Discovery medicine最新文献

Background: Many cytokines play essential roles in the occurrence and development of acute graft-versus-host-disease (aGVHD). This study aims to validate whether 11 proinflammatory and anti-inflammatory cytokines can be a candidate for aGVHD biomarkers to predict its occurrence and outcome.

Methods: Out of 178 patients who underwent allogeneic hematopoietic stem cell transplantation, we retrospectively enrolled 32 cases into the pre-transplant cohort and 45 cases into the post-transplant cohort. The serum cytokine concentrations were determined by flow cytometry. The control and experimental groups were non-aGVHD, I-II aGVHD and III-IV aGVHD groups, respectively. Risk factors and overall survival (OS) were also evaluated.

Results: In the pre-transplant cohort, interleukin (IL)-2 decreased in patients with aGVHD, and IL-4 only reduced in patients with III-IV aGVHD. In the post-transplant cohort, only IL-4 increased 1.79 times more in patients with III-IV aGVHD than in the other two groups. Patients with gastrointestinal (GI) aGVHD had lower IL-2, IL-4 and IL-17F levels pre-transplant and lower IL-2 post-transplant. None of the other cytokines was significantly different. Logistic regression analysis showed that no cytokine could predict the occurrence and outcome of aGVHD. Diarrhea within 15 days post-transplant is an independent risk factor for the occurrence of aGVHD and a risk factor for a fatal outcome. Patients without diarrhea had longer survival time of 672 (586-757) days vs 444 (229-548) days and better 2-year OS (85.7% vs 46.4%) than those with diarrhea. Compared to patients with aGVHD, patients without aGVHD had a longer survival time of 618 (530-706) days vs 449 (353-545) days and better 2-year OS (76.2% vs 47.1%).

Conclusions: Proinflammatory and anti-inflammatory cytokines can provide specific indications for the occurrence and progression of aGVHD. However, to truly guide the diagnosis and prognosis, cytokines with larger sample sizes, more detection time points and more accurate diagnostic efficacy need to be further studied.

Background: Noninvasive prenatal testing (NIPT) has been widely adopted in prenatal examination for fetal chromosomal aneuploidy. The present study aimed to evaluate the clinical features of NIPT for both common trisomy and sex chromosome aneuploidy (SCA).

Methods: A total of 24,164 pregnant women with NIPT testing from July 2020 to June 2022 were recruited at the Linping Maternity and Child Health Care Hospital.

Results: Ninety cases showed high risk of trisomy 21/18/13 with karyotype results available, and the sensitivity, specificity, and positive predictive value (PPV) were 98.41%, 99.88% and 68.89%, respectively. The three most important reasons for screening were advanced maternal age (AMA, 28.06%), intermediate risk of prenatal screening (20.34%) and Multiple of medium (MoM) abnormality of prenatal screening (17.38%). High risk of NIPT results with Z-score ≥15 have a higher PPV when compared to those with 3 ≤ Z-score < 10, and 10 ≤ Z-score < 15. Meanwhile, 97 pregnant women received positive results for fetal sex chromosome aneuploidy (SCA) in NIPT. In addition, the rate for further diagnostics of SCA was 64.95% and the PPV of SCA was 50.79%.

Conclusions: Our data show that NIPT has a promising future in prenatal screening for genetic abnormalities of the fetus, and that the accuracy of NIPT is closely related to Z-score.

Hepatocellular carcinoma development and many other tumors are closely related to alpha-fetoprotein (AFP), its determination can be used as a positive test for tumors. It is mainly used clinically as a serum marker to diagnose and monitor the efficacy of primary hepatocellular carcinoma. Therefore, a variety of biosensors have been developed to detect AFP. Electrochemical sensors integrate a variety of detection methods. They have inherent advantages over other types of sensors, they are fast, portable, simple, and highly sensitive. Some meaningful electrochemical biosensors work with nanomaterials acting as signal amplification elements or as signal amplification catalysts. This review introduced the field of biosensors and discuss about the use of nanomaterials in electrochemical sensing, specificity electrochemical biosensing of AFP. The study ends with a discussion about the prospects for nanomaterial-based signal amplification and future research directions.

Background: The red blood cell distribution width to platelet ratio (RPR) is an inflammatory marker that is a convenient and reliable prognostic indicator for several solid malignancies. However, the correlation between RPR and myeloma prognosis has not been reported. Therefore, this study aims to explore the correlation between RPR level and the prognosis of multiple myeloma (MM) patients.

Methods: We retrospectively analyzed 145 newly diagnosed patients with MM. The receiver operating characteristic curve (ROC) method was used to determine the RPR cut-off value. In addition, we studied the correlation between pre-treatment RPR levels and clinical characteristics, immunophenotype, cytogenetics, and its impact on the disease prognosis.

Results: The optimal cut-off value for RPR was 0.12 and was divided into high RPR and low RPR groups. Patients in the high RPR group are more likely to have anemia, thrombocytopenia, high β2-macroglobulinemia, a high percentage of bone marrow plasma cells, late-stage status by Dury-Salmon (DS) and international staging system (ISS) (p < 0.05). More notably, between the high RPR and low RPR groups, the incidence rates of CD56-positive, D13S319-positive, RB1-positive, and 1q21 amplification were statistically significant (p < 0.05). Additionally, survival analysis revealed that compared with patients in the low RPR group, the median progression-free survival (PFS) and overall survival (OS) of patients in the high RPR group were substantially shortened (p < 0.05). Multivariate analysis confirmed that RPR ≥0.12, D13S319-positive, and 1q21 amplification were independent risk factors for poor PFS and OS.

Conclusions: RPR is a practical and effective prognostic marker in newly diagnosed patients with MM, and a high RPR is an independent poor prognostic factor.

Background: At present, there is no comprehensive evaluation of the efficacy and safety of low molecular weight heparin (LMWH) for the treatment of thrombophilia during pregnancy in clinical practice. This study aimed to systematically evaluate the efficacy of LMWH in the treatment of patients and its effects on coagulation function, thereby providing a reference for the clinical treatment and prognosis evaluation of thrombophilia during pregnancy.

Methods: Database PubMed, Web of Science and Embase as well as China National Knowledge Infrastructure and Wanfang Database were applied for the search of data. A comparative study on the efficacy of LMWH in the treatment of gestational thrombophilia was enrolled. Stata 16.0 software (Stata, College Station, TX, USA) was utilized to conduct the meta-analysis.

Results: A total of 487 relevant articles were retrieved and 14 studies were finally included. Patients in the LMWH combined with the low-dose aspirin group had a significantly higher live birth rate than those in the aspirin or LMWH treat group (OR (odds ratio) = 4.54, 95% CI (confidence interval): 2.76, 7.45). The adverse effects rate was lower in the LMWH combined with the low-dose aspirin group than in the aspirin or LMWH treatment group (OR = 0.40, 95% CI: 0.29, 0.56). After treatment, patients in the LMWH combined with the low-dose aspirin group had significantly lower D-dimer (SMD (standardized mean differences) = -1.50, 95% CI: -2.19, 0.80) and platelet count (PLT; SMD = -0.13, 95% CI: -0.35, 0.09) than those in the aspirin or LMWH treatment group. However, activated partial thromboplastin time (APTT; SMD = 0.16, 95% CI: -0.10, 0.42), thrombin time (TT; SMD = 0.60, 95% CI: -0.14, 1.34), plasma prothrombin time (PT; SMD = 0.42, 95% CI: -0.71, 1.56), and fibrin values (FIB; SMD = -0.92, 95% CI: -2.12, 0.28) were significantly higher in the LMWH combined with low-dose aspirin group than those in the aspirin or LMWH treatment group.

Conclusions: LMWH heparin combined with low-dose aspirin can effectively correct coagulation function in pregnant women, improve prothrombotic state and increase the live birth rate, which has high clinical value.

Background: The therapeutic outcomes for acute ischemic stroke (AIS) with early neurological deterioration (END) are adverse. Argatroban is a novel direct thrombin inhibitor, which is safe in the treatment of AIS, but its efficacy is controversial. This study sought to assess the therapeutic effect of argatroban as an adjunct to aspirin in the treatment of AIS patients with END. Patients' prognosis for the presence of END was also evaluated.

Methods: Overall, 166 AIS patients with END were included in the study from June 2018 to June 2021 in The Affiliated Zhangjiagang Hospital of Soochow University. Patients were divided in the control group (aspirin alone) and the study group (aspirin combined with argatroban). General data of the patients were collected. Clinical indexes such as the modified Edinburgh-Scandinavian stroke scale (MESSS), and the serum fibrinogen (FIB) and neuropeptide Y (NPY) levels before and after treatment were also collected. Correlations between prognosis and general data, and FIB and NPY levels in AIS patients with END were analyzed by multivariate logistic regression. The performance of FIB and NPY levels in predicting patients' prognosis was further analyzed using receiver operating characteristic (ROC) curves.

Results: There was no significant difference in the general data, such as sex, age, course of disease and basic diseases between the 2 groups. After treatment, the MESSS score (13.08 ± 3.24 vs. 16.48 ± 3.32, p < 0.001), serum FIB level (2.72 ± 0.81 vs. 3.52 ± 0.71, p < 0.001), and NPY level (121.28 ± 17.34 vs. 152.09 ± 18.25, p < 0.001) of the study group was significantly lower than that of the control group. A further analysis revealed that the serum FIB (OR, odds ratio = 2.296, 95% confidence interval, CI: 1.437-3.669, p = 0.001) and NPY (OR = 1.020, 95% CI: 1.002-1.039, p = 0.031) levels were independent risk factors of patients' prognosis for the presence of END.

Conclusions: Aspirin combined with argatroban significantly improved neurological impairment of AIS patients with END, which is worthy of clinical application.

Purpose: Establishing a cross-species animal model of human immunodeficiency virus (HIV) infection is crucial for the study of HIV/acquired immunodeficiency syndrome (AIDS). However, due to the species-specific characteristics of HIV-1, the virus can only infect directly humans and a small number of non-human primates. It cannot directly infect mouse cells across species.

Methods: A mouse leukemia cell line with high CD4 (clusters of differentiation 4)/CCR5 (CC-chemokine receptor 5)/CyclinT1 expression was constructed in this study. First, CD4/CCR5/CyclinT1 lentiviral vector was used to infect a murine leukemia cell line L1210 to express the receptor CD4, co-receptor CCR5 and tat protein driving factor CyclinT1, which are required to infect L1210 cells with HIV-1.

Results: The results of sequencing identification and fluorescence expression showed that the plasmid expressing CD4, CCR5, and CyclinT1 vector was successfully constructed and wrapped as the lentiviral vector. Moreover, it was observed that CD4, CCR5, and CyclinT1 proteins were highly expressed in mouse leukemia cells L1210 compared to empty lentiviral vector-transfected cells. Next, viral entry and replication were demonstrated when HIV-1 RNA was detected in body cells and cultured supernatants. Transgenic mice cells L1210 showed significantly greater content of HIV-1 RNA compared to control L1210 cells. Finally, CEMx174 was infected with cell culture supernatants to clarify that the progeny virus is an active virus with infection ability. HIV-1 RNA was highly expressed in CEMx174 cells.

Conclusions: This study made the foundation for future studies evaluating HIV-1 cross-species infection in a murine animal model. The results provided new direction for studies investigating the development of vaccines, antiviral drugs screening, and HIV/AIDS pathogenesis.

Background: With the wide application of multislice spiral computed tomography (CT), the frequency of detection of multiple lung cancer is increasing. This study aimed to analyze gene mutations characteristics in multiple primary lung cancers (MPLC) using large panel next-generation sequencing (NGS) assays.

Methods: Patients with MPLC surgically removed from the Affiliated Hospital of Guangdong Medical University from Jan 2020 to Dec 2021 enrolled the study. NGS sequencing of large panels of 425 tumor-associated genes was performed.

Results: The 425 panel sequencing of 114 nodules in 36 patients showed that epidermal growth factor receptor (EGFR) accounted for the largest proportion (55.3%), followed by Erb-B2 Receptor Tyrosine Kinase 2 (ERBB2) (9.6%), v-Raf murine sarcoma viral oncogene homolog B1 (BRAF), and Kirsten rat sarcoma viral oncogene (KRAS) (8.8%). Fusion target variation was rare (only 2, 1.8%). ERBB2 Y772_A775dup accounted for 73%, KRAS G12C for about 18%, and BRAF V600E for only 10%. AT-rich interaction domain 1A (ARID1A) mutations were significantly higher in invasive adenocarcinoma (IA) which contained solid/micro-papillary malignant components (p = 0.008). The tumor mutation burden (TMB) distribution was low, with a median TMB of 1.1 MUTS/Mb. There were no differences in the TMB distribution of different driver genes. In addition, 97.2% of MPLC patients (35/36) had driver gene mutations, and 47% had co-mutations, mainly in IA (45%) and invasive adenocarcinoma (MIA) (37%) nodule, with EGFR (39.4%), KRAS (9.1%), ERBB2 (6.1%), tumor protein 53 (TP53) (6.1%) predominately.

Conclusions: MPLC has a unique genetic mutation characteristic that differs from advanced patients and usually presents with low TMB. Comprehensive NGS helps to diagnose MPLC and guides the MPLC clinical treatment. ARID1A is significantly enriched in IA nodules containing micro-papillary/solid components, suggesting that these MPLC patients may have a poor prognosis.

Background: COVID-19 (coronavirus disease 2019) is a pandemic around the world, and its treatment options often fail to achieve ideal results. There is a lot of controversy in the treatment of COVID-19 with mesenchymal stem cells (MSCs). The study aims to assess the safety and efficacy of mesenchymal treatment of new coronary pneumonia.

Methods: We manually searched electronic databases including PubMed, Embase, Cochrane Library, and Web of Science until 25th July 2022, and Stata 15.0 (StataCorpLLC: College Station, TX, USA) was used to analyze the data.

Results: A total of 8 randomized controlled trials were included, involving a total of 345 people, of which 180 were in the MSCs group and 165 were in the placebo group. The analysis results showed that MSCs can reduce mortality in COVID-19 patients compared to placebo [RR (Risk Ratio) = 0.56, 95% CI (Confidence Interval) (0.36, 0.89); p = 0.003]. There was no significant difference between the mesenchymal stem cell group and the placebo group in the incidence of adverse reactions [RR = 0.64, 95% CI (0.34, 1.18); p = 0.281]; In the SpO₂/FiO₂ (Oxygen Saturation/Fraction of Inspiration O₂) [WMD (Weighted Mean Difference) = 9.07, 95% CI (-38.01, 56.15); p = 0.080]; In ICU (Intensive Care Unit) stay [WMD = -1.66, 95% CI (-7.23, 3.91); p = 0.131].

Conclusions: Mesenchymal stem cells can reduce the mortality of COVID-19 patients.