甲磺酸伊马替尼治疗慢性髓系白血病的临床研究及血药浓度监测

目的 观察甲磺酸伊马替尼(IM)治疗慢性髓系白血病(CML)的疗效,并分析血浆药物谷浓度水平与临床疗效及不良反应的关系.方法 观察101例CML患者接受IM治疗的疗效,并采用液相色谱-串联质谱法检测其中30例CML-慢性期(CP)患者IM血浆药物谷浓度.结果 ①89例CML-CP患者总的完全血液学缓解率(CHR)、主要细胞遗传学缓解率(MCyR)、完全细胞遗传学缓解率(CCyR)和BCR-ABL融合基因转阴率分别为96.6%、86.5%、77.5%和47.2%;12例CML进展期(加速期和急变期)患者的CHR、MCyR、CCyR、BCR-ABL转阴率分别为58.3%、25.0%、25.0%、8.3%.②服用IM 1年时获得CCyR患者的平均血浆药物谷浓度[(1472±482)μg/L]明显高于未获得CCyR者[(1067±373)μg/L],两者间差异有统计学意义(P＜0.05).服用IM 1年时获得主要分子学缓解(MMR)患者的平均血浆药物谷浓度[(1624 ±468)μg/L]也明显高于未获得MMR的患者[(1137±404)μg/L,P＜0.05].结论 IM明显提高CML患者细胞遗传学和分子学疗效.CML-CP期患者的疗效(1年时CCyR与MMR)与IM血浆药物谷浓度之间存在相关性.

Abstract：

Objective To analyze the clinical efficacy of imatinib mesylate (IM) for Ph-positive or BCR-ABL positive chronic myeloid leukemia( CML) to couple the trough plasma concentrations(Cmins) of IM with clinical responses and adverse events (AEs).Methods One hundred and one CML patients received IM therapy, and Cmins of IM were determmined in 30 patients.Results ①Cumulative complete hematological response( CHR) , major cytogenetic response ( MCyR ), complete cytogenetic response ( CCyR ) and negative BCR/ABL fusion gene rates were 96.6% , 86.5% ,77.5% and 47.2% , respectively, in CMLCP patients.In accelerated and blastic phases(AP and BC) patients, CHR, MCyR, CCyR and negative BCR-ABL fusion gene rates were 58.3% , 25.0% , 25.0% , 8.3%, respectively.②Mean Cmins of IM was significantly higher in the CCyR at 1 year[( 1472 ±482) μg/L]group than in the non-CCyR at 1 years group[(1067 ±373)μg/L](P＜0.05), and higher in the MMR at 1 year group than in the non-MMR at 1 years group[( 1624 ±468) μg/L as (1137 ±404) μg/L, P ＜0.05].Conclusion IM significantly improves cytogenetic and molecular response, envent-free survival, and overall survival for patients with Ph-positive CML.The Cmins of IM exerts a significant impact on clinical response (CCyR and MMR at 1 year).     

我国慢性髓系白血病患者服用伊马替尼血药浓度的初步分析

目的 评价我国慢性髓系白血病(CML)患者接受伊马替尼治疗的血浆谷浓度水平,以及伊马替尼血药浓度对临床个体化治疗的指导意义.方法 对全国6家综合性医院入组的416例CML患者进行伊马替尼治疗后血浆谷浓度检测,评价伊马替尼血浆谷浓度与患者年龄、体重、体表面积的相关性以及与剂量、疗效的关系.结果 ①伊马替尼血浆谷浓度与患者年龄、体重和体表面积均无明显相关性.②中位伊马替尼血浆谷浓度为1271( 109 ～4329) μg/L.伊马替尼血浆谷浓度与伊马替尼服用剂量有关,服用剂量＜400 mg/d、400 mg/d和＞400 mg/d组在伊马替尼血浆谷浓度分别为(969±585)、(1341±595)和(1740±748)μg/L(P ＜0.01).③获得完全细胞遗传学反应(CCyR)与未获得CCyR患者伊马替尼血浆谷浓度分别为(1337±571) μg/L和(1354±689) μg/L,差异无统计学意义(P =0.255).④伊马替尼血浆谷浓度对部分患者治疗具有指导意义.结论 我国CML患者服用伊马替尼后血药浓度的个体差异大;伊马替尼血浆谷浓度与其获得CCyR之间无明显相关性;增加伊马替尼剂量能提高伊马替尼血浆谷浓度,对于部分患者的治疗有一定的指导意义.     

慢性髓系白血病患者尼洛替尼血药浓度与临床疗效相关性的研究

目的:通过监测慢性髓系白血病慢性期(CML-CP)患者尼洛替尼(NIL)血清谷浓度水平,探讨其与临床疗效及不良反应的关系。方法:根据患者服用NIL剂量将其分为A组(44例),600-800 mg/d;B组(10例),400mg/d。通过液相色谱-单联质谱法分析服用不同剂量NIL治疗的CML-CP患者的血清药物谷浓度,探讨其与患者治疗反应的相关性。结果:54例患者中位NIL血清药物谷浓度为1.71(0.52-5.93)μg/ml,其中A组和B组NIL血清药物谷浓度分别为2.09±1.21μg/ml和0.94±0.27μg/ml,A组非常显著高于B组(P=0.001)。A组中服用NIL治疗12月累计达主要分子学缓解(MMR)者24例,未达MMR者20例;血清药物谷浓度分别为1.70±0.75μg/ml和2.03±0.82μg/ml(P=0.154)。发生Ⅲ-Ⅳ级重度不良反应患者13例,0-Ⅱ级轻度不良反应患者31例;血清药物谷浓度分别为3.09±1.76μg/ml和1.76±0.68μg/ml(P=0.018)。B组服用NIL治疗12月累计达MMR者4例,未达MMR者6例;血清药物谷浓度分别为1.15±0.27μg/ml和0.83±0.24μg/ml(P=0.051)。服用NIL治疗12月累计达MMR比率在A组、B组分别为24/44(54.5%)和4/10(40%),(P=0.494);但Ⅲ-Ⅳ级不良反应发生率在A组、B组分别为13/44(29.5%)、0/10(0%),B组不良反应发生率显著低于A组。结论:CML患者NIL血药浓度个体差异较大,与患者服药剂量及不良反应密切相关,低剂量服用NIL治疗可维持较好的治疗效果且可以明显减少不良反应的发生。     

降钙素原对脓毒血症的预测价值

目的探讨降钙素原(procalcitonin,PCT)在预测脓毒血症中的价值。方法疑诊脓毒血症患者648例,血培养阴性568例,血培养阳性80例中脓毒血症76例(脓毒血症组)、真菌感染4例;同期非脓毒血症患者298例为感染组,体检健康者98例为对照组,测定各组PCT、C反应蛋白(C-reactive protein,CRP)、白细胞计数(white blood cell count,WBC)、中性粒细胞百分比(the percentage of neutrophile,NEU)、血小板计数(platelet,PLT)及血沉水平;采用ROC曲线分析PCT诊断脓毒血症的效能;采用Pearson相关分析PCT与PLT、WBC、NEU的相关性。结果脓毒血症组PCT[1.08(0.48,2.00)μg/L]高于血培养阴性组[0.42(0.12,0.78)μg/L](P0.01),PLT[(136.30±44.37)×10~9/L]低于血培养阴性组[(206.20±81.85)×10~9/L](P0.01),CRP、WBC、NEU、血沉与血培养阴性组比较差异无统计学意义(P0.05);脓毒血症组中革兰阳性菌感染35例,革兰阴性菌感染41例,革兰阳性菌感染者PCT[0.76(0.46,1.76)μg/L]低于革兰阴性菌者[1.08(0.63,1.48)μg/L]、PLT[(160.61±39.19)×10~9/L]高于革兰阴性菌者[(113.65±34.61)×10~9/L](P0.05),CRP、WBC、NEU、血沉与革兰阴性菌者比较差异无统计学意义(P0.05);ROC曲线分析结果显示,PCT诊断脓毒血症的cut-off值为0.8μg/L,AUC为0.76,敏感性为0.75,特异性为0.80;脓毒血症组PCT[1.08(0.48,2.00)μg/L]、CRP[(98.16±34.20)mg/L]、WBC[(13.73±6.62)×10~9/L]、NEU[(88.62±23.35)%]、血沉[(72.66±25.33)mm/h]高于对照组[0.09(0.28,0.44)μg/L、(5.94±2.10)mg/L、(6.42±1.85)×10~9/L、(59.91±14.33)%、(10.82±3.77)mm/h],PLT[(136.30±44.37)×10~9/L]低于对照组[(210.16±48.62)×10~9/L](P0.01);感染组PCT[0.31(0.18,0.77)μg/L]、CRP[(33.84±10.23)mg/L]、WBC[(11.61±3.34)×10~9/L]、NEU[(85.66±25.45)%]、血沉[(39.42±10.21)mm/h]均高于对照组(P0.01);脓毒血症组PCT、CRP、血沉高于感染组,PLT低于感染组,差异均有统计学意义(P0.01);Pearson相关分析结果显示,脓毒血症患者PCT与WBC、NEU、PLT均呈负相关(r=-0.252,P=0.004;r=-0.148,P=0.008;r=-0.474,P=0.002)。结论脓毒血症患者PCT水平增高,PLT水平降低;PCT诊断脓毒血症具有较高的敏感性与特异性;PCT与PLT呈明显负相关,二者联合可能提高对脓毒血症的预测价值。     

唐草片对注射丝裂霉素C小鼠造血功能的保护作用

目的探讨唐草片对化疗药物引起的小鼠白细胞减少症的防治作用。方法成年健康小鼠60只,随机分为正常对照组、模型组、低剂量组、中剂量组、高剂量组和阳性药物对照组,每组10只。唐草片低、中、高剂量组分别灌服0.5、1.0、2.0g/kg唐草片,模型组、正常对照组灌服0.1mL/10g水。5d后除正常对照组外,每只动物腹腔注射3.0g/kg丝裂霉素C,第10天,再次腹腔注射2.0g/kg丝裂霉素C,阳性药物对照组在造模成功后皮下注射重组人粒细胞集落刺激因子50μg/kg,连续注射4d。各组在完成2次丝裂霉素C注射后,每周测定1次外周血细胞。实验结束时取各组小鼠一侧股骨骨髓细胞,培养14d后计数红细胞集落生成单位、粒细胞-巨噬细胞集落生成单位、粒细胞-红细胞-巨噬细胞-巨核细胞集落生成单位数量,取另一侧股骨骨髓细胞,计数有核细胞数。结果注射丝裂霉素C后24d时,中、低剂量组和阳性药物对照组白细胞计数[(9.91±2.73)×109/L、(10.00±3.10)×109/L、(9.68±3.19)×109/L]明显高于模型组[(6.92±1.61)×109/L](P0.05),与正常对照组[(9.60±2.07)×109/L]比较差异无统计学意义(P0.05);40d时,低剂量组白细胞计数[(15.13±2.41)×109/L]高于模型组[(10.06±2.17)×109/L](P0.05);33d时,低剂量组红细胞数[(10.47±0.57)×1012/L]高于模型组[(9.10±1.15)×1012/L](P0.05);低剂量组红细胞集落生成单位[(29.0±9.9)个/105]、粒细胞-巨噬细胞集落生成单位[(31.0±9.9)个/105]克隆数明显高于模型组[(6.5±0.7)、(17.5±2.1)个/105](P0.05),中剂量组粒细胞-红细胞-巨噬细胞-巨核细胞集落生成单位克隆数[(16.0±2.8)个/105]明显高于模型组[(8.0±1.4)个/105](P0.05)。结论唐草片对丝裂霉素C造成的白细胞降低模型小鼠有升高白细胞计数、保护造血功能的作用。     

高尔基体蛋白73及其基因检测对原发性肝癌诊断的价值

目的 评价分析GP73和GP73 mRNA在PHC中的诊断价值,探讨血清中GP73和AFP联合检测对PHC诊断和高危人群普查的意义,为PHC诊断和普查提供一种新方法 .方法 采用ELISA对73例PHC、13例肝硬化、32例肝炎和62名健康人的血清GP73、AFP水平进行检测,采用SYBR Green实时荧光定量PCR法检测各组外周血单个核细胞GP73 mRNA的相对表达量,以Ct值比较法计算GP73 mRNA相对表达水平,同时检测分析8份正常肝组织和8份肝癌组织的GP73 mRNA相对表达水平.结果 ELISA检测4组血清GF73、AFP结果 显示,总体比较经Kruskal-Wallis检验,4组间差异有统计学意义(H值分别为89.6、52.0,P均＜0.01),全血GP73 mRNA含量4组间差异无统计学意义(H=4.33,P＞0.05).组间多重比较Mann-Whitney检验结果显示,PHC组血清GP73的含量[166.7(162.7-231.8)μL]与肝硬化[57.3(46.6～113.6)μg/L]、肝炎[29.6(26.2～54.5)μg/L]及健康对照组[25.1(20.8～29.4)μg/L]比较,差异有统计学意义(U值分别为246、297、349,P均＜0.01),各组血清AFP的含量分别为380.9(258.5～ 503.2)μg/L、3.8(1.3～14.5)μg/L、5.1(2.4～7.8)μg/L、2.8(2.2～5.7)μg/L,差异亦有统计学意义(U值分别为246、419、790,P均＜0.01).肝癌组织GP73 mRNA表达量(12.64)显著高于正常肝组织(1.00).以ROC曲线确定诊断PHC的GP73临界值为123.2μg/L和AFP临界值为10.6 μg/L时,PHC组血清GP73、AFP单项检测的敏感度分别为65.8%和53.4%,特异度分别为95.3%和92.5%,两者联合检测的敏感度为79.5%,特异度为90.7%.结论 GP73蛋白对PHC诊断具有较好的敏感度和特异度;全血标本GP73 mRNA检测不能作为诊断PHC的肿瘤标志,肝组织标本GP73 mRNA检测可作为诊断PHC的肿瘤标志,但存在创伤性大、风险大、患者痛苦等缺点.血清GP73联合AFP检测可有效提高PHC诊断,可用于PHC高危人群的普查及筛选.     

叶酸受体1在鼻咽癌紫杉醇耐药细胞系中表达及意义

目的探讨鼻咽癌紫杉醇耐药细胞系中叶酸受体1(folate receptor 1,FOLR1)的表达及其作用。方法人鼻咽癌亲本细胞株CNE1采用大剂量冲击和小剂量维持方式诱导建立耐药指数(resistance index,RI)分别为2.0、5.8、10.5的耐药细胞系,采用反转录PCR法检测不同耐药指数细胞的FOLR1mRNA表达情况;选择耐药指数为10.5的耐药细胞为耐药组,人鼻咽癌亲本细胞株CNE1为对照组,2组细胞采用20、40、80μg/L FOLR1抗体预处理后,检测细胞增殖抑制率;将耐药组和对照组细胞分别再分为预处理和未预处理2个亚组,其中预处理组均采用低浓度20μg/L FOLR1抗体进行预处理,未预处理组均正常培养,然后各组分别添加5、10、15μg/L紫杉醇,检测各组细胞增殖抑制率。结果 RI为10.5耐药细胞FOLR1mRNA表达水平(2.49±0.29)高于RI为5.8、2.0细胞和对照细胞(1.28±0.31、0.51±0.16、0.12±0.04),RI为5.8耐药细胞高于RI为2.0耐药细胞和对照细胞,RI为2.0耐药细胞高于对照细胞(P0.05);耐药组和对照组细胞20μg/L FOLR1抗体预处理下细胞增殖抑制率比较差异无统计学意义(P0.05),40、80μg/L FOLR1抗体预处理下,耐药组细胞增殖抑制率[(14.45±2.03)%、(47.85±7.07)%]明显高于对照组[(11.92±2.74)%、(29.19±5.17)%](P0.05);2组细胞80μg/L FOLR1抗体预处理下细胞增殖抑制率高于20、40μg/L FOLR1抗体预处理下,40μg/L FOLR1抗体预处理下高于20μg/L FOLR1抗体预处理下(P0.05);对照组中预处理组和未处理组细胞在5、10、15μg/L紫杉醇处理下细胞增殖抑制率比较差异均无统计学意义(P0.05),耐药组中预处理组细胞在5、10、15μg/L紫杉醇处理下细胞增殖抑制率[(10.85±0.74)%、(33.91±3.17)%、(46.39±2.87)%]明显高于未预处理组[(4.31±0.33)%、(24.68±2.02)%、(29.25±2.53)%](P0.05);对照组中预处理组和未预处理组在5、10、15μg/L紫杉醇处理下细胞增殖抑制率均明显高于耐药组中预处理组和未预处理组(P0.05)。结论 FOLR1表达与鼻咽癌细胞抵抗紫杉醇耐药相关,低浓度FOLR1抗体可使耐药细胞对紫杉醇敏感性提高,有效逆转鼻咽癌耐药,高浓度FOLR1抗体可直接杀死鼻咽癌耐药细胞。     

骨髓增殖性肿瘤患者血清血管调控细胞因子水平变化及意义

目的探讨骨髓增殖性肿瘤(myeloproliferative neoplasms,MPN)患者血清血管调控相关细胞因子水平及其临床意义。方法 30例MPN患者为MPN组,20例体检健康者为对照组,2组采用双抗体夹心ELISA法检测血清血管内皮生长因子(vascular endothelial growth factor,VEGF)、血小板衍生生长因子(platelet derived growth factor,PDGF)、内皮抑素(endostatin,ES)、基质金属蛋白酶-9(matrix metalloproteinase-9,MMP-9)及基质金属蛋白酶抑制剂-1(tissue inhibitors of metalloproteinase-1,TIMP-1)水平,分析MPN组各血管调控细胞因子间的相关性,及临床因素与血管调控细胞因子间的关系。结果MPN组血清VEGF[(610.10±295.70)ng/L]、PDGF[(9.50±3.68)μg/L]、ES[(6.80±2.70)μg/L]、MMP-9[(856.32±544.28)μg/L]、TIMP-1[(464.45±216.71)μg/L]水平及MMP-9/TIMP-1比值(2.41±1.77)均高于对照组[(355.82±155.29)ng/L、(6.03±1.07)μg/L、(4.04±0.90)μg/L、(382.90±171.36)μg/L、(202.37±28.35)μg/L、1.88±0.71](P0.05);MPN组VEGF与PDGF呈正相关(r=0.429,P=0.018),PDGF与ES呈正相关(r=0.418,P=0.022);MPN组白细胞计数≥10×109/L者血清MMP-9水平[(1 059.95±625.22)μg/L]明显高于10×109/L者[(623.60±316.93)μg/L](P0.05),血红蛋白≥160g/L者血清TIMP-1水平[(385.66±178.38)μg/L]明显低于160g/L者[(554.49±227.31)μg/L](P0.05),≥60岁患者血清PDGF[(10.70±4.14)μg/L]、ES[(7.93±2.85)μg/L]、TIMP-1[(533.89±200.88)μg/L]水平高于60岁患者[(7.71±1.83)μg/L、(5.10±1.19)μg/L、(360.29±204.25)μg/L](P0.05),2项血管危险因素者血清PDGF水平[(14.01±4.99)μg/L]明显高于≤2项危险因素者[(8.38±2.45)μg/L](P0.05);多因素logistic回归分析结果显示,高龄和低血红蛋白是TIMP-1水平增高的独立危险因素(OR=1.005,95%CI:1.000~1.010,P=0.049;OR=0.996,95%CI:0.992~1.000,P=0.046);高龄和2项血管危险因素是PDGF水平增高的独立危险因素(OR=1.462,95%CI:1.008~2.119,P=0.045;OR=1.282,95%CI:0.988~1.663,P=0.041)。结论 MPN患者白细胞计数、血红蛋白增多与血管新生调控因子表达增加有关,通过炎症导致血管新生促进和抑制因子的表达失衡,进而参与MPN的发生、发展。     

肝细胞生长因子激活剂的抑制剂-1基因对宫颈癌细胞自噬及凋亡调控的影响

目的探讨肝细胞生长因子激活剂的抑制剂-1(hepatocyte growth factor activator inhibitor-1, HAI-1)基因对宫颈癌细胞自噬及凋亡调控的机制。方法对数生长期HeLa细胞分为转染组和对照组,转染组转染HAI-1质粒,对照组细胞正常培养。采用实时荧光定量PCR法检测2组细胞HAI-1 mRNA表达情况,采用AO染色和流式细胞术检测2组细胞自噬情况,采用ELISA检测2组细胞自噬相关因子LC3-Ⅱ、LC3-Ⅰ和Beclin-1蛋白水平,应用流式细胞仪检测2组细胞凋亡率,采用Western blot法检测细胞Bax和Bcl-2蛋白相对表达量。结果转染组细胞HAI-1 mRNA相对表达量(1.57±0.26)、AO细胞荧光强度(52.14±3.88)、LC3-Ⅱ蛋白[(3.42±0.85)μg/L]、Beclin-1蛋白[(14.69±1.96)μg/L]水平、细胞凋亡率[(86.75±6.42)%]、Bax蛋白相对表达量(1.24±0.13)和Bax/Bcl-2(7.75±0.83)高于对照组[0.48±0.09、5.47±0.32、(1.10±0.22)μg/L、(10.12±0.53)μg/L、(12.64±1.33)%、0.25±0.06、0.17±0.05)](P0.05),LC3-Ⅰ蛋白水平[(0.59±0.11)μg/L]、Bcl-2蛋白相对表达量(0.16±0.04)低于对照组[(3.26±0.82)μg/L、1.47±0.15](P0.05)。结论 HAI-1转染通过增加HeLa细胞中LC3-Ⅱ和Beclin-1蛋白表达,降低LC3-Ⅰ蛋白表达,提高Bax/Bcl-2来调节宫颈癌细胞的自噬和凋亡。     

特应性皮炎患者外周血单个核细胞、血清及泪液中MIF检测的临床意义

目的 探讨MIF在AD患者PBMC、血清及泪液中的表达水平及其在AD诊断中的临床意义.方法 AD患者按SCORAD指数分3个亚组,轻度AD组11例、中度AD组23例、重度AD组9例;并用实时定量RT-PCR检测43例AD患者和31名健康对照者(健康对照组)PBMC中MIFmRNA的表达水平,用ELISA法检测血清和泪液中MIF含量.结果 AD组PBMC中MIF mRNA的表达水平为7.46(3.38～8.90),明显高于健康对照组[1.67(1.24～2.45),Z=-6.141,P<0.05];轻、中、重度AD组MIF mRNA的表达水平分别为2.35(2.12～2.49)、7.83(6.54～8.90)和8.76(8.22～9.73),中、重度AD组均显著高于健康对照组(Z值分别为-6.237、-4.520,P均<0.05).AD组血清中MIF的含量为36.32(11.89～43.80)μg/L,明显高于健康对照组[7.89(6.13～9.54)μg/L,Z=-6.180,P<0.05];轻、中、重度AD组血清中MIF的含量分别为8.98(7.90～10.51)μg/L、36.50(29.78～43.23)μg/L、45.70(41.27～48.84)μg/L,中、重度AD组均显著高于健康对照组(Z值分别为-6.238、-4.521,P均<0.05).AD组泪液中MIF的含量为12.66(2.01～20.12)μg/L,较健康对照组[0.85(0.77～1.06)μg/L]明显升高(Z=-4.118,P<0.05);轻、中、重度AD组泪液中MIF的含量分别为1.10(0.83～1.35)μg/L、12.66(9.76～15.87)μg/L、24.65(19.29～30.94)μg/L,中、重度AD组均显著高于健康对照组(Z值分别为-4.062、-3.372,P均<0.05).中、重度AD组PBMC中MIF mRNA表达水平及血清、泪液中MIF的含量与疾病严重程度SCORAD指数均呈明显正相关(r值分别为0.395、0.404、0.515,P均<0.05).结论 不同AD病程患者PBMC、血清和泪液中MIF表达增高,MIF可作为判断AD病情活动和评价AD疾病严重程度的有效检验指标.     

儿童遗传性心律失常的诊治进展

回顾在遗传性心律失常领域最新发表的相关研究,主要关注与儿童心源性猝死关系密切的离子通道病,包括长QT综合征（LQTS）、短QT综合征（SQTS）、Brugada综合征（BrS）和儿茶酚胺敏感性多形性室性心动过速（CPVT）,总结它们在发病机制及诊治方面的进展。     

The acoustic characteristics of the skull

Many investigators have stated that the difficulties of imaging with acoustical energy through the skull result from the marked attenuation of the energy by the skull. In the literature measurements of total attenuation have been confused with those for absorption.Measurements made by us show that absorption by compact bone varies between 2–3 dB cm^?1 MHz^?1 and, in the low megaHertz region appears to be directly proportional to frequency.It has also between shown that the convoluted inner surface of the ivory bone of the inner table of the skull may degrade the collimation and directionality of the beam by refraction.Cancellous bone, such as is present in the dipole of the skull, greatly attenuates the energy. It is postulated that this largely results from scattering. It is also postulated that the energy propagates through cancellous bone as two components, one in the soft tissues and the other partly in the bony spicules. Observations suggest that attenuation due to scattering much more markedly affects the latter of these components and scatters more greatly the higher frequencies in a pulse of broad bandwidth.The energy in each component has varying propagation paths so that the later cycles in the pulse of each component are subject to increasing interference as a result of the variations in propagation times. The two components moreover may have different propagation times so that interference may occur between the pulses of each component as well.All of these phenomena degrade the collimation, coherence, directionality, beam width, pulse length, frequency and other properties of the ultrasonic energy upon which imaging through the skull depends.The interference effects described above are least for the first cycle in the pulse which usually is not the cycle of highest amplitude. Since, in the free field, most of the energy is concentrated around the beam axis, most of the energy in the field which is deflected from its normal propagation path is deflected away from the beam axis. Thus the directionality of the beam is least degraded in the beam axis. The effects of the skull in degrading the properties of the ultrasonic pulse would therefore be lessened if the amplitude of the first cycle of the pulse and the directionality of its energy could be used for imaging.     

Organ Preservation: Current Concepts and New Strategies for the Next Decade

SUMMARY: Organ transplantation has developed over the past 50 years to reach the sophisticated and integrated clinical service of today through several advances in science. One of the most important of these has been the ability to apply organ preservation protocols to deliver donor organs of high quality, via a network of organ exchange to match the most suitable recipient patient to the best available organ, capable of rapid resumption of life-sustaining function in the recipient patient. This has only been possible by amassing a good understanding of the potential effects of hypoxic injury on donated organs, and how to prevent these by applying organ preservation. This review sets out the history of organ preservation, how applications of hypothermia have become central to the process, and what the current status is for the range of solid organs commonly transplanted. The science of organ preservation is constantly being updated with new knowledge and ideas, and the review also discusses what innovations are coming close to clinical reality to meet the growing demands for high quality organs in transplantation over the next few years.     

2017年呼吸疾病主要进展

2017年,国内外学者在呼吸系统疾病的临床和基础领域均进行了深入研究,不仅对相关指南进行了更新,并且针对一些临床热点、难点问题达成专家共识,现就2017年呼吸疾病相关进展作一简单介绍。     

COVID‐19 and COVID‐19 vaccine‐related dermatological reactions: An interesting case series with a narrative review of the potential critical and non‐critical mucocutaneous adverse effects related to virus,therapy, and the vaccination

This narrative review article was conducted to lay out a summarized but exhaustive review of current literature over mucocutaneous manifestations in 4 dimensions of SARS‐CoV‐2 pandemic: virus itself, treatment‐related, vaccine‐induced, and alteration of chronic dermatologic diseases following infection. Virus and vaccine‐related were mainly self‐limited and non‐severe. Treatment‐related reactions could be life‐threatening.     

家族性噬血细胞性淋巴组织细胞增生症1例并文献复习

目的加强对家族性噬血细胞性淋巴组织细胞增生症（familially hemophagocytic lymphohistiocytosis,FHL）的认识。方法报道确诊为FHL的新病例1例,结合国内外报道的FHL的病例,对该病的临床特点进行汇总分析。结果FHL2常与PRF1基因突变相关,约20%~40%的患者存在穿孔素基因突变。结论对于有阳性家族史,基因诊断明确,应尽早行化疗或者造血干细胞移植。若无家族史,未发现与继发性HLH相关的原发病因,可考虑行基因筛查以明确是否存在FHL的可能。     

Burkitt's lymphoma of maxillary gingiva: A case report

Burkitt's lymphoma(BL) is an aggressive form of nonHodgkin's B-cell lymphoma with three variants namely endemic, sporadic, and immunodeficiency-associated types. It is endemic in Africa and sporadic in other parts of the world. While the endemic form is widely reported to occur in early childhood and commonly involves the jaw bones, the sporadic form typically presents as an abdominal mass. This presentation reports a rare case of sporadic form of BL clinically manifesting as a generalized gingival enlargement in an immunocompetent adult male which demonstrated an aggressive behavior. The patient reported with a prominent anterior gingival swelling of 6 mo duration which slowly enlarged in size and associated with multiple lymph node involvement. Microscopic examination of the lesion using H, E and immunohistochemical diagnosis confirmed the diagnosis as BL. The patient succumbed to the disease before any therapy could be instituted. Since a wide array of causes can be attributed to gingival enlargements, it is necessary to consider malignancies as one of the important differential diagnosis so as to facilitate the need for appropriate diagnosis and prompt treatment.     

Recalcitrant giant orf recurrence after amputation: A case report and review of the literature

Orf is caused by a parapoxvirus. We present a recurrent, giant digital orf case in a female patient with a history of hairy cell leukemia. In spite of shave excision, the lesion progressed and recurred after digital amputation. Treatment with topical imiquimod cream and systemic subcutaneous interferon alfa‐2a was successful.     

动态心电图临床操作标准化方法

动态心电图,又称Holter或Holter检查,是一种评价各种心脏病患者心电图异常的简便、高效、准确、安全的无创检查,广泛用于心律失常的相关症状评价,心肌缺血的诊断,心脏病患者的预后和日常生活能力评估,药物疗效评价,起搏器等埋藏式心脏电治疗装置监测等领域。目前动态心电图已广泛用于于临床各级医疗机构,为了更好地发挥其作用,有必要对该项技术进行规范化培训。本文参考相关指南、共识及专家建议,结合作者经验,撰写动态心电图临床操作标准化方法供临床使用时参考。