幽门螺杆菌cagⅡ对胃上皮细胞IL-8基因转录的影响及机制

目的探讨HpcagⅡ对胃上皮细胞IL-8基因转录的影响及信号传导机制。方法构建 cagⅡ基因位点缺失Hp突变株及带有IL-8报告基因的人胃癌细胞系L5F11,用液体闪烁计数仪测定荧光素酶(IL8转录)活性,用ELISA法测定IL8蛋白浓度。结果所有Hp突变株诱导荧光素酶活性与IL8蛋白浓度较亲代菌株26695均降低[(0．13±0．01)×cpm比(0．59±0．05)×(P<0．01);(0．73±0．13)ng／ml比(2．22±0．65)ng／ml,(P<0．05)]。PTK抑制剂herbimycinA不仅抑制Hp诱导的荧光素酶活性[(0．71±0．18)×cpm比(1．51±0．23)×cpm,(P<0．05)],而且抑制IL-8蛋白表达[(0．83±0．41)ng／ml比(3．22±0．59)ng／ml,(P<0．05)],但herbimycinA对TNFα诱导的荧光素酶活性及IL8蛋白表达均无影响(P均>0．05);PKA抑制剂H7抑制TNFα诱导的荧光素酶活性[(0．74±0．16)×cpm比(2．62±0．26)×cpm,(P<0．001)]及IL8蛋白表达[(1．45±0．38)ng／ml比(4．12±0．43)ng／ml,(P<0．01)],而对Hp诱导的荧光素酶活性无影响(P>0．05)。结论HpcagⅡ中的多基因能够调节胃上皮细胞IL-8基因转录,且这一作用主要经蛋白酪氨酸激酶途径。     

In-hospital outcomes of transapical versus surgical aortic valve replacement: from the U.S. national inpatient sample

OBJECTIVETo compare the outcomes of transapical transcatheter aortic valve replacement (TA-TAVR) and surgical aortic valve replacement (SAVR) using a large US population sample.METHODSThe U.S. National Inpatient Sample was queried for all patients who underwent TA-TAVR or SAVR during the years 2016−2017. The primary outcome was all-cause in-hospital mortality. Secondary outcomes were in-hospital stroke, pericardiocentesis, pacemaker insertion, mechanical ventilation, vascular complications, major bleeding, acute kidney injury, length of stay, and cost of hospitalization. Outcomes were modeled using multi-variable logistic regression for binary outcomes and generalized linear models for continuous outcomes.RESULTSA total of 1560 TA-TAVR and 44,280 SAVR patients were included. Patients who underwent TA-TAVR were older and frailer. Compared to SAVR, TA-TAVR correlated with a higher mortality (4.5% vs. 2.7%, effect size (SMD) = 0.1) and higher periprocedural complications. Following multivariable analysis, both TA-TAVR and SAVR had a similar adjusted risk for in-hospital mortality. TA-TAVR correlated with lower odds of bleeding with (adjusted OR (aOR) = 0.26; 95% CI: 0.18−0.38;P < 0.001), and a shorter length of stay (adjusted mean ratio (aMR) = 0.77; 95% CI: 0.69−0.84; P < 0.001), but higher cost (aMR = 1.18; 95% CI: 1.10−1.28; P < 0.001). No significant differences in other study outcomes. In subgroup analysis, TA-TAVR in patients with chronic lung disease had higher odds for mortality (aOR = 3.11; 95%CI: 1.37−7.08; P = 0.007). CONCLUSIONThe risk-adjusted analysis showed that TA-TAVR has no advantage over SAVR except for patients with chronic lung disease where TA-TAVR has higher mortality.

Trans-apical aortic valve replacement (TA-TAVR) is typically reserved for patients who have unfavorable transfemoral approach.^[1] Several studies investigated the clinical outcomes of transfemoral-(TF) TAVR vs. surgical aortic valve replacement (SAVR); but there is paucity of data about the outcomes of TA-TAVR compared to SAVR. The STACCATO trial was the first randomized controlled trial to compare TA-TAVR versus SAVR. Though it was small trial (included only 70 operable patients) and was terminated prematurely (due to major adverse events in the TA-TAVR), it heralded a better outcome of SAVR when compared to TA-TAVR.^[2] Current trends in the U.S. show a steady decline in TA-TAVR procedures with a decrease in the rates of TAVR-related complications, such as stroke and need for pacemaker insertion. However, there has been no change in the risk of mortality or other peri-procedural complications.^[3]In this study, we aim to elucidate the applicability and safety of TA-TAVR when compared with SAVR. To our knowledge, this is the first retrospective cohort in the literature that compares the outcomes of TA-TAVR vs. SAVR in a national sample representative of the U.S. population.     

The anti-leukaemic activity of novel synthetic naphthoquinones against acute myeloid leukaemia: induction of cell death via the triggering of multiple signalling pathways

Naphthoquinones, such as menadione, display lower toxicity than anthracyclins used in cancer chemotherapy. Novel anti-leukaemic compounds comprised of chloro-amino-phenyl naphthoquinones with substitutions on the benzoic ring were developed. Structure–activity relationship studies indicated that the analogue with both methyl and amine substitutions (named TW-92) was the most efficient in killing leukaemic cells. Treatment of U-937 promonocytic cells with TW-92 induced apoptotic or necrotic cell death, dependent on incubation and dose conditions. TW-92 induced rapid phosphorylation of p38 mitogen-activated protein kinase (p38^MAPK) and of extracellular signal-regulated protein kinases (ERK1/2). The generation of apoptosis was preceded by intracellular H₂O₂ accumulation accompanied by glutathione depletion, the former inhibited by di-phenyl-iodonium (DPI), an inhibitor of NADPH oxidase. TW-92 induced swelling of isolated rat liver mitochondria, indicative of a direct effect on mitochondria. Apoptosis in intact cells was accompanied by a decrease in mitochondrial membrane potential, cytochrome c release and caspase activation. In addition, the level of Mcl-1, an anti-apoptotic regulatory protein, was down-regulated, whereas the expression of the pro-apoptotic BAX was elevated. Finally, TW-92 exerted strong pro-apoptotic and necrotic effects in primary acute myeloid leukaemia samples when given in submicromolar concentrations. Together, these findings demonstrate that TW-92 may provide an effective anti-leukaemic strategy.     

Effects of the Natural β-Carboline Alkaloid Harmine,a Main Constituent of Ayahuasca,in Memory and in the Hippocampus: A Systematic Literature Review of Preclinical Studies

Harmine is a natural β-carboline alkaloid found in several botanical species, such as the Banisteriopsis caapi vine used in the preparation of the hallucinogenic beverage ayahuasca and the seeds of Syrian rue (Peganum harmala). Preclinical studies suggest that harmine may have neuroprotective and cognitive-enhancing effects, and retrospective/observational investigations of the mental health of long-term ayahuasca users suggest that prolonged use of this harmine-rich hallucinogen is associated with better neuropsychological functioning. Thus, in order to better investigate these possibilities, we performed a systematic literature review of preclinical studies analyzing the effects of harmine on hippocampal neurons and in memory-related behavioral tasks in animal models. We found two studies involving hippocampal cell cultures and nine studies using animal models. Harmine administration was associated with neuroprotective effects such as reduced excitotoxicity, inflammation, and oxidative stress, and increased brain-derived neurotrophic factor (BDNF) levels. Harmine also improved memory/learning in several animal models. These effects seem be mediated by monoamine oxidase or acetylcholinesterase inhibition, upregulation of glutamate transporters, decreases in reactive oxygen species, increases in neurotrophic factors, and anti-inflammatory effects. The neuroprotective and cognitive-enhancing effects of harmine should be further investigated in both preclinical and human studies.     

Body mass index, migraine, migraine frequency and migraine features in women

We evaluated the association of body mass index (BMI) with migraine and migraine specifics in a cross-sectional study of 63 467 women aged ≥ 45 years, of whom 12 613 (19.9%) reported any history of migraine and 9195 had active migraine. Compared with women without migraine and a BMI < 23 kg/m², women with a BMI ≥ 35 kg/m² had adjusted odds ratios (ORs) (95% confidence intervals) of 1.03 (0.95, 1.12) for any history of migraine. Findings were similar for active migraineurs. Women with a BMI of ≥ 35 kg/m² had increased risk for low and high migraine frequency, with the highest estimate for women who reported daily migraine. Compared with women with the lowest associated risk (migraine frequency < 6 times/year; BMI between 27.0 and 29.9 kg/m²), women with a BMI ≥ 35 kg/m² had an OR of daily migraine of 3.11 (1.12, 8.67). Among the women with active migraine, a BMI ≥ 35 kg/m² was associated with increased risk of phonophobia and photophobia and decreased risk of a unilateral pain characteristic and migraine aura. Our data confirm previous findings that the association between BMI with migraine is limited to migraine frequency and specific migraine features.     

Early postoperative constrictive pericarditis: value of echocardiography. Report of 4 cases

In the present study, four cases of early postoperative constrictive pericarditis have been described which serve as a basis for recalling the current main echographic features of this disorder: pericardial thickening, abnormal septal movement with inspiratory expansion of the right ventricle, respiratory variations in ventricular filling, characteristic modifications in the supra-hepatic pulmonary venous flow, and pulmonary insufficiency. Some hypotheses have also been presented on the possible etiology of this disease. The necessity of making a precise and rapid diagnosis, which should also be confirmed by catheterization to ensure the appropriateness of therapy, has been emphasized. Pericardectomy can determine the long-term prognosis.     

Regressed retinopathy of prematurity: the relationship between clinical risk factors of the newborn period and regressed retinopathy of prematurity severity in a preterm born population of Stockholm county 1976-81

In a retrospective study, clinical risk factors of the neonatal period were correlated with the severity of regressed retinopathy of prematurity (ROP) in a population of preterm infants (bw less than 1500 g and or gestational age less than 33 weeks). At the age of 5-11 years 134 out of 528 preterm born infants (25.4%) were found to be under ophthalmic care. Reliable information on eye fundus status could be obtained in 105 of them. Regressed ROP was found in 61, the moderate form in 48 (9.1%) and the severe form in 13 (2.5%) patients. Twelve patients (2.3%) had visual acuity of less than 0.3 on the worst eye and two (0.4%) of these patients were blind from ROP. Twenty-four clinical factors of the newborn period were correlated with the severity of regressed ROP. The results suggest that long oxygen exposure in combination with other factors interfering with retinal vasotonus are associated with the degree of the disease developed.     

Rofecoxib Reduces Polyp Recurrence in Familial Polyposis

The long-term (mean of 16.4±4.2 months) efficacy and safety of rofecoxib (a specific COX-2 inhibitor) in maintaining the colon free of polyps in familial polyposis patients was assessed. Eight patients were treated with rofecoxib 25 mg every day. Sigmoidoscopy/colonoscopy was performed at study entry and every six months. At each endoscopy the number, size, and histological grade of all polyps were assessed, and the polyps were removed. The drug was well tolerated with no significant adverse events throughout the study. A highly significant reduction in the rate of polyp formation (70–100%) was observed in all patients from a mean number of 15.1±11.7 at baseline to 6.0±5.8 at one year and 1.6±1.6 at the end of follow-up (P =0.016 and 0.008, respectively). No patient developed cancer or high-grade adenoma. In conclusion, Long-term use of rofecoxib is well tolerated and effective in inhibiting polyp formation in polyposis patients.     

Status cataplecticus induced by abrupt withdrawal of clomipramine

Introduction: Cataplexy is one of the main narcoleptic symptoms and is characterized by sudden loss of muscle tone triggered by emotional stimuli while consciousness is mantained. Clomipramine is an effective treatment of cataplexy. Cataplexy that occurs repeatedly for hours or days is referred to as status cataplecticus.Patients: We report three adults with narcolepsy in whom cataplexy was chronically and effectively treated with clomipramine (75-150 mg/day). For diverse reasons, these three patients had an abrupt withdrawal of clomipramine, and after 2-9 days patients showed an invalidant status cataplecticus characterized by a marked increase of the frequency, duration and severity of their cataplectic attacks that were now elicited by mild emotional stimuli. After introduction of anticataplectic agents (clomipramine in two patients and fluoxetine in one patient), status cataplecticus was resolved in less than a week.Conclusion: In patients with narcolepsy, abrupt withdrawal of chronic treatment with clomipramine may be associated with status cataplecticus. This condition may be resolved with the reintroduction of anticataplectic agents.