养血清脑颗粒对颅脑损伤后记忆障碍的影响

目的:评价养血清脑颗粒对颅脑损伤后记忆减退的治疗作用.方法:选择颅脑损伤后记忆减退患者130例,随机分为养血清脑颗粒治疗组和常规治疗加淀粉对照组.每组各65例,两组在常规治疗的基础上分别服养血清脑颗粒和淀粉每次4.0 g,3次·d-1,共4周,于治疗前和治疗4周后进行记忆商的测定,同时进行不良反应的观察.结果:按临床疗效标准.养血清脑颗粒组总有效率87.7%,对照组为40.3%,两组经统计学分析示有显著差异(P＜0.01).患者的记忆力提高.养血清脑颗粒组平均增值17±11分,对照组平均增值5±7分,两组间比较P＜0.01.养血清脑颗粒的不良反应较小.结论:养血清脑颗粒对颅脑损伤后的记忆减退有较好的恢复作用.     

脑出血患者NOX4表达与脑出血后脑水肿程度及功能预后的关系

目的探讨脑出血患者的血清NADPH氧化酶4（NOX4）表达水平与脑出血后脑水肿程度及功能预后的关系。 方法选取深圳市龙华区人民医院神经外科自2019年1月至2020年4月前来就诊的58例脑出血患者为脑出血组,测量脑出血量及发病后5 d的脑水肿量。选取同期的10名健康体检者为对照组。对脑出血组患者发病后1~6 h、3、5、7 d的血清NOX4水平与对照组进行比较。采用改良Rankin量表（mRs）评分、GOS评分、美国国立卫生研究院卒中量表、日常生活活动能力评分评估患者脑出血后6个月的神经功能,将脑出血患者根据mRs评分,分为预后良好组和预后不良组,分析脑出血患者预后相关的影响因素,进一步分析血清NOX4水平与预后的关系。 结果脑出血组在发病后1~6 h、3、5、7 d的血清NOX4水平与对照组相比均显著升高,差异有统计学意义（P<0.05）。预后不良组的NOX4表达水平、入院GCS评分、出血量、脑水肿量比例均高于预后良好组,差异均有统计学意义（P<0.05）。患者NOX4表达水平高、入院GCS评分低、脑出血量大、脑水肿量大是脑出血患者预后的影响因素。 结论NOX4可能是反映脑出血患者脑组织水肿程度、氧化应激和功能的潜在生物标志物,该细胞因子值得在脑出血背景下进一步研究。     

慢病毒介导的hTERT-shRNA联合光动力治疗对宫颈癌细胞SiHa的影响

目的：探讨慢病毒介导的人端粒酶逆转录酶（hTERT）联合四甲基吡啶卟啉（TMPyP4）及光动力疗法对宫颈癌细胞SiHa的影响。方法实验分4组：空白对照组、单纯基因治疗组、单纯光动力治疗组、联合治疗组。体外化学合成Lenti-hTERT-shRNA并转染SiHa细胞,确定最适感染复数（MOI）值,成功稳定转染后给予浓度为7．5μmol／L的TMPyP4行光动力治疗。RT-PCR法检测hTERT、p53、HPV-16 E6、Caspase-8 mRNA的表达;免疫荧光检测hTERT蛋白的表达;细胞增殖及细胞毒性（CCK-8）检测各组中人宫颈癌细胞SiHa的抑制作用;AnnexinV-PE／7-AAD双染试剂盒检测各组细胞的凋亡率;Transwell实验检测各组细胞侵袭能力的改变。结果与空白对照组比较,其他3组hTERT、HPV-16 E6、Caspase-8 mRNA的表达水平均下降,p53mRNA的表达水平升高,hTERT蛋白表达水平相应下降,其中联合治疗组最明显（P＜0．05）;联合治疗组较其他组明显抑制SiHa细胞的增殖（P＜0．05）;流式细胞学AnnexinV-PE／7-AAD和Transwell实验检测结果显示,联合治疗组较单纯基因治疗组和单纯光动力治疗组的凋亡率明显升高,细胞侵袭能力明显减弱（P＜0．05）。结论慢病毒介导的hTERT-shRNA联合光动力治疗明显抑制宫颈癌SiHa细胞的增殖和侵袭能力,并促进细胞凋亡。     

Diagnostic value of anti-cyclic citrullinated peptide antibodies in northern Chinese Han patients with rheumatoid arthritis and its correlation with disease activity

This study was to evaluate the diagnostic value of anti-cyclic citrullinated peptide (CCP) antibodies in northern Chinese Han patients with rheumatoid arthritis (RA) and its correlation with disease activity. Clinical data and serum samples were collected from 112 RA patients and 55 non-RA patients. Statistical analyses of the correlations among anti-CCP antibodies, other serological markers, and the RA patients’ clinical characteristics were performed using SPSS 11.5 software. Anti-CCP antibodies were detected in 77.7% of all RA patients and 80.4% of the RA patients with a disease duration of 3 years or less. The combined diagnosis using high titer anti-CCP antibodies (≥100 RU/ml) with a concomitant positive rheumatoid factor (RF) test exhibited the greatest diagnostic specificity; it achieved 87.9% for all RA patients and 90.1% for the patients with disease duration of three years or less. Moreover, anti-CCP antibodies showed medium correlations to the RA patient’s serum RF titer (r?=?0.560, P?<?0.001) and disease activity (DAS28 score; r?=?0.404, P?<?0.001). Compared with the patients with low anti-CCP antibody titers (<100 RU/ml), patients with high anti-CCP antibody titers showed higher RF titers, worse DAS28 scores, and severe morning stiffness (P?<?0.01). This study suggests that anti-CCP antibodies can be used for RA diagnosis and disease activity evaluation for northern Han Chinese patients. A combined diagnosis using both high titers of anti-CCP antibodies (≥100 RU/ml) and a positive RF test markedly improves RA diagnostic specificity. Patients’ DAS28 scores rise and morning stiffness intensifies with increasing anti-CCP antibody titers.     

辅助生殖技术子代出生缺陷的meta分析

目的评价辅助生殖技术(Assisted Reproductive Technology,ART)子代的出生缺陷状况。方法计算机检索中国学术期刊网络出版总库,维普中文科技期刊全文数据库,中国博士学位论文全文数据库,PubMed,EBSCO全文数据库,德国SPRINGER公司期刊数据库,和Cochrane Library等,并辅助其他检索方式,纳入ART术后妊娠和自然妊娠(Spontaneous Conception,SC)的子代出生缺陷状况比较的队列研究,并使用RevMan 5.0进行Meta分析。结果共纳入15个研究,出生儿共189376例。Meta分析结果显示:辅助生殖技术子代先天畸形率高于自然妊娠儿(P<0.05),其OR(95%CI)为1.32(1.22,1.43)。结论本研究结果表明,辅助生殖技术子代的出生缺陷的风险比自然妊娠儿高。因此,告知不孕患者ART的潜在风险是必要的。     

Pediatric reference intervals for bone markers

Bone markers are specific bone-derived molecules that reflect bone remodeling activity and can be classified into two categories: bone formation and bone resorption markers. Children have significantly elevated bone marker levels due to high skeletal growth velocity and rapid bone turnover during childhood growth. Many physiological and pathological processes may influence bone metabolism and bone marker concentrations during childhood growth. Measurements of bone markers may be useful in investigating skeletal diseases in children and monitoring the response to treatment. This review documents recent advances in analytical methods, preanalytical considerations related to each marker and particularly highlights the most valuable bone formation markers, bone alkaline phosphatase and osteocalcin, and bone resorption markers, pyridinium cross-links and cross-linked telopeptides. Age- and sex-specific pediatric reference intervals and their limitations in clinical application are also discussed.     

Cytotoxicity, DNA adduct formation and DNA repair induced by 2-hydroxyamino-3-methylimidazo[4,5-f]quinoline and 2-hydroxyamino-1-methyl-6-phenylimidazo[4,5-b]pyridine in cultured human mammary epithelial cells

2-Amino-3-methylimidazo[4,5-f]quinoline (IQ) and 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine(PhIP) are heterocyclic amines (HAs) found in cooked meats.Both compounds are mammary gland carcinogens in rats. The initiationof carcinogenesis by the HAs is believed to be associated withtheir DNA adduct formation that occurs after metabolic activationof the parent amines via cytochrome P-450-mediated N-hydroxylationand esterification. To assess the capacity of the human mammaryepithelium to metabolically activate the HAs, we used the ³²P-postlabelingmethod to measure the levels of DNA adducts in a culture ofhuman mammary epithelial cells exposed to IQ, PhIP or theirN-hydroxylamine metabolites. Whereas 50 µM parent aminesdid not form detectable levels of DNA adducts in cultured humanmammary epithelial cells after 24 h incubations, concentrationsas low as 1 µM N-hydroxylamines produced detectable levelsof adducts after 2 h incubations. N-Hydroxy-PhIP formed higheradduct levels than N-hydroxy-IQ at all concentrations tested.For example, following a 2 h incubation at 50 µM, adductlevels (per 10⁷ nucleotides) were 674 and 16 for N-hydroxy-PhIPand N-hydroxy-IQ, respectively. At similar initial adduct levels(10–11/10⁷ nucleotides), 60–80% of IQ- and PhIP—DNAadducts were removed after 24 h, indicating that the mammaryepithelial cell culture showed efficient repair of HA adducts.Whereas neither IQ nor PhIP was cytotoxic, both N-hydroxy-IQand N-hydroxy-PhIP were cytotoxic as assessed by a dose-dependentinhibition of colony formation. After exposure to 0.1, 1, 10or 50 µM N-hydroxy-PhIP (or N-hydroxy-IQ), colony formationwas 103 (94), 84 (74), 37 (29) and 3 (2)% of the control values,respectively. Only N-hydroxy-PhIP (at 10 and 50 µM), however,was cytotoxic as assessed by the MTT cell survival assay (whichmeasures the capacity of mitochondria to metabolize a tetrazoliumsalt). The ability of the N-hydroxylamines to form DNA adductsand to be cytotoxic in a culture of human mammary epithelialcells may implicate these metabolites as proximate carcinogenicforms of IQ and PhIP in the human mammary gland. However, whetherthere are inter-individual differences in N-hydroxylamine metabolism,adduct formation and repair in human mammary epithelial cellsrequires further study. The results from this study support the usefulness of culturedhuman mammary epithelial cells for studies on the genotoxicityand metabolism of the N-hydroxylamines of HA food mutagens.     

阿得贝利单抗联合化疗一线治疗广泛期小细胞肺癌的成本效果分析

目的 从中国医疗卫生体系角度评价阿得贝利单抗联合化疗对比化疗一线治疗广泛期小细胞肺癌的成本效果。方法 采用CAPSTONE-1临床试验所获数据(阿得贝利单抗组230例,化疗组232例),建立马尔可夫模型模拟广泛期小细胞肺癌疾病过程。分别计算每组的总成本、质量调整生命年(quality-adjusted life-years,QALYs)、增量成本效果比(incremental cost-effectiveness ratio,ICER)。对关键参数进行敏感性分析。结果 与单纯化疗方案(依托泊苷联合卡铂)相比,在考虑慈善援助的情景下,阿得贝利单抗联合化疗的ICER为157128.79元·QALY^-1,在不考虑慈善援助的条件下,阿得贝利单抗联合化疗的ICER为351367.27元·QALY^-1。敏感性分析结果显示效用值和阿得贝利单抗的价格是主要的影响因素。结论 阿得贝利单抗联合化疗方案对比单纯化疗方案治疗广泛期小细胞肺癌在中国现有的经济水平下不具有成本效果优势;考虑慈善赠药时,阿得贝利单抗联合化疗方案具有成本效果优势的概率为44.5%。     

Exploration for the effect of renal function and renal replacement therapy on pharmacokinetics of remdesivir and GS‐441524 in patients with COVID‐19: A limited case series

Remdesivir, an antiviral agent for the treatment of coronavirus disease 2019 (COVID‐19), is metabolized intracellularly, with these metabolites eliminated predominantly in urine. Because of a lack of safety and pharmacokinetic (PK) data, remdesivir is not currently recommended for patients with estimated glomerular filtration rate less than 30 ml/min/1.73 m² and those on hemodialysis. This study evaluated the PKs of remdesivir and its metabolite, GS‐441524, in patients with COVID‐19 who were and were not receiving renal replacement therapy (RRT). This study enrolled two patients with normal renal function, two with impaired renal function not receiving RRT, two receiving continuous RRT (CRRT), and three undergoing intermittent hemodialysis (IHD). Patients were administered 200 mg remdesivir on the first day, followed by 100 mg/day for 5–10 days. Serial blood samples were collected for PK analysis, and PK parameters were assessed by a noncompartmental method. Systemic exposure to remdesivir was higher in patients with impaired renal function and those receiving CRRT than in patients with normal renal function, but was similar in patients undergoing IHD and those with normal renal function. By contrast, systemic exposure to GS‐441524 was highest in patients undergoing IHD, followed by patients with impaired renal function and those receiving CRRT, and lowest in patients with normal renal function. The PK profiles of remdesivir and GS‐441524 varied according to renal function and RRT. The impact of PK changes of remdesivir and its metabolite on safety and efficacy should be considered when administering remdesivir to patients with COVID‐19 with renal impairment.

Study Highlights

• WHAT IS THE CURRENT KNOWLEDGE ON THE TOPIC?

Renal impairment can alter systemic exposure to remdesivir and its metabolites. Although the pharmacokinetics (PKs) of remdesivir and its metabolite have been assessed in patients with coronarvirus disease 2019 (COVID‐19) with reduced renal function, the use of remdesivir in patients with an estimated glomerular filtration rate less than 30 ml/min/1.73 m² and those on hemodialysis is still limited due to a lack of information.

• WHAT QUESTION DID THIS STUDY ADDRESS?

This study evaluated the effect of renal function and renal replacement therapy on the PKs of remdesivir and its metabolite, GS‐441524, in patients with COVID‐19.

• WHAT DOES THIS STUDY ADD TO OUR KNOWLEDGE?

Systemic exposure to remdesivir was higher in patients with impaired renal function and those receiving continuous renal replacement therapy (CRRT) than in patients with normal renal function, whereas exposure was similar in patients undergoing intermittent hemodialysis (IHD) and those with normal renal function. By contrast, systemic exposure to GS‐441524 was highest in patients undergoing IHD, followed by patients with impaired renal function and those receiving CRRT, and lowest in patients with normal renal function.

• HOW MIGHT THIS CHANGE CLINICAL PHARMACOLOGY OR TRANSLATIONAL SCIENCE?

The results of this study may enable remdesivir dosage selection for patients with COVID‐19 with renal impairment who have great demand for remdesivir use. Despite this study including a small number of patients, small‐sized studies have advantages, as their results can be generated and shared rapidly, especially during the COVID‐19 pandemic.