阿霉素脂质体肝动脉栓塞治疗大鼠肝癌的药效学研究

目的:观察阿霉素脂质体(Lip-ADM)碘油乳剂肝动脉栓塞治疗大鼠W256肝癌模型的疗效,并与阿霉素水溶液(ADM)及阿霉素加空白脂质体(Lip ADM)相比较。方法:建立大鼠移植性W256肝癌模型并随机分为四组,经肝动脉分别灌注生理盐水,ADM碘油乳剂,游离ADM 空白脂质体及Lip-ADM碘油乳剂,用高效液相色谱测定阿霉素在各器官中的含量。结果:与ADM及ADM 空白脂质体组相比:Lip-ADM组对肿瘤生长的抑制明显增加(P<0.05),治疗后的大鼠生存期亦明显延长(P<0.05),阿霉素在体内的分布以肝、脾组织为主。结论:阿霉素脂质体经肝动脉栓塞化疗可明显降低阿霉素毒副作用,提高治疗效果。     

Short-Chain Fatty Acids Regulate Cytokines and Th17/Treg Cells in Human Peripheral Blood Mononuclear Cells in vitro

Short-chain fatty acids (SCFAs) have been recognized as mediators of immune responses, including pathways of cytokine production. In this study, we investigated the immune-regulatory effects of SCFAs on human peripheral blood mononuclear cells (PBMCs) from buffy coat of healthy donors. PBMCs were exposed to varying concentrations of individual SCFAs or of their mixtures of acetate, propionate and butyrate. The productions of interleukin (IL) IL-1β, IL-2, IL-6, IL-10, IL-17, IL-21, IL-23 and transforming growth factor beta 1 (TGF-β1) were assessed. T cell differentiation after exposure to SCFAs was also examined. Compared with lipopolysaccharide (LPS)-stimulated cells (controls), SCFAs slightly decreased TGF-β1 production and reduced IL-6 production; butyrate was more effective than acetate or propionate. SCFAs particularly butyrate caused the induction of CD4+CD25+ regulatory T cells (Treg) rather than Th17 cells. SCFAs may up-regulate the production of anti-inflammatory cytokines in PBMCs, resulting in the induction of CD4+CD25+ Treg cells.     

Identities and frequencies of mutations of the otoferlin gene (OTOF) causing DFNB9 deafness in Pakistan

Mutations in OTOF , encoding otoferlin, cause non-syndromic recessive hearing loss. The goal of our study was to define the identities and frequencies of OTOF mutations in a model population. We screened a cohort of 557 large consanguineous Pakistani families segregating recessive, severe-to-profound, prelingual-onset deafness for linkage to DFNB9 . There were 13 families segregating deafness consistent with linkage to markers for DFNB9 . We analyzed the genomic nucleotide sequence of OTOF and detected probable pathogenic sequence variants among all 13 families. These include the previously reported nonsense mutation p.R708X and 10 novel variants: 3 nonsense mutations (p.R425X, p.W536X, and p.Y1603X), 1 frameshift (c.1103_1104delinsC), 1 single amino acid deletion (p.E766del) and 5 missense substitutions of conserved residues (p.L573R, p.A1090E, p.E1733K, p.R1856Q and p.R1939W). OTOF mutations thus account for deafness in 13 (2.3%) of 557 Pakistani families. This overall prevalence is similar, but the mutation spectrum is different from those for Western populations. In addition, we demonstrate the existence of an alternative splice isoform of OTOF expressed in the human cochlea. This isoform must be required for human hearing because it encodes a unique alternative C-terminus affected by some DFNB9 mutations.     

绞股蓝总苷对老龄大鼠的抗氧化作用观察

目的：观察口服绞股蓝总苷对老龄大鼠的抗氧化作用。方法：测定药后大鼠红细胞超氧化物歧化酶（ＳＯＤ）和全血谷胱甘肽过氧化物酶（ＧＳＨ－Ｐｘ）等抗氧化酶含量及肾上腺内维生素Ｃ（ＶｉｔＣ）含量。结果：绞股蓝总苷４０和２０ｍｇ／ｋｇ连续用药２０ｄ能升高大鼠红细胞ＳＯＤ和全血ＧＳＨ－Ｐｘ酶活力,且能降低大鼠肾上腺皮质中ＶｉｔＣ含量。结论：绞股蓝总苷能增强老龄大鼠机体抗氧化能力及提高肾上腺皮质的功能。     

The effect of DDAVP on plasma levels of von Willebrand antigen II in normal individuals and patients with von Willebrand's disease

The infusion of 1-deamino-(8-D-arginine)-vasopressin (DDAVP) causes not only an elevation in factor VIII-related antigen (FVIIIR:Ag), but also a marked elevation of plasma von Willebrand antigen II (vWAgII). vWAgII reaches a peak concentration at 60 min and is elevated 3-8-fold over basal levels in normal individuals and individuals with type I, IIA, and IIB von Willebrand's disease. As the mechanism of hemostatic alteration brought about by DDAVP might be due to release of endothelial cell proteins, endothelial cell cultures were performed. The cultures demonstrated synthesis and secretion of vWAgII, as evidenced by the incorporation of 35S-methionine into the vWAgII molecule. Thus, vWAgII, like FVIIIR:Ag, is an endothelial cell protein.     

Endometrial carcinoma with ovarian metastases incidentally detected in a 30-year-old infertile patient--case report

This is a case of invasive endometrial carcinoma with ovarian metastases incidentally detected in a 30-year-old infertile woman. The patient was asymptomatic. Carcinoma was discovered during hysteroscopy. She was submitted to surgical treatment involving total hysterectomy, bilateral salpingo-oophorectomy and dissection of the pelvic and paraaortal lymph nodes. Postoperative irradiation therapy was performed. Since treatment the patient has been well.     

Factor V Leiden mutation in one family of Chinese origin

Objective　To investigate the factor V Leiden mutation associated with activated protein C resistance (APCR) in Chinese. Methods　Thirty “normal' individuals and twenty patients with thrombotic disease from Chinese Han Nationality were studied with APTT±APC, PCR followed by MnLI restriction enzyme analysis,PCR based direct sequence-specific primers (PCR-SSP) and DNA sequence analysis. Results　In one healthy control, the activated protein C (APC) sensitivity ratio (SR) was found to be significantly lower (0.8) than that in other normal control (&gt;2.0). This individual was identified to be heterozygous for FV Leiden mutaiton (Arg506-Gln). His grand-uncle, father, brother and son were also identified to be heterozygous for FV Leiden. The APC resistance was found in 3 other cases of thrombotice diseases, but with no FV Leiden mutation. Conclusion　This is the first four generations family case of FV Leiden mutation associated with APCR reported within Chinese ethnic population. It is note-worthy that more FV Leiden or whether other gene defects may be associated with APC resistance and acquired APCR causing thrombosis in Chinese population.