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简介：摘要在脓毒性休克患者早期诊治中，常规血流动力学参数及氧供参数并不能准确判断组织缺氧的存在，而与这些参数相比，静-动脉二氧化碳分压差/动-静脉氧含量差比值(Pv-aCO2/Ca-vO2)能够迅速地反映机体无氧代谢的状态，且与乳酸及乳酸清除率有较强的相关性。因此，在脓毒性休克患者早期复苏阶段，Pv-aCO2/Ca-vO2比值可以作为一个较好的生物标志物来评估液体反应性及预测不良预后。

简介：摘要目的总结2例腺苷脱氨酶2(ADA2)缺乏症患儿的临床表型及基因特点，并进行文献复习，提高对该病的认识。方法对2019年3月至12月就诊于青岛大学附属医院的2例ADA2缺乏症患儿的临床资料和基因型进行分析。查阅国内外数据库相关文献，总结该病的临床特征及基因变异特点。结果1．本组2例患儿均存在ADA2基因突变，例1表现为反复发热、网状青斑、结节性多动脉炎及免疫缺陷，为ADA2基因c.571delC(p.Q191Sfs*5)纯合突变，国内外均未见报道，为新发变异；例2表现为反复发热、脂膜炎、下肢血管炎及免疫缺陷，为ADA2基因c.1358A>G(p.Y453C)纯合突变，该位点在国内尚未见报道。2.国外基因确诊患儿共171例，国内仅报道3例，加上本研究2例国内共5例，该5例主要临床表现反复发热(5/5例)，皮肤网状青斑(4/5例)，脂膜炎(1/5例)，皮肤坏疽(1/5例)，生长迟缓(1/5例)，脑梗死(3/5例)，体液免疫缺陷(4/5例)，血液系统受累(3/5例)，肌痛(2/5例)，炎性指标C反应蛋白、红细胞沉降率升高(5/5例)。结论ADA2缺乏症临床表现多样，掌握其临床特点，有助于提高临床诊治水平。c.571delC突变位点国内外均未见报道，为新发现的ADA2基因突变类型，进一步丰富了ADA2基因谱。

简介：摘要例1男，16岁，面部、颈部及双腋下见密集褐色毛囊角化性丘疹，部分融合成斑块，局部可见疣状增生；母亲与其有相似的病史及临床表现。例2男，21岁，头面部、颈部、躯干、双腋下及臀部见弥漫性毛囊角化性丘疹，部分融合成片，局部可见疣状增生；家族成员均无类似症状。例2颈部皮损组织病理：表皮角化过度伴灶状角化不全，棘层部分区域棘刺松解并有腔隙形成，可见绒毛、圆体和谷粒细胞，真皮浅层炎症细胞浸润。2例患者及其父母基因检测：例1及母亲ATP2A2基因存在第15外显子c.2300A>G错义突变；例2第15外显子与第15内含子交界处存在c.2097+5G>A剪切区域突变。2例患者其他家族成员未见上述突变。

简介：AbstractBackground:Since its discovery in December 2019, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has infected more than 2 180 000 people worldwide and has caused more than 150 000 deaths as of April 16, 2020. SARS-CoV-2, which is the virus causing coronavirus disease 2019 (COVID-19), uses the angiotensin-converting enzyme 2 (ACE2) as a cell receptor to invade human cells. Thus, ACE2 is the key to understanding the mechanism of SARS-CoV-2 infection. This study is to investigate the ACE2 expression in various human tissues in order to provide insights into the mechanism of SARS-CoV-2 infection.Methods:We compared ACE2 expression levels across 31 normal human tissues between males and females and between younger (ages ≤ 49 years) and older (ages > 49 years) persons using two-sided Student's t test. We also investigated the correlations between ACE2 expression and immune signatures in various tissues using Pearson's correlation test.Results:ACE2 expression levels were the highest in the small intestine, testis, kidneys, heart, thyroid, and adipose tissue, and were the lowest in the blood, spleen, bone marrow, brain, blood vessels, and muscle. ACE2 showed medium expression levels in the lungs, colon, liver, bladder, and adrenal gland. ACE2 was not differentially expressed between males and females or between younger and older persons in any tissue. In the skin, digestive system, brain, and blood vessels, ACE2 expression levels were positively associated with immune signatures in both males and females. In the thyroid and lungs, ACE2 expression levels were positively and negatively associated with immune signatures in males and females, respectively, and in the lungs they had a positive and a negative correlation in the older and younger groups, respectively.Conclusions:Our data indicate that SARS-CoV-2 may infect other tissues aside from the lungs and infect persons with different sexes, ages, and races equally. The different host immune responses to SARS-CoV-2 infection may partially explain why males and females, young and old persons infected with this virus have markedly distinct disease severity. This study provides new insights into the role of ACE2 in the SARS-CoV-2 pandemic.

简介：摘要目的探究E2F2基因在子宫内膜癌中的表达及与生物学行为的相关性。方法选择2015年3月至2018年4月本院妇科获取的30例正常子宫内膜标本、25例子宫内膜增生标本及73例子宫内膜癌组织纳入研究。采用RT-PCR及链霉菌抗生物素蛋白-过氧化酶连接(SP)法测定3种组织E2F2 mRNA表达情况，并分析子宫内膜癌组织E2F2蛋白表达与临床病理参数之间的关系。结果子宫内膜癌组织E2F2 mRNA表达量高于子宫内膜增生组织及正常子宫内膜组织，差异有统计学意义(P<0.05)；正常子宫内膜、子宫内膜增生及子宫内膜癌组织E2F2蛋白阳性表达率分别为10.00%、16.00%及52.05%，组间比较差异有统计学意义(P<0.05)；国际妇产科联盟(FIGO)分期为Ⅲ～Ⅳ期、中低分化、有淋巴结转移及肌层浸润≥1/2的子宫内膜癌患者E2F2蛋白阳性表达程度显著高于FIGO分期为Ⅰ～Ⅱ期、高分化、无淋巴结转移及肌层浸润<1/2的患者(P<0.05)。结论子宫内膜癌组织E2F2表达上调，其表达程度与患者FIGO分期、分化程度、淋巴结转移及肌层浸润相关。

简介：摘要目的观察蓝萼甲素预处理对H2O2诱导H9c2心肌细胞损伤模型的保护作用，并采用网络药理学方法预测蓝萼甲素抗H9c2心肌细胞凋亡的作用机制。方法将H9c2心肌细胞按随机数字表法分为空白对照组、模型组及蓝萼甲素低、中、高剂量组。空白对照组使用无血清培养液处理。模型组采用无血清培养4 h后，加入250 μmol/L H2O2干预6 h。蓝萼甲素低、中、高剂量组分别给予蓝萼甲素0.125、0.250、0.500 μg/ml预处理4 h后，加入浓度为250 μmol/L H2O2干预6 h。采用MTT法检测心肌细胞活力，观察细胞形态，采用Annexin Ⅴ-FITC/PI荧光双染及Hoechst 33258荧光染色检测细胞凋亡情况。通过Pubchem数据库获得蓝萼甲素的化学结构式，使用Swiss Target Prediction和Pharmmapper平台预测蓝萼甲素潜在靶点，利用GeneCards数据库筛选蓝萼甲素抗H9c2心肌细胞凋亡的作用靶点。采用Cytoscape软件构建蓝萼甲素作用的靶点网络，通过String数据库和Cytoscape软件绘制蛋白相互作用网络，并用Metascape数据库对靶点进行GO及KEGG通路富集分析。结果与模型组比较，蓝萼甲素低、中、高剂量组H9c2心肌细胞活力[(66.56±6.51)%、(79.21±6.89)%、(94.06±5.19)%比(51.75±4.14)%]升高(P<0.01)，细胞凋亡率[(24.12±4.71)%、(17.42±4.39)%、(7.65±1.56)%比(36.73±5.65)%]降低(P<0.01)。网络药理学分析结果提示，蓝萼甲素有22个与抗H9c2心肌细胞凋亡相关的靶点，主要调节氧化应激、细胞迁移、激酶结合活性等，可调节MAPK1、VEGFA、MMP9、NOS3、MMP2、MAPK14等靶点通路，发挥抗H9c2心肌细胞凋亡作用。结论蓝萼甲素预处理对H2O2诱导H9c2心肌细胞损伤有保护作用，其机制可能通过多靶点-多途径发挥抗氧化应激和减少细胞凋亡的作用。

简介：摘要目的探讨2型糖尿病（T2DM）患者SLC2A2 rs5393、rs5400位点基因多态性与二甲双胍疗效的相关性。方法选取2016年1月至2019年4月期间在山西医科大学第一医院就诊的T2DM患者90例（T2DM组）及90例体检健康者（对照组）作为研究对象，通过PCR-限制性片段长度多态性（PCR-RELP）法检测SLC2A2 rs5393、rs5400位点基因多态性分布频率。对T2DM患者进行二甲双胍治疗，随访90 d，分析二甲双胍疗效与各基因型的关系。结果对照组与T2DM组SLC2A2 rs5393、rs5400各基因型符合Hardy-Weinberg平衡定律。与对照组相比，T2DM组rs5393位点AC型、CC型比例显著升高（P<0.05），rs5400位点CT、TT型频率显著升高（P<0.05）。rs5393位点中，治疗前AA型、AC型、CC型空腹血糖（FBG）、餐后2 h血糖（2 h PBG）、糖化血红蛋白（HbA1c）水平差异无统计学意义（P>0.05）；二甲双胍治疗后AC型、CC型患者FPG、2 h PBG、HbA1c降低幅度低于AA型（P<0.05），CC型FPG、HbA1c降低幅度低于AC型（P<0.05）。rs5400位点中，治疗前CC型、CT型、TT型FPG、2 h PBG、HbA1c水平差异无统计学意义（P>0.05）；二甲双胍治疗后CT型、TT型患者FPG、2 h PBG、HbA1c降低幅度低于CC型（P<0.05），TT型FPG、HbA1c降低幅度低于CT型（P<0.05）。结论SLC2A2基因多态性位点rs5393 AA型患者、rs5400 CC型T2DM患者对二甲双胍敏感，降糖疗效较好。

简介：AbstractIntroduction:Darier’s disease is a rare autosomal dominant skin disorder caused by mutations in ATP2A2. Recently, the high prevalence of neuropsychiatric symptoms is frequently reported in Darier’s disease patients.We present a case of patient with concurrence of Darier’s disease and depression and detected the mutations in ATP2A2.Case presentation:A 29-year-old man presented with a 15-year history of brown, harsh keratotic papules on his scalp, face, neck, trunk, axilla, ingunia and upper limbs. Meanwhile, he had persistent depression. He was diagnosed as Darier’s disease according to clinical manifestations and result of histological examination. We sequenced all coding regions of ATP2A2. The mutation c.2993_2994del (p. Val998Alafs*33) in exon 20 of ATP2A2 was detected.Discussion:Darier’s disease has been associated with several extracutaneous manifestations, in particular neuropsychiatric morbidity. Likely gene disrupting mutations in ATP2A2 was reported to have a close relationship to Darier’s disease cases with reported co-occurring neuropsychiatric features. Consistent with the previous reports, an likely gene disrupting mutations was detected in our patient with concurrence of DD and depression.Conclusion:The psychiatric disorders in patients with Darier’s disease should be well appreciated .The underlying mechanism in correlation between the mutation in ATP2A2 and neuropsychiatric phenotypes in Darier’s disease remain unclarified and warrants further investigation.

简介：摘要KCNQ2基因编码电压门控钾离子通道，在大脑中表达。KCNQ2变异导致临床上严重程度不同的疾病，包括从临床症状较轻、精神运动发育良好的良性家族性新生儿惊厥1型，到临床症状严重、伴有中至重度精神运动发育障碍的早期婴儿癫痫性脑病7型等一系列的癫痫谱系疾病。目前，根据变异位点所做的研究，KCNQ2相关疾病发病机制主要包括两个方面：变异导致功能受损及异常功能的增多。该文对KCNQ2基因及与KCNQ2相关的疾病的发病机制、临床表现进行了综述。

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简介：摘要回顾性分析2例儿童良性外展神经麻痹患者的临床资料，总结其临床特征。2例患儿就诊时均为双眼外展神经受累，第2例发病前1周有上呼吸道感染，左眼外展受限8 d后又出现右眼外展受限。2例患儿各项辅助检查均未见异常，排除其他病因，诊断儿童良性外展神经麻痹。给予B族维生素营养神经，甲泼尼龙及丙种球蛋白等免疫治疗，患儿在病程5～6周症状稍有好转，在病程12～14周完全恢复，各种症状消失，双眼视物无重影，无外展受限，预后良好，无后遗症。提示儿童良性外展神经麻痹病因不明，可能与病毒感染后的免疫因素有关，经治疗预后良好。

简介：AbstractBackground:Pancreatic stellate cells (PSCs) activation plays a critical role in the development of chronic pancreatitis. Previous studies confirmed that thromboxane A2 receptor (TxA2r) was overexpressed in activated PSCs in rats. The purpose of this study was to investigate the role of TxA2r in the activation of PSCs induced by 8-epi-prostaglandin F2α (8-epi-PGF2α).Methods:TxA2r expression in both quiescent and activated PSCs was detected by immunocytochemistry and immunoblot assay. Isolated PSCs were treated with 8-epi-PGF2α (10-6, 10-7, 10-8 mol/L) for 48 h, and SQ29548 (10-4, 10-6, and 10-7 mol/L), a TxA2r-specific antagonist, for 48 h, respectively, to identify the drug concentration with the best biological effect and the least cytotoxicity. Then isolated PSCs were treated with SQ29548 (10-4 mol/L) for 2 h, followed by 10-7 mol/L 8-epi-PGF2α for 48 h. Real-time polymerase chain reaction was performed to detect the messenger RNA (mRNA) levels of α-smooth muscle actin (α-SMA) and collagen I. Comparisons between the groups were performed using Student’s t test.Results:TxA2r was up-regulated in activated PSCs in vitro compared with quiescent PSCs (all P < 0.001). Compared with the control group, different concentrations of 8-epi-PGF2a significantly increased mRNA levels of α-SMA (10-6 mol/L: 2.23 ± 0.18 vs. 1.00 ± 0.07, t= 10.70, P < 0.001; 10-7 mol/L: 2.91 ± 0.29 vs. 1.01 ± 0.08, t= 10.83, P <0.001; 10-8 mol/L, 1.67 ± 0.07 vs. 1.00 ± 0.08, t= 11.40, P < 0.001) and collagen I (10-6 mol/L: 2.68 ± 0.09 vs. 1.00 ± 0.07, t = 24.94, P < 0.001; 10-7 mol/L: 2.12 ± 0.29 vs. 1.01 ± 0.12, t = 6.08, P < 0.001; 10-8 mol/L: 1.46 ± 0.15 vs. 1.00 ± 0.05, t = 4.93, P = 0.008). However, different concentrations of SQ29548 all significantly reduced the expression of collagen I (10-4 mol/L: 0.55 ± 0.07 vs. 1.00 ± 0.07, t = 10.47, P < 0.001; 10-6 mol/L: 0.56 ± 0.10 vs. 1.00 ± 0.07, t = 6.185, P < 0.001; 10-7 mol/L: 0.27 ± 0.04 vs. 1.00 ± 0.07, t= 15.41, P < 0.001) and α-SMA (10-4 mol/L: 0.06 ± 0.01 vs. 1.00 ± 0.11, t= 15.17, P < 0.001; 10-6 mol/L: 0.28 ± 0.03 vs. 1.00 ± 0.11, t= 11.29, P < 0.001; 10-7 mol/L: 0.14 ± 0.04 vs. 1.00 ± 0.11, t= 12.86, P < 0.001). After being treated with SQ29548 (10-4 mol/L) and then 8-epi-PGF2α (10-7 mol/L), the mRNA levels of a-SMA (0.20 ± 0.08 vs. 1.00 ± 0.00, t= 17.46, P < 0.001) and collagen I (0.69 ± 0.13 vs. 1.00 ± 0.00, t = 4.20, P = 0.014) in PSCs were significantly lower than those of the control group.Conclusions:The results show that 8-epi-PGF2α promoted PSCs activation, while SQ29548 inhibited PSCs activation induced by 8-epi-PGF2α. The result indicated that TxA2r plays an important role during PSC activation and collagen synthesis induced by 8-epi-PGF2αin vitro. This receptor may provide a potential target for more effective antioxidant therapy for pancreatic fibrosis.

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简介：摘要悬吊肝脏，于横结肠中部大网膜附着处向左切开网膜，分离切断胃网膜左血管，至胃短血管第二支，清扫第4sb组淋巴结；分离横结肠系膜前叶右侧部分至大网膜完全从结肠离断，显露胰头、十二指肠球部，离断胃网膜右动静脉，清扫第4d、6组淋巴结；从右向左，从下向上剥离胰腺被膜；显露胰腺上缘，分离肝总动脉表面，清扫第8a、12a组淋巴结；分离切断胃左动静脉，沿脾动脉向左分离至胃后血管为止，清扫第7、9、11p组淋巴结；解剖胃小弯区域，离断肝胃韧带，分离胃右动静脉并清扫肝十二指肠韧带的第5、12a组淋巴结；暴露右侧膈肌角，游离至食管裂孔，清扫第1、3组淋巴结。胃肠重建采用直线切割闭合器行BillrothⅡ式吻合，共同开口以倒刺线缝闭。

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简介：AbstractSevere acute respiratory syndrome coronavirus 2 (SARS-CoV-2) viruses spread unscrupulously virtually every corner on the planet in a very quick speed leading to an unprecedented world pandemic of COVID-19 claiming a great many of people’s life. Paramount importance has been given to the studies on the virus itself including genomic variation and viron structure, as well as cell entry pathway and tissue residence. Other than that, to learn the main characteristic of host immunity responding to SARS-CoV-2 infection is an eminent task for restraining virus and controlling disease progress. Beside antibody production in response to SARS-CoV-2 infection, host cellular immunity plays an indispensable role in impeding virus replication and expansion at various stages of COVID-19 disease. In this review, we summarized the recent knowledge regarding the aberrant regulation and dysfunction of multiple immune cells during SARS-CoV-2 infection. This includes the dysregulation of immune cell number, Th polarity, cytokine storm they implicated with, as well as cell function exhaustion after chronic virus stimulation. Notwithstanding that many obstacles remain to be overcome, studies on immunotherapy for COVID-19 treatment based on the known features of host immunity in response to SARS-CoV-2 infection offer us tangible benefits and hope for making this SARS-CoV-2 pandemic under control.

简介：摘要对2016年1月至2017年12月首都医科大学附属北京儿童医院呼吸科诊断的2例急性间质性肺炎(AIP)患儿的临床表现、影像学变化及病理表现进行回顾性分析。例1，女，8岁4个月；例2，男，1岁11个月。2例患儿均以"咳嗽、气促20 d"为主诉入院，病初有一过性低热，于院外分别按照肺炎支原体肺炎、病毒性肺炎治疗，效果不佳。入院查体均可见呼吸促，三凹征(＋)，口唇、指/趾端发绀，未见杵状指，无啰音。心腹及神经系统查体无异常。均存在低氧血症，二氧化碳分压正常。病原学检查、自身抗体和抗中性粒细胞胞质抗体均为阴性。肺高分辨CT(HRCT)提示双肺透光度减低，以下肺为著，弥散磨玻璃影，实变以及受牵拉的支气管。肺组织病理表现为弥散性肺泡损伤，可见肺泡间隔增厚，肺泡腔内可见纤维样组织。病例1可见透明膜形成。2例患儿均使用糖皮质激素治疗，其中例1应用鼻导管吸氧，例2应用经鼻持续气道正压通气(NCPAP)呼吸支持，均存活，随访2例患儿激素应用逐渐减停，疗程分别为8个月和1年，肺内病变基本吸收。

简介：摘要钠-葡萄糖协同转运蛋白2(SGLT2)抑制剂是一种新型降糖药，可控制血糖、降低心血管事件、改善肾功能等。越来越多的数据表明，SGLT2抑制剂也可降低血尿酸水平。可能的机制是近端肾小管腔内葡萄糖的排泄增强，通过顶端膜上葡萄糖转运蛋白(GLUT)9亚型2促进细胞内尿酸盐的交换，导致尿酸分泌增加，且SGLT2抑制剂抑制肾小管重吸收葡萄糖，导致尿中葡萄糖增加，这可能会抑制集合管中GLUT9亚型2介导的尿酸重吸收。另一种可能的机制是SGLT2抑制剂通过降低血清胰岛素浓度，减少尿酸盐重吸收转运蛋白1(URAT1)对尿酸的重吸收。

简介：摘要目的探讨非瓣膜性心房颤动(房颤)患者脑微出血(CMBs)与CHA2DS2-VASc评分的相关性，分析房颤CMBs患者的相关危险因素。方法回顾性病例对照研究，选取2015年1月至2017年12月在浙江医院住院且行头颅磁共振加权成像检查的164例非瓣膜性房颤患者，其中CMBs组43例(26.2%)，无CMBs组121例(73.8%)。采集患者临床资料，进行CHA2DS2-VASc评分，并对CMBs的数量进行计数；分析房颤患者CMBs与CHA2DS2-VASc评分年龄、高血压等危险因素的相关性。结果CHA2DS2-VASc评分越高CMBs的出现比例越高(P<0.05)；其中CMBs数量≥5个的比例也与CHA2DS2-VASc评分呈正相关(P<0.05)。CMBs组年龄(81.0±8.1)岁，高于无CMBs组患者(75.4±11.2)岁(P<0.01)。CMBs组与无CMBs组患者高血压36例(83.7%)比79例(63.2%)、中重度脑白质疏松19例(44.2%)比31例(33.9%)、抗凝治疗15例(34.9%)比23例(19.0%)，差异有统计学意义(均P<0.05)。CMBs组患者CHA2DS2-VASc评分的中位数为4分，高于无CMBs患者组3分(P<0.01)。Logistic回归分析提示年龄和抗凝治疗是房颤患者CMBs的独立危险因素(P<0.05)。结论房颤患者CMBs与CHA2DS2-VASc评分呈正相关，年龄和抗凝治疗是房颤患者发生CMBs的危险因素。对CHA2DS2-VASc评分高的高龄房颤患者，抗凝前及抗凝期间应监测CMBs。