Clinical and Experimental Medicine

Ung thư vú là một trong những loại ung thư phổ biến nhất toàn cầu. Liệu pháp miễn dịch đã chứng tỏ hiệu quả trong việc cải thiện tỷ lệ sống sót tổng thể của bệnh nhân ung thư vú. Mục tiêu của chúng tôi là phát triển một chữ ký mới dựa trên các gen liên quan đến điểm kiểm soát miễn dịch (ICGs) có thể dự đoán tiên lượng và phân tích tình trạng miễn dịch của bệnh nhân ung thư vú. Sau khi thu thập dữ liệu, chúng tôi đã xác định được các ICGs chính thức để xây dựng mô hình tiên lượng cho ung thư vú. Chúng tôi đã xây dựng một mô hình tiên lượng mới và tạo ra một điểm rủi ro mới có tên gọi là Điểm Rủi Ro Liên Quan Đến Điểm Kiểm Soát Miễn Dịch trong ung thư vú (ICRSBC). Nomogram đã được xây dựng để đánh giá độ chính xác của mô hình, và một công cụ trực tuyến mới đã được phát triển để thân thiện hơn trong việc dự đoán tiên lượng. Chúng tôi cũng đã điều tra đáp ứng với liệu pháp miễn dịch và phân tích khối lượng đột biến khối u (TMB) trong các nhóm ICRSBC. ICRSBC đã được phát hiện có mối tương quan đáng kể với môi trường miễn dịch, khả năng đáp ứng với điều trị bằng liệu pháp miễn dịch và TMB. Mức độ biểu hiện của 9 ICGs cấu thành mô hình tiên lượng và mức độ methyl hóa của chúng cũng khác biệt đáng kể giữa ung thư vú và mô bình thường. Hơn nữa, hồ sơ đột biến, biến đổi số bản sao và mức độ biểu hiện protein cũng cho thấy sự chênh lệch rõ rệt giữa 9 ICGs. Chúng tôi đã xác định và xác thực một chữ ký mới liên quan đến ICGs có liên hệ chặt chẽ với sự tiến triển của ung thư vú. Chữ ký này cho phép chúng tôi tạo ra một điểm rủi ro để dự đoán sức sống và đánh giá tình trạng miễn dịch của các cá nhân bị ảnh hưởng bởi ung thư vú.

Peripheral blood cell counts and cytokines can be used as predictors of multiple myeloma (MM) patients’ outcomes. 313 newly diagnosed MM patients treated with novel agents were divided into training and validation cohorts. We selected the common peripheral blood cell counts, including the lymphocyte/monocyte ratio (LMR), neutrophil/lymphocyte ratio (NLR), and platelet/lymphocyte ratio (PLR), systemic inflammation response index (SIRI), and serum cytokines which contained tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), interleukin-2 receptor (IL-2R), interleukin-8 (IL-8), interleukin-6 (IL-6), and interleukin-10 (IL-10) as related variables. The least absolute shrinkage and selection operator (LASSO) regression was conducted to sort the predictor variables in the training cohort, and then the developed nomogram was assessed in the training and validation cohort. Our study showed that SIRI, PLR, and IL-8 were independent prognostic factors for the survival of MM patients. Patients with lower SIRI (≤ 0.87) had superior survival than patients with higher SIRI (> 0.87). Further, according to the LASSO regression, a nomogram embracing LMR (> 3.78), SIRI (> 0.87), PLR (≤ 106.44), and IL-8 was established. The nomogram demonstrated a better correlation with the outcomes of MM patients in the training cohort than International Staging System (ISS) and Revised-International Staging System (R-ISS). The same results were verified in the validation cohort. The nomogram incorporating inflammatory cells and cytokines could be a helpful tool to stratify MM patients in the era of novel agents.

Hepcidin is a key hormone governing mammalian iron homeostasis and may be directly or indirectly involved in the development of most iron deficiency/overload and inflammation-induced anemia. The objective of this study was to investigate the expression of hepcidin in anemia of chronic disease. To characterize serum hepcidin, iron and inflammatory indicators associated with anemia of chronic disease (ACD), we studied ACD, ACD concomitant iron-deficiency anemia (ACD/IDA), pure IDA and acute inflammation (AcI) patients and analyzed the associations between hepcidin levels and inflammation parameters in various types of anemia. Serum hepcidin levels in patient groups were statistically different, from high to low: ACD, AcI > ACD/IDA > the control > IDA. Serum ferritin levels were significantly increased in ACD and AcI patients but were decreased significantly in ACD/IDA and IDA. Elevated serum EPO concentrations were found in ACD, ACD/IDA and IDA patients but not in AcI patients and the controls. A positive correlation between hepcidin and IL-6 levels only existed in ACD/IDA, AcI and the control groups. A positive correlation between hepcidin and ferritin was marked in the control group, while a negative correlation between hepcidin and ferritin was noted in IDA. The significant negative correlation between hepcidin expression and reticulocyte count was marked in both ACD/IDA and IDA groups. All of these data demonstrated that hepcidin might play role in pathogenesis of ACD, ACD/IDA and IDA, and it could be a potential marker for detection and differentiation of these anemias.

The novel severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) causes major challenges to the healthcare system. SARS-CoV-2 infection leads to millions of deaths worldwide and the mortality rate is found to be greatly associated with pre-existing clinical conditions. The existing dataset strongly suggests that cardiometabolic diseases including hypertension, coronary artery disease, diabetes and obesity serve as strong comorbidities in coronavirus disease (COVID-19). Studies have also shown the poor outcome of COVID-19 in patients associated with angiotensin-converting enzyme-2 polymorphism, cancer chemotherapy, chronic kidney disease, thyroid disorder, or coagulation dysfunction. A severe complication of COVID-19 is mostly seen in people with compromised medical history. SARS-CoV-2 appears to attack the respiratory system causing pneumonia, acute respiratory distress syndrome, which lead to induction of severe systemic inflammation, multi-organ dysfunction, and death mostly in the patients who are associated with pre-existing comorbidity factors. In this article, we highlighted the key comorbidities and a variety of clinical complications associated with COVID-19 for a better understanding of the etiopathogenesis of COVID-19.

We aimed to explore the activation of monoacylglycerol lipase (MAGL)/cyclooxygenase-2 (COX-2)/prostaglandin E2 (PGE2) axis in hepatocellular carcinoma (HCC), evaluating circulating PGE2 as prognostic biomarker in HCC patients. PGE2 levels were measured in blood samples from 24 cirrhotics, and 34 HCC patients were consecutively collected between January 2016 and December 2017. In a subgroup of patients, tissue expression of MAGL mRNA and immunohistochemistry for MAGL and COX-2 were obtained. Despite tumor tissues showing overexpression of MAGL mRNA and higher levels of both MAGL and COX-2 at immunohistochemistry, PGE2 levels were not significantly different in HCC and cirrhotics. HCC patients with circulating PGE2 levels > 14 pg/mL had a significantly shorter overall survival (19.4 vs. 49.9 months; p = 0.03), the finding being confirmed by the multivariate analysis (HR 3.37 [95% CI 1.00–11.60]; p = 0.05). The MAGL/COX-2/PGE2 axis is activated in HCC, and circulating PGE2 proved to be a potential prognostic biomarker.

Recently, many studies show that long non-coding RNAs (lncRNAs) play important roles in cancer biology. Although its expression was reported dysregulated during tumorigenesis, the contributions of lncRNAs to hepatocellular carcinoma (HCC) are still largely unknown. In particular, the lncRNA CARLo-5 has a functional role in cell-cycle regulation in colon cancer, while the clinical significance and biological function of CARLo-5 in HCC remain unelucidated. In order to fill those study blanks, the expression level of CARLo-5 in human HCC specimens was tested, and its correlation with clinicopathologic features as well as the prognosis for patients with HCC was analyzed. Additionally, MTT, wound healing and transwell assays were employed to investigate the biological function of CARLo-5. The results showed that CARLo-5 levels were significantly overexpressed in HCC tissues compared to ANLT. Besides, high expression of CARLo-5 was associated with liver cirrhosis (P = 0.001), tumor number (P < 0.001), vascular invasion (P = 0.001), capsular formation (P = 0.014) and Edmondson–Steiner grade (P < 0.001), which proved that CARLo-5 was an independent risk factor for overall survival and disease-free survival. In addition, in highly metastatic HCC cell lines (HCCLM3 and MHCC97-L), CARLo-5 was up-regulated, but in lowly metastatic HCC cell lines (HepG2, SNU387), it showed down-regulated. Besides, by using gain and loss of function experiments in HCC cell lines (HCCLM3 and HepG2), the results showed that CARLo-5 overexpression significantly enhanced cell proliferation, migration and invasion in vitro. Our study also revealed that CARLo-5 was prominently up-regulated in HCC specimens and its high expression was associated with poor prognosis of HCC patients. Totally, those findings together indicate that CARLo-5 promotes proliferation and metastasis of HCC and potentially emerged as a novel therapeutic target.

Adverse pregnancy outcomes (APOs) have been a devastating actuality in clinic. However, the pre-onset risk factors, that correlated with pregnancy failure, including antiphospholipid antibodies (APLs) and angiogenic factors, remain unclear. A retrospective study was performed in this research, and data from 145 pregnant women were collected during their pregnancy. Patients were finally divided into non-APO group (n = 89) and APO group (n = 56) according to their pregnancy outcomes. The associations among their characteristics, laboratory tests, therapies, and outcomes were analyzed. Univariate analysis demonstrated that patients with APOs showed significant prevalence of lupus anticoagulant (LAC) positive (P < 0.001), antiphospholipid syndrome (P = 0.030), and heparin prior to pregnancy (P = 0.041). LAC positive was correlated with shorter gestational age (P = 0.043) and gestational weeks of pre-term delivery (P = 0.011). Increased ratio of soluble vascular endothelial growth factor receptor-1/placental growth factor in pregnancies with APLs was correlated with the APOs and worse neonatal outcomes, including gestational age (P = 0.028), fetal death (P = 0.011), gestational weeks of pre-term delivery (P = 0.002), and birth weight percentile (P = 0.016). Angiogenic markers in pregnancies with APLs were correlated with the incidence of APOs.