Salivary proteins and microbiota as biomarkers for early childhood caries risk assessment

Early childhood caries （ECC） is a term used to describe dental caries in children aged 6 years or younger. Oral streptococci, such as Streptococcus mutans and Streptococcus sorbrinus, are considered to be the main etiological agents of tooth decay in children. Other bacteria, such as Prevotella spp. and Lactobacillus spp., and fungus, that is, Candida albicans, are related to the development and progression of ECC. Biomolecules in saliva, mainly proteins, affect the survival of oral microorganisms by multiple innate defensive mechanisms, thus modulating the oral microflora. Therefore, the protein composition of saliva can be a sensitive indicator for dental health. Resistance or susceptibility to caries may be significantly correlated with alterations in salivary protein components. Some oral microorganisms and saliva proteins may serve as useful biomarkers in predicting the risk and prognosis of caries. Current research has generated abundant information that contributes to a better understanding of the roles of microorganisms and salivary proteins in ECC occurrence and prevention. This review summarizes the microorganisms that cause caries and tooth-protective salivary proteins with their potential as functional biomarkers for ECC risk assessment. The identification of biomarkers for children at high risk of ECC is not only critical for early diagnosis but also important for preventing and treating the disease.

Matricellular proteins as possible biomarkers for early brain injury after aneurysmal subarachnoid hemorrhage

Aneurysmal subarachnoid hemorrhage remains devastating,and the most important determinant of poor outcome is early brain injury（EBI）.In clinical settings,as a surrogate marker of EBI,loss of consciousness at ictus,poor initial clinical grades,and some radiographic findings are used,but these markers are somewhat subjective.Thus,it is imperative to find biomarkers of EBI that have beneficial prognostic and therapeutic implications.In our opinion,an ideal biomarker is a molecule that is implicated in the pathogenesis of both EBI and subsequently developing delayed cerebral ischemia（DCI）,being a therapeutic target,and can be measured easily in the peripheral blood in an acute stage.A good candidate of such a biomarker is a matricellular protein,which is a secreted,inducible and multifunctional extracellular matrix protein.There are many kinds of matricellular proteins reported,but only tenascin-C,osteopontin,galectin-3 and periostin are reported relevant to EBI and DCI.Reliable biomarkers of EBI may stratify aneurysmal subarachnoid hemorrhage patients into categories of risk to develop DCI,and allow objective monitoring of the response to treatment for EBI and earlier diagnosis of DCI.This review emphasizes that further investigation of matricellular proteins as an avenue for biomarker discovery is warranted.

Biological Analysis of HSV-1 Immediate-early Proteins ICP0, ICP22, and ICP27 in Neuroblastoma Cells

The three immediate-early proteins of HSV-1, ICP0, ICP22, and ICP27, have specific and pivotal functions in transcriptional activation and inhibition, multiple regulatory and control processes of viral genes. In this paper, the expression and localization of these three proteins were studied in neuroblastoma cells using biochemical assays, and their possible and potential interactive functions are discussed. The data show that the three proteins are localized in different structures, specifically in the PML-NB-associated structure, which is a specific nuclear structure composed of many protein molecules and bound tightly to the nuclear matrix in neuroblastoma cells. The results suggest that the activating and suppressive functions of ICPs are mostly dependent on their transcriptional and regulatory roles, including the PML-NB-associated structure.

Role of Glucose-regulated Protein 78 in Early Brain Injury after Experimental Subarachnoid Hemorrhage in Rats

Early brain injury（EBI） plays a key role in the pathogenesis of subarachnoid hemorrhage（SAH）. This study investigated the role of glucose-regulated protein 78（GRP78） in EBI after SAH. Male Sprague-Dawley rats（n=108） weighing 260±40 g were divided into control, sham-operated, and operated groups. Blood was injected into the prechiasmatic cistern of rats in the operated group. Neurological scores, ultrastructures of neurons, apoptosis, and GRP78 expression in the hippocampus were examined using Garcia scoring system, transmission electron microscopy, terminal deoxynucleotidyl transferase-mediated d UTP nick-end labelling, and Western blotting at 1, 6, 12, 24, 48, and 72 h after SAH, respectively. The results showed that neurological scores were significantly decreased in the operated group as compared with those in control and sham-operated groups at 12, 24, 48, and 72 h. Metachromatin, chromatin pyknosis at the edge, endoplasmic reticulum swelling, and invagination of nuclear membrane were observed at 24 h in the operated group, indicating the early morphological changes of apoptosis. The number of apoptotic cells was significantly increased in the operated group as compared with that in control and sham-operated groups at 6, 12, 24, 48, and 72 h. The GRP78 protein expression levels in the operated group were significantly elevated at all time points and reached the peak at 12 h. GRP78 expression was positively associated with apoptosis cells and negatively with neurological scores. In conclusion, EBI was demonstrated to occur after SAH and GRP78 was involved in the development of EBI after SAH.

Early Aerobic Exercise Promotes Neurological Function Recovery of Rats after Cerebral Ischemia/Reperfusion by Upregulating the Expression of Heat Shock Protein A5

Objective The neuroprotective function of heat shock protein A5(HSPA5)in ischemic stroke has been confirmed.This study aimed to investigate the effects of early aerobic exercise on neurological function recovery from cerebral ischemia/reperfusion and to determine whether these effects are associated with the expression level of HSPA5 in the ischemic penumbra.Methods A total of 72 male Sprague-Dawley rats were randomly assigned to the ischemia and exercise group[middle cerebral artery occlusion(MCAO)-Ex,n=18],ischemia and sedentary group(MCAO-St,n=18),sham-surgery and exercise group(Sham-Ex,n=18),or sham-surgery and sedentary group(Sham-St,n=18).The MCAO-Ex and MCAO-St groups were subjected to MCAO for 60 min,whereas the Sham-Ex and Sham-St groups were subjected to an identical operation without MCAO.Rats in the MCAO-Ex and Sham-Ex groups then ran on a treadmill for 30 min once a day for 5 consecutive days.After reperfusion,the motor function of the rats was scored by the Bederson neurological function test,balance beam test,and screen test.Nissl staining was conducted to assess morphological and structural change of nerve cells in the ischemic penumbra.The reverse transcription-quantitative polymerase chain reaction was applied to detect the mRNA expression of HSPA5.Western blot analysis was conducted to determine the protein expression of HSPA5.Terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling(TUNEL)staining was carried out in the ischemic penumbra after MCAO.Results Rats receiving early treadmill exercise had lower Bederson neurological function,balance beam,and screen test scores on the 3rd,7th,and 14th days after MCAO;in addition,more neurons survived in the ischemic penumbra after MCAO,and higher mRNA and protein expression of HSPA5 and fewer TUNEL-positive stained cells were observed.Conclusion Our study demonstrated that early aerobic exercise can improve neurological function recovery after ischemia/reperfusion.Furthermore,the increased level of HSPA5 in the ischemic penumbra might be one of the mechanisms of enhanced neurological function recovery.

Optogenetic activation of intracellular signaling based on light-inducible protein-protein homo-interactions

Dynamic protein-protein interactions are essential for proper cell functioning.Homointeraction events—physical interactions between the same type of proteins—represent a pivotal subset of protein-protein interactions that are widely exploited in activating intracellular signaling pathways.Capacities of modulating protein-protein interactions with spatial and temporal resolution are greatly desired to decipher the dynamic nature of signal transduction mechanisms.The emerging optogenetic technology,based on genetically encoded light-sensitive proteins,provides promising opportunities to dissect the highly complex signaling networks with unmatched specificity and spatiotemporal precision.Here we review recent achievements in the development of optogenetic tools enabling light-inducible protein-protein homo-interactions and their applications in optical activation of signaling pathways.

Influence of early weaning beef cows on the performance of male progeny and the need for winter protein supplementation

One hundred and three Hereford × Angus crossbred, spring-calving cows were used to determine the influence of early weaning performance of their male progeny and the need for cowherd winter supplementation. Treatments were early weaned (EW;115-d of age) and normal weaned calves (NW;220-d of age). Both intact and castrated male progeny were randomly allotted to early and normal weaning calf management treatments. Following summer grazing and weaning protocols, cows within each weaning group were randomly assigned to receive winter supplementation treatments of LOW (1.26 kg/hd/d) or HIGH (1.81 kg/hd/d) amounts of a protein supplement containing 450 g/kg CP (DM basis). Cows whose calves were weaned early gained more BW and BCS (P P P P = 0.04) BCS but similar (P = 0.74) BW when compared with cows with normally weaned calves that received 100% of their supplement (NWHIGH). Early weaning has the potential to reduce the amount of supplement required during the winter grazing period.

Advantage of Introducing Quantitative Light-Induced Fluorescence in School Dental Checkups

Background: Caries detection in school oral examinations insufficient accuracy. Objective: To evaluate advantages of introducing quantitative light-induced fluorescence-digital (QLF-D) in school oral examinations. Methods: Experiment No. 1. Early demineralized lesions in the upper and lower incisors and canines were visually inspected by three dentists and by QLF-D. The numbers of tooth planes with early demineralized lesions were compared between the methods. Experiment No. 2. Approximal demineralized lesions in molars were assessed by visual inspection, x-ray imaging, and QLF-D. The numbers of tooth planes with demineralized lesions were compared among the methods. Experiment No. 3. Plaque distribution was evaluated by QLF-D and a traditional staining method. The ratio of the diameter of plaque to tooth crown in the tooth axis direction in each method was calculated. The results were evaluated by Pearson’s correlation coefficient analysis and Bland-Altman plot. Results: Experiment No. 1. The three dentists found 0.67 tooth planes on average. QLF-D found 22 tooth planes with early demineralized lesions in the same samples. Experiment No. 2. Fourteen approximal tooth planes of molars were found to have demineralized lesions by x-ray imaging. QLF-D detected 71.4% of the tooth planes out of the 14, whereas visual inspection found 7.1%. Experiment No. 3. The Pearson’s correlation coefficient for the evaluations of plaque distribution between the QLF-D and traditional staining methods was 0.77 (P Conclusion: The results support introduction of QLF-D for use in school dental examinations.

Expression of insulin-like growth factor-1 mRNA and protein level of corpora striata in ischemic side at the early stage of middle cerebral artery ischemia/reperfusion in rhesus monkeys

BACKGROUND： Insulin-like growth factor-I（IGF-1）, as one of the important members of growth factor family, participants in the regulation of many physiological functions and behaviors, having very strong neuroprotective effect. However, the expression of IGF-1 following cerebral ischemia/reperfusion is still disputed. OBJECTIVE： To observe the expression of IGF-1 and protein of corpora striata in ischemic side at the early stage of middle cerebral artery ischemia/reperfusion in rhesus monkey. DESIGN ： A completely randomized grouping design, controlled animal experiment SETTING ： Institute of Cerebrovascular Disease, Affiliated Hospital of Medical College of Qingdao University MATERIALS： ① Totally 17 rhesus monkeys , of either gender, aged 4 to 5 years, were enrolled . Seven rhesus monkeys observed with gene chip were randomly divided into 2 groups： sham operation group （n=3） and ischemia/reperfusion group 〈n=4〉. Ten rhesus monkeys observed with in situ hybridization and immunohistochemistry method were randomly divided into 2 groups： sham operation group 〈n=3 〉and ischemia/reperfusion group （n=7）. Rhesus monkeys observed under microscope were divided into 2 groups： sham operation group （n=6） and ischamia/reperfusion group （n=-11）.②Materials used in the experiment： cresyl violet （Sigma Company, America）; immunohistochemical reagent kit （ Huamei Bio-engineering Company）; In situ hybridization reagent kit （Boshide Bio-engineering Co.Ltd, Wuhan）; 12 800 dots chip （Boxing Company, Shanghai）. METHODS ： This experiment was carried out at the Institute of Cerebrovascular Disease, Affiliated Hospital of Medical College of Qingdao University from January 2001 to December 2003.① The onset area of middle cerebral artery was blocked for 2 hours, middle cerebral artery ischemia/reperfusion models were created.② After ischemia/reperfusion for 24 hours, cerebral tissue sections of rhesus monkeys were prepared and stained with cresyl violet. Image analysis was performed with 5001W image analysis software. Morphological change of corpora striata of operative side was observed in the rhesus monkeys between two groups. Total RNA was extracted from cerebral tissue. ③ Detection of gene chip： Cy3-duTP and Cy5-duTP were used to respectively perform reverse transcription labeling. The sample was reversely transcribed into cDNA, then hybridized with cDNA of cerebral tissue. Genes with the separate absolute value of cy3 and cy5〉800, cY3/cy5 〉 2（high expression） or 〈 0.5 （low expression） were found out. Those were genes with differential expression. ④ The expressions of IGF-1 mRNA and protein level of corpora striata in ischemic side of rhe- sus monkeys were detected between sham operation group and ischemia/reperfusion group at 9 and 24 hours after ischemia/reperfusion with in situ hybridization method and immunohistochemical method. Brown granules were IGF-1 protein positive cells. ⑤ Analysis of variance was used in the difference comparison of measurement data among groups. MAIN OUTCOME MEASURES ： ① Change of morphological structure of corpora striata at ischemic side in rhesus monkeys. ② Change of cerebral gene expression profiles at ischemia/reperfusion in rhesus monkeys between two groups.③ Expression of IGF-1 mRNA and protein level of corpora striata at ischemia/reperfu- sion in rhesus monkeys between two groups. RESULTS ： ① Pathological change ： Obvious pathological change of cerebral infarction appeared in the ischemia and reperfusion group, while there was no such pathological change in the sham operation group.② Change of gene expression profile ： There were 4480 genes with difference expression in the ischemia/reperfusion group and sham-operation group, in which, 260 genes had high expression and their absolute value was over 800, and 63 genes had low expression, cy3/cy5 of IGF-1 was 0.379, being relative low ex- pression. ③ IGF-1 mRNA and protein positive cell counts in corpora striata at cerebral ischemic side[IGF-1 mRNA： 〈9.72±1.18）,（9.11 ±0.76）,（14.77±0.60） counts/field：lGF-1 protein： （15.11 ±1.83）,（15.39±0.78）, （34.62±0.97）counts/field, P 〈 0.05-0.01]. CONCLUSION： IGF-1 mRNA and protein are lowly expressed in middle cerebral artery of rhesus monkeys at ischemia/reperfusion.

THE VALUE OF URINE PROTEIN EXCRETION IN DIAGNOSING EARLY DIABETIC NEPHROPATHY

We tested urine albumin excretion rate (UAER), urine transrerrin (TRF ), retinolulnding protein (RBP), N --acetyl--aD-gi ucosamlnldase (N AG ), P, - mi c rogl obu I in (P, -- M G ) and lgGIn 45 cases of NIDDM. Thirty cases with UAER<300 mg/d were divided into two groups. Data wereshown with urine protein index (urine protein/urine creatlne). ResultS showed that urine transferrinwas more seusltlve than albumlu, and the combined test or urine Protein is nontraumatic, which hadsteatncance to diagnose early diabetic nepkropatby.

血清淀粉样蛋白A在新生儿败血症、坏死性小肠结肠炎早期诊断中的价值

新生儿早/晚发型败血症(EOS/LOS)、坏死性小肠结肠炎(NEC)是新生儿期常见疾病,严重病例预后不良。因早期临床表现不特异、诊断较困难,现非特异性实验室检查(C反应蛋白,降钙素原等)尚存缺点,可能导致漏诊误诊。血清淀粉样蛋白A(SAA)是一种新型急性期反应物,其在EOS/LOS、NEC早期即明显升高、持续时间久,与疾病严重程度相关、且能反映治疗效果,可作为这两种疾病诊治的生物标记物。本文就SAA及其在EOS/LOS、NEC早期诊断中的价值进行综述,为该类疾病诊治提供新的参考。

C反应蛋白、降钙素原和白细胞介素6在早期急性胰腺炎合并感染中的诊断价值分析

目的探讨C反应蛋白(CRP)、降钙素原(PCT)、白细胞介素6(IL-6)在早期急性胰腺炎(AP)合并感染中的诊断价值。方法选择2022年1月至2024年1月滕州市中心人民医院消化内科收治的112例AP患者,依据患者入院时的严重程度将其划分为3组分别为轻症组、中重症组、重症组。记录入院首日、3 d、7 d,IL-6、CRP、PCT水平;同时以Spearman相关性分析病情严重程度与IL-6、CRP、PCT相关性。结果入院首日,3组患者IL-6、CRP、PCT水平均高于各指标正常参考范围。IL-6水平入院首日、入院3 d、入院7 d,重症组>中重症组>轻症组(P<0.05),且入院7 d>入院3 d>入院首日(P<0.05)。CRP水平,重症组、中重症组入院首日无差异(P>0.05),重症组、中重症组>轻症组(P<0.05);入院3 d、入院7 d,重症组>中重症组>轻症组(P<0.05),且入院7 d>入院3 d>入院首日(P<0.05)。入院不同时间三组PCT水平,均重症组>中重症组>轻症组(P<0.05);轻症组、中重症组入院不同时间段PCT水平,均入院3 d>入院7 d>入院首日(P<0.05);重症组入院3 d、入院7 d比较无差异(P>0.05),入院3 d、入院7 d>入院首日(P<0.05)。IL-6、CRP、PCT、IL-6+CRP+PCT对AP的AUC分别为0.82、0.85、0.90、0.94。IL-6、CRP、PCT预测AP的截断值分别为50.77 ng/L、124.56 mg/L、3.25μg/L。经ROC曲线分析显示,PCT为最佳AP预测因子,IL-6、CRP、PCT联合诊断准确性更高。结论PCT、CRP、IL-6单一或联合用于AP合并感染的诊断评估均具有一定价值,且三者联合应用诊断价值更高,可早期评价患者病情严重程度,指导疾病治疗,建议将其作为AP早期病情评估、预后预测参考指标。

子宫动脉舒张早期切迹联合妊娠相关血浆蛋白A对子痫前期的预测价值

目的研究子宫动脉舒张早期切迹联合妊娠相关血浆蛋白A(PAPP-A)对子痫前期的预测价值。方法回顾性选取2020年6月至2023年6月入邯郸市第一医院的86例子痫前期孕妇为观察对象,设为研究组;同时选取同期入院86名健康孕妇,设为对照组。两组均于妊娠11~13+6周对PAPP-A水平与右、左侧子宫动脉舒张早期切迹指数予以测定。比较两组孕妇的右切迹指数、左切迹指数及PAPP-A水平,同时计算并比较右切迹指数、左切迹指数、PAPP-A单独及联合诊断子痫前期的受试者操作特征(ROC)曲线下面积(AUC),并比较右切迹指数联合PAPP-A与左切迹指数联合PAPP-A的AUC。结果研究组孕妇右、左切迹指数与PAPP-A水平分别为0.71±0.21、0.65±0.27、(3504.84±1598.38)mU/L,均明显低于对照组[0.84±0.18、0.82±0.29、(5019.47±2498.96)mU/L],差异均有统计学意义(P<0.05)。子痫前期预测中右切迹指数的临界值为0.79,敏感度为64.38%,特异度为60.08%,AUC为0.658,95%CI为0.585~0.731;子痫前期预测中左切迹指数的临界值为0.71,敏感度为61.57%,特异度为71.76%,AUC为0.684,95%CI为0.612~0.757;子痫前期预测中PAPP-A的临界值为4003.5 mU/L,敏感度为68.47%,特异度为56.89%,AUC为0.673,95%CI为0.604~0.742;子痫前期预测中联合预测的敏感度为71.18%,特异度为75.47%,AUC为0.772,95%CI为0.711~0.834;右、左切迹指数与PAPP-A联合预测子痫前期的AUC大于单一指标预测,差异有统计学意义(P<0.05)。子痫前期预测中右切迹指数联合PAPP-A的敏感度为54.76%,特异度为80.27%,AUC为0.739,95%CI为0.674~0.804;左切迹指数联合PAPP-A的敏感度为80.79%,特异度为62.79%,AUC为0.757,95%CI为0.695~0.818;左切迹指数联合PAPP-A预测子痫前期AUC大于右切迹指数联合PAPP-A,差异有统计学意义(P<0.05)。结论单一子宫动脉舒张早期右、左切迹指数或者PAPP-A在预测子痫前期中均有良好效果,而子宫动脉舒张早期右、左切迹指数与PAPP-A联合检测的预测价值更高,同时左切迹指数联合PAPP-A预测子痫前期价值要高于右切迹指数联合PAPP-A。

脂肪酸结合蛋白4在2型糖尿病肾病中的诊断价值

目的:探讨2型糖尿病(type 2 diabetes mellitus,T2DM)患者血清脂肪酸结合蛋白4(fatty acid-binding protein 4,FABP4)与糖尿病肾病(diabetic nephropathy,DN)的相关性及其作为DN早期诊断的应用价值。方法:纳入T2DM患者218例及健康体检者(对照组)20名,收集受试者的一般临床资料如身高、体质量、腰围、糖尿病病程等,计算BMI;收集血糖、糖化血红蛋白、空腹胰岛素、空腹C肽、肝肾功能、血脂等指标,计算稳态模型胰岛素抵抗指数(homeostasis model assessment-insulin resistance index,HOMA-IR)。采用ELISA测定血清FABP4水平;采用联合血肌酐(serum creatinine,Scr)和胱抑素C(cystatin C,Cys C)的慢性肾脏病流行病学协作方程式计算肾小球滤过率;测定尿白蛋白和肌酐水平,计算尿微量蛋白与肌酐比值(urinary albumin to creatinine ratio,UACR)。根据估算的肾小球滤过率(estimated glomerular filtration rate,eGFR)水平将T2DM患者分为肾功能正常组(eGFR≥90 mL/min/1.73 m^(2))、轻度肾功能不全组(eGFR 60~<90 mL/min/1.73 m^(2))和中度肾功能不全组(eGFR 30~<60 mL/min/1.73 m^(2));根据UACR水平分为正常蛋白尿组(UACR<30 mg/g)、微量蛋白尿组(UACR 30~<300 mg/g)和大量蛋白尿组(UACR≥300 mg/g)。采用回归分析评估FABP4与eGFR、UACR严重程度的相关性。结果:(1)与对照组相比,T2DM患者的血清FABP4显著升高。(2)在根据eGFR分层的3个亚组中,随着eGFR的下降,血清FABP4水平显著增加(P<0.001)。但在UACR亚组中差异无统计学意义(P=0.382)。(3)Spearman相关分析显示FABP4与eGFR呈负相关(r=-0.203,P=0.001),与UACR无相关性(r=0.130,P=0.055)。(4)多元线性回归表明,FABP4与eGFR呈独立负相关(r=-0.211,P<0.001),与UACR无相关性(r=-0.047,P=0.534)。(5)ROC曲线显示FABP4诊断DN的最佳截断值为103.9μg/L,AUC为0.745(灵敏度51.2%,特异度92.7%)。结论:T2DM患者血清FABP4水平升高与DN发生发展相关,有可能作为DN早期诊断的生物标志物。

血清IGFBP-3、Gd-IgA1在儿童紫癜性肾炎早期诊断中的应用价值

目的 探索血清胰岛素样生长因子结合蛋白-3(IGFBP-3)及半乳糖缺乏免疫球蛋白A1(Gd-IgA1)联合检测在儿童紫癜性肾炎(HSPN)早期诊断中的应用价值。方法 选取2021年6月至2023年4月在该院确诊的105例首发过敏性紫癜(HSP)患儿作为研究对象,在入院后按照HSP是否累及肾脏将患儿分为HSPN组及无肾炎组(HSP组),同期选择在该院体检的52例健康儿童作为对照组(NC组)。收集3组临床资料,采用酶联免疫吸附试验(ELISA)对血清及尿液中IGFBP-3、Gd-IgA1表达水平进行检测,受试者工作特征(ROC)曲线分析血清IGFBP-3、Gd-IgA1对HSPN的早期诊断价值,多因素Logistic回归分析HSPN早期发生的影响因素。结果 与NC组相比,HSPN组及HSP组的IgA、IgG、补体C3、IgA/C3、白细胞计数(WBC)、红细胞计数(RBC)、血小板计数(PLT)及血清光抑素C(CysC)、血肌酐(sCr)水平显著升高(P<0.05),但HSPN组与HSP组的临床资料差异无统计学意义(P>0.05);HSPN组及HSP组血清IGFBP-3、Gd-IgA1及尿液IGFBP-3/尿肌酐(uCr)、Gd-IgA1/uCr表达水平较NC组显著升高(P<0.05),并且,与HSP组相比,HSPN组血清IGFBP-3、Gd-IgA1及尿液Gd-IgA1/uCr表达水平进一步升高(P<0.05);ROC曲线分析显示,联合IGFBP-3、Gd-IgA1诊断HSPN的曲线下面积(AUC)显著大于IGFBP-3单独诊断的AUC(Z=3.629,P<0.001)和Gd-IgA1单独诊断的AUC(Z=2.274,P=0.023);多因素Logistic回归分析显示,血清CysC、IGFBP-3、Gd-IgA1、尿液Gd-IgA1/uCr是HSPN早期发生的影响因素(P<0.05)。结论 HSPN患儿血清IGFBP-3、Gd-IgA1的表达水平均显著上升,二者是HSPN早期发生的影响因素,血清IGFBP-3、Gd-IgA1水平联合检测对HSPN的早期诊断具有较高的应用价值。

血清胱抑素C、尿微量白蛋白、中性粒细胞明胶酶相关脂质运载蛋白联合检测在早期肾损伤患者中应用价值

目的:探究血清胱抑素C(CysC)、尿微量白蛋白(mAlb)、中性粒细胞明胶酶相关脂质运载蛋白(NGAL)联合诊断在早期肾损伤中应用效果。方法:将2022年1月—2024年1月在漳州市中医院诊治糖尿病患者80例,根据肾小球滤过率(GFR)水平分为早期肾损伤组(A组)38例、单纯糖尿病组(B组)42例,并选择同期体检健康人员38例纳入对照组(C组),检测所有患者血清CysC、NGAL、尿mAlb水平,分析其对早期肾损伤的诊断价值。结果:与C组比较,A组、B组CysC、mAlb、NGAL水平均升高,差异均有统计学意义(P<0.05);与B组比较,A组CysC、mAlb、NGAL水平均高,差异均有统计学意义(P<0.05)。CysC、mAlb、NGAL敏感度均低于联合诊断,差异均有统计学意义(P<0.05);CysC、mAlb、NGAL单独诊断特异度与联合诊断特异度差异均无统计学意义(P>0.05);CysC、mAlb、NGAL准确度均低于联合诊断,差异均有统计学意义(P<0.05)。结论:CysC、mAlb、NGAL水平在早期肾损伤患者中呈异常高表达,且联合诊断早期肾损伤有着较高效能,可对早期肾损伤进行较为准确的鉴别。

血清金属蛋白酶组织抑制剂3和性别决定区Y框蛋白2在2型糖尿病肾损伤早期诊断中的临床应用

目的探究血清金属蛋白酶组织抑制剂3(tissue inhibitors of metalloproteinases 3,TIMP3)和性别决定区Y框蛋白2(transcription factor determining region Y box protein 2,SOX2)对2型糖尿病(type 2 diabetes mellitus,T2DM)肾损伤的早期诊断。方法选取2022年4月至2023年4月在华北石油管理局总医院就诊的102例T2DM患者为研究对象,根据24 h尿蛋白排泄率(uri-nary albumin excretion rate,UAER)将T2DM患者分为肾损伤组(n=40)和无肾损伤组(n=62),另选取同期在华北石油管理局总医院行体检的健康者50名为对照组。酶联免疫吸附法测定所有受试者血清TIMP3、SOX2水平;比较3组受试者一般资料、糖化血红蛋白(hemoglobin A1c,HbA1c)、UAER、血肌酐(serum creatinine,Scr)、估算肾小球滤过率(estimated glomerular filtration rate,eGFR)、血清TIMP3、SOX2水平;Pearson相关性分析血清TIMP3与SOX2及两者与HbA1c、UAER、Scr、eGFR之间的关系;受试者工作特征曲线(receiver operating characteristic curve,ROC)分析血清TIMP3、SOX2对T2DM患者肾损伤的诊断价值。结果T2DM患者血清TIMP3[(0.68±0.17)μg/L比(1.35±0.35)μg/L]及eGFR[(105.99±20.56)mL·min^(-1)·(1.73 m^(2))比(133.15±26.18)mL·min^(-1)·(1.73 m^(2))^(-1)]显著低于对照组(P<0.05),且肾损伤患者血清TIMP3[(0.47±0.11)μg/L比(0.82±0.21)^(-1)μg/L]及eGFR[(74.69±10.22)mL·min^(-1)·(1.73 m^(2))比(126.18±27.23)mL·min^(-1)·(1.73 m^(2))^(-1)]显著低于无肾损伤患者(P<0.05);血清SOX2[(8.91±1.82)kU/L比(5.15±1.31)kU/L]及HbA1c[(8.80±1.55)%比(5.52±0.83)%]、UAER[(70.13±18.06)mg/24 h比(13.22±3.61)mg/24 h]、Scr[(82.14±15.23)µmol/L比(53.19±5.62)µmol/L]显著高于对照组(P<0.05),且肾损伤患者血清SOX2[(10.81±2.13)kU/L比(5.15±1.31)kU/L]及UAER[(156.83±40.29)mg/24 h比(13.22±3.61)mg/24 h]、Scr[(113.77±13.58)µmol/L比(53.19±5.62)µmol/L]显著高于无肾损伤患者(P<0.05)。Pearson相关性分析结果显示,TIMP3与UAER、Scr、HbA1c呈显著负相关(P<0.05),与eGFR呈显著正相关(P<0.05);SOX2与UAER、Scr、HbA1c呈显著正相关(P<0.05),与eGFR呈显著负相关(P<0.05);血清TIMP3与SOX2呈显著负相关(r=-0.590,P<0.05)。ROC结果显示,血清TIMP3联合SOX2诊断T2DM患者肾损伤的敏感度和特异度分别为95.0%、85.3%,显著高于TIMP3、SOX2单独测定。结论T2DM肾损伤患者血清TIMP3水平显著降低,SOX2水平显著升高,且两者与T2DM患者肾损伤密切相关,可用于T2DM患者肾损伤早期诊断。

尿液蛋白激酶Y基因启动子位点甲基化在前列腺癌早期诊断中的价值

目的 探讨尿液蛋白激酶(PRKY)基因启动子位点甲基化在前列腺癌(PCa)早期诊断中的临床价值。方法 收集50例疑似PCa患者的尿液,提取DNA后,通过定量甲基化特异性PCR(qMSP)法检测PRKY基因启动子位点cg05163709、cg08045599及cg05618150甲基化水平,同时将患者分为良性前列腺增生(BPH)组和PCa组,并分析两组患者临床指标差异以及两组患者尿液中的PRKY基因启动子位点甲基化状态。建立受试者工作特征曲线(ROC),计算曲线下面积(AUC),分析其在PCa中的诊断价值,并联合临床指标进行联合诊断。结果 PCa患者尿液标本中cg05163709和cg05618150甲基化率明显高于BPH患者,其中cg05163709甲基化诊断PCa的AUC为0.762,敏感度为86.70%。与前列腺特异性抗原(tPSA)等临床指标相比,PRKY甲基化在PCa早期筛查中表现更好。cg05618150甲基化与前列腺特异抗原密度(PSAD)联合诊断的AUC为0.787,敏感度为86.70%;cg05163709甲基化与PSAD联合诊断PCa的AUC为0.855,特异度为95.00%。结论 尿液PRKY基因启动子cg05163709和cg05618150位点甲基化在诊断PCa上具有较高的敏感度和特异度,有望成为PCa早期诊断的生物标志物。

血清肝素结合蛋白对重度烧伤患者预后及脓毒症发生的早期预警价值

目的·分析重度烧伤患者早期血清肝素结合蛋白(heparin-binding protein,HBP)表达水平,探讨其对患者预后及脓毒症发生的预警价值。方法·回顾性分析上海交通大学医学院附属瑞金医院灼伤整形科2021年1月—2023年5月收治的52例重度烧伤患者的临床资料。收集患者性别、年龄、烧伤总面积、身体质量指数(body mass index,BMI)、是否行气管插管或气管切开等一般资料。收集患者入院48 h内的HBP、血清降钙素原(procalcitonin,PCT)、血清C反应蛋白(C reactive protein,CRP)水平和白细胞计数,以及入院48 h内急性生理与慢性健康评估Ⅱ(acute physiology and chronic health evaluationⅡ,APACHEⅡ)和序贯性器官衰竭评估(sequential organ failure assessment,SOFA)的评分。根据出院时的状态,将患者分为死亡组和存活组;根据住院期间是否发生脓毒症,将患者分为脓毒症组和非脓毒症组;根据是否发生休克,将脓毒症患者分为脓毒症无休克组和脓毒症休克组。采用Logistic回归分析重度烧伤患者死亡、脓毒症及脓毒症休克的危险因素。绘制受试者操作特征曲线(receiver operator characteristic curve,ROC曲线)评估上述指标对患者死亡、脓毒症,以及脓毒症休克的早期预警作用。结果·与存活组比较,死亡组患者年龄较大,差异有统计学意义(P=0.036);烧伤总面积及行气管插管或切开在是否发生脓毒症患者中差异有统计学意义(P=0.011,P=0.001)。与存活组相比,死亡组患者血清HBP较高,差异具有统计学意义(P=0.002);与非脓毒症组相比,脓毒症组患者血清HBP水平、APACHEⅡ评分、SOFA评分较高,差异具有统计学意义(均P<0.05),其余指标差异均无统计学意义。与脓毒症无休克组比较,脓毒症休克组患者HBP水平较高,差异有统计学意义(P=0.008)。Logistic回归分析显示,HBP是住院期间重度烧伤患者死亡的独立危险因素,同时也是重度烧伤后脓毒症患者发生脓毒症休克的独立危险因素。ROC曲线分析显示,HBP水平预测住院期间患者死亡的ROC曲线下面积(area under the curve,AUC)为0.798;当HBP≥147.03 ng/mL时,其敏感度和特异度分别为88.33%和70.00%。HBP水平预测重度烧伤后脓毒症患者出现脓毒症休克的AUC为0.789;当HBP≥147.03 ng/mL时,其敏感度和特异度分别为90.00%和63.20%。结论·入院48 h内的血清HBP水平可作为重度烧伤患者预后以及重度烧伤脓毒症患者是否发生脓毒症休克的预警指标。

日粮添加蛹虫草缓解脂多糖诱导的仔猪肝损伤和骨骼肌蛋白质降解

【目的】探讨日粮中添加蛹虫草对断奶仔猪生长和免疫性能的影响及调节断奶仔猪免疫应激的机制,为新型饲料添加剂筛选提供依据。【方法】选取相同日龄、初始体重相似的杜×长×大早期断奶仔猪144头并随机分为4组:NC组(基础日粮)、LPS组(LPS+基础日粮)、LPS+500CM组(LPS+基础日粮+500 mg·kg^(-1)CM)、LPS+1000 CM(LPS+基础日粮+1000 mg·kg^(-1)CM)。NC组和LPS组饲喂基础日粮,LPS+500CM组和LPS+1000CM组分别按照比例将蛹虫草粉与基础日粮充分混匀后饲喂。饲养结束后,每组随机挑选6头(公母各半)屠宰,屠宰前4h对LPS组、LPS+500CM组和LPS+1000CM组腹腔注射LPS,NC组注射等量生理盐水。屠宰后采集背最长肌、心脏、肝脏、脾脏、胰脏和肾脏进行检测。【结果】对体重及采食量统计分析,结果显示,日粮添加蛹虫草饲喂仔猪对仔猪平均日采食量无显著影响,而添加500 mg·kg^(-1)CM和1000 mg·kg^(-1)CM的仔猪分别比对照组仔猪体重提高了8.58%(P<0.05)和9.08%(P<0.05)。相比于NC组,LPS组仔猪脾脏指数显著降低(P<0.05),而LPS+500CM组和LPS+1000CM组仔猪脾脏指数均显著高于LPS组(P<0.05)。肝功能生物标志物和总胆汁酸检测表明,LPS组仔猪肝脏ALT水平比NC组显著升高(P<0.05),AST、LDH、总胆汁酸水平有上升趋势。而饲料中添加有蛹虫草的LPS+500CM组和LPS+1000CM组的ALT、AST、LDH和总胆汁酸水平均比LPS组的指标显著降低。肝脏抗氧化指标和炎症因子表达检测显示,LPS组仔猪肝脏的MDA、LPO、T-AOC水平及炎症因子表达显著升高(P<0.05),而CAT、GSH-Px、T-SOD水平显著降低(P<0.01),而用蛹虫草饲喂仔猪可以显著缓解这些指标的升高或降低。LPS组骨骼肌粗蛋白和氨基酸含量显著减低(P<0.01),而日粮添加蛹虫草饲喂可以显著缓解LPS导致的蛋白和氨基酸含量减少(P<0.01)。与NC相比,LPS组炎症因子表达显著升高(P<0.05),而日粮添加蛹虫草饲喂后炎症因子表达比LPS组显著降低(P<0.05)。LPS组仔猪背最长肌中的MDA和LPO和水平显著高于NC组(P<0.01),而T-AOC、CAT、GSH-Px和T-SOD水平则显著降低(P<0.01),日粮添加蛹虫草可缓解这种异常的升高或降低。对Akt、t-mTOR、4EBP1、FOXO1磷酸化水平进行检测,发现LPS组相比于NC组具有降低的趋势,而MAFbx、MuRF1的蛋白表达水平显著升高(P<0.05)。日粮中添加蛹虫草饲喂后,仔猪背最长肌Akt、FOXO1磷酸化水平显著提高(P<0.05),而MAFbx、MuRF1蛋白表达水平显著降低(P<0.05)。【结论】日粮中添加蛹虫草可以提高断奶仔猪生长性能和免疫性能;蛹虫草可以抑制LPS导致的背最长肌粗蛋白和总氨基酸含量降低;蛹虫草可以抑制肝脏炎症和肝细胞过度增殖和凋亡,并提高了肝脏抗氧化能力;蛹虫草可以抑制断奶仔猪背最长肌炎症、氧化应激和蛋白质分解。总之,日粮中添加蛹虫草可以提高断奶仔猪生长和免疫性能,缓解LPS导致的肝损伤及蛋白质的降解,为筛选新型饲料添加剂及预防断奶仔猪免疫应激提供理论依据。