小型颅内动脉瘤的临床特点及血管内栓塞治疗

目的总结小型颅内动脉瘤的临床特点以及血管内栓塞的技术要点与疗效。方法对45例小型颅内动脉瘤患者采用电解可脱性弹簧圈(GDC)或Trufill DCS Orbit微型三维填塞型水解铂金弹簧圈进行动脉瘤囊内栓塞。结果45个动脉瘤中41个瘤腔100%闭塞,3个95%闭塞,1个90%闭塞。术后44例临床痊愈,其治疗结果根据Glasgow预后评分:Ⅰ级29例,Ⅱ级11例,Ⅲ级3例,Ⅳ级1例,Ⅴ级1例;全组死亡率2.2%。栓塞术中并发脑血管痉挛6例。术后随访3-69个月均无再出血及复发。结论对小型颅内动脉瘤采用GDC或Truffill DCS Orbit微型三维填塞型水解铂金弹簧圈进行血管内囊内栓塞疗效可靠;根据小型颅内动脉瘤的临床特点进行栓塞是提高治愈率、降低并发症及死亡率的重要方法。     

一次采样测定人体咖啡因清除率的研究

咖啡因主要经肝细胞色素Ｐ４５０ＩＡ２代谢，测定其药代动国学参数可反映该Ｐ４５０亚型的活性。本研究显示咖啡因清除相为一级动力学；唾液和血浆的药代动力学参数有良好的相关性；含体重因素的清除率的变异系数比半减期小；用一次采样测定其清除率以８ｈ时点为宜。     

Disappearance of molsidomine effects on pulmonary circulation of patients with chronic obstructive pulmonary disease after a three week treatment

The effect of oral molsidomine (M) on the pulmonary artery hypertension of patients with chronic obstructive pulmonary disease (COPD) was investigated during an acute study (4 mg once) and after a 3 week-treatment (3 times 4 mg a day), on a double-blind basis in 16 patients, 8 receiving a placebo, and 8 molsidomine. Ventilatory and cardiocirculatory indices were obtained at rest and during exercise. When acutely given, molsidomine reduces the mean pulmonary arterial pressure (PAP), the pulmonary vascular resistance (PVR) and the arterial O2 partial pressure (PaO2), increasing heart rate (HR) as well as the alveo-arterial O2 partial pressure difference (P(A-a)O2). During exercise, pulmonary arterial pressure and pulmonary vascular resistance decrease while heart rate increases without modification of arterial blood gases. After a 3-week treatment, molsidomine no more improves any index but significantly reduces cardiac output during exercise and consequently the O2 delivery to the tissues. The same feature has already been observed for other nitrates. It thus seems inappropriate to prescribe nitrates or nitrate-like drugs to chronic obstructive pulmonary disease patients with a view to lower their pulmonary hypertension.     

Inclusion of CpG adjuvant with plasmid DNA coding for NcGRA7 improves protection against congenital neosporosis

The present study showed that incorporation of CpG adjuvant into plasmid DNA coding for NcGRA7 antigen resulted in a twofold increase in the level of protection against congenital transfer of Neospora caninum. The level of protection was considerably higher than that observed in pups born from dams immunized with nonrecombinant plasmid.     

老年急性阑尾炎的诊治体会

目的：探讨老年急性阑尾炎的诊治。方法：对近年来收治的60岁以上老年阑尾炎104例患者的诊治进行分析总结。结果：104例患者行手术治疗,病理证实。手术在48h以内72例患者均痊愈出院,48h以上32例患者术后有2例切口感染,104例患者中伴有心血管疾患和肺部感染者13例,死亡率为0％。结论：老年急性阑尾炎症状及体征不典型,穿孔率高,应力求早期诊断,及时手术治疗。     

10年早产儿及新生儿结果分析

目的 探讨早产儿的发生因素和对母儿的影响及防治。方法 收集１９８９年１月至１９９８年１２月,１０年中我院住院分娩的全部早产病例８１６例,按产５年和后５年分为两组进行回顾性分析。结果 前组早产数为５３４例,早产发生率为３．２０％;后组早产数为２８２例,发生率为３．０５％,两组发生率对比无统计学差异（Ｐ〉０．０５）。其流行病学调查显示在职业、流动人口数和产前检查方面两组对比有极其显著性差异（Ｐ〈０．０     

以组蛋白去乙酰化酶为靶标的抗癌药物研发进展

基因表达的精确控制是细胞增殖分化和器官正常生长和发育的基础。基因转录和激活程序依赖于组蛋白乙酰化酶(histone acetylase，HAT)和组蛋白去乙酰化酶(histone deacetylase，HDAC)的协同作用。当HDAC过度表达并被转录因子募集，就会导致特定基因的不正常抑制，从而导致癌症及其他疾病。目前以HDAC作为抗癌靶点的研究方兴未艾，现综述HDAC类似蛋白(HDLP)的晶体结构和当前存在的HDAC抑制剂的作用机制、结构种类、研发状况和构效关系，以及新的HDAC抑制剂CS055的研发策略。     

Whole-exome sequencing identifies novel mutations in genes responsible for retinitis pigmentosa in 2 nonconsanguineous Chinese families

AIM: To detect the pathogenetic mutations responsible for nonsyndromic autosomal recessive retinitis pigmentosa (RP) in 2 nonconsanguineous Chinese families. METHODS: The clinical data, including detailed medical history, best corrected visual acuity (BCVA), slit-lamp biomicroscope examination, fundus photography, optical coherence tomography, static perimetry, and full field electroretinogram, were collected from the members of 2 nonconsanguineous Chinese families preliminarily diagnosed with RP. Genomic DNA was extracted from the probands and other available family members; whole-exome sequencing was conducted with the DNA samples provided by the probands, and all mutations detected by whole-exome sequencing were verified using Sanger sequencing in the probands and the other available family members. The verified novel mutations were further sequenced in 192 ethnicity matched healthy controls. RESULTS: The patients from the 2 families exhibited the typical symptoms of RP, including night blindness and progressive constriction of the visual field, and the fundus examinations showed attenuated retinal arterioles, peripheral bone spicule pigment deposits, and waxy optic discs. Whole-exome sequencing revealed a novel nonsense mutation in FAM161A (c.943A>T, p.Lys315*) and compound heterozygous mutations in RP1L1 (c.56C>A, p.Pro19His; c.5470C>T, p.Gln1824*). The nonsense c.5470C>T, p.Gln1824* mutation was novel. All mutations were verified by Sanger sequencing. The mutation p.Lys315* in FAM161A co-segregated with the phenotype, and all the nonsense mutations were absent from the ethnicity matched healthy controls and all available databases. CONCLUSION: We identify 2 novel mutations in genes responsible for autosomal recessive RP, and the mutation in FAM161A is reported for the first time in a Chinese population. Our result not only enriches the knowledge of the mutation frequency and spectrum in the genes responsible for nonsyndromic RP but also provides a new target for future gene therapy.     

Granulocyte-macrophage colony-stimulating factor protects mice against hepatocellular carcinoma by ameliorating intestinal dysbiosis and attenuating inflammation

BACKGROUND Hepatocellular carcinoma(HCC) is the third leading cause of cancer mortality worldwide. The gut microbiota can help maintain healthy metabolism and immunity. Granulocyte-macrophage colony-stimulating factor(GM-CSF) is a critical factor in promoting health and homeostasis; it promotes intestinal immunity, stimulates bone marrow precursors to generate macrophage colonies, and enhances the antibacterial and antitumor activity of circulating monocytes. As such, GM-CSF may protect against HCC development by regulating immunity as well as intestinal microecology.AIM To investigate the impact of GM-CSF on the gut microbiome and metabolic characteristics of HCC.METHODS Thirty-six male BALB/c nude mice were divided into three groups: Control(n = 10), HCC(n = 13), and HCC + GM-CSF(GM-CSF overexpression, n = 13). We utilized HCC cells to establish orthotopic transplantation tumor models of HCC with normal and over-expressing GM-CSF. Liver injury, immune inflammatory function and intestinal barrier function were evaluated. The fecal microbiome and metabolome were studied using 16S rRNA absolute quantification sequencing and gas chromatography-mass spectrometry.RESULTS GM-CSF overexpression significantly affected the gut microbiome of mice with HCC and resulted in a high abundance of organisms of the genera Roseburia, Blautia and Butyricimonass, along with a significant reduction in Prevotella, Parabacteroides, Anaerotruncus, Streptococcus, Clostridium, and Mucispirillum. Likewise, GM-CSF overexpression resulted in a substantial increase in fecal biotin and oleic acid levels, along with a prominent decrease in the fecal succinic acid, adenosine, fumaric acid, lipoic acid, and maleic acid levels. Correlation analysis revealed that the intestinal microbiota and fecal metabolites induced by GM-CSF were primarily involved in pathways related to reducing the inflammatory response, biotin metabolism, and intestinal barrier dysfunction.CONCLUSION GM-CSF can protect against HCC development by regulating immunity and modulating the abundance of specific intestinal microorganisms and their metabolites. This study provides new insights into the therapeutic approaches for HCC.