胡星 蔣炘紋 蔣禮 雷遷
【摘要】目的 分析尿液中性粒細(xì)胞明膠酶相關(guān)脂質(zhì)運(yùn)載蛋白(NGAL)和白細(xì)胞介素-6(IL-6)水平對(duì)心臟外科術(shù)后患者嚴(yán)重液體超負(fù)荷(FO)的風(fēng)險(xiǎn)價(jià)值。方法 選取2020年4月—2023年3月在成都市第三人民醫(yī)院接受心臟外科手術(shù)的患者220例,根據(jù)術(shù)后24 h FO,將FO≥10%的患者記為A組,將FO<10%的患者記為B組。分析兩組一般資料,比較兩組術(shù)前及術(shù)后尿液NGAL和IL-6水平,采用logistic回歸模型分析心臟外科術(shù)后24 h內(nèi)患者發(fā)生嚴(yán)重FO的危險(xiǎn)因素,繪制ROC曲線,分析尿液NGAL、IL-6對(duì)患者發(fā)生嚴(yán)重FO的風(fēng)險(xiǎn)價(jià)值。亞組分析不同原發(fā)病對(duì)FO的影響。結(jié)果 A組男性ICU停留時(shí)間比例高于B組(P<0.05),術(shù)前白蛋白水平及術(shù)后當(dāng)天尿量低于B組(P<0.05),兩組體重指數(shù)、年齡、病程、手術(shù)時(shí)間、術(shù)中尿量、原發(fā)疾病類型、術(shù)前左室射血分?jǐn)?shù)、肌酐水平、白細(xì)胞計(jì)數(shù)、血紅蛋白水平、機(jī)械通氣時(shí)間、體外循環(huán)時(shí)間,以及急性腎損傷、左心功能不全、高血壓、心力衰竭、糖尿病占比比較無(wú)差異(P>0.05);兩組術(shù)后2 h、術(shù)后12 h尿液NGAL和IL-6水平均高于術(shù)前(P<0.05),術(shù)后12 h尿液NGAL和IL-6水平均高于術(shù)后2 h(P<0.05),且A組術(shù)前、術(shù)后2 h及術(shù)后12 h均高于B組(P<0.05);logistic回歸分析發(fā)現(xiàn),術(shù)前尿液NGAL和IL-6水平高是心臟外科術(shù)后患者發(fā)生嚴(yán)重FO的危險(xiǎn)因素(P<0.05);ROC結(jié)果顯示,術(shù)前尿液NGAL和IL-6水平對(duì)心臟外科術(shù)后患者發(fā)生嚴(yán)重FO的最佳截?cái)帱c(diǎn)分別為48.04 ng/mL和32.26 pg/mL,AUC分別為0.865和0.704,二者聯(lián)合檢測(cè)AUC為0.894。冠心病、先天性心臟病、心臟瓣膜病亞組之間FO情況、ICU停留時(shí)間、體外循環(huán)時(shí)間、術(shù)后當(dāng)天尿量及術(shù)前NGAL和IL-6之間無(wú)顯著差異(P均>0.05)。結(jié)論 心臟外科術(shù)后患者尿液NGAL和IL-6水平異常升高,術(shù)前尿液NGAL和IL-6水平是其發(fā)生嚴(yán)重FO的危險(xiǎn)因素。
【關(guān)鍵詞】心臟外科手術(shù);液體超負(fù)荷;中性粒細(xì)胞明膠酶相關(guān)脂質(zhì)運(yùn)載蛋白;白細(xì)胞介素-6
【DOI】10.16806/j.cnki.issn.1004-3934.2024.03.020
Risk Value of Urinary Neutrophil Gelatinase-Associated Lipocalin and Interleukin-6 Levels on Severe Fluid Overload in Patients After Cardiac Surgery
HU Xing1,JIANG Xinwen2,JIANG Li1,LEI Qian2
(1.Department of Cardiac Surgery ICU,The Third Peoples Hospital of Chengdu,Chengdu 610034,Sichuan,China;2.Department of Anesthesiology,Sichuan Provincial Peoples Hospital,Sichuan Academy of Medical Sciences,Chengdu 610072,Sichuan,China)
【Abstract】Objective To analyze the risk value of urinary neutrophil gelatinase-associated lipocalin (NGAL) and interleukin-6 (IL-6) levels on severe fluid overload (FO) in patients after cardiac surgery.Methods A total of 220 patients underwent cardiac surgery in The Third Peoples Hospital of Chengdu from April 2020 to March 2023 were enrolled.Patients with FO≥10% were classified into group A and FO<10% into group B according to FO within 24 h after surgery.General data were analyzed and urinary NGAL and IL-6 levels were compared before and after surgery.Logistic regression model was used to analyze risk factors for severe FO after surgery.ROC curve was plotted to analyze the risk value of urinary NGAL and IL-6 on severe FO.The influence of different primary diseases on FO was analyzed by subgroups.Results The proportion of male patients and stay time in ICU were higher in group A than group B (P<0.05),while the preoperative albumin level and urine volume the day after surgery were lower (P<0.05).There was no significant difference in body mass index,age,course of disease,operation time,urine volume during operation,primary disease types,preoperative left ventricular ejection fraction,creatinine,leukocytes,hemoglobin,mechanical ventilation time,extracorporeal circulation time,intraoperative urine volume,the proportion of acute kidney injury,left cardiac insufficiency,hypertension,heart failure and diabetes between the two groups (P>0.05).Urinary NGAL and IL-6 levels of two groups were increased (P<0.05) at 2 h and 12 h after surgery,not only the higher at 12 h than 2 h (P<0.05),but also the higher in group A than group B before surgery,after surgery and 12 h after surgery (P<0.05).Logistic results showed high urinary NGAL and IL-6 levels before operation were risk factors for severe FO in patients after cardiac surgery (P<0.05).ROC results showed the optimal cut-off point of preoperative NGAL and IL-6 levels on severe FO after surgery was 48.04 ng/mL and 32.26 pg/mL,with the AUC of 0.865,0.704 respectively and 0.894 for their combined detection.There was no difference in FO,ICU stay time,cardiopulmonary bypass time,urine volume the day after operation and preoperative NGAL and IL-6 among the subgroups of coronary,congenital and valvular heart diseases (all P>0.05).Conclusion Urinary NGAL and IL-6 were abnormally elevated in patients after cardiac surgery,the levels of which before surgery could be risk factors for severe FO.
【Keywords】Cardiac surgery;Fluid overload;Neutrophil gelatinase-associated lipocalin;Interleukin-6
液體超負(fù)荷(fluid overload,F(xiàn)O)是腹腔間隙綜合征的原因之一,臨床將液體蓄積大于或等于基線體重10%定義為FO[1]。FO是心臟病外科手術(shù)后常見且嚴(yán)重的并發(fā)癥之一,嚴(yán)重影響患者的康復(fù)及預(yù)后結(jié)局[2]。液體管理是心臟病外科手術(shù)后的重要組成部分,早期積極的液體復(fù)蘇能增加心臟前負(fù)荷以及心輸出量,促進(jìn)氧氣輸送,提升組織器官的氧狀態(tài),改善患者預(yù)后,但由于無(wú)法統(tǒng)一液體復(fù)蘇目標(biāo),多數(shù)心臟外科術(shù)后患者在經(jīng)過液體復(fù)蘇后血流動(dòng)力學(xué)改善不明顯,且部分患者出現(xiàn)不同程度FO[3-4]。液體過多對(duì)腎臟不利,會(huì)造成腎間質(zhì)水腫、腎盂壓力升高,靜脈及腎小管壓力升高,導(dǎo)致腎血流減少、腎小球?yàn)V過率下降、腎小管滲漏增加,進(jìn)而造成胸腔內(nèi)壓劇增、組織器官水腫、血管擴(kuò)張,對(duì)患者術(shù)后治療及康復(fù)造成不良影響[5]。有研究[6]顯示,腎替代治療的危重癥患兒FO>10%與死亡在內(nèi)的不良結(jié)局有關(guān)。有研究[7]顯示,F(xiàn)O≥10%可增加急性肺損傷患者不良事件的發(fā)生風(fēng)險(xiǎn)。因此,臨床上對(duì)行重癥外科手術(shù)患者進(jìn)行FO風(fēng)險(xiǎn)評(píng)估對(duì)患者的預(yù)后結(jié)局具有重要意義。鑒于此,現(xiàn)探討尿液中性粒細(xì)胞明膠酶相關(guān)脂質(zhì)運(yùn)載蛋白(neutrophil gelatinase-associated lipocalin,NGAL)和白細(xì)胞介素(interleukin,IL)-6水平評(píng)估心臟外科術(shù)后患者嚴(yán)重FO的風(fēng)險(xiǎn)價(jià)值,對(duì)臨床診斷FO具有重要意義。
1 資料與方法
1.1 一般資料
經(jīng)醫(yī)院倫理委員會(huì)審核批準(zhǔn)(FA-2020220A),選取2020年4月—2023年3月在成都市第三人民醫(yī)院接受心臟外科手術(shù)的患者220例,根據(jù)術(shù)后24 h FO,將FO≥10%的患者記為A組,將FO<10%的患者記為B組。納入標(biāo)準(zhǔn):年齡>18歲;均接受體外循環(huán)下心臟病開胸根治術(shù)治療;患者及家屬簽署知情同意書。排除標(biāo)準(zhǔn):心功能>Ⅳ級(jí)者;近期服用過腎損傷藥物或糖皮質(zhì)激素類藥物;心臟移植者;合并自身免疫性疾病者;近期或術(shù)后伴有尿路感染者;術(shù)前存在腎功能損傷或急慢性腎臟病者;術(shù)前存在氣道或肺部疾病氣管插管者;合并惡性腫瘤者;妊娠及哺乳期者。
1.2 方法
患者均經(jīng)心臟中心熟練手術(shù)醫(yī)師,遵循相同手術(shù)標(biāo)準(zhǔn),在體外循環(huán)下實(shí)施根治手術(shù),根據(jù)患者情況改良超濾,最大限度減輕水腫。均于術(shù)后進(jìn)行標(biāo)準(zhǔn)的液體治療,動(dòng)態(tài)檢測(cè)中心靜脈壓,結(jié)合病情判斷容量,保證循環(huán)穩(wěn)定、心率正常的前提下做利尿處理使FO降至最低。根據(jù)術(shù)后24 h FO值以FO=10%為截?cái)帱c(diǎn)進(jìn)行分組。FO值計(jì)算方法為:FO=[輸入液體量(L)-排出液體量(L)]/手術(shù)前體重(kg)×100%。
1.3 觀察指標(biāo)
比較兩組一般資料,包括性別、年齡、病程、體重指數(shù)、術(shù)前白蛋白水平、術(shù)后當(dāng)天尿量、術(shù)前左室射血分?jǐn)?shù)(left ventricular ejection fraction,LVEF)、肌酐水平、白細(xì)胞計(jì)數(shù)、血紅蛋白水平、機(jī)械通氣時(shí)間、手術(shù)時(shí)間、體外循環(huán)時(shí)間、術(shù)中尿量、急性腎損傷(acute kidney injury,AKI)、左心功能不全、高血壓、心力衰竭、糖尿??;比較兩組術(shù)前及術(shù)后尿液NGAL和IL-6水平,分別于術(shù)前及術(shù)后2 h收集患者尿液,采用酶聯(lián)免疫吸附法檢測(cè)尿液NGAL和IL-6水平,操作步驟嚴(yán)格按照說明書進(jìn)行;分析心臟外科術(shù)后24 h內(nèi)患者發(fā)生嚴(yán)重FO的危險(xiǎn)因素;分析尿液NGAL和IL-6對(duì)患者發(fā)生嚴(yán)重FO的風(fēng)險(xiǎn)價(jià)值;亞組分析不同原發(fā)疾病類型對(duì)FO的影響。
1.4 統(tǒng)計(jì)學(xué)方法
采用SPSS 26.0處理分析數(shù)據(jù),以±s表示計(jì)量資料,以t檢驗(yàn)分析兩樣本數(shù)據(jù);計(jì)數(shù)資料以n(%)表示,采用χ2檢驗(yàn),P<0.05為差異有統(tǒng)計(jì)學(xué)意義;以logistic回歸分析法分析導(dǎo)致心臟外科術(shù)后24 h內(nèi)患者發(fā)生嚴(yán)重FO的OR及95%CI;通過建立ROC曲線分析尿液NGAL和IL-6對(duì)患者發(fā)生嚴(yán)重FO的風(fēng)險(xiǎn)價(jià)值。
2 結(jié)果
2.1 比較兩組一般資料
A組男性比例、ICU停留時(shí)間均高于B組(P<0.05),術(shù)前白蛋白水平及術(shù)后當(dāng)天尿量低于B組(P<0.05),兩組體重指數(shù)、年齡、病程、手術(shù)時(shí)間、術(shù)中尿量、原發(fā)疾病類型、術(shù)前LVEF、肌酐、白細(xì)胞計(jì)數(shù)、血紅蛋白水平、機(jī)械通氣時(shí)間、體外循環(huán)時(shí)間以及AKI、左心功能不全、高血壓、心力衰竭、糖尿病占比比較無(wú)差異(P>0.05),見表1。
2.2 比較兩組術(shù)前及術(shù)后尿液NGAL和IL-6水平
兩組術(shù)后2 h、術(shù)后12 h尿液NGAL和IL-6水平均高于術(shù)前(P<0.05),術(shù)后12 h尿液NGAL和IL-6水平均高于術(shù)后2 h(P<0.05),且A組術(shù)前、術(shù)后2 h及術(shù)后12 h均高于B組(P<0.05),見表2。
2.3 心臟外科術(shù)后患者嚴(yán)重FO的多因素分析
以心臟外科術(shù)后患者是否發(fā)生嚴(yán)重FO為因變量,以性別、原發(fā)疾病類型、術(shù)前LVEF、體外循環(huán)時(shí)間、術(shù)前白蛋白水平、ICU停留時(shí)間、術(shù)后當(dāng)天尿量以及術(shù)后2 h尿液NGAL和IL-6水平為自變量賦值;logistic回歸分析發(fā)現(xiàn),術(shù)前尿液NGAL和IL-6水平高是心臟外科術(shù)后患者發(fā)生嚴(yán)重FO的危險(xiǎn)因素(P<0.05),見表3。
2.4 術(shù)前尿液NGAL和IL-6水平對(duì)心臟外科術(shù)后患者發(fā)生嚴(yán)重FO的預(yù)測(cè)價(jià)值
ROC曲線分析結(jié)果顯示,術(shù)前尿液NGAL和IL-6水平對(duì)心臟外科術(shù)后患者發(fā)生嚴(yán)重FO的最佳截?cái)帱c(diǎn)分別為48.04 ng/mL和32.26 pg/mL,AUC分別為0.865和0.704,二者聯(lián)合檢測(cè)AUC為0.894,見表4,圖1。
2.5 亞組分析結(jié)果
冠心病、先天性心臟病、心臟瓣膜病亞組之間FO情況、ICU停留時(shí)間、體外循環(huán)時(shí)間、術(shù)后當(dāng)天尿量及術(shù)前NGAL和IL-6之間無(wú)顯著差異(P均>0.05),見表5~7。
3 討論
FO在心臟外科術(shù)后患者中具有較高的發(fā)病率及死亡率[8],早期發(fā)現(xiàn)并及時(shí)治療FO可逆轉(zhuǎn),多數(shù)患者腎功能及組織損傷都可恢復(fù),因此早期預(yù)測(cè)FO風(fēng)險(xiǎn)對(duì)臨床意義重大[9]。本研究以心臟外科術(shù)后患者FO=10%為截?cái)帱c(diǎn),探討尿液NGAL和IL-6水平對(duì)心臟外科術(shù)后患者發(fā)生FO的預(yù)測(cè)價(jià)值。
心臟外科術(shù)后患者出現(xiàn)FO是臨床常見問題,會(huì)對(duì)腎功能造成明顯影響,而心臟外科術(shù)后患者FO與炎癥因子、腎功能損傷有關(guān)。NGAL是在激活的中性粒細(xì)胞中發(fā)現(xiàn)的小分子量蛋白,可直接反映早期腎功能損傷情況,在腎臟組織正常形態(tài)下水平極低,但心臟外科術(shù)后FO患者腎小管上皮細(xì)胞受損導(dǎo)致腎功能損傷,激活中性粒細(xì)胞,分泌大量NGAL,造成尿液NGAL水平異常升高[10-11]。IL-6是趨化因子,也是臨床常用的感染性檢測(cè)指標(biāo),在機(jī)體發(fā)生炎癥反應(yīng)或組織受傷時(shí)水平升高[12]。心臟外科術(shù)后FO患者出現(xiàn)明顯的臨床炎癥反應(yīng),使機(jī)體處于微炎癥反應(yīng)狀態(tài),體內(nèi)多種物質(zhì)對(duì)機(jī)體免疫系統(tǒng)反應(yīng)刺激促進(jìn)IL-6的分泌,導(dǎo)致IL-6水平顯著升高[13]。本研究對(duì)比分析發(fā)現(xiàn),心臟外科術(shù)后患者尿液NGAL和IL-6水平持續(xù)升高,且A組水平更高,說明心臟外科術(shù)后出現(xiàn)FO的患者存在腎損傷、炎癥狀態(tài)。此外,術(shù)后發(fā)生嚴(yán)重FO患者在ICU停留時(shí)間明顯延長(zhǎng),說明FO會(huì)加重患者病情,從而延長(zhǎng)患者停留ICU時(shí)間。
本研究進(jìn)一步分析發(fā)現(xiàn),術(shù)后當(dāng)天尿量少、術(shù)前尿液NGAL和IL-6水平高是心臟外科術(shù)后患者發(fā)生嚴(yán)重FO的危險(xiǎn)因素。有研究[14]顯示,F(xiàn)O是老年ICU患者發(fā)生AKI的獨(dú)立危險(xiǎn)因素,造成靜脈壓升高,加重心力衰竭,繼發(fā)腹腔間隙綜合征,影響腎臟灌注。腎功能受損會(huì)引起腎血流量減少、腎小球?yàn)V過率下降,導(dǎo)致患者尿量減少。術(shù)后發(fā)生嚴(yán)重FO可造成腎功能損傷,促進(jìn)NGAL分泌,腎功能受損時(shí)腎小球?yàn)V過率下降,NGAL經(jīng)過腎小管重吸收受阻,而腎小管上皮細(xì)胞受損可造成NGAL從腎小管溢出到尿液中,因此患者發(fā)生嚴(yán)重FO后尿液NGAL水平升高[15]。術(shù)后FO患者更易發(fā)生炎癥反應(yīng),促進(jìn)IL-6等炎性因子的分泌,引起肺水腫或外周組織水腫,加重機(jī)體感染,進(jìn)一步促進(jìn)炎癥反應(yīng),而腎間質(zhì)水腫可損害腎功能,導(dǎo)致腎血流量及腎小球?yàn)V過率降低,IL-6經(jīng)過腎小管重吸收時(shí)大量溢出至尿液中,導(dǎo)致尿液IL-6水平升高[16]。
ROC曲線分析結(jié)果顯示,術(shù)前尿液NGAL和IL-6水平對(duì)心臟外科術(shù)后患者發(fā)生嚴(yán)重FO的AUC分別為0.865和0.704,準(zhǔn)確度分別為77.27%和69.09%,二者聯(lián)合檢測(cè)AUC為0.894,準(zhǔn)確度為80.91%,因此術(shù)前尿液NGAL和IL-6聯(lián)合檢測(cè)能提高嚴(yán)重FO的檢出率。Thompson等[17]研究顯示,術(shù)后早期的尿液NGAL與術(shù)后48 h內(nèi)FO相關(guān)。Elitok等[18]研究表明ICU患者入院時(shí)的尿液NGAL和IL-6水平可能有助于預(yù)測(cè)心臟手術(shù)后的嚴(yán)重FO。因此,臨床可在術(shù)前動(dòng)態(tài)檢測(cè)心臟外科手術(shù)患者尿液NGAL和IL-6水平,根據(jù)實(shí)測(cè)值評(píng)估患者術(shù)后發(fā)生FO的風(fēng)險(xiǎn),以利于在術(shù)后對(duì)患者及時(shí)進(jìn)行有效的針對(duì)性措施,盡早改善腎臟灌注、減少腎損傷及耗氧量,改善患者預(yù)后。此外,本研究還進(jìn)一步亞組分析冠心病、先天性心臟病、心臟瓣膜病等不同原發(fā)病對(duì)FO的影響,結(jié)果顯示各亞組臨床指標(biāo)無(wú)明顯差異,可能與納入樣本量的范圍有關(guān)。
綜上所述,術(shù)前尿液NGAL和IL-6檢測(cè)均可預(yù)測(cè)早期FO的發(fā)生,聯(lián)合檢測(cè)效能更高,可大幅提高心臟外科術(shù)后患者嚴(yán)重FO的檢出率。
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收稿日期:2023-06-29
基金項(xiàng)目:2019年四川省衛(wèi)生健康委員會(huì)科研課題(普及應(yīng)用項(xiàng)目)立項(xiàng)課題(19PJ126)
通信作者:胡星,E-mail:mei90512@163.com