Cu-MOFs@AuPtNPs nanozyme-based immunosorbent assay for colorimetric detection of alpha-fetoprotein.

Accurate detection of tumor biomarkers in blood is crucial for diagnosing and treating tumor disease. In this study, a metal enzyme-linked immunosorbent assay (MeLISA) was fabricated for the ultrasensitive and naked-eye detection of tumor biomarker alpha-fetoprotein (AFP) in clinical serum samples. Herein, novel copper metal-organic frameworks and gold platinum nanoparticle composites (Cu-MOFs@AuPtNPs) were synthesized for the first time by an in situ method, which showed an enormous specific surface area and excellent peroxidase (POx) mimicking properties. Cu-MOFs@AuPtNPs linked with antibodies targeting AFP served as a signal nanoprobe to amplify the detection signal. Additionally, the specificity of MeLISA was significantly enhanced through a conventional antigen-antibody reaction and efficient blocking of non-specific sites with BSA. Under optimal conditions, the sandwich-type MeLISA exhibited a wide range from 0.001 to 1000 ng mL-1 (R2 = 0.997) and a low detection limit of 0.86 pg mL-1 (S/N = 3) with acceptable stability, selectivity, and reproducibility. It is noteworthy that the suggested MeLISA performed exceptionally well in detecting clinical serum samples, which were visible to the naked eye and did not require complex platforms. To sum up, the innovative MeLISA based on Cu-MOFs@AuPtNPs provides an alternative method for early cancer diagnosis, particularly in economically backward areas where simple diagnostic apparatus is extremely desirable.

Comparative analysis of hemoglobin, potassium, sodium, and glucose in arterial blood gas and venous blood of patients with COPD.

The study aims to assess the accuracy of the arterial blood gas (ABG) analysis in measuring hemoglobin, potassium, sodium, and glucose concentrations in comparison to standard venous blood analysis among patients diagnosed with chronic obstructive pulmonary disease (COPD). From January to March 2023, results of ABG analysis and simultaneous venous blood sampling among patients with COPD were retrospectively compared, without any intervention being applied between the two methods. The differences in hemoglobin, potassium, sodium, and glucose concentrations were assessed using a statistical software program (R software). There were significant differences in the mean concentrations of hemoglobin (p < 0.001), potassium (p < 0.001), and sodium (p = 0.001) between the results from ABG and standard venous blood analysis. However, the magnitude of the difference was within the total error allowance (TEa) of the United States of Clinical Laboratory Improvement Amendments (US-CLIA). As for the innovatively studied glucose concentrations, a statistically significant difference between the results obtained from ABG (7.8 ± 3.00) mmol·L-1 and venous blood (6.72 ± 2.44) mmol·L-1 was noted (p < 0.001), with the difference exceeding the TEa of US-CLIA. A linear relationship between venous blood glucose and ABG was obtained: venous blood glucose (mmol·L-1) = - 0.487 + 0.923 × ABG glucose (mmol·L-1), with R2 of 0.882. The hemoglobin, potassium, and sodium concentrations in ABG were reliable for guiding treatment in managing COPD emergencies. However, the ABG analysis of glucose was significantly higher as compared to venous blood glucose, and there was a positive correlation between the two methods. Thus, a linear regression equation in this study combined with ABG analysis could be helpful in quickly estimating venous blood glucose during COPD emergency treatment before the standard venous blood glucose was available from the medical laboratory.

Combinations of plasma cfDNA concentration, integrity and tumor markers are promising biomarkers for early diagnosis of non-small cell lung cancer.

Background: Circulating cell-free DNA (cfDNA) concentration and integrity as noninvasive biomarkers play an important role in cancer diagnosis, prognosis and therapy monitoring. However, few studies have been conducted on the combination of plasma cfDNA concentration, integrity and tumor markers (CEA, CA125, NSE and CYFRA21-1) for cancer detection. Thus, the purpose of this study was to investigate the diagnostic value of combining plasma cfDNA concentration, integrity and tumor markers in early detection of non-small cell lung cancer (NSCLC). Methods: Plasma cfDNA concentration from 50 healthy controls and 84 NSCLC patients were assessed by quantitative real-time PCR of ALU repeated sequence. Plasma cfDNA integrity was calculated as the ratio of long to short fragments (ALU115/60). Results: Plasma cfDNA concentration (ALU60 and ALU115) and integrity ALU115/60 were significantly higher in NSCLC patients with stage III/IV than in healthy controls (p = 0.0002, p < 0.0001, and p = 0.0093, respectively). The receiver operating characteristic (ROC) curve for discriminating NSCLC patients from healthy controls had an area under the curve (AUC) of 0.936 (95 % CI, 0.939-0.996). Moreover, the combination of plasma cfDNA concentration, integrity and tumor markers (CEA, CA125, NSE and CYFRA21-1) had higher diagnostic performance than either plasma cfDNA concentration alone, integrity alone or tumor markers alone, with sensitivity, specificity and AUC value of 94.05%, 90.00% and 0.968, respectively. These results demonstrated that the combination of plasma cfDNA concentration, integrity and tumor markers could significantly improve the diagnostic accuracy of NSCLC. Conclusion: Combination of plasma cfDNA concentration, integrity and tumor markers is a promising biomarker for early diagnosis of NSCLC.

SP-8356: A Novel Verbenone Derivative Exerts In Vitro Anti-Non-Small Cell Lung Cancer Effects, Promotes Apoptosis via The P53/MDM2 Axis and Inhibits Tumor Formation in Mice.

OBJECTIVE: Non-small cell lung cancer (NSCLC) stands as a prominent contributor to cancer-related fatalities on a global scale, necessitating the search for novel therapeutic agents. SP-8356, a derivative of (1S)-(-)-verbenone, has shown promise as an anticancer agent in preclinical studies. However, specific mechanisms underlying its effects in NSCLC remain to be elucidated. The aim of this research was to explore the in vitro anti-NSCLC effects of SP-8356, elucidate its mechanisms of action, and assess its efficacy in inhibiting tumor formation in a murine model. MATERIALS AND METHODS: In this experimental study, NSCLC cell lines were treated with various concentrations of SP- 8356. Cell viability and proliferation were assessed using MTT and colony formation assays, respectively. Cell cycle distribution was analyzed by flow cytometry, and apoptosis was evaluated by determining apoptotic protein expression. Western blot analysis was conducted to assess protein expression levels of the both p53 and MDM2. Additionally, we evaluated efficacy of the SP-8356 in inhibiting tumor formation of the nude mouse model. RESULTS: SP-8356 demonstrated a concentration-dependent inhibition of cell proliferation in the NSCLC cell lines. Flow cytometric analysis showed that SP-8356 led to cell cycle arrest at the G2/M phase, indicating its potential influence on regulating the cell cycle. SP-8356 treatment was associated with the downregulation of CDK1 and Cyclin B1. Additionally, SP-8356 significantly enhanced apoptosis in NSCLC cells. SP-8356 treatment was associated with the downregulation of Bcl-2, while Bax expression was upregulated. Mechanistically, SP-8356 led to accumulation of the p53 protein levels within the NSCLC cells. This accumulation was mediated through inhibition of its negative regulator, MDM2. Using a nude mouse model demonstrated that SP-8356 effectively inhibited tumor formation in vivo. CONCLUSION: Our findings shed light on the molecular mechanisms underlying anticancer activity of SP-8356 and highlight its potential as a promising therapeutic candidate for NSCLC treatment.

Association Between High Serum Anion Gap and All-Cause Mortality in Non-Traumatic Subarachnoid Hemorrhage: A Retrospective Analysis of the MIMIC-IV Database.

Background: High serum anion gap (AG) on admission is often correlated with poor outcomes in critically ill patients; however, data in patients with non-traumatic subarachnoid hemorrhage (SAH) are lacking. Herein, we aimed to identify the association between serum AG and all-cause mortality in patients with non-traumatic SAH. Methods: A retrospective analysis of data from the Medical Information Mart for Intensive Care (MIMIC-IV) database was performed on critically ill patients with non-traumatic SAH. Serum AG was collected on Intensive Care Unit (ICU) admission, and ICU and hospital all-cause mortality were analyzed. The multivariate Cox proportional hazard regression model and Kaplan-Meier survival curve analysis were used to analyze the correlation of serum AG with ICU and hospital all-cause mortality. Furthermore, interaction and subgroup analyses were evaluated for the consistency of these correlations. Results: A total of 893 patients with non-traumatic SAH were included in this study. The all-cause mortality in ICU and hospital were 14.8% (132/893), and 18.9% (169/893), respectively. Multivariate analysis after adjusting for potential confounders indicated that high serum AG levels (≥16 mmol/L) were associated with increased risk of ICU and hospital all-cause mortality as compared to that with low serum AG levels (<16mmol/L), (hazards ratio (HR): 2.31 [95% CI: 1.58-3.38]) and HR: 1.91 [95% CI: 1.36-2.67)], respectively). Similarly, the Kaplan-Meier (K-M) survival curve also showed that patients with high serum AG levels presented with a lower survival rate. Stratified analyses further showed that depending on the variable testes, an association between higher serum AG levels and hospital all-cause mortality in different subgroups was observed. Conclusion: Among patients with non-traumatic SAH, high serum AG level at ICU admission was associated with increased ICU and hospital all-cause mortality.

Serum miR-200c and miR-371-5p as the Useful Diagnostic Biomarkers and Therapeutic Targets in Kawasaki Disease.

Kawasaki disease (KD) has complexly clinical features and laboratory parameters and there is no definitive biomarker for this disease and the therapy of KD also is complex and uncertain. In this study, 102 KD patients and 80 healthy controls were enrolled in this study and the serum microRNAs were detected by qRT-PCR. The results showed that, compared with KD patients with a good response to high-dose intravenous immunoglobulin (IVIG) therapy, serum miR-200c and miR-371-5p were significantly higher in KD patients with no response to IVIG therapy; compared with KD patients not needing plasma exchange, these two microRNAs were also significantly higher in KD patients needing plasma exchange. In addition, combination of serum miR-200c and miR-371-5p reflected obvious separation between KD patients and healthy controls or between KD patients with no response to IVIG therapy and KD patients with good response to IVIG therapy or KD patients needing plasma exchange and KD patients not needing plasma exchange. Finally, both serum miR-200c and miR-371-5p were also significantly lower in KD under different kinds of therapy. Therefore, serum miR-200c and miR-371-5p have ability as the useful diagnostic biomarkers and therapeutic targets in Kawasaki disease.

The impact of metformin use on survival in kidney cancer patients with diabetes: a meta-analysis.

PURPOSE: The effects of metformin on the prognosis of kidney cancer patients with diabetes are in controversial. The present study is conducted to classify the association of metformin use with the survival of patients with kidney cancer. METHODS: Electronic databases, namely PubMed and Web of Science, were used to search the eligible studies up to December, 2016. Pooled hazard ratio (HR) and its corresponding 95% confidence interval (95% CI) were calculated. It was considered as statistically significant when P value was <0.05. RESULTS: Eight cohorts were eligible for the present meta-analysis, including 254,329 kidney cancer patients. The combined HR suggested that the use of metformin could improve the overall survival (OS) (HR 0.643, 95% CI 0.520-0.795, P < 0.001) and cancer-specific survival (CSS) (HR 0.618, 95% CI 0.446-0.858, P = 0.004) in kidney cancer patients. In subgroup analysis, positive associations were found between metformin use and OS/CSS of localized renal cell carcinoma patients (OS: HR 0.634, 95% CI 0.440-0.913, P = 0.014; CSS: HR 0.476, 95% CI 0.295-0.768, P = 0.002). Moreover, we also found that the use of metformin could reduce the risk of death in kidney cancer patients (HR 0.711, 95% CI 0.562-0.899, P = 0.004). CONCLUSION: Our findings suggest that the use of metformin is in favor of the prognosis of patients with kidney cancers. Further investigations are needed to evaluate the prognostic value of metformin on kidney cancer patients.

Association of MTDH immunohistochemical expression with metastasis and prognosis in female reproduction malignancies: a systematic review and meta-analysis.

Various literatures have demonstrated that overexpression of Metadherin (MTDH) is correlated with tumor metastasis and it can predict poor survival outcomes in female reproduction malignancies. In order to enhance the statistical power and reach a recognized conclusion, we conducted a systematic review and meta-analysis to thoroughly investigate the association of MTDH expression with tumor metastasis and survival outcomes following PRISMA guidelines. Odds ratios (ORs) and hazard ratios (HRs) were used to demonstrate the impact of MTDH on tumor metastasis and prognosis respectively. Data were pooled with appropriate effects model on STATA12.0. Our results indicated that high MTDH expression is significantly correlated with higher mortality for breast, ovarian and cervical cancer. High immunohistochemical expression of MTDH is remarkably associated with shorter disease-free survival (DFS) in breast cancer but not in ovarian cancer. The pooled results suggested that high level of MTDH significantly predicted distant metastasis and lymph node metastasis in breast cancer. Strong associations were observed between MTDH expression and lymph node metastasis in ovarian and cervical cancer. In conclusion, MTDH might be a novel biomarker which can effectively reflect metastasis status and prognosis of breast cancer. However, its application in clinical practice needs more prospective studies with large samples.

Laboratory reference intervals of complete blood count for apparently healthy elderly people in Shuyang, China.

BACKGROUND: Currently, there are no appropriate RIs of blood cells available for the elderly in most clinical laboratories in China. The aim of this study is to establish the RIs of complete blood cell count for apparently healthy elderly people. METHODS: Blood specimens were collected from elderly residents by standard procedures. Complete blood counts were determined by Sysmex XE-2100 analyzer. The RIs and 95% confidence intervals were calculated by the robust method recommended by CLSI C28-A3 guideline. RESULTS: RIs established for healthy elderly include: total WBC 3.63 - 10.3 x 10(9)/L for males and 3.64 - 10.3 x 10(9)/L for females; RBC 3.74 - 5.49 x 10(12)/L for males and 3.74 - 5.53 x 10(12)/L for females; Hb 109 - 167 g/L for males and 109 - 168 g/L for females; HCT 36.0 - 51.8% for males and 35.7 - 51.8% for females; MCV 86.0 - 105 fL for males and 86.2 - 106 fL for females; MCH 26.4 - 33.6 pg for males and 26.4 - 33.8 pg for females; MCHC 293 - 333 g/L for males and 291 - 335 g/L for females; RDW-SD 39.3 - 53.7 fL for males and 39.6 - 54.5 fL for females; RDW-CV 11.7 - 15.1% for males and 11.7 - 15.2% for females; PLT 122 - 355 x 10(9)/L for males and 122 - 350 x 10(9)/L for females; PCT 14.1 - 37.6 x 10(-1) mL/L for males and 13.9 - 37.9 x 10(-1) mL/L for females; MPV 11.3 - 15.5 fL for males and 11.3 - 15.5 fL for females; PDW 9.74 - 17.0% for males and 9.72 - 17.0% for females; platelet-LCR (P-LCR) 21.3 - 51.2% for males and 21.1 - 51.4% for females. CONCLUSIONS: We established scientific and reasonable RIs of blood cell analysis for the healthy elderly in our region.

[Serological investigation on Toxoplasma gondii infection in patients with unknown central nervous system diseases].

Totally 207 patients with unknown central nervous system diseases and 203 healthy persons were investigated for serum IgG of anti-Toxoplasma antibody assessed by ELISA. The serum IgG positive rate in 207 patients with unknown central nervous system diseases was 19.81%, and that in 203 health people was 5.42%, and there was a significant difference between them (P < 0.01). The IgG positive rates in different types of central nervous system diseases were different, which were 22.81%, 24.32%, 16.05%, and 18.75%, respectively in encephalopathy, epilepsy, mental disorder and neurasthenia. The IgG positive rate in different types of central nervous system diseases were significantly higher than that in healthy population (P < 0.01). The IgG positive rates in patients who contacted or did not contact cats or dogs were 32.97% and 9.48% respectively (P < 0.01). In conclusion, the infection rate in patients with unknown central nervous system diseases is higher than that in healthy persons; therefore, it is necessary to assay the serum IgG in them.

CIK cells from patients with HCC possess strong cytotoxicity to multidrug-resistant cell line Bel-7402/R.

AIM: To investigate the cytotoxicity of the cytokine-induced killer (CIK) cells from the post-operation patients with primary hepatocellular carcinoma (HCC) to multidrug-resistant (MDR) cell of HCC both in vitro and in vivo. METHODS: A drug-resistant cell line was established by culturing human HCC cell line Bel-7402 in complete RPMI 1640 medium with increasing concentrations of adriamycin from 10 to 2,000 nmol/L. CIK cells were obtained by inducing the peripheral blood mononuclear cells with rhIFN-gamma, monoclonal anti-CD3 antibody, rhIL-1alpha as well as rhIL-2, which were added into the culture. To detect the cytotoxicity of the CIK cells from HCC patients, the Bel-7402/R was taken as target (T) cells and CIK cells as effect (E) cells. Cytotoxic test was performed and measured by MTT. As to in vivo test, CIK cells were transfused into patients with HCC. The tumor specimens of the patients were obtained and immunohistochemistry was carried out to detect CD3, CD45, CD45RO as well as CD68. RESULTS: A MDR 1 HCC cell line Bel-7402/R was established. Its MDR1 mRNA overexpressed which was shown by RT-PCR; the P-glycoprotein expression increased from 1.32% of parent cells to 54%. CIK cells expanded vigorously by more than 70-fold and the CD3+CD56+ increased by more than 600-fold after 3-wk incubation on average. The cytotoxicity of CIK from HCC patients to Bel-7402/R was about 50% and to L-02 below 10% (t = 8.87, P<0.01), the same as that of CIK from normal individuals. Each of the 17 patients received 1-5 x 10(10) of CIK cell transfusion. No side effects were observed. After CIK treatment, the tumor tissue nodules formed and a large amount of lymphocytes infiltrated in the liver cancer tissue and CD3, CD45, CD45RO, and CD68 increased greatly which was shown by immunohistochemistry. CONCLUSION: A stable MDR1 HCC cell line has been established which could recover from liquid nitrogen and CIK from HCC patients has strong cytotoxicity to MDR HCC cell. CIK adoptive immunotherapy is safe and has no side effects. Receivers improved their immunity to tumor evidently. CIK treatment may be a better choice for HCC patients after operation to prevent the recurrence, especially when tumors have developed drug resistance.