前列腺增生症患者膀胱逼尿肌超微结构的研究

目的：探讨前列腺增生症(BPFI)患者(BPH组)膀胱逼尿肌超微结构的改变。方法：对15例BPH患者和6例无膀胱颈梗阻老年人(无BOO组)膀胱逼尿肌进行透射电镜观察。结果：无BOO组膀胱逼尿肌呈退行性变，肌细胞间隙增宽，细胞中间连接减少，细胞间隙中有胶原纤维分布。BPH组逼尿肌细胞外形肥大，扭曲变形，胞浆内空泡形成，密体明显减少，细胞中间连接减少甚至消失，细胞间隙明显增宽，内含较多的胶原及弹性蛋白。尤其慢性尿潴留患者改变更为显著。结论：逼尿肌超微结构的改变导致BPH患者膀胱排空障碍，对BPH患者的预后评估具有一定的意义。     

前列腺增生症所致膀胱出口梗阻患者逼尿肌中神经生长因子mRNA的变化及意义

目的　探讨前列腺增生症 (BPH)所致膀胱出口梗阻 (BOO)患者膀胱逼尿肌中神经生长因子 (NGF)mRNA的表达变化及意义。方法　对同龄对照组 8例膀胱癌患者、BPH梗阻逼尿肌稳定组 2 4例患者和BPH梗阻逼尿肌不稳定组 16例患者的膀胱壁逼尿肌组织 ,采用逆转录聚合酶链反应(RT PCR)检测膀胱逼尿肌细胞中NGFmRNA的表达。结果　NGFmRNA在同龄对照组、BPH梗阻逼尿肌稳定组和梗阻逼尿肌不稳定组患者的膀胱逼尿肌细胞中均有表达 ,三组患者的平均表达水平两两之间差异均有显著性意义 (P <0 0 1) ,而且NGFmRNA在同龄对照组、BPH梗阻逼尿肌稳定组和梗阻逼尿肌不稳定组的平均表达水平逐渐增加。结论　前列腺增生症引起膀胱出口梗阻后 ,膀胱逼尿肌细胞中NGFmRNA表达水平增高 ,并可能与逼尿肌不稳定 (DI)的发生有关。     

良性前列腺增生症尿动力学检查的意义

目的:探讨尿动力学检查对良性前列腺增生症（BPH）治疗的意义。方法：通过对48例BPH患者的尿动力学检查,发现3例无膀胱出口梗阻（BOO）,6例可疑BOO,39例有不同程度的BOO,并发逼尿肌不稳定（DI）9例,逼尿肌收缩无力（逼尿肌收缩为W－以下）5例,高顺应性膀胱2例,低顺应性膀胱6例。结果：根据检查结果分别采用TURP或耻骨后前列腺开放切除术、耻骨上膀胱穿刺造瘘加药物治疗一段时间后再手术、药物治疗三种方法,取得较好的效果。结论：尿动力学检查是判定BPH患者是否需要手术治疗的客观量化指标,引流尿液及使用新斯的明和加兰他敏是治疗逼尿肌收缩无力的有效方法。     

The significance of the American Urological Association symptom index score in the evaluation of women with bladder outlet obstruction

PURPOSE: The American Urological Association (AUA) symptom index was originally designed to assess the severity of lower urinary tract symptoms in men with benign prostatic hyperplasia. Data concerning the clinical application of the AUA symptom index to women are sparse. We evaluated the significance of the AUA symptom index in women with urodynamically defined bladder outlet obstruction. MATERIALS AND METHODS: From a urodynamic database of 587 consecutive women 38 (6.5%) were identified with bladder outlet obstruction, defined as a maximum flow rate of less than 12 ml. per second on repeat noninvasive uroflowmetry studies with a detrusor pressure at a maximum flow of greater than 20 cm. water on pressure flow study. All patients underwent a complete clinical and urodynamic evaluation, and completed the AUA symptom index questionnaire. Results in women with urodynamic obstruction were compared with those in 2 control groups, including women without obstruction but with sphincteric incontinence and asymptomatic healthy women. RESULTS: Mean symptom score was significantly higher in women with obstruction than in those with sphincteric incontinence or no symptoms (15.8+/-8.4 versus 10.3+/-6.4 and 2.1+/-2.7, respectively). Likewise, scores were classified as severe in 34% of women with obstruction compared with only 7% of those with sphincteric incontinence. However, no correlation was noted between symptom index scores and objective urodynamic parameters, which is similar to data already reported in male populations. CONCLUSIONS: The AUA symptom index score may be useful as a bothersomeness index in women with bladder outlet obstruction. However, subjective symptoms associated with bladder outlet obstruction are nonspecific and a complete urodynamic evaluation is essential for making the diagnosis.     

Mirabegron for Male Lower Urinary Tract Symptoms

Benign prostatic hyperplasia (BPH) is a common cause of lower urinary tract symptoms (LUTS) in men. Patients with BPH often present with a combination of obstructive and overactive bladder (OAB) symptoms. It is postulated that bladder outlet obstruction (BOO) from BPH results in concomitant OAB symptoms through ischemic induced variations in the response to neurotransmitters of both the detrusor and the urothelium. This altered response leads to the pathologic activation of the micturition reflex, generating sensory dysfunction and involuntary bladder contractions. Alpha-1 adrenoceptor antagonists (alpha-blockers) and 5-alpha reductase inhibitors (5-ARIs) are commonly used to treat the BOO caused by BPH. Anticholinergic agents are frequently used to treat concurrently OAB symptoms caused by the BOO. Unfortunately, anticholinergic medications demonstrate bothersome side effects and a theoretical risk of urinary retention. Basic science and clinical research has led to the development of a new class of pharmaceuticals for the treatment of overactive bladder with diminished risk of urinary retention and lacking many anticholinergic side effects. This novel compound, mirabegron (Mybertriq, Astellas Pharma US, Inc.), is a β₃-adrenoceptor agonist and represents a promising new class of oral agents designed for the treatment of OAB symptoms, with minimal effect on voiding.     

Surgery (TUR-P) as a recommended initial treatment modality for the presented case

The pathophysiology of lower urinary tract dysfunction in the presented case comprised voiding dysfunction and overactive bladder. Two etiologies for voiding dysfunction in this case could be considered, bladder outlet obstruction due to benign prostatic hyperplasia (BPH) or detrusor underactivity. Prospected efficacies of pharmacological and surgical treatment (transurethral resection of prostate: TUR-P) for this case were compared based on a literature review. Alpha-1 blockers improve both voiding and storage symptoms in patients with BPH. However, improvement of maximum flow rate (Qmax) on uroflowmetry is limited within a small range and there is no evidence of significant reduction in residual urine volume. Alpha-1 blockers have no significant efficacy in improvement of objective measures in patients with detrusor underactivity. Although anticholinergics improve overactive bladder symptoms, they are contraindicated for patients with severe voiding dysfunction with residual urine. There is a lack of study on efficacy of apha-1 blocker administration combined with anticholinergics available in our hands for patients with BPH and overactive bladder. On the other hand, TUR-P brings remarkable improvement in voiding and storage symptoms, increase of flow rate and reduction of residual urine as a gold-standard surgical treatment for BPH. Urge incontinence and uninhibited detrusor contraction on cystometry reportedly disappeared in 60% of patients following TUR-P. TUR-P also improves subjective symptom and objective measures in patients with BPH and detrusor underactivity. Based on the literature review, surgery is recommended as a standard initial therapy for the presented patient with significant voiding dysfunction (Qmax 9.4 ml/sac and residual urine 72 ml).     

Defining female voiding dysfunction: ICI-RS 2011

Whilst symptoms of bladder outlet obstruction (BOO) and post micturition symptoms are more commonly reported in men a significant number of women may also complain of voiding dysfunction. However, despite the recent advances in the standardisation of terminology of lower urinary tract dysfunction there remains a lack of consensus regarding a precise diagnosis and definition of voiding abnormalities in women. In addition voiding symptoms may co-exist with storage symptoms as well as those associated with urinary incontinence. Consequently many patients present with a spectrum of different urinary symptoms, related to both storage and voiding, which may be multifactorial in origin or be related to one another. The purpose of this paper is to review the current literature in order to accurately define and classify female voiding dysfunction including causes and aetiology. In addition to reviewing the investigation and management of those women with voiding dysfunction recommendations are proposed for management in clinical practice as well as suggestions for future research.     

排尿期尿道测压在BPH中的应用价值

目的探讨前列腺增生症（ＢＰＨ）致膀胱流出道梗阻（ＢＯＯ），及其相关问题。方法采用排尿期尿道测压（ＭＵＰＰ）检测４３例ＢＰＨ患者，以压力下降梯度（ＭＵＰＰＧ）计算梗阻程度，同时行膀胱等容收缩试验测最大逼尿肌等容收缩压（Ｐｉｓｏ）；进行国际前列腺症状评分（ＩＰＳＳ），经腹壁Ｂ超测前列腺体积（Ｖ）。结果４３例ＢＰＨ中３８例存在ＢＯＯ（８８％），梗阻位于膀胱颈部２８例（７７％）；ＭＵＰＰＧ与ＩＰＳＳ、Ｖ、Ｐｉｓｏ呈正相关。结论ＭＵＰＰ能检测并计算ＢＯＯ程度；ＢＯＯ是ＢＰＨ的病理基础，临床症状、逼尿肌代偿与其相关。     

Correlation of the AUA symptom index with urodynamics in patients with suspected benign prostatic hyperplasia

The AUA symptom index is widely used to access patients with suspected benign prostatic hyperplasia (BPH). In order to determine how well symptoms as assessed by this index correlate with urodynamic findings, we evaluated 83 patients referred to our urology clinics with symptoms of BPH. All patients completed the AUA symptom index and then underwent a multichannel urodynamic evaluation. Patients were classified as obstructed, unobstructed, or equivocal according to the Abrams Griffiths nomogram. The AUA symptom index was recorded as the total score and, for purposes of symptom classification, further subdivided into an obstructive score (questions 3, 5, and 6) and an irritative score (questions 1, 2, 4, and 7). The mean age of the 83 patients was 67 (45–84). The mean total AUA symptom score was 16.6 (6–34), mean obstructive score was 6.1 (0–15), and the mean irritative score 10.4 (3–20). Pressure flow analysis using the Abrams-Griffiths nomogram classified 28 patients (34%) as obstructed, 17 (20%) as unobstructed, and 38 (46%) as equivocal. Using the analysis of variance procedure (ANOVA) there was no statistically significant difference in the mean total (P = 0.446), obstructive (P = 0.979), or irritative (P = 0.136) scores. Detrusor instability was present in 45 patients (54%). While total and obstructive scores were not significantly different in patients with detrusor instability vs. those with stable bladders, irritative scores were higher in patients with instability (P = 0.028) using the T-test procedure. Using ANOVA, the difference in post void residual (PVR) between the groups was not quite statistically significant (P = 0.057). The AUA symptom score does not appear to correlate with urodynamic obstruction. However, higher irritative symptom scores are associated with detrusor instability. It is likely that in many men with “BPH,” symptoms are not caused by outlet obstruction and may be related to changes in the aging bladder. © 1994 Wiley-Liss, Inc.     

良性前列腺增生患者逼尿肌功能的评估和治疗对策

目的　为了解良性前列腺增生（BPH）患者产生下尿路症状的成因,为正确诊治下尿路症状提供准确的证据。　方法　采用尿动力学方法分析无神经系统疾病的良性前列腺增生患者的膀胱尿道功能。　结果　164例良性前列腺增生患者,平均年龄67±7.04岁,膀胱出口梗阻者占61.6％（101/164）,无梗阻者占38.4％（63/164）;逼尿肌收缩力正常者为83%（136/164）,逼尿肌收缩力减弱者17％（28/164）,以上各组之间I-PSS评分和年龄无显著性差异。膀胱出口无梗阻者中逼尿肌收缩力减弱者占44.4%（28/63）,逼尿肌收缩力正常占55.6％（35/63）。在膀胱出口无梗阻者中,逼尿肌收缩力减弱合并不稳定膀胱患者为28.6％（8/28）,而逼尿肌收缩力正常合并不稳定膀胱患者57.1％（20/35）,膀胱出口无梗阻逼尿肌收缩力减弱合并不稳定膀胱患者明显少于膀胱出口无梗阻逼尿肌收缩力正常者（P＜0.02）,两组患者I-PSS评分和膀胱顺应性均无明显差异。　结论　BPH患者下尿路症状的产生不仅与前列腺增生引起的膀胱出口梗阻有关,部分患者并不存在膀胱出口梗阻,其下尿路症状的成因为逼尿肌功能变化所致,尿动力学检查能为下尿路症状患者的诊治提供可靠的依据。     

BPH梗阻致膀胱功能改变的尿动力学研究

为探讨前列腺增生症（ＢＰＨ）梗阻致膀胱功能改变的临床意义，对５９例ＢＰＨ病人进行全面尿动力学检查。结果：（１）最大逼尿肌等容收缩压（Ｐｉｓｏ）与逼尿肌收缩速度呈正相关（ｒ＝０．７１６７，Ｐ＜０００１）。（２）Ｐｉｓｏ随膀胱充盈量增加而显著下降（Ｐ＜０００１）。（３）Ｐｉｓｏ与ＢＰＨ梗阻程度呈正相关性（ｒ＝０．６７８１，Ｐ＜０００１）。（４）当剩余尿量≥１００ｍｌ，逼尿肌储能显著下降（Ｐ＜０００１）。（５）不稳定膀胱组的Ｐｉｓｏ显著高于稳定膀胱组。结果认为：不稳定膀胱是引起ＢＰＨ病人临床症状的主要因素之一，膀胱等容收缩试验应用于ＢＰＨ病人有重要的临床价值     

前列腺增生患者膀胱出口梗阻程度对尿动力学指标的影响

目的探讨前列腺增生患者膀胱出口梗阻程度对尿动力学指标的影响及临床意义。方法分析113例前列腺增生患者的尿动力学资料,根据膀胱出口有无梗阻分为梗阻组和非梗阻组,梗阻组又根据梗阻级别分Ⅲ、Ⅳ、Ⅴ、Ⅵ级四组。结果梗阻组的最大尿流率、膀胱顺应性值和逼尿肌收缩力减弱发生率明显低于非梗阻组,逼尿肌不稳定和急性尿潴留发生率明显高于非梗阻组。梗阻组内各梗阻级别之间在顺应性值、逼尿肌不稳定和急性尿潴留的发生率上无显著性差异,随梗阻级别增加尿流率和逼尿肌收缩功能受损发生率下降。结论一些反映排尿异常和逼尿肌功能的尿动力学指标受膀胱出口梗阻程度影响,在无法进行压力/流率分析时综合分析这些指标有助于判断出口梗阻及其程度。     

The International Prostate Symptom score in both sexes: a urodynamics-based comparison.

The aim of our study was to determine the urodynamic basis for the observation that aging women report comparable benign prostatic hyperplasia (BPH) symptom scores as age-matched men. Sixty-seven women (mean age, 60.4 +/- 1.5 years; mean +/- standard error of the mean) and 70 age-matched men (mean age, 63.7 +/- 0.9 years; P > 0.05) entered this prospective study. Men were referred for the diagnostic workup of lower urinary tract symptoms (LUTS) due to BPH and women predominantly for urinary incontinence. All patients completed the International Prostate Symptom score (IPSS) with quality-of-life assessment and underwent a detailed clinical and urodynamic evaluation including a multichannel pressure-flow study. Results of the IPSS, quality-of-life assessment, and irritative and obstructive component of the IPSS were correlated with urodynamic findings and the respective data were compared in both sexes. The mean IPSS was 15.7 for men and 13.0 for women (P = 0.02), quality-of-life score was higher in women (4.2 vs. 3.4; P = 0.0008). The irritative score was significantly higher in women (8.7 vs. 6.8; P = 0.003). Incidence of detrusor instability (DI), however, was higher in men (women, 38.1%; men, 48.6%; P = 0.015) and bladder capacity was higher in women (425 vs. 333 ml; P = 0.0001). There was no correlation between incidence and degree of DI with the irritative score in both sexes. The obstructive score was significantly higher in men (8.8 vs. 4.4; P = 0.0001). Ninety-one percent (64/70) of men had urodynamically documented bladder outlet obstruction (BOO), whereas this was the case in only 9% (6/67) of women. In parallel to the irritative score, we could not identify a correlation between the degree of urodynamically proven BOO and the obstructive score in both sexes. This urodynamics-based comparison fails to give an explanation for the observation that aging women report similar BPH scores as men. These data suggest that other mechanisms, such as changes in diurnal urine production, structural alterations of the aging detrusor, endocrine disturbances affecting lower urinary tract function, and subtle urodynamic changes are responsible.     

Urodynamic analysis in 245 patients with benign prostatic hypertrophy

To study the mechanism of voiding disorder and promote thediagnosic accuracy of bladder outlet obstruction (BOO), a full setof urodynamic examination were employed with self-made semi-supine bed and Manneu Danec Urodynamic device in 245 patients.The results showed definite BOO in 161 cases, doubtful BOO in 50cases, detrusor muscle dysfunction in 65 cases, depressed bladdercompliance in 70 cases, urethral sphincter dyssynergia in 114 cas-es , and unstable bladder in 59 cases. There is a close relationshipbetween the functional urethral length and the prostatic urethrallength as determined by B ultrasound. It suggests that both the dy-namic and mechanical factors are attributed to voiding disorder inpatients with BPH. The urodynamic examination plays an importantrole in the diagnosis of BOO. (Chin J Androl 2000; 4: 234 - 236)     

良性前列腺增生患者膀胱出口梗阻和逼尿肌功能的分析

目的：探讨尿动力学检查对BPH患者膀胱出口梗阻（BOO）和逼尿肌功能的诊断意义.方法：对95例BPH患者进行压力-容积和压力-流率测定.结果：95例BPH患者中BOO 57例,无BOO23例,其余15例为可疑或分析困难.BOO组前列腺体积大于无BOO组（62.4±16.1）cm^3 vs（41.0±7.1）cm^3（P＜0.05）,最大尿流率（Qmax）小于无BOO组（5.4±1.9）ml/s vs（12.4±5.0）ml/s（P＜0.05）,两组IPSS评分无差别（23.7±4.4）分vs（25.2±4.9）分（P＞0.05）.BOO组有逼尿肌不稳定收缩（DD34例,无BOO组D119例.结论：尿动力学检查有助于判断有无BOO存在,了解BPH患者的逼尿肌功能.IPSS不能判断患者的下尿路症状（LUTS）是否因BOO导致.BPH患者前列腺体积不足很大,但LUTS明显时,应行尿动力学检查.自由尿流率测定对BOO诊断有一定帮助.DI是无BOO患者发生LUTS的重要因素.     

DETRUSOR INSTABILITY IN MEN: CORRELATION OF LOWER URINARY TRACT SYMPTOMS WITH URODYNAMIC FINDINGS

PURPOSE: We evaluated the correlation of lower urinary tract symptoms suggestive of detrusor instability with urodynamic findings in men. MATERIALS AND METHODS: Enrolled in our prospective study were 160 consecutive neurologically intact men referred for urodynamic evaluation of persistent lower urinary tract symptoms. All patients had storage symptoms suggestive of detrusor instability. Patients were further clinically categorized according to the chief complaint of urge incontinence, frequency and urgency, nocturia or difficult voiding. The clinical and urodynamic diagnosis in all patients as well as specific urodynamic characteristics of those with detrusor instability were analyzed according to the these 4 clinical categories. RESULTS: Mean patient age was 61 +/- 15 years. The chief complaint was urge incontinence in 28 cases (17%), frequency and urgency in 57 (36%), nocturia in 30 (19%) and difficult voiding in 45 (28%). Detrusor instability was diagnosed in 68 cases (43%). A higher incidence of detrusor instability was associated with urge incontinence than with the other clinical categories (75% versus 36%, p <0.01). Of the patients 109 (68%) had bladder outlet obstruction, including 50 (46%) with concomitant detrusor instability. The prevalence of bladder outlet obstruction was similar in all patients regardless of the chief complaint. All other urodynamic diagnoses were also similar in the 4 clinical categories. The mean bladder volume at which involuntary detrusor contractions occurred were lower in patients with urge incontinence and frequency and urgency than in those with nocturia and difficult voiding (277.1 +/- 149.4 and 267.7 +/- 221.7 versus 346.7 +/- 204.6 and 306.2 +/- 192.1 ml., respectively, not statistically significant, p = 0.07). CONCLUSIONS: Detrusor instability and bladder outlet obstruction are common in men with lower urinary tract symptoms. The symptom of urge incontinence strongly correlated with detrusor instability. Other lower urinary tract symptoms did not correlate well with any urodynamic findings. Therefore, we believe that an accurate urodynamic diagnosis may enable focused and more efficient management of lower urinary tract symptoms in men.     

膀胱出口梗阻后逼尿肌肾上腺素β3受体mRNA表达和作用

目的：初步研究前列腺增生患者膀胱出口梗阻后逼尿肌肾上腺素能β3受体亚型mRNA表达和作用.方法：选择前列腺增生膀胱出口无梗阻（对照组）9名和膀胱出口梗阻患者（实验组）21名,根据尿动力学将实验组分为逼尿肌稳定组和不稳定组,半定量RT-PCR方法检测三组逼尿肌β3受体亚型mRNA的表达,离体逼尿肌拉力实验检测β3受体激动剂对三组逼尿肌收缩力的影响.结果：对照组、逼尿肌稳定组和不稳定组β3受体mRNA相对含晕为（18.48±2.84）、（17.28±2.57）和（10.42±1.22）,不稳定组β3受体明显降低（P＜0.05）;β受体激动剂和β3受体激动剂诱导逼尿肌松驰效应呈浓度依赖性,对不稳定组作用小于稳定组和对照组（P＜0.05）,对照组与稳定组没有差别.结论：膀胱出口梗阻逼尿肌不稳定患者β3受体mRNA含量下降,并且对β3激动剂的松驰反应降低,逼尿肌肾上腺素能受体β3亚型可能参与膀胱出口梗阻后逼尿肌收缩力变化.     

尿动力学检查在前列腺增生症术前评估中的临床意义

目的探讨前列腺增生症(BPH)手术治疗前尿动力学检查的必要性。方法对166例拟行手术治疗的BPH患者的尿动力学检查结果进行分析。结果在166例患者中,125例(75.3%)证实存在膀胱出口梗阻(BOO ),25例(15.1%)为可疑BOO(BOO±),16例(9.6%)无BOO(BOO-),3组之间在最大尿流率(Qmax)、残余尿量(PVRV)、逼尿肌/外括约肌协同失调(DSD)上差异无统计意义,BOO( )组的逼尿肌不稳定(DI)、低顺应性膀胱的发生率明显高于其他两组,逼尿肌收缩力减弱(DUA)的发生率明显低于其他两组。结论尿动力学检查对诊断BPH、选择治疗方法和预测疗效有重要意义,手术治疗前应常规检查。     

前列腺增生症术后疗效不良的尿动力学分析

目的探讨前列腺增生症术后疗效不良的原因。方法应用尿动力学方法对50例BPH术后症状改善不良的患进行检查分析。结果本组患术后疗效不良的主要原因为逼尿肌不稳定20例(40％)，逼尿肌收缩无力12例(24％)，膀胱出口梗阻18(36％)例。结论BPH术后疗效不良的原因是多方面的，逼尿肌不稳定、逼尿肌收缩无力和膀胱出口梗阻是常见原因。尿动力学检查对确定前列腺术后疗效不良的原因具有重要意义。     

良性前列腺增生患者膀胱内前列腺突入测定的临床意义

目的探讨良性前列腺增生（BPH）患者前列腺突入膀胱内的程度对膀胱出口梗阻及逼尿肌功能的预测与评价。方法以经腹超声证实前列腺突入膀胱内的BPH患者为研究组,无突入的患者为对照组,分析两组间临床资料及尿动力学检查结果的关系。结果研究组临床资料中,前列腺体积、残余尿量、急性尿潴留及膀胱小梁化的比率与对照组相比差异有统计学意义（p〈0．05）,膀胱内前列腺突入程度与前列腺体积、残余尿量呈正相关（r分别为0．401,0．342,p值分别为0．013,0．0231）;在尿动力学结果中,研究组排尿期最大尿流率（Qmax）、逼尿肌不稳定及低顺应性膀胱的比率与对照组相比差异显著（p〈0．01）,排尿期最大逼尿肌压力（Pdet.max）及梗阻指数显著高于对照组（p〈0．05）,膀胱内前列腺突入程度与Qmax呈负相关（r=-0．284,p=0．045）,与Pdet．max及膀胱出口梗阻指数（BOOI）呈正相关（r分别为0．252,0．456,p值分别为0．041,0．032）。结论前列腺突入膀胱的BPH患者膀胱出口梗阻及膀胱功能受损的程度明显高于无突入患者;经B超测定膀胱内前列腺突入的程度,可以预测及评价膀胱出口梗阻的程度和膀胱功能的改变。