Objective: To explore the utility of stool-based DNA test of methylated SDC2 (mSDC2) for colorectal cancer (CRC) screening in residents of Shipai Town, Dongguan City. Methods: This was a cross-sectional study. Using a cluster sampling method, residents of 18 villages in Shipai Town, Dongguan City were screened for CRC from May 2021 to February 2022. In this study, mSDC2 testing was employed as a preliminary screening method. Colonoscopy examination was recommended for individuals identified as high-risk based on the positive mSDC2 tests. The final screening results, including the rate of positive mSDC2 tests, the rate of colonoscopy compliance, the rate of lesions detection, and the cost-effectiveness of screening, were analyzed to explore the benefits of this screening strategy. Results: A total of 10 708 residents were enrolled and completed mSDC2 testing, giving a participation rate of 54.99% (10 708/19 474) and a pass rate of 97.87% (10 708/10 941). These individuals included 4 713 men (44.01%) and 5 995 women (55.99%) with a mean age of (54.52±9.64) years. The participants were allocated to four age groups (40-49, 50-59, 60-69, and 70-74 years), comprising 35.21%(3770/10 708), 36.25% (3882/10 708), 18.84% (2017/10 708), and 9.70% (1039/10 708) of all participants, respectively. mSDC2 testing was positive in 821/10 708 (7.67%) participants, 521 of whom underwent colonoscopy, resulting in a compliance rate of 63.46% (521/821). After eliminating of 8 individuals without pathology results, data from 513 individuals were finally analyzed. Colonoscopy detection rate differed significantly between age groups (χ²=23.155, P<0.001),ranging from a low of 60.74% in the 40-49 year age group to a high of 86.11% in the 70-74 year age group. Colonoscopies resulted in the diagnosis of 25 (4.87%) CRCs, 192 (37.43%) advanced adenomas, 67 (13.06%) early adenomas, 15 (2.92%) serrated polyps, and 86 (16.76%) non- adenomatous polyps. The 25 CRCs were Stage 0 in 14 (56.0%) individuals, stage I in 4 (16.0%), and Stage II in 7(28.0%). Thus, 18 of the detected CRCs were at an early stage. The early detection rate of CRCs and advanced adenomas was 96.77% (210/217). The rate of mSDC2 testing for all intestinal lesions was 75.05% (385/513). In particular, the financial benefit of this screening was 32.64 million yuan, and the benefit-cost ratio was 6.0. Conclusion: Screening for CRCs using stool-based mSDC2 testing combined with colonoscopy has a high lesion detection rate and a high cost-effectiveness ratio. This is a CRC screening strategy that deserves to be promoted in China.
Male ; Humans ; Female ; Adult ; Middle Aged ; Cross-Sectional Studies ; Early Detection of Cancer/methods* ; Colorectal Neoplasms/pathology* ; Colonoscopy/methods* ; Mass Screening/methods* ; Adenoma/diagnosis* ; DNA ; Syndecan-2/genetics*

Objective: To investigate the value of stool-based methylated SDC2 test in physical examination population for the screening of colorectal neoplasms. Methods: Using the prospective cohort study method, from December 2020 to November 2021, 2 107 participants from the First People's Hospital of Xiushui County, Jiangxi Province were enrolled, consisted of 1 012 males and 1 094 females, aged 20-90 years with the median age of 49 years old. Fresh stool samples were collected and SDC2 DNA methylation tests were carried out as the primary screening method. The participants with positive results were recommended to undergo colonoscopy, and those who were negative were followed up by telephone. The positive rate of screening, the compliance of colonoscopy, and the detection of colorectal lesions were analyzed by chi-square test. Combined the follow-up results of negative subjects, the value of SDC2 DNA methylation test for the screening of colorectal neoplasms was evaluated. Results: Among the 2 107 participants, 2 106 completed the SDC2 methylation test. 113 participants (5.4%) were positive. The positive rate of primary screening increased with age significantly (χ²=32.135, P<0.001). Out of 113 cases, 72 (63.7%) underwent colonoscopy examinations. Finally, 3 (4.2%) cases of colorectal cancer, 12 (16.7%) cases of advanced adenoma, 31 (43.1%) cases of non-advanced adenoma, and 16 (22.2%) cases of non-adenomatous polyp were detected. The positive predictive value (PPV) of stool-based SDC2 DNA methylation test for intestinal lesions and colorectal neoplasms were 86.1% and 63.9%, respectively. Among the 1 374 follow-up participants, the negative predictive value (NPV) of this test for intestinal lesions and colorectal neoplasms were 97.7% and 99.4%, respectively. Conclusion: Primary stool-based SDC2 DNA methylation test and subsequent colonoscopy examination can effectively find colorectal neoplasms. This strategy may be a potential tool for the screening of colorectal neoplasms in general risk population.
Male ; Female ; Humans ; Middle Aged ; Sensitivity and Specificity ; Prospective Studies ; Early Detection of Cancer/methods* ; Colorectal Neoplasms/diagnosis* ; Mass Screening/methods* ; Feces ; DNA Methylation ; Colonoscopy ; Physical Examination ; Syndecan-2/genetics*

OBJECTIVE: To compare the effects of direct fluorescence in situ hybridization (D-FISH) detection without sorting and CD138 immunomagnetic bead sorting technology combined with FISH (MACS-FISH) on cytogenetic analysis of patients with multiple myeloma (MM). METHODS: FISH test results of 229 patients with initial MM were retrospectively analyzed. The patients were divided into two groups, 140 patients were tested with D-FISH and 89 patients with MACS-FISH. The combination probe was designed as P53, D13S319, RB1, 1q21, and IgH. Cytogenetic detection results were compared between the two groups. RESULTS: The total detection rate of cytogenetic abnormalities in D-FISH group was 52.9%, and that in MACS-FISH group was 79.8%. There was a significant difference in the cytogenetic abnormality rate between the two groups (P=0.020). The abnormal genes with the highest detection rate in the two groups were 1q21 and IgH, respectively, while the lowest was P53. There was no significant difference in the percentage of P53 positive cells (positive rate) between the two groups, while D13S319, RB1, 1q21, and IgH showed significant difference in positive cell rate (P=0.0002, P<0.0001, P=0.0033, P=0.0032). There was no significant correlation between the proportion of plasma cells (PC) detected by bone marrow morphology and cytogenetic abnormality rate in the D-FISH group, while there was a correlation between the proportion of PC detected by flow cytometry and cytogenetic abnormality rate (r=0.364). The PC proportion detected by bone marrow morphology and flow cytometry in the MACS-FISH group had no correlation with the cytogenetic abnormality rate and positive cell rate of the 5 genes mentioned above. Additionally, the PC proportion detected by bone marrow morphology and flow cytometry showed significant difference (P<0.0001). CONCLUSION CD138 immunomagnetic bead sorting combined with FISH technology can significantly improve the abnormality detection rate of MM cytogenetics.
Chromosome Aberrations ; Humans ; In Situ Hybridization, Fluorescence/methods* ; Multiple Myeloma/genetics* ; Retrospective Studies ; Syndecan-1/immunology* ; Tumor Suppressor Protein p53/genetics*

OBJECTIVE: To study the change and significance of serum pentraxin-3 (PTX-3) and syndecan-4 in children with chronic heart failure (CHF). METHODS: A total of 40 children with CHF who were admitted to the Department of Pediatrics of the First Affiliated Hospital of Zhengzhou University were enrolled as the heart failure group, and 30 children who underwent physical examination in the outpatient service during the same period of time were enrolled as the control group. The serum levels of PTX-3, syndecan-4, and N-terminal pro-brain natriuretic peptide (NT-proBNP) were compared between the two groups. RESULTS: The children with CHF had significant reductions in the serum levels of PTX-3, syndecan-4, and NT-proBNP after treatment. The levels of these markers in children with CHF were significantly higher than the control group before and after treatment ( CONCLUSIONS Serum PTX-3 and syndecan-4 may be involved in the development and progression of ventricular remodeling in children with CHF and may be used as markers for the diagnosis, cardiac function grading, and treatment outcome evaluation of children with heart failure.
Biomarkers ; Child ; Chronic Disease ; Heart Failure ; Humans ; Natriuretic Peptide, Brain ; Peptide Fragments ; Stroke Volume ; Syndecan-4 ; Ventricular Function, Left

Multiple myeloma (MM), considered an incurable hematological malignancy, is characterized by its clonal evolution of malignant plasma cells. Although the application of autologous stem cell transplantation (ASCT) and the introduction of novel agents such as immunomodulatory drugs (IMiDs) and proteasome inhibitors (PIs) have doubled the median overall survival to eight years, relapsed and refractory diseases are still frequent events in the course of MM. To achieve a durable and deep remission, immunotherapy modalities have been developed for relapsed/refractory multiple myeloma (RRMM). Among these approaches, chimeric antigen receptor (CAR) T-cell therapy is the most promising star, based on the results of previous success in B-cell neoplasms. In this immunotherapy, autologous T cells are engineered to express an artificial receptor which targets a tumor-associated antigen and initiates the T-cell killing procedure. Tisagenlecleucel and Axicabtagene, targeting the CD19 antigen, are the two pacesetters of CAR T-cell products. They were approved by the US Food and Drug Administration (FDA) in 2017 for the treatment of acute lymphocytic leukemia (ALL) and diffuse large B-cell lymphoma (DLBCL). Their development enabled unparalleled efficacy in combating hematopoietic neoplasms. In this review article, we summarize six promising candidate antigens in MM that can be targeted by CARs and discuss some noteworthy studies of the safety profile of current CAR T-cell therapy.
ADP-ribosyl Cyclase 1/immunology* ; B-Cell Maturation Antigen/immunology* ; Humans ; Immunotherapy, Adoptive/methods* ; Multiple Myeloma/therapy* ; Receptors, Chimeric Antigen/immunology* ; Receptors, G-Protein-Coupled/immunology* ; Signaling Lymphocytic Activation Molecule Family/immunology* ; Syndecan-1/immunology* ; T-Lymphocytes/immunology*

Animals ; Epithelial-Mesenchymal Transition ; Lung/metabolism* ; Male ; Pulmonary Disease, Chronic Obstructive ; Rats ; Rats, Sprague-Dawley ; Signal Transduction ; Smad2 Protein/metabolism* ; Syndecan-1 ; Transforming Growth Factor beta1/metabolism*

PURPOSE: Transglutaminase type 2 (TG2) is an extracellular matrix crosslinking enzyme with a pivotal role in kidney fibrosis. We tested whether quantification of urinary TG2 may represent a noninvasive method to estimate the severity of kidney allograft fibrosis. METHODS: We prospectively collected urine specimens from 18 deceased donor kidney transplant recipients at 1-day, 7-day, 1-month, 3-month, and 6-month posttransplant. In addition, kidney allograft tissue specimens at 0-day and 6-month posttransplant were sampled to analyze the correlation of urinary TG2 and kidney allograft fibrosis. RESULTS: Thirteen recipients had increased interstitial fibrosis and tubular atrophy (IFTA) scores at the 6-month protocol biopsy (IFTA group). The mean level of urinary TG2 in the IFTA group was higher compared to that of 5 other recipients without IFTA (no IFTA group). Conversely, the mean level of urinary syndecan-4 in the IFTA group was lower than levels in patients without IFTA. In the IFTA group, double immunofluorescent staining revealed that TG2 intensity was significantly upregulated and colocalizations of TG2/heparin sulfate proteoglycan and nuclear syndecan-4 were prominent, usually around tubular structures. CONCLUSION: Urinary TG2 in early posttransplant periods is a potent biomarker for kidney allograft inflammation or fibrosis.
Allografts ; Atrophy ; Biomarkers ; Biopsy ; Extracellular Matrix ; Fibrosis ; Humans ; Inflammation ; Kidney Transplantation ; Kidney ; Methods ; Prospective Studies ; Proteoglycans ; Syndecan-4 ; Tissue Donors ; Transplant Recipients

To explore the effect of ulinastatin on perioperative glycocalyx and lung function in patients undergoing mitral valve replacement surgery.
 Methods: Fourty patients, undergoing mitral valve replacement, were randomly allocated into a control group and an ulinastatin group, which were administrated 50 mL normal saline or 2×104 U/kg ulinastatin at the beginning of cardiopulmonary bypass (CPB), respectively. The radical artery blood was collected at 4 time points: After induction of anesthesia (T0), at 10 min after the start of CPB (T1), 1 h after the end of CPB (T2), and 8 h after operation. The concentration of syndecan-1 and TNF-α in blood was measured. Moreover, the blood gas analysis was preformed and the oxygen index (OI) and difference in alveolar arterial oxygen partial pressure (PA-aO2) were calculated at T0, T2, and T3.
 Results: There were no significant difference between the 2 groups in OI, PA-aO2, and the concentration of syndecan-1 and TNF-α at T0 (P>0.05). The concentration of syndecan-1 and TNF-α was significantly increased at T1 and T2 in the 2 groups, and reached peak at T2. Compared with the control group, the concentration of syndecan-1 and TNF-α was decreased in the ulinastatin group at T1, T2, and T3 (P<0.05). Compared with T0, OI was lower and PA-aO2 was higher at T2 and T3 in both groups, but the 2 indexes were improved in the ulinastatin group compared with those in the control group (P<0.05).
 Conclusion: Ulinastatin can improve the post-operative pulmonary ventilation function in patients with mitral valve replacement. The mechanism may be associated with the inhibition of TNF-α release and the reduction of glycocalyx shedding induced by ulinastatin.
Cardiopulmonary Bypass ; Glycocalyx ; drug effects ; Glycoproteins ; pharmacology ; Heart Valve Prosthesis Implantation ; Humans ; Lung ; drug effects ; Mitral Valve ; surgery ; Oxygen ; blood ; Syndecan-1 ; blood ; Time Factors ; Tumor Necrosis Factor-alpha ; blood

BACKGROUND: Syndecan-1 (sCD138) has recently been suggested to predict the clinical course of early-stage chronic lymphocytic leukemia (CLL), but few studies have been reported. This study assessed the role of syndecan-1 in the prognosis of patients with CLL and its correlation with other prognostic markers. METHODS: This prospective study was performed in the hematology department of an Indian tertiary care center, over nineteen months (Jun. 2009–Jan. 2011). Forty-nine new patients with CLL presented during this period and were included. Twenty age- and gender-matched healthy patients served as controls, and six patients with multiple myeloma were included as positive controls. Baseline serum syndecan-1 concentrations were measured for all patients at presentation using ELISA (Diaclone, Besancon, France). At baseline, patients were divided into low (N=10), intermediate (N=18) and high (N=21) risk cohorts. Serum syndecan-1 levels in these patient subgroups were compared with clinical and laboratory parameters. RESULTS: The median syndecan-1 level in patients with CLL (73.32 ng/mL, range, 28.71–268.0 ng/mL) was marginally higher than that in healthy patients (63.10 ng/mL, range, 55.0–75.11 ng/mL). At presentation, syndecan-1 levels in patients with CLL correlated strongly with symptomatic disease (cytopenias, P=0.004) and higher clinical stage (Rai stage III and IV, P=0.001) markers and poorly with β2-microglobulin level (P=0.270), diffuse BM infiltration (P=0.882), and surrogate mutation status markers (CD 38, P=0.174 and ZAP-70, P=0.459). Syndecan-1 levels dichotomized by the median value were higher with progressive disease markers, e.g. shorter lymphocyte doubling time (LDT, P=0.015) and increased treatment (P=0.099). CONCLUSION: In CLL, serum syndecan-1 (sCD138) levels at presentation correlate with disease burden, and higher baseline levels may predict early treatment.
Cohort Studies ; Enzyme-Linked Immunosorbent Assay ; Hematology ; Humans ; Leukemia, Lymphocytic, Chronic, B-Cell* ; Lymphocytes ; Multiple Myeloma ; Prognosis ; Prospective Studies ; Syndecan-1* ; Tertiary Care Centers

BACKGROUND/AIMS: Syndecan-2 (SDC2) methylation was previously reported as a sensitive serologic biomarker for the early detection of colorectal cancer (CRC). The purpose of this study was to investigate whether SDC2 methylation is detectable in precancerous lesions and to determine the feasibility of using SDC2 methylation for the detection of CRC and precancerous lesions in bowel lavage fluid (BLF). METHODS: A total of 190 BLF samples were collected from the rectum at the beginning of colonoscopy from patients with colorectal neoplasm and healthy normal individuals. Fourteen polypectomy specimens were obtained during colonoscopy. A bisulfite pyrosequencing assay and quantitative methylation-specific polymerase chain reaction were conducted to measure SDC2 methylation in tissues and BLF DNA. RESULTS: SDC2 methylation was positive in 100% of villous adenoma (VA) and high-grade dysplasia, and hyperplastic polyp samples; 88.9% of tubular adenoma samples; and 0% of normal mucosa samples. In the BLF DNA test forSDC2 methylation, the sensitivity for detecting CRC and VA was 80.0% and 64.7%, respectively, at a specificity of 88.9%. The BLF of patients with multiple tubular adenomas, single tubular adenoma and hyperplastic polyps showed 62.8%, 26.7% and 28.6% rates of methylation-positive SDC2, respectively. CONCLUSIONS: Our results demonstrated that SDC2 methylation was a frequent event in precancerous lesions and showed high potential in BLF for detecting patients with colorectal neoplasm.
Adenoma ; Adenoma, Villous ; Colonoscopy ; Colorectal Neoplasms* ; DNA ; Feces ; Humans ; Methylation* ; Mucous Membrane ; Polymerase Chain Reaction ; Polyps ; Rectum ; Sensitivity and Specificity ; Syndecan-2* ; Therapeutic Irrigation*