以肺动脉高压为首发表现的先天性中枢性低通气综合征临床特征和基因分析

目的探讨先天性中枢性低通气综合征(CCHS)的临床和基因变异特征。方法分析1例首发表现为不明原因肺动脉高压的CCHS患儿的临床资料,并总结国内外文献中CCHS病例的临床特点、致病机制和基因变异情况。结果11月龄女婴,主要表现为浮肿、尿少、低血压、嗜睡、发绀、抽搐及颅内压增高。B型脑利钠肽、丙氨酸氨基转移酶升高,凝血酶原时间延长。颅脑磁共振示右侧额叶出血;超声心动图示中重度肺动脉高压。靶向捕获二代测序未发现可能的致病基因。采用Sanger法验证示患儿PHOX 2 B基因第3外显子存在多聚丙氨酸重复扩展变异,基因型为20/25。患儿入院后采用无创通气,睡眠时呼吸浅慢、微弱,伴血氧下降;血气分析提示二氧化碳潴留。随后改用夜间无创通气、降肺压药物治疗。复查肺动脉压力明显下降,生命体征稳定。随访至24月龄,夜间只需较低压力水平的无创通气,生长发育无异常。结论对于不明原因的肺动脉高压伴撤机困难患儿,需警惕CCHS。疑诊者应尽早针对CCHS相关基因进行靶向捕获二代测序及PHOX 2 B基因Sanger法验证。早期给予无创通气有望改善预后。     

Perioperative,short-, and long-term outcomes of gastric cancer surgery: Propensity score-matched analysis of patients with or without prior solid organ transplantation

BackgroundDetails of perioperative outcomes and survival after gastric cancer surgery in prior transplant recipients have received minimal research attention.MethodsWe performed an observational cohort study using the database of 20,147 gastric cancer patients who underwent gastrectomy at a single gastric cancer center in Korea. Forty-one solid organ recipients [kidney (n = 35), liver (n = 5), or heart (n = 1)] were matched with 205 controls using propensity score matching.ResultsOperation time, blood loss, and postoperative pain were similar between groups. Short-term complication rates were similar between transplantation and control groups (22.0% vs. 20.1%, P = 0.777). Transplantation group patients with stage 1 gastric cancer experienced no recurrence, while those with stage 2/3 cancer had significantly higher recurrence risk compared to the controls (P = 0.049). For patients with stage 1 cancer, the transplantation group had a significantly higher rate of non-gastric cancer-related deaths compared to the controls (19.2% vs. 1.4%, P = 0.001). For those with stage 2/3 cancer, significantly lower proportion of the transplantation group received adjuvant chemotherapy compared to the control group (26.7% vs. 80.3%, P < 0.001). The transplantation group had a higher (albeit not statistically significant) rate of gastric cancer-related deaths compared to the controls (40.0% vs. 18.0%, P = 0.087).ConclusionTransplant recipients and non-transplant recipients exhibited similar perioperative and short-term outcomes after gastric cancer surgery. From long-term outcome analyses, we suggest active surveillance for non-gastric cancer-related deaths in patients with early gastric cancer, as well as strict oncologic care in patients with advanced cancer, as effective strategies for transplant recipients.     

Optimizing Prescribing and Deprescribing of Proton Pump Inhibitors

Prescribing of proton pump inhibitors (PPIs) has markedly increased since their inception more than 30 years ago. The increase is related to inappropriate and long-term prescribing of PPIs, associated with a lack of education and unclear prescribing and deprescribing guidelines. The implementation of prescribing stewardship programs influences the reduction and inappropriate use of this medication. The purpose of this review is to address the gaps that exist regarding the use of PPIs along with determining methods for deprescribing. Guidelines and stewardship programs, along with education, are needed to reduce the adverse health effects of long-term PPI therapy.     

Influence of SNPs in cytokine-related genes on the severity of food allergy and atopic eczema in children

Although many single nucleotide polymorphism (SNP) studies have reported an association of atopy, allergic diseases and total serum immunoglobulin E (IgE) levels, almost all of these studies sought risk factors for the onset of these allergic diseases. Furthermore, many studies have analyzed a single gene and hardly any have analyzed environmental factors. In these analyses, the results could be masked and the effects of other genes and environmental factors may be decreased. Here, we described the correlation between four genes [interleukin (IL)-4 (C-590T), IL-4 receptor (A1652G), FCER1B (G6842A) and STAT6 (G2964A)] in connection with IgE production; the role of IL-10 (C-627A) as a regulatory cytokine of allergy; and the severity of food allergy (FA) and atopic eczema (AE) in 220 Japanese allergic children. In addition to these SNPs, environmental factors, i.e., patient's attitude, indoor environment, and so on, were also investigated in this study. Our study was retrospective, and the correlation was analyzed by our defined clinical scores divided into three terms: worst symptoms, recent symptoms and general amelioration at the most recent examination during the disease course. Our results indicated that IL-10 AA, the genotype with lower IL-10 production, is associated with higher IgE levels in the serum (p < 0.0001, estimate; 0.912). Marginal liver abnormalities were observed in the subject group with both FA and AE (p < 0.1191, estimate; 0.1490). Our defined clinical scores enabled evaluation of various aspects of disease severity. Based on the scores, while no single SNP selected in this study determined severity, the combination of the SNP with laboratory data and environmental factors appeared to determine severity.     

Ets-1、MMP-1及TIMP-1在膀胱移行细胞癌中的表达

目的研究Ets-1、基质金属蛋白酶1(MMP-1)及基质金属蛋白酶1抑制物(TIMP-1)在膀胱移行细胞癌(BTCC)中的表达及意义。方法用免疫组化方法检测40例BTCC组织和12例正常膀胱黏膜组织中Ets-1、MMP-1及TIMP-1的表达;分析Ets-1与BTCC临床病理特征间的关系;研究BTCC中MMP-1、TIMP-1表达与Ets-1表达的相关性。结果①Ets-1在BTCC中高度表达,阳性率为82.5%(P<0.01),且随BTCC临床分期和病理分级的升高而增加,肿瘤复发组高于无复发组,肿瘤转移组高于无转移组(P<0.05)。②MMP-1阳性表达率膀胱癌组(85.0%)明显高于对照组(58.3%)(p<0.05);TIMP-1阳性表达率对照组(83.3%)明显高于膀胱癌组(47.5%)(P<0.05)。③MMP-1与Ets-1表达呈正相关(Rs为0.824,P<0.01),而TIMP-1与Ets-1表达呈负相关(Rs为-0.821,P<0.01)。结论①Ets-1在BTCC中高度表达,并随BTCC分期分级升高而增加;Ets-1与BTCC转移及复发密切相关。②BTCC中Ets-1上调MMP-1表达,而下调TIMP-1表达,从而参与BTCC侵袭与转移。     

肝细胞核因子-κB异常激活与肝细胞癌变

核因子-κB（nuclear factor-κB，NF-κB）是具有和某些基因上启动子区固定核苷酸序列结合而启动该基因转录的蛋白质。NF-κB是具有多向性调节作用的核转录因子，可调控多种基因（免疫、炎症反应、病毒和原癌基因）的转录表达。激活的NF-κB参与癌症的启动、发生及发展过程，在炎症性相关的肝癌（HCC）发生发展中呈高表达，在肝细胞炎症与癌变间起桥梁作用，其中包括肝脏免疫炎症反应相关基因、肝炎病毒相关基因和原癌基因的转录表达。在肝癌组织中异常激活，可抑制细胞凋亡，促进肝细胞存活，与肝癌的发生发展密切相关。     

三列凹顶藻中倍半萜成分的研究

目的从三列凹顶藻Laurenciatristicha中寻找具有多样性结构的倍半萜化学成分,供药理活性筛选。方法采用凝胶柱色谱、硅胶柱色谱、重结晶和高效液相色谱等方法进行分离;借助包括一维和二维NMR等波谱方法和X-单晶衍射鉴定化合物的结构;用MTT法对得到的化合物进行细胞毒活性评价。结果分离得到5个倍半萜类化合物,分别鉴定为海兔阿普里素(aplysin,)、海兔阿普里醇(aplysinol,)、去溴海兔阿普里醇(debro-moaplysinol,)、凹顶藻联苯(laurebiphenyl,)、约翰斯顿醇(johnstonol,);在人肿瘤细胞株HCT-8、Bel-7402、BGc-823、A549和HeLa模型上,化合物对所有细胞株均显示毒性,化合物对HeLa细胞显示中等强度的细胞毒活性,其他化合物对所有细胞株均无明显毒性,IC50均大于10.0μg/mL。结论化合物~均为首次从三列凹顶藻中得到,化合物对HeLa细胞具有中等强度的选择性细胞毒活性,化合物对所有细胞株均显示毒性。