1.Development and Validation of a High-Performance Liquid Chromatography-Tandem Mass Spectrometry Method for Detecting Adrenocortical Hormones and Establishment of Age-Stratified Reference Intervals in Reproductive-Aged Women from Guangxi, China
Yixuan LIU ; Tingwei JIN ; Yushuang WEI ; Xuelian QIN ; Siyu DENG ; Jie ZHENG ; Boteng YAN ; Yuanyuan NONG ; Yu YE ; Shengzhu HUANG ; Yu LONG ; Jianmin LI ; Ganqin WANG ; Pei HUANG ; Jinghang JIANG ; Fan WU ; Zengnan MO ; Yonghua JIANG
Annals of Laboratory Medicine 2026;46(2):146-154
Background:
Adrenocortical hormones, particularly 11-oxygenated androgens, are pivotal in female reproductive health and fertility. Standardized detection kits and population-specific reference intervals are lacking in China, hindering related clinical applications.
Methods:
A HPLC-tandem mass spectrometry (HPLC-MS/MS) pipeline was developed, rigorously validated, and applied to simultaneously quantify corticosterone, cortisone, cortisol, 18-OH cortisol, androstenedione (A4), 11β-hydroxyandrostenedione (11-OH A4), dehydroepiandrosterone, and dehydroepiandrosterone sulfate in serum samples from 455 reproductive-aged women (18–45 yrs) in Guangxi, China. Age-dependent concentration trends were analyzed, and reference intervals stratified by age (2.5th to 97.5th percentiles) were established. Correlations with body-composition metrics, ethnicity, and the menstrual cycle were investigated.
Results:
The HPLC-MS/MS method demonstrated high precision (intra- and inter-assay CVs < 15%), accuracy, and sensitivity. All eight hormones exhibited significant age-related declines (P < 0.001 for seven hormones; P = 0.001 for 11-OH A4). Notably, 11-OH A4 levels were significantly lower in the 35–45-yr (3.05 nmol/L) and 25–34-yr (3.09 nmol/L) age groups than in the 18–24-yr (3.57 nmol/L) age group, whereas no significant difference was observed between the 35–45-yr and 25–34-yr age groups. Weak negative correlations were observed between the body mass index and corticosterone and cortisone levels, whereas ethnicity and the menstrual cycle showed no significant associations with hormone levels.
Conclusions
We developed an HPLC-MS/MS-based method for simultaneously quantifying eight adrenocortical hormones, including 11-OH A4, and defined age-specific reference intervals for reproductive-aged Chinese women. These findings advance the clinical utility of adrenocortical hormones in diagnosing and managing reproductive disorders.
2.Methacrylated dermal extracellular matrix hydrogel promotes repair of abdominal wall defects
Zhongyu LIU ; Wenya LI ; Yonghong FAN ; Shuang LYU ; Juan PEI ; Yaqin CHEN ; Beiyu LIU ; Hongyu SUN
Chinese Journal of Tissue Engineering Research 2025;29(10):2074-2082
BACKGROUND:Synthetic polymers,such as polypropylene and polyester,used for the treatment of abdominal wall defects not only lack biodegradability and bioactivity but also fail to meet the demands of complex and irregular wounds.Therefore,finding bioactive materials with low immunogenicity and good histocompatibility has become a hot spot in the repair of abdominal wall defects. OBJECTIVE:To prepare methacryloyl modified dermal extracellular matrix hydrogel and explore its potential application in abdominal wall defect. METHODS:(1)The porcine dermis was acellular with 0.25%trypsin and 1%Triton X-100 in turn to obtain the dermal extracellular matrix.After pepsin digestion and methacrylic anhydride modification,the methacrylated dermal extracellular matrix hydrogel was formed by photocrosslinking.The microscopic morphology of the hydrogel was observed by scanning electron microscope,and its rheological properties,swelling properties and other physical and chemical properties were tested.(2)Mice fibroblasts(L929)were inoculated into methacrylated dermal extracellular matrix hydrogel to detect the cell compatibility.(3)Totally 12 SD rats were randomly divided into two groups(n=6)to create abdominal wall defect model with peritoneum preserved.The defect site of the polypropylene group was filled with polypropylene material,and the hydrogel group was filled with methacrylated dermal extracellular matrix hydrogel.The wound skin of both groups was covered with polypropylene material.The wound healing was observed and histological analysis was carried out. RESULTS AND CONCLUSION:(1)Enzymatic hydrolysis had a good decellularization effect on porcine dermis after decellularization,and the original glycosaminoglycans and collagen were well retained.Scanning electron microscope observation revealed that the dermal extracellular matrix hydrogel presented loose and porous structure.The aperture was between 70 and 120 μm.The swelling ratio was(16.88±3.24)%and the water absorption was(94.24±1.11)%.The rheological property test showed that the methacrylated dermal extracellular matrix hydrogel was stable and had shear thinning characteristics,with injectability.(2)CCK-8 assay and live/dead staining showed that methacrylated dermal extracellular matrix hydrogel had good cell compatibility.(3)The results of animal experiments showed that the skin wound healing rate of the experimental group was higher than that of the control group at 7,10,and 14 days after operation(P<0.05).Hematoxylin-eosin and Masson staining of skin and muscle tissue exhibited that compared with the polypropylene group,the skin wound epithelialization,hair follicle formation,collagen fiber arrangement,and neovascularization were better in the hydrogel group 14 days after surgery.The skin wound new tissue structure was similar to the normal tissue at 28 days after surgery,and scar hyperplasia was less.A small amount of muscle regeneration was observed on day 28 after operation.(4)The results show that the methacrylated dermal extracellular matrix hydrogel can promote wound skin healing and muscle tissue regeneration in rats with abdominal wall defect.
3.Comparative study of MS-39, Sirius, and Pentacam in assisting size selection of implantable collamer lens
Jiaqi YUE ; Xindi WANG ; Yimeng FAN ; Zhao LIU ; Cheng PEI
International Eye Science 2025;25(9):1505-1510
AIM: To assess the consistency of the new anterior segment analyzer, MS-39, the Sirius and Pentacam in measuring corneal white-to-white(WTW)and central anterior chamber depth(ACD), and to compare their differences in guiding implantable collamer lens(ICL)size selection.METHODS: Retrospective case study. A total of 210 consecutive patients(420 eyes)who treated at the Ophthalmology Refractive Surgery Center of the First Affiliated Hospital of Xi'an Jiaotong University between September 2019 and September 2020 were enrolled. Three anterior segment analysis systems, MS-39, Sirius, and Pentacam, were utilized to assess the WTW and ACD, with comparative analysis of the results. The sizing of the ICL V4c was simulated using the method recommended by the STAAR company. Data correlation and consistency were evaluated.RESULTS: The WTW measurement results obtained from MS-39, Sirius, and Pentacam were 11.39±0.35, 11.42±0.36, and 11.46±0.35 mm, respectively. Notably, the WTW measurement value from MS-39 was significantly lower than that from Pentacam(P=0.002), while no statistically significant differences were observed between MS-39 and Sirius, or between Sirius and Pentacam(all P>0.05). The WTW measurements from the three devices exhibited a strong positive correlation, with correlation coefficients(r)of 0.942 between MS-39 and Sirius, 0.925 between MS-39 and Pentacam, and 0.882 between Sirius and Pentacam(all P<0.0001). The ACD measurements values from the MS-39, Sirius and Pentacam were 3.28±0.22, 3.28±0.24, and 3.21±0.23 mm, respectively. While, no statistically significant difference was found between MS-39 and Sirius(P>0.05), both measurements were significantly higher than that of Pentacam(both P<0.0001). The ACD measurements also demonstrated a strong positive correlation, with r values of 0.959 between MS-39 and Sirius, 0.947 between MS-39 and Pentacam, and 0.932 between Sirius and Pentacam(all P<0.0001). In terms of ICL size selection based on the measurements from the three devices, the 12.6 mm size was the most frequently selected, while the 13.7 mm size was the least common, the distribution of size selections across the devices was similar.CONCLUSION: MS-39 demonstrated strong positive correlation with both Sirius and Pentacam for WTW and ACD measurements, indicating that the results can be considered clinically interchangeable. Furthermore, the outcomes derived from MS-39 for ICL size selection were closely aligned with those from Sirius and Pentacam, suggesting its clinical feasibility.
4.Analysis of risk factors for diaphragmatic dysfunction after cardiovascular surgery with extracorporeal circulation: A retrospective cohort study
Xupeng YANG ; Yi SHI ; Fengbo PEI ; Simeng ZHANG ; Hao MA ; Zengqiang HAN ; Zhou ZHAO ; Qing GAO ; Xuan WANG ; Guangpu FAN
Chinese Journal of Clinical Thoracic and Cardiovascular Surgery 2025;32(08):1140-1145
Objective To clarify the risk factors of diaphragmatic dysfunction (DD) after cardiac surgery with extracorporeal circulation. Methods A retrospective analysis was conducted on the data of patients who underwent cardiac surgery with extracorporeal circulation in the Department of Cardiovascular Surgery of Peking University People's Hospital from January 2023 to March 2024. Patients were divided into two groups according to the results of bedside diaphragm ultrasound: a DD group and a control group. The preoperative, intraoperative, and postoperative indicators of the patients were compared and analyzed, and independent risk factors for DD were screened using multivariate logistic regression analysis. Results A total of 281 patients were included, with 32 patients in the DD group, including 23 males and 9 females, with an average age of (64.0±13.5) years. There were 249 patients in the control group, including 189 males and 60 females, with an average age of (58.0±11.2) years. The body mass index of the DD group was lower than that of the control group [(18.4±1.5) kg/m2 vs. (21.9±1.8) kg/m2, P=0.004], and the prevalence of hypertension, chronic obstructive pulmonary disease, heart failure, and renal insufficiency was higher in the DD group (P<0.05). There was no statistical difference in intraoperative indicators (operation method, extracorporeal circulation time, aortic clamping time, and intraoperative nasopharyngeal temperature) between the two groups (P>0.05). In terms of postoperative aspects, the peak postoperative blood glucose in the DD group was significantly higher than that in the control group (P=0.001), and the proportion of patients requiring continuous renal replacement therapy was significantly higher than that in the control group (P=0.001). The postoperative reintubation rate, tracheotomy rate, mechanical ventilation time, and intensive care unit stay time in the DD group were higher or longer than those in the control group (P<0.05). Multivariate logistic regression analysis showed that low body mass index [OR=0.72, 95%CI (0.41, 0.88), P=0.011], preoperative dialysis [OR=2.51, 95%CI (1.89, 4.14), P=0.027], low left ventricular ejection fraction [OR=0.88, 95%CI (0.71, 0.93), P=0.046], and postoperative hyperglycemia [OR=3.27, 95%CI (2.58, 5.32), P=0.009] were independent risk factors for DD. Conclusion The incidence of DD is relatively high after cardiac surgery, and low body mass index, preoperative renal insufficiency requiring dialysis, low left ventricular ejection fraction, and postoperative hyperglycemia are risk factors for DD.
5.Review of chemical constituents, pharmacological effects, and quality control status of Eucommiae Cortex and prediction of its Q-markers.
Meng-Fan PENG ; Bao-Song LIU ; Pei-Pei YAN ; Cai-Xia LI ; Xiao-Fang ZHANG ; Yi ZHENG ; Ya-Gang SONG ; Tong LIU ; Lei YANG ; Ming-San MIAO
China Journal of Chinese Materia Medica 2025;50(4):946-958
Eucommiae Cortex, the dried bark of Eucommia ulmoides( Eucommiaceae), has both medicinal and edible values.Modern research has shown that Eucommiae Cortex contains various components such as flavonoids, lignans, iridoids, phenolic acids,terpenoids, and steroids, which have anti-osteoporosis, antioxidant, anti-inflammatory, blood glucose-lowering, and gastrointestinal tract-protecting effects. Eucommiae Cortex has applications in multiple fields such as healthcare, industry, and animal husbandry,demonstrating broad development prospects. This article reviews the chemical constituents, pharmacological effects, and quality control status of Eucommiae Cortex. Furthermore, according to the concept of quality marker(Q-marker), this article predicts the Q-markers of Eucommiae Cortex from traditional medicinal properties, traditional medicinal effects, new medicinal effects, measurability of chemical components, compatibility, harvesting periods, and geographical origins. The components such as pinoresinol diglucoside,chlorogenic acid, caffeic acid, quercetin, baicalein, baicalin, olivil, coniferyl ferulate, and kaempferol can be used as Q-markers for Eucommiae Cortex, which provide reference for establishing a systematic quality control system for Eucommiae Cortex.
Eucommiaceae/chemistry*
;
Drugs, Chinese Herbal/pharmacology*
;
Quality Control
;
Humans
;
Animals
6.Predicting Clinically Significant Prostate Cancer Using Urine Metabolomics via Liquid Chromatography Mass Spectrometry
Chung-Hsin CHEN ; Hsiang-Po HUANG ; Kai-Hsiung CHANG ; Ming-Shyue LEE ; Cheng-Fan LEE ; Chih-Yu LIN ; Yuan Chi LIN ; William J. HUANG ; Chun-Hou LIAO ; Chih-Chin YU ; Shiu-Dong CHUNG ; Yao-Chou TSAI ; Chia-Chang WU ; Chen-Hsun HO ; Pei-Wen HSIAO ; Yeong-Shiau PU ;
The World Journal of Men's Health 2025;43(2):376-386
Purpose:
Biomarkers predicting clinically significant prostate cancer (sPC) before biopsy are currently lacking. This study aimed to develop a non-invasive urine test to predict sPC in at-risk men using urinary metabolomic profiles.
Materials and Methods:
Urine samples from 934 at-risk subjects and 268 treatment-naïve PC patients were subjected to liquid chromatography/mass spectrophotometry (LC-MS)-based metabolomics profiling using both C18 and hydrophilic interaction liquid chromatography (HILIC) column analyses. Four models were constructed (training cohort [n=647]) and validated (validation cohort [n=344]) for different purposes. Model I differentiates PC from benign cases. Models II, III, and a Gleason score model (model GS) predict sPC that is defined as National Comprehensive Cancer Network (NCCN)-categorized favorable-intermediate risk group or higher (Model II), unfavorable-intermediate risk group or higher (Model III), and GS ≥7 PC (model GS), respectively. The metabolomic panels and predicting models were constructed using logistic regression and Akaike information criterion.
Results:
The best metabolomic panels from the HILIC column include 25, 27, 28 and 26 metabolites in Models I, II, III, and GS, respectively, with area under the curve (AUC) values ranging between 0.82 and 0.91 in the training cohort and between 0.77 and 0.86 in the validation cohort. The combination of the metabolomic panels and five baseline clinical factors that include serum prostate-specific antigen, age, family history of PC, previously negative biopsy, and abnormal digital rectal examination results significantly increased AUCs (range 0.88–0.91). At 90% sensitivity (validation cohort), 33%, 34%, 41%, and 36% of unnecessary biopsies were avoided in Models I, II, III, and GS, respectively. The above results were successfully validated using LC-MS with the C18 column.
Conclusions
Urinary metabolomic profiles with baseline clinical factors may accurately predict sPC in men with elevated risk before biopsy.
7.Intelligent handheld ultrasound improving the ability of non-expert general practitioners in carotid examinations for community populations: a prospective and parallel controlled trial
Pei SUN ; Hong HAN ; Yi-Kang SUN ; Xi WANG ; Xiao-Chuan LIU ; Bo-Yang ZHOU ; Li-Fan WANG ; Ya-Qin ZHANG ; Zhi-Gang PAN ; Bei-Jian HUANG ; Hui-Xiong XU ; Chong-Ke ZHAO
Ultrasonography 2025;44(2):112-123
Purpose:
The aim of this study was to investigate the feasibility of an intelligent handheld ultrasound (US) device for assisting non-expert general practitioners (GPs) in detecting carotid plaques (CPs) in community populations.
Methods:
This prospective parallel controlled trial recruited 111 consecutive community residents. All of them underwent examinations by non-expert GPs and specialist doctors using handheld US devices (setting A, setting B, and setting C). The results of setting C with specialist doctors were considered the gold standard. Carotid intima-media thickness (CIMT) and the features of CPs were measured and recorded. The diagnostic performance of GPs in distinguishing CPs was evaluated using a receiver operating characteristic curve. Inter-observer agreement was compared using the intragroup correlation coefficient (ICC). Questionnaires were completed to evaluate clinical benefits.
Results:
Among the 111 community residents, 80, 96, and 112 CPs were detected in settings A, B, and C, respectively. Setting B exhibited better diagnostic performance than setting A for detecting CPs (area under the curve, 0.856 vs. 0.749; P<0.01). Setting B had better consistency with setting C than setting A in CIMT measurement and the assessment of CPs (ICC, 0.731 to 0.923). Moreover, measurements in setting B required less time than the other two settings (44.59 seconds vs. 108.87 seconds vs. 126.13 seconds, both P<0.01).
Conclusion
Using an intelligent handheld US device, GPs can perform CP screening and achieve a diagnostic capability comparable to that of specialist doctors.
8.Early results and indications of Stand-alone oblique lateral interbody fusion in lumbar lesions.
Zhong-You ZENG ; Xing ZHAO ; Wei YU ; Yong-Xing SONG ; Shun-Wu FAN ; Xiang-Qian FANG ; Fei PEI ; Shi-Yang FAN ; Guo-Hao SONG
China Journal of Orthopaedics and Traumatology 2025;38(5):454-464
OBJECTIVE:
To summarize the early clinical results and safety of Stand-alone OLIF application of lumbar lesions, and explored its surgical indications.
METHODS:
Total of 92 cases of lumbar spine lesions treated with Stand-alone OLIF at two medical centers from October 2014 to December 2018 were retrospectively analyzed, including 30 males and 62 females with an average age of (61.20±12.94) years old ranged from 32 to 83 years old. There were 20 cases of lumbar spinal stenosis, 15 cases of lumbar disc degeneration, 11 cases of lumbar degenerative spondylolisthesis, 6 cases of discogenic low back pain, 7 cases of giant lumbar disc herniation, 13 cases of primary lumbar discitis, 6 cases of adjacent vertebral disease after lumbar internal fixation surgery, and 14 cases of degenerative lumbar scoliosis. Pre-operative dual energy X-ray bone density examination 31 cases' T-values ranged from -1 to -2.4, 8 cases' T-values ranged from -2.5 to -3.5, and the rest had normal bone density. The number of fusion segments: 68 cases of single segment, 9 cases of two segment, 12 cases of three segment , and 3 cases of four segment. Fusion site:L1,2 1 case, L2,3 4 cases, L3,4 10 cases, L4,5 53 cases, L2,3-L3,4 3 cases, L3,4-L4,5 6 cases, L1,2L2,3L3,4 1 case, L1,2L3,4L4,5 1 case, L2,3L3,4L4,5 10 cases, L1,2L2,3L3,4L4,5 3 cases. The clinical results and imaging results of this group of cases were observed, as well as the complications.
RESULTS:
The surgical time ranged from 40 to 140 minutes with an average of (60.92±27.40) minutes. The intraoperative bleeding volume was 20 to 720 ml with an average of (68.22±141.60) ml. The patients had a follow-up period of 6 to 84 months with an average of (38.50±12.75) months. The height of the intervertebral space recovered from (9.23±1.94) mm in preoperative to (12.68±2.01) mm in postoperative, and (9.11±1.72) mm at the last follow-up, there was a statistically significant difference(F=6.641, P=0.008);there was also a statistically significant difference between the postoperative and preoperative height of the intervertebral space(t=9.27, P<0.000 1);and there was also a statistically significant difference (t=10.06, P<0.000 1) between the last follow-up and postoperative height of the intervertebral space. At the last follow-up, cage subsidence grading was as follows:level 0 in 69 cases (76 segments), levelⅠin 17 cases (43 segments), level Ⅱin 5 cases (14 segments), and level Ⅲ in 1 case (1 segment);according to the number of segments, normal subsidence accounts for 56.72%, abnormal subsidence accounts for 43.28%. Bone mineral desity of normal subsidence groups was -0.50±0.07 whinch was better than that the abnormal subsidence groups -2.10±0.43, and the difference was statistically significant(χ2=2.275, P=0.014). As well as there was a statistically significant difference in the patient's VAS of backache from (6.28±2.11) in preoperative to (1.48±0.59) in last follow-up(t=8.56, P<0.05). The ODI recovered from (36.30±7.52)% before surgery to (10.20±2.50)% at the last follow-up, with a statistically significant difference (t=7.79, P<0.000 1). Complications involved 4 cases of intraoperative vascular injury, 21 cases of endplate injury, and 4 cases of combined vertebral fractures. The incision skin has no necrosis or infection. There were 4 cases of left sympathetic chain injury, 4 cases of transient left hip flexion weakness, 2 cases of left thigh anterolateral numbness with quadriceps femoris weakness, and 1 case of incomplete intestinal obstruction;8 cases were treated with posterior pedicle screw fixation due to fusion cage settlement accompanied by stubborn lower back pain, and 6 cases were treated with fusion cage settlement and lateral displacement. According to the actual number of cases, there were 38 complications, with an incidence rate of 41.3%.
CONCLUSION
The application of Stand alone OLIF in lumbar spine disease fusion has achieved good early results, with obvious clinical advantages, but also there are high probability of complications. It is recommended to choose carefully. It is necessary to continuously summarize and gradually clarify and complete the surgical indications and specific case selection criteria.
Humans
;
Male
;
Female
;
Middle Aged
;
Spinal Fusion/methods*
;
Lumbar Vertebrae/injuries*
;
Aged
;
Adult
;
Retrospective Studies
;
Aged, 80 and over
9.Non-Down-syndrome-related acute megakaryoblastic leukemia in children: a clinical analysis of 17 cases.
Ding-Ding CUI ; Ye-Qing TAO ; Xiao-Pei JIA ; An-Na LIAN ; Qiu-Xia FAN ; Dao WANG ; Xue-Ju XU ; Guang-Yao SHENG ; Chun-Mei WANG
Chinese Journal of Contemporary Pediatrics 2025;27(9):1113-1118
OBJECTIVES:
To investigate the clinical features and prognosis of children with non-Down-syndrome-related acute megakaryoblastic leukemia (non-DS-AMKL).
METHODS:
A retrospective analysis was conducted on the medical data of 17 children with non-DS-AMKL who were admitted to Children's Hospital of The First Affiliated Hospital of Zhengzhou University from January 2013 to December 2023, and their clinical features, treatment, and prognosis were summarized.
RESULTS:
Among the 17 children with non-DS-AMKL, there were 8 boys and 9 girls. Fourteen patients had an onset age of less than 36 months, with a median age of 21 months (range:13-145 months). Immunophenotyping results showed that 16 children were positive for CD61 and 13 were positive for CD41. The karyotype analysis was performed on 16 children, with normal karyotype in 6 children and abnormal karyotype in 9 children, among whom 5 had complex karyotype and 1 had no mitotic figure. Detected fusion genes included EVI1, NUP98-KDM5A, KDM5A-MIS18BP1, C22orf34-BRD1, WT1, and MLL-AF9. Genetic alterations included TET2, D7S486 deletion (suggesting 7q-), CSF1R deletion, and PIM1. All 17 children received chemotherapy, among whom 16 (94%) achieved complete remission after one course of induction therapy, and 1 child underwent hematopoietic stem cell transplantation (HSCT) and remained alive and disease-free. Of all children, 7 experienced recurrence, among whom 1 child received HSCT and died of graft-versus-host disease. At the last follow-up, six patients remained alive and disease-free.
CONCLUSIONS
Non-DS-AMKL primarily occurs in children between 1 and 3 years of age. The patients with this disorder have a high incidence rate of chromosomal abnormalities, with complex karyotypes in most patients. Some patients harbor fusion genes or gene mutations. Although the initial remission rate is high, the long-term survival rate remains low.
Humans
;
Male
;
Female
;
Leukemia, Megakaryoblastic, Acute/etiology*
;
Child, Preschool
;
Infant
;
Child
;
Retrospective Studies
;
Prognosis
;
Down Syndrome/complications*
10.Predicting Clinically Significant Prostate Cancer Using Urine Metabolomics via Liquid Chromatography Mass Spectrometry
Chung-Hsin CHEN ; Hsiang-Po HUANG ; Kai-Hsiung CHANG ; Ming-Shyue LEE ; Cheng-Fan LEE ; Chih-Yu LIN ; Yuan Chi LIN ; William J. HUANG ; Chun-Hou LIAO ; Chih-Chin YU ; Shiu-Dong CHUNG ; Yao-Chou TSAI ; Chia-Chang WU ; Chen-Hsun HO ; Pei-Wen HSIAO ; Yeong-Shiau PU ;
The World Journal of Men's Health 2025;43(2):376-386
Purpose:
Biomarkers predicting clinically significant prostate cancer (sPC) before biopsy are currently lacking. This study aimed to develop a non-invasive urine test to predict sPC in at-risk men using urinary metabolomic profiles.
Materials and Methods:
Urine samples from 934 at-risk subjects and 268 treatment-naïve PC patients were subjected to liquid chromatography/mass spectrophotometry (LC-MS)-based metabolomics profiling using both C18 and hydrophilic interaction liquid chromatography (HILIC) column analyses. Four models were constructed (training cohort [n=647]) and validated (validation cohort [n=344]) for different purposes. Model I differentiates PC from benign cases. Models II, III, and a Gleason score model (model GS) predict sPC that is defined as National Comprehensive Cancer Network (NCCN)-categorized favorable-intermediate risk group or higher (Model II), unfavorable-intermediate risk group or higher (Model III), and GS ≥7 PC (model GS), respectively. The metabolomic panels and predicting models were constructed using logistic regression and Akaike information criterion.
Results:
The best metabolomic panels from the HILIC column include 25, 27, 28 and 26 metabolites in Models I, II, III, and GS, respectively, with area under the curve (AUC) values ranging between 0.82 and 0.91 in the training cohort and between 0.77 and 0.86 in the validation cohort. The combination of the metabolomic panels and five baseline clinical factors that include serum prostate-specific antigen, age, family history of PC, previously negative biopsy, and abnormal digital rectal examination results significantly increased AUCs (range 0.88–0.91). At 90% sensitivity (validation cohort), 33%, 34%, 41%, and 36% of unnecessary biopsies were avoided in Models I, II, III, and GS, respectively. The above results were successfully validated using LC-MS with the C18 column.
Conclusions
Urinary metabolomic profiles with baseline clinical factors may accurately predict sPC in men with elevated risk before biopsy.

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