Table of Content

28 April 2023, Volume 38 Issue 4

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Clinical application of novel tumor biomarkers：prospects and challenges

GAO Feng

2023, 38(4):  303-306.  DOI: 10.3969/j.issn.1673-8640.2023.04.001

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Early diagnosis and individualized precise treatment are the keys to improve the survival rate and the quality of life and prolong the survival time of cancer patients. In the recent years，with the development of liquid biopsy technology，more and more novel tumor biomarkers have been found，showing potential in tumor diagnosis，prognostic judgment and treatment monitoring，and some indicators have been put into clinical practice. Future researches should focus on solving the problems that hinder the clinical transformation of novel tumor biomarkers，and promote more liquid biopsy indicators with clinical application prospects to optimize the diagnosis and treatment process of cancer patients，thereby reducing their disease burden.

Clinical role of serum S1P in the early diagnosis of colorectal cancer

JIANG Mengying, LIU Yiwen, HE Yiqing, XU Jing, YANG Cuixia, GAO Feng, DU Yan

2023, 38(4):  307-312.  DOI: 10.3969/j.issn.1673-8640.2023.04.002

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Objective To investigate the clinical role of serum sphingosine-1-phosphate（S1P） in the early diagnosis of colorectal cancer. Methods A total of 42 patients with colorectal cancer and 30 patients with colorectal benign lesions were enrolled. Totally，38 healthy subjects were enrolled as healthy control group. The clinicopathologic data of colorectal cancer group were collected. Serum S1P levels were determined. Receiver operating characteristic（ROC） curve was used to evaluate the diagnostic efficacy of S1P single and combined determinations with carcinoembryonic antigen（CEA） and carbohydrate antigen 19-9（CA19-9）in colorectal cancer. Results Serum S1P level in colorectal cancer group was higher than those in colorectal benign lesion group and healthy control group（P<0.05，P<0.001）. Serum S1P level of stage Ⅰ to Ⅱ colorectal cancer group was higher than those of stage Ⅲ to Ⅳ colorectal cancer group，colorectal benign lesion group and healthy control group（P<0.05，P<0.05，P<0.001）. Serum S1P level in colorectal benign lesion group was higher than that in healthy control group（P<0.001）. Serum S1P levels in colorectal cancer patients with lymph metastasis were lower than those without lymph metastasis（P<0.05），but there was no statistical significance in serum S1P levels among patients with other clinicopathologic characteristics（P>0.05）. ROC curve analysis results showed that，using healthy control group as control，the areas under curves（AUC） of serum S1P，CEA and CA19-9 for the diagnosis of colorectal cancer were 0.924，0.701，0.579 and 0.943，respectively. The AUC for the diagnosis of stage Ⅰ to Ⅱ colorectal cancer were 0.944，0.663，0.611 and 0.955，respectively，and the AUC for the diagnosis of single or simultaneous negative CEA and CA19-9 colorectal cancer were 0.919，0.628，0.526 and 0.932，respectively. Using colorectal benign lesion group as control，the AUC of the single and combined determinations of the 3 indicators were 0.655，0.720，0.582 and 0.787，respectively. Conclusions S1P may be a biomarker for the diagnosis of early colorectal cancer.

Roles of serum HYAL1 and HA in the auxiliary diagnosis and therapeutic monitoring of colorectal cancer

ZHANG Guoliang, LIU Yiwen, HE Yiqing, XU Jing, YANG Cuixia, GAO Feng, LIU Hua

2023, 38(4):  313-319.  DOI: 10.3969/j.issn.1673-8640.2023.04.003

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Objective To investigate the levels of serum hyaluronidase 1（HYAL1） and hyaluronan（HA） and their clinical values in patients with colorectal cancer. Methods Totally，51 healthy subjects（healthy control group），46 patients with colorectal benign lesions（benign lesion group） and 75 colorectal cancer patients（colorectal cancer group） from Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine were enrolled. The clinical data were collected，and serum HYAL1 and HA levels were determined. Serum HYAL1 and HA levels were determined in 41 patients with colorectal cancer after surgery. Pearson correlation analysis was used to evaluate the correlation among all the indicators. Receiver operating characteristic（ROC） curve was used to evaluate the efficacy of single and combined determination of serum HYAL1，HA，carcinoembryonic antigen（CEA） and carbohydrate antigen 19-9（CA19-9） in the diagnosis of colorectal cancer. Results Serum HYAL1 levels in healthy control group，benign lesion group and colorectal cancer group were increased successively（P<0.000 1）. The serum HA level in colorectal cancer group was higher than that in healthy control group （P<0.000 1），but there was no statistical significance in serum HA level between benign lesion group and healthy control group，or between benign lesion group and colorectal cancer group（P>0.05）. Pearson correlation analysis showed that there was no correlation between HYAL1 and HA in healthy control group，benign lesion group and colorectal cancer group（r values were 0.147，0.072 and -0.029，P>0.05）. The areas under curves（AUC） of HYAL1，HA，CEA and CA19-9 in the diagnosis of colorectal cancer were 0.899，0.723，0.717 and 0.669，respectively. The AUC of HYAL1 combined with CEA and CA19-9 were 0.917，0.905 and 0.916，respectively. The AUC of HYAL1，CEA and CA19-9 single and combined determinations were 0.860，0.686，0.685 and 0.885 in the diagnosis of early stage（TNM stage Ⅰ to Ⅱ） colorectal cancer. Serum HYAL1 levels were related with TNM stage，lymph metastasis，vascular invasion and nerve invasion in patients with colorectal cancer（P<0.001）. The levels of serum HYAL1，HA and CEA in patients with colorectal cancer after surgery were lower than those before surgery（P<0.01），and the decrease of HYAL1 was the most obvious. There was no statistical significance in serum CA19-9 before and after surgery（P>0.05）. Conclusions Serum HYAL1 may be used as a serological indicator for the auxiliary diagnosis of early colorectal cancer and efficacy monitoring.

Role of hyaluronan in thyroid nodule fine-needle aspiration washout fluid in differential diagnosis of papillary thyroid cancer

LIU Qinqing, XU Jing, LIU Hua, LIU Yiwen, HE Yiqing, DU Yan, ZHANG Guoliang, GAO Feng, YANG Cuixia

2023, 38(4):  320-324.  DOI: 10.3969/j.issn.1673-8640.2023.04.004

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Objective To determine the role of hyaluronan（HA） in the washout of ultrasound-guided thyroid nodule fine-needle aspiration（FNA） in differential diagnosis of papillary thyroid cancer. Methods Totally，60 patients who underwent ultrasound-guided thyroid nodule FNA were enrolled from Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine from September 2021 to March 2022. According to the pathological diagnosis，the patients were classified into 2 groups，benign nodule group（24 cases） and thyroid cancer group（36 cases）. The HA level in FNA washout fluid and the expression of hyaluronic acid synthetase（HAS） mRNA in trace cells of FNA washout fluid were determined. Receiver operating characteristic（ROC）curve was used to analyze the diagnostic efficiency of HA in FNA washout fluid. Results The HA level of FNA washout fluid in thyroid cancer group was higher than that in benign nodule group（P<0.001）. The relative expression level of HAS2 mRNA in thyroid cancer group was higher than that in benign nodule group（P<0.05），but there was no statistical significance in the relative expression level of HAS1 mRNA and HAS3 mRNA between the 2 groups（P>0.05）. ROC curve analysis showed that the area under curve of HA level was 0.793 2. The cut-off value was 30.30 ng/mL，the sensitivity was 79.41%，and the specificity was 75.00%. Conclusions The level of HA in ultrasound-guided thyroid nodule FNA washout fluid plays a role in differential diagnosis of benign and malignant thyroid nodule diseases and may be a potential marker of papillary thyroid cancer.

Correlation between tumor miR-7-5p and NOVA2 levels and clinical prognosis in cancer tissues of patients with gastric cancer

LIU Ruili, LI Lanjun, JIA Minlei, WANG Yihui, HAO Weina

2023, 38(4):  325-329.  DOI: 10.3969/j.issn.1673-8640.2023.04.005

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Objective To investigate the expression changes of microRNA-7-5p（miR-7-5p） and neuro-oncological ventral antigen 2（NOVA2） in patients with gastric cancer，and to analyze the correlation with clinical prognosis. Methods A total of 86 patients with gastric cancer who underwent surgical treatment in the First Hospital of Handan from March 2014 to March 2015 were enrolled. Their cancer tissues and adjacent tissues（5 cm from tumor edge） were collected. The clinical data were collected. The miR-7-5p levels and the expression of NOVA2 were determined. Kaplan-Meier survival curve was used to analyze the survival of patients with gastric cancer，and Cox regression analysis was used to evaluate the risk factors affecting the prognosis of patients with gastric cancer. Results The relative expression level of miR-7-5p in cancer tissues was lower than that in adjacent tissues（P<0.05），and the positive expression of NOVA2 was higher than that in adjacent tissues（P<0.05）. The relative expression level of miR-7-5p and positive expression of NOVA2 had statistical significance with age，sex，tumor diameter，TNM stage，lymph metastasis，depth of invasion and histopathological grade of patients with gastric cancer（P<0.05）. Kaplan-Meier survival curve analysis showed that the 5-year survival rate of high miR-7-5p expression group was higher than that of low miR-7-5p expression group（χ²=15.226，P<0.05），and the 5-year survival rate of NOVA2 negative expression group was higher than that of NOVA2 positive expression group（χ²=22.547，P<0.05）. The miR-7-5p and NOVA2 were factors that affected the total survival rate of patients with gastric cancer [hazard ratios（HR） were 1.668 and 1.764，95% confidence intervals（CI） were 1.523-1.799 and 1.315-2.214]. Conclusions The expression of miR-7-5p is down-regulated，and NOVA2 is up-regulated in cancer tissues of patients with gastric cancer，which is correlated with clinicopathologic features. Therefore，miR-7-5p and NOVA2 may be used as indicators for the monitoring and prognostic judgment of gastric cancer.

Expression and interaction of TRX and TXNIP in colorectal cancer

YANG Jielin, WANG Xiaoyuan, LI Haixia

2023, 38(4):  330-336.  DOI: 10.3969/j.issn.1673-8640.2023.04.006

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Objective To investigate the interaction of thioredoxin（TRX） and thioredoxin-interacting protein（TXNIP） in colorectal cancer. Methods Totally，116 patients with colorectal cancer and 116 patients with rectal adenoma who underwent surgical treatment in the First Affiliated Hospital of Hebei North University from January 2019 to June 2020 were enrolled. The tissue samples [cancer tissue，adjacent tissue（4-5 cm from the lower edge of tumor） and adenoma tissue（precancerous lesion）] were collected，and the clinical data from all the patients were collected. The expressions of TRX and TXNIP in the 3 tissue samples were determined by immunohistochemistry. Immunoblotting and real-time fluorescence quantitative polymerase chain reaction（RT-qPCR） were used to determine the relative expressions of TRX，TXNIP protein and mRNA in the 3 tissue samples. The interaction between TRX and TXNIP in colorectal cancer was evaluated by generalized multifactor dimensionality reduction（GMDR）. Results The positive expression rates of TRX and TXNIP among cancer tissue，adenoma tissue and adjacent tissue had statistical significance（P<0.05）. The relative expressions of TRX mRNA and protein were decreased in turn（P<0.05），and the relative expressions of TXNIP mRNA and protein were increased in turn（P<0.05）. The positive expression rate of TRX had statistical significance among colorectal cancer patients with or without lymph metastasis，different depths of invasion，different levels of carcinoembryonic antigen，different TNM stages and different tumor locations（P<0.05）. The positive expression rate of TXNIP had statistical significance among colorectal cancer patients with or without lymph metastasis，different clinical stages，different depths of invasion，different T stages and different N stages（P<0.05）. GMDR interaction analysis showed that there was an interaction between low expressions of TXNIP protein and mRNA and high expressions of TRX protein and mRNA in colorectal cancer. Conclusions Both TRX and TXNIP are abnormally expressed in colorectal cancer，and they may play a role in the occurrence and development of colorectal cancer.

Relation of miR-433 in endometrial cancer tissues and its relationship with chemotherapy sensitivity

YUAN Shuang, FENG Lei, GUO Xiaofen, FU Xiaoling, XU Jing, LIU Hongyang

2023, 38(4):  337-341.  DOI: 10.3969/j.issn.1673-8640.2023.04.007

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Objective To investigate the expression level of microRNA-433（miR-433） in patients with endometrial cancer and its relationship with chemotherapy sensitivity. Methods From May 2019 to July 2020，98 endometrial cancer patients in Nanyang Central Hospital were enrolled as endometrial cancer group. The clinical data were collected. According to the determination of sensitivity after 4 cycles of chemotherapy，the patients with endometrial cancer were classified into sensitive group（79 cases） and insensitive group（19 cases）. Tumor tissues and paracancer tissues （3 cm from the edge of tumors）removed after chemotherapy were collected. Real-time fluorescence quantitative polymerase chain reaction（RT-qPCR） was used to determine the expression level of miR-433. Multiple Logistic regression analysis was used to analyze the factors affecting the chemotherapy sensitivity of endometrial cancer. Results Compared with adjacent tissue，the expression level of miR-433 in endometrial cancer tissue was lower（P<0.05）. The expression level of miR-433 in patients with the International Federation of Gynecology and Obstetrics（FIGO） stage Ⅲ-Ⅳ，lymph metastasis and low differentiated endometrial cancer was lower than that in patients with FIGO stage Ⅰ-Ⅱ，non-lymph metastasis and medium/high differentiated endometrial cancer（P<0.05）. Compared with sensitive group，the expression level of miR-433 in insensitive group was decreased（P<0.05）. Tumor diameter，FIGO stage，lymph metastasis and the degree of tissue differentiation were related to chemotherapy sensitivity（P<0.05）. Multiple Logistic regression analysis showed that FIGO stage and miR-433 relative expression level were risk factors affecting the chemotherapy sensitivity of endometrial cancer [odds ratios（OR） were 2.716 and 0.847，95% confidence intervals（CI） were 1.420-5.196 and 0.766-0.936，respectively]. Conclusions MiR-433 is low-expressed in endometrial cancer tissues，which is a factor affecting chemotherapy sensitivity.

Roles of IL-8 and MMP-2 in the prognosis of non-small cell lung cancer patients after thoracoscopic segmentectomy

YANG Zhongxin, LI Xiaoyu, CHEN Tao, CAO Wenjun

2023, 38(4):  342-346.  DOI: 10.3969/j.issn.1673-8640.2023.04.008

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Objective To investigate the roles of serum interleukin-8（IL-8）and matrix metalloproteinase-2（MMP-2） levels in predicting the prognosis of non-small cell lung cancer（NSCLC） patients undergoing thoracoscopic segmentectomy. Methods Totally，101 patients with NSCLC who underwent thoracoscopic segmentectomy were enrolled. The general data were collected. IL-8 and MMP-2 were determined. The patients were followed up for 3 years. According to whether the patients had recurrence，they were classified into recurrence group and non-recurrence group. Binary Logistic regression analysis was used to analyze the risk factors affecting recurrence. Receiver operating characteristic（ROC） curve was used to analyze the clinical value of preoperative serum IL-8 and MMP-2 levels in predicting the prognosis of patients. Kaplan-Meier survival curve and Log-rank χ² analysis were used to analyze the recurrence rate of NSCLC patients. Results Compared with non-recurrence group，the preoperative serum IL-8 and MMP-2 levels were higher in recurrence group（P<0.05）. The levels of IL-8 and MMP-2 were taken as cut-off values，and all the patients were classified into high expression group and low expression group. The results of binary Logistic regression analysis showed that preoperative serum IL-8≥87.52 ng/L and MMP-2≥477.86 ng/mL are independent risk factors that affected recurrence[odds ratios（OR） were 24.50 and 23.56，95% confidence intervals（CI） were 18.94-37.23 and 18.01-38.29]. ROC curve results showed that the area under curve（AUC） of IL-8 predicting recurrence was 0.834，and the AUC of MMP-2 predicting recurrence was 0.858. The results of Kaplan-Meier survival curve analysis showed that compared with IL-8 low expression group or MMP-2 low expression group，IL-8 high expression group or MMP-2 high expression group had a higher cumulative recurrence rate（P<0.001）. Conclusions The preoperative serum IL-8 and MMP-2 levels can be used as biological markers to evaluate the prognosis of patients with NSCLC after thoracoscopic segmentectomy.

Relationship between GPNMB and non-small cell lung cancer immune infiltration and prognosis

SONG Shiwei, LI Jingwu, LIN Tao, LIU Zeyu, WANG Zhiqiang, SUN Weidong

2023, 38(4):  347-351.  DOI: 10.3969/j.issn.1673-8640.2023.04.009

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Objective To investigate the clinical significance of glycoprotein non-metastatic melanoma protein B（GPNMB） expression in non-small cell lung cancer（NSCLC）. Methods Totally，124 patients with NSCLC were enrolled from Tangshan People's Hospital from April 2016 to April 2018，and the patients' cancer tissue and adjacent tissue（2-3 cm from the edge of tumor） samples were collected. The expression level of GPNMB in the patients' cancer and adjacent tissues was determined by immunohistochemistry. The expressions of CD44，CD206 and F4/80 in cancer tissue samples were determined，and the patients were classified into high and low immunoinfiltration groups. The clinicopathologic data of all the patients were collected，and all the patients were followed up for 4.5 to 36.0 months. Kaplan-Meier survival curve analysis and Log-rank χ² test were used to evaluate NSCLC patients' survival. Results Compared to adjacent tissues，the expression level of GPNMB in cancer tissues of NSCLC patients was up-regulated（P<0.001）. There was statistical significance in GPNMB expression among NSCLC patients with different TNM stages（P<0.001），and there was no statistical significance in GPNMB expression among NSCLC patients with different ages，sex and tissue types （P>0.05）. The proportion of GPNMB high expression in high immunoinfiltration group was higher than that in low immunoinfiltration group（P<0.001）. Kaplan-Meier survival curve analysis showed that the overall survival（OS） time and progression-free survival（PFS） time of high，medium and low GPNMB expression groups were gradually prolonged（P<0.05）. Conclusions GPNMB is highly expressed in cancer tissues of NSCLC patients，and the up-regulation of its expression level is related to the degree of tumor immunoinfiltration and poor prognosis.

Comparison of SARS-CoV-2 neutralizing antibody and specific antibody determination results

XIAO Xiumei, LIANG Chao, LIU Caihong, LI Xiaoguang

2023, 38(4):  352-356.  DOI: 10.3969/j.issn.1673-8640.2023.04.010

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Objective To compare severe acute respiratory syndrome coronavirus 2（SARS-CoV-2） neutralizing antibody and specific antibody determination results，and to provide a reference for clinical interpretation of specific antibody determination results in vaccinated population. Methods Totally，148 health care personnels who were excluded from SARS-CoV-2 infection were enrolled. Among them，127 cases were inoculated with SARS-CoV-2 vaccine，and they were classified into 14-30 d group，31-60 d group，61-90 d group，91-120 d group，121-150 d group and >150 d group according to the time interval between the date of sample collection and the date of the second injection of vaccine. Totally，21 cases were not inoculated with SARS-CoV-2 vaccine. Lateral flow immunoassay（LFIA） and enzyme-linked immunosorbent assay（ELISA） were used to determine SARS-CoV-2 neutralizing antibodies，and magnetic particle chemiluminescence immunoassay was used to determine SARS-Cov-2 specific IgM and IgG antibodies. The consistency of 3 methods was analyzed. Results The positive rates of ELISA neutralizing antibody，LFIA neutralizing antibody and specific IgG antibody were 100.00%，and the positive rate of specific IgM antibody was 27.27% in the 14-30 d group. With the extension of vaccination time，the positive rates of the 3 methods were decreased gradually. The positive rate of specific IgG antibody was the highest in 31-120 d groups，and the positive rate of ELISA neutralizing antibody was the highest in 121-150 d group and >150 d group. The total consistency between ELISA and LFIA for neutralizing antibody was 85.14%，and the Kappa value was 0.698. The total consistency for specific IgM antibody was 60.14%，and the Kappa value was 0.144. The total consistency for specific IgG antibody was 82.43%，and the Kappa value was 0.649. The total consistency of specific IgG antibody and LFIA neutralizing antibody was 83.78%，and the Kappa value was 0.677. Conclusions The consistency between the determination results of specific IgG antibody by magnetic particle chemiluminescence immunoassay and the determination results of neutralizing antibody by LFIA and ELISA is >80%，and the consistency is general. The positive results of specific IgG antibody should be interpreted with caution.

Correlation of Staphylococcus aureus drug resistance with drug resistance genes and virulence genes

FANG Yongmei, ZHANG Yan, XU Xueying, ZHONG Feng

2023, 38(4):  357-361.  DOI: 10.3969/j.issn.1673-8640.2023.04.011

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Objective To analyze the distribution of drug resistance genes and virulence genes of different drug resistant Staphylococcus aureus，and to investigate the correlation between drug resistance genes，virulence genes and drug resistance. Methods Totally，220 isolates of Staphylococcus aureus isolated in the Second Affiliated Hospital of Wannan Medical College from January 2018 to January 2021 were collected and classified into methicillin-resistant Staphylococcus aureus（MRSA，110 isolates） and methicillin-sensitive Staphylococcus aureus（MSSA，110 isolates）. The drug resistance genes（mecA，mecC and ermA） and virulence gene（SEA） were determined by polymerase chain reaction（PCR）. Results Among the 220 isolates of Staphylococcus aureus，MSSA had a high drug resistance rate to penicillin，there were low drug resistance rates to chloramphenicol，tetracycline，quinolone，sulfonamide and aminoglycoside. MRSA had high drug resistance rates to many types of antibacterial drugs，and the drug resistance rates to oxacillin and penicillin were 100%. Among MRSA isolates，the rates of carrying drug resistance genes and virulence genes were higher than those of MSSA isolates（P<0.01）. The drug resistance of Staphylococcus aureus with mecA drug resistance gene was higher than that of Staphylococcus aureus without mec A（P<0.01）. The drug resistance rates of Staphylococcus aureus with SEA virulence gene and ermA drug resistance gene，except for compound trimethoprim，were higher than those of Staphylococcus aureus without SEA virulence gene and ermA drug resistance gene（P<0.05）. Conclusions Drug resistance genes，mecA，mecC and ermA，and virulence gene SEA are related to the drug resistance of Staphylococcus aureus.

Clinical characteristics，molecular typing and drug resistance genes of carbapenem-resistant Klebsiella pneumoniae isolated from blood culturing

WANG Jiawei, ZHU Weinan, CHEN Yingying, JI Ping, WANG Ying

2023, 38(4):  362-367.  DOI: 10.3969/j.issn.1673-8640.2023.04.012

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Objective To analyze the clinical characteristics and drug resistance genes of carbapenem-resistant Klebsiella pneumoniae（CRKP） isolated from blood culturing，and to provide a reference for clinical antibiotic usage. Methods Totally，153 CRKP isolates from blood culturing in Xinhua Hospital of Shanghai Jiao Tong University School of Medicine from 2010 to 2019 were collected. Multilocus sequence typing（MLST） was carried out in the 153 CRKP isolates. The drug resistance genes of carbapenemase were determined. The clinical data were collected，and the clinical characteristics of CRKP were analyzed. Results The determination rate of CRKP showed a trend of increasing from 2010 to 2019. The 71.24%（109/153） CRKP were isolated from intensive care unit（ICU），and 52.29% of the patients were adults，which were >60 years old（72.50%）. Meanwhile，64.38% of the patients were infants ≤1 year old. The 64.71% of patients were discharged. According to the MLST results，86.92% CRKP（153 isolates） were ST11，29.32% of related patients were from pediatric ICU，and 18.80% were from surgery ICU. The carbapenem-resistant gene screening results showed that 131 isolates of CRKP carried bla_KPC-2，11 isolates carried bla_NDM-1，4 isolates bla_NDM-5，and the other 7 isolates had no carbapenem-resistant genes. The 129 of 131（98.47%） bla_KPC-2 carried CRKP were ST11，and the determination rate reached 84.31%（129/153）. Both bla_NDM-1 CRKP and bla_NDM-5 CRKP were non-ST11，and most of the related patients were infants ≤1 year old. Conclusions The determination rate of CRKP from blood culturing shows an increasing trend in Xinhua Hospital of Shanghai Jiao Tong University School of Medicine. The main drug resistance gene is ST11 bla_KPC-2，and the prevalence is mainly occurred in ICU.

Relationship between neutrophil/lymphocyte ratio，fibrinogen and carotid intima-media thickness in type 2 diabetes mellitus patients

DENG Xu, ZHUANG Wenlong, XUE Hui, ZHU Shuqin, LI Ying

2023, 38(4):  368-372.  DOI: 10.3969/j.issn.1673-8640.2023.04.013

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Objective To evaluate the relationship between neutrophil/lymphocyte ratio（NLR），fibrinogen（Fib） and carotid intima-media thickness（CIMT） in patients with type 2 diabetes mellitus. Methods Totally，327 patients with type 2 diabetes mellitus from Suqian First People's Hospital of Nanjing Medical University from January 2019 to April 2020 were enrolled and classified into normal CIMT group（116 cases），thickened CIMT group（38 cases） and plaque group（173 cases），according to CIMT. The differences of general data，blood routine test results and biochemical indicator determination results among the 3 groups were compared. Logistic regression analysis was used to analyze the risk factors for CIMT abnormalities in type 2 diabetes mellitus，and receiver operating characteristic（ROC） curves were used for the diagnosis efficiency of CIMT abnormalities. Results There was no statistical significance in sex，body mass index，diastolic blood pressure，renal function，blood lipid，white blood cell count，prothrombin time and international normalized ratio（INR） among normal CIMT，thickened CIMT and plaque 3 groups（P>0.05）. Compared with normal CIMT group，there was statistical significance in age，NLR and Fib in thickened CIMT group and plaque group（P<0.05）. Compared with normal CIMT group，diabetes mellitus disease course，systolic blood pressure and lymphocyte count in plaque group had statistical significance（P<0.05），and neutrophil count and glycated hemoglobin in thickened CIMT group had statistical significance（P<0.05）. Age，systolic blood pressure，NLR and Fib were risk factors for CIMT abnormality in type 2 diabetes mellitus patients [odds ratios（OR） were 1.062，1.041，1.285 and 1.477，P<0.05]. The areas under curves of NLR and Fib for diagnosing CIMT abnormality were 0.588 and 0.604，respectively（P<0.05）. Conclusions NLR and Fib play roles in screening and the diagnosis of CIMT abnormality.

Development and application of intelligent blood collection management system

LIU Lu, WANG Li, LI Kexin, CUI Wei

2023, 38(4):  373-377.  DOI: 10.3969/j.issn.1673-8640.2023.04.014

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Objective To achieve the automation and intellectualization of venous blood collection and sorting by developing and setting the functions of the blood collection management system. Methods According to the main steps in the pre-collection，collection and post-collection of venous blood，the functions of a newly introduced blood collection management system were developed and set. The changes of patients' data before and after intelligent development were analyzed. Results The functions of blood collection appointment，generation and intelligent allocation of different types of blood collection queue，patient call and patient information acquisition，blood tube selection and labeling，sample scanning and collection time generation，and sample recovery and sorting were achieved in the management system. The 87.06% and 89.78% of patients took self-service in 2020 and 2021，respectively. The proportions of regular collection were 65.11% and 65.12%，the scheduled collection proportions were 29.84% and 29.40%，and the fast-track collection proportions were 5.06% and 5.48%，respectively. The proportions were almost the same between the past 2 years. The appointment in the 7：00-8：00 was the most in 2020 and 2021，reaching 95.00% and 93.75% of the capacity，close to the saturation point. In 2020 and 2021，the proportions of waiting time ≤20 min were 77.94% and 57.02%，the waiting time ≤60 min reached 97.55% and 93.36%，respectively. In 2020 and 2021，the proportions of patients who completed blood collection within 5 min reached 90.17% and 90.57%，respectively. In 2021，the peak period of blood collection on weekdays was shortened by 1 h compared with that in 2018 when the intelligent blood collection management system had not been introduced. Conclusions The intelligent rules in the blood collection management system work well. It has complete functions to realize blood collection appointment，reduce the waiting time and improve the work efficiency of venous blood collection.

Antimicrobial drugs combined with drug susceptibility test in vitro

DENG Jin, LIU Ya, WU Siying, LIAO Quanfeng, ZHANG Weili, XIAO Yuling, XIE Yi, MA Ying, KANG Mei

2023, 38(4):  385-393.  DOI: 10.3969/j.issn.1673-8640.2023.04.017

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Due to the increasing prevalence of multi-drug resistant bacteria（MDR） and the limited options for treating these infections，the detection of interactions between antimicrobial drugs has become research hotspots in the past decade. The in vitro synergistic drug susceptibility test can provide whether there is a synergistic effect between 2 or more antimicrobial drugs and provide a reference for clinic in choosing a combination of antimicrobial drugs. Among the various in vitro methods of drug interaction，the time-kill assay（TKA），the checkerboard（CB） assay，the E test and the disc-based method are the most used. In this review，the above methods were summarized to provide a reference for clinical application.