【摘要】 目的 探討銀屑病患者的高尿酸血癥及低尿酸血癥的發(fā)生情況,及其對(duì)銀屑病合并心血管疾病(CVD)的影響。方法 選擇2022年1月至2023年9月在喀什地區(qū)第一人民醫(yī)院皮膚科住院的銀屑病患者,收集其臨床資料和實(shí)驗(yàn)室檢查結(jié)果。分析銀屑病患者合并低尿酸血癥、高尿酸血癥及CVD情況,比較合并CVD和無(wú)CVD者的臨床特征,并應(yīng)用多因素Logistic回歸分析其血尿酸濃度與CVD發(fā)生風(fēng)險(xiǎn)的關(guān)系。結(jié)果 共納入206例銀屑病患者,患者年齡為(52.0±13.7)歲,男性130例(63.1%),合并CVD 33例(16.0%),伴高尿酸血癥、低尿酸血癥者的比例分別為26.2%、10.2%。高尿酸血癥與正常尿酸的銀屑病患者相比,合并CVD者的比例升高(27.8% vs. 9.2%,P = 0.011);低尿酸血癥與正常尿酸的銀屑病患者相比,合并CVD者的比例也升高(28.6% vs. 9.2%,P = 0.001);合并CVD與無(wú)CVD的銀屑病患者相比,合并高尿酸血癥者(45.5% vs.22.5%)、低尿酸血癥者(18.2% vs. 8.8%)、高血壓者(63.3% vs. 13.3%)、糖尿病者(30.3% vs. 8.1%)、總膽固醇濃度≥5.2 mmol/L者(39.4% vs. 20.8%)和高敏C反應(yīng)蛋白質(zhì)量濃度gt;5 mg/L者(57.6% vs. 27.7%)的比例均升高(均P lt; 0.05)。多因素Logistic回歸分析顯示,與正常尿酸患者相比,高尿酸血癥(OR=1.668,95%CI 1.022~2.722,P = 0.041)、低尿酸血癥(OR=4.520,95%CI 1.210~16.877,P = 0.025)均為銀屑病患者合并CVD的危險(xiǎn)因素。結(jié)論 高尿酸血癥及低尿酸血癥均可能為銀屑病患者合并CVD的潛在風(fēng)險(xiǎn)因素。
【關(guān)鍵詞】 銀屑病;心血管疾??;血尿酸;低尿酸血癥;高尿酸血癥
Effect of serum uric acid levels on cardiovascular diseases in patients with psoriasis
WEI Xiuning1,2, TUERHONGJIANG·Axirejiang2, ZHENG Gang 2, RENAGULI·Maimaiti2, TANG Zengqi2, 3
(1. Department of Rheumatology and Immunology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou 510120, China; 2. Department of Dermatology, the First People’ s Hospital of Kashi Prefecture, Kashi 844099, China; 3. Department of Dermatology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou 510120, China)
Corresponding author: TANG Zengqi, E-mail: tangzq@mail.sysu.edu.cn
【Abstract】 Objective To explore the prevalence of hyperuricemia and hypouricemia in patients with psoriasis and explore their potential impact on the occurrence of cardiovascular disease (CVD). Methods Patients with psoriasis who were hospitalized in the Department of Dermatology at the First People’s Hospital of Kashi Prefecture from January 2022 to September 2023 were enrolled. Clinical data and laboratory test results were collected. The occurrence of hypouricemia, hyperuricemia, and cardiovascular disease (CVD) among these patients was analyzed. Clinical characteristics were compared between patients with and without CVD. Multivariate logistic regression analysis was performed to assess the associations between serum uric acid levels and the risk of CVD. Results A total of 206 psoriasis patients were included in the study. The mean age was (52.0±13.7) years and 130 patients (63.1%) were male. 33 patients (16.0%) had comorbid cardiovascular disease (CVD). The prevalence of hyperuricemia and hypouricemia was 26.2% and 10.2%, respectively. Compared with patients with normal uric acid levels, those with hyperuricemia had a higher prevalence of CVD (27.8% vs. 9.2%, P = 0.011), and similarly, patients with hypouricemia also had an increased prevalence of CVD (28.6% vs. 9.2%, P = 0.001), even without higher traditional cardiovascular risk factors. Compared with psoriasis patients without CVD, those with CVD showed higher proportions of hyperuricemia (45.5% vs. 22.5%), hypouricemia (18.2% vs. 8.8%), hypertension (63.3% vs. 13.3%), diabetes (30.3% vs. 8.1%), total cholesterol ≥ 5.2 mmol/L (39.4% vs. 20.8%), and hsCRPgt; 5 mg/L (57.6% vs. 27.7%) (all P lt; 0.05). Multivariate logistic regression analysis indicated that, compared with patients with normal uric acid levels, both hyperuricemia (OR=1.668, 95%CI 1.022-2.722, P = 0.041) and hypouricemia (OR=4.520, 95%CI 1.210-16.877, P = 0.025) were independent risk factors for CVD in patients with psoriasis. Conclusions Both hyperuricemia and hypouricemia may be potential risk factors of CVD in patients with psoriasis.
【Key words】 Psoriasis; Cardiovascular disease; Serum uric acid; Hypouricemia; Hyperuricemia
銀屑病是一種慢性炎癥性皮膚病,與心血管疾?。╟ardiovascular disease,CVD)、類(lèi)風(fēng)濕關(guān)節(jié)炎、炎癥性腸病等多種疾病有相似的免疫遺傳基礎(chǔ)[1-2]。銀屑病患者的冠狀動(dòng)脈疾病、心肌梗死、心力衰竭等CVD發(fā)病風(fēng)險(xiǎn)升高[1]。然而,傳統(tǒng)的CVD危險(xiǎn)因素并不能完全準(zhǔn)確評(píng)估銀屑病患者合并CVD的風(fēng)險(xiǎn)。重度銀屑病患者發(fā)生心肌梗死、CVD相關(guān)死亡和腦卒中的風(fēng)險(xiǎn)升高,在排除傳統(tǒng)危險(xiǎn)因素(年齡、性別、高血脂、高血壓、吸煙、糖尿?。┖?,重度銀屑病仍是CVD致死的重要危險(xiǎn)因素[3-4]。在普通人群中,血尿酸水平與CVD發(fā)生及死亡風(fēng)險(xiǎn)呈U型相關(guān),血尿酸水平過(guò)高或過(guò)低均與CVD風(fēng)險(xiǎn)升高有關(guān)[5]。2022年Zou等[6]報(bào)道與正常尿酸水平的類(lèi)風(fēng)濕關(guān)節(jié)炎患者相比,低尿酸血癥的類(lèi)風(fēng)濕關(guān)節(jié)炎患者CVD風(fēng)險(xiǎn)明顯升高(校正OR = 4.707,95% CI 2.570~8.620)。目前低尿酸血癥與銀屑病合并CVD的關(guān)系未見(jiàn)報(bào)道。本研究通過(guò)回顧性病例研究,分析銀屑病患者血尿酸水平的特點(diǎn)以及不同尿酸水平與銀屑病合并CVD風(fēng)險(xiǎn)的關(guān)系,探討低尿酸血癥對(duì)銀屑病合并CVD的潛在風(fēng)險(xiǎn)。
1 對(duì)象與方法
1.1 研究對(duì)象
回顧性收集2022年1月至2023年9月在喀什地區(qū)第一人民醫(yī)院皮膚科住院的銀屑病患者。納入標(biāo)準(zhǔn):①患者的臨床表現(xiàn)及病理活檢符合銀屑病的診斷標(biāo)準(zhǔn)[7];②年齡為18~75歲;③病歷資料完整并行實(shí)驗(yàn)室檢查。排除合并活動(dòng)性感染、腫瘤、痛風(fēng)、其他自身免疫疾病和正在服用降尿酸藥物及妊娠期患者。本研究經(jīng)喀什地區(qū)第一人民醫(yī)院倫理委員會(huì)審批(批件號(hào):〔2023〕快研第34號(hào)),所有入組患者均已簽署知情同意書(shū)。
1.2 研究方法
收集銀屑病患者的年齡、性別、病程、主動(dòng)吸煙史、身體質(zhì)量指數(shù)(body mass index,BMI)、臨床表現(xiàn)、疾病嚴(yán)重程度、既往史、合并癥、藥物治療史、血液學(xué)及影像學(xué)檢查結(jié)果。根據(jù)皮膚臨床表現(xiàn),將伴或不伴關(guān)節(jié)炎型的銀屑病患者分為以下3種類(lèi)型:斑塊型、紅皮病型、膿皰型[8-9]。同時(shí)根據(jù)皮損面積評(píng)價(jià)銀屑病疾病嚴(yán)重度[10]:輕度,皮損面積lt; 3%體表面積(body surface area,BSA);中度:皮損累及3%~10%BSA;重度:皮損累及gt;10%BSA。
正常尿酸水平指血尿酸濃度為180~420 μmol/L,
低尿酸血癥指血尿酸濃度lt;180 μmol/L,高尿酸血癥指血尿酸濃度gt; 420 μmol/L[6, 11]。CVD被定義為有明確證實(shí)的心絞痛、心肌梗死、心力衰竭、缺血性或出血性卒中和外周動(dòng)脈疾病病史[6, 12],根據(jù)患者的病史記錄及心血管影像學(xué)檢查結(jié)果獲取。
1.3 統(tǒng)計(jì)學(xué)方法
使用SPSS 20.0進(jìn)行數(shù)據(jù)分析。使用Shapiro-Wilk檢驗(yàn)評(píng)估數(shù)據(jù)分布的正態(tài)性。正態(tài)分布的計(jì)量資料以表示,2組間比較采用t檢驗(yàn);偏態(tài)分布的計(jì)量資料以M(P25,P75)表示,2組間比較采用Mann-Whitney U檢驗(yàn)。計(jì)數(shù)資料以n(%)表示,2組間比較采用χ 2檢驗(yàn)。采用Kruskal-Wallis H檢驗(yàn)或χ 2檢驗(yàn)比較低尿酸血癥組、正常尿酸水平組及高尿酸血癥組患者的臨床特征,進(jìn)一步兩兩比較行Bonferroni法校正(P lt; 0.017為差異有統(tǒng)計(jì)學(xué)意義)。采用單因素Logistic回歸分析CVD發(fā)生的風(fēng)險(xiǎn)因素,對(duì)單因素Logistic回歸分析中差異具有統(tǒng)計(jì)學(xué)意義的因素進(jìn)行多因素Logistic回歸分析。P lt; 0.05為差異有統(tǒng)計(jì)學(xué)意義。采用G*Power事后分析統(tǒng)計(jì)功效(1-β)均超過(guò)0.8。
2 結(jié) 果
2.1 銀屑病患者的臨床特點(diǎn)
本研究共納入206例銀屑病患者,年齡為(52.0±13.7)歲,男性130例(63.1%),中位病程為12.0(5.0,20.0)年。銀屑病皮膚分型為斑塊型180例(87.4%),膿皰型14例(6.8%),紅皮病型12例(5.8%);重度119例(57.8%),中度87例(42.2%),無(wú)輕度銀屑病患者。178例(86.4%)銀屑病患者為初治患者,即既往未接受過(guò)銀屑病的系統(tǒng)性藥物治療。
33例(16.0%)銀屑病患者合并CVD,其中心絞痛12例(5.8%),心肌梗死7例(3.4%),心力衰竭6例(2.9%),腦梗死6例(2.9%),外周動(dòng)脈疾病2例(1.0 %)。
2.2 銀屑病患者的血尿酸濃度
206例銀屑病患者的血尿酸濃度為(337.8±120.7)μmol/L,男性患者的血尿酸濃度高于女性患者[(368.4±125.4)μmol/L vs. (285.5±91.6)μmol/L,t = 5.435,P lt; 0.001],絕經(jīng)后女性患者的血尿酸濃度高于未絕經(jīng)的女性患者[(303.5±108.5)μmol/L vs. (264.9±79.5)μmol/L,t = 2.218,P = 0.023]。
高尿酸血癥患者的比例為26.2%(54/206),男性高尿酸血癥患者比例高于女性患者(34.6% vs. 11.8 %,χ 2 =12.860,P lt; 0.001)。低尿酸血癥患者的比例為10.2%(21/206),中度銀屑病患者低尿酸血癥的比例高于重度銀屑病患者(16.1% vs. 5.9%,χ 2 = 5.722,P = 0.017)。見(jiàn)表1。
2.3 不同血尿酸濃度銀屑病患者的臨床特征及CVD風(fēng)險(xiǎn)因素比較
高尿酸血癥銀屑病患者與正常尿酸水平患者相比,合并CVD的比例更高(27.8% vs. 9.2%),年齡更大,高敏C反應(yīng)蛋白(hypersensitive C-reactive protein,hsCRP)、血尿酸、總膽固醇、甘油三酯、低密度脂蛋白膽固醇(low-density lipoprotein cholesterol,LDL-C)水平升高,血白蛋白水平降低,差異均具有統(tǒng)計(jì)學(xué)意義(均P lt; 0.017)。低尿酸血癥銀屑病患者與正常尿酸水平患者相比,合并CVD的比例更高(28.6% vs. 9.2%),hsCRP水平升高、血尿酸濃度及血白蛋白質(zhì)量濃度更低,差異均有統(tǒng)計(jì)學(xué)意義(均P lt; 0.017),傳統(tǒng)的心血管危險(xiǎn)因素比較差異無(wú)統(tǒng)計(jì)學(xué)意義(均P gt; 0.017)。
高尿酸血癥銀屑病患者與低尿酸血癥患者相比,BMI、總膽固醇、甘油三酯、LDL-C、血白蛋白及血尿酸濃度均升高(均P lt; 0.017)。見(jiàn)表1。
2.4 合并CVD與無(wú)CVD的銀屑病患者臨床特征比較
合并CVD的銀屑病患者與無(wú)CVD的銀屑病患者相比,年齡更大、病程更長(zhǎng),合并低尿酸血癥、高尿酸血癥、高血壓、糖尿病、總膽固醇≥
5.2 mmol/L及hsCRPgt; 5 mg/L的患者比例均升高(均P lt; 0.05)。見(jiàn)表2。
2.5 銀屑病患者血尿酸濃度和CVD的關(guān)系及Logistic回歸分析
單因素Logistic回歸分析顯示,與正常尿酸相比,高尿酸血癥、低尿酸血癥是銀屑病患者合并CVD風(fēng)險(xiǎn)升高的危險(xiǎn)因素;高血壓、糖尿病、總膽固醇≥ 5.2 mmol/L,hsCRPgt; 5 mg/L也是銀屑病患者合并CVD風(fēng)險(xiǎn)升高的危險(xiǎn)因素(均P lt; 0.05),見(jiàn)表3。多因素Logistic回歸分析顯示,與正常尿酸相比,高尿酸血癥、低尿酸血癥均是銀屑病合并CVD的危險(xiǎn)因素(均P lt; 0.05),見(jiàn)表4。
3 討 論
銀屑病患者的CVD共病率隨著年齡的增長(zhǎng)而增加,并且與性別、肥胖、吸煙、高血壓、糖尿病、藥物過(guò)敏史、銀屑病家族史以及銀屑病的嚴(yán)重程度有關(guān)[13]。一項(xiàng)包含75項(xiàng)研究、涵蓋50萬(wàn)例銀屑病患者的薈萃分析顯示,與無(wú)銀屑病的人群相比,銀屑病患者的CVD患病率約高出50%[14]。然而,大規(guī)模的流行病學(xué)研究和嚴(yán)格控制的心血管影像學(xué)研究表明,銀屑病與CVD的關(guān)聯(lián)獨(dú)立于傳統(tǒng)的心血管風(fēng)險(xiǎn)因素(年齡、性別、高血脂、高血壓、吸煙、糖尿?。?,并且呈劑量-反應(yīng)關(guān)系[14]。因此,對(duì)于銀屑病的CVD風(fēng)險(xiǎn)應(yīng)關(guān)注傳統(tǒng)心血管風(fēng)險(xiǎn)因素以外的因素,本研究探討了血尿酸濃度對(duì)銀屑病合并CVD的影響。
尿酸是人類(lèi)嘌呤代謝的最終產(chǎn)物,是痛風(fēng)的病因,是心血管結(jié)局的預(yù)測(cè)標(biāo)志物之一[15]。高尿酸血癥通過(guò)引起內(nèi)皮功能障礙、氧化應(yīng)激、炎癥放大、代謝紊亂和直接血管損傷等多途徑,與銀屑病/銀屑病關(guān)節(jié)炎的慢性炎癥協(xié)同,增加胰島素抵抗,促進(jìn)動(dòng)脈粥樣硬化,顯著增加心血管事件風(fēng)險(xiǎn)[16]。此外,尿酸可能作為“損傷相關(guān)分子模式”(damage associated molecular patterns,DAMP)激活先天免疫,進(jìn)一步連接代謝異常與免疫失調(diào)[16]。高尿酸血癥不僅與肥胖、高血壓、血脂異常、2型糖尿病、慢性腎臟病、心房顫動(dòng)及CVD等有關(guān)[17-18],還與一般人群的全因病死率及CVD病死率之間呈正相關(guān)[19-21]。
銀屑病患者高尿酸血癥的比例為20%[22]。薈萃分析顯示,銀屑病患者組的血尿酸濃度(MD=0.99,95% CI 0.48~1.49,P = 0.000 1)和高尿酸血癥的發(fā)生率(OR=5.39,95%CI 1.88~15.40,P ="0.002)均高于對(duì)照組[23]。伴有高尿酸血癥的銀屑病關(guān)節(jié)炎患者與正常尿酸的銀屑病關(guān)節(jié)炎患者相比,高血壓(57.5% vs. 29.6%)、主要心血管不良事件(16.0% vs. 5.0%)、急性冠脈綜合征(9.6% vs. 3.0%)、缺血性腦卒中(8.2% vs. 1.8%)及糖尿?。?0.1% vs. 14.2%)比例均明顯升高[24]。本研究顯示,銀屑病患者中高尿酸血癥的比例為26.2%,男性銀屑病患者高尿酸血癥的比例為34.6%,略高于文獻(xiàn)報(bào)道[23]及一般人群(均為20%)[25]。本研究進(jìn)一步分析顯示,高尿酸血癥的銀屑病患者與正常尿酸水平的銀屑病患者相比,合并CVD的比例升高(27.8% vs. 9.2%);與正常尿酸水平的銀屑病患者相比,高尿酸血癥的銀屑病患者合并CVD的風(fēng)險(xiǎn)升高1.668倍,提示高尿酸血癥是銀屑病患者合并CVD的風(fēng)險(xiǎn)因素。
血尿酸過(guò)高或過(guò)低均可能增加心血管事件發(fā)生率及死亡風(fēng)險(xiǎn),血尿酸濃度與心血管代謝疾?。ㄈ绺哐獕骸⒀惓:湍I功能減退)之間存在J型關(guān)系,男性血清尿酸lt;4.5 mg/dL或gt;5.2 mg/dL及女性血清尿酸lt;3.2 mg/dL或gt;3.9 mg/dL時(shí),發(fā)生心血管事件或死亡風(fēng)險(xiǎn)明顯增加[26-27]。一項(xiàng)對(duì)韓國(guó)成年人的研究結(jié)果顯示,男性血清尿酸水平與10年CVD風(fēng)險(xiǎn)評(píng)分呈近似U型關(guān)系,即血清尿酸水平在6.9 mg/dL時(shí),CVD風(fēng)險(xiǎn)最低,而當(dāng)血清尿酸水平過(guò)高或過(guò)低時(shí),CVD風(fēng)險(xiǎn)均明顯升高;女性血清尿酸水平與10年CVD風(fēng)險(xiǎn)呈近似J型關(guān)聯(lián)[28]。日本學(xué)者的研究發(fā)現(xiàn),男性血尿酸gt;7.8 mg/dL或lt; 4.3 mg/dL及女性血尿酸gt;5.9 mg/dL或lt;3.5 mg/dL時(shí)心房顫動(dòng)患病率均升高[29]。低尿酸血癥的老年人全因病死率和CVD病死率分別比正常人高出20%和35%[30]。過(guò)度的尿酸水平降低與痛風(fēng)患者更高的病死率相關(guān)[31]。當(dāng)血清尿酸lt;4 mg/dL時(shí),一般人群的心血管病死率升高,在慢性腎臟病及血液透析患者中,CVD病死率更高[31-32]。
低尿酸血癥增加CVD及心血管病死率的機(jī)制可能為:血尿酸是一種抗氧化劑,低尿酸時(shí),由于抗氧化能力下降,不能中和內(nèi)源性活性氧,促進(jìn)動(dòng)脈粥樣硬化,增加了CVD的風(fēng)險(xiǎn)及增加心血管病死率[33]。因此,維持適宜的尿酸水平對(duì)于預(yù)防心血管代謝疾病非常重要。中國(guó)痛風(fēng)診療規(guī)范建議尿酸控制不宜lt;180 μmol/L[34]。
本研究首次探討了低尿酸血癥對(duì)銀屑病合并CVD的潛在風(fēng)險(xiǎn),報(bào)告了銀屑病患者中低尿酸血癥的比例為10.2%,女性及男性銀屑病患者低尿酸血癥比例分別為14.5%及7.7%,高于一般人群(65歲以上老年人為1.2%[30],成人男性為1.4%,成人女性為6.3%[35]),與類(lèi)風(fēng)濕關(guān)節(jié)炎患者低尿酸血癥比例(10.6%)接近[6]。本研究中,伴有低尿酸血癥的銀屑病患者與正常尿酸水平的銀屑病患者相比,合并CVD的比例升高(28.6% vs. 9.2%);與正常尿酸水平的銀屑病患者相比,低尿酸血癥的銀屑病患者合并CVD的風(fēng)險(xiǎn)升高4.520倍,提示低尿酸血癥可能是銀屑病患者合并CVD的一種新的潛在風(fēng)險(xiǎn)因素。本研究結(jié)果提示,低尿酸血癥和高尿酸血癥均與銀屑病患者合并CVD的風(fēng)險(xiǎn)升高有關(guān),血尿酸濃度在銀屑病患者合并CVD的風(fēng)險(xiǎn)中可能呈U型相關(guān)。
本研究同時(shí)也發(fā)現(xiàn),與高尿酸血癥的銀屑病患者相比,低尿酸血癥的銀屑病患者傳統(tǒng)心血管危險(xiǎn)因素(BMI、總膽固醇、甘油三酯、LDL-C)水平更低。與正常尿酸的銀屑病患者相比,低尿酸血癥的銀屑病患者傳統(tǒng)心血管危險(xiǎn)因素?zé)o統(tǒng)計(jì)學(xué)差異,具有差異的是hsCRP水平,hsCRP水平在低尿酸血癥患者中明顯升高,提示炎癥可能是低尿酸血癥銀屑病患者合并CVD風(fēng)險(xiǎn)升高的主要因素。銀屑病患者的傳統(tǒng)心血管危險(xiǎn)因素雖然也增加,但炎癥是銀屑病患者獨(dú)立的心血管危險(xiǎn)因素[36]。慢性持續(xù)性炎癥是銀屑病CVD風(fēng)險(xiǎn)增加的重要因素,同時(shí)慢性持續(xù)性炎癥反應(yīng)可引起高分解代謝狀態(tài),導(dǎo)致體質(zhì)量減輕、能量消耗增加、營(yíng)養(yǎng)不良,甚至惡病質(zhì)[6]。本研究結(jié)果提示,低尿酸血癥組的患者h(yuǎn)sCRP水平明顯升高,且BMI、白蛋白及血脂水平明顯降低,提示低尿酸血癥組的患者可能存在更高的炎癥狀態(tài),而慢性持續(xù)性炎癥導(dǎo)致患者能量消耗增加、營(yíng)養(yǎng)不良。提示炎癥可能是引起低尿酸血癥的原因之一,也是銀屑病患者合并CVD風(fēng)險(xiǎn)升高的重要因素。
本研究為單中心、小樣本的回顧性病例分析,存在多種混雜因素,目前僅能觀察到高尿酸血癥和低尿酸血癥的患者合并CVD的風(fēng)險(xiǎn)升高,暫不能得出因果關(guān)系;另外,本研究沒(méi)有考慮到食物或其他藥物對(duì)尿酸水平的影響,未來(lái)需要大規(guī)模多中心前瞻性研究來(lái)解決這些局限性。
綜上所述,銀屑病患者中高尿酸血癥和低尿酸血癥都可能與CVD風(fēng)險(xiǎn)升高有關(guān),維持適宜的尿酸水平對(duì)于預(yù)防CVD具有重要意義。
利益沖突聲明:本研究未受到企業(yè)、公司等第三方資助,不存在潛在利益沖突。
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(責(zé)任編輯:林燕薇)