Table of Content

30 December 2024, Volume 39 Issue 12

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Expert consensus on interference factors and solutions for immunological testing

Beijing Medical Association Laboratory Medicine Branch, Shanghai Medical Association Laboratory Medicine Branch

2024, 39(12):  1131-1139.  DOI: 10.3969/j.issn.1673-8640.2024.12.001

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Immunological testing is a qualitative or quantitative determination of analytes based on the binding of antigens and antibodies. In clinic，there are multiple interfering factors that can affect the results of immunological testing，mainly involving in the pre-，mid-，and post- analysis stages. Therefore，Beijing Medical Association Laboratory Medicine Branch and Shanghai Medical Association Laboratory Medicine Branch have formed an expert consensus on the interference factors and solutions for immunological testing，which can provide a reference for accurate determination of immunological projects.

Research progress on determination and mechanism of drug resistance and tolerance to Cryptococcus neoformans

WANG Ziwen, WU Wenjuan

2024, 39(12):  1140-1144.  DOI: 10.3969/j.issn.1673-8640.2024.12.002

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Cryptococcus neoformans is a globally distributed opportunistic fungal pathogen，which causes cryptococcal meningitis，a factor in the mortality of acquired immune deficiency syndrome patients. At present，the kinds of antifungal drugs are limited，which causes in drug resistance and tolerance to Cryptococcus neoformans. In some cases，even if the in vitro drug susceptibility test suggests sensitivity，the treatment with the drug is still prolonged or relapses. This may be associated with drug tolerance. The discovery of drug tolerance responds to more complex mechanisms of antifungal drug resistance. Understanding the drug resistance and tolerance to Cryptococcus neoformans as well as the mechanisms is critical，which can provide ideas for clinical treatment regimen design and the development of new antifungal drugs.

Diagnostic roles of mNGS and Mucorales PCR in pulmonary mucormycosis in patients with blood diseases

XU Chunhui, ZHOU Xinyue, YI Huiming, ZHANG Lining, CHEN Shulian, ZHU Guoqing, FENG Sizhou

2024, 39(12):  1145-1149.  DOI: 10.3969/j.issn.1673-8640.2024.12.003

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Objective To investigate the diagnostic roles of metagenomic next-generation sequencing（mNGS） and Mucorales poly merase chain reaction（PCR） detection in pulmonary mucormycosis in patients with blood diseases. Methods From June 2021 to December 2023，66 patients with Mucorales infection and 39 patients with non-Mucorales infection were enrolled from Institute of Hematology and Blood Diseases Hospital of Chinese Academy of Medical Sciences and Peking Union Medical College. The fungal culture，microscopy and nNGS determination data of 196 clinical samples from 105 patients with Mucorales infection were collected. According to the consensus definition of invasive fungal diseases published by European Organization for Research and Treatment of Cancer/Community for Education and Research of Fungal Research Groups，they were classified into mucormycosis group（65 cases，including 3 confirmed cases，8 clinically diagnosed cases and 54 suspected cases） and control group（40 cases，of which 1 case was positive for Mucorales mNGS）. The clinical characteristics and laboratory determination results of the 2 groups were compared. The results of mNGS were verified by PCR. The efficacy of PCR，traditional method single and combined determinations in the diagnosis of mucormycosis was compared. Results Among the 65 patients with mucormycosis，the highest determination rate of mNGS was Rhizobacterium（46.2%），and the PCR results showed 59（90.8%）positive cases. The sensitivities of PCR for determining Mucorales in blood samples and non-blood samples were 89.7% and 76.9%，respectively. The sensitivities of fungal culture and microscopy were 7.1% and 26.2%. The sensitivity of traditional methods combined with PCR for non-blood samples was 84.6%. The median determination time of mNGS for Mucorales was 1 d，and the difference between traditional methods and mNGS for the median determination time was 12 d. Conclusions The determination of Mucorales by mNGS and PCR is shorter and more sensitive than traditional methods，which has advantages in the early diagnosis of pulmonary mucormycosis.

Hospital and external environmental fungal screening and drug susceptibility analysis

LIU Ruiguang, GUO Jian

2024, 39(12):  1150-1156.  DOI: 10.3969/j.issn.1673-8640.2024.12.004

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Objective To investigate the distribution and drug resistance characteristics of fungi in the external environments of hospitals，pastures，lakes，wetlands and oceans by culture omics，so as to provide a reference for the diagnosis and treatment of fungal infections in animals and humans. Methods Samples were collected from different environments，such as hospitals，pastures，lakes，wetlands and oceans. Based on the fungal culture omics，Sabouraud dextrose agar，CHROM Agar Candida and pan-fungal medium were used to culture the samples from different environments. The cultured fungi were identified by matrix-assisted laser desorption ionization time-of-flight mass spectrometry（MALDI-TOF MS），and the fungi that were rarely isolated in clinic were confirmed by internal transcribed spacer（ITS） sequencing analysis. Microbroth dilution method was used to determine fungal susceptibility. Results From 612 samples of different environments，327 isolates of fungi were isolated by co-culture，distributed in 72 different species. The highest isolation rate of yeast-like fungi was Candida krusei（11.01%，36/327），followed by Candida tropicalis（8.26%，27/327）. The filamentous fungi were followed by Aspergillus fumigatus（7.65%，25/327），Aspergillus niger（6.12%，20/327） and Aspergillus flavus（2.75%，9/327）. The yeast-like fungi，which were concerned in the diagnosis and treatment of clinical fungal infections，were also isolated，and these included Candida auris，Candida rugosa，Candida lipolytica Candida catenulata and Candida membranaefaciens. The resistance rates of Candida tropicalis to posaconazole （66.67%），voriconazole （57.90%），fluconazole （52.63%） were high, and the resistance rate to echinocinins was 29.62%. The resistance rates of Candida membranaefaciens to voriconazole and micafungin were 33.33% and 66.67%，respectively. Conclusions There are differences in the distribution of fungi in different environments，and the environmental isolates have certain drug resistance. Among the yeast-like fungi，the isolation rate of Candida krusei is the highest，and partial yeast-like fungi have been determined as well. Among filamentous fungi，Aspergillus has a high isolation rate，mainly including Aspergillus fumigatus，Aspergillus niger and Aspergillus flavus. Affention should be paid to the prevention of fungal disenses，not limited to the hospital environmen.

Role of cryptococcal antigen determination in pulmonary cryptococcosis patients with normal immune function

ZHANG Yan, ZHENG Jie, LIU Jiaxing, GAO Shuo, XU Xuejing, LIU Chang, CAO Xiaoli, ZHOU Wanqing, SHEN Han

2024, 39(12):  1157-1162.  DOI: 10.3969/j.issn.1673-8640.2024.12.005

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Objective To evaluate the role of serum cryptococcal antigen（CrAg） determination in pulmonary cryptococcosis（PC） patients with normal immune function. Methods The clinical data of 60 PC patients with normal immune function at Nanjing Drum Tower Hospital，the Affiliated Hospital of Nanjing University School of Medicine from January 2022 to December 2023 were analyzed retrospectively. The differences in clinical characteristics between serum CrAg negative group and CrAg positive group were compared. The outcome was monitored. Results Among the 60 patients，13 cases had cough and sputum，5 cases had cough and sputum with asthma，3 cases had cough and sputum with chest pain，2 cases had cough and sputum with fever，and the remaining 37 cases（61.7%） had no obvious clinical symptoms. There were 46 cases（76.7%） in serum CrAg positive group and 14 cases（23.3%） in serum CrAg negative group. There was no statistical significance in clinical manifestations of cough，sputum，chest pain，asthma and fever between the 2 groups（P>0.05）. The proportion of multiple nodules in CrAg positive group（71.7%） was higher than that in CrAg negative group（35.7%），and the proportion of single nodules in CrAg positive group（17.4%） was lower than that in CrAg negative group（64.3%）（P<0.05）. There were 15 patients（32.6%）turning to serum CrAg negative within 6 months. Conclusions The determination of serum CrAg can be used to rapidly screen PC patients with normal immune function. It is recommended that CrAg titer is dynamically determined and combined with clinical factors in the course of treatment to provide a reference for the adjustment of treatment plan.

Drug resistance in clinical isolates of Candida parapsilosis species complex in eastern China region from 2017 to 2023

WANG Dongjiang, HU Liang, GUO Jian, LI Teng, TIAN Wenjie, YANG Simin, ZHANG Min, LIN Huiping, WAN Feifei, WANG Ziwen, ZHOU Aiping

2024, 39(12):  1163-1168.  DOI: 10.3969/j.issn.1673-8640.2024.12.006

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Objective To monitor the drug resistance of clinical isolates of Candida parapsilosis species complex（CPC） in eastern China region. Methods CPC isolates were isolated from 47 hospitals in eastern China region from January 2017 to December 2023. The reference laboratory was the Department of Clinical Laboratory of Shanghai East Hospital （South Branch） of Tongji University. The minimum inhibitory concentrations（MIC） of the isolates against 10 antifungal drugs were determined by microbroth dilution method. The in vitro drug susceptibility test results were analyzed according to the Clinical and Laboratory Standards Institute（CLSI） M27M44s and M57s documents. Results A total of 941 isolates of CPC were collected. The proportions of different CPC were as follows：Candida parapsilosis（83.21%，783 isolates），Candida orthopsilosis（10.20%，96 isolates）and Candida metapsilosis（6.59%，62 isolates）. The drug resistance rates of Candida parapsilosis to fluconazole and voriconazole were 12.80% and 3.50%，respectively. The non-wild-type Candida metapsilosis to fluconazole and voriconazole were 39.6% and 37.7%，respectively. Non-wild-type Candida orthopsilosis showed 14.0%，9.3% and 12.8% to caspofungin，fluconazole and voriconazole，respectively. The MIC of isavuconazole against CPC was 0.008 mg·L^-1，which was lower than the other 9 antifungal drugs. Conclusions There is a certain difference in the resistance of CPC to the tested antifungal drugs. Candida parapsilosis and Candida metapsilosis have higher resistance rates to fluconazole and voriconazole. All the isolates have low MIC for isavuconazole and can be recommended as first-line drugs for antifungal therapy.

Peripheral blood expressions of PD-1，LAG-3 and related cytokines in patients with acute and chronic brucellosis

ZHU Xiaoyu, LI Zhiwei, JIA Jintong, LI Shuling, LIU Yezi, WANG Lingling, WANG Qian, LU Peipei, SHI Qinghai

2024, 39(12):  1173-1180.  DOI: 10.3969/j.issn.1673-8640.2024.12.008

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Objective To study the changes in peripheral blood CD8⁺T cell surface programmed death receptor 1（PD-1），lymphocyte activation gene 3（LAG-3） expressions and serum interleukin-2（IL-2） and gamma-interferon（IFN-γ） levels in patients with acute and chronic brucellosis. Methods Totally，50 brucellosis patients were enrolled from the People's Hospital of Xinjiang Uygur Autonomous Region from December 2022 to August 2023，of which 25 cases were in acute stage（acute stage group） and 25 cases were in chronic stage（chronic stage group）. A total of 35 healthy subjects during the same period were enrolled as healthy control group. The clinical data and serologic determination results of all the patients were collected，and the expressions of PD-1 and LAG-3 on the surface of peripheral blood CD8⁺T cells，as well as serum IL-2 and IFN-γ levels were determined. Spearman correlation analysis was used to assess the correlation between PD-1 and LAG-3 expressions. The efficacy of each index in acute and chronic stages of brucellosis was evaluated by receiver operating characteristic（ROC） curve. Results Compared with healthy control group，the percentage of PD-1⁺CD8⁺T cells，the percentage of LAG-3⁺CD8⁺T cells，the percentage of PD-1⁺LAG-3⁺CD8⁺T cells and the levels of serum IL-2 and IFN-γ were higher in acute stage group and chronic stage group（P<0.000 1）. The percentage of PD-1⁺CD8⁺T cells and the percentage of LAG-3⁺CD8⁺T cells in chronic stage were higher than those in acute stage group（P<0.01），and the differences of PD-1⁺LAG-3⁺CD8⁺T cell percentage and serum IL-2 and IFN-γ levels between the 2 groups were not statistically significant（P>0.05）. The PD-1⁺CD8⁺T cell percentage and LAG-3⁺CD8⁺T cell percentage were positively correlated in acute and chronic stage brucellosis patients（r_s=0.591 and 0.545，P<0.01）. PD-1⁺LAG-3⁺CD8⁺T cell percentage，LAG-3⁺CD8⁺T cell percentage，PD-1⁺CD8⁺T cell percentage and IFN-γ were positively correlated with disease severity（r_s=0.726，0.425，0.368 and 0.395，P<0.05），and IL-2 did not correlate with disease severity（r_s=0.235，P=0.113）. The areas under curves（AUC） of the percentage of PD-1⁺LAG-3⁺CD8⁺T cells，the percentage of PD-1⁺CD8⁺T cells，the percentage of LAG-3⁺CD8⁺T cells，IL-2 and IFN-γ in distinguishing acute and chronic stages of brucellosis were 0.968，0.945，0.758，0.754 and 0.762，respectively. Conclusions High expressions of peripheral blood CD8⁺T cell surface inhibitory receptors（PD-1 and LAG-3） and down-regulation of pro-inflammatory factors（IL-2 and IFN-γ） in patients with chronic brucellosis suggest that patients with chronic brucellosis may undergo T-cell depletion.

Colorectal cancer screening model based on ProteomeXchange database

ZOU Chen, XU Runhao, DING Yi, ZHANG Jie, WENG Wenhao, WANG Zhenhua, CAO Yun

2024, 39(12):  1181-1189.  DOI: 10.3969/j.issn.1673-8640.2024.12.009

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ObjectiveTo screen blood protein markers of colorectal cancer（CRC） in ProteomeXchange database，and to establish a screening model for evaluating its diagnostic value for CRC. Methods The differentially expressed protein of CRC was screened in PXD018304 dataset of ProteomeXchange database，and bioinformatics analysis was performed. From May 2021 to January 2022，108 newly diagnosed CRC patients（CRC group） and 100 healthy subjects（healthy control group） in Renji Hospital Affiliated to Shanghai Jiao Tong University School of Medicine were enrolled and classified into training set and validation set according to the ratio of 8∶2. The differentially expressed proteins and 5 tumor markers [carcinoembryonic antigen（CEA），carbohydrate antigen（CA） 19-9，CA242，CA50，CA72-4] were determined. Stepwise binary Logistic regression analysis（backward likelihood ratio method） was used to establish a CRC screening model. Receiver operating characteristic（ROC） curve was used to evaluate the efficacy of single and combined determinations in the diagnosis of CRC. Results A total of 350 differentially expressed proteins were screened from the PXD018304 dataset，which included 214 up-regulated proteins and 136 down-regulated proteins. According to the results of Gene Ontology（GO） enrichment analysis，Kyoto Encyclopedia of Genes and Genomes（KEGG） pathway analysis，protein-protein interaction（PPI） network and other bioinformatics analysis for differentially expressed proteins，taking into account clinical popularity，10 candidate proteins were screened out. The down-regulated proteins were apolipoprotein A1（apo A1），fibronectin（FN），glutathione reductase（GR） and transferrin（TRF），and the up-regulated proteins were apolipoprotein C3（apo C3），ceruloplasmin（CER），C-reactive protein（CRP），complement 4（C4），fibrinogen（Fib）and beta₂-microglobulin（β₂-MG）. Compared with healthy control group，CRC group had lower serum levels of apo A1，apo C3，FN，GR and TRF（P<0.001）. The levels of serum CER，CRP，C4，β₂-MG，CEA，CA19-9 and plasma Fib were increased（P<0.001）. There was no statistical significance in serum CA242，CA50 and CA72-4 levels between the 2 groups（P>0.05）. The markers with areas under curves（AUC） >0.7 for CRC diagnosis were apo A1，apo C3，CRP，FN，GR，TRF，β₂-MG and CEA. The highest single determination efficiency was apo A1（AUC=0.898），with a sensitivity of 81.48% and a specificity of 86.00%. The AUC of the screening model combined with apo A1，CRP，FN，TRF and CEA was 0.959，the sensitivity was 87.21%，the specificity was 92.50%，and the accuracy was 89.76%. Conclusions Apo A1 and other 10 proteins may be used as biomarkers for CRC screening. The screening model combined with apo A1，CRP，FN，TRF and CEA has a high diagnostic efficacy for CRC，which can provide a reference for clinical CRC screening.

Stroke recurrence prediction model based on machine learning algorithms using routine blood test

SHEN Zhan, BIAN Xiaobo, HUANG Ying, WANG Siyang, SHEN Tingting, ZHANG Xian, SONG Yunxiao, XIE Lianhong

2024, 39(12):  1190-1195.  DOI: 10.3969/j.issn.1673-8640.2024.12.010

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Objective To construct a prediction model for stroke recurrence based on machine learning algorithms using routine laboratory tests. Methods A total of 437 stroke patients admitted to Shanghai Xuhui District Central Hospital from January 2010 to December 2023 were retrospectively followed up. Patients with stroke recurrence during the follow-up period were classified as recurrence group，while those without stroke recurrence were classified as non-recurrence group. The dataset was randomly divided into a training set and a validation set in a 7∶3 ratio. Blood lipid and routine blood test parameters at the initial stroke occurrence were collected. A 5-fold cross-validation method was used to develop prediction model in the training set based on machine learning algorithms including random forest（RF），XGboost，Adaboost，K-nearest neighbors（KNN） and Logistic regression（LR）. The predictive performance of stroke recurrence prediction model was evaluated using receiver operating characteristic（ROC） curves and precision-recall（PR） curves. Results The average follow-up duration for the 437 stroke patients was 6.2 years，which 184 patients experienced stroke recurrence. In the training set，red blood cell（RBC） count，hemoglobin（Hb），mean corpuscular volume（MCV），the absolute value of lymphocytes（LYMPH#），total cholesterol（TC） and triglyceride（TG） were higher in recurrence group than those in non-recurrence group（P<0.05）. The other parameters showed no statistical significance（P>0.05）. In the validation set，RBC count，Hb，MCV，TC and TG were higher in recurrence group（P<0.05），with no statistical significance observed in the other parameters（P>0.05）. In the training set，the XGboost demonstrated superior performance in predicting stroke recurrence，with higher areas under curves（AUC） and the area under precision-recall curve（PRAUC） compared to RF，Adaboost，KNN and LR. In the validation set，the prediction model constructed using XGboost achieved an AUC of 0.86 and a PRAUC of 0.82. Conclusions The stroke recurrence prediction model based on blood lipid and routine blood test parameters demonstrates promising clinical application value.

Changes of lipid levels in ovarian epithelial cancer patients treated with bevacizumab and their influence on prognosis

LIU Guoli, WANG Ying, WANG Ying, DUAN Xudong, JIN Hua

2024, 39(12):  1196-1201.  DOI: 10.3969/j.issn.1673-8640.2024.12.011

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Objective To study the effect of bevacizumab treatment on the lipid levels in ovarian epithelial cancer patients and its correlation with prognosis. Methods The clinical and laboratory determination data of 198 patients with ovarian epithelial cancer who were treated in the Affiliated Hospital of Inner Mongolia University for Nationalities from January 2019 to February 2023 were analyzed retrospectively. A total of 84 patients were treated with paclitaxel+platinum，and the remaining 114 patients were treated with paclitaxel+platinum+bevacizumab. Total cholesterol（TC），triglyceride（TG），high-density lipoprotein cholesterol（HDL-C），low-density lipoprotein cholesterol（LDL-C） and lipoprotein（a）[Lp（a）] determination results were collected before treatment and 2 d after chemotherapy in the 2 groups. The follow-up endpoint was defined as the occurrence of tumor progression，and the progression-free survival（PFS） was recorded. The differences in PFS in patients with ovarian epithelial cancer were assessed using Kaplan-Meier survival curve. The factors on PFS in patients with ovarian epithelial cancer were assessed using Cox proportional risk regression analysis. Results The differences in TC，TG，LDL-C，HDL-C and Lp（a） levels between paclitaxel+platinum group and paclitaxel+platinum+bevacizumab group before treatment had no statistical significance（P>0.05）. The differences in TC，TG，LDL-C，HDL-C and Lp（a） levels before and after treatment in paclitaxel+platinum group were also not statistically significant（P>0.05）. The levels of TC and TG were higher in paclitaxel+platinum+bevacizumab group after treatment than those before treatment（P<0.05），while the differences in the levels of LDL-C，HDL-C and Lp（a） were not statistically significant before and after treatment（P>0.05）. The bevacizumab group was classified into 2 subgroups based on whether TC and/or TG were increased（bevacizumab lipid increased group and bevacizumablipid non-increased group）. The progression-free survival rate was sequentially higher inpaclitaxel+platinumgroup，bevacizumab lipid increased groupandbevacizumablipid non-increased group（Log-rank χ²=17.98，P<0.001）. The International Federation of Gynecology and Obstetrics（FIGO） stage Ⅲ-Ⅳ and increased TC and TG after treatment were independent risk factors for shorter PFS in bevacizumab group [hazard ratios（HR） were 2.53，1.89 and 1.32，95% confidence intervals（CI） were 1.85-4.52，1.05-2.82 and 1.11-3.01，respectively]. Conclusions Bevacizumab may benefit patients with ovarian epithelial cancer，but its treatment may lead to increased TC and TG levels with shortened PFS in some patients，which should be of clinical concern.

Sequencing analysis of hearing-impaired children with negative hearing loss gene screening results and carrying only a single heterozygous variant in GJB2 or SLC26A4

LIU Fadi, LE Ping, WU Yinglong, LIU Huihua, YI Ting, FU Jingjing, KE Jiangwei

2024, 39(12):  1202-1207.  DOI: 10.3969/j.issn.1673-8640.2024.12.012

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Objective To investigate the carrier status of hearing loss gene mutations beyond the 9 commonly screened variants (GJB2: 35delG,235delC, 176del16bp, 299-300delAT; SLC26A4: 919-2A>G,2168A>G;12S rRNA:1494C>T,1555A>G; GJB3: 538C>T) among pediatric hearing loss patients in Jiangxi, China. Methods A total of 118 pediatric patients diagnosed with hearing impairment at Jiangxi Provincial Children's Hospital between January 1, 2018 and September 30, 2021 were screened. Patients who tested negative for the 9 variants or carried a single heterozygous mutation in GJB2 and/or SLC26A4 were included. Multiplex polymerase chain reaction (PCR) amplification and capture techniques were employed to detect all known pathogenic variants in GJB2, SLC26A4 and 12S rRNA genes. Variant patterns were analyzed. Results Totally, 19 additional variants were detected among 118 patients, including 2 in the GJB2 gene, 16 in the SLC26A4 gene, and 1 in the 12S rRNA gene. Among these patients, 32 cases exhibited the GJB2 c.109G>A variant, with 20 in homozygous form. Additionally, one presented with the GJB2 c.139G>T heterozygous variant. Among the 16 other pathogenic variants detected in the SLC26A4 gene, the c.1229C>T variant appeared 3 times, while c.916dup, c.1226G>A and c.1905G>A were detected twice. The remaining variants (c.2T>G, c.84C>A, c.349del, c.757A>G, c.1079C>T, c.1174A>T, c.1286C>A, c.1692dup, c.1707+5G>A, c.1983C>A, c.2000T>C and c.2162C>T) were identified once. One case carried the m.1027A>G variant in the mitochondrial 12S rRNA gene. Conclusions In addition to the 9 commonly screened mutations, the GJB2 c.109G>A variant shows the highest detection rate in pediatric hearing impairment patients in Jiangxi. A diverse range of additional SLC26A4 gene variants is identified, with c.1229C>T, c.1226G>A, c.916dup and c.1905G>A occurring at relatively high frequencies and warranting further attention. The use of multiplex PCR amplification and capture techniques significantly improves the detection rate of gene variants in pediatric hearing impairment patients.

Development and application of quality control materials for GCA in serum

JIN Zhonggan, LU Liu, YE Zhihan, JU Yi, OU Yuanzhu, YU Xiaoxuan, ZHANG Sujie

2024, 39(12):  1208-1213.  DOI: 10.3969/j.issn.1673-8640.2024.12.013

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Objective To develop and evaluate quality control materials of glycocholic acid（GCA），and to investigate the performance and capability. Methods Remaining sera from Shanghai East Hospital（hepatitis B surface antigen，hepatitis C virus antibody，human immunodeficiency virus antibody，Treponema pallidum antibody all negative） were collected，and high-level and low-level GCA quality control materials were prepared. The homogeneity，stability and commutability of quality control materials were evaluated. They were distributed to 14 clinical laboratories in Shanghai for applicability investigation，in order to understand the difference of GCA determination results between mass spectrometry and immunological methods （latex enhanced immunochromatography，homogeneous enzyme immunoassay）. Results The homogeneity of GCA quality control materials was good （F values were 1.151 and 0.889，respectively）. The storage at 4 ℃ for 7 d and at-20 ℃ and -80 ℃ for 6 months showed good stability [linear equation slope /b1/<t_{（0.95，n-2）}·S（b1），the difference between slope and 0 was not statistically significant]. The results of quality control materials were all within the 95% confidence interval of the fitted regression line established by the fresh serum samples，which had good commutability. The preliminary investigation results showed that the GCA levels of high level quality control material by mass spectrometry，latex enhanced immunochromatography and homogeneous enzyme immunoassay were 13.65，37.54 and 44.56 μg·mL^-1，respectively，and those of low level quality control material were 0.49，2.76 and 2.39 μg·mL^-1，respectively. Conclusions The prepared GCA quality control materials have good homogeneity，stability and commutability. The results of GCA determination by mass spectrometry and immunoassay are different. The development of reference materials and the establishment of traceability system are the efforts to promote the comparability of clinical GCA determination results.

Effect of preterm birth and low birth weight on 17α-OHP level and its cut-off value in screening neonatal genetic metabolic diseases in Weihai

WANG Yichun, LAN Xinqiang

2024, 39(12):  1214-1218.  DOI: 10.3969/j.issn.1673-8640.2024.12.014

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Objective To investigate the changes of 17 alpha-hydroxyprogesterone（17α-OHP） levels in preterm birth and low birth weight newborns in Weihai，and to establish a cut-off value for screening congenital adrenal hyperplasia（CAH）. Methods Totally，78 147 dry blood samples of neonatal genetic metabolic diseases from the Screening Center of Weihai Maternal and Child Health Care Hospital from January 2019 to December 2023 were collected. According to gestational age and birth weight，the newborns were classified into preterm birth group（4 596 cases），non-preterm birth group（73 551 cases），low birth weight group（2 775 cases） and non-low birth weight group（75 372 cases），respectively. The level of 17α-OHP was determined，and the positive rate of initial screening，positive rate of screening and positive predictive value of each group were compared. The cut-off value of 17α-OHP screening for CAH was established using the percentile method，with the 99.5th percentile（P_99.5） value as the upper limit of the cut-off value. Results Totally，745（0.953%） cases were positive at initial screening，229（0.293%） cases were positive at screening，and 3 cases of CAH were confirmed. The positive rates of initial screening and screening in preterm birth newborns and low birth weight newborns were higher than those in non-preterm birth newborns and non-low birth weight newborns，respectively（P<0.001）. Based on the P_99.5 value，the cut-off value was set at 38.0 nmol·L^-1 for preterm birth and/or low birth weight newborns and 10.5 nmol·L^-1 for other newborns. Compared with the current cut-off value，the number of recall reviews was decreased by 50.20%，and the positive predictive value was increased by 102.25%. No cases had been missed. Conclusions Preterm birth and low birth weight have effects on neonatal 17α-OHP levels. Each region should establish its own 17α-OHP cut-off value for neonatal CAH screening.

Influence of common hemoglobin variants on different glycated hemoglobin determination systems

SONG Beiling, WU Jiong, HU Jiahua, WANG Yufei

2024, 39(12):  1219-1223.  DOI: 10.3969/j.issn.1673-8640.2024.12.015

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Objective To evaluate the recognition ability and the accuracy of quantitative determination results of 6 commonly used clinical glycated hemoglobin A_1c（HbA_1c） determination systems for hemoglobin（Hb） variants. Methods A total of 245 suspected Hb variant interference samples were collected from HbA_1c routine test in Shanghai Jiahui International Hospital and the Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine from December 2020 to December 2022. Six commonly used clinical determination systems（5 systems were high performance liquid chromatography，and 1 system was capillary electrophoresis） were used to determine suspected interference samples，and the types of Hb variants were confirmed by sequencing method. Based on the results of cobas c513 automatic glycated hemoglobin analyzer，the accuracy of 6 determination systems was evaluated. Results Totally，245 suspected Hb variant interference samples were verified by sequencing，141 Hb variant interference samples were determined. Eleven Hb variants（Hb G-Coushatta，Hb G-Taipei，Hb J-Bangkok，Hb D-Los Angeles，Hb Pyrgos，Hb Q-Thailand，Hb Queens，Hb Quong Sze，Hb C，Hb E，Hb S） were determined. Only Hb D-Los Angeles and Hb S can be determined by all the 6 determination systems，and the determination systems for the other 9 Hb variants had different recognition abilities. Except for Hb S，the results of 6 determination systems for the interference samples of other 10 Hb variants were different from those of cobas c513. Conclusions The commonly used clinical HbA_1c determination system is not able to identify most of the Hb variants. For the interference of Hb variants，different methods can be used for determination and sequencing verification if necessary.

Predictive roles of serum MIP-1α and hBD3 in postoperative endophthalmitis of cataract patients

ZHOU He, DONG Wanjiang, LUO Zhong

2024, 39(12):  1224-1228.  DOI: 10.3969/j.issn.1673-8640.2024.12.016

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Objective To investigate the predictive roles of serum macrophage inflammatory protein-1 alpha（MIP-1α） and human beta defensin 3（hBD3） in postoperative endophthalmitis of cataract patients. Methods A total of 162 patients who underwent cataract surgery in Mianyang Wanjiang Ophthalmology Hospital from March 2020 to March 2022 were enrolled. According to whether endophthalmitis occurred after operation，162 patients were classified into endophthalmitis group（18 cases） and non-endophthalmitis group（144 cases）. In addition，98 patients with non-cataract eye diseases in Mianyang Wanjiang Ophthalmology Hospital were enrolled as control group. The correlation between serum MIP-1α and hBD3 was evaluated by Pearson correlation analysis. Multi-variate Logistic regression analysis was used to evaluate the risk factors for postoperative endophthalmitis in cataract patients. Receiver operating characteristic（ROC） curve was used to evaluate the diagnostic efficacy of serum MIP-1α and hBD3 levels on postoperative endophthalmitis in cataract patients. Results The levels of preoperative MIP-1α in endophthalmitis group and non-endophthalmitis group were higher than those in control group，and preoperative hBD3 levels were lower（P<0.05）. Serum preoperative MIP-1α level in endophthalmitis group was higher than that in non-endophthalmitis group，and serum preoperative hBD3 level was lower than that in non-endophthalmitis group（P<0.05）. Compared with the preoperative results，serum MIP-1α level was decreased，and hBD3 level was increased in cataract patients at 1，3 and 7 d after operation（P<0.05）. Compared with non-endophthalmitis group，serum MIP-1α level in endophthalmitis group was increased before and at 1，3 and 7 d after operation，while serum hBD3 level was decreased（P<0.05）. Serum MIP-1α was negatively correlated with hBD3 in endophthalmitis group（r=-0.859，P<0.05）. MIP-1α was a risk factor for postoperative endophthalmitis in cataract patients（P<0.05），and hBD3 was a protective factor（P<0.05）. The areas under curves（AUC） of preoperative MIP-1α and hBD3 to predict postoperative endophthalmitis in cataract patients were 0.769 and 0.819，respectively，while the AUC of combined determination of MIP-1α and hBD3 to predict postoperative endophthalmitis in cataract patients was 0.954，which was higher than those of serum MIP-1α and hBD3 single determinations（P<0.05）. Conclusions Serum MIP-1α and hBD3 levels are related to the occurrence of postoperative endophthalmitis in cataract patients. The combined determination of MIP-1α and hBD3 is more effective in predicting postoperative endophthalmitis than MIP-1α and hBD3 single determinations.

HBV PreS/S region gene mutation inducing hepatocyte endoplasmic reticulum stress causing hepatocellular carcinoma

LIU Yang, HE Chengshan, JIANG Xiudi, LU Zhicheng

2024, 39(12):  1229-1233.  DOI: 10.3969/j.issn.1673-8640.2024.12.017

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Hepatitis B virus（HBV） infection is a public global health problem that leads to a variety of diseases including cirrhosis and hepatocellular carcinoma（HCC）. HBV S region genome encodes hepatitis B virus large surface protein（LHB），hepatitis B virus middle surface protein（MHB） and hepatitis B virus small surface protein（SHB），and mutations in its genome that form variant S proteins accumulate in large quantities in the endoplasmic reticulum of hepatocytes，which in turn produce endoplasmic reticulum stress（ERS）. ERS and unfolded protein response（UPR） activation are involved in the onset，development and response to therapy of HCC and play roles in the pathogenesis of HCC. This review focuses on the progress of research related to ERS causing HCC by the accumulation of variant S proteins in the endoplasmic reticulum due to HBV PrsS/S region gene mutation.