Clinical application of serum CST4 combined with tumor markers in the diagnosis of digestive system malignant tumors.

The aim of the present study was to evaluate the diagnostic value of plasma human cystatin-S (CST4) in patients with digestive system malignant tumors. CST4 and tumor markers, such as α-fetoprotein (AFP), carcinoembryonic antigen (CEA), carbohydrate antigen (CA)199, CA125, CA153 and CA724, were detected in blood samples from 100 patients with a digestive system malignant tumor and 100 patients with benign digestive system diseases. The tumor markers AFP, CEA, CA199, CA125, CA153 and CA724 were detected using an electrochemiluminescence immunoassay, and CST4 levels were detected using a human CST4 ELISA kit. The results demonstrated that the sensitivities of AFP and CA153 (both 5.00%) were significantly lower than that of CST4 (38.00%) in the diagnosis of digestive system malignancy (P<0.001), and CA724 (18.00%) was also less sensitive than CST4 (P<0.05). The sensitivities of CA199 (26.00%), CEA (31.00%) and CA125 (25.00%) were similar to that of CST4 (P>0.05). There was no significant difference in the CEA, CA125, CA724 and CST4 specificities (P>0.05), which were 91.00, 95.00, 94.00 and 83.00%, respectively. The specificities of AFP (99.00%), CA199 (98.00%) and CA153 (100.00%) were significantly higher than that of CST4 (P<0.01). By constructing a receiver operating characteristic curve and comparing the area under the curve as well as sensitivity, the findings of the present study demonstrated that combining CST4 with AFP, CEA, CA199, CA125, CA153 and CA724 can significantly enhance the diagnostic sensitivity for malignancies of the digestive system. However, the introduction of CST4 into the traditional diagnostic groups (CEA + AFP, CA199 + CA125 + CA153 + CA724 and AFP + CEA + CA199 + CA125 + CA153 + CA724) resulted in an increased sensitivity and loss of specificity, thereby not offering significant advantages in terms of comprehensive diagnostic efficiency compared with the traditional diagnostic groups. In conclusion, CST4 detection may be a promising diagnostic tool. Nonetheless, the potential false positive results in tumor diagnosis should be taken into consideration when developing new diagnostic groups involving CST4.

Clinical application of serum seven tumour-associated autoantibodies in patients with pulmonary nodules.

Background: The incidence of pulmonary nodules is increasing because of the promotion and popularisation of low-dose computed tomography (LDCT) screening for populations with suspected lung cancer. However, a high rate of false positives and concerns regarding the radiation-related cancer risk of repeated CT scanning remain major obstacles to its wide application. This study aimed to investigate the clinical value of seven tumour-associated autoantibodies (7-TAAbs) in the differentiation of malignant pulmonary tumours from benign ones and the early detection of lung cancer in routine clinical practice. Methods: We included 377 patients who underwent both the 7-TAAbs panel test and LDCT screening, and were diagnosed with pulmonary nodules using LDCT. An enzyme-linked immunosorbent assay (ELISA) was used to measure the serum levels antibodies for P53, PGP9.5, SOX2, GAGE7, GBU4-5, CAGE, and MAGE-A1. The relationships between the positive rates of the 7-TAAbs and the patient sex, and age, and the number, size, and composition of pulmonary nodules were analysed. We then statistically evaluated the clinical application value. Results: The positive rates of the 7-TAAbs did not correlate with sex, age, number, size, or composition of pulmonary nodules. The serum antibody level of GBU4-5 in patients with pulmonary nodules tended to increase with age; the serum antibody level of SOX2 tended to increase with nodule size and was the highest among patients with mixed ground-glass opacity (mGGO) nodules. The antibody positive rate for CAGE in female patients with pulmonary nodules was significantly higher than that in male patients (P < 0.05). The positive rate of GBU4-5 antibody in patients aged 60 years and above was higher than that in younger patients (P < 0.05). The positive rate of GAGE7 antibody in patients with pulmonary nodules sized 8-20 mm was also significantly higher than that in patients with pulmonary nodules sized less than 8 mm (P < 0.01). Significant differences were observed in the GAGE7 antibody levels of patients with pulmonary nodules of different compositions (P < 0.01). The positive rate of the 7-TAAbs panel test in patients with lung cancer was significantly higher than in patients with pulmonary nodules (P < 0.01). Serum levels of P53, SOX2, GBU4-5, and MAGE-A1 antibodies were significantly higher in patients with lung cancer than in those with pulmonary nodules (P < 0.05). Conclusion: The low positive rates of serum 7-TAAbs in patients with lung cancer and pulmonary nodules may be related to different case selection, population differences, geographical differences, different degrees of progression, and detection methods. The combined detection of 7-TAAbs has some clinical value for screening and early detection of lung cancer.

Endoplasmic Reticulum Stress Promotes Prostate Cancer Cells to Release Exosome and Up-regulate PD-L1 Expression via PI3K/Akt Signaling Pathway in Macrophages.

Mounting evidence has demonstrated that endoplasmic reticulum stress (ERS) serves an important role in shaping the immunosuppressive microenvironment by modulating resident tumor-associated macrophages (TAMs). However, the communication between ER­stressed tumor cells and TAMs is not fully understood. Exosomes have been reported to play a vital role in intercellular communication. Therefore, in order to investigate the role of ER stress­related exosomes in prostate cancer cells promoting macrophage infiltration and polarization, laser scanning confocal microscope, RT-PCR, flow cytometric analysis, western­blotting and cytokine bead array analyses were performed.The results demonstrated that TG-EXO downregulated the expression of PD-L1 on macrophages through flow cytometry analysis. In addition, Compared with CON-EXO, the expression of macrophage-associated inflammatory cytokines IL-12, TNF-α and IL-1ßwas significantly decreased in TG-EXO treatment (P< 0.05). TG-EXO upregulated the expression levels of IL-6, IL-10 and TGF-ß cytokinesin macrophages. Our research shows that TG-EXO increased PI3K/AKT signaling pathway compared to the CON-EXO group. In summary, we found exosomes from TG-treated prostate cancer cells altered the immunosupression status and affected macrophages polarization by up-regulating the expression of PD-L1 and inflammatory factors and PI3K/AKT pathway.

Relationship Between Drug Resistance Characteristics and Biofilm Formation in Klebsiella Pneumoniae Strains.

Objective: To conduct epidemiological analysis of Klebsiella pneumoniae (K. pneumoniae) with hypervirulence, and to investigate its drug resistance phenotype, Extended-spectrum ß-lactamase (ESBLs) gene, virulence factor, capsular serotype and biofilm formation, so as to provide theoretical basis for further understanding of the drug resistance mechanism of K. pneumoniae with hypervirulence. Methods: K. Pneumoniae were isolated from clinical samples collected from inpatients. All strains were identified by VITEK2 Compact using fully automatic microbial analyzer, the minimal inhibitory concentration (MIC) of antibiotics was determined by microbroth dilution test. The double disk diffusion method was used to detect the production of ESBLs, modified carbapenem inactivation method (mCIM) was used to detect the production of carbapenemase, and hypermucoviscosity phenotype was detected by wire drawing test. PCR was used to detect ESBLs gene, virulence factor and capsular serotype. Crystal violet staining was used to detect the ability of biofilm formation. Results: The ESBLs genes detected in this study included strains blaTEM 35 (36.5%), blaSHV 51 (53.1%), and blaCTX-M 49 (51.0%). Most strains carried multiple ESBLs genes, but not all of them produce ESBLs. K1 and K2 accounted for 14.6% and 11.5% respectively. Most (91.7%) strains carried the fimH gene, and the other virulence genes were ybtS (53.1%), entB (46.9%), rmpA (41.7%), aerobactin (32.3%), allS (15.6%), kfu (15.6%). Of all the Klebsiella pneumoniae strains, 33 (34.4%) exhibited ESBLs phenotype, 16 (16.7%) were carbapenemase-producing, and 20 (20.8%) with ESBLs phenotype tested were resistant to all four drugs. The correlation between ESBLs-producing strains and biofilm formation was significantly increased compared to strains without ESBLs phenotype (P=0.035). Conclusion: Compared to hypervirulent Klebsiella pneumoniae (hvKP), classical Klebsiella pneumoniae (cKP) has a tendency to acquire antibiotic resistance. Our study showed that genes encoding rmpA, K1 or K2, and kfu were highly associated with hvKP.