日本汉方药企业近十年申请专利的分析及思考——以津村制药和Kracie为例＊

目的 对日本医疗用汉方医药品和一般用汉方医药品市场占有率最大的企业日本津村制药公司和Kracie制药公司2008-2020年间申请的专利内容进行综述，为国内中药经典名方和保健食品研发、知识产权保护提供参考。方法 通过日本专利局的官方检索渠道J-PlatPat平台，检索日本津村制药公司和Kracie制药公司在2008年至2020年间申请的专利，并进行专利布局和技术内容分析。结果 共收集43项日本津村制药公司特许和实用新案专利，其围绕汉方制剂产品全过程质量控制构建了坚实的专利技术体系；共收集52项Kracie制药公司特许和实用新案专利，其致力于功能性制剂和组合物的开发，重点在生活改善、老龄化和癌症等领域进行专利布局，还创建了多种产品功效和功能的客观评价方法。结论 津村制药近十年专利布局提示在中药现代化制造和走向国际的过程中，应把提高品质作为主攻方向，树立持续质量改进理念，完善产品有效性证据链。Kracie制药公司践行的以人为中心的汉方药设计理念，以及精准满足消费者健康需求的研发模式值得借鉴。     

562名医务人员子女心理行为状况调查

目的 了解儿童心理行为状况,为改善儿童心理行为问题提供依据。方法 针对本院医务人员子女采用整群随机抽样的方法,通过手机端发放长处和困难问卷(Strengths and Difficulties Questionnaire,SDQ)电子版进行调查,收集儿童心理行为健康相关信息。结果 本研究纳入观察病例共562份,年龄均值(8.06±3.251)岁。其中,男275名(48.9%),女287名(51.1%);学龄期儿童311名(55.3%),学龄前期儿童251名(44.7%)。SDQ困难总分评定异常者12.9%,边缘状态者18.1%,正常者69%。情绪问题 、品行问题 、同伴关系问题 、多动问题 、困难总分、亲社会行为各因子异常检出率分别为9.6%、9.8%、19.2%、18.1%、12.9%、7.8%。不同性别儿童SDQ困难总分、情绪症状、亲社会行为、品行问题差异无统计学意义(P>0.05)。男生多动问题、同伴关系问题评分分别为(3.87±1.471)分、(4.53±1.542)分,分别高于女生的(3.65±1.415)分、(4.31±1.554)分,差异有统计学意义(t=0.96、7.65,P<0.05)。学龄前期儿童与学龄期儿童情绪症状、品行问题、亲社会行为差异无统计学意义(P>0.05)。学龄期儿童同伴关系问题、多动问题、困难总分评分分别为(4.53±1.507)分、(3.85±1.298)分、(12.15±3.613)分,分别高于学龄前期儿童的(4.26±1.652)分、(3.54±1.402)分、(11.45±4.39)分,差异有统计学意义(t=5.36、6.57、14.32,P<0.05)。结论 调查发现,本院医务人员子女心理行为问题发生率较高。应进一步核实诊断,根据不同的心理特征及年龄分类,及早给予心理支持和干预,并由心理医生对这一群体进行长期随访。     

肾周脂肪梅奥粘连概率评分系统在肾癌后腹腔镜肾部分切除术中的应用

目的探讨肾周脂肪梅奥粘连概率评分系统（MAP）在肾癌后腹腔镜肾部分切除术中的临床应用价值。 方法回顾性分析2015年1月至2020年6月徐州医科大学附属淮安医院泌尿外科收治的行后腹腔镜肾部分切除术的153例肾癌患者的临床病例资料。依据MAP评分系统将其分为低度复杂组、中度复杂组和高度复杂组三组。比较各组间的手术时间、术中出血量、术中及术后并发症、术中热缺血时间、术后住院时间及术后血肌酐变化情况。 结果在153例患者中，低度复杂组68例，中度复杂组58例和高度复杂组27例。三组患者在年龄、性别、术前血肌酐水平、肿瘤最大径、肿瘤位置、BMI、RENAL评分等方面差异无统计学意义（P>0.05）。随着复杂程度的提高，手术时间、术中出血量也在不断增加（P<0.05）；而术中热缺血时间、术后住院时间及术后血肌酐水平无明显变化（P>0.05）。在术中并发症方面，随着复杂程度的提高，术中并发症的发生率也在增加（P<0.05），且高度复杂组的术后并发症发生风险是低度复杂组的13.895倍（P=0.002)，MAP评分系统预测术中并发症发生的精度较高（AUC=0.757，P=0.002）。但是术后并发症各组比较差异无统计学意义（P>0.05）。 结论MAP评分系统在肾癌后腹腔镜肾部分切除术中，对预估手术难度及术中并发症发生风险有较好的临床应用价值。     

Professional Steps: The Certification Path

Obtaining certification is a critical step on the road to professionalism. There are many questions to consider in this decision. Included among these are cost, preparation, and return on the investment. Important answers to these questions are discussed.     

New approaches to moderate CRISPR-Cas9 activity: Addressing issues of cellular uptake and endosomal escape

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Prediction and validation of hematopoietic stem and progenitor cell off-target editing in transplanted rhesus macaques

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A candidate multi-epitope vaccine against porcine reproductive and respiratory syndrome virus and Mycoplasma hyopneumoniae induces robust humoral and cellular response in mice

Porcine reproductive and respiratory syndrome virus (PRRSV) and Mycoplasma hyopneumoniae (M. hyopneumoniae, Mhp) are two of the most common pathogens involved in the porcine respiratory disease complex (PRDC) resulting in significant economic losses worldwide. Vaccination is the most effective approach to disease prevention. Since PRRSV and Mhp co-infections are very common, an efficient dual vaccine against these pathogens is required for the global swine industry. Compared with traditional vaccines, multi-epitope vaccines have several advantages, they are comparatively easy to produce and construct, are chemically stable, and do not have an infectious potential. In this study, to develop a safe and effective vaccine, B cell and T cell epitopes of PRRSV-GP5, PRRSV-M, Mhp-P46, and Mhp-P65 protein had been screened to construct a recombinant epitope protein rEP-PM that has good hydrophilicity, strong antigenicity, and high surface accessibility, and each epitope is independent and complete. After immunization in mice, rEP-PM could induce the production of high levels of antibodies, and it had good immunoreactivity with anti-rEP-PM, anti-PRRSV, and anti-Mhp antibodies. The anti-rEP-PM antibody specifically recognizes proteins from PRRSV and Mhp. Moreover, rEP-PM induced a Th1-dominant cellular immune response in mice. Our results showed that the rEP-PM protein could be a potential candidate for the development of a safe and effective multi-epitope peptide combined vaccine to control PRRSV and Mhp infections.