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Tumour mutational burden is overestimated by target cancer gene panels

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Journal of the National Cancer Center 2023年第1期3卷 56-64页

作者： Hu Fang Johanna Bertl Xiaoqiang Zhu Tai Chung lam Song Wu David J.H.Shih Jason W.H.Wong School of Biomedical Sciences Li Ka Shing Faculty of MedicineThe University of Hong KongHong KongChina South China Hospital Health Science CenterShenzhen UniversityShenzhenChina Department of Mathematics Aarhus UniversityAarhusDenmark Department of Clinical Oncology Li Ka Shing Faculty of MedicineThe University of Hong KongHong KongChina

Background:Tumour mutational burden(TMB)has emerged as a predictive marker for responsiveness to immune checkpoint inhibitors(ICI)in multiple tumour *** can be calculated from somatic mutations detected from whole exome or targeted panel sequencing *** mutations are unevenly distributed across the cancer genome,the clinical implications from TMB calculated using different genomic regions are not ***:Pan-cancer data of 10,179 samples were collected from The Cancer Genome Atlas cohort and 6,831 cancer patients with either ICI or non-ICI treatment outcomes were derived from published *** was calculated as the count of non-synonymous mutations and normalised by the size of genomic *** method,linear regression and Poisson calibration models are used to unify TMB from different gene ***:We found that panels based on cancer genes usually overestimate TMB compared to whole exome,potentially leading to misclassification of patients to receive *** overestimation is caused by positive selection for mutations in cancer genes and cannot be completely addressed by the removal of mutational *** compared different approaches to address this discrepancy and developed a generalised statistical model capable of interconverting TMB derived from whole exome and different panel sequencing data,enabling TMB correction for patient stratification for ICI *** show that in a cohort of lung cancer patients treated with ICI,when using a TMB cutoffof 10 mut/Mb,our corrected TMB outperforms the original panel-based ***:Cancer gene-based panels usually overestimate TMB,and these findings will be valuable for unifying TMB calculations across cancer gene panels in clinical practice.

关键词： Tumour mutational burden Immune checkpoint inhibitor Immune response Biomarker

B-cell-targeted therapies in systemic lupus erythematosus

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Cellular & Molecular Immunology 2013年第2期10卷 133-142页

作者： Vera Sau-Fong Chan Helen Hoi-lun Tsang Rachel Chun-Yee Tam Liwei Lu Chak-Sing Lau Department of Medicine Li Ka Shing Faculty of Medicine The University of Hong Kong Hong Kong China Department of Pathology Li Ka Shing Faculty of Medicine The University of Hong Kong Hong Kong China

Autoreactive B cells are one of the key immune cells that have been implicated in the pathogenesis of systemic lupus erythematosus （SLE）. In addition to the production of harmful auto-antibodies （auto-Abs）, B cells prime autoreactive T cells as antigen-presenting cells and secrete a wide range of pro-inflammatory cytokines that have both autocrine and paracrine effects. Agents that modulate B cells may therefore be of potential therapeutic value. Current strategies include targeting B-cell surface antigens, cytokines that promote B-cell growth and functions, and B- and T-cell interactions. In this article, we review the role of B cells in SLE in animal and human studies, and we examine previous reports that support B-cell modulation as a promising strategy for the treatment of this condition. In addition, we present an update on the clinical trials that have evaluated the therapeutic efficacy and safety of agents that antagonize CD20, CD22 and B-lymphocyte stimulator （BLyS） in human SLE. While the results of many of these studies remain inconclusive, belimumab, a human monoclonal antibody against BLyS, has shown promise and has recently been approved by the US Food and Drug Administration as an indicated therapy for patients with mild to moderate SLE. Undoubtedly, advances in B-cell immunology will continue to lead us to a better understanding of SLE pathogenesis and the development of novel specific therapies that target B cells.

关键词： Systemic lupus erythematosus B-cell autoimmunity therapy

Spray freeze drying of small nucleic acids as inhaled powder for pulmonary delivery

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Asian Journal of Pharmaceutical Sciences 2018年第2期13卷 163-172页

作者： Wanling Liang Alan Y.L.Chan Michael Y.T.Chow Fiona F.K.Lo Yingshan Qiu Philip C.L.Kwok Jenny K.W.lam Department of Pharmacology and Pharmacy Li Ka Shing Faculty of Medicine The University of Hong Kong Advanced Drug Delivery Group Faculty of Pharmacy The University of Sydney

The therapeutic potential of small nucleic acids such as small interfering RNA(siRNA) to treat lung diseases has been successfully demonstrated in many in vivo studies. A major barrier to their clinical application is the lack of a safe and efficient inhaled *** this study, spray freeze drying was employed to prepare dry powder of small nucleic *** and herring sperm DNA were used as bulking agent and model of small nucleic acid therapeutics, respectively. Formulations containing different solute concentration and DNA concentration were produced. The scanning electron microscope(SEM) images showed that the porosity of the particles increased as the solute concentration decreased. Powders prepared with solute concentration of 5% w/v were found to maintain a balance between porosity and robustness. Increasing concentration of DNA improved the aerosol performance of the formulation. The dry powder formulation containing 2% w/w DNA had a median diameter of 12.5 μm, and the aerosol performance study using next generation impactor(NGI) showed an emitted fraction(EF) and fine particle fraction(FPF) of 91% and 28% respectively. This formulation(5% w/v solute concentration and 2% w/w nucleic acid) was adopted subsequently to produce siRNA powder. The gel retardation and liquid chromatography assays showed that the siRNA remained intact after spray freeze drying even in the absence of delivery vector. The siRNA powder formulation exhibited a high EF of 92.4%and a modest FPF of around 20%. Further exploration of this technology to optimise inhaled siRNA powder formulation is warranted.

关键词： Inhalation Pulmonary delivery Small interfering RNA Spray freeze drying

经皮Chevron截骨术治疗轻中度足拇外翻畸形

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国际骨科学杂志 2015年第2期36卷 137-140页

作者：林嘉莉江少华香港屯门医院骨科

目的评估经皮Chevron截骨术治疗轻中度足拇外翻畸形的疗效。方法2010年6月至2012年5月，采用经皮Chevron截骨术治疗24位（26例）轻中度足拇外翻患者。所有患者均为女性，平均年龄48岁，其中右足14例，左足12例。术前和末次随访时测量足... 详细信息

目的评估经皮Chevron截骨术治疗轻中度足拇外翻畸形的疗效。方法2010年6月至2012年5月，采用经皮Chevron截骨术治疗24位（26例）轻中度足拇外翻患者。所有患者均为女性，平均年龄48岁，其中右足14例，左足12例。术前和末次随访时测量足拇外翻角、跖骨间角，并进行美国足踝骨科学会（AOFAS）前足评分。术前足拇外翻角20°～40°，跖骨间角小于20°，跖骨远端关节角小于10°。结果术后平均随访26．3个月，足拇外翻角由术前平均31．68°纠正至术后平均14．39°，跖骨间角由术前平均13．77°纠正至术后平均7．98°，AOFAS前足评分由术前平均59．26分改善至术后平均88．35分。术后4例出现内侧关节囊折叠缝合引起的刺激症状，4例出现螺钉尾端刺激症状，但无伤口感染、关节僵硬及跖骨头坏死等并发症发生。结论经皮Chevron截骨术中期随访结果较好，可有效治疗轻中度足拇外翻畸形。

关键词：经皮Chevron截骨足拇外翻跖骨截骨

A flexible ultra-broadband multi-layered absorber working at 2 GHz-40 GHz printed by resistive ink

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Chinese Physics B 2024年第2期33卷 329-333页

作者：汪涛闫玉伦陈巩华李迎胡俊毛剑波 School of Microelectronics Hefei University of TechnologyHefei 230601China Special Display and Imaging Technology Innovation Center of Anhui Province Academy of Photoelectric TechnologyHefei University of TechnologyHefei 230027China

A flexible extra broadband metamaterial absorber(MMA)stacked with five layers working at 2 GHz–40 GHz is *** layer is composed of polyvinyl chloride(PVC),polyimide(PI),and a frequency selective surface(FSS),which is printed on PI using conductive *** investigate this absorber,both one-dimensional analogous circuit analysis and three-dimensional full-wave simulation based on a physical model are *** crucial electromagnetic properties,such as absorption,effective impedance,complex permittivity and permeability,electric current distribution and magnetic field distribution at resonant peak points,are studied in *** shows that the working frequency of this absorber covers entire S,C,X,Ku,K and ka bands with a minimum thickness of 0.098λ_(max)(λ_(max) is the maximum wavelength in the absorption band),and the fractional bandwidth(FBW)reaches 181.1%.Moreover,the reflection coefficient is less than-10 dB at 1.998 GHz–40.056 GHz at normal incidence,and the absorptivity of the plane wave is greater than 80%when the incident angle is smaller than 50°.Furthermore,the proposed absorber is experimentally validated,and the experimental results show good agreement with the simulation results,which demonstrates the potential applicability of this absorber at 2 GHz–40 GHz.

关键词： extra broadband physical model flexible metamaterial absorber multi-layer frequency selective surface

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中国香港加入RCEP的必要性研究

对外经贸 2024年第11期 25-30页

作者：蓝家达何茂春清华大学社会科学学院北京100084

《区域全面经济伙伴关系协定》(RCEP)于2022年1月1日正式生效,实施该协定将提升区域经济发展水平。RCEP对成员在货物贸易、服务贸易、贸易便利化、电子商务等领域的开放水平提出了更高要求,有助于重构区域产业链。中国香港加入RCEP具有... 详细信息

《区域全面经济伙伴关系协定》(RCEP)于2022年1月1日正式生效,实施该协定将提升区域经济发展水平。RCEP对成员在货物贸易、服务贸易、贸易便利化、电子商务等领域的开放水平提出了更高要求,有助于重构区域产业链。中国香港加入RCEP具有必要性。在加入后,中国香港可以在国家对外经贸发展中发挥重要作用,特别在扩大开放和自贸区建设方面有助于推动人民币国际化和完善内地自贸区金融管理机制。得益于中央政府的支持,香港特区政府已向RCEP保管方提出加入申请,建议中国香港尽快加入,配合国家深化对外开放政策,为亚太经济复苏注入新动力。

关键词：中国香港 RCEP 中国自贸区对外开放

针刺结合言语康复训练治疗脑卒中后构音障碍的临床研究

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中华中医药杂志 2015年第7期30卷 2593-2596页

作者：李季胡卡明杨玲屈云罗伦李德华成都中医药大学附属医院成都610072 四川大学华西医院成都610041 成都市第二人民医院成都610017

目的:观察针刺结合言语康复训练治疗脑卒中后构音障碍的临床疗效,为针刺治疗脑卒中后构音障碍提供高质量的临床证据。方法:采用随机、对照临床试验方法,将270例脑卒中后构音障碍患者随机分成针刺结合言语康复训练组(A组),单纯针刺组(B组... 详细信息

目的:观察针刺结合言语康复训练治疗脑卒中后构音障碍的临床疗效,为针刺治疗脑卒中后构音障碍提供高质量的临床证据。方法:采用随机、对照临床试验方法,将270例脑卒中后构音障碍患者随机分成针刺结合言语康复训练组(A组),单纯针刺组(B组)和言语康复训练组(C组),每组90例,各组均每日治疗1次,每周5次,治疗4周,以Frenchay构音障碍评价量表作为疗效评价指标,评价3组治疗后组间的疗效差异。结果:A组总有效率(94.4%)明显优于B组(81.4%)和C组(61.2%)。结论:针刺结合言语康复训练的综合治疗方法安全有效,对脑卒中后构音障碍的临床疗效要优于单纯针刺或单纯言语康复训练。

关键词：针刺言语康复训练构音障碍脑卒中

Phenylketonuria in Hong Kong Chinese： a call for hyperphenylalaninemia newborn screening in the Special Administrative Region, China

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Chinese Medical Journal 2011年第16期000卷 2556-2558页

作者： Chloe Miu Mak Chun-hung Ko Ching-wan lam Wai-ling Lau Wai-kwan Siu Sammy Pak-lam Chen Chun-yiu Law Chi-kong Lai Chak-man Yu Albert Yan-wo Chan Kowloon West Cluster Laboratory Genetic Service ChemicalPathology Laboratory Department of Pathology Princess MargaretHospital Hong Kong China Department of Paediatrics and Adolescent Medicine CaritasMedical Centre Hong Kong China Department of Pathology Li Ka Shing Faculty of Medicine TheUniversity of Hong Kong Hong Kong China

Hyperphenylalaninemia is one of the commonest inborn errors of metabolism affecting approximately 1 in 15 000 live births. Among Chinese, BH4 deficiency leading to hyperphenylalaninemia is much commoner than in Caucasians. Exact diagnosis is important for the treatment and genetic counseling. In 2000, newborn screening for phenylketonuria is mandatory by law in China throughout the whole country. However, it is not yet included in the newborn screening program of the Hong Kong Special Administrative Region, China. Published data on hyperphenylalaninemia among Hong Kong Chinese are largely lacking. We report a 1-year-old Hong Kong Chinese girl with severe 6-pyruvoyl-tetrahydropterin synthase （PTPS） deficiency. The patient presented with infantile hypotonia and was misdiagnosed as cerebral palsy. She had very mild hyperphenylalaninemia （95 IJmol/L）, significantly high phenylalnine-to-tyrosine ratio （3.1）, and ele~,ated prolactin of 1109 m lU/L. Genetic analysis confirmed a homozygous known disease-causing mutation PTS NM_000317.1： c.259C〉T; NP_000308.1： p.P87S in the proband. In our local experience, while the estimated prevalence of hyperphenylalaninemia due to PTPS deficiency was reported to be 1 in 29 542 live births, not a single case of phenylalanine hydroxylase deficiency has been reported. Furthermore, there is a general lack of awareness of inherited metabolic diseases in the community as well as among the medical professionals. Very often, a low index of clinical suspicion will lead to delay in diagnosis, multiple unnecessary and costly investigations, prolonged morbidity and anxiety to the family affected. We strongly recommend that expanded newborn screening for hyperphenylalaninemia should be implemented for every baby born in the Hong Kong Special Administrative Region, China.

关键词： Hong Kong Chinese hyperphenylalaninemia newborn screening phenylketonuria 6-pyruvoyl-tetrahydropterin synthase deficiency

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卡培他滨联用华法林致消化道出血1例

中国新药与临床杂志 2015年第8期34卷 647-648页

作者：唐波王若伦叶丽卡冯霞王一西广州医科大学附属第二医院药学部广东广州510260

卡培他滨（capecitabine）是一种口服氟尿嘧啶（5-FU）前体药物，可用于治疗结直肠癌和乳腺癌。华法林（warfarin）是目前广泛应用的香豆素类口服抗凝药，用于预防和治疗深静脉血栓、肺栓塞、心脏瓣膜置换术及心房颤动导致的血栓形成，... 详细信息

卡培他滨（capecitabine）是一种口服氟尿嘧啶（5-FU）前体药物，可用于治疗结直肠癌和乳腺癌。华法林（warfarin）是目前广泛应用的香豆素类口服抗凝药，用于预防和治疗深静脉血栓、肺栓塞、心脏瓣膜置换术及心房颤动导致的血栓形成，降低心肌梗死复发及心肌梗死后血栓栓塞死亡的危险。

关键词：卡培他滨华法林消化道出血药物相互作用