霉酚酸酯与环磷酰胺治疗新月体性狼疮性肾炎的疗效比较

目的:回顾性对照研究霉酚酸酯(MMF)与环磷酰胺(CTX)治疗新月体性狼疮性肾炎(CLN)的疗效、复发率、远期预后和副作用的差异。方法:对1998年1月至2005年6月在解放军肾脏病研究所住院肾活检确诊(新月体形成率≥50%)CLN且经MMF或CTX诱导治疗的患者进行一般状况、临床表现、病理特征、治疗缓解率、复发率、副作用发生率及预后的回顾性对比分析。结果:52例CLN患者中,接受CTX治疗25例(2例失访),MMF治疗27例(1例失访)。CTX组和MMF组患者一般状况、临床表现及狼疮活动性指数(SLEDAI)、病理损害程度间无显著性差异,两组治疗12个月时缓解率分别为69.6%和73.1%,MMF组完全缓解率(53.8%)显著高于CTX组(26.1%),复发率(10.5%)则显著低于CTX组(43.8%),CTX组复发者多来自部分缓解者(占部分缓解患者的40.0%)。CTX组有部分患者出现药物副作用,包括肺部感染(3例,占13.0%)、肝损害(2例,占8.70%)和白细胞下降(1例,占4.35%);MMF组带状疱疹1例(占3.85%)、白细胞下降1例(占3.85%)。CTX组和MMF组随访时间分别为:10～80(38.5±21.2)月和12～90(41.1±27.0)月,无显著性差异。CTX组有2例(8.70%)患者分别在随访第48个月和第60个月进入终末期肾衰(ESRF),3例(13.0%)死亡,其中2例死于重症肺部感染,1例患者死于尿毒症后脑出血;MMF组有2例(7.41%)患者分别在随访第8个月和第24个月进入ESRF,无死亡病例。结论:与传统CTX方案比较,MMF治疗CLN取得更高的完全缓解率和低复发率,且感染副作用较CTX少见,安全性好。     

Human fatality associated with Pacific ciguatoxin contaminated fish

Ciguatera is a food poisoning identified as the principal risk factor in the consumption of tropical fish in Oceania. The syndrome, which follows ingestion of ciguatoxin-contaminated ciguateric fishes, is characterised by an array of gastrointestinal and neurological features. In this report we examine forensic samples associated with a human fatality using a ³H-brevetoxin binding assay and reversed-phase HPLC/MS and HPLC/MS/MS. Three Pacific ciguatoxins (P-CTX) were detected in the implicated fish flesh sample by LC-MS/MS, implicating multiple P-CTXs in the fatal case. Additionally, ciguatoxin was identified in a liver sample obtained at post-mortem. The level of ciguatoxin detected (0.14 ppb P-CTX-1 equivalents by binding assay) indicated that at least 10% of the ingested P-CTX-1 remained in the human liver 6 days after the toxic fish was consumed. This study confirms the potential of tropical reef fish to accumulate sufficient P-CTX to be lethal to humans, especially if the liver and viscera are consumed as part of the meal.     

莪术提取物ERC61对化疗小鼠造血功能的影响

目的:观察莪术提取物ERC61对环磷酰胺(CTX)抑制小鼠造血功能的影响并确定其最佳给药方式。方法:实验小鼠ipCTX(100mg.kg-1.d-1),连续给药3d,复制白细胞减少症模型;将ERC61按照单纯预防、单纯治疗和预防+治疗3种给药方式ip给药,常规方法计数小鼠白细胞数、骨髓有核细胞数,并测定脾指数。结果:ERC61对CTX抑制小鼠的白细胞数、骨髓有核细胞数、脾指数均有不同程度的改善。结论:ERC61可改善CTX抑制小鼠的造血功能,其中预防+治疗的给药方式效果最好。     

郑州地区ESBLs基因型分布研究

目的 明确ESBLs在郑州地区的基因型分布.方法 收集78株临床分离产ESBLs革兰阴性杆菌,混合后提取总质粒作为模版,用特异性引物进行PCR扩增.结果 显示TEM、SHV、OXA1、OXA20、CTX-M1、CTX-M14和CTX-M25的泳道有阳性条带.结论 郑州地区目前已有TEM、SHV、OXA和CTX-M四种亚型的ESBIs流行.     

Associations between Postprandial Gut Hormones and Markers of Bone Remodeling

Gut-derived hormones have been suggested to play a role in bone homeostasis following food intake, although the associations are highly complex and not fully understood. In a randomized, two-day cross-over study on 14 healthy individuals, we performed postprandial time-course studies to examine the associations of the bone remodeling markers carboxyl-terminal collagen type I crosslinks (CTX) and procollagen type 1 N-terminal propeptide (P1NP) with the gut hormones glucose-dependent insulinotropic polypeptide (GIP), glucagon-like peptide 1 (GLP-1), and peptide YY (PYY) using two different meal types—a standardized mixed meal (498 kcal) or a granola bar (260 kcal). Plasma concentrations of total GIP, total GLP-1, total PYY, CTX, and P1NP were measured up to 240 min after meal intake, and the incremental area under the curve (iAUC) for each marker was calculated. The iAUC of CTX and P1NP were used to assess associations with the iAUC of GIP, GLP-1, and PYY in linear mixed effect models adjusted for meal type. CTX was positively associated with GIP and GLP-1, and it was inversely associated with PYY (all p < 0.001). No associations of P1NP with GIP or GLP-1 and PYY were found. In conclusion, the postprandial responses of the gut hormones GIP, GLP-1, and PYY are associated with the bone resorption marker CTX, supporting a link between gut hormones and bone homeostasis following food intake.     

Characteristic Distribution of Ciguatoxins in the Edible Parts of a Grouper,Variola louti

Ciguatera fish poisoning (CFP) is one of the most frequently encountered seafood poisoning syndromes; it is caused by the consumption of marine finfish contaminated with ciguatoxins (CTXs). The majority of CFP cases result from eating fish flesh, but a traditional belief exists among people that the head and viscera are more toxic and should be avoided. Unlike the viscera, scientific data to support the legendary high toxicity of the head is scarce. We prepared tissue samples from the fillet, head, and eyes taken from five yellow-edged lyretail (Variola louti) individuals sourced from Okinawa, Japan, and analyzed the CTXs by LC-MS/MS. Three CTXs, namely, CTX1B, 52-epi-54-deoxyCTX1B, and 54-deoxyCTX1B, were confirmed in similar proportions. The toxins were distributed nearly evenly in the flesh, prepared separately from the fillet and head. Within the same individual specimen, the flesh in the fillet and the flesh from the head, tested separately, had the same level and composition of toxins. We, therefore, conclude that flesh samples for LC-MS/MS analysis can be taken from any part of the body. However, the tissue surrounding the eyeball displayed CTX levels two to four times higher than those of the flesh. The present study is the first to provide scientific data demonstrating the high toxicity of the eyes.     

Glutamate dehydrogenase 1 and SIRT4 regulate glial development

Congenital hyperinsulinism/hyperammonemia (HI/HA) syndrome is caused by an activation mutation of glutamate dehydrogenase 1 (GDH1), a mitochondrial enzyme responsible for the reversible interconversion between glutamate and α‐ketoglutarate. The syndrome presents clinically with hyperammonemia, significant episodic hypoglycemia, seizures, and frequent incidences of developmental and learning defects. Clinical research has implicated that although some of the developmental and neurological defects may be attributed to hypoglycemia, some characteristics cannot be ascribed to low glucose and as hyperammonemia is generally mild and asymptomatic, there exists the possibility that altered GDH1 activity within the brain leads to some clinical changes. GDH1 is allosterically regulated by many factors, and has been shown to be inhibited by the ADP‐ribosyltransferase sirtuin 4 (SIRT4), a mitochondrially localized sirtuin. Here we show that SIRT4 is localized to mitochondria within the brain. SIRT4 is highly expressed in glial cells, specifically astrocytes, in the postnatal brain and in radial glia during embryogenesis. Furthermore, SIRT4 protein decreases in expression during development. We show that factors known to allosterically regulate GDH1 alter gliogenesis in CTX8 cells, a novel radial glial cell line. We find that SIRT4 and GDH1 overexpression play antagonistic roles in regulating gliogenesis and that a mutant variant of GDH1 found in HI/HA patients accelerates the development of glia from cultured radial glia cells. © 2012 Wiley Periodicals, Inc.     

老年骨质疏松性骨折患者血清B-ALP、PTH、s-PINP和s-CTX表达

目的探讨老年骨质疏松性骨折(OPF)患者血清骨特异性碱性磷酸酶(B-ALP)、甲状旁腺激素(PTH)、I型前胶原氨基端前肽(s-PINP)和I型胶原羧基端交联肽(s-CTX)水平及临床意义。方法选取2019年3月至2020年3月本院收治76例老年OPF患者作为OPF组,同期收治80例未发生骨折骨质疏松症(OP)患者作为对照组。比较两组腰椎(L2-4)、股骨颈、桡骨远端骨密度(BMD)、B-ALP、PTH、s-PINP和s-CTX水平;分析B-ALP、PTH、s-PINP和s-CTX水平与BMD的相关性;利用受试者工作特征曲线(ROC)评价B-ALP、PTH、s-PINP和s-CTX水平与发生OPF的关系。结果 OPF组腰椎(L2-4)、股骨颈、桡骨远端三个部位BMD水平均低于对照组,差异有统计学意义(P<0.05)。OPF组B-ALP、PTH、s-PINP、s-CTX水平均高于对照组,差异有统计学意义(P<0.05)。OPF组腰椎(L2-4)、股骨颈、桡骨远端三个部位BMD水平与B-ALP、PTH、s-PINP和s-CTX水平呈负相关(P<0.05)。绘制ROC曲线,B-ALP、PTH、s-PINP、s-CTX诊断OPF发生的AUC分别为0.663、0.625、0.729、0.690,四者联合诊断OPF发生的AUC为0.856,高于四者单独诊断AUC值。结论OPF患者血清B-ALP、PTH、s-PINP、s-CTX与BMD密切相关,且对评估OPF发生具有较高的诊断价值。     

Faecal carriage of extended‐spectrum β‐lactamase‐producing Enterobacteriaceae among humans in Java,Indonesia, in 2001–2002

Objective To characterise commensal Escherichia coli and other Enterobacteriaceae with reduced susceptibility to cefotaxime that were collected in a large survey carried out among 3995 patients and healthy persons in two urban regions on Java, Indonesia, in 2001–2002. Methods The putative extended‐spectrum β‐lactamase (ESBL)‐producing Enterobacteriaceae were analysed using double‐disk synergy tests, isoelectric focusing, PCR assays, DNA sequencing, and pulsed‐field gel electrophoresis (PFGE). Results On the day of discharge after five or more days of hospitalisation, at least 95 of 999 (9.5%) patients carried ESBL‐positive Enterobacteriaceae as dominant faecal flora. Six patients were simultaneously colonised with E. coli and Klebsiella pneumoniae isolates with ESBL activity. On admission, only 6 of 998 (0.6%) patients were colonised. Faecal carriage of ESBL‐producing Enterobacteriaceae among healthy persons or persons visiting a public health centre was not detected. The 107 ESBL‐positive strains included 68 E. coli, 35 K. pneumoniae, and four other Enterobacteriaceae. bla_CTX‐M‐15 was the most prevalent ESBL in both E. coli (47.1%) and K. pneumoniae (45.7%), but the E. coli O25b‐ST131 clone was virtually absent. Other ESBL types found were: SHV‐2, ‐2a, ‐5, ‐12, CTX‐M‐3, ‐9, ‐14, and TEM‐19. PFGE revealed extensive genetic diversity among the isolates. Conclusions In 2001–2002, faecal carriage of ESBL‐producing Enterobacteriaceae as dominant flora in Indonesia was almost exclusively hospital‐associated. The presence of various bla_ESBL genes and the extensive genetic diversity among isolates argue against a single/dominant strain outbreak.     

Morphological damage to the premature fetal rat brain after acute carbon monoxide exposure

For most brain regions the responses of neurons to stimulation of the primary visual cortex (CTX) are unknown. The objective of this study was to determine how neurons (single-unit activity) in major limbic, thalamic, hypothalamic, and visual regions respond to electrical stimulation of the CTX. Cats underwent low cerveau isolé surgery (isolate forebrain) and electrode implantation. Unit activity was analyzed as action potentials recorded extracellularly under control (spontaneous firing rate) and experimental (poststimulus rate) conditions. A total sample of 2055 units were localized anatomically. The effect of CTX stimulation was primarily inhibitory in the initial 500-ms poststimulus responses. Only 20 cells (<1%) showed initial excitatory responses. Highly responsive regions included areas 17, 18, 19 and the hippocampal formation. Subcortical regions which showed marked (P < 0.01) inhibitory responses form part of the ascending reticular system (anterior, intralaminar, and reticular thalamic nuclei, and tegmental nucleus). Similar effects were also observed in the anteromedial hypothalamus. Only two regions showed significant (P < 0.05) prolonged responses (1 to 5 s) to CTX stimuli. One of them, the prostriatal cortex, exhibited increases in firing rates. The other, the cingulate cortex, showed inhibitory initial and prolonged responses. Therefore, information provided by CTX stimulation is distributed to different limbic and subcortical targets. We suggest that the mechanisms responsible for the effects of visual stimuli on arousal and emotion may be mediated by inhibition of ascending reticular pathways.