简介：摘要目的本实验旨在进一步验证与评价M2BP与M2BPGi在胆道闭锁（biliary atresia，BA）患儿肝纤维化中的作用。方法收集2019年9月至2020年11月天津市儿童医院普外科收治的48例行肝相关手术的患儿肝组织标本，患儿按疾病类型分为实验组（BA组）35例，其中男17例，女18例，年龄为60(30, 60) d；对照组（DC组）13例，其中男7例，女6例，年龄为120(60, 720) d。DC组中包括2例胆汁淤积，7例胆总管囊肿（choledochal cyst，CC），4例胆管发育不良（biliary hypoplasia，BH）。通过免疫组织化学检测肝组织中M2BP蛋白含量，分析其与肝组织纤维化分级的相关性；通过实时荧光定量聚合酶链反应（real-time reverse transcription polymerase chain reaction，qRT-PCR），检测肝组织中M2BP mRNA含量，分析其转录、翻译水平是否表达一致。另收集患儿中26例BA、4例BH的血清，检测患儿肝功能相关的生化指标，采用酶联免疫吸附测定（enzyme-linked immunosorbent assay，ELISA）检测其血清M2BPGi浓度。患儿组间比较采用Mann-Whitney U秩和检验；用Spearman相关分析评价M2BP及M2BPGi水平与肝纤维化分级的相关性，建立ROC曲线评价血清M2BPGi浓度在肝纤维化中的作用。结果①免疫组织化学结果显示，M2BP表达于肝细胞、巨噬细胞胞质内；BA组患儿肝组织中M2BP蛋白的含量为0.187(0.116, 0.222），高于DC组的0.122(0.072, 0.141），组间比较，差异有统计学意义（P=0.004）；肝组织中M2BPGi的含量与肝纤维化分级存在正相关（rs=0.847，P< 0.001）。②qRT-PCR结果显示，BA组患儿肝组织中M2BP mRNA水平为0.099(0.059, 0.138），高于DC组的0.036(0.015，0.064），组间比较，差异有统计学意义（P<0.001）；Ⅲ~Ⅳ级肝纤维化中M2BP mRNA水平为0.129(0.093, 0.194），高于Ⅰ~Ⅱ级肝纤维化的0.060 （0.027, 0.098），组间比较，差异有统计学意义（P<0.001）；与肝组织中M2BP蛋白含量表达一致，随着肝纤维化分级增加，M2BP mRNA水平也随之增加。③ELISA结果显示，Ⅲ~Ⅳ级肝纤维化的血清中M2BPGi含量为6.07 （5.03 ，10.33) ng/ml，高于Ⅰ~Ⅱ级肝纤维化的2.70(2.03, 3.68) ng/ml，组间比较，差异有统计学意义（P<0.001）。单独建立血清中M2BPGi评估肝纤维化分级的ROC曲线，当评估Ⅲ~Ⅳ级肝纤维化时，显示曲线下面积为0.972 （95%的置信区间为0.918~1.000），敏感度、特异度、准确度、PPV和NPV分别为0.889、1.000、94.45%、100.00%和90.01 %，M2BPGi的临界值4.48 ng/ml。结论M2BP在BA肝组织中高表达且随肝纤维化程度加重而增加，血清中其糖基化异构体M2BPGi在预测BA患儿肝纤维化的严重程度方面有一定价值。

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。

简介：摘要目的评价A2DS2评分诊断中国缺血性脑卒中相关性肺炎患者的准确性及临床适应性。方法通过检索Medline、PubMed、Embase、Cochrane、Web of Science、万方、中国知网、维普、中国生物医学数据库自建库至2020年2月发表的文献，筛选应用A2DS2评分预测中国缺血性脑卒中患者发生肺炎的相关文献，采用QUADAS-2风险评估标准对纳入文献进行质量评价，采用Meta分析评价A2DS2评分诊断中国缺血性脑卒中相关性肺炎患者的准确性，采用Deek检验评价文献发表偏倚，采用范根图评价A2DS2评分的临床适用性。结果最终纳入12篇文献，共7719例患者。Meta分析显示A2DS2评分的诊断比值比(DOR)为18(95%CI：12~27)，合并灵敏度为0.76(95%CI：0.68~0.82)，合并特异度为0.85(95%CI：0.80~0.88)，合并阳性似然比为5.02(95%CI：3.91~6.44)，合并阴性似然比为0.29(95%CI：0.22~0.38)。A2DS2评分诊断中国缺血性脑卒中相关性肺炎的综合受试者工作特征(SROC)曲线的曲线下面积(AUC)为0.88(95%CI：0.85~0.91)。Deek检验结果显示各纳入文献无明显发表偏倚(P>0.05)。范根图显示A2DS2评分的临床适用性较好。结论A2DS2评分对中国缺血性脑卒中相关性肺炎具有较好的诊断价值，可用于临床初步筛查缺血性脑卒中相关性肺炎患者。

简介：AbstractObjective:This study was aimed to determine the changes in CXCR2 expression in preeclampsia placenta and its correlation with clinical parameters.Methods:Sixty-four gravidas ranging in age from 25 to 42 years referred to the obstetrics unit of the West China Second University Hospital from April 2012 to October 2012 were recruited in this case-control study; women were diagnosed and divided into early-onset preeclampsia group (n= 22), late-onset preeclampsia group (n= 22), and healthy pregnancy group (n= 20). After immunolocalized in human placenta, the levels of CXCR2 protein and messenger ribonucleic acid (mRNA) were detected by enzyme-linked immunosorbent assay and real-time quantitative polymerase chain reaction. Correlations between placental CXCR2 protein expression with systolic blood pressure and lactate dehydrogenase (LDH) in early-onset preeclampsia were examined using Pearson or Spearman’s correlation coefficients.Results:Placental CXCR2 protein and mRNA expression in early-onset preeclampsia was significantly lower than it was in placentas from healthy pregnancy pregnancies and late-onset preeclampsia (P < 0.05). The placental CXCR2 protein expression correlated negatively with systolic blood pressure and LDH in early-onset preeclampsia (r= -0.51, P < 0.05; r=-0.43, P < 0.05).Conclusion:Significant abnormal placental CXCR2 expression in early-onset preeclampsia, and its correlations with some clinical parameters (systolic blood pressure and LDH) were discovered, suggesting that CXCR2 may play a role in the pathogenesis of early-onset preeclampsia.

简介：摘要目的探讨平肝健脾汤治疗青光眼的疗效及对房水基质金属蛋白酶2（MMP-2）及其组织抑制剂-2（TIMP-2）表达的影响。方法选取2018年10月至2020年1月本院收治的126例（131眼）青光眼患者，采用随机数字法分成两组，对照组63例（65眼）行常规西医药物治疗，观察组63例（66眼）在对照组的基础上加用自拟平肝健脾汤，观察两组眼压、视野缺损情况及房水中MMP-2、TIMP-2的变化。结果两组治疗前眼压比较差异无统计学意义（P＞0.05），随治疗时间延长，两组患者眼压均降低（F=5.862，P=0.017），两组组间眼压比较，差异有统计学意义（F=4.881，P=0.040），且两组眼压组间、时点间交互作用比较，差异有统计学意义（F=5.841，P=0.026）；治疗后8周两组AGIS评分较治疗前均呈显著降低（均P＜0.05），治疗后8周观察组AGIS评分为（5.84±1.20）分，明显低于对照组的（6.01±1.44）分，差异有统计学意义（P＜0.05）；治疗后8周两组房水MMP-2、TIMP-2及MMP-2/TIMP-2较治疗前显著降低（均P＜0.05），且观察组房水MMP-2为（21.09±5.04）μg/L、TIMP-2为（22.15±5.82）μg/L，均低于对照组（均P＜0.05），而MMP-2/TIMP-2为（0.96±0.03），明显高于对照组（P＜0.05。结论平肝健脾汤能有效降低眼压，改善视野缺损，保护视神经功能，调节MMP-2/TIMP-2平衡可能是其对青光眼视神经的保护机制之一。

简介：摘要目的观察敲除腺苷A2A受体基因对慢性低O2高CO2模型小鼠前额叶皮质细胞凋亡以及磷酸化p38丝裂原活性蛋白激酶(p-p38MAPK)蛋白表达的影响。方法采用随机数字表法将16只腺苷A2A受体野生型(+/+)小鼠和16只腺苷A2A受体基因敲除型(-/-)小鼠各分为2个亚组，分别是对照-野生基因组、4周低O2高CO2-野生基因组(简称模型-野生基因组)、对照-基因敲除组、4周低O2高CO2-基因敲除组(简称模型-基因敲除组)，每组各8只小鼠。将模型-野生基因组、模型-基因敲除组小鼠置于常压低O2高CO2动物舱内，舱内O2浓度维持在9%～11%水平，CO2浓度维持在5.5%～6.5%水平，每天干预8 h，每周干预6 d，持续干预4周。于4周制模结束后采用原位末端标记法(TUNEL)检测各组小鼠前额叶皮质细胞凋亡情况，采用蛋白免疫印迹法检测各组小鼠前额叶皮质磷酸化p38MAPK蛋白表达水平。结果两模型亚组前额叶皮质凋亡细胞数量均较相应的对照亚组明显增加(P<0.05)，并且模型-野生基因组皮质凋亡情况较模型-基因敲除组更显著(P<0.05)；两模型亚组前额叶皮质p-p38MAPK蛋白表达均较相应的对照亚组明显上调(P<0.05)，并且模型-野生基因组p-p38MAPK蛋白表达上调幅度较模型-基因敲除组更显著(P<0.05)。结论敲除腺苷A2A受体基因能抑制慢性低O2高CO2模型小鼠前额叶皮质p38MAPK信号转导通路活化，减少前额叶皮质神经细胞凋亡，为改善慢性阻塞性肺疾病(COPD)患者认知功能提供更多实验依据。

简介：AbstractSevere acute respiratory syndrome coronavirus 2 (SARS-CoV-2) continues to evolve, generating new variants that pose a threat to global health; therefore, it is imperative to obtain safe and broad-spectrum antivirals against SARS-CoV-2 and its variants. To this end, we screened compounds for their ability to inhibit viral entry, which is a critical step in virus infection. Twenty compounds that have been previously reported to inhibit SARS-CoV-2 replication were tested by using pseudoviruses containing the spike protein from the original strain (SARS-CoV-2-WH01). The cytotoxicity of these compounds was determined. Furthermore, we identified six compounds with strong antagonistic activity against the WH01 pseudovirus, and low cytotoxicity was identified. These compounds were then evaluated for their efficacy against pseudoviruses expressing the spike protein from B.1.617.2 (Delta) and B.1.1.529 (Omicron), the two most prevalent circulating strains. These assays demonstrated that two phenothiazine compounds, trifluoperazine 2HCl and thioridazine HCl, inhibit the infection of Delta and Omicron pseudoviruses. Finally, we discovered that these two compounds were highly effective against authentic SARS-CoV-2 viruses, including the WH01, Delta, and Omicron strains. Our study identified potential broad-spectrum SARS-CoV-2 inhibitors and provided insights into the development of novel therapeutics.

简介：AbstractOmicron (B.1.1.529), the fifth variant of concern (VOC) of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), was firstly identified in November 2021 in South Africa. Omicron contains far more genome mutations than any other VOCs ever found, raising significant concerns about its increased transmissibility and immune evasion. Here, we report the importation of the Omicron variant into Beijing, China, in December 2021. Full-length genome sequences of five imported strains were obtained, with their genetic features characterized. Each strain contained 57 to 61 nucleotide substitutions, 39 deletions, and 9 insertions in the genome. Thirty to thirty-two amino acid changes were found in the spike proteins of the five strains. The phylogenetic tree constructed by the maximum likelihood method showed that all five imported genomes belonged to Omicron (BA.1) (alias of B.1.1.529.1), which is leading to the current surge of coronavirus disease 2019 (COVID-19) cases worldwide. The globally increased COVID-19 cases driven by the Omicron variant pose a significant challenge to disease prevention and control in China. Continuous viral genetic surveillance and increased testing among international travellers are required to contain this highly contagious variant.

简介：AbstractAt present, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spread worldwide, which has emerged multiple variants and brought a threat to global public health. To analyze the genomic characteristics and variations of SARS-CoV-2 imported into Beijing, we collected the respiratory tract specimens of 112 cases of coronavirus disease 2019 (COVID-19) from January to September 2021 in Beijing, China, including 40 local cases and 72 imported cases. The whole-genome sequences of the viruses were sequenced by the next-generation sequencing method. Variant markers and phylogenic features of SARS-CoV-2 were analyzed. Our results showed that in all 112 sequences, the mutations were concentrated in spike protein. D614G was found in all sequences, and mutations including L452R, T478K, P681R/H, and D950N in some cases. Furthermore, 112 sequences belonged to 23 lineages by phylogenetic analysis. B.1.1.7 (Alpha) and B.1.617.2 (Delta) lineages were dominant. Our study drew a variation image of SARS-CoV-2 and could help evaluate the potential risk of COVID-19 for pandemic preparedness and response.

简介：摘要ObjectiveTo investigate a 5-generation Chinese Han family with PRKAG2 cardiac syndrome resulting from mutations in the PRKAG2 gene encoding the AMP-activated protein kinase (AMPK) gamma 2 subunit and the treatment of myocardial hypertrophy in patients with PRKAG2 cardiac syndrome.MethodIn this study, a 5-generation Chinese Han family (n = 40) with complete atrioventricular block and asymmetric interventricular septal hypertrophy was taken as the research object, and the DNA were obtained from 30 of them (6 patients and 24 normal persons). Objective gene capture combined with high-throughput sequencing technique was used to detect the genes of family members. After the gene diagnosis was confirmed, the cardiac data of patients taking beta-blockers in this family were analyzed retrospectively with the average annual increase in thickness of interventricular septum (expressed in mm/year) as an index.ResultsA total of 6 family members were associated with PRKAG2 (c.905G>A; pR302Q) heterozygous variation. The phenotype of pedigree patients is characterized by complete atrioventricular block and asymmetric interventricular septal hypertrophy, which has high homogeneity. No syncope occurs after implantation of permanent pacemaker, but atrial flutter and atrial fibrillation occur. The 5 patients with PRKAG2 cardiac syndrome in the family took beta-blockers for a long time, and the progress of cardiac hypertrophy was significantly delayed.ConclusionsOur results suggest that the possibility of PRKAG2 mutations should be considered in patients with complete atrioventricular block and asymmetric interventricular septal hypertrophy, and that prompt implantation of pacemakers and long-term use of beta blockers may improve the prognosis of PRKAG2 cardiac syndrome patients.

简介：摘要长期以来，人们一直认为2型糖尿病（T2DM）是一种终身性疾病。近年的临床实践显示，一些T2DM患者在采取某些干预措施后可停用降糖药而血糖仍处于正常或接近正常水平，目前多数学者用“缓解”来描述T2DM患者这种代谢持续改善至接近正常的状态。该文对T2DM缓解的概念和判断标准、实现T2DM缓解的策略、T2DM缓解的影响和预测因素进行介绍，并阐述诱导T2DM缓解的可能机制。T2DM缓解具有重要的临床意义，不仅使患者在一段时间内免于药物治疗，而且可降低患者并发症的发生风险，针对缓解机制的研究还有望衍生出新的干预靶点，但该领域仍存在若干需要解决的问题。临床上对已经缓解的T2DM患者仍不能放松管理，需要定期复查，如患者血糖超过控制标准应按照指南及时启动相应的治疗。

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简介：摘要非酒精性脂肪性肝病（NAFLD）和2型糖尿病（T2DM）十分常见，两者常常互为因果。大量流行病学研究结果显示NAFLD显著增加T2DM发病风险，其机制尚不十分清楚。肝脏是机体糖脂代谢的重要调节器官，在维持机体血糖和血脂稳态上发挥关键作用。该文系统阐述了NAFLD的发生发展规律和机制，尤其介绍了肝脏糖代谢异常与高血糖之间的关系。NAFLD肝脏通过产生大量的17羟孕酮，增加去泛素化酶USP14基因表达促进糖异生过程，增加肝糖输出，升高血糖。通过改善脂肪肝可有效减少糖尿病的发病风险，对于糖尿病的防治具有重要意义。

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简介：摘要本文报道2例胎儿Pierre Robin序列征（PRS），由胎儿MRI诊断并在引产或生后得以证实。PRS在胎儿MRI上表现为小下颌、舌根后坠、气道变窄及腭裂。MRI诊断PRS有较高的敏感性，可诊断胎儿PRS伴随的结构畸形，给予围生期咨询提供一定指导建议。

简介：摘要本文报道椎管内孤立性纤维性肿瘤2例。该2例患者分别因双下肢无力伴小便失禁2个月余和右下肢麻木半年就诊，MRI上表现为与椎管平行的椭圆形肿块，边界清晰，T1WI呈等信号，T2WI呈等或稍高信号；增强扫描呈明显均匀或不均匀强化。最终术后病理诊断为椎管内孤立性纤维性肿瘤。

简介：摘要椎动脉外伤后出血量大且凶猛，容易被误诊为颈动脉损伤，临床中颈部外伤单纯伤及椎动脉少见，我们诊治2例椎动脉破裂出血患者。患者1，女性，41岁，颈部外伤4 h，探查后行左侧椎动脉吻合+左侧椎前静脉修补+左侧颈内、颈外静脉结扎术，术后10 d患者出现头晕，颅脑MR检查考虑左侧小脑半球脑梗死，椎动脉闭塞、狭窄，应用抗凝药物治疗4个月后头晕症状消失。患者2，女性，28岁，右侧颈部肿胀10 h，数字减影血管造影（DSA）检查示椎动脉起始段假性动脉瘤，介入手术止血困难，暂行颈部填塞后予抗感染治疗，术后4 d行颈部探查+气管切开术，术后18 d再行介入手术，患者出院前气管套管拔除，右上肢肌力0级。

简介：摘要患儿 男，11月龄，以频繁成簇抽搐发作起病，予地西泮、苯巴比妥及丙戊酸钠联合治疗无效，每天抽搐发作数十次，起病第4天因癫痫持续状态入住重症监护病房治疗，并出现嗜睡、意识模糊、不能认人、不自主动作、偶兴奋尖叫、夜间睡眠时间减少，脑电图背景活动慢化，监测到频繁后头部起源的临床发作及电发作，脑脊液抗AMPA2受体IgG抗体阳性，诊断抗AMPA2受体脑炎。予人免疫球蛋白及激素冲击免疫治疗，加用拉考沙胺并减停丙戊酸后抽搐缓解，意识转清。临床上以频繁局灶抽搐发作伴有意识水平下降为主要表现的婴儿，应注意鉴别抗AMPA2受体脑炎，尽早启用免疫治疗改善预后至关重要。