白内障术后生物学参数变化及IOL计算公式的准确性研究

目的：运用新型光学生物测量仪IOL Master 700测量白内障超声乳化手术前后眼部生物学参数的变化，并探讨人工晶状体(IOL)屈光度数计算公式的选择。

方法：前瞻性研究。收集2021-01/06在苏州大学附属第一医院就诊的白内障患者52例57眼。术前和术后3mo使用IOL Master 700完成眼轴长度(AL)、前房深度(ACD)、角膜曲率(Km)的测量并分析。对不同IOL公式计算时预留的目标屈光值与术后3mo全自动验光仪实际屈光值结果进行比较并分析。

结果：手术前后测量的AL平均值分别为24.20±1.86、24.09±1.86mm，术后AL缩短了0.11mm； ACD值分别为3.08±0.44、4.55±0.36mm(P<0.001)，术后ACD加深1.49mm； Km值分别为44.14±1.86、44.14±1.82D(P>0.05)。术前选用Barrett Universal Ⅱ公式所测结果的屈光误差最小，其次是Holladay Ⅱ及SRK/T公式，Holladay Ⅰ公式所测结果的误差最大(P<0.05)。

结论：白内障术后AL缩短以及ACD加深，度数测算时可考虑增加0.1mm的校正因子。IOL屈光度数计算公式中Barrett Universal Ⅱ公式预测性最佳，其次是Holladay Ⅱ及SRK/T公式。     

黄连NRAMP3基因的克隆与生物信息学分析＊

目的 克隆黄连（Coptis chinensis Franch.）中自然抗性相关巨噬细胞蛋白（Natural Resistance-Associated Macrophage Protein，NRAMP）的编码基因，并进行生物信息学分析。方法 从黄连基因组中比对NRAMP3基因，并根据比对的基因序列设计特异性引物，经PCR扩增得到的黄连NRAMP3编码序列，进行克隆、测序和生物信息学分析，并利用qPCR技术对黄连NRAMP3基因进行时空表达分析。结果 得到黄连NRAMP3基因cDNA序列，全长1617 bp，编码538个氨基酸，通过与GenBank上的其他蛋白序列比对，将其命名为CcNRAMP3；序列分析显示，黄连NRAMP3基因编码的氨基酸序列包含一个典型的NRAMP结构域（PF01566），有12个跨膜结构域，亚细胞定位于液泡膜上，具有疏水性强的特点。二级结构中肽链构象主要包括α-螺旋与无规则卷曲两部分；三级结构模型具有葡萄球菌锰转运突变体（MntH）的晶体结构。利用系统进化关系分析推测它可能具有转运重金属元素Cd功能。对黄连NRAMP3基因的组织表达分析表明，CcNRAMP3基因在黄连叶片中表达量最高。在遭受镉胁迫时，在须根中表达量先升高后降低，该基因很可能主要在根部对镉进行响应并发挥作用。结论 本研究首次通过克隆得到黄连NRAMP3基因，并运用生物信息学方法对其理化性质、结构特征等进行了分析预测，这些结果将为黄连NRAMP3基因的功能研究以及其对镉转运的调控机制提供理论依据和基因资源。     

Limited clinical activity of palbociclib and ribociclib monotherapy in advanced cancers with cyclin D-CDK4/6 pathway alterations in the Dutch DRUP and Australian MoST trials

The Dutch Drug Rediscovery Protocol (DRUP) and the Australian Cancer Molecular Screening and Therapeutic (MoST) Program are similar nonrandomized, multidrug, pan-cancer trial platforms that aim to identify signals of clinical activity of molecularly matched targeted therapies or immunotherapies outside their approved indications. Here, we report results for advanced or metastatic cancer patients with tumors harboring cyclin D-CDK4/6 pathway alterations treated with CDK4/6 inhibitors palbociclib or ribociclib. We included adult patients that had therapy-refractory solid malignancies with the following alterations: amplifications of CDK4, CDK6, CCND1, CCND2 or CCND3, or complete loss of CDKN2A or SMARCA4. Within MoST, all patients were treated with palbociclib, whereas in DRUP, palbociclib and ribociclib were assigned to different cohorts (defined by tumor type and alteration). The primary endpoint for this combined analysis was clinical benefit, defined as confirmed objective response or stable disease ≥16 weeks. We treated 139 patients with a broad variety of tumor types; 116 with palbociclib and 23 with ribociclib. In 112 evaluable patients, the objective response rate was 0% and clinical benefit rate at 16 weeks was 15%. Median progression-free survival was 4 months (95% CI: 3-5 months), and median overall survival 5 months (95% CI: 4-6 months). In conclusion, only limited clinical activity of palbociclib and ribociclib monotherapy in patients with pretreated cancers harboring cyclin D-CDK4/6 pathway alterations was observed. Our findings indicate that monotherapy use of palbociclib or ribociclib is not recommended and that merging data of two similar precision oncology trials is feasible.     

Zhang Weishen: A Pioneer in the Development and Industrial Production of Penicillin in New China

The research and development of penicillin started with difficulty before 1949 and achieved certain results. In 1951, after the founding of the People's Republic of China, Zhang Weishen, as the only Chinese scientist who had been trained and worked in a penicillin research and development center in the United States for many years, overcame many difficulties and returned to China. In 1953, with the efforts of Zhang Weishen and his colleagues, China realized the industrialized production of penicillin, alleviating the urgent needs of the masses. Antibiotics has also become the first discipline to achieve major scientific and technological achievements after the founding of the New China. In the mid-1950s, the technical breakthrough in the localization of lactose substitutes marked the localization of the raw materials of the penicillin-producing culture medium, which paved the way for the industrialized production of penicillin with Chinese characteristics. Antibiotics have become one of the most widely used and affordable drugs for hundreds of millions of patients in China, and China has since ended the humiliating history of the “Sick Man of East Asia".     

CD19+CD24hiCD38hi B细胞比例预测肝移植术后急性细胞性排斥反应发生的临床研究

目的分析肝移植术后受者外周血CD19⁺CD24^hiCD38^hi B细胞占单个核细胞比例变化情况及其与急性细胞性排斥反应(ACR)之间的关系。 方法回顾性分析2013年12月至2015年12月在浙江大学医学院附属第一医院接受心脏死亡器官捐献肝移植的80例成人受者临床资料，根据术后是否发生ACR，将受者分为ACR组(25例)和非ACR组(55例)。术前、术后各个时间点抽取参加研究者静脉血并分离外周血单个核细胞，加入异硫氰酸荧光素-单克隆鼠抗人CD19抗体、藻红蛋白-单克隆鼠抗人CD24抗体和别藻蓝蛋白-单克隆鼠抗人CD38抗体，流式细胞仪检测各组CD19⁺CD24^hiCD38^hi B细胞百分比。采用t检验和单因素方差分析比较正态分布计量资料，采用χ²检验比较计数资料，采用Kaplan-Meier法绘制受试者工作特征曲线(ROC曲线)。P<0.05为差异有统计学意义。 结果ACR组、非ACR组受者术前外周血平均CD19⁺CD24^hiCD38^hi B细胞比例分别为(3.13±0.91)%、(3.49±0.83)%，差异无统计学意义(t＝1.636，P>0.05)。ACR组术后发生ACR前外周血平均CD19⁺CD24^hiCD38^hi B细胞比例为(1.87±0.70)%。非ACR组受者术后3个月、6个月和1年外周血平均CD19⁺CD24^hiCD38^hi B细胞比例分别为(1.64±0.52)%、(1.63±0.56)%和(2.04±1.24)%，术后3、6个月平均值均低于术前和术后1年，差异均有统计学意义(P均<0.05)。ACR组受者发生ACR时外周血平均CD19⁺CD24^hiCD38^hi B细胞比例为(0.8±0.5)%，低于发生ACR前的平均水平(t＝5.752，P<0.05)，且低于非ACR组术后3个月、6个月和1年的平均水平(P<0.05)。ACR组受者接受抗排斥反应治疗后，CD19⁺CD24^hiCD38^hi B细胞比例也逐渐增加，ACR发生后7 d为(0.84±0.08)%，与ACR发生时相比差异无统计学意义(P>0.05)；而发生30 d后达(1.65±0.18)%，与ACR发生时相比差异有统计学意义(P<0.05)。当截断值为1.015%时，CD19⁺CD24^hiCD38^hi B细胞比例预测ACR发生的敏感度和特异度分别为0.786和0.702，ROC曲线下面积为0.775(95%CI: 0.671~0.879，P<0.05)。 结论CD19⁺CD24^hiCD38^hi B细胞比例下降与肝移植术后ACR反应发生有关，并可作为预测ACR发生的细胞标志物。     

脑血管介入治疗患者穿刺点压迫方法的研究进展

综述了脑血管介入术穿刺点压迫方法（包括人工压迫、弹力带加压、压迫器加压、血管闭合装置压迫、止血敷料压迫、气囊加压6种）、止血压力以及压迫时间，提出由于穿刺点和压迫方法的不同，其压迫时间、减压时间和压力大小等需要进一步探讨，为脑血管介入术后患者穿刺点的临床护理提供参考。