临床研究中,我们会经常遇到多重检验的问题。当同时检验多个假设时,如何控制犯Ⅰ类错误的概率,保证结果的准确性,是研究者面对的首要问题。然而未对多重检验进行校正的文章比例仍较大。本文从简单的单个检验假设出发,回答为什么需要进行多重校正,何时进行多重校正,同时介绍总体错误率(FWER)和错误发现率(FDR)两种重要的错误率以及在此基础上的Bonferroni和Benjamini-Hochberg校正方法,从而避免因多重检验问题带来的混乱。

In clinical research, we often encounter the problem of multiple testing. When testing many hypotheses at the same time, how to control the type I error to ensure the accuracy of the results is the primary problem faced by researchers. However, the proportion of articles that didn't correct the multiple testing remains substantial. Starting with the simple hypothesis of a single test, this article provides an introduction to multiple testing issues, answers why and when multiple corrections are needed, introduces two important error rates which are family-wise error rate (FWER) and false discovery rate (FDR), and the Bonferroni and Benjamini-Hochberg correction methods based on them, thereby avoiding confusion caused by multiple testing.

纳米材料作为一种新兴材料,在疾病诊断与治疗中拥有极大的应用潜力。为平衡纳米材料的生物活性和生物毒性之间的关系,清楚了解纳米材料在体内的清除机制和清除速率至关重要。其中,肾脏,作为人体重要的清除器官,直接影响纳米材料从血液清除到尿液的速率,进而影响其在生物体内的血液循环、肿瘤靶向效率和体内滞留等系列问题,最终影响其临床应用。基于近年来已报道的关于纳米材料与肾脏相互作用的诸多研究,本文系统介绍了肾脏结构、纳米材料在肾脏中的传输机制、理化性质对其肾脏清除效率的影响以及纳米材料在肾脏疾病诊疗中的应用。本文有望为精准纳米医学的发展以及纳米材料未来的临床转化起到促进作用。

Nanomaterials, as emerging materials, show great promise for the detection, diagnosis and treatment of diseases. Fully understanding their elimination pathway and clearance efficiency is important to better balance the bioactivity and biotoxicity of nanomaterials. Kidneys, as a major organ, play a key role in the clearance of nanomaterials from blood to urine. The clearance rate of nanomaterials in the kidneys directly affects their blood circulation, retention in the body and tumor targeting efficiency as well as final clinical applications. Based on current understanding of nano-bio interactions of nanomaterials in the kidneys, in this review, we introduced the kidney structure and elimination mechanism of nanomaterials in the kidneys. Then, how the physicochemical properties of nanomaterials affect their renal clearance efficiency are summarized. Finally, their applications in the kidney disease detection and treatment are presented. The basic understanding of nano-bio interactions of nanomaterials in the kidneys would promote the development of precise nanomedicine and their future clinical translation.

目的 观察超声心动图(UCG)+心肌损伤标志物水平检测在急性心肌梗死(AMI)患者诊断中的应用价值。方法 选取2020年6月—2021年9月我院收治的74例AMI患者为观察组,另选取同期65例疑似AMI患者为对照组,2组均进行UCG检测,并对比入院后0~2 h、2~12 h、12~24 h心肌损伤标志物[肌酸激酶同工酶(CK-MB)、氨基末端脑钠肽前体(NT-proBNP)、肌钙蛋白(cTnI)、心脏型脂肪酸结合蛋白(H-FABP)]水平,分析心肌损伤标志物与AMI病情程度的关联性及UCG+心肌损伤标志物水平检测对AMI诊断的应用价值。结果 UCG检查结果显示观察组阳性率86.79%高于对照组9.23%(P＜0.001);对照组入院后各时间段CK-MB、NT-proBNP、cTnI、H-FABP水平差异无统计学意义(P＞0.05)观察组入院后各时间段CK-MB、NT-proBNP、cTnI、H-FABP水平均高于对照组(P＜0.05);Spearman相关分析可知,血清CK-MB、NT-proBNP、cTnI、H-FABP水平与AMI患者病情程度呈正相关(r₁=0.648,r₂=0.692,r₃=0.704,r₄=0.683,P＜0.05);受试者工作特征曲线(ROC)曲线分析显示,UCG+血清CK-MB、NT-proBNP、cTnI、H-FABP联合检测对AMI患者的诊断敏感度(85.14%)、特异度(100.00%)较高(P＜0.05)。结论 UCG+心肌损伤标志物水平检测应用于AMI患者有利于提高诊断敏感度、特异度,诊断价值较高。

目的 比较宫腔镜下子宫内膜息肉切除术(TCRP)后采用地屈孕酮以及少腹逐瘀汤两种不同治疗方法对预防息肉复发的效果。方法 从北京中医药大学深圳医院(龙岗)妇科2019年1月—2020年7月间收治的子宫内膜息肉患者中随机选取150例作为研究对象,采取随机数字表法将患者随机分为对照组、地屈孕酮组和少腹逐瘀汤组,每组各50例。对照组患者实施TCRP治疗,地屈孕酮组实施TCRP+地屈孕酮治疗,少腹逐瘀汤组实施TCRP+地屈孕酮+少腹逐瘀汤治疗,术后对3组患者随访12个月,比较3组患者干预3、6、12个月息肉复发情况、子宫内膜厚度以及不良情况应发生率。结果 治疗第6、12个月时,地屈孕酮组及少腹逐瘀汤组复发率情况均低于对照组(P＜0.05),地屈孕酮组及少腹逐瘀汤组子宫内膜息肉复发率比较差异无统计学意义(P＞0.05)。少腹逐瘀汤组及地屈孕酮组3次复查子宫内膜厚度均小于对照组(P＜0.05);少腹逐瘀汤组治疗12个月时子宫内膜厚度小于地屈孕酮组(P＜0.05)。3组患者不良反应发生率比较,差异不具有统计学意义(P＞0.05)。结论 宫腔镜下息肉切除术后加服少腹逐瘀汤与地屈孕酮片对宫腔镜下子宫内膜息肉切除术后患者进行干预,可有效降低患者子宫内膜息肉复发率,促进患者术后月经恢复正常,且将两者联合应用疗效安全,具有较高的应用价值。

目的 探讨低强度体外冲击波联合本体感觉训练治疗双侧颞下颌关节紊乱病的临床疗效。方法 给予1例双侧颞下颌关节紊乱病半年余患者低强度体外冲击波联合本体感觉训练治疗2周,比较治疗前、治疗2周后的最大张口度(MIO)、疼痛压力阈值(PPT)和Fricton颞下颌关节紊乱指数量表 (CMI),并于2个月后随访。结果 经过2周治疗,MIO、PPT和CMI均出现明显改善,2个月后随访未出现反弹,持续改善。结论 低强度体外冲击波联合本体感觉训练治疗颞下颌关节关节紊乱病临床疗效显著。

Objective To investigate the clinical efficacy of low intensity extracorporeal shock wave combined with proprioceptive training in the treatment of bilateral temporomandibular disorders (TMD). Methods A patient with bilateral TMD was treated with low intensity extracorporeal shock wave combined with proprioceptive training for 2 weeks.The maximal interincisal opening (MIO)、pain pressure thresholds (PPT), and Fricton's craniomandibular index (CMI) were compared before and after treatment,and followed up for 2 months. Results After 2 weeks of treatment, MIO, PPT and CMI were significantly improved, and there was no relapse after 2 months of follow-up. Conclusions Low intensity extracorporeal shock wave combined with proprioceptive training was effective in treating TMD.

目的 观察百令胶囊辅助缬沙坦治疗IgA肾病效果及对患者肾功能、细胞免疫调节、尿足细胞标志蛋白的影响。方法 选取2019年5月—2021年5月西部战区总医院肾内科收治经肾活检确诊为IgA肾病,筛选治疗方案中尚未使用激素及免疫抑制剂的80例患者,按住院先后顺序随机分为观察组和对照组,每组各40例。对照组给予缬沙坦治疗,观察组给予百令胶囊辅助缬沙坦治疗,治疗12周后,比较2组的疗效、治疗前后肾功能指标[24 h蛋白尿(24 h Upro)、尿素氮(BUN)、血肌酐(SCr)、尿红细胞(RBC)计数]、1型/2型辅助性T细胞(Th1/Th2)代表细胞因子[γ-干扰素(IFN-γ)、白介素-4(IL-4)]、尿足细胞标志蛋白[尿足萼糖蛋白(PCX)、尿足细胞B7-1分子(B7-1)]水平。结果 治疗12周后,观察组的治疗总有效率为95.0%,高于对照组的82.5%;观察组的24 h Upro、BUN、SCr、尿RBC计数低于对照组,IFN-γ、Th1/Th2低于对照组、IL-4高于对照组,尿PCX、B7-1水平低于对照组;差异均有统计学意义(P<0.05)。结论 百令胶囊辅助缬沙坦治疗IgA肾病患者,可以提高临床疗效,有效保护患者肾功能,调节其免疫状态,减轻肾损伤。

Objective To observe the effects of Bailing capsules assisting valsartan in the treatment of IgA nephropathy and its influence on renal function, cellular immune regulation and urine prodocytes marker protein. Methods From May 2019 to May 2021, 80 patients with IgA nephropathy confirmed by renal biopsy in the Nephrology Department of Western Theatre Command General Hospital, who had not used hormones or immunosuppressants in the treatment were selected.Patients were divided into observation group and control group according to the order of hospitalization, 40 cases in each group.The control group was given valsartan, and the observation group was given Bailing capsules and valsartan.After 12 weeks of treatment, the efficacy, the levels of renal function indexes [24 h proteinuria (24 h Upro), urea nitrogen (BUN), serum creatinine (SCr), urinary red blood cell (RBC) count], type 1/type 2 helper T cells (Th1/Th2) represent cytokines [interferon-γ (IFN-γ), interleukin-4 (IL-4)], urine prodocytes marker protein [urine podocalyxin (PCX), urinary podocyte B7-1 molecule (B7-1)] before and after treatment were compared between the two groups. Results After treatment, the total effective rate in observation group was higher than that in control group (95.0% vs 82.5%).The 24 h Upro, BUN, SCr levels and urine RBC count in observation group were lower than those in control group, IFN-γ and Th1/Th2 levels were lower than those in control group, the IL-4 level was higher than that in control group, and the levels of urine PCX and B7-1 were lower than those in control group.Those differences were statistically significant (P<0.05). Conclusions Bailing capsules assisting valsartan in the treatment of IgA nephropathy can improve clinical efficacy, effectively protect the renal function of patients, regulate the immune status, and alleviate renal injury.

目的 探讨暴露喉返神经的甲状腺手术后患者发生声音嘶哑的原因。方法 选取于2019年1月—2020年12月间在我院接受甲状腺手术且在术中暴露喉返神经的患者,对出现术后声音嘶哑的19例患者进行为期12个月的临床随访,观察研究对象术后声音嘶哑的发生特点、持续时间并进行直接喉镜及颈部超声检查。结果 发生声音嘶哑的19例患者中,5例存在术中喉返神经损伤情况,其余14例患者术中喉返神经暴露及保护良好。直接喉镜检查示,该14例患者中,4例存在声带充血水肿现象,1例发生勺状软骨半脱位。术后1周左右的超声检查显示,该14例患者中有11例存在不同程度的创腔内积液。结论 虽常规暴露喉返神经减少了术后声嘶的发生率,但术中喉返神经损伤仍然是造成患者术后声嘶的原因之一。此外,术后创腔积液、麻醉插管导致的声带损伤及其他插管相关并发症等非直接手术因素也是造成这些患者术后声嘶的重要原因,应引起临床重视。

Objective To explore the cause of hoarseness of voice in patients after thyroidectomy with recurrent laryngeal nerve exposure. Methods The patients from January 2019 to December 2020 underwent thyroidectomy with exposure of recurrent laryngeal nerve during operation were selected. There were 19 cases of hoarseness of voice after operation followed up for 12 months. Postoperative observations included the characteristics of the hoarseness of voice, duration, and direct laryngoscope neck ultrasonography. Results A total of 19 patients had voice hoarseness, only 5 of them had recurrent laryngeal nerve injury during operation, the other 14 patients had good exposure and protection of recurrent laryngeal nerve. Direct laryngoscope showed that 4 of 14 patients had vocal cord edema and 1 had subluxation of arytenoid cartilage. About 1 week after operation, ultrasound examination showed that 11 of 14 patients had varying degrees hydrops of wound cavity. Conclusions Although the routine exposure of recurrent laryngeal nerve reduces the incidence of postoperative hoarseness of voice, the injury of recurrent laryngeal nerve is still a cause of postoperative hoarseness of voice. In addition, non-operative direct factors, such as fluid accumulation in the operative field, vocal cord injury caused by anesthetic intubation and other intubation related complications, are also important reasons for postoperative hoarseness of voice in these patients, which we should pay more attention to.

目的 探索胸部CT值在胸腔积液鉴别诊断的价值。方法 81例胸腔积液患者纳入本研究,胸腔积液分为渗出液、漏出液、恶性胸腔积液及良性胸腔积液。建立平均CT值的ROC曲线,计算曲线下面积。结果 81例胸腔积液患者中59例为渗出液,22例为漏出液;恶性胸腔积液33例,良性胸腔积液48例。渗出液组平均CT值(16.68±6.76)Hu高于漏出液组(5.50±3.42)Hu(P<0.000 1)。ROC曲线分析结果显示,胸腔积液平均CT值对区分渗出液和漏出液具有较高的准确性(曲线下面积为0.944 5)。当最佳界值为≥9.99 Hu时,其敏感度为88.14%,特异度为90.91%;恶性胸腔积液组平均CT值(15.38±7.29)Hu与良性胸腔积液组平均CT值(12.45±8.03)Hu没有差异(P=0.098 1)。结论 在胸腔积液的鉴别诊断过程中,胸部CT的CT值在鉴别漏出液及渗出液中有一定的价值,但尚不能用于鉴别良性及恶性胸腔积液。

Objective To explore the value of chest CT value in the differential diagnosis of pleural effusion. Methods A total of 81 patients with pleural effusion were included in this study, including exudate, transudate, malignant pleural effusion and benign pleural effusion.The ROC curve of average CT value was established and the area under the curve was calculated. Results Among 81 patients with pleural effusion, 59 cases were exudative, 22 cases were transudative, 33 cases were malignant pleural effusion and 48 cases were benign pleural effusion.The mean CT value of the exudate group, (16.68±6.76) Hu, was significantly higher than (5.50±3.42) Hu of the transudate group (P<0.000 1).ROC curve analysis showed that the mean CT value of pleural effusion had high accuracy in distinguishing exudate from transudate (area under the curve was 0.9445).When the cut-off value for exudative effusion was over 9.99 Hu, the sensitivity and specificity were 88.14% and 90.91%, respectively.The mean CT value of malignant pleural effusion group, (15.38±7.29) Hu, was not significantly different from (12.45±8.03) Hu of benign pleural effusion group (P=0.098 1). Conclusions In the differential diagnosis of pleural effusion, the chest CT value can be used to identify transudate and exudate, but not benign and malignant pleural effusion.

目的 探究腔内微波消融(EMA)联合泡沫硬化剂治疗与腔内射频消融(RFA)联合泡沫硬化剂治疗下肢静脉曲张的临床疗效和并发症情况。方法 回顾性选择收集106例下肢静脉曲张患者的临床资料,其中54例患者(观察组)接受EMA联合泡沫硬化剂治疗,52例患者(对照组)接受RFA联合泡沫硬化剂治疗。比较2组患者相关临床指标及并发症发生情况。结果 观察组手术时间(34.92±2.35)min,对照组手术时间(46.33±2.71)min,观察组手术时间较短,差异有统计学意义(P＜0.05),其余手术参数差异不明显(P＞0.05)。观察组的住院费用(21 063.74±850.47)元,对照组住院费用(23 312.40±1 035.86)元,观察组住院费用较低,有统计学差异(P＜0.05)。2组间并发症发生率、总有效率和总满意度均无显著差异。对比2组患者手术前和手术治疗后1年的静脉临床严重程度评分、阿伯丁静脉曲张问卷评分,组间对比没有统计学差异(P＞0.05);而在患者手术1年之后的静脉临床严重程度评分、阿伯丁静脉曲张问卷评分均呈现出明显的下降趋势(P＜0.05)。结论 微波消融是有效治疗下肢静脉曲张的术式,与射频消融比较,具有同样良好的短期效果;微波消融所需的手术时间较短且费用较低。

Objective To compare the clinical efficacy and complications between endovascular microwave ablation (EMA) combined with foam sclerotherapy and radiofrequency ablation (RFA) combined with foam sclerotherapy in patients with varicose veins of lower extremity. Methods A total of 106 patients with varicose veins of lower extremity were included in the retrospective study.Among them, 54 patients (observation group) were treated with EMA combined with foam sclerotherapy, and 52 patients (control group) were treated with RFA combined with foam sclerotherapy.The related clinical indexes and complications between the two groups were compared. Results The observation group had a shorter procedure time than the control group (34.92±2.35 minutes vs 46.33±2.71 minutes, P＜0.05), and no significant differences were observed in the other procedure parameters.The hospitalization cost was (21063.74±850.47) yuan for the observation group and (23312.40±1035.86) yuan for the control group, and the hospitalization cost of the observation group was lower(P＜0.05).No significant differences were found in the total effective rate,total satisfaction and complication rate between the two groups.Comparison of venous clinical severity score (VCSS) and Aberdeen varicose vein questionnaire (AVVQ) scores before and one year after operation between the two groups showed no statistical differences (P＞0.05). While the VCSS and AVVQ scores of the patients showed a significant downward trend one year after operation (P＜0.05). Conclusions Microwave ablation is an effective treatment for varicose veins in the lower extremity, which has the same good short-term effect as radiofrequency ablation. Microwave ablation requires a shorter operation time and less cost.

目的 研究白藜芦醇通过抑制T样受体4/核因子-κB(TLR4/NF-κB)通路对呼吸道合胞病毒(RSV)毛细支气管炎小鼠的保护作用。方法 选取30只小鼠随机分为对照组、RSV组、给药组,建立RSV毛细支气管炎小鼠模型,检测小鼠肺组织中TLR4、NF-κB的变化;利用肺组织HE染色、ELISA法检测白藜芦醇给药前后气道炎症病变、IL-6、TNF-α因子水平,Western Blot法及实时定量PCR法检测TLR4、 NF-κB蛋白及基因表达等相关变化。结果 与对照组相比,RSV组小鼠组肺组织中TLR4、NF-κB水平升高,肺组织切片HE染色显示气道炎症细胞浸润加剧,ELISA检测炎性因子IL-6、TNF-α升高;而给药组处理后,肺组织TLR4、NF-κB的表达下调,病理改变减轻,炎性因子IL-6、TNF-α下降。结论 白藜芦醇可通过抑制TLR4/NF-κB通路抑制炎性因子的释放,从而减轻毛细支气管炎小鼠的气道炎症反应。

Objective To study the protective effect of resveratrol on lung tissue of respiratory syncytial virus(RSV) bronchiolitis mice by regulating TLR4/NF-κB pathway. Methods Thirty mice were randomly divided into control group, RSV group and resveratrol group. The mice models of RSV bronchiolitis were established, and the changes of TLR4 and NF-κB levels in lung tissues of mice were detected. HE staining and ELISA were used to detect airway inflammation, IL-6 and TNF-α levels before and after resveratrol administration. TLR4 and NF-κB protein and gene expressions were detected by Western Blot and real-time quantitative PCR. Results Compared with the control group, the levels of TLR4 and NF-κB in the lung tissues of mice with bronchiolitis were significantly increased. Airway inflammatory cell infiltration was aggravated in HE staining of lung tissue sections, and inflammatory factors IL-6 and TNF-α were significantly increased showing by ELISA. The expressions of TLR4 and NF-κB in resveratrol group were down-regulated after treatment. Conclusions Resveratrol can inhibit the release of inflammatory factors by inhibiting the TLR4/NF-κB pathway, play a protective role in mice with bronchiolitis.