医疗领域人工智能应用的研究进展＊

人工智能引发了医疗领域的数字革命，在推动行业发展方面具有极大潜力。本研究围绕临床诊疗、医学研究和公共卫生三个基本场景，聚焦人工智能与传统中医药的交叉与融合，并着重介绍人工智能在疾病诊断、决策支持、医学研究以及重大公共卫生事件中的应用。虽然人工智能在诸多方面显示出独特优势，但仍存在透明度不高、缺乏安全性评估和相关法律法规监管等问题需要谨慎解决，以促进人工智能技术在医疗领域的推广。     

Proxalutamide in metastatic castration-resistant prostate cancer: Primary analysis of a multicenter,randomized, open-label,phase 2 trial

We aim to assess the safety and efficacy of proxalutamide, a novel androgen receptor antagonist, for men with metastatic castration-resistant prostate cancer (mCRPC) in a multicenter, randomized, open-label, phase 2 trial. In our study, the enrolled mCRPC patients were randomized to 100, 200 and 300 mg dose groups at 1:1:1. The primary efficacy endpoint was prostate-specific antigen (PSA) response rate. The secondary endpoints included objective response rate (ORR), disease control rate (DCR) and time to PSA and radiographic progression. Safety and pharmacokinetics were also assessed. Finally, there were 108 patients from 17 centers being enrolled. By week 16, there were 13 (35.1%), 12 (36.4%) and 15 (42.9%) patients with confirmed 50% or greater PSA decline in 100 mg (n = 37), 200 mg (n = 33) and 300 mg (n = 35) groups, respectively. Among the 19 patients with target lesions at study entry, three (15.8%) had a partial response and 12 (63.2%) had stable disease. The ORRs of 20.0%, 22.2%, 0% and DCRs of 80.0%, 88.9%, 60.0% were, respectively, achieved in 100, 200 and 300 mg groups. By the maximum follow-up time of 24 weeks, there were 42.6% and 10.2% of cases experiencing PSA progression and radiographic progression, respectively. Overall, adverse events (AEs) were experienced by 94.4% of patients, most of which were mild or moderate. There were 28 patients experiencing ≥grade 3 AEs. The most common AEs were fatigue (17.6%), anemia (14.8%), elevated AST (14.8%) and ALT (13.0%), decreased appetite (13.0%). These findings preliminarily showed the promising antitumor activity of proxalutamide in patients with mCRPC with a manageable safety profile. The proxalutamide dose of 200 mg daily is recommended for future phase 3 trial (Clinical trial registration no. CTR20170177).     

进食障碍患者家庭顺应量表的汉化及信效度检验

目的 汉化进食障碍患者家庭顺应量表，并检验其信效度。方法 根据Brislin翻译模式将量表翻译成中文，通过专家函询和预调查对量表进行文化调适和修订。将量表应用于300例进食障碍患者照顾者检验信效度。结果 中文版进食障碍患者家庭顺应量表的量表水平内容效度指数为0.918。探索性因子分析结果显示5个因子可解释总变异量的49.862%。量表的各维度得分与量表总分呈中高度相关，各维度得分之间呈中低度相关或不相关。量表总Cronbach′s α为0.877，重测信度为0.883。结论 中文版进食障碍患者家庭顺应量表具有较好的信效度，可用于测量进食障碍患者的家庭顺应情况。     

黄花蒿Dof基因家族鉴定及在GA-UV处理下对青蒿素生物合成的影响＊

目的 Dof（DNA binding with one finger）家族是高等植物中特有的一类转录因子家族，参与植物中光、激素、非生物胁迫等多种胁迫响应调控。本研究基于全基因组数据对黄花蒿Dof（AaDof）转录因子家族进行鉴定及表达模式分析，探究Dof家族基因在青蒿素合成调控中的作用。方法 经PFAM数据库鉴定获得AaDof序列，通过生物信息学软件分析其理化性质、亚细胞定位、基因结构、蛋白保守结构以及启动子序列结合元件等，并基于赤霉素（Gibberellic acid， GA）、紫外线B（UV-B）及二者协同胁迫下黄花蒿转录组数据对其表达模式进行分析。结果 本研究从全基因组水平共鉴定出51个AaDof基因，均含有保守的C₂-C₂单锌指结构，依据系统发育分析分为8个亚族，同一亚族内基因结构与蛋白保守结构域相对保守。亚细胞定位预测显示12个AaDof蛋白定位在细胞外，其余均定位在细胞核。启动子元件分析发现AaDof家族基因启动子区富含光、激素等多种响应元件。对AaDof在GA、UV-B和GA+UV-B处理下的表达模式分析发现，AaDof基因对GA胁迫处理响应较弱，仅有少量基因敏感，其表达主要受到UV-B胁迫影响。C1及C2.1亚族大部分基因在UV-B胁迫下上调表达，而A亚族大部分基因在UV-B胁迫下下调表达。qRT-PCR验证表明AaDof1、AaDof17和AaDof44在GA和UV-B处理下表达量显著上调，推测其可能通过参与GA和UV-B调控网络，正向调控青蒿素生物合成。结论 本研究系统鉴定了黄花蒿AaDof家族基因并筛选了3个可能正向调控青蒿素生物合成的候选AaDof基因，为黄花蒿Dof家族基因功能研究及其在青蒿素生物合成中的调控机制解析奠定基础。     

聚甲酚磺醛溶液治疗外阴硬化性苔藓病变的临床分析

目的观察使用聚甲酚磺醛溶液治疗外阴硬化性苔藓病变的临床疗效。方法对经临床诊断确诊为外阴硬化性苔藓病变且自愿接受本次研究的36例患者使用聚甲酚磺醛溶液,观察其疗效。结果36例外阴硬化性苔藓病变患者经过聚甲酚磺醛溶液3个月疗程治疗,痊愈率达76.9%,显效率为15.4%,有效率为7.7%。结论聚甲酚磺醛溶液能有效治疗外阴硬化性苔藓病变,无论是缓解瘙痒症状,还是改善病灶皮肤病变效果均较好,为广大临床医生提供了治疗此疾患的新思路。     

Comparison of survival outcomes between primary and secondary muscle-invasive bladder cancer: An updated meta-analysis

Objective: Studies have showed that different follow-up starting points might potentially impact the comparison between primary (PMIBC) and secondary muscle-invasive bladder cancer (SMIBC), but the only previous meta-analysis did not differentiate the follow-up starting points of included studies. With more trials published, we aim to update the meta-analysis comparing PMIBC and SMIBC.Methods: PubMed, Embase, Cochrane Library and ClinicalTrial.gov. systematically searched. Literatures comparing the survival outcomes of PMIBC and SMIBC were selected. Outcomes of cancer-specific mortality (CSM), overall mortality (OM) and recurrence-free survival (RFS) were pooled and grouped based on the starting point of follow-up (after initial diagnosis or radical cystectomy (RC)). Newcastle-Ottawa Scale (NOS) and funnel plot were employed to assess the study quality and publication bias, respectively.Results: A total of 17 high-quality studies were selected, with 5558 patients aged from 59.8 to 72.7 (mean value) involved. The male-to-female ratio was roughly 4:1 (4390/1124). SMIBC had lower risk of CSM after initial diagnosis (HR 0.81, 95%CI 0.67-0.98, P=0.03, I²=70%), but higher risk of CSM after RC (HR 1.45, 95%CI 1.27-1.65, P<0.00001, I²=64%). In terms of OM and recurrence, outcomes were pooled only after RC, which both turned out to be higher for SMIBC (OM: HR 1.50, 95%CI 1.30-1.73, P<0.00001, I²=0%; Recurrence: HR 1.66, 95%CI 1.36-2.02, P<0.00001, I²=48%). No obvious publication bias was observed from funnel plot.Conclusion: The current study suggested SMIBC had higher risk of CSM, OM and recurrence after RC, but lower risk of CSM after initial diagnosis.     

Evidence of association between single-nucleotide polymorphisms in lipid metabolism-related genes and type 2 diabetes mellitus in a Chinese population

Background: Type 2 diabetes mellitus (T2DM) is a complex chronic metabolic disorder triggered by insulin resistance in peripheral tissues. Evidence has shown that lipid metabolism and related genetic factors lead to insulin resistance. Hence, it is meaningful to investigate the association between single-nucleotide polymorphisms (SNPs) in lipid metabolism-related genes and T2DM.Methods: A total of 1,194 subjects with T2DM and 1,274 Non-diabetic subjects (NDM) were enrolled. Five SNPs in three genes (rs864745 in JAZF1, rs35767 in IGF1, and rs4376068, rs4402960, and rs6769511 in IGF2BP2) that contribute to insulin resistance involving lipid metabolism were genotyped using the MassArray method in a Chinese population.Results: The allele and genotypes of rs6769511 in IGF2BP2 were associated with T2DM (P=0.009 and P=0.002, respectively). In inheritance model analysis, compared with the T/T-C/T genotype, the C/C genotype of rs6769511 in IGF2BP2 was a risk factor for the development of T2DM (P<0.001, odds ratio [OR] =1.76; 95% confidence interval [CI]: 1.29-2.42). Haplotype analysis revealed associations of the rs4376068-rs4402960-rs6769511 haplotypes in IGF2BP2 with the development of T2DM (P=0.015). Additionally, rs4376068C-rs4402960T-rs6769511C was a risk haplotype for T2DM (OR=1.179; 95% CI: 1.033-1.346).Conclusion: The rs6769511 in IGF2BP2 was associated with T2DM susceptibility, and the rs4376068-rs4402960-rs6769511 haplotypes in IGF2BP2 was associated with the development of T2DM in a Chinese population.     

浅谈新型冠状病毒肺炎合并基础病的中医药防治策略＊

2019年12月始，新型冠状病毒肺炎（Corona Virus Disease 2019，COVID-19）以湖北武汉为中心向全国各地蔓延。目前数据显示，COVID-19合并糖尿病、高血压、肿瘤等基础病的患者病情较为严峻，病死率相对较高。该类患者的临床治疗策略有待进一步深入研究。在此次疫情防治过程中，中西医结合治疗手段于COVID-19的防治及患者基础疾病的兼顾治疗方面展现出了一定的特色及优势。本文结合中医“未病先防，既病防变，瘥后防复”思想，拟从COVID-19合并糖尿病、高血压、肿瘤三个方面，探讨COVID-19爆发形势下合并基础病患者的中医药防治策略。     

Spectrum-Toxicity Correlation Study Revealed the Influence of the Nine-Time Steaming and Sun Drying Method on Hepatotoxic Components of Polygoni Multiflori Radix

Objective: Polygoni Multiflori Radix (PM) is a traditional herbal medicine with repeated reports of liver injury events in recent years. We wondered whether the classical processing method, namely, nine-time steaming and sun drying (NSSD), had toxicity-attenuating effects on PM and the relationships between toxicity and times of processing, as well as with the alteration trends of its compounds. Materials and Methods: The chemical fingerprints of different PM extracts were developed using ultra-high-performance liquid chromatography. The spectrum-toxicity correlation between the chemical fingerprints and hepatocellular toxicity was analyzed with multiple correlation analysis. Results: The results suggested that the hepatotoxicity of NSSD processing products markedly decreased with the repeated steaming and sun drying, which was obviously superior to the product processed by the modern method. Comprehensive analysis revealed that the contents of cis-stilbene glycoside and emodin-8-O-β-D-glucoside related to liver injury susceptibility were reduced with the times of NSSD processing, which was consistent with the decreased trend of hepatocellular toxicity. After the five times of NSSD, the contents of them as well as the hepatotoxicity of PM were steady. Moreover, we found that the contents of catechin and physcion declined rapidly after the one time of NSSD and then remained stable until the nine times of NSSD. Based on the fact, they could be utilized to indicate whether PM products were processed by steaming and sun drying. Conclusions: This paper confirmed that the NSSD had a good influence on the toxicity attenuating to PM and found four compounds which could apply for the quality control of PM.     

Phase 1 trial of ADI-PEG20 plus cisplatin in patients with pretreated metastatic melanoma or other advanced solid malignancies

Background Arginine depletion interferes with pyrimidine metabolism and DNA damage-repair pathways, and pairing arginine deiminase pegylated with 20,000-molecular-weight polyethylene glycol (ADI-PEG20) with platinum enhances cytotoxicity in vitro and in vivo in arginine auxotrophs.Methods This single-centre, Phase 1 trial was conducted using a 3 + 3 dose escalation designed to assess safety, tolerability and determine the recommended Phase 2 dose (RP2D) of ADI-PEG20.Results We enrolled 99 patients with metastatic argininosuccinate synthetase 1 (ASS1) deficient malignancies. We observed no dose-limiting toxic effects or treatment-related mortality. Three percent of patients discontinued treatment because of toxicity. After treatment, 5% (5/99) of patients had partial responses, and 41% had stable disease. The median progression-free and overall survival durations were 3.62 and 8.06 months, respectively. Substantial arginine depletion and citrulline escalation persisted in most patients through weeks 24 and 8, respectively. Tumour responses were associated with anti-ADI-PEG20 antibody levels at weeks 8 and 16 (p = 0.031 and p = 0.0357, respectively).Conclusion Concurrently administered ADI-PEG20 and cisplatin had an acceptable safety profile and had shown antitumour activity against metastatic ASS1-deficient solid tumours. Further evaluation of this treatment combination is warranted.Subject terms: Cancer, Cancer therapy