Alpha-bisabolol逆转ABCB1介导的肿瘤多药耐药及机制

目的研究alpha-红没药醇(alpha-bisabolol)是否能有效逆转ATP结合盒转运体B1(ABCB1)介导的肿瘤多药耐药(MDR)并探讨其机制。方法应用网络药理学技术分析仙鹤草(Agrimonia Eupatoria)的活性成分,预测其靶基因,并进行基因本体论(GO)与京都基因与基因组百科全书(KEGG)通路分析。进一步通过分子对接及热稳定性实验分析alpha-bisabolol和ABCB1的互作。通过MTT法检测alpha-bisabolol能否有效逆转ABCB1介导的肿瘤MDR。通过Western blot法、免疫荧光与流式细胞术研究alpha-bisabolol逆转ABCB1介导肿瘤MDR的机制。结果网络药理学实验结果表明,Agrimonia Eupatoria的活性成分alpha-bisabolol与肿瘤的发生密切相关。分子对接及热稳定性实验结果显示,alpha-bisabolol能够与ABCB1形成稳定的结合。逆转实验结果表明,alpha-bisabolol能够有效逆转ABCB1介导的肿瘤MDR。此外,机制实验结果显示,alpha-bisabolol对肿瘤细胞内ABCB1蛋白的表达及定位并不产生影响。alpha-bisabolol通过抑制ABCB1蛋白的外排功能,提高了细胞内药物的蓄积水平,从而有效逆转肿瘤MDR。结论alpha-bisabolol能够有效逆转ABCB1介导的肿瘤MDR,为化疗耐药的肿瘤患者提供了一种新的治疗策略。

Alpha-1 antitrypsin deficiency and Pi^(*)Z allele as important co-factors in the development of liver fibrosis

BACKGROUND Alpha-1 antitrypsin deficiency(AATD)is a codominant autosomal hereditary condition that predisposes patients to the development of lung and/or liver disease,and Pi*Z allele is the most clinically relevant mutation.AIM To evaluate the impact of clinical parameters and AATD phenotypes,particularly the Pi*Z allele,in liver fibrosis.METHODS Cross-sectional cohort study including consecutive patients with AATD followed in Pulmonology or Hepatology consultation.RESULTS Included 69 patients,49.3%had Pi*MZ phenotype and 10.1%Pi*ZZ.An age≥55 years,age at diagnosis≥41 years and AAT at diagnosis<77 mg/dL predicted a nonalcoholic fatty liver disease fibrosis score(NFS)not excluding advanced fibrosis[area under the curve(AUC)=0.840,P<0.001;AUC=0.836,P<0.001;AUC=0.681,P=0.025].An age≥50 years and age at diagnosis≥41 years predicted a fibrosis-4 index of moderate to advanced fibrosis(AUC=0.831,P<0.001;AUC=0.795,P<0.001).Patients with hypertension,type 2 diabetes mellitus(DM),dyslipidaemia,metabolic syndrome,and regular alcohol consumption were more likely to have a NFS not excluding advanced fibrosis(P<0.001,P=0.002,P=0.008,P<0.001,P=0.033).Patients with at least one Pi*Z allele and type 2 DM were 8 times more likely to have liver stiffness measurement≥7.1 kPa(P=0.040).CONCLUSION Risk factors for liver disease in AATD included an age≥50 years,age at diagnosis≥41 years,metabolic risk factors,regular alcohol consumption,at least one Pi*Z allele,and AAT value at diagnosis<77 mg/dL.We created an algorithm for liver disease screening in AATD patients to use in primary care,selecting those to be referred to Hepatology consultation.

Alpha-黑素细胞刺激素对内毒素血症小鼠肝肺组织表达高迁移率族蛋白1的抑制作用

目的研究Alpha-黑素细胞刺激素(α-MSH)对内毒素血症小鼠肝、肺组织中表达高迁移率族蛋白1(HMGB1)的调控作用。方法腹腔内注射(ip)LPS(25g/kg)和D-Gal(100mg/kg)建立内毒素血症小鼠模型,分别在LPS刺激小鼠1、2、3h后腹腔注射α-MSH(2.5mg/kg),24h后处死小鼠,取小鼠肺、脑、脾、肝、肾组织,应用RT-PCR和Westernblot的方法,从基因、蛋白两个水平检测α-MSH对HMGB1表达的调节作用。结果HMGB1mRNA及蛋白在内毒素血症小鼠肺、脑、脾、肝、肾中均有表达,但在肝、肺中的表达量高于其他组织;于LPS刺激小鼠3h之内腹腔注射α-MSH,能显著下调HMGB1mRNA及蛋白的表达,并且1h之内给药效果最理想。结论α-MSH能有效抑制内毒素血症小鼠肝、肺组织中HMGB1的表达。

Efficacy of thymosin alpha-1 and interferon alpha in treatment of chronic viral hepatitis B:A randomized controlled study

AIM： To observe the efficiency and safety of thymosin-α1 treatment in patients with hepatitis B e antigen （HBeAg） and HBV DNA positive chronic hepatitis. METHODS： Sixty-two patients were randomly divided into groups A and B. The patients in group A received subcutaneous injection of 1.6 mg thymosin-α1, twice a week （T-α1 group） for six months, and the patients in group B received 5 MU interferon alpha （IFN-α） each day for fifteen days, then three times weekly （IFN-α group） for six months. The results between two groups treated with and the group untreated with IFN-α which was followed up for 12 mo （historical control group consisting of 30 patients） were compared, and three groups were comparable between each other （P 〉 0.05） at baseline （age, sex, clinical history, biochemical, and serological parameters）. RESULTS： At the end of treatment, complete response, which was defined as alanine aminotransferase （ALT） normalization and HBV DNA and HBeAg loss, occurred in 9 of 29 （31.0%） patients in the T-α1 group and in 15 of 33 （45.5%） patients in the IFN-α group （χ^2= 1.36, P 〉 0.05）. After a follow-up period of six months, a complete response was observed in 14 of 29 （48.3%） patients in the T-α1 group and in 9 of 33 （27.3%） patients in the IFN-α group （χ^2= 2.93, P 〉 0.05）. Compared with the results observed in the historical control （HC） group untreated with IFN-α which was followed up for 12 mo, the rate of complete response was significantly higher in IFN-α group at the end of therapy （1 of 30 vs 15 of 33, 7：2 = 14.72, P 〈 0.001） and in the T-α1 group at the end of follow-up （1 of 30 vs 14 of 29,χ^2 = 15.71, P 〈 0.001）. In T-α1 and IFN-α treatment groups, the area under （the plasma concentration time） curve （AUC） of negative HBV DNA and HBeAg was 340, 17%, 31% and 19% smaller than that in the HC group. By the end of the follow-up period, the proportions of ALT normalization and negative HBV DNA in the T-α1 group were significantly higher than those in the IFN-α and HC groups. The odds of ALT normalization and negative HBV DNA at the end of the follow-up was three-fold higher in the T-α1 group than in the IFN-α group. Unlike IFN-α, T-α1 was well tolerated by all patients, and no side effects appeared in T-α1 group. CONCLUSION： The results suggest that a 6-too course of T-α1 therapy is effective and safe in patients with chronic hepatitis B. T-α1 is able to reduce HBV replication in patients with chronic hepatitis B. Furthermore, T-α1 is better tolerated than IFN-α and can gradually induce more sustained ALT normalization and HBV DNA and HBeAg loss. However, a response rate of 48.3% is still less ideal. A more effective therapeutic approach warrants further study.

Alpha-1 antitrypsin deficiency and the risk of hepatocellular carcinoma in end-stage liver disease

AIM:To evaluate the association between alpha-1 antitrypsin deficiency(A1ATD) and hepatocellular carcinoma(HCC) in patients with end-stage liver disease(ESLD).METHODS:Patients with cirrhosis and ESLD referred to the Cleveland Clinic Foundation for liver transplantation between 2003 and 2014 were included in the study(N = 675). ESLD was defined as having histological features of cirrhosis and/or radiological evidence of cirrhosis in the context of portal hypertension(ascites,variceal bleeding,thrombocytopenia,or hepatic encephalopathy). A1 ATD was diagnosed using phenotype characterization(MZ or ZZ),liver biopsy detection of PAS-positive diastaseresistant(PAS+) globules,or both. Patients with other causes of liver diseases such as hepatitis C virus(HCV),alcoholic liver disease and non-alcoholic steatohepatitis(NASH) or NASH were also included in the study. HCC was diagnosed by using imaging modalities,biopsy findings,or explanted liver inspection. Follow-up time was defined as the number of years from the diagnosis of cirrhosis to the diagnosis of hepatocellular carcinoma,or from the diagnosis of cirrhosis to the last follow up visit. The rate of HCC was assessed using time-tointerval analysis for interval censored data.RESULTS:This study included 675 patients. 7% of subjects had A1ATD(n = 47). Out of all subjects who did not have A1 ATD,46% had HCV,17% had alcoholic liver disease,19% had NASH and 18% had another primary diagnosis. Of the 47 subjects with A1 ATD,15 had a primary diagnosis of A1ATD(PI*ZZ phenotype and PAS+ globules),8 had a PI*MZ phenotype alone,14 had PAS+ alone,and 10 had both the PI*MZ phenotype and PAS+. Median follow-up time was 3.4(25th,75 th percentiles:1,5.2) years. The overall rate of hepatocellular carcinoma in all subjects was 29%(n = 199). In the A1 ATD group,the incidence rate of HCC was 8.5% compared to 31% in the group of patients with other causes of cirrhosis(P = 0.001). Patients with ESLD due to A1 ATD had the lowest yearly cumulative rate of hepatocellular carcinoma at 0.88% per year compared to 2.7% for those with HCV cirrhosis,1.5% in patients with NASH and 0.9% in alcohol-induced liver disease(P < 0.001).CONCLUSION:Within this group of patients with ESLD,there was no significant association between A1 ATD and increased risk of HCC.

Delayed diagnosis of alpha-1-antitrypsin deficiency following post-hepatectomy liver failure: A case report

Post-hepatectomy liver failure(PHLF) is a leading cause of morbidity and mortality following major liver resection. The development of PHLF is dependent on the volume of the remaining liver tissue and hepatocyte function. Without effective pre-operative assessment, patients with undiagnosed liver disease could be at increased risk of PHLF. We report a case of a 60-year-old male patient with PHLF secondary to undiagnosed alpha-1-antitrypsin deficiency(AATD) following major liver resection. He initially presented with acute large bowel obstruction secondary to a colorectal adenocarcinoma, which had metastasized to the liver. There was no significant past medical history apart from mild chronic obstructive pulmonary disease. After colonic surgery and liver directed neo-adjuvant chemotherapy, he underwent a laparoscopic partially extended right hepatectomy and radio-frequency ablation. Post-operatively he developed PHLF. The cause of PHLF remained unknown, prompting reanalysis of the histology, which showed evidence of AATD. He subsequently developed progressive liver dysfunction, portal hypertension, and eventually an extensive parastomal bleed, which led to his death; this was ultimately due to a combination of AATD and chemotherapy. This case highlights that formal testing for AATD in all patients with a known history of chronic obstructive pulmonary disease, heavy smoking, or strong family history could help prevent the development of PHLF in patients undergoing major liver resection.

DETECTION OF ALPHA-1 ANTICHYMOTRYPSIN IN HEPATOCELLULAR CARCINOMA TISSUE

One hundred and fifty-three consecutive cases of HCC and 25 controls from autopsy material were studied by immunohistochemical method in this paper. A review of the histopathology and demonstration of AFP, alpha- 1-antichymotrypsin (AACT), alpha 1-antitrypsin (AAT) and CEA were made.Among the tumor markers. AACT yielded the highest positive rate, 109 cases (71%) out of 153 HCC. CEA was the next, 95 cases (62%) .AFP and AAT gave the same result, 72 cases (47%) . AACT, AAT and CEA were not found in the controls. AFP was present in a few hepatocytes in 1 of 25 controls. The results were in keeping with serum tests so far as the highest positive rate being AACT was concerned. Therefore, combined determination of AACT and AFP would seem a better screening method than by that of AFP alone for survey of HCC.

On the Activities of Pancreatic Proteases and Alpha-1 Proteinase Inhibitor in Meat-Type Chicken

The study was aimed at the evaluation of the effects of breed, age, different digestion stimulators, and dietary crude protein (CP) level on the activities of proteolytic enzymes in pancreatic tissue and duodenal chymus (in vivo), serum trypsin and α1-proteinase inhibitor (A1PI) concentrations in meat-type chicks. The study of age dynamics of trypsin and A1PI concentrations was performed on the chicks of hybrid cross “Smena-8”and two parental lines (Plymouth Rock and Cornish) fed standard commercial corn-wheat-SBM diets. Twenty birds per breed were euthanized at 1, 7, 14, 21, 28 and 35 days of age to obtain blood samples and pancreatic homogenate. Experiments on the effects of different digestion promotors (probiotic, acidifier, phytobiotic, enzymatic preparation) and different CP levels (finisher diet, CP 20%, vs. ground corn, CP 8.5%) were performed on 12 hybrid chicks with fistulated duodenum from 14 to 50 days of age. The following conclusions were made: 1) At 1 day of age high proteolytic activity in pancreatic tissue and maximal serum concentrations of trypsin and A1PI were found in both hybrid and parental lines. Since 7 to 35 days of age A1PI concentration was nearly constant, serum trypsin concentration decreased while proteolytic activity in pancreatic tissue exhibited undulate increase;2) Proteolytic activity in pancreatic tissue was higher in hybrids compared to the parental lines from 7 to 35 days of age (p 0.05);3) Supplementation of diet with exogenous enzymes stimulated the digestion due to the increase in protease activity in duodenal chymus by 9.1% compared to unsupplemented control (p 0.05);4) Proteolytic activity in duodenal chymus significantly responded to the substitution of ground corn for the complete diet by 2-fold decrease while serum trypsin concentration responded by 2.5-fold increase (p 0.001). This fact can indicate that physiological functions of digestive proteases are not confined to the digestive processes.

IMMUNOHISTOCHEMICAL STUDY OF ALPHA-1-ANTICHYMOTRYPSIN IN GLIOMA

GFAP is a specific antigen of glial element, but Alpha-1-antichymotrypsin has not been reported in the literature. Alpha-1-antichymotrypsin was guided by GFAP using PAP method to the astrocytes of 137 gliomas. 120 (87%) gliomas were positive for Alpha-1-antichymotrypsin. Of these 120 gliomas, 86 (72%) gave diffuse distribution, 17 (14%) gave focal distribution, and 17 (14%) gave scattered distributions. Alpha-1-antichymotrypsin in glioma tissue may be an important tumor marker for diagnosis.

Alpha-1 Antitrypsin Deficiency Family Study

According to the latest World Health Organization report 64 million people suffer from Chronic Obstructive Pulmonary Disease （COPD）, 3 million people died from COPD and it is predicted that COPD will become the third leading cause of death worldwide by 2030. The alpha-1 antitrypsin deficiency is a rarely diagnosed hereditary disease caused by a genetic mutation and it is one of the most prevalent genetic disorders primarily affecting the lungs, especially in the form of COPD or emphysema, but in some cases also the liver or skin. The Global Initiative for Chronic Obstructive Lung Disease recommends all patients with COPD at a young age or significant family history to be examined for alpha-1 antitrypsin deficiency. This article presents the case of a 42 year old, female patient, Portuguese, with history of Chronic Obstructive Pulmonary Disease, 40 pack units/year smoker, with unknown family history, coming to her family doctor with breath shortness, especially during physical activities, with unsatisfying response to pharmacological prescribed therapy. Physical examination was normal. Alpha- 1 antitrypsin deficiency was confirmed by blood testing. All patient＇s first degree relatives were investigated showing low alpha-1 antitrypsin blood concentrations thus genetic tests were later performed. This case reinforces the need for primary care physicians to be aware of alphal-antitrypsin deficit as an underdiagnosed clinical entity.

Managing panniculitis in alpha-1 antitrypsin deficiency: Systematic review of evidence behind treatment

AIM To systematically review literature for management of alpha-1 antitrypsin deficiency(AATD) panniculitis. METHODS Multiple databases were searched using combinations of pertinent terms. Articles were selected describing panniculitis treatment in patients with AAT < 11 μmol and/or PiZZ genotype, with no language limitation. All relevant articles were accessed in full text. Independent review of abstracts and full manuscripts was conducted by 2 reviewers, and quality assessment by one reviewer(checked by a second). Data extraction was conducted byone reviewer(checked by a second). Narrative synthesis only was conducted, as data were unsuitable for metaanalysis.RESULTS Thirty-two case reports and 4 case series were found. Augmentation therapy(infusions of plasma-derived AAT) was the most successful, with complete resolution of symptoms in all patients. Dapsone is a less expensive option, and it achieved clinical resolution in 62% of patients, but it is very poorly tolerated. Among other single-agent antibiotics, doxycycline was the most successful with complete clinical resolution seen in 33% of patients. Immunosuppressants were largely unsuccessful; 80% of patients exhibited no response. Liver transplantation and therapeutic plasma exchange displayed complete resolution in 66% of patients. Other strategies, such as non-steroidal anti-inflammatory drugs or antibiotics other than dapsone did not show sufficient response rates to recommend their use. Authors note the risk of bias imposed by the type of evidence(case reports, case series) available in this field.CONCLUSION Dapsone is the recommended first line therapy for AATD panniculitis, followed by augmentation therapy. Plasma exchange may be an alternative in the setting of rapidly progressive disease.

SlimQuick ^_(TM)-associated hepatotoxicity in a woman with alpha-1 antitrypsin heterozygosity

Green tea (Camellia sinensis)-associated hepatotoxicity is reported. However, the presence of alpha-1 antitrypsin MZ phenotype as a predisposing factor to green tea-associated drug-induced liver injury (DILI) is unknown. A previously healthy woman with alpha-1 antitrypsin MZ phenotype who took SlimQuick?, an herbal supplement containing green tea extract, developed severe hepatotoxicity requiring corticosteroid treatment. Green tea-associated hepatotoxicity is reviewed and alpha-1 antitrypsin MZ phenotype as a predisposing factor to green tea-associated DILI is discussed. Liver biopsy demonstrated marked inflammation with necrosis suggestive of toxic injury with diffuse alpha-1 antitrypsin globule deposition on immunostaining. Corticosteroid therapy resulted in rapid clinical improvement. Alpha-1 antitrypsin MZ phenotype may increase vulnerability to herbal hepatotoxicity.

长链非编码RNA alpha-2-巨球蛋白反义RNA 1靶向微小RNA-106b-5p调控氧化型低密度脂蛋白诱导的人脑微血管内皮细胞损伤

目的探讨长链非编码RNA(lncRNA)alpha-2-巨球蛋白反义RNA 1(A2M-AS1)靶向微小RNA(miR)-106b-5p对氧化型低密度脂蛋白(ox-LDL)诱导的人脑微血管内皮细胞损伤的影响。方法用ox-LDL诱导人脑微血管内皮细胞设为ox-LDL组,正常培养细胞为对照(Ctrl)组;A2M-AS1过表达(pcDNA-A2M-AS1组)、空载体(pcDNA组)、miR-106b-5p抑制剂(anti-miR-106b-5p组)、阴性对照(anti-miR-NC组)、pcDNA-A2M-AS1与对照mimic NC(miR-NC组)、pcDNA-A2M-AS1与miR-106b-5p模拟物(miR-106b-5p mimics组)转染细胞后加ox-LDL处理,n=9;Real-time PCR检测A2M-AS1与miR-106b-5p表达;试剂盒检测丙二醛(MDA)、超氧化物歧化酶(SOD)和过氧化氢酶(CAT)水平;流式细胞术及TUNEL法检测细胞凋亡;双荧光素酶报告基因实验检测A2M-AS1与miR-106b-5p靶向关系;Western blotting检测Bcl-2和Bax蛋白表达量。结果与Ctrl组比较,ox-LDL组A2M-AS1表达水平、SOD和CAT活性、Bcl-2蛋白水平降低,miR-106b-5p表达水平、MDA水平、凋亡率、Bax蛋白水平升高(P<0.05);过表达A2M-AS1或干扰miR-106b-5p降低ox-LDL诱导细胞后MDA水平、凋亡率与Bax蛋白水平,升高SOD、CAT活性和Bcl-2蛋白水平(P<0.05);A2M-AS1靶向miR-106b-5p;上调miR-106b-5p逆转过表达lncRNA A2M-AS1对ox-LDL诱导的人脑微血管内皮细胞损伤的作用。结论A2M-AS1通过靶向miR-106b-5p减轻ox-LDL诱导的人脑微血管内皮细胞损伤。

Study of the Effect of Zhuang Medicine Aponeurotic System Triple Therapy on Lumbar Disc Herniation and Alpha-1 Acid Glycoprotein Level

Objective:To analyze the application effect of Zhuang medicine aponeurotic system triple therapy in the treatment of lumbar disc herniation and its effect on the level of alpha-1 acid glycoprotein(alpha-1 AGP).Methods:200 patients with lumbar disc herniation were selected and randomly divided into a treatment group and a control group,100 cases in each group.The control group was given conventional acupuncture,and the treatment group was treated with manipulation+fire needling+cupping.The alpha-1-AGP levels before and after treatment,as well as the lumbar spine function and pain scores before and after treatment,and the adverse reactions occurred during treatment between the two groups were compared.Results:Before treatment,there was no significant difference in alpha-1 AGP levels,lumbar function,and pain scores between the two groups(P>0.05).After treatment,the lumbar function scores of the two groups were significantly increased,with the treatment group having higher scores than the control group(P<0.05);the incidence of adverse reactions in the treatment group was 2.00%,which was much lower than the control group(P>0.05).Conclusion:Appropriate application of Zhuang medicine aponeurotic system triple therapy in the clinical treatment of lumbar disc herniation can promote the improvement of alpha-1 AGP index level,reduce the pain degree of patients,and improve their lumbar spine function.At the same time,Zhuang medicine also has significant advantages in terms of safety,while ensuring the efficacy and safety of the treatment.

肺结核患者血浆中性粒细胞防御素1-3浓度与病情活动的关系

目的探讨肺结核患者血浆中性粒细胞防御素1-3(HNP1-3)浓度与肺结核病情活动的关系。方法选择2009年5月～2010年6月我院收治的肺结核患者125例,其中活动性肺结核组患者61例,静止期肺结核组患者64例。另选择健康体检者100例作为对照组。采用ELISA法检测各组血浆中HNP1-3浓度。结果三组血浆HNP1-3浓度比较存在显著性差异(F=8.291,P<0.05),组间两两比较,活动性肺结核组血浆HNP1-3浓度明显高于静止期肺结核组和对照组(t=6.429,8.195,P<0.05),静止期肺结核组略高于对照组,但两组间差异无显著意义(t=0.784,P>0.05)。相关性分析发现,肺结核患者血浆HNP1-3水平与血沉无相关性(P>0.05),而与外周血白细胞及中性粒细胞计数、C反应蛋白水平和影像学计分呈正相关(r=0.574,0.692,0.658,0.608,P<0.05)。结论 HNP1-3可能在肺结核发病机制中起着重要的作用,且与肺结核病情活动性有关。

血浆人中性粒细胞防御素1-3在肺结核患者中的动态变化研究

目的探讨人中性粒细胞防御素1-3(HNP1-3)在初治及复治肺结核患者群体中的作用。方法将研究对象分为初治组(21例)、复治组(27例)及健康对照组(25例),于治疗前后分别测定血浆HNP1-3浓度(ELISA法)。结果初治组基线血浆HNP1-3水平明显高于复治组及对照组(均P<0.001),治疗6个月后水平明显降低(P<0.01);复治组基线血浆HNP1-3水平明显低于初治组及对照组(均P<0.01),经过治疗后变化不明显(P>0.05);治疗前血浆HNP1-3水平与外周血白细胞(r=0.538,P=0.027)及中性粒细胞数(r=0.676,P=0.011)呈正相关,与痰菌阴转时间呈负相关(r=-0.602,P=0.013)。结论血浆HNP1-3在初治患者中可作为反应治疗效果的指标,HNP1-3分泌不足可能造成结核杆菌难以杀灭。

外周血LRG1和HIF-1α联合Nrf-2蛋白对肛瘘镜下手术治疗肛瘘患者切口感染的早期诊断价值

目的探讨外周血富含亮氨酸的Alpha-2糖蛋白-1(LRG1)和缺氧诱导因子1α(HIF-1α)联合核因子-红细胞-2相关因子2(Nrf-2)蛋白对肛瘘镜下手术治疗肛瘘患者切口感染的早期诊断价值。方法回顾性选取2019年6月至2021年12月在秦皇岛市第一医院肛肠外科接受肛瘘镜下手术治疗肛瘘的126例患者作为研究对象,根据是否发生术后切口感染分为感染组(n=20)和非感染组(n=106)。采集术前、术后第1天和术后第3天外周静脉血,酶联免疫吸附试验分析血清LRG1、HIF-1α和Nrf-2水平,并采用操作者工作特征(ROC)曲线分析血清LRG1、HIF-1α和Nrf-2水平对术后切口感染发生的预测价值。结果感染组术后第1天和第3天血清LRG1、HIF-1α和Nrf-2水平均高于术前,且术后第1天高于术后第3天,差异均有统计学意义(P<0.05);非感染组术后第1天血清Nrf-2水平高于术前及术后第3天,差异均有统计学意义(P<0.05);术后第1天和第3天,感染组血清LRG1、HIF-1α和Nrf-2水平分别为(23.58±2.40)pg/mL、(85.12±14.06)pg/mL、(236.58±32.74)ng/mL和(15.09±2.85)pg/mL、(55.07±11.38)pg/mL、(186.19±27.04)ng/mL,均高于非感染组[第1天:(5.18±1.34)pg/mL、(44.89±7.30)pg/mL、(30.70±4.57)ng/mL;第3天:(5.04±1.12)pg/mL、(45.32±7.25)pg/mL、(28.56±4.72)ng/mL],差异均有统计学意义(P<0.05)。术后第1天血清LRG1、HIF-1α和Nrf-2水平单独及联合预测评估术后切口感染发生的ROC曲线下面积(95%CI)分别为0.805(0.642~0.971)、0.750(0.655~0.829)、0.763(0.592~0.946)、0.874(0.791~0.940)。结论肛瘘镜下手术治疗肛瘘患者有术后切口感染风险,术后第1天血清LRG1、HIF-1α和Nrf-2水平对术后切口感染的发生有一定预测价值,3者联合检测的预测价值更高。

Use of Cross-Fostering to Enhance Growth of Pigs That Are Predicted to Grow Poorly Based on Plasma α-1 Acid Glycoprotein Concentration

Porcine α-1 acid glycoprotein (AGP) in newborn pigs can be used to predict growth rate through weaning and is a marker for growth impairment. This study examined whether nutritional support can improve the growth rate of piglets identified as having poor growth potential. Cross-fostering (CF) and CF plus a milk supplement (CF + MS) were used to attempt to improve the growth performance of pigs. Blood was collected at d1 post-parturition for measurement of plasma AGP for all pigs in 28 litters contributing to the experiment. Piglets with the highest plasma AGP level were weight and sex matched to a littermate with a low plasma AGP concentration and four pairs of these weight and sex matched pigs were grouped into four foster litters per treatment (control, CF, CF + MS). The control group was assembled by pairing littermates remaining in donor litters. Pigs stayed on treatment until weaning at 21 days of age. At 35 days of age, dual energy X-ray absorptiometry (DXA) was performed on CF and CF + MS pigs to evaluate carcass composition. Control pairs differed in weaning weight, with pigs with higher plasma AGP at 1 day of age having smaller weaning weights than their littermates of similar birth weight (P < 0.05). However, CF eliminated the difference in weaning weight between the slow growing pigs and their birth weight matched littermates. CF + MS produced a similar effect as CF (P > 0.05). At 35 days of age, body weights were still similar between CF littermates and between CF + MS littermates (P > 0.05). DXA analysis demonstrated that body composition was similar between CF or CF + MS treated pigs and their littermates. These data demonstrate that CF can be used to correct the growth impairment in pigs predicted using plasma AGP as the marker. CF + MS can do the same, but at greater expense.

Role of biomarkers in community-acquired pneumonia management

Community-acquired pneumonia(CAP)poses a significant global health threat,particularly affecting vulnerable populations.Biomarkers and scoring systems play a crucial role in diagnosing,assessing severity,and guiding treatment decisions for CAP patients.Biomarkers like C reactive protein,procalcitonin,and the neutrophil-to-lymphocyte ratio aid in diagnosis and severity assessment,while scoring systems such as CURB-65 and Pneumonia Severity Index classify patients into risk categories.Emerging biomarkers(uremia,elevated respiratory rate,hypotension,and age≥65)like serum amyloid A and S100 proteins show promise in predicting disease severity and prognosis.However,further research is needed to determine their precise roles and clinical utility in CAP management.

Liver Characterization of a Cohort of Alpha-1 Antitrypsin Deficiency Patients with and without Lung Disease

Background and Aims:Alpha-1 antitrypsin deficiency(AATD)is a genetic disorder characterized by the misfolding and accumulation of the mutant variant of alpha-1 antitrypsin(AAT)within hepatocytes,which limits its access to the circulation and exposes the lungs to protease-mediated tissue damage.This results in progressive liver disease secondary to AAT polymerization and accumulation,and chronic obstructive pulmonary disease(COPD)due to deficient levels of AAT within the lungs.Our goal was to characterize the unique effects of COPD secondary to AATD on liver disease and gene expression.Methods:A subcohort of AATD individuals with COPD(n=33)and AATD individuals without COPD(n=14)were evaluated in this study from our previously reported cross-sectional cohort.We used immunohistochemistry to assess the AATD liver phenotype,and RNA sequencing to explore liver transcriptomics.We observed a distinct transcriptomic profile in liver tissues from AATD individuals with COPD compared to those without.Results:A total of 339 genes were differentially expressed.Canonical pathways related to fibrosis,extracellular matrix remodeling,collagen deposition,hepatocellular damage,and inflammation were significantly upregulated in the livers of AATD individuals with COPD.Histopathological analysis also revealed higher levels of fibrosis and hepatocellular damage in these individuals.Conclusions:Our data supports a relationship between the development of COPD and liver disease in AATD and introduces genes and pathways that may play a role in AATD liver disease when COPD is present.We believe addressing lung impairment and airway inflammation may be an approach to managing AATD-related liver disease.