China special issue on gastrointestinal tumors-Radiological features of pathological complete response in mismatch repair deficient colorectal cancer after neoadjuvant PD-1 blockade: A post hoc analysis of the PICC phase II trial

Neoadjuvant programmed cell death protein 1 (PD-1) blockade exhibits promising efficacy in patients with mismatch repair deficient (dMMR) colorectal cancer (CRC). However, discrepancies between radiological and histological findings have been reported in the PICC phase II trial (NCT 03926338). Therefore, we strived to discern radiological features associated with pathological complete response (pCR) based on computed tomography (CT) images. Data were obtained from the PICC trial that included 36 tumors from 34 locally advanced dMMR CRC patients, who received neoadjuvant PD-1 blockade for 3 months. Among the 36 tumors, 28 (77.8%) tumors achieved pCR. There were no statistically significant differences in tumor longitudinal diameter, the percentage change in tumor longitudinal diameter from baseline, primary tumor sidedness, clinical stage, extramural venous invasion status, intratumoral calcification, peritumoral fat infiltration, intestinal fistula and tumor necrosis between the pCR and non-pCR tumors. Otherwise, tumors with pCR had smaller posttreatment tumor maximum thickness (median: 10 mm vs 13 mm, P = .004) and higher percentage decrease in tumor maximum thickness from baseline (52.9% vs 21.6%, P = .005) compared to non-pCR tumors. Additionally, a higher proportion of the absence of vascular sign (P = .003, odds ratio [OR] = 25.870 [95% CI, 1.357-493.110]), nodular sign (P < .001, OR = 189.000 [95% CI, 10.464-3413.803]) and extramural enhancement sign (P = .003, OR = 21.667 [2.848-164.830]) was observed in tumors with pCR. In conclusion, these CT-defined radiological features may have the potential to serve as valuable tools for clinicians in identifying patients who have achieved pCR after neoadjuvant PD-1 blockade, particularly in individuals who are willing to adopt a watch-and-wait strategy.     

小儿腹股沟斜疝日间手术与专科住院手术的卫生经济学评价

目的对小儿日间手术模式和专科住院手术模式的卫生经济学进行评价,为小儿腹股沟斜疝手术的优选和决策提供参照依据。方法收集2016年6月至2017年7月间所有在重庆医科大学附属儿童医院治疗且符合纳入标准的单侧腹股沟斜疝患儿的临床资料,其中日间手术患儿324例(日间组),专科住院手术患儿65例(专科组)。比较两种手术模式下的患儿一般资料、治疗指标、容错情况、术后需要留院处理的并发症发生率、复发率、院内的感染等卫生效果指标;比较两种模式的HCAHPS优化星表满意度、住院时间、住院费用等卫生经济学指标。统计分析两种模式的成本-效果:治疗效果权重W、治疗效果指数(EI)、成本-效果比(CER)。结果日间外科组和专科组在性别、区域方面的差异无统计学意义,专科组年龄分布更广。日间组与专科组占用床位时间分别为(23.17±0.49)h和(112.06±19.75)h,差异具有统计学意义(P<0.01);两组的医疗费用分别为(3372±430)元和(6063±2104)元,差异具有统计学意义(P<0.01)。两组麻醉分级ASA比例的差异具有统计学意义,两组术后并发症发生率的差异无统计学意义(P>0.05)。日间组与专科组治疗EI分别为0.98和1.02,CER分别为3305和6184,日间组经济学效益较大。结论日间手术的成本-效果优于专科住院手术模式,患儿满意度和术后复发率与专科住院模式的差异无统计学意义,推荐符合日间手术指征的患儿采用该模式。     

术前血清CA125、HE4和中性粒细胞与淋巴细胞比值联合检测在子宫内膜癌诊断中的作用

目的:探讨血清糖类抗原125（carbohydrate antigen 125，CA125）、人附睾蛋白4（human epididymis protein 4，HE4）、中性粒细胞与淋巴细胞比值（neutrophil-lymphocyte ratio，NLR）联合检测在子宫内膜癌诊断中的作用。方法:选取42例子宫内膜癌患者、50例子宫内膜良性疾病患者和50例健康体检人群。采用SYSMEX XN550全自动血液分析仪计数术前外周血中性粒细胞和淋巴细胞，计算NLR；采用Maglumi4000全自动化学发光仪检测术前血清CA125、HE4水平。采用ROC曲线分析CA125、HE4、NLR和三者联合指标在诊断子宫内膜癌中的作用。结果:外周血NLR在健康组、良性组和子宫内膜癌组中逐渐增高，且差异有统计学意义（P<0.05）；子宫内膜癌组HE4表达量显著高于良性组与健康组（P<0.05），而良性组与健康组之间差异无统计学意义（P>0.05）；CA125表达量在三组中差异无统计学意义（P>0.05）。CA125、HE4、NLR及三者联合标记物的AUC分别为0.530、0.733、0.795、0.823，当分别取它们的临界值时，特异性分别为70.8%、85.1%、61.7%、83.0%，敏感性分别为40.0%、63.3%、86.7%、73.3%。单项指标NLR的敏感性最高，HE4的特异性最高，联合指标的特异性和敏感性都很高。结论:术前血清CA125、HE4和NLR联合检测具有较高的特异性和敏感性，联合检测可以互为补充，提高子宫内膜癌的诊断准确率，对子宫内膜癌的诊断具有指导意义。     

扶正消瘤颗粒对原发性肝癌血清中VEGF、HIF-1α表达的影响及临床意义＊

目的 探讨扶正消瘤颗粒对原发性肝癌血清中血管内皮生长因子（Vascular endothelial growth factor，VEGF）和缺氧诱导因子-1α（Hypoxia inducible factor-1α，HIF-1α）表达的影响及临床意义。方法 选择符合纳入标准的原发性肝癌患者66例，按1∶1随机分试验组和对照组。观察治疗过程中两组VEGF、HIF-1α水平的变化及对患者临床疗效指标的影响。结果 （1）在性别、年龄、合并乙型肝炎、Child-Pugh分级、AFP值、临床分期方面，试验组和对照组差异无统计学意义（P > 0.05）。（2）肝癌患者在治疗各时间节点的VEGF和HIF-1α表达水平呈线性正相关（r = 0.829，P < 0.001）。（3）VEGF浓度在经导管动脉化疗栓塞术（Transcatheter arterial chemoembolization，TACE）后3月降至术前水平（P > 0.05），HIF-1α在TACE后3月仍高于术前（P < 0.05）。（4）扶正消瘤颗粒可降低HIF-1α水平，下调VEGF的表达。（5）扶正消瘤颗粒可减少TACE序贯RFA治疗后的不良反应，提高患者的生活质量（P < 0.05）。（6）血清中VEGF水平与生活质量无明显相关性（P > 0.05，r = 0.251），HIF-1α水平与生活质量存在正相关性（P < 0.05，r = 0.450）。结论 扶正消瘤颗粒可明显改善TACE序贯RFA治疗后患者生活质量，降低HIF-1α水平，下调VEGF的表达，抑制肿瘤血管生成。     

Improvements in epidermal function prevent relapse of psoriasis: a self‐controlled study

While therapeutic approaches for psoriasis are widely available, preventive regimens are lacking. We aimed to determine whether improvements in epidermal function could prevent psoriasis relapse. Two self‐controlled cohort studies were designed, enrolling two cohorts of patients with psoriasis (n = 30 and n = 60) to be treated topically with an in‐house‐prepared emollient or ATOPALM^® cream applied twice daily to one forearm for 20 and 30 days, respectively, while the same sites on the contralateral arm served as the untreated control. Epidermal function on both arms was assessed prior to and at the end of the trials. Delayed relapse on the treated arm was seen in 54.5% and 71% of patients in the first and second cohort, respectively. The time of psoriatic relapse correlated with the extent of abnormalities in baseline epidermal function. These results suggest that improvements in epidermal function with topical emollients can prevent/attenuate the development of psoriasis.     

Investigation of the mechanisms of Genkwa Flos hepatotoxicity by a cell metabolomics strategy combined with serum pharmacology in HL-7702 liver cells

1. To investigate Genkwa Flos hepatotoxicity, a cell metabolomics strategy combined with serum pharmacology was performed on human HL-7702 liver cells in this study.

2. Firstly, cell viability and biochemical indicators were determined and the cell morphology was observed to confirm the cell injury and develop a cell hepatotoxicity model. Then, with the help of cell metabolomics based on UPLC-MS, the Genkwa Flos group samples were completely separated from the blank group samples in the score plots and seven upregulated as well as two down-regulated putative biomarkers in the loading plot were identified and confirmed. Besides, two signal molecules and four enzymes involved in biosynthesis pathway of lysophosphatidylcholine and the sphingosine kinase/sphingosine-1-phosphate pathway were determined to investigate the relationship between Genkwa Flos hepatotoxicity and these two classic pathways. Finally, the metabolic pathways related to specific biomarkers and two classic metabolic pathways were analyzed to explain the possible mechanism of Genkwa Flos hepatotoxicity.

3. Based on the results, lipid peroxidation and oxidative stress, phospholipase A₂/lysophosphatidylcholine pathway, the disturbance of sphingosine-1-phosphate metabolic profile centered on sphingosine kinase/sphingosine-1-phosphate pathway and fatty acid metabolism might be critical participators in the progression of liver injury induced by Genkwa Flos.     

Quantile regression and empirical likelihood for the analysis of longitudinal data with monotone missing responses due to dropout,with applications to quality of life measurements from clinical trials

The analysis of quality of life (QoL) data can be challenging due to the skewness of responses and the presence of missing data. In this paper, we propose a new weighted quantile regression method for estimating the conditional quantiles of QoL data with responses missing at random. The proposed method makes use of the correlation information within the same subject from an auxiliary mean regression model to enhance the estimation efficiency and takes into account of missing data mechanism. The asymptotic properties of the proposed estimator have been studied and simulations are also conducted to evaluate the performance of the proposed estimator. The proposed method has also been applied to the analysis of the QoL data from a clinical trial on early breast cancer, which motivated this study.