Background Immunotherapy shows promise as a treatment option for various cancers. However, there is growing concern over potential complications from hepatitis B virus (HBV) reactivation after checkpoint blockade immunotherapy. Although most of the previous clinical trials on immune checkpoint inhibitors (ICIs) excluded patients with HBV, a few case reports and retrospective studies of HBV reactivation have been published. The aim of this study is to assess the risk of hepatitis B virus reactivation (HBVr) in patients receiving ICIs for advanced cancer. Methods English and Chinese language literature published prior to April 30, 2023, was searched in PubMed, EMBASE, Web of Science, Cochrane, SinoMed, CNKI and Wanfang Data for studies reporting HBVr rates in cancer patients treated with ICIs. A pooled risk estimate was calculated for HBVr rates with 95% confidence intervals ( CI ). Results Data from 34 studies including 7126 patients were retrieved and analyzed. The pooled HBVr rate in cancer patients treated with ICIs was 1.3% ( I 2 = 90.44%, 95% CI : 0.2–2.9%, P < 0.001). Subgroup analysis revealed that patients diagnosed with hepatocellular carcinoma (HCC), HBV carriers, and patients from Asian regions or in developing countries have a higher rate of HBVr. Conclusions Our meta-analysis demonstrated a low risk of HBVr in patients treated with ICIs for advanced cancer. ICI treatment may be safely used in patients with existing HBV infection or chronic hepatitis B, accompanied by regular monitoring and appropriate antiviral prophylaxis if necessary. Graphical Abstract

目的:探讨适合我国研究型临床药师培养发展的路径.方法:通过文献调研和实践经验总结,对"具备科研能力的临床药师"赋予新的名称和内涵,并提出其培养和职业发展的具体路径和方法.结果:根据发达国家"医师科学家""临床科学家"的内涵和发展现状,结合我国的具体国情,本团队创新性地提出"研究型临床药师"的概念,并从高等教育和继续教育2个层面对研究型临床药师的培养发展路径进行深入剖析,找到适合中国临床药师科研发展的路径.结论:培养研究型临床药师具有很强的必要性和广阔的前景,将产出一批既能在药物治疗领域有新发现和新突破,又能为人民生命健康保驾护航的卓越人才.

目的 探讨肿瘤专科临床药师理论考核试题库的建设方法.方法 分析肿瘤专科临床药师培训大纲,参考国外临床药师相关理论考试经验,分别从4个培训模块的内容与要求、试题题型与性能参数、选题组卷等方面阐述理论考核试题库的建设.结果 以培训大纲为依据,以选择题为主导题型,题目数量控制在50～100题为宜,结合临床药师培训特点设置试题性能参数;另外,需定期维护与更新试题库.结论 结构完整、与临床实践结合的理论考核试题库的建设可科学地评估肿瘤专科临床药师的培训效果.

目的 以1例服用奥拉帕利的患者为例,探讨医生与临床药师共同对铂敏感复发卵巢癌患者服用奥拉帕利致血小板减少症进行药学监护的过程.方法 临床药师全程参与患者的治疗,主要针对药物不良反应对症处理以及引发不良反应药物的剂量调整两方面来优化治疗.结果 该患者既往化疗后曾出现持续、严重的血小板减少症.服用奥拉帕利之后再次出现血小板减少症,通过医生与临床药师的密切配合,将该患者服用奥拉帕利导致的血小板减少症控制在Ⅱ度及以下,同时针对患者的特殊情况给予适当的对症处理,使得患者在治疗选择极为有限的情况下,能坚持服用奥拉帕利达九个多月,取得了令人满意的临床获益.结论 临床药师深入病例,与医生各自发挥专业优势,有利于提高患者用药的安全性和有效性.

《新型冠状病毒肺炎诊疗方案(试行第七版)》延续第六版,推荐5种抗新型冠状病毒(SARS-CoV-2)的药物,同时强调药物毒性反应、相互作用的警示,关注特殊患者群抗病毒药物的选择.肿瘤患者是具有高感染率、高死亡率的特殊患者群,选择抗病毒药物应慎重,以期获得高效低毒的治疗效果.本文根据小分子口服肿瘤靶向药物的临床应用与毒性特点,结合肿瘤患者病理、生理特征,参考抗病毒药物临床及基础研究的相关文献数据,对长期口服靶向药物肿瘤患者的抗病毒药物选择进行了分析与探讨.以期为临床肿瘤患者抗病毒药物的选择提供参考.

Abstract Objective To clarify the distribution of lorlatinib in the brain and elucidate the molecular mechanisms of lorlatinib penetration across the blood‐brain barrier (BBB). Methods Cytological experiments were performed to investigate the growth inhibitory effect of lorlatinib on different cells (endothelial cells HUVEC, HMEC‐1, and HCMEC/D3) and to investigate the protective effect of lorlatinib on neuronal cells after SH‐SY5Y hypoxia/reoxygenation injury. Furthermore, rat brain tissue was sequenced, and the differentially expressed genes (secreted phosphoprotein 1 (SPP1), vascular endothelial growth factor (VEGF), transforming growth factor beta (TGF‐β), Claudin, ZO‐1 and P‐gp) in several different drug treatment groups were verified by Real‐Time PCR. Lorlatinib brain distribution was predicted by physiologically based pharmacokinetics (PBPK). Results Lorlatinib and crizotinib both had inhibitory effects on endothelial cells, however lorlatinib inhibited the growth of HCMEC/D3 more efficaciously than crizotinib. In the SH‐SY5Y hypoxia model, lorlatinib had a greater protective effect on nerve cell damage caused by hypoxia and reoxygenation than crizotinib. The expression of SPP1, VEGF, TGF‐β, and Claudin in brain tissue was significantly downregulated after lorlatinib administration, and the expression level of early growth transcription factor 1 (Egr‐1) was significantly increased. The PBPK model successfully described lorlatinib concentrations in blood and brain tissue in the mouse model and gave a brain tissue partition coefficient of 0.7. Conclusion Lorlatinib can increase the permeability of the blood‐brain barrier whereby we suggest its underlying working mechanism is related to downregulating SPP1, inhibiting VEGF, TGF‐β, and Claudin subsequently reducing the number of tight junctions between BBB cells. Lorlatinib plays a protective role on injured nerve cells and does not change the amount of P‐gp expression in brain tissue, which may be important for its ability to be efficacious across the BBB with a low incidence of resistance.

Purpose: The aim of this study was to investigate risk factors for esophageal squamous cell carcinoma (ESCC) treated with radiotherapy (RT) with or without chemotherapy to guide how to reduce the occurrence of esophageal fistula (EF). Methods: 414 patients with ESCC who underwent RT with or without chemotherapy were collected in Shandong Cancer Hospital from February 2012 to June 2018 retrospectively. The clinical characters and dosimetric parameters were recorded. Univariate and multivariate logistic regression analyses were provided to determine the risk factors associated with EF. Results: The cumulative incidences of EF were 11.1% (46/414 patients). The median follow-up period was 15.8 months (range: 0.2-82.6months). The median survival time (MST) of patients with EF was 5.3 months. In univariate analysis, age, T4 stage, N3 stage, chemotherapy regimens, re-RT, ulcerative esophageal cancer (EC), esophageal stenosis, the maximum thickness of the tumor and the length of tumor had a correlation with the prevalence of EF. In multivariable logistic regression analysis, T4 stage, N3 stage, re-RT, ulcerative EC, esophageal stenosis, the maximum thickness of the tumor was confirmed as risk factors for EF. Conclusion: This study revealed that T4 stage, N3 stage, re-RT, ulcerative EC, esophageal stenosis, the maximum thickness of the tumor were risk factors associated with EF. We ought to attach importance to the prevention of EF. Patients with risk factors for EF should be paid close attention.

原发性肝癌是我国第4位常见恶性肿瘤和第3位恶性肿瘤致死病因,严重地威胁我国人民的生命及健康.2015年,我国肝癌有46.6万新发癌症病例和42.1万死亡病例[1].原发性肝癌的病理类型,主要是肝细胞癌(hepatocellular carcinoma,HCC),肝内胆管癌(intrahepatic cholangiocarcinoma,ICC)和HCC-ICC混合型,其中肝细胞癌占85％以上.三者在发病机制、生物学行为、临床表现、治疗方法、预后等方面存在较大差异.本共识中“肝癌”指肝细胞癌[2].

基于流体包裹体测试资料,应用PetroMod-1D软件恢复泰康隆起带代表井的埋藏史、热史和生烃史,对松辽盆地泰康隆起带青二、三段储层油气成藏期次特征进行了综合分析.研究表明:泰康隆起带青二、三段砂岩储层中包含液态烃、气液烃、气态烃和含烃盐水4种包裹体,包裹体颜色主要显示为淡黄色、黄绿色、绿色、蓝白色和蓝色荧光;流体包裹体均一温度和盐度均呈现双峰特征,其中均一温度2个峰值分别为80～90℃和100～110℃,盐度2个峰值分别为2％ ～ 4％和6％ ～ 8％,表明储层中主要有2期油气充注;第1期包裹体形成于嫩江组沉积末,该期圈闭初具雏形,齐家—古龙凹陷青山口组烃源岩进入排烃门限,泰康隆起带青二、三段储层充注少量低成熟的气态烃和液态烃;第2期包裹体形成于明水组沉积末,圈闭已定型,齐家—古龙凹陷青山口组烃源岩达到排烃高峰,且与区域性构造运动时期相对应,是泰康隆起带青二、三段储层的关键油气成藏期.该研究成果为泰康隆起带油气成藏地质时期研究和勘探目标优选提供了依据.

目的 了解"医教协同"培养模式下,临床医学专业学位硕士生接受指导情况.方法 对北京协和医学院总计584名临床医学专业型硕士进行了问卷调查.结果 "医教协同"政策的推行,带来了培养模式的改变和培养要求的提高.结论 建议结合培训要求和学生需求,调整指导模式,建立指导教师团队,开展有针对性的培训,以期保证学员得到及时、有效的指导.

分析当前研究生思想政治教育工作中存在的主要问题,为加强医学研究生思想政治教育工作提供参考依据.采用问卷调查方式对一所三甲教学医院402名在读研究生的思想政治觉悟、集体荣誉观、导师专业水平和职业期望等维度进行评价.结果 显示,当前医学研究生具有较高的政治觉悟、强烈的集体荣誉感和对导师专业水平的高度认同感;调查提示在职业期望方面男生对事业的发展追求要高于女生.应树立以人为本的教育理念,充分发挥导师的引导作用,有效利用新媒体手段多渠道开展思想政治教育,为实现健康中国培养优秀医学人才.

In the present study, we developed and validated a rapid and simple liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for the determination of lorlatinib in mouse serum and tissue samples, and such a method was successfully applied to investigate the pharmacokinetic study and tissue distribution of lorlatinib after oral administration. Samples were processed with methanol to precipitate protein and extract drugs, and Afatinib-d6 was used as the internal standard (IS). For LC-MS/MS analysis, compounds were separated on a C18 column by gradient elution (0.1% of formic acid and methanol) at 0.5 mL/min in the positive-ion mode with m/z 407.28 [M + H]+ for lorlatinib and m/z 492.10 [M + H]+ for IS. Good linearity was observed within the calibration ranges. Selectivity, accuracy (−6.42% to 8.84%), precision (1.69% to 10.98%), recoveries (91.4% to 115.0%), and matrix effect (84.2% to 110.6%) were all within the acceptable ranges. After oral administration, serum concentration of lorlatinib quickly achieved the maximal concentration (2,705.683 ± 539.779 μg/L) at 0.625 ± 0.231 h. The highest concentration was detected in the liver (3,153.93 ng/100 mg), followed by the stomach (2,159.92 ng/100 mg) and the kidney (548.83 ng/100 mg). In conclusion, a simple and rapid detection method was established and validated for determination of lorlatinib in blood and tissue samples of mouse. The pharmacokinetic study and tissue distribution of lorlatinib were successfully investigated using this method.

[Purpose] To survey the employment intention and demand for employment guidance among graduate students in a cancer hospital. [Methods] The employment information of all graduate students in a cancer hospital who graduated from 2012 to 2016 was collected;and a questionnaires survey was conducted among graduate students in 2017. All data were recorded and analyzed with SPSS 10.0 software. [Results] The graduation data showed that slightly more graduates were employed in Beijing municipality,and the employment in hospitals and research/teaching institutions accounted for 75.95％. The proportion of employment in hospitals among students with academic degree was lower than those with clinical professional degree;in the contrast,the proportion of employment in scientific research institutes and companies or pursuing study abroad among students with academic degree was higher than those with clinical degree. Employment intention survey showed that students in cancer specialized teaching hospital were more willing to work in first-tier cities,85.72％ choose Beijing,Shanghai,Guangzhou and other more developed cities in the east coast of China;85.71％ were willing to work in the cancer or related fields;and 50.89％ of students wanted to choose a stable job. The 39.29％ of the graduate students wanted to have a self-potential job,and the female students preferred to have relatively stable jobs. The employment information was mainly obtained from the recommendation of the mentor and fellow students of from the job fairs,and the students wanted to get experience sharing and consulting services for employment from the colleges or universities. [Conclusion] The employment prospect of students with clinical professional degree seems to be better. To improve the employment of medical graduate students,it is important to enhance the quality and ability training of students themselves,as well as to develop the employment education and guidance.

OBJECTIVE To discuss the new ideas and new methods of pharmaceutical management of cancer hospital based on the background of the new health care reform.METHODS Read and summarize the effective management measures and methods carried out by clinical pharmacists in cancer quality control in recent years of several countries,to discussthe new ideas of the pharmacy administration quality control according to China's health care reform policy at the same time.RESULTS Oncology pharmacists have more extensive work and space on quality control,but the number of oncology pharmacists is insufficient.CONCLUSION Various ways are attempted by oncology pharmacists on quality control depend on existing conditions of hospital,to insure clinical medication safe,effective,economy and appropriate.

Objective:To probe into the operation and management of pharmaceutical care on the elderly patients with non-small cell lung cancer.Methods:By adjusting the chemotherapy drug dosage and analgesia drug,combined with the clinical guidelines,clinical pharmacist can summarize the main points of pharmaceutical care of elderly patient with NSCLC.Results:The elderly patients of have better clinical tolerance with carboplatin,and should be monitored the renal function because of the nephrotoxicity of platinum and renal excretion of pemetrexed;pharmacist can adjust the dose of chemotherapy combination drugs (anticoagulant,lipid-lowering drug,analgesia) in order to improve patients' compliance with chemotherapy,and reduce the adverse drug reaction.Conclusion:With the pharmacists' participating in clinical chemotherapy of elderly NSCLC patients,it was to formulate individualized dosage regimen,and improve the patient's medication compliance and quality of life.

Objectives:To evaluate the effect of training courses by comparing the clinical medical post-graduates' scores between those who took the doctor-patient communication training courses and those not.Methods:Medical post-graduates of Grade 2013 from different majors were divided into intervention group and control group using stratified sampling method.Only the intervention group got access to doctor-patient communication courses.Evaluate all participants' doctorpatient communication ability in the end.Results:Intervention group performed better both in clinical communication principles and attitude except appearance.Although there is no signification difference between two groups,intervention group is superior to control group among "proper eye contact","no improper interruption or put words in patients' mouths","answer patients' questions clearly "and "clarify problems profoundly and accurately" Conclusions:After taking doctor-patient communication courses,students improved their communication ability.During the course-taking period use inspection to find problems,timely adjust doctor-patient communication skills,teaching modes and content,to improve the medical postgraduate'communication ability over the long term.

Objective: To explore the influence on pharmacokinetics parameters of paclitaxel after pretreatment with aidi injection in rats. Methods: 12 SD rats, half male and half female with body weight of 180 ~ 220 g, were randomly divided into control and experimental groups. Rats in experimental group were pretreated with aidi injection at the dose of 1 mL?kg-1once a day for consecutively 5 days, while rats in control groups were treated with saline solution instead. 30 minutes after the last treatment, both groups were treated with paclitaxel at the dose of 12 mL?kg-1. Blood samples were obtained from rat eyes at 0, 0.5, 1, 2, 4, 8, 12, 24 and 48 h after administration. LC-MS/MS was used to determine plasma concentration of paclitaxel. Pharmacokinetic parameters were calculated by DAS2.0 software and SPSS software was used for statistical analysis. Results: Cmaxlevels of paclitaxel in rats of control and experimental groups was (39 555.69±1 728.70) and (79 957.62±18 067.58) μg?L-1respectively (P < 0.05). AUC0→tin control and experimental group was (28 616.24±7 059.78) and (76 066.42±32 518.88) μg?L-1?h (P < 0.05) while t1/2in control and experimental group was (3.49±1.17) and (5.99±0.75) h (P < 0.05). No significant difference was detected in other pharmacokinetic parameters of the both groups.Conclusion:aidi injection could significantly increase Cmaxand AUC0→twhile decrease t1/2of paclitaxel.

[Purpose] To survey the current status of awareness of doctor-patient communication among medical postgraduates.[Methods] A survey was conducted with a self-evaluation questionnaire among 41 master degree medical students.The items of questionnaire included the awareness and the attitude towards doctor-patient communication,the factors affecting the doctor-patient communication and self-assessment.SPSS 18.0 software was used for data analysis.[Results] Among all participants 95.12％ thought that doctor-patient communication was important.There were various factors affecting the doctor-patient communication,among which insufficient time and efforts of doctors were the most important ones affecting doctor-patient communication.[Conclusion] The training should be strengthened to improve the awareness and ability of doctor-patient communication for medical postgraduate students.

目的 探讨肿瘤专科医院药师参与化疗药事质控的内容及方法,以促进抗肿瘤药物的合理使用.方法 通过对目前肿瘤医院药师参与化疗药物使用工作的内容及方式进行总结分析,结合国内外文献关于药师参与化疗质控的报道与研究,对化疗药物的概念与范围、药师参与化疗质控的内容及存在的问题进行阐述与分析.结果 肿瘤专科医院化疗药事质控内容涉及肿瘤药物治疗的全过程,药师参与化疗药事质控的内容包括药事管理质控及临床药学监护.结论 药师在肿瘤治疗中,不仅要注重药品管理质控,更应积极参与到肿瘤治疗团队中,对肿瘤治疗用药的全过程进行质量控制,从而确保临床用药安全有效、经济适宜.

[目的]分析临床医学硕士生对医患沟通培训课程的满意度,探索可提高培训效果的医患沟通课程改进措施.[方法]采取分层抽样的方法,抽取2013级不同专业临床硕士20人在临床训练阶段开展医患沟通技巧培训课程,问卷调查学生对培训课程的满意度.[结果]85％的学生认为讲授内容通俗易懂,提供了及时的信息;一致认为讲座内容切合临床需求.45％的学生认为该课程提供了新方法.[结论]学生对在临床训练阶段开设医患沟通技巧培训比较满意,但认为内容形式不够新颖.提示今后医患沟通培训可通过多阶段承接模式开展:课程设计增加岗前培训、进入临床训练阶段后3～6个月开展专家座谈、录制微课网络公开推送,在实践过程中结合临床实际进行及时沟通教育,最终改革沟通技巧授课模式和内容,进一步提高医学生沟通能力.