases were indicated by the B-ultrasonograpgy that the liver parenchyma echo did not see abnormalities, 18 cases showed the liver parenchyma echo slightly was enlarged, 17 cases showed the liver parenchyma echo density was a bit enhanced and 4 cases were diffuse liver damage,which respectively were 37.01％、29.03％、27.42％and 6.45％. Pathologically it indicated that 45 cases were 5％≤liver steatosis≤19％. Among the 45 cases, 18 cases were indicated by the B-ultrasonograpgy that the liver parenchyma echo was not seen abnormalities, 8 cases showed the liver parenchyma echo slightly was enlarged, 17 cases showed the liver parenchyma echo density was a bit enhanced, and 2 cases were diffuse liver damage, and the change of ultrasound was mainly showed by the liver parenchyma echo not seen abnormalities and the enhanced liver parenchyma echo density. Pathologically it indicated that 17 cases were 20％≤liver steatosis≤33％, 6 cases were indicated by the B-ultrasonograpgy that the liver parenchyma echo did not see abnormalities, 5 cases showed the liver parenchyma echo slightly was enlarged, 5 cases showed the liver parenchyma echo density was a bit enhanced, and 1 case was diffuse liver damage, and the change of ultrasound was mainly showed by the liver parenchyma echo not seen abnormalities, the slightly enlarged liver parenchyma echo and the enhanced liver parenchyma echo density. By analyzing the influence to the ultrasound changes by patients' liver function, body mass index, blood fat and blood sugar, and with logistic regression analysis through a disorderly classification, it was found that the larger value of the glutamine transferase, alkaline phosphatase, body mass index, triglyceride and low density lipoprotein cholesterol, the higher possibility of diffuse liver damage, and the higher level of fatty degeneration, the higher possibility of diffuse liver damage. Conclusion In the diagnosis of fatty liver, when the fatty degeneration is below 1/3, B-ultrasonic examination can't show characteristic changes of fatty liver. It should be closely observed or take liver puncture biopsy to make a definite diagnosis of fatty liver.

Effect of Blocking PYR Complex Binding to DNA Site by Peptide Nucleic Acid on γ-Globin Gene Expression / 中国实验血液学杂志

<p><b>OBJECTIVE</b>To investigate the effect of blocking polypyrimidine complex binding to DNA site by using peptide nucleic acid (PNA) on γ-globin gene expression.</p><p><b>METHODS</b>PYR-PNA, β-PNA and RS-PNA (random sequence-PNA) were designed and synthesized, then were transfected into K562 cells with the cationic liposome lipofectamine 2000 used as vector. The expression of γ-globin gene at both the transcriptional and translational level was detected by RT-PCR and the Western blot respectively at 24 h, 48 h and 72 h after transfection with PNAs.</p><p><b>RESULTS</b>Compared with RS-PNA and control groups, the expression of γ-globin gene at mRNA and protein levels in PYR-PNA group was significantly up-regulated(P<0.05), especially at 48 h after tranfection, the levels of mRNA and protein in PYR-PNA group were increased by 2.0 and 2.5 times than those in control group, respectively.</p><p><b>CONCLUSION</b>PYR-PNA can significantly up-regulate the expression of γ-globin gene in K562 cells, this study may provide a new research idea for gene therapy of β-thalassemia.</p>

Clinical Study on Yishen Huoxue Decoction Combined with Low-Frequency Pulse Magnetic Fields for Treatment of Hemiplegia with Osteoporosis / 中国中医药信息杂志

Objective To observe the clinical efficacy and safety of Yishen Huoxue Decoction combined with low-frequency pulse magnetic fields (PEMFs) for treatment of hemiplegia with osteoporosis (OP). Methods Totally 144 patients were divided into TCM group and control group with randomized parallel controlled method, with 72 cases in each group. Patients in control group were treated with Western routine therapy, rehabilitation training, PEMFs (putting the magnetic head on the back, five times every week, 20-30 minutes each time). On the basis of control group,TCM group received Yishen Huoxue Decoction,one dosage per day,twice a day,orally.The therapeutic course for both groups was 6 weeks. The Fugl-Meyer assessment (FMA), Barthel index (MBI), NIH stroke scale (NIHSS), and visual analogue scale (VAS) before and after treatment were observed in the two groups of patients. Bone mineral density (BMD) was measured. Blood calcium, serum phosphorus, osteocalcin (BGP) content, type 1 procollagen amino-terminal peptide (P1NP), alkaline phosphatase (BALP) were tested. Safety was tested and adverse reactions were observed. Results Compared with before treatment, the scores of FMA, MBI, NIHSS and VAS improved in both groups (P<0.05); the scores of FMA, NIHSS and VAS in the TCM group were significantly improved than the control group after treatment (P<0.05). Compared with before treatment, the levels of BMD, bone metabolic index were improved in both groups (P<0.05). The levels of BMD, BGP, BALP in the TCM group were better than the control group (P<0.05). There was no abnormality in blood routine, liver and kidney function in the 2 groups after treatment, and no obvious adverse reactions were observed. Conclusion Yishen Huoxue Decoction combined with PEMFs can enhance the motor function, improve the neurological deficit symptoms and decrease the pain in hemiplegia patients with OP, and the bone metabolism.

Detection of Novel Antigen MLAA-34 Gene Mutation in Acute Monocytic Leukemia and Its Correlation with Efficacy / 中国实验血液学杂志

<p><b>OBJECTIVE</b>To investigate the correlation of all exone mutation in MLAA-34 gene with chemotherapeutic efficacy for leukemia.</p><p><b>METHODS</b>The expression level of MLAA-34 gene in 40 patients with AML-M5 and 5 healthy volunteers as control was detected by RT-PCR and its effect on chemotherapeutic efficacy were analyzed by RT-PCR; the effect of MLAA-34 gene mutation on overall survival (OS) and progression-free survival (PFS) of AML-M5 patients was analyzed by sequencing of all 12 exoues in MLAA-34 gene, the correlation between the mutation of prognostic genes important to leukemia and the mutation of MLAA-34 gene was explored.</p><p><b>RESULTS</b>The expression level of MLAA-34 gene was significantly up-regulated as compared with that of healthy volunteers, moreover this up-regulation was related with a C59T SNP site located in second exon of MLAA-34 gene, meanswhile this SNP site is affinitive to the well-known mdecular markers of AML, inclinding Fms-like tyrosine kinase (FLT-3) and DNA methyltransferase-3A(DNAMT3A). The AML-M5 patients with high expression of MLAA-34 gene poorly responded to chemotherapy, the AML-M5 patients with MLAA-34 C59T mulation had even more high expression of MLAA-34 gene and significantly short OS and PFS in comparison with those of patients without C59T mutation.</p><p><b>CONCLUSION</b>The C59T mutation in MLAA-34 gene is a high risk factor for recurrence of AML, and may be a cadidate target for treatment of AML.</p>

Drug-Resistant Mechanism of Multiple Myeloma and Its Therapy Combined with HDACi -Review / 中国实验血液学杂志

Drug resistance of multiple myeloma(MM) has become more and more common, and greatly decreased the survival rate of these patients. The occurence of drug-resistance involves in many factors such as bone marrow microenveronment, tumor cell self-metabolism, cytokines, specific targets and so on. In this review, the potential mechanisms of resistance to glucocorticoid/proteasome inhibitor/immunomodulatory druges are briefly expounded in the aspect of tumor cell self-metabolism, including the changes of heat slock protein expression, mRNA expression, related cytokine levels and down-regulation of thalidomid-effecting site CRBN expression. In this review, the researches on the effect of histone deacetylase inhibitors(HDACi) combined with glucocorticoid, proteasome inhibitors, immunomodulatory drugs and monoclonal antibodies on multiple myeloma, specially, drug-resistant multiple myeloma are also summarized.

Correlation of insulin-like growth factor-1 and bone metabolism-related indexes in postmenopausal osteoporosis / 中国组织工程研究

BACKGROUND:Increasing evidence has shown that insulin-like growth factor-1 (IGF-1) plays a regulatory role in bone metabolism and increases bone formation,stimulates osteoblast number and activity,as well as reduces osteoclast differentiation and bone resorption.The mechanism of IGF-1 is an issue of concern.OBJECTIVE:To review the research advance in IGF-1 and the bone metabolism-related indexes in postmenopausal osteoporosis.METHODS:The first author searched the PubMed and CNKI databases between January 2012 and July 2016 using the keywords of "postmenopausal osteoporosis,insulin-like growth factor,bone metabolism,biochemical markers" in English and Chinese,respectively.The repetitive articles were excluded,and 36 eligible articles were enrolled for overview.RESULTS AND CONCLUSION:Bone resorption is increased in postmenopausal woman through the regulation of a variety of cytokines,in which IGF-1 in the blood is combined with IGF binding protein 3,making growth hormone play its biological role.In addition,the growth hormone in the blood directly acts on the adipose tissue,and muscle and bones.Growth hormone exerts a direct effect on bone tissue,promotes osteoblast maturation and differentiation,and enhances the expression of collagen and non-collagen through IGF-1-mediated indirect effect,thus promoting bone formation.The process of bone metabolism is able to reflect the activities of osteoblasts and osteoclasts and the changes of bone matrix and bone mineralization.In vitro experiments show that IGF-1 stimulates the proliferation of osteoblast precursors and differentiate into osteoblasts in a dose-dependent manner,promotes the expression of osteogenic markers such as alkaline phosphatase,type Ⅰ collagen,and osteocalcin,and also stimulates the activity and number of osteoclasts.However,there are few clinical reports and few observation indicators,resulting in a lack of reference range for the detection and treatment of osteoporosis,which needs further exploration.

Clinical Characteristics,Treatment Strategies and Prognostic Factors of 254 Cases of Non Hodgkin's Lymphoma / 中国实验血液学杂志

<p><b>OBJECTIVE</b>To analyze the clinical characteristics and prognostic factors of patients with non-Hodgkin's lymphoma (NHL) in single center of the Northwest area in China for 10 years, so as to provide the evidences for early diagnosis, stratified treatmetn, evaluation of therapeutic efficacy and prognosis, as well as early prevation and so on.</p><p><b>METHODS</b>The clinical data of 254 patients with NHL were analyzed retrospectively, the clinical characteristics were evaluated by unvariate analysis; then the single factors affecting prognosis were enrolled in multivariate analysis and the independent prognostic factors affecting the survival of patients were summarized.</p><p><b>RESULTS</b>A total of 182 cases achieved CR（71.6%）, PR 30 cases（11.8%）, SD 22 cases（8.7%）, PD 20 cases（7.9%）, and RR 212 cases（83.5%). The statistically significant unfavorable prognostic factors for NHL revealed by univariate analysis included age, invasive, Ann Arbor stage, relapse, and total course of chemotherapy. Cox regression model analysis showed that the Ann Arbor stage, IPI, ECOG, B symptoms, peripheral blood cell levels, short-term efficacy, course to achieve CR, and total course of chemotherapy all were the independent prognostic factors.</p><p><b>CONCLUSION</b>The incidence characteristics of NHL in this center displayed mainly middle and high-risk B cell type with attacks at young age, aggression and in lymph nodes. For aggressive lymphoma, the single and multiple prognostic factors may provide the significant guides for the treatment, individualized plan and evaluation of prognosis. The course number of chemotherapy is one of the important factors for survival and prognosis, possessed clinical significance, and worth further clinical research for aggressive lymphoma.</p>

ApoE4 increases glycogen synthase kinase 3β expression and Tau phosphorylation in U87 cells / 南方医科大学学报

<p><b>OBJECTIVE</b>To explore the relations among apolipoprotein E4, Tau protein and glycogen synthase kinase 3β (GSK-3β).</p><p><b>METHODS</b>U87 cells were transfected with pIRES-EGFP (control) or the recombinant plasmids ApoE4/pIRES-EGFP or ApoE3/pIRES-EGFP, and the expression levels of p-Tau/Tau and GSK-3β in the cells were examined with Western blotting. To further confirm the effect of ApoE on GSK-3β and p-Tau expressions, a short interfering RNA (siRNA) targeting ApoE (ApoE-siRNA) was transfected into U87 cells via Lipofectamine 2000 and the protein expressions were examined 24 h later.</p><p><b>RESULTS</b>Compared with those in the control group, the expressions levels of both GSK-3β and p-Tau/Tau increased significantly in the cells transfected with ApoE4 and ApoE3 plasmids (P<0.01), and the ApoE4 plasmid produced a more potent effect than the ApoE3 plasmid on the protein expressions (P<0.01). ApoE knockdown resulted in significantly reduced expressions of GSK-3β (P<0.001) and p-Tau (P<0.01) in the cells.</p><p><b>CONCLUSION</b>ApoE4 can enhance Tau phosphorylation though upregulating GSK-3β, which sheds light on a new role of ApoE4 in Alzheimer's disease.</p>

Genetic Basis of Gastric Cancer / 中国医学科学杂志(英文版)

Gastric cancer is the result of multiple risk factors, including environmental factors, genetic factors and the interaction between them. The environmental factors mainly include dietary, Helicobacter pylori infection and family history of gastric cancer. Genetic factors mainly refer to the susceptible genes that cause epigenetic alterations in oncogenes, tumor suppress genes, cell cycle regulators, DNA repair genes and signaling molecules. This paper summarizes the susceptible genes of gastric cancer and explores the genetic basis of it.

Therapeutic effects of porcine versus rabbit antithymocyte globulins for treatment of severe aplastic anemia / 南方医科大学学报

<p><b>OBJECTIVE</b>To compare the efficacy of porcine and rabbit antithymocyte globulins (ATG) in the treatment of severe aplastic anemia (SAA).</p><p><b>METHODS</b>We reviewed the clinical data of 43 SAA patients receiving porcine ALG treatment and 32 patients receiving rabbit ATG treatment between 2004 and 2013 in our hospital. The overall response rates of the patients at 6 month were compared, and the patients' survival in the two groups was analyzed using Kaplan-Meier survival curves.</p><p><b>RESULTS</b>The overall response rates at 6 months was significantly higher in porcine ALG group than in rabbit ATG group (79.07% vs 56.25%, P=0.034). The 5-year overall survival was also higher in porcine ALG group than in rabbit ATG group, but this difference was not statistically significant (86.047% vs 72.878%, P=0.190).</p><p><b>CONCLUSIONS</b>Porcine ALG is superior over rabbit ATG in terms of hematological response but is comparable with rabbit ATG in view of the patients' survival and safety.</p>

Comparison of the Effectiveness and Safety of Combined Chemotherapy with PEG-Asp for Treatment of ALL and T-NHL Patients / 中国实验血液学杂志

<p><b>OBJECTIVE</b>To explore the effectiveness and safety of combined chemotherapy with pegasparaginase (PEG-Asp) for treatment of patients with acute lymphoblastic leukemia (ALL) and T cell non-Hodgkin's lymphoma (T-NHL) patients.</p><p><b>METHODS</b>A total of 62 ALL or T-NHL patients were diagnosed and treated in our department and were enrolled in this study. Among them, 22 patients received the combined chemotherapy with PEG-Asp, while the other 40 patients received the standard chemotherapy with L-asparaginase (L-Asp) as the control. Therapeutic effectiveness, adverse effects, duration and expense of hospitalization, treatment-related mortality and survival were evaluated and compared in 2 different groups.</p><p><b>RESULTS</b>In group of combined chemotherapy with PEG-Asp, the overall response rate was 90.91% (20 cases), among them CR rate and PR rate are 77.27% (17 cases) and 13.64% (3 cases), respectively. In the group of standard chemotherapy with L-Asp, the overall response rate was 87.5% (35 cases), among them CR rate and PR rate were 72.5% (29 cases) and 15% (6 cases), respectively. The difference neither between PEG-Asp and L-Asp chemotherapy groups nor between ALL and T-NHL subgroups was significant (P > 0.05). The 6-month and 12-month overall survival rates were not significantly different between the PEG-Asp and L-Asp chemotherapy groups, respectively (P > 0.05). The adverse effects were identified as degree 1-2 according to the WHO criteria of drug toxicity. Neither the adverse effects identified as degree 3-4 nor the treatment-related death were observed. Expect for allergy and hyperglycaemia, the difference of side-effect incidence between the two groups were not significant (P > 0.05). The treatment for all the patients in PEG-Asp chemotherapy group was completed, while the treatment with L-Asp was completed only in 29 cases. Moreover, both average duration and expense of hospitalization after the combined chemotherapy were less than the control.</p><p><b>CONCLUSION</b>With higher response rate, lower drug toxicity and allergy incidence, the combined chemotherapy with PEG-Asp can replace the standard chemotherapy with L-Asp in the treatment of ALL and T-NHL. The optimization of the combined chemotheropeutic protocols for more cases and long-term survival rates need to further and deeply explorate.</p>

Preparation of rabbit monoclonal antibody against cGMP and development of competitive ELISA for cGMP / 浙江大学学报·医学版

<p><b>OBJECTIVE</b>To prepare rabbit monoclonal antibody (RabMab) against guanosine 3', 5'-cyclic monophosphate (cGMP) and to develop a competitive ELISA for the detection of cGMP.</p><p><b>METHODS</b>New Zealand white rabbits were immunized with synthesized cGMP-keyhole limpet hemoeyanin (cGMP-KLH) to prepared a RabMAb with monoclonal antibody technique of Epitomics. A competitive ELISA kit was produced with cGMP RabMAb. The specificity, the precision and the recoveries of the method were determined.</p><p><b>RESULTS</b>The RabMAb with high sensitivity towards cGMP were prepared with an antibody timer of 3.1 ng/mL and 50% inhibitive concentration (IC50) of 12.57 ng/mL. The cGMP RabMAb had 33% cross-reactivity to inosine 3', 5'-cyclic monophosphate (cIMP) and little or no cross-reactivity to other compounds. A competitive ELISA was developed for detection of cGMP. The range of detection was 0~120 ng/mL with a minimal limit of 1.95 ng/mL. The recovery of assay was 89%~103%. The inter-assay and intra-assay coefficient variations were below 11.68% and 13.85%, respectively.</p><p><b>CONCLUSION</b>The RabMab against cGMP with high affinity and high specificity has been generated successfully, and a competitive ELISA for detection of cGMP has been developed with the prepared cGMP RabMAb.</p>