1.Establishment of indirect ELISA based on gD protein of porcine pseudorabies virus and its application in immune evaluation
Yining LIU ; Xiaohang YU ; Jin ZHENG ; Zhenyu YANG ; Shiqing XIE ; Meiting LIN ; Tongtong LIANG ; Ye LUO ; Xinglong YU
Chinese Journal of Veterinary Science 2024;44(10):2116-2122
The aim of this study is to establish a simple and accurate method for vaccine immune e-valuation of porcine pseudorabies virus.In this research,PRV-gD recombinant protein was ex-pressed from mammalian cell HEK-293F as coating antigen,and then the reaction conditions of gD-iELISA were optimized according to checkerboard titration method.The gD-iELISA was used to detect the antibody levels of 211 clinical pig serum samples and the consistency with the neu-tralizing antibody levels wasanalyzed.The results showed that the antigen coating concentration was 0.90 mg/L;the serum to be detected was diluted 1∶100 and incubated at 37 ℃ for 30 min;goat anti-pig IgG-HRP antibody was diluted 1∶55 000 and incubated at 37 ℃ for 30 min;TMB sub-strate was developed at 37 ℃ for 20 min.The method could detect 1∶6 400 diluted PRV positive serum.The results of CSFV,PRRSV,PCV-2,PEDV and FMDV positive sera were all negative by gD-iELISA,and there was no cross-reaction between the method and the above positive sera.The coincidence rate of gD-iELISA and commercial kits was 95.26%,and the intra-and inter-batch co-efficients of variation were both less than 10%.Correlation analysis showed that the correlation coefficient(r)between gD antibody level and neutralizing antibody level was significantly greater than that of gB antibody level,and the gD antibody level had a good linear relationship with the neutralizing antibody level.The results indicated that gD-iELISA was more suitable for vaccine im-mune evaluation of PRV than gB-iELISA.Therefore,the method will have a good prospect of ap-plication in the immunization control of the PRV.
2.Treatment status of tyrosine kinase inhibitor for newly-diagnosed chronic myeloid leukemia: a domestic multi-centre retrospective real-world study
Xiaoshuai ZHANG ; Bingcheng LIU ; Xin DU ; Yanli ZHANG ; Na XU ; Xiaoli LIU ; Weiming LI ; Hai LIN ; Rong LIANG ; Chunyan CHEN ; Jian HUANG ; Yunfan YANG ; Huanling ZHU ; Ling PAN ; Xiaodong WANG ; Guohui LI ; Zhuogang LIU ; Yanqing ZHANG ; Zhenfang LIU ; Jianda HU ; Chunshui LIU ; Fei LI ; Wei YANG ; Li MENG ; Yanqiu HAN ; Li'e LIN ; Zhenyu ZHAO ; Chuanqing TU ; Caifeng ZHENG ; Yanliang BAI ; Zeping ZHOU ; Suning CHEN ; Huiying QIU ; Lijie YANG ; Xiuli SUN ; Hui SUN ; Li ZHOU ; Zelin LIU ; Danyu WANG ; Jianxin GUO ; Liping PANG ; Qingshu ZENG ; Xiaohui SUO ; Weihua ZHANG ; Yuanjun ZHENG ; Qian JIANG
Chinese Journal of Hematology 2024;45(3):215-224
Objective:To retrospectively analyze the treatment status of tyrosine kinase inhibitors (TKI) in newly diagnosed patients with chronic myeloid leukemia (CML) in China.Methods:Data of chronic phase (CP) and accelerated phase (AP) CML patients diagnosed from January 2006 to December 2022 from 77 centers, ≥18 years old, and receiving initial imatinib, nilotinib, dasatinib or flumatinib-therapy within 6 months after diagnosis in China with complete data were retrospectively interrogated. The choice of initial TKI, current TKI medications, treatment switch and reasons, treatment responses and outcomes as well as the variables associated with them were analyzed.Results:6 893 patients in CP ( n=6 453, 93.6%) or AP ( n=440, 6.4%) receiving initial imatinib ( n=4 906, 71.2%), nilotinib ( n=1 157, 16.8%), dasatinib ( n=298, 4.3%) or flumatinib ( n=532, 7.2%) -therapy. With the median follow-up of 43 ( IQR 22-75) months, 1 581 (22.9%) patients switched TKI due to resistance ( n=1 055, 15.3%), intolerance ( n=248, 3.6%), pursuit of better efficacy ( n=168, 2.4%), economic or other reasons ( n=110, 1.6%). The frequency of switching TKI in AP patients was significantly-higher than that in CP patients (44.1% vs 21.5%, P<0.001), and more AP patients switched TKI due to resistance than CP patients (75.3% vs 66.1%, P=0.011). Multi-variable analyses showed that male, lower HGB concentration and ELTS intermediate/high-risk cohort were associated with lower cytogenetic and molecular responses rate and poor outcomes in CP patients; higher WBC count and initial the second-generation TKI treatment, the higher response rates; Ph + ACA at diagnosis, poor PFS. However, Sokal intermediate/high-risk cohort was only significantly-associated with lower CCyR and MMR rates and the poor PFS. Lower HGB concentration and larger spleen size were significantly-associated with the lower cytogenetic and molecular response rates in AP patients; initial the second-generation TKI treatment, the higher treatment response rates; lower PLT count, higher blasts and Ph + ACA, poorer TFS; Ph + ACA, poorer OS. Conclusion:At present, the vast majority of newly-diagnosed CML-CP or AP patients could benefit from TKI treatment in the long term with the good treatment responses and survival outcomes.
3.Influencing factors of adaptive ability development of children aged 2 - 6 in China
Jiayin CUI ; Ruili LI ; Lihong WANG ; Xiaoguo ZHENG ; Huimin YANG ; Liqi ZHU ; Shuling GUO ; Lu ZHAO ; Wenhua ZHAO ; Zhenyu YANG ; Qian ZHANG ; Yuying WANG ; Tao XU ; Bowen CHEN
Chinese Journal of Child Health Care 2024;32(3):280-285
【Objective】 To investigate the development of adaptability in children aged 2 - 6, and to explore its influencing factors, so as to provide reference for promoting the development of adaptability in young children. 【Methods】 Data were from the National Nutrition and Health Systematic Survey for Children in China, and 3 319 children aged 2 - 6 and their parents from 28 sites across 14 provinces were recruited in this study.The Development Scale for Children Aged 0 - 6 years (WS/T 580-2017) was used to measure the developmental quotient of children′s adaptive ability, and a survey questionnaire was used to collect relevant information about children and their parents. 【Results】 Among 3 319 children aged 2 - 6, the proportion of slightly low or low level of adaptability, moderate adaptability development, good and excellent adaptability development was 7.68%,66.25% and 26.06%, respectively.The proportion of children aged 5 - 6 with good and excellent adaptability was lower in 3-year-old and 4-year-old groups (χ2=59.29, P<0.05).Multiple stepwise linear regression showed that children′s gender (β=0.06), gestational age of birth (β=-0.05), only child (β=-0.04), left-behind child (β=-0.04), the main caregiver (β=-0.06), and the education level of parents (β=0.09, 0.10), whether parents actively pay attention to children′s emotions (β=-0.06) and whether children play with homemade toys (β=-0.04) were the influencing factors of children′s adaptive development quotient.Girls, full-term children, only children, non-left-behind children, children with parents as main caregivers, parents with a high level of education, parents who often take the initiative to pay attention to children′s emotions, and children who play with homemade toys had a higher level of adaptability development quotient. 【Conclusions】 The development level of adaptability in children aged 2 - 6 in China is mostly above the average level and is related to multiple factors.Targeted intervention work can be carried out on relevant factors in order to promote the development of children′s adaptability.
4.Analysis of oligoclonal bands detection results of 3 217 patients with neurological disorders
Zhenyu NIU ; Haiqiang JIN ; Hongjun HAO ; Yiming ZHENG ; Jing GUO ; Yan YAO ; Feng GAO ; Zhaoxia WANG
Chinese Journal of Laboratory Medicine 2024;47(1):57-64
Objective:To study positive rates and typing of oligoclonal bands (OCB) in patients with neurological disorders, and to reveal the clinical significance and applicational value of OCB test.Methods:A retrospective analysis was performed on the detection results of 3 217 patients with neurological disorders who undertook both serum and cerebrospinal fluid OCBs in the First Hospital of Peking University from January 2012 to August 2022. According to the final diagnosis, the patients were divided into 13 groups including multiple sclerosis (479 cases), neuromyelitis optica spectrum disorders (935 cases), autoimmune encephalitis (192 cases), viral encephalitis (94 cases), nervous system complication after HSCT (232 cases), Guillain-Barré syndrome (644 cases), chronic inflammatory demyelinating polyneuropathy (157 cases), etc. Cerebrospinal fluid and serum OCBs were detected using isoelectric focusing electrophoresis combining immunofixation, then classified into Ⅰ-Ⅴ types according to the morphology. Consequently, positive rates and types were analyzed for each group. χ2 test was used for comparison between groups. Results:The positive rates of cerebrospinal fluid OCB in multiple sclerosis, nervous system complication after hematopoietic stem cell transplantation (HSCT), autoimmune encephalitis, viral encephalitis, neuromyelitis optica spectrum disorders, Guillain-Barré syndrome and chronic inflammatory demyelinating polyneuropathy were respectively 66.8% (320/479), 48.7% (113/232), 46.4%(89/192), 19.1% (18/94), 17.6% (165/935), 9.9% (64/644), 5.1% (8/157). For patients with multiple sclerosis, neuromyelitis optica spectrum disorders, viral encephalitis, and autoimmune encephalitis, Type Ⅱ bands took the majority of cerebrospinal fluid OCB-positive cases with the rates of 94.1% (301/320), 78.7% (70/89), 77.8% (14/18), and 77.6% (128/165) respectively, indicating intrathecal IgG synthesis; for patients with nervous system complication after HSCT, Guillain-Barré syndrome and chronic inflammatory demyelinating polyneuropathy, type Ⅳ bands took the majority of cerebrospinal fluid OCB-positive cases with the rates of 94.7% (107/113), 82.8% (53/64) and 100% (8/8), indicating no obvious intrathecal IgG synthesis. The positive rates of cerebrospinal fluid oligoclonal bands were significantly different among all groups (χ 2=1 268.31, P<0.001). Conclusion:The positive rates of cerebrospinal fluid oligoclonal bands are different among different neurological disorders, in which the positive rate of cerebrospinal fluid OCB is higher with type Ⅱ bands as the majority type in multiple sclerosis, which indicates that the detection and typing of cerebrospinal fluid OCB are helpful for the diagnosis of various neurological diseases, especially for multiple sclerosis.
5.Comparison of clinical medicine proficiency tests of China and Japan and the enlightenment
Kan LIU ; Fei YU ; Zhenyu WANG ; Zidong LIU ; Tian TIAN ; Shuyuan ZHENG
Chinese Journal of Medical Education Research 2024;23(2):280-284
The Clinical Medicine Proficiency Test developed by the National Medical Examination Center of China in 2020 aims to assess whether clinical medical students possess the necessary medical humanities and basic medical theoretical knowledge and skills required for clinical internships. Since 2002, Japan has implemented the pre-clinical clerkship objective structured clinical examination and computer-based testing, which share similarities with China's proficiency test in terms of examination objectives, content, format, and score evaluation. Through comparing the examinations of China and Japan, this article concludes that it is necessary to learn from Japan's experience to expedite the process of promoting the Clinical Medicine Proficiency Test as an industry admission examination in China. We suggest that medical schools should keep tracking the development of the proficiency test and fully leverage its role in urging students to pay more attention to clinical internships. We also urge medical schools to establish a three-level examination system based on post competency criteria in line with the standards of the National Medical Licensing Examination to improve the quality of medical education.
6.Study on the quality markers of Curcumae Radix standard decoction based on fingerprint and network pharmacology
Zhiwen DUAN ; Xiaoxia LIU ; Minyou HE ; Cuijie WEI ; Yongwei FENG ; Haibao QIU ; Ronghui ZHENG ; Dongmei SUN ; Xiangdong CHEN ; Zhenyu LI
International Journal of Traditional Chinese Medicine 2024;46(12):1622-1628
Objective:To establish the ultra-high performance liquid chromatography (UPLC) fingerprint and high performance liquid chromatography (HPLC) content determination method of Curcumae Radix standard decoction; To predict the quality markers of Curcumae Radix standard decoction combined with network pharmacology.Methods:UPLC method was used to establish the fingerprint of Curcumae Radix standard decoction, and the common peaks were determined. Combined with chemical pattern recognition techniques such as similarity analysis and clustering analysis, Curcumae Radix standard decoction from different producing areas was studied, and curcumol was used as an index to determine the content of 24 batches of Curcumae Radix standard decoction. At the same time, network pharmacology was used to predict potential of curcumol and (1S, 6β)-1β-Methyl-4-(1-methylethylidene)-7β-(3-oxobutyl) bicyclo [4.1.0] heptan-3-one.Results:A total of 24 batches of Curcumae Radix standard decoction from different habitats were compared and analyzed, and 10 common peaks were calibrated. The similarity of 24 batches of samples ranged from 0.982 to 0.999. Clustering analysis and principal component analysis divided them into three categories. Heat map analysis showed that peak 8 (curcumol) and peak 9 ((1S, 6β)-1β-Methyl-4-(1-methylethylidene)-7β-(3-oxobutyl) bicyclo [4.1.0] heptan-3-one) were the main components. The content of curcumol in 24 batches of Curcumae Radix standard decoction was 0.69-1.87 mg/g; curcumol and (1S, 6β)-1β-Methyl-4-(1-methylethylidene)-7β- (3-oxobutyl) bicyclo [4.1.0] heptan-3-one may regulate the neuroactive ligand-receptor interaction signaling pathway, calcium signaling, and excitation by regulating neuroactive ligand-receptor interaction signaling pathway, calcium signaling, and excitation. It was preliminarily predicted that curcumol and (1S, 6β)-1β-Methyl-4-(1-methylethylidene)-7β-(3-oxobutyl) bicyclo [4.1.0] heptan-3-one were potential quality markers of Curcumae Radix.Conclusion:Curcumol and (1S, 6β)-1β-Methyl-4-(1-methylethylidene)-7β-(3-oxobutyl) bicyclo [4.1.0] heptan-3-one are potential quality markers of Curcumae Radix standard decoction, and the established fingerprint can be used for the quality control of Curcumae Radix standard decoction.
7.Early clinical outcomes of dynamization versus superior capsular reconstruction for the treatment of irreparable post-superior massive rotator cuff tears
Jun WANG ; Zhou ZHOU ; Huaisheng LI ; Yatao LIAO ; Guo ZHENG ; Chenke ZHANG ; Zhenyu WANG ; Binghua ZHOU
Chinese Journal of Orthopaedics 2024;44(14):938-946
Objective:To explore and compare early postoperative clinical outcomes between dynamic and classical superior capsular reconstruction for the treatment of irreparable post-superior massive rotator cuff tears (MIRCTs).Methods:29 patients with MIRCTs treated with autologous fascia dynamic SCR (14) and classical SCR (15) at Department of Sports Medicine of the First Affiliated Hospital of Army Medical University from September 2019 to March 2022 were retrospectively analyzed on preoperative and final follow-up pain visual analogue scale (VAS), Constant-Murley score, American Shoulder and Elbow Surgeons (ASES) score, University of California Los Angeles (UCLA) score, range of motion (ROM), acromiohumeral distance (AHD), Sugaya classification and Goutallier classification.Results:All 29 patients were followed up with an average follow-up time of 36.50±8.18 months for dynamized SCR and 29.33±9.15 months for classical SCR, respectively. There was no significant difference between the two groups in terms of gender, age, course of disease and preoperative AHD ( P>0.05). At the final follow-up, there was no significant difference in the degree of improvement in forward flexion (81.79°±36.14° vs. 69.00°±40.19°, t=0.899, P=0.377), abduction [87.50°(71.25°, 122.50°) vs. 80.00°(45.00°, 95.00°), Z=-1.400, P=0.172] and internal rotation [5.00°(5.00°, 6.00°) vs. 4.00°(1.00°, 6.00°), Z=-0.871, P=0.400]; external rotation improved significantly in the dynamic SCR group compared to classical SCR group [37.50°(30.00°, 41.25°) vs. 25.00°(15.00°, 30.00°), Z=-2.285, P=0.019]. Although both groups showed clinical improvements, no significant difference was found between the dynamic SCR group and the classical SCR group on VAS [4.00(3.75, 5.00) vs. 4.00(3.00, 5.00), Z=-0.029, P=0.949], ASES score (50.99±7.98 vs. 46.47±13.73, t=1.074, P=0.293), Constant-Murley score [62.50(54.00, 69.50) vs. 56.00(47.00, 62.00), Z=-1.956, P=0.112] and UCLA score (20.21±3.53 vs. 18.40±3.87, t=1.315, P=0.199). At the final follow-up, patients in the dynamic SCR group had a higher degree of improvement in AHD (3.66±2.22 mm vs. 2.00±1.75 mm, t=2.247, P=0.033). There was no significant difference in Sugaya grading between the two groups at the final follow-up ( Z=-0.370, P=0.747). As for the degree of improvement in Goutallier's grading, there was an improvement in the dynamic SCR group at the final follow-up versus the preoperative period ( Z=-2.101, P=0.036), while there was no significant difference in the degree of improvement in the classical SCR group at the final follow-up versus the preoperative period ( Z=-0.700, P>0.05). Conclusion:Both dynamic SCR and classical SCR for MIRCTs significantly improved shoulder function. Significant improvements in external rotation, AHD and Goutallier grading were observed in the dynamic SCR group compared to the classical SCR group.
8.A preliminary study on the effects of fecal microbiota transplantation on the intestinal microecology of patients with severe pneumonia during the convalescence period.
Peiyan ZHONG ; Yimeng XU ; Shixian YE ; Feng YANG ; Lulu WU ; Guansheng SU ; Yuxin LIU ; Jiajie FENG ; Yu WANG ; Zhenyu WU ; Zeguang ZHENG
Chinese Critical Care Medicine 2023;35(4):352-357
OBJECTIVE:
To investigate the effects of fecal microbiota transplantation (FMT) on intestinal microbiome and organism in patients with severe pneumonia during the convalescence period.
METHODS:
A prospective non-randomized controlled study was conducted. From December 2021 to May 2022, patients with severe pneumonia during the convalescence period who received FMT (FMT group) and patients with severe pneumonia during the convalescence period who did not receive FMT (non-FMT group) admitted to the First Affiliated Hospital of Guangzhou Medical University were enrolled. The differences of clinical indicators, gastrointestinal function and fecal traits between the two groups were compared 1 day before and 10 days after enrollment. The 16S rDNA gene sequencing technology was used to analyze the changes of intestinal flora diversity and different species in patients with FMT before and after enrollment, and metabolic pathways were analyzed and predicted by Kyoto Encyclopedia of Genes and Genomes database (KEGG). Pearson correlation method was used to analyze the correlation between intestinal flora and clinical indicators in FMT group.
RESULTS:
The level of triacylglycerol (TG) in FMT group was significantly decreased at 10 days after enrollment compared with before enrollment [mmol/L: 0.94 (0.71, 1.40) vs. 1.47 (0.78, 1.86), P < 0.05]. The level of high-density lipoprotein cholesterol (HDL-C) in non-FMT group was significantly decreased at 10 days after enrollment compared with before enrollment (mmol/L: 0.68±0.27 vs. 0.80±0.31, P < 0.05). There were no significant differences in other clinical indexes, gastrointestinal function or fecal character scores between the two groups. Diversity analysis showed that the α diversity indexes of intestinal flora in FMT group at 10 days after enrollment were significantly higher than those in non-FMT group, and β diversity was also significantly different from that in non-FMT group. Differential species analysis showed that the relative abundance of Proteobacteria at the level of intestinal flora in FMT group at 10 days after enrollment was significantly lower than that in non-FMT group [8.554% (5.977%, 12.159%) vs. 19.285% (8.054%, 33.207%), P < 0.05], while the relative abundance of Fusobacteria was significantly higher than that in non-FMT group [6.801% (1.373%, 20.586%) vs. 0.003% (0%, 9.324%), P < 0.05], and the relative abundance of Butyricimonas, Fusobacterium and Bifidobacterium at the genus level of the intestinal flora was significantly higher than that in non-FMT group [Butyricimonas: 1.634% (0.813%, 2.387%) vs. 0% (0%, 0.061%), Fusobacterium: 6.801% (1.373%, 20.586%) vs. 0.002% (0%, 9.324%), Bifidobacterium: 0.037% (0%, 0.153%) vs. 0% (0%, 0%), all P < 0.05]. KEGG metabolic pathway analysis showed that the intestinal flora of FMT group was changed in bisphenol degradation, mineral absorption, phosphonate and phosphinate metabolism, cardiac muscle contraction, Parkinson disease and other metabolic pathways and diseases. Correlation analysis showed that Actinobacteria and prealbumin (PA) in intestinal flora of FMT group were significantly positively correlated (r = 0.53, P = 0.043), Bacteroidetes was positively correlated with blood urea nitrogen (BUN; r = 0.56, P = 0.029) and complement C3 (r = 0.57, P = 0.027), Firmicutes was positively correlated with BUN (r = 0.56, P = 0.029) and complement C3 (r = 0.57, P = 0.027), Fusobacteria was significantly positively correlated with immunoglobulin M (IgM; r = 0.71, P = 0.003), Proteobacteria was significantly positively correlated with procalcitonin (PCT; r = 0.63, P = 0.012) and complement C4 (r = 0.56, P = 0.030).
CONCLUSIONS
FMT can reduce TG level, reconstruct intestinal microecological structure, change body metabolism and function, and alleviate inflammatory response by reducing the relative abundance of harmful bacteria in patients with severe pneumonia during the convalescence period.
Humans
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Fecal Microbiota Transplantation
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Complement C3
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Convalescence
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Prospective Studies
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Feces
9.Relationship between red blood cell distribution width and short-term mortality of hip fractures in the elderly
Xiaofeng LIU ; Jinshan ZHANG ; Yongquan XU ; Liang LIN ; Zhenyu LIN ; Hongpeng ZHANG ; Xiaopeng HUANG ; Yangzhen FANG ; Yongqiang ZHENG
Chinese Journal of Geriatrics 2023;42(6):707-710
Objective:To study the relationship between red blood cell distribution width(RDW)and short-term mortality in elderly patients with hip fragility fractures.Methods:The clinical data and blood routine test at admission of 205 elderly patients with brittle hip fractures who were admitted to our hospital from 2020 to 2021 and were followed up for one year were retrospectively analyzed.The comorbid conditions, RDW and cumulative mortality at 6 months and 1 year after fractures were counted, and the relationship between RDW and short-term mortality were analyzed.Results:The 6-month(6.7% and 20.8%, χ2=8.591, P=0.003)and 1-year(6.7% and 26.7%, χ2=14.818, P<0.001)mortality of patients with ≤1 comorbidity were significantly lower than those of patients with ≥2 comorbidities.Moreover, the 6-month and 1-year mortality in patients with RDW>13.5% were significantly higher than those of patients with RDW ≤ 13.5%.The proportion of RDW>13.5 % in patients with at least two comorbidities was significantly higher than that in patients with ≤1 comorbidity.Taking RDW=13.6% as the cut-off value of 6-month and 1-year mortality, the sensitivity and specificity for predicting 6-month mortality were 71.4 % and 59.9 %, respectively, and the sensitivity and specificity for predicting 1-year mortality were 64.7 % and 59.6 %, respectively. Conclusions:Red cell distribution width is associated with short-term mortality, and higher RDW is associated with a higher risk of mortality among elderly patients with brittle hip fractures.
10.Diagnostic value of a combined serology-based model for minimal hepatic encephalopathy in patients with compensated cirrhosis
Shanghao LIU ; Hongmei ZU ; Yan HUANG ; Xiaoqing GUO ; Huiling XIANG ; Tong DANG ; Xiaoyan LI ; Zhaolan YAN ; Yajing LI ; Fei LIU ; Jia SUN ; Ruixin SONG ; Junqing YAN ; Qing YE ; Jing WANG ; Xianmei MENG ; Haiying WANG ; Zhenyu JIANG ; Lei HUANG ; Fanping MENG ; Guo ZHANG ; Wenjuan WANG ; Shaoqi YANG ; Shengjuan HU ; Jigang RUAN ; Chuang LEI ; Qinghai WANG ; Hongling TIAN ; Qi ZHENG ; Yiling LI ; Ningning WANG ; Huipeng CUI ; Yanmeng WANG ; Zhangshu QU ; Min YUAN ; Yijun LIU ; Ying CHEN ; Yuxiang XIA ; Yayuan LIU ; Ying LIU ; Suxuan QU ; Hong TAO ; Ruichun SHI ; Xiaoting YANG ; Dan JIN ; Dan SU ; Yongfeng YANG ; Wei YE ; Na LIU ; Rongyu TANG ; Quan ZHANG ; Qin LIU ; Gaoliang ZOU ; Ziyue LI ; Caiyan ZHAO ; Qian ZHAO ; Qingge ZHANG ; Huafang GAO ; Tao MENG ; Jie LI ; Weihua WU ; Jian WANG ; Chuanlong YANG ; Hui LYU ; Chuan LIU ; Fusheng WANG ; Junliang FU ; Xiaolong QI
Chinese Journal of Laboratory Medicine 2023;46(1):52-61
Objective:To investigate the diagnostic accuracy of serological indicators and evaluate the diagnostic value of a new established combined serological model on identifying the minimal hepatic encephalopathy (MHE) in patients with compensated cirrhosis.Methods:This prospective multicenter study enrolled 263 compensated cirrhotic patients from 23 hospitals in 15 provinces, autonomous regions and municipalities of China between October 2021 and August 2022. Clinical data and laboratory test results were collected, and the model for end-stage liver disease (MELD) score was calculated. Ammonia level was corrected to the upper limit of normal (AMM-ULN) by the baseline blood ammonia measurements/upper limit of the normal reference value. MHE was diagnosed by combined abnormal number connection test-A and abnormal digit symbol test as suggested by Guidelines on the management of hepatic encephalopathy in cirrhosis. The patients were randomly divided (7∶3) into training set ( n=185) and validation set ( n=78) based on caret package of R language. Logistic regression was used to establish a combined model of MHE diagnosis. The diagnostic performance was evaluated by the area under the curve (AUC) of receiver operating characteristic curve, Hosmer-Lemeshow test and calibration curve. The internal verification was carried out by the Bootstrap method ( n=200). AUC comparisons were achieved using the Delong test. Results:In the training set, prevalence of MHE was 37.8% (70/185). There were statistically significant differences in AMM-ULN, albumin, platelet, alkaline phosphatase, international normalized ratio, MELD score and education between non-MHE group and MHE group (all P<0.05). Multivariate Logistic regression analysis showed that AMM-ULN [odds ratio ( OR)=1.78, 95% confidence interval ( CI) 1.05-3.14, P=0.038] and MELD score ( OR=1.11, 95% CI 1.04-1.20, P=0.002) were independent risk factors for MHE, and the AUC for predicting MHE were 0.663, 0.625, respectively. Compared with the use of blood AMM-ULN and MELD score alone, the AUC of the combined model of AMM-ULN, MELD score and education exhibited better predictive performance in determining the presence of MHE was 0.755, the specificity and sensitivity was 85.2% and 55.7%, respectively. Hosmer-Lemeshow test and calibration curve showed that the model had good calibration ( P=0.733). The AUC for internal validation of the combined model for diagnosing MHE was 0.752. In the validation set, the AUC of the combined model for diagnosing MHE was 0.794, and Hosmer-Lemeshow test showed good calibration ( P=0.841). Conclusion:Use of the combined model including AMM-ULN, MELD score and education could improve the predictive efficiency of MHE among patients with compensated cirrhosis.

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