艾尔巴韦/格拉瑞韦治疗慢性丙型肝炎患者疗效初步观察

目的 初步探讨应用艾尔巴韦/格拉瑞韦治疗慢性丙型肝炎(CHC)患者的疗效。方法 2017年3月~2018年3月仙桃市第一人民医院感染病科收治的CHC患者82例,被随机分为对照组41例和观察组41例,分别给予聚乙二醇干扰素-α联合利巴韦林治疗和艾尔巴韦/格拉瑞韦治疗,两组均连续治疗24周。采用RT- PCR法检测血清 HCV RNA,采用全基因序列测定法行病毒基因分型。比较两组早期病毒学应答(EVR)、治疗结束时病毒学应答(ETVR)和持续病毒学应答(SVR)。结果 在治疗结束时,观察组血清丙氨酸氨基转移酶(ALT)水平为(47.9±19.7)U/L,显著低于对照组【(63.5±21.2)U/L,P<0.05】,天冬氨酸氨基转移酶(AST)水平为(55.5±22.3)U/L,显著低于对照组【(81.3±25.8)U/L,P<0.05】;观察组EVR、ETVR和SVR分别为48.8%、63.4%和70.7%,与对照组的41.5%、53.7%和65.8%比,无统计学差异(P>0.05);18例观察组非HCV Ⅰ型感染者EVR、ETVR和SVR分别为88.9%、94.4%和88.9%,显著高于同组23例HCV Ⅰ型感染者(分别为52.2%、60.9%和52.2%, P<0.05),而与对照组15例非HCV Ⅰ型感染者比,无统计学差异(分别为86.7%、93.3%和73.3%, P>0.05);观察组SVR₁₂为87.8%(36/41),显著高于对照组的73.2%(30/41,P<0.05)。结论 应用直接抗病毒(DAA)药物艾尔巴韦/格拉瑞韦治疗CHC患者近期疗效达到,但远期疗效似优于标准治疗方案, 值得临床进一步验证。     

Alternating repetition time balanced steady state free precession.

A novel balanced SSFP technique for the separation or suppression of different resonance frequencies (e.g., fat suppression) is presented. The method is based on applying two alternating and different repetition times, TR(1) and TR(2). This RF scheme manipulates the sensitivity of balanced SSFP to off-resonance effects by a modification of the frequency response profile. Starting from a general approach, an optimally broadened stopband within the frequency response function is designed. This is achieved with a TR(2) being one third of TR(1) and an RF-pulse phase increment of 90 degrees . With this approach TR(2) is too short ( approximately 1 ms) to switch imaging gradients and is only used to change the frequency sensitivity. Without a significant change of the spectral position of the stopband, TR(1) can be varied over a range of values ( approximately 2.5-4.5 ms) while TR(2) and phase cycling is kept constant. On-resonance spins show a magnetization behavior similar to balanced SSFP, but with maximal magnetization at flip angles about 10 degrees lower than in balanced SSFP. The total scan time is increased by about 30% compared to conventional balanced SSFP. The new technique was applied on phantoms and volunteers to produce rapid, fat suppressed images.     

Detergent fractionation with subsequent subtractive suppression hybridization as a tool for identifying genes coding for plasma membrane proteins

Abstract:  The identification of tumor-specific proteins located at the plasma membrane is hampered by numerous methodological pitfalls many of which are associated with the post-translational modification of such proteins. Here, we present a new combination of detergent fractionation of cells and of subtractive suppression hybridization (SSH) to gain overexpressed genes coding for membrane-associated or secreted proteins. Fractionation of subcellular components by digitonin allowed sequestering mRNA of the rough Endoplasmatic reticulum and thereby increasing the percentage of sequences coding for membrane-bound proteins. Fractionated mRNAs from the cutaneous T-cell lymphoma (CTCL) cell line HuT78 and from normal peripheral blood monocytes were used for SSH leading to the enrichment of sequences overexpressed in the tumor cells. We identified some 21 overexpressed genes, among them are GPR137B, FAM62A, NOMO1, HSP90, SLIT1, IBP2, CLIF, IRAK and ARC. mRNA expression was tested for selected genes in CTCL cell lines, skin specimens and peripheral blood samples from CTCL patients and healthy donors. Several of the detected sequences are clearly related to cancer, but have not yet been associated with CTCL. qPCR confirmed an enrichment of these mRNAs in the rough endoplasmic reticulum fraction. RT-PCR confirmed the expression of these genes in skin specimens and peripheral blood of CTCL patients. Western blotting verified protein expression of HSP90 and IBP2 in HuT78. GPR137B could be detected by immunohistology in HuT78 and in keratinocytes of dysplastic epidermis, but also in sweat glands of healthy skin. In summary, we developed a new technique, which allows identifying overexpressed genes coding preferentially for membrane-associated proteins.     

Proliferation of DU145 prostate cancer cells is inhibited by suppressing insulin-like growth factor binding protein-2

BACKGROUND: Insulin-like growth factor binding protein-2 (IGFBP-2) is expressed by all human prostate cancer cell lines and dramatically increases in the serum of prostate cancer patients. However, the role of IGFBP-2 in prostatic tumorigenesis is not known. The aim of the present study was to investigate the effects of IGFBP-2 on the proliferation of DU145 human prostate cancer cells in culture. METHODS: Using cell proliferation assays, we examined the effects of exogenously administered and endogenously modulated levels of IGFBP-2 on the proliferation of DU145 cells. RESULT: Cell growth was stimulated by exogenously administered IGFBP-2, but significantly retarded (P < 0.05) by its neutralizing antibody. Overexpression of IGFBP-2 by transfection also stimulated cell growth, which was significantly (P < 0.05) inhibited in transfectants expressing antisense mRNA to IGFBP-2. Furthermore, the proliferation of IGFBP-2 overexpressing cells was significantly dampened by exogenously administered IGFBP-2 antibody. CONCLUSIONS: IGFBP-2 is an autocrine growth factor for DU145 human prostate cancer cells and cell proliferation can be significantly retarded by neutralizing or inhibiting its synthesis. These findings provide a strong rationale for targeting IGFBP-2 in the testing of novel strategies to treat prostate cancer.     

Identification of differentially expressed genes in omental adipose tissues of obese patients by suppression subtractive hybridization

To identify differentially expressed genes between obese individuals and normal control, we have undertaken suppression subtractive hybridization （SSH）. Omental adipose tissues were obtained via abdominal surgery for appendicitis in both 13 obese subjects[BMI （body mass index） 〉 30 kg/m（2）] and 13 normal subjects （BMI 〉 18 and 〈 25 kg/m（2））.     

MANAGEMENT OF UNCONTROLLED GLAUCOMA WITH THE MOLTENO SYSTEM

In glaucomatous eyes refractory to medication, laser techniques and conventional drainage surgery, intraocular pressure is often high, and visual loss rapid. In this situation a reliable, robust artificial outflow system is required. Molteno has evolved a plastic tube and plate device combined with a fibrosis suppression medication regimen. Thirty-eight eyes of 32 patients with uncontrolled glaucoma were treated with the Molteno system. Six months after operation mean intraocular pressure had been reduced from 41.0 ± 13.6 to 16.2 ± 5.6 mmHg. Eighteen eyes had pressures of 20 mmHg or less on no hypotensive therapy, 17 on reduced treatment. Three eyes had a pressure of 21 to 35 mmHg on treatment at six months. The 13 aphakic eyes responded as well as 25 phakic eyes. Five eyes with rubeotic glaucoma demonstrated pressures of less than 20 mmHg without therapy, four eyes with traumatic glaucoma required continuing medication with three having pressures below 22 mmHg. Of the seven eyes with uveitic glaucoma, one was lost, two required maintenance therapy; five of six surviving eyes had pressures below 20 mmHg. Fifteen eyes with congenital or juvenile glaucoma achieved pressures below 20 mmHg, three of these with timolol drops, three with timolol and acetazolamide, and nine with no treatment. While seven of seven eyes with refractory primary open-angle glaucoma attained pressures below 20 mmHg. all seven needed continuing mild hypotensive therapy. Eleven eyes underwent a one-stage procedure, while 27 eyes required a two-stage operation. Twenty-eight eyes received fibrosis suppression medication after the second stage, and 24 maintained or improved their preoperative visual acuity. Results have been encouraging: in general the Molteno system is recommended as the second drainage operation in all glaucomatous eyes in which conventional therapy has failed, and as the primary surgical procedure (after laser techniques) in eyes with rubeotic and uveitic glaucoma. Ciliary body destructive procedures should be restricted to control of symptoms in blind eyes.     

Exteroceptive suppression periods in jaw-closing muscles. Variability and relation to experimental pain and sustained muscle contraction

The duration of the late exteroceptive suppression period (ES₂) of temporal muscle EMG activity has been reported to be reduced in patients suffering from chronic tension-type headache. Methods of recording and analysing ES₂ have varied between centers and reproducibility of results within subjects , although insufficiently studied, has generally been poor. ES₂ was investigated in 30 healthy subjects, using a computerized technique of recording, rectifying and averaging the EMG signals. Hour to hour and week to week variations of ES₂ durations were calculated, and the influence of pain during a cold pressor test and of sustained muscle contraction on ES₂ durations was investigated. The intra-individual variation of ES₂ durations was 16.0% from hour to hour and 20.7% from week to week. The inter-individual variation was 36.7%. The present method for analysis of ES₂ periods proved to be reliable, as the intra-observer variation was 4.2% and the inter-observer variation 4.6%. ES₂ periods were significantly shorter on the first compared to the second day of examination ( p = 0.006) and during experimental pain ( p = 0.0005). We recommend the use of the computerized averaging technique in future studies and caution against the dependence of results upon factors such as conditioning and pain.     

Use of superparamagnetic contrast media to suppress signal from flowing spins: Preliminary experience

The authors describe their preliminary experience with the use of superparamagnetic magnetic resonance (MR) imaging contrast media for suppression of signal from flowing blood. The goal of this work was to determine if a superparamagnetic contrast agent could successfully eliminate blood signal during cardiac-gated MR imaging, thereby eliminating or reducing flow artifacts associated with the complex and variable hemodynamics within the heart chambers. Imaging and data analysis were performed in 17 dogs subjected to experimental myocardial infarction as part of a parallel project. Six doses (0.2, 1, 2, 3.5, 4, 5, and 10 mg/kg) of AMI-25, an experimental contrast agent, were used in the study. Spin-echo imaging was performed immediately before and every 5 minutes (for an average of 25 minutes) after bolus injection of the contrast agent. Variations in the image signal-to-noise ratio relative to a baseline (before injection of contrast agent) image were assessed as a function of dose and time. Preliminary results suggest that a considerable reduction in blood flow artifacts and, hence, increases in image signal-tonoise ratio can be achieved at doses greater than or equal to 3.5 mg/kg, for approximately 20 minutes after injection. Doses equal to or less than 2 mg/kg and images obtained more than 20 minutes after injection (regardless of dose) did not reliably show hemodynamic artifact suppression.