Progress in Gene Therapy of Sickle Cell Disease Based on Hemoglobin F--Review / 中国实验血液学杂志

Sickle cell disease (SCD) is a single gene genetic disease, which seriously threatens the life span and quality of patients. On the basis of the pathogenesis of SCD and the alternative therapy based on fetal hemoglobin F (HbF), the research progress of transcription factors involved in the regulation of HbF gene expression, such as BCL11A, ZBTB7A, KLF-1, c-MYB and SOX6, as well as the application of CRISPR / Cas9, TALEN, zinc finger nuclease and other gene editing technologies in this field has been made, providing a solid theoretical basis for the exploration of new treatment schemes for β- like hemoglobin diseases, such as sickle cell disease and β- thalassemia.

Mechanism of butyl alcohol extract of Baitouweng Decoction (BAEB) on Candida albicans biofilms based on pH signal pathway / 中国中药杂志

This study aimed to investigate the effect of butyl alcohol extract of Baitouweng Decoction( BAEB) on Candida albicans biofilms based on pH signal pathway. The morphology of biofilms of the pH mutants was observed by scanning electron microscope. The biofilm thickness of the pH mutants was measured by CLSM. The biofilm activity of the pH mutants was analyzed by microplate reader.The biofilm damage of the pH mutants was detected by flow cytometry. The expression of pH mutant biofilm-related genes was detected by qRT-PCR. The results showed that the deletion of PHR1 gene resulted in the defect of biofilm,but there were more substrates for PHR1 complementation. BAEB had no significant effect on the two strains. RIM101 gene deletion or complementation did not cause significant structural damage,but after BAEB treatment,the biofilms of both strains were significantly inhibited. For the biofilm thickness,PHR1 deletion or complementation caused the thickness to decrease,after BAEB treatment,the thickness of the two strains did not change significantly. However,RIM101 gene deletion or complementation had little effect on the thickness,and the thickness of the two strains became thinner after adding BAEB. For biofilm activity,PHR1 deletion or complementation and RIM101 deletion resulted in decreased activity,RIM101 complementation did not change significantly; BAEB significantly inhibited biofilm activity of PHR1 deletion,PHR1 complemetation,RIM101 deletion and RIM101 complemetation strains. For the biofilm damage,PHR1 gene deletion or complementation,RIM101 gene deletion or complementation all showed different degrees of damage; after adding BAEB,the damage rate of PHR1 deletion or complementation was not significantly different,but the damage rate of RIM101 deletion or complementation was significantly increased. Except to the up-regulation of HSP90 gene expression,ALS3,SUN41,HWP1,UME6 and PGA10 genes of PHR1 deletion,PHR1 complementation,RIM101 deletion,and RIM101 complementation strains showed a downward expression trend. In a word,this study showed that mutations in PHR1 and RIM101 genes in the pH signaling pathway could enhance the sensitivity of the strains to the antifungal drug BAEB,thus inhibiting the biofilm formation and related genes expression in C. albicans.

Effects of butyl alcohol extract of Baitouweng Decoction on Candida albicans adhesion based on pH-mutant strains under acidic conditions / 中草药

Objective: To investigate the effect and mechanism of butyl alcohol extract of Baitouweng Decoction (BAEB) on adhesion of Candida albicans based on pH signaling pathway. Methods: Spot assay method was used to detect the sensitivity of pH mutants to BAEB under acidic conditions. XTT assay was used to detect the effect of BAEB on metabolic activity of pH mutants. The effect of BAEB on the adhesion activity of pH mutants was observed by fluorescence microscopy. The effect of BAEB on hydrophobicity of pH mutant was determined by n-octane inclusion method. The effect of BAEB on the expression of adhesion genes related to pH mutants was detected by qRT-PCR. Results: Under acidic conditions, spot assay observation showed that pH mutants were less sensitive to BAEB, 512 μg/mL BAEB interfered with pH mutants for 24 h and 48 h, there was no significantly decrease in bacterial colony. XTT assay showed that the metabolic activity of WT, PHR2 complementation, rim101/rim101 and RIM101 complementation was significantly inhibited in 512 μg/mL BAEB, and there was no significantly difference in the inhibition of phr2/phr2 metabolic activity. Fluorescence microscopy showed that the cell adhesion activity of WT, PHR2 complementation, rim101/rim101, RIM101 complementation was significantly inhibited in 512 μg/mL BAEB, the cell adhesion activity of phr2/phr2 had no obvious effect in 512 μg/mL BAEB. The n-octane inclusion method showed that the effect of 512 μg/mL BAEB on the cell surface hydrophobicity of WT, phr2/phr2, PHR2 complementation, rim101/rim101, RIM101 complementation was not significant. The qRT-PCR assay showed that the adhesion genes of pH mutants was inhibited in 1024 μg/mL BAEB. Conclusion: Under acidic conditions, the Candida albicans pH mutants was inhibited by BAEB to a certain extent.

Activity of essential oil extracted from Artemisia argyi in inducing apoptosis of Candida albicans / 中国中药杂志

To explore the activity of essential oil extracted from Artemisia argyi (AAEO) in inducing the apoptosis of Candida albicans SC5314. The effect of AAEO on reactive oxygen species(ROS) and mitochondria membrane potential(MMP) of C. albicans SC5314 was detected by flow cytometry. Phosphatidylserine externalization was observed under fluorescence microscopic with Annexin-V/PI staining at the early stage of apoptosis in C. albicans. Metacaspase activity was observed under fluorescence microscopic with FITC-VAD-FMK staining at the early stage of apoptosis in C. albicans. C. albicans morphology was observed by DAPI nuclear staining and fluorescence microscopy. After intervention with 0.5 mL•L⁻¹ AAEO, apoptosis of C. albicans significantly increased, metacaspase activity increased, nuclear pyknosis and fragmentation, and intracellular ROS were significantly increased, and mitochondrial membrane potential decreased significantly. The certain concentrations of AAEO could induce the apoptosis of C. albicans.

Efficacy of Bortezomib for Maintenance therapy of Patients with Multiple Myeloma / 中国实验血液学杂志

<p><b>OBJECTIVE</b>To observe the efficacy of chemotherapy consisted of bortezomib as main druy in maintenance therapy for recurrence of newly diagnosed MM patients.</p><p><b>METHODS</b>The clinical data and outcome of 37 MM patients during 2008-2013 were analyzed retrospectively, the 37 MM patients were divided into 2 group: 19 cases including 13 cases of newly diagnosed MM with symptoms and 6 cases of relapsed refractory MM were enrolled in group A; 17 cases of newly diagnosed MM with symptoms were enrolled in group B. The patients of group A received maintenance therapy consisted of bortezomib plus dexamethasone (VD group), while the patient group B received maintenance therapy consisted of melphalan plus prednisone(MP group), then the therapeutic efficacy of 2 group was compared.</p><p><b>RESULTS</b>The overall response rate(ORR) in VD groupe was 84.2%(16/19), out of which CR rate reached 42%(8/19), PR rate reached 31.6%(6/19), MR rate reached 10.5%(3/19). During median follow-up for 21.8(5-51) months, death occurred, while the ORR in MP group was 52(9/17), out of which CR rate was 23.5%(4/17), PR rate reached 23.5%(4/17), MR rate reached 5.9%(1/17). Druing median follow-up for 16.4(4-39) months, the worteity reaced 64.7%(11/17). The differencr between 2 groups was significant(P<0.05). The median OS time of patients in VD group was 21.6 months, that in MP group was 17.9 months(P<0.05). The median PFS in VD group and MP group were 13.4 and 9.4 months respectively(P<0.001).</p><p><b>CONCLUSION</b>The ORR and CR rates of bortezomib maintenance therapy for newly diagnosed and relapsed / refractory MM patients are very high, and its toxicity can be controlled, therefore, the patients need maintenance therapy after remission.</p>

Correlation of Thrombosis and Prothrombotic State with Coagulation Factor V Gene Polymorphism and APCR. HHcy / 中国实验血液学杂志

<p><b>OBJECTIVE</b>To investigate the correlation of patients with thrombosis or prothrombotic status with hyperhomocysteinemia (HHcy), activated protein C-resistance(APCR) and gene polymorphism of coagulation factor V.</p><p><b>METHODS</b>Three hundred healthy voluteers were selected as controls, 223 cases of thrombosis (80 cases of cerebral infarction of CT, the MI of 82 cases of myocardial infarction, venous thrombosis of VTE 61 cases), 270 cases of patients with prothrombotic state (76 cases of pregnancy disease of PIH, 62 cases of chronic obstructive pulmonary disease (COPD), 60 cases of diabetes(DM) and 72 cases of cancer) were enrolled in this study. The plasma APCR and hyperhomocysteinemia were detected by APTT coagulation method and cycling enzyme method respectively, and restriction fragment length polymorphism(RFLP) were was used to detect the gene polymorphism of FV G1691-A, G1091-C and A1090-G in the patient and control groups.</p><p><b>RESULTS</b>APCR positive rate was 62.29% and 7.33%, and the positive hyperhomocysteinemia accounted for 68.42% and 10.00% respectively in the group of the patients with venous thrombosis and the normal control group. 3 cases of heterozygous FV gene mutations were found in the APCR-positive patients with venous thrombosis.</p><p><b>CONCLUSION</b>HHcy possitive rate of patients with venous thrombosis is signiticantly higher than that in control, the HHcy is one of the important causes resulting in thrombosis, the patients with venous thrombosis have proved to be with APCR, and the possitive APCR may be related with the coagulation factor V gene polymorphism.</p>

In vitro osteoclast-suppressing effect of sodium ibandronate / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Bisphosphonates (BPs) have been reported to reduce local recurrence in giant cell tumor (GCT) of bone because of their osteoclast-suppressing effect; however, the optimal mode of delivery and the dose and duration of treatment of BPs remain to be established. To address these issues, it is first necessary to clarify the manner of action of BPs on osteoclasts. We herein evaluated the osteoclast-suppressing effect of sodium ibandronate in vitro.</p><p><b>METHODS</b>Mouse osteoclasts (OCLs) were generated in vitro using mouse bone marrow mononuclear cells. First, various concentrations of sodium ibandronate and equal amounts of phosphate-buffered saline were added to cell culture media. The number of multinucleated cells (over three nuclei) was recorded in each group, OCL formation was compared, and the most effective concentration of sodium ibandronate was determined. Then, high concentrations of sodium ibandronate were added to the experimental cell culture media; no ibandronate was given in the control group. Comparisons were made between the two groups in terms of OCL adhesion, migration, and bone resorption.</p><p><b>RESULTS</b>OCL formation was suppressed by sodium ibandronate in vitro; the most pronounced effect was observed at the concentration of 10(-5) mol/L. OCL migration and bone resorption were significantly suppressed at this concentration, though there was no effect on OCL adhesion.</p><p><b>CONCLUSIONS</b>Sodium ibandronate was effective in suppressing OCLs and decreasing resorption in GCT. The strong anti-OCL effectiveness at a high concentration in vitro indicates a topical mode of application.</p>

Roles of cytokines in stress-induced depression / 生理学报

Depression is a very common mental health problem in our modern society. Stress is involved in the provocation of depression. The pathogenesis of depressive disorder is still not well known. The development of neuroendocrine immunology opens a new sight for clarification of mechanism underlying stress-induced depression. Chronic stress activates peripheral and central immune systems accompanied with the release of inflammatory mediators, including cytokines. Activated immune system mediates the process of depression through the interaction with neuron system and neuroendocrine system, including regulating the monoamine neurotransmitter system in synthesis, metabolism and reuptake, inducing the overactivation of hypothalamus-pituitary-adrenal (HPA) axis and its negative feedback regulation, and reducing neurogenesis. This present paper reviews the cytokines mechanisms underlying stress-induced depression.

Effect on expression of vascular smooth muscle cell calcium channel in rats exposed in low temperature / 中华劳动卫生职业病杂志

<p><b>OBJECTIVE</b>To observe the expression of vascular smooth muscle cells calcium channel α1C subunit (LTCCα1C) in rats exposed in low temperature.</p><p><b>METHODS</b>Cold-induced hypertension was established and blood pressure was measured every two weeks. The mRNA expression of L type calcium channel α1C was determined by RT-PCR.</p><p><b>RESULTS</b>The blood pressure of the rats exposed to cold environment increased. The blood pressure of experimental groups [(102.8 ± 2.25) mm Hg] began to increase from the first two weeks, compared with the control group [(89.2 ± 3.73) mm Hg], there were significant difference (P < 0.05). The blood pressure of experimental groups were (114.5 ± 4.21), (121.9 ± 3.03) mm Hg respectively at 4, 6 weeks. Compared with the control group, the expression of LTCCα1C mRNA of the cold exposure group increased significantly (P < 0.01). There was a significant correlation between the expression of LTCCα1C mRNA and the blood pressure of the rats (r = 0.86, P < 0.01).</p><p><b>CONCLUSION</b>Repeated cold exposure can establish cold-induced hypertension, and the level of vascular smooth muscle cells LTCCα1C expression increase.</p>

Application of two auricular cartilage-perichondrium complexes in tympanoplasty / 南方医科大学学报

<p><b>OBJECTIVE</b>To compare the effects of cartilage-perichondrium palisade complex and cartilage-perichondrium horseshoe complex in tympanoplasty for large tympanic membrane perforation.</p><p><b>METHODS</b>Nineteen patients (19 ears) undergoing tympanoplasty with cartilage-perichondrium palisade complex and 20 patients (20 ears) with cartilage-perichondrium horseshoe complex were compared for postoperative hearing and closure rate of tympanic membrane perforation.</p><p><b>RESULTS</b>The closure rates of the tympanic membrane were all 100% in both groups 3 months after the operation, while tympanoplasty with cartilage- perichondrium horseshoe complex resulted in significantly greater improvement of the postoperative air-bone gap in speech frequency.</p><p><b>CONCLUSION</b>Both of the two auricular cartilage-perichondrium complexes produced good effects for repair large tympanic membrane perforation, but cartilage-perichondrium horseshoe complex can achieve better results in speech frequency.</p>

Expressions of VEGF and Ki-67 in eutopic endometrium of patients with endometriosis and effect of Quyu Jiedu Recipe on VEGF expression / 中国结合医学杂志

<p><b>OBJECTIVE</b>To observe the clinical efficacy of Quyu Jiedu Recipe (, QJR) in treating endometriosis (EM), and to explore the levels of vascular endothelial growth factor (VEGF) and cell proliferative nucleoprotein antigen (Ki-67), their changes before and after treatment and the clinical significance in the trial.</p><p><b>METHODS</b>Fifty patients of EM were randomly assigned to two groups. The 26 patients in the QJR group were treated with QJR, and the 24 patients in the gestrinone (GT) group with gestrinone. Besides, a normal control group with 20 healthy women was set up. The therapeutic effects in the two treated groups were compared. Expressions of VEGF and Ki-67 in eutopic endometrium of all subjects (with both patients and healthy women at the median secretive phase) were determined with immunohistochemical stain before treatment, and the determination in the two treated groups was repeated after 3-month treatment in the same phase.</p><p><b>RESULTS</b>Before treatment, the VEGF and Ki-67 expression positive rates and their mean optic density (MOD) were higher in patients than in healthy women (P<0.05). After treatment, the positive rate and MOD of VEGF expression lowered significantly than before treatment (P<0.05), but those of Ki-67 changed insignificantly, and comparison between the two treated groups showed no significant difference (P>0.05).</p><p><b>CONCLUSION</b>QJR could markedly improve the symptoms of menorrhagia and menstrual disorder, and its mechanism might be related with the lowering of eutopic endometrial VEGF expression. VEGF and Ki-67 show a high expression in eutopic endometrium of patients with EM.</p>

Study on mechanism of Quyujiedu method in treating endometriosis of stasis-toxic syndrome type / 中国中西医结合杂志

<p><b>OBJECTIVE</b>To observe the mechanism of Quyujiedu (QYJD, a method for removing stasis and detoxicating) in treating endometriosis of stasis-toxic syndrome type.</p><p><b>METHODS</b>Clinical study: Sixty patients were randomly divided into two groups, the treated group treated with QYJD and the control group treated with Danazol. The changes of clinical symptoms, physical signs, pregnancy rate, as well as levels of interleukin-1 (IL-1), interleukin-6 (IL-6) and endometrial antibody (EMAb) in them before and after treatment were observed. Experimental study: Sixty rats were established into endometriosis model, and randomly divided into the QYJD treated group, the Danazol treated group for positive control and the untreated group for negative control to observe the expression of Bax.</p><p><b>RESULTS</b>Clinical study showed that in the treated group and the control group, after treatment, dysmenorrhea score were 2.40 +/- 1.85 and 3.47 +/- 2.03, the menoxenia score 1.67 +/- 2.04 and 3.73 +/- 1.72 (P < 0.05), and the pregnancy rate 63.2% and 23.5% respectively, the difference between them was significant (all P < 0.05). Both of the two treatments can rectify immunity, reduce levels of IL-1 and IL-6, and lower the positive rate of EMAb. Experimental study showed that QYJD could improve the expression of Bax in ectopic endometrium, but could not affect the on-side expression of Bax in endometrium and muscle tissue.</p><p><b>CONCLUSION</b>QYJD is effective in improving the stasis-toxic syndrome of endometriosis, its mechanism related with the regulation of the immune condition and the promotion of cell apoptosis in ectopic endometrium, indicating that QYJD is an effective remedy for endometriosis of stasis-toxic syndrome type.</p>