Clinical Analysis of 57 Patients with Ovarian Dysgerminoma

Objective  Ovarian dysgerminoma is an uncommon ovarian malignancy, Its clinicai features are special and there are many factors affecting its prognosis. If treated properly, the patient can be cured. Otherwise it may endanger the patient’s life. The aim of this study is to investigate the clinical features and factors related to prognosis of ovarian dysgerminoma. Methods  Data from 57 patients with pure ovarian dysgerminoma were analyzed retrospectively. The patients were admitted to the Cancer Center, Sun Yat-sen University from January 1.1964 to December 31, 2000. Results  The main clinical features were abdominal mass (56.1% ), abdominal pain (21.1% ), abdominal swelling (17.5%.), vaginal bleeding (5.3% )and genital tract abnormalities (5.3%). Twenty-six patients had stage I diseases, 8 stage II.9 stage III.1 stage IV and 13 recurrent and persistent diseases. The uterus was involved in 41.2% of patients with stage II -III diseases. Combined modality was given to 52 cases and a single-method treatment to 5 cases. The total overall 5 and 10-year survival rates for stages I-IV was 80.1 % and 70.0% respectively. The 5-year survival rate for stage I was 100%, stage II 55.2%. stage III 55.6% and stage IV 0%; for recurrent and persistent diseases, 72.7%. The stage I group of 12 patients. received adnexectomy and 14 patients underwent hysterectomy and adnexa removal. There was no significant difference between the 5 and 10-year survival rates (all 100%). Of the 23 patients in the stage I group to whom oniy chemotherapy was given after operation, 19 cases received 3 or more courses and were well without recurrence; 4 patients received only one course and one of them recurred 21 months after the operation. In the group of stages II and III cases, the 5-year survival rate was 86.7% for those whose chemotherapy courses were 3≥ 4 and 25.0% for patients who received less than 4 courses of chemotherapy (P<0.05). Conclusions  The prognosis of ovarian dysgerminoma is closely related to the disease stage and treatment modality. A fertility-preserving operation can be considered in early -staged patients, but caution needs to be exercised in the middle to late staged cases. Good results can be achieved with an operation-based combined modality in recurrent patients.     

灯盏花素对豚鼠单一心室肌细胞ICa的抑制作用

目的：观察灯盏花素对豚鼠单一心室肌细胞钙离子电流（ＩＣａ）的影响。方法：应用全细胞膜片钳制技术。结果：灯盏花素能明显抑制心室肌细胞的Ｃａ＾２＋通道,使ＩＣａ减小。此作用有明显的电压依赖性。在峰电流电压下作用最明显,而对其反转电位无明显影响。在指令电位０ｍＶ时,０．５ｍｇ％灯盏花素使ＩＣａ减小５．４％,１ｍｇ％灯盏花素使ＩＣａ减小２２．９％（Ｐ〈０．０１）,２ｍｇ％灯盏花素使ＩＣａ减小４５．０％（Ｐ     

Oral administration of PEGylated TLR7 ligand ameliorates alcohol-associated liver disease via the induction of IL-22

Effective therapies for alcohol-associated liver disease (ALD) are limited; therefore, the discovery of new therapeutic agents is greatly warranted. Toll-like receptor 7 (TLR7) is a pattern recognition receptor for single-stranded RNA, and its activation prevents liver fibrosis. We examined liver and intestinal damage in Tlr7^−/− mice to determine the role of TLR7 in ALD pathogenesis. In an alcoholic hepatitis (AH) mouse model, hepatic steatosis, injury, and inflammation were induced by chronic binge ethanol feeding in mice, and Tlr7 deficiency exacerbated these effects. Because these results demonstrated that endogenous TLR7 signaling activation is protective in the AH mouse model, we hypothesized that TLR7 activation may be an effective therapeutic strategy for ALD. Therefore, we investigated the therapeutic effect of TLR7 agonistic agent, 1Z1, in the AH mouse model. Oral administration of 1Z1 was well tolerated and prevented intestinal barrier disruption and bacterial translocation, which thus suppressed ethanol-induced hepatic injury, steatosis, and inflammation. Furthermore, 1Z1 treatment up-regulated the expression of antimicrobial peptides, Reg3b and Reg3g, in the intestinal epithelium, which modulated the microbiome by decreasing and increasing the amount of Bacteroides and Lactobacillus, respectively. Additionally, 1Z1 up-regulated intestinal interleukin (IL)-22 expression. IL-22 deficiency abolished the protective effects of 1Z1 in ethanol-induced liver and intestinal damage, suggesting intestinal IL-22 as a crucial mediator for 1Z1-mediated protection in the AH mouse model. Collectively, our results indicate that TLR7 signaling exerts protective effects in the AH mouse model and that a TLR7 ligand, 1Z1, holds therapeutic potential for the treatment of AH.

Alcohol-associated liver disease (ALD) is caused by chronic and excessive consumption of alcohol. The disease ranges from alcohol-associated fatty liver to alcoholic hepatitis (AH), fibrosis, cirrhosis, and hepatocellular carcinoma (HCC) (1). Alcohol-associated fatty liver is considered reversible and nonprogressive. Nearly 35% of heavy alcohol drinkers develop AH, and up to 40% of severe AH patients die within 6 mo (2). AH patients who survive may progress to alcohol-associated cirrhosis. Treatment options for AH involve the use of corticosteroids and have remained largely unchanged since the early 1970s. Unfortunately, not all patients respond to corticosteroids, and the benefits are temporary in responders (1, 2). Early liver transplant has been shown to be superior to medical management for severe AH, but it still has limitations and can only be considered in a highly selective group of patients (1, 2). Thus, the identification of a better molecular therapeutic target for ALD is a significantly unmet medical need for the development of effective therapies for AH.Previous studies have demonstrated the involvement of Toll-like receptors (TLRs), including TLR2, TLR4, and TLR9, in the development of ALD (3–8). In addition to the direct effect of alcohol and its metabolite, acetaldehyde, in hepatocytes, ethanol intake affects the function of the intestinal epithelial barrier. Chronic alcohol consumption disrupts intestinal tight junction integrity and increases gut permeability, resulting in elevated bacterial lipopolysaccharide (LPS) concentrations in the portal and systemic circulation (4). Translocated LPS activates resident hepatic macrophages, known as Kupffer cells, via TLR4, thereby promoting ALD (1, 2, 7, 8). Other TLRs, such as TLR2 and TLR9, recognize gram-positive bacterial components and bacterial CpG-DNA, respectively (3, 4). Furthermore, TLR2, TLR9, and MyD88 are required for the development of the preclinical AH murine model (5), whereas TLR4 and TLR9 exert protective effects against intestinal inflammation (9, 10).TLR7 signaling has been shown to be protective against liver fibrosis in mice (11). Tlr7^−/− mice exhibit augmented cholestasis and carbon tetrachloride (CCl₄)-induced liver fibrosis (11). TLR7 signaling also induces IFN-α production in dendritic cells (DCs), followed by interleukin (IL)-1 receptor antagonist (IL-1Ra) induction in Kupffer cells. IL-1Ra suppresses IL-1-induced hepatic stellate cell (HSC) activation, resulting in inhibition of liver fibrosis (11). Among the TLRs, TLR3 and TLR7 activation has been reported to ameliorate some liver diseases (11, 12). However, a major disadvantage of the currently available synthetic ligands for TLR3 and TLR7, such as poly I:C, imiquimod, and R848, is the excessive induction of proinflammatory cytokines (3, 4). Thus, developing agents without undesirable adverse effects is of great clinical interest.IL-22 is a hepatoprotective cytokine produced by T helper (Th) 17 cells, Th22 cells, γδ T cells, natural killer (NK) T cells, and innate lymphoid cells (ILCs) (13). Exogenous administration of IL-22 has a profound effect on tissue repair following liver injury via the promotion of proliferation and inhibition of apoptosis in hepatocytes of mouse models of AH (14), liver fibrosis, and drug- and LPS-induced liver injury. Also, IL-22 promotes tissue repair in the intestines and is protective against intestinal epithelial damage and inflammation (13). These findings suggest that IL-22 may suppress ALD via the maintenance of intestinal barrier function, thereby preventing increased intestinal permeability and bacterial translocation due to intestine-derived microbial products that promote ethanol-induced liver injury (15, 16).Here, we have developed a synthetic TLR7 ligand, 1Z1, that possesses antiinflammatory effects via IL-22 induction and that is devoid of systemic toxicity after oral administration (17–19). Treatment with 1Z1 has already been reported to be effective for allergic encephalomyelitis, arthritis, dextran sodium sulfate (DSS)-induced colitis, and type I diabetes in mice (17–20). We hypothesize that targeting TLR7 activation may be an effective treatment strategy for ALD. Our experimental results demonstrate that 1Z1 oral administration inhibits ethanol-induced liver and intestinal damage and that these beneficial effects are due to intestinal IL-22 induction in an AH murine model.     

Acute coronary syndromes

The first 150 words of the full text of this article appear below. Key points Coronary artery disease accounts for >30% ofdeaths in Western society. The diagnosis of myocardial infarctionshould be qualified by size, causation and time from occurrence. Mortalityis reduced by immediate or ‘primary’ percutaneouscoronary intervention or thrombolysis within the first 24 hof onset of ST-segment elevation myocardial infarction. Strategiesto reduce platelet activation (glycoprotein IIb/IIIa receptorantagonists, or clopidogrel) are now recommended in the treatmentof high-risk non-ST-segment myocardial infarction/unstable angina. Elevatedserum troponins may be the result of non-ischaemic myocardialdamage, especially in critical illness.