Efficient and stable transduction of dopaminergic neurons in rat substantia nigra by rAAV 2/1, 2/2, 2/5, 2/6.2, 2/7, 2/8 and 2/9

Dysfunction of the nigrostriatal system is the major cause of Parkinson's disease (PD). This brain region is therefore an important target for gene delivery aiming at disease modeling and gene therapy. Recombinant adeno-associated viral (rAAV) vectors have been developed as efficient vehicles for gene transfer into the central nervous system. Recently, several serotypes have been described, with varying tropism for brain transduction. In light of the further development of a viral vector-mediated rat model for PD, we performed a comprehensive comparison of the transduction and tropism for dopaminergic neurons (DNs) in the adult Wistar rat substantia nigra (SN) of seven rAAV vector serotypes (rAAV 2/1, 2/2, 2/5, 2/6.2, 2/7, 2/8 and 2/9). All vectors were normalized by titer and volume, and stereotactically injected into the SN. Gene expression was assessed non-invasively and quantitatively in vivo by bioluminescence imaging at 2 and 5 weeks after injection, and was found to be stable over time. Immunohistochemistry at 6 weeks following injection revealed the most widespread enhanced green fluorescence protein expression and the highest number of positive nigral cells using rAAV 2/7, 2/9 and 2/1. The area transduced by rAAV 2/8 was smaller, but nevertheless almost equal numbers of nigral cells were targeted. Detailed confocal analysis revealed that serotype 2/7, 2/9, 2/1 and 2/8 transduced at least 70% of the DNs. In conclusion, these results show that various rAAV serotypes efficiently transduce nigral DNs, but significant differences in transgene expression pattern and level were observed.     

CLUSTER, NEURALGIAS, AND TACS

A number of primary headache syndromes are marked by their short duration of pain. Many of these syndromes have their own unique treatment, so they must be recognized by practicing physicians. In this article, a number of the short-lasting headache disorders are reviewed, including chronic paroxysmal hemicrania, SUNCT syndrome, hypnic headache, exploding head syndrome, primary stabbing headache, and cough headache.     

COPD相关性疲劳的研究进展

疲劳是COPD患者的第二大常见的症状,发生率高,干扰了患者正常的工作生活。本文综述了疲劳的概念和发病机制,以及COPD 患者疲劳症状的诱因和治疗方法,为医务人员加深对疲劳的了解,以采取有效的措施,缓解患者疲劳,提高其生活质量提供参考。     

个体化护理干预对胆汁回输患者生活质量的影响研究

目的 探讨个体化护理干预对胆汁回输患者生活质量的影响。方法 将44例PTBD置管患者分为干预组22例,观察组22例；于置管前、置管后4天对两组患者的肝功能与电解质指标变化情况进行比较；采用个体化护理干预后对两组患者的生活质量进行比较。结果 两组PTBD置管患者置管后总胆红素(TBIL)、丙氨酸氨基转移酶(ALT)指标与置管前比均有明显下降(P＜0.05)；两组患者血清白蛋白(ALB)均有显著上升(P＜0.05)；干预组总胆红素(TBIL)、丙氨酸氨基转移酶(ALT)下降幅度和血清白蛋白(ALB)升高幅度较对照组明显,差异有统计意义(P＜0.05)；两组患者钾(K)和钠(Na)差异均无统计学意义。采用个体化护理干预后干预组在生理功能、躯体疼痛、总体健康、生命活力、心理健康均高于对照组,干预组干预后生活质量明显高于对照组,两组患者差异有统计学意义(P＜0.01)。结论 个体化护理干预有效提高胆汁回输患者生活质量,改善患者肝功能,提高了护理质量。     

Further Observations on the Blood Factors RhA, RhB, RhC and RhD

The findings in 18 cases of individuals with Rh_o-positive blood who had antibodies in their serum resembling anti-Rh_o in specificity are briefly summarized. One interesting finding is the relatively high frequency of such individuals among Negroes, especially with the blood type Rh^d_o and Rh^abd_o. The significance of these findings is discussed.     

A New Rh Phenotype, Rhorh, G-Negative

A new Rh phenotype, Rh_orh, G-negative is described in a Negro woman who developed anti-G (rhG) antibodies during pregnancy. The baby was Rh_o, G-positive and had mild hemolytic disease with a positive direct antiglobulin test. The mother's titer was 1:1024 at delivery, dropping to 1:8 after 14 months. The baby's direct antiglobulin test became negative after two months. The mother most likely became sensitized alter a blood transfusion five years prior.     

TNM/Okuda/Barcelona/UNOS/CLIP International Multidisciplinary Classification of Hepatocellular Carcinoma: concepts,perspectives, and radiologic implications

Hepatocellular carcinoma (HCC) is a major health problem worldwide. Moreover, the liver cancer field is evolving rapidly, with early diagnosis, new therapies, and a better understanding of HCC’s biology and development. Accurate staging is important for determining prognosis and selecting the most appropriate treatment for each patient. Surgical intervention remains the most effective treatment for HCC and is the only potentially curative modality. However, in HCC patients, overall survival is also independently affected by underlying liver disease and cirrhosis, which in turn affect the applicability and efficacy of treatment. Although several staging classification and prognostic scoring systems have been proposed for determining the stage and prognosis of HCC, no consensus exists on the best classification method. The most common staging classification systems include tumor-node-metastasis stage, Okuda staging, Cancer of the Liver Italian Program score, Barcelona Clinic Liver Cancer staging classification, the French, the Chinese University Prognostic Index, Japanese Integrated Scoring, and the Tokyo score. Radiologists should be aware of the different staging classification systems for HCC and familiar with the system relevant to their respective referring clinicians, as it will provide pertinent radiological evaluation for multidisciplinary management.     

Pentagalloylglucose, an antisecretory component of Paeoniae radix, inhibits gastric H, K-ATPase

We purified a compound with strong inhibitory effect on H⁺, K⁺-ATPase from Paeoniae radix, which has been used in Japan for the treatment of gastritis and peptic ulcers. The compound was identified as 1,2,3,4,6,-penta-o-galloyl-β- -glucose by proton nuclear magnetic resonance, carbon-13 nuclear magnetic resonance, and fast atomic bombardment mass spectrometry. The IC₅₀ of the compound for H⁺, K⁺-ATPase was 166 nmol/l. Kinetic analyses indicated that the inhibition of the enzyme by pentagalloylglucose was noncompetitive with respect to K⁺. Pentagalloylglucose had relatively weak inhibitory effects for Mg⁺-ATPase (IC₅₀: >10 μmol/l) and Na⁺, K⁺-ATPase (IC₅₀: 2.7 μmol/l). Pentagalloylglucose also inhibited the accumulation of [¹⁴C]aminopyrine in parietal cells that had been isolated from guinea pig stomach and stimulated by 10 μmol/l histamine (IC₅₀: 7.8 μmol/l) and 1 mmol/l dbc-AMP (IC₅₀: 10 μmol/l). These results suggest that pentagalloylglucose is a potent inhibitor of H⁺, K⁺-ATPase and may be responsible for inhibition of acid secretion by Paeoniae radix.     

Gu, a Variant of G

G^u, analogous to D^u and E^u, is a weak variant of G appearing in a haplotype lacking C, D, and E but having e^s.
In a preliminary survey, the red blood cells ot three of 186 Negro blood donors found negative when tested for C, D (incuding D^u), and E were shown to be G^u-positive when tested with anti-CD by the antiglobulin technic.
Fourteen additional examples from unrelated persons and five members of a family have been investigated in this study. All G^u-positive individuals tested are VS-positive, but V-negative, and all are Negro. Although G cells show greater antibody uptake when used to absorb anti-CD, G^u cells elute anti-G in substantially greater amounts than do G cells. Comparative studies demonstrate similarity of specificity but a difference of avidity, which could be due to the influence of e^s(VS) in cis position.
G^u-positive bloods have been shown to stimulate the production of anti-G in Rh-negative recipients. The test for G^u can be incorporated in the test for D^u by substituting anti-CD or anti-CDE for anti-D serum.     

A New Rh Allele, ryn (R-1,2,w3,w4)

The inheritance in a large Brazilian family of a new Rh allele r ^yn (R^{-1,2,w3,w4,-6,-7,-8,-10,-20,-27}) is described.     

Susceptibility of Haemophilus influenzae to amoxicillin/clavulanic acid, erythromycin, cefaclor, and trimethoprim/sulfamethoxazole

A total of 126 strains of Haemophilus influenzae were examined for susceptibility to amoxicillin/clavulanic acid, trimethoprim/sulfamethoxazole, cefaclor, and erythromycin by an agar dilution procedure. Fifty strains (eight type B, 42 non-type B), all with ampicillin minimal inhibitory concentrations (MIC) of greater than or equal to 6.2 micrograms/ml, produced beta-lactamase. The remaining 76 strains (18 type B, 59 non-type B) were beta-lactamase-negative. All of these strains had ampicillin MICs of less than or equal to 0.8 micrograms/ml. The combination of amoxicillin and clavulanic acid (2:1) was highly active against all strains tested. With the exception of two strains with amoxicillin/clavulanic acid MICs of 1.6/0.8 ug/ml, all strains were inhibited by concentrations of less than or equal to 0.8/0.4 ug/ml. Trimethoprim/sulfamethoxazole was also found to be highly active (MICs uniformly less than or equal to 0.1/1.9 ug/ml). Cefaclor and erythromycin were the least active of the agents tested. Fourteen strains (10.6%) had cefaclor MICs of greater than 32 ug/ml. Forty-seven strains (35.6%) had erythromycin MICs of greater than 8 micrograms/ml. With the exception of amoxicillin/clavulanic acid beta-lactamase production did not seem to influence the activity of any of the antimicrobials tested. Minimum inhibitory concentrations of amoxicillin/clavulanic acid, although still well within achievable serum levels, were approximately one twofold dilution higher with beta-lactamase-producing H. influenzae type B strains than with beta-lactamase-negative strains.     

左室压力-应变环技术评估甲状腺功能减退患者左室心肌做功

目的 应用左室压力-应变环（LV-PSL）技术评估甲状腺功能减退患者左室心肌做功情况，探讨其临床价值。方法 连续纳入于四川省人民医院就诊的甲状腺功能减退患者42例（甲减组），另选健康志愿者44例为对照组。应用常规超声心动图获取舒张末期室间隔厚度（IVSd）、舒张末期左室后壁厚度（LVPWd）、二尖瓣口舒张早期和晚期血流峰值速度（E、A）、左室侧壁二尖瓣环舒张早期和晚期运动峰值速度（e’、a’）、左室射血分数（LVEF），并计算E/A和E/e’；应用斑点追踪技术获取左室整体纵向应变（GLS）,LV-PSL技术获取心肌整体做功指数（GWI）、整体做功效率（GWE）、整体有效做功（GCW）、整体无效做功（GWW），计算左室基底段、中间段和心尖段心肌做功指数（MWI）、做功效率（MWE）、有效做功（CW）、无效做功（WW），比较两组上述参数的差异。结果 (1)常规超声心动图参数比较：与对照组比较，甲减组IVSd、LVPWd均增高，E、A、e’、E/A均降低，差异均有统计学意义（均P<0.05）；两组LVEF、a’、E/e’比较差异均无统计学意义；(2)左室整体心功能参数比较：与对照组比较...     

超声造影与二维超声引导下骨肿瘤穿刺活检的临床对比研究

目的比较超声造影与二维超声引导下骨肿瘤穿刺活检的临床应用价值。方法选取105例拟行骨肿瘤穿刺活检的患者,根据引导方式不同分为二维超声组52例和超声造影组53例,分别行二维超声及超声造影引导下穿刺活检,比较两组的穿刺时间、穿刺次数。以术后病理结果或临床综合诊断为金标准,计算并比较两组的诊断敏感性、特异性、阳性预测值、阴性预测值及准确率,绘制二维超声及超声造影引导下穿刺活检诊断骨肿瘤的受试者工作特征(ROC)曲线,并计算其曲线下面积。结果两组在性别、年龄、病灶直径、肿瘤位置等比较差异均无统计学意义。两组间穿刺时间及穿刺次数比较差异均无统计学意义(P=0.913、0.854)。超声造影组的诊断特异性与准确率(95.45%、98.11%)均明显高于二维超声组(76.92%、86.54%),差异均有统计学意义(均P0.05);超声造影组的诊断敏感性、阳性预测值及阴性预测值(100%、96.88%、100%)均高于二维超声组(96.15%、80.65%、95.24%),但差异均无统计学意义。超声造影引导下穿刺活检的ROC曲线下面积为0.987,二维超声引导下穿刺活检的ROC曲线下面积为0.908。结论超声造影引导下穿刺骨肿瘤伴周围软组织肿块的穿刺活检较二维超声引导下有更高的特异性及诊断准确率。     

Rapid detection of K-, N-, H-RAS, and BRAF hotspot mutations in thyroid cancer using the multiplex primer extension

Objectives

The objective of this study is to develop a multiplex PCR and primer extension to detect K-, N-, H-RAS, and BRAF mutations.

Design and methods

DNA samples were isolated from 76 thyroid cancer patients. Multiplex amplification of exons 2 and 3 of three RAS genes and exon 15 of the BRAF gene using three pairs of primers was performed in a single tube. The products were split into three tubes. First, we used nine different-sized N-RAS and BRAF primers to detect base changes in N-RAS and BRAF. The other two tubes used seven separate different-sized K-RAS and H-RAS primers to detect base changes.

Results

We compared these results with direct sequencing. The two methods generated identical results, but our method was superior to direct sequencing in terms of the amount of work and time involved.

Conclusions

We present a rapid method to detect mutations of K-, N-, H-RAS, and BRAF in human cancers.     

Antibiotics--TAZ/PIPC, synercid, linezolid, everninomicin

The increasing resistance among Gram-positive cocci have been accompanied by their increasing frequency as cause of severe infection. Thus new antimicrobial agents, TAZ/PIPC, synercid and linezolid, are in various stages of development. TAZ/PIPC, a combination drug of a new beta-lactamase inhibitor tazobactam and piperacillin at ratio in 1 to 4 has a broad spectrum of antimicrobial activity. Evidence from randomized clinical trials in adults in Japan has shown that TAZ/PIPC is superior to PIPC as a drug for complicated urinary tract infection. Synercid is a streptogramin antibiotic. The spectrum of activity of synercid is similar to vancomycin. Furthermore, most of E. faecium were susceptible. The efficacy of synercid in clinical trials in patients infected with VREF was 65-70%. Linezolid is a member of the oxazolidinones. The antimicrobial spectrum of linezolid is similar to that of vancomycin. In the US, patients with significant infection caused by resistant Gram-positive organisms(mostly VREF) were treated with linezolid. The efficacy of linezolid was about 75%. The clinical trials for everninomicin had been discontinued because of insufficient clinical data supporting its efficacy and safety.     

子午流注针法配合辩证取穴针刺治疗产后缺乳的疗效观察

目的 探讨子午流注针法配合辩证取穴针刺治疗产后缺乳的临床疗效。方法 选择石家庄市第四医院2019年1月到2019年12月间收治的产后缺乳患者60例,随机分为对照组和观察组,各30例。对照组采用针刺治疗,此基础上,观察组给予子午流注针法治疗,比较两组治疗后泌乳量、配方奶粉补乳量改善情况及临床疗效。结果 治疗后,两组泌乳量高于治疗前,配方奶粉补乳量均低于治疗前(P<0.05);观察组治疗后泌乳量高于对照组,配方奶粉补乳量低于对照组(P<0.05);观察组总有效率(96.67%)明显高于对照组(70.00%),(P<0.05)。结论 子午流注针法配合辩证取穴针刺可有效促进产后缺乳产妇泌乳,提高泌乳量,减少配方奶粉补乳量,临床疗效满意,值得进一步应用和推广     

Vaginal bleeding/spotting with conjugated estrogens/bazedoxifene,conjugated estrogens/medroxyprogesterone acetate,and placebo

ABSTRACT

Objective: In the 1-year phase 3 Selective estrogens, Menopause, And Response to Therapy-5 trial, cumulative amenorrhea rates with conjugated estrogens/bazedoxifene (CE/BZA) were similar to placebo and higher than with conjugated estrogens/medroxyprogesterone acetate (CE/MPA). This post hoc analysis reports bleeding/spotting rates in 4-week intervals (cycles) and 3-month intervals (quarters) with these therapies and the percentage of cases attributable to spotting only.

Methods: Generally healthy postmenopausal women with menopausal symptoms recorded vaginal bleeding/spotting in daily diaries while receiving CE 0.45 mg/BZA 20 mg, CE 0.625 mg/BZA 20 mg, CE 0.45 mg/MPA 1.5 mg, or placebo.

Results: A total of 1596 women in the modified intent-to-treat population contributed data. Incidence of bleeding/spotting was significantly (p < 0.001) lower with CE 0.45 mg/BZA 20 mg (0.54?4.44%), CE 0.625 mg/BZA 20 mg (1.26?5.02%), and placebo (1.55?4.82%) compared with CE 0.45 mg/MPA 1.5 mg (8.81?25.63%) in all 4-week cycles. Each quarter, <10% of women taking CE/BZA doses or placebo had bleeding/spotting, significantly (p < 0.001) less than the 21–36% with CE 0.45 mg/MPA 1.5 mg. Odds ratio for bleeding/spotting with CE 0.45 mg/BZA 20 mg vs CE 0.45 mg/MPA 1.5 mg was 0.1 in each quarter (95% CI, Q1–Q3: 0.1–0.2; Q4: 0.1–0.3). Across all treatments, most (88–100%) bleeding/spotting cases were spotting only. Mean days of bleeding/spotting were <1 per quarter with CE/BZA doses and placebo, which was significantly (p < 0.01) less than the 3–5 days per quarter with CE/MPA.

Conclusions: Bleeding/spotting with CE/BZA treatment was similar to placebo and significantly less frequent than with CE/MPA treatment. Most cases were spotting only across all treatments.