Rising Interest in the Development of Metal Complexes in Cancer Immunotherapy.

Metal complexes have shown great potential in cancer immunotherapy. This review briefly introduces the basic concepts and strategies of cancer immunotherapy and summarizes the recent discoveries on the immune effects of traditional platinum-based anticancer compounds. In addition, we also outline the latest research progresses on metal complexes for cancer immunotherapy focusing on platinum, ruthenium, iridium, rhenium and copper complexes. Finally, the research perspectives and unsolved problems on the applications of metallo-anticancer agents in cancer immunotherapy are purposed.

[Value of N-terminal pro-brain natriuretic peptide in evaluating early septic cardiac dysfunction in neonates].

OBJECTIVE: To investigate the significance of N-terminal pro-brain natriuretic peptide (NT-proBNP) in the early assessment of neonatal cardiac dysfunction in sepsis. METHODS: The children diagnosed with neonatal sepsis and common infection neonates admitted to the department of pediatric neonatal intensive care unit (NICU) of Liaocheng People's Hospital from January 2016 to January 2019 were enrolled. Data of clinical sign, laboratory results, bedside echocardiography and survival data were collected, and the differences of clinical indexes were compared among sepsis patients with and without cardiac dysfunction and common infection. The risk factors of sepsis with cardiac dysfunction were analyzed by multivariate Logistic regression, and the early prediction value of NT-proBNP for neonatal septic cardiac dysfunction was evaluated by the receiver operating characteristic (ROC) curve. RESULTS: There were 112 neonates with sepsis (49 with cardiac dysfunction and 63 without cardiac dysfunction) and 67 children with common infection included in the analysis. The onset time of neonates in septic cardiac dysfunction group was significantly earlier than that of septic non-cardiac dysfunction group and common infection group [hours: 52.9 (0, 180.3) vs. 53.9 (0, 183.6), 81.0 (45.6, 202.4), both P < 0.05]. Compared with the general infection group, albumin (ALB), white blood cell count (WBC), left ventricular ejection fraction (LVEF) in septic cardiac dysfunction group significantly decreased, NT-proBNP, hypersensitive C-reactive protein (hs-CRP)/ALB, pulmonary artery systolic pressure (PASP) significantly increased, while right ventricular (RV) and Tei index significantly increased [ALB (g/L): 24.1±3.8 vs. 27.8±3.6, WBC (×109/L): 12.7 (3.7, 18.9) vs. 15.4 (9.9, 23.2), LVEF: 0.626±0.123 vs. 0.700±0.021, NT-proBNP (ng/L): 20 230.6 (15 890.0, 35 000.0) vs. 7 324.5 (2 426.5, 13 890.0), hs-CRP/ALB: 0.33 (0.29, 0.81) vs. 0.06 (0.00, 0.21), PASP (mmHg, 1 mmHg = 0.133 kPa): 52.25±14.12 vs. 41.07±27.73, RV (mm): 10.74±2.42 vs. 8.55±1.41, Tei index: 0.52±0.03 vs. 0.30±0.04, all P < 0.05]. NT-proBNP and Tei index in septic cardiac dysfunction group were significantly higher than those in septic non-cardiac dysfunction group [NT-proBNP (ng/L): 20 230.6 (15 890.0, 35 000.0) vs. 13 057.6 (8 946.0, 35 000.0), Tei index: 0.52±0.03 vs. 0.39±0.02, both P < 0.05], and LVEF was significantly lower than that in septic non-cardiac dysfunction group (0.626±0.123 vs. 0.671±0.086, P < 0.05). Multivariate Logistic regression analysis showed that NT-proBNP, Tei index and hs-CRP/ALB were independent risk factors for cardiac dysfunction in sepsis neonates [odds ratio (OR) and 95% confidence interval (95%CI) were 8.73 (1.54-5.67), 1.97 (1.26-2.87), 1.87 (1.03-3.40) respectively, all P < 0.05]. ROC curve analysis showed that NT-proBNP, Tei index and hs-CRP/ALB had good predictive value for the occurrence of cardiac dysfunction in septic neonates, the area under ROC curve (AUC) was 0.81 (95%CI was 0.84-0.91), 0.78 (95%CI was 0.65-0.79) and 0.77 (95%CI was 0.61-0.77), respectively. The sensitivity and specificity of NT-proBNP were 80.0% and 79.0% respectively with 12 291.5 ng/L as the cut-off value, the sensitivity and specificity of Tei index were 74.0% and 77.0% respectively with 0.45 as the cut-off value, and the sensitivity and specificity of hs-CRP/ALB were 76.0% and 76.3% respectively with 0.10 as the cut-off value. CONCLUSIONS: NT-proBNP can be used as a diagnostic marker of early cardiac dysfunction, and for rapid diagnosis of neonatal cardiac dysfunction in sepsis. The application may guide clinicians to use drugs better to improve cardiac function and treatment effect.

[Clinical significance of oral motor intervention on the prognosis of early premature infant].

OBJECTIVE: To explore the clinical significance of early oral intervention measures in the prognosis of premature infants. METHODS: 151 preterm infants admitted to neonatal intensive care unit (NICU) of Liaocheng People's Hospital from January 2015 to January 2017 were enrolled. Premature infants were divided into intervention group and control group according to random number table method and with the consent of legal guardian. Both groups received routine treatment of preterm infants after stable vital signs. The intervention group received the oral massage method adopted by none-nutritive sucking, stimulating swallowing function and SandraFucile on the basis of routine treatment, once a day for 14 consecutive days. Both groups were followed up for 6 months. The oral feeding ability of premature infants was evaluated by the proficiency (PRO), rate of transfer (RT), feeding process and non-nutritive suction (NNS). At 40 weeks of postmenstrual age (PMA), neonatal behavioral neurological (NBNA) was used to assess neonatal brain development; Infanib was used for early motor development evaluation at 3 months and 6 months after birth. RESULTS: Finally, 151 premature infants were enrolled, including 78 in the intervention group and 73 in the control group. The time to complete oral feeding of the intervention group was significantly shorter than that of the control group (days: 18.1±3.7 vs. 23.4±5.8, P < 0.05). Compared with the control group, at the time of complete oral feeding, the PMA of the intervention group was significantly decreased (weeks: 33.4±0.9 vs. 35.9±1.9, P < 0.05), the feeding efficiency was significantly increased (mL/min: 10.6±5.1 vs. 8.1±4.7, P < 0.05), and PRO was significantly increased [(95±8)% vs. (72±28)%, P < 0.05], and the body weight was significantly decreased (g: 1 836.0±193.0 vs. 2 000.8±204.5, P < 0.05). The NNS scores of the intervention group and the control group were increased gradually with time (F values were 86.21 and 75.23, respectively, both P < 0.01), and the NNS scores of the intervention group at 10 days and 14 days were significantly higher than those of the control group (52.89±6.26 vs. 46.74±6.24, 73.90±7.01 vs. 63.53±6.80, both P < 0.01). The NBNA scores of the two groups were lower, but there was no significant difference between the intervention group and the control group (32.7±3.6 vs. 32.0±4.1, P > 0.05). Infanib evaluation at 3 months of age showed that the proportion of normal children in the intervention group was significantly higher than that in the control group [67.95% (53/78) vs. 49.31% (36/73), P < 0.05], and at 6 months of age, the proportion of normal children in the intervention group was significantly higher than that in the control group [84.62% (66/78) vs. 58.90% (43/73), P < 0.01]. CONCLUSIONS: Early oral exercise intervention can shorten the transition time from tube feeding to full oral feeding in NICU premature infants and improve the performance of infants during feeding.

Galectin-1 gene silencing inhibits the activation and proliferation but induces the apoptosis of hepatic stellate cells from mice with liver fibrosis.

Liver fibrosis is a serious threat to human health, and there is currently no effective clinical drug for treatment of the disease. Although Galectin­1 is effective, its role in liver function, inflammation, matrix metalloproteinases and the activation of hepatic stellate cells (HSCs) remains to be elucidated. The aim of the present study was to elucidate the effect of Galectin­1 on the activation, proliferation and apoptosis of HSCs in a mouse model of liver fibrosis. Following successful model establishment and tissue collection, mouse HSCs (mHSCs) were identified and an mHSC line was constructed. Subsequently, to determine the role of Galectin­1 in liver fibrosis, the expression levels of transforming growth factor (TGF)­ß1, connective tissue growth factor (CTGF) and α­smooth muscle actin (α­SMA) pre­ and post­transfection were evaluated by reverse transcription­quantitative polymerase chain reaction and western blot analyses. In addition, the effects of Galectin­1 on the biological behavior and mitochondrial function of mHSCs were determined using a 3­(4,5­dimethylthiazol­2­yl)­2,5­diphenyltetrazolium bromide assay, flow cytometry and a scratch test. It was first observed that the expression levels of Galectin­1, TGF­ß1, CTGF and α­SMA were downregulated by silencing the gene expression of Galectin­1. Additionally, silencing the gene expression of Galectin­1 inhibited cell cycle progression, proliferation and migration but induced the apoptosis of mHSCs from mice with liver fibrosis. Furthermore, the in vivo experimental results suggested that silencing the gene expression of Galectin­1 improved liver fibrosis. Collectively, it was concluded that silencing the gene expression of Galectin­1 ameliorates liver fibrosis and that functionally suppressing Galectin­1 may be a future therapeutic strategy for liver fibrosis.

Galectin-1 Restores Immune Tolerance to Liver Transplantation Through Activation of Hepatic Stellate Cells.

BACKGROUND/AIMS: Immune tolerance is considered the only way to manage liver transplantation (LT). The current study hypothesized that galectin-1 via the activation of hepatic stellate cells (HSCs) is capable of inducing immune tolerance in LT. METHODS: Lentiviral-mediated gene knockdown and overexpression of galectin-1 were conducted in HSC-T6 cells. Reverse transcription quantitative polymerase chain reaction and western blot analysis were used to determine galectin-1 expression. LT was performed in 20 C57BL/J6 mice and 20 C3H mice. T-cells were assigned into control, Galectin-1 shRNA, Galectin-1 OE, Galectin-1 OE SB431542, Galectin-1 OE Sulforaphane, Galectin-1 OE Y27632, and Galectin-1 OE UO126 groups. CFSE, flow cytometry, and ELISA were respectively employed to detect T-cell proliferation, CD4+/ CD8+ ratio and IL-2, IL-10 and TGF-ß levels. After establishing mouse models of immune tolerance and acute rejection, immunohistochemistry, TUNEL, and immunofluorescence assay were performed to determine CD3+ expression, apoptosis, α-SMA, and desmin. Mouse models of CCl4-induced liver fibrosis were established, followed by assigning the control1 and CCl4 groups. ELISA was used to determine ALT, AST, TBIL and Hyp levels. A total of 3 C57BL/J6 mice (donor) and 6 C3H mice (recipient) were grouped into the control2 and UO126 groups, followed by ELISA detection for IL-2, IL-10 and TGF-ß. RESULTS: In T-cells, galectin-1 shRNA increased cell proliferation and IL-2 levels with reduced IL-10 and TGF-ß levels, while the Galectin-1 OE and Galectin-1 OE UO126 groups revealed the opposite results. Galectin-1 overexpression elevated the ratio of the CD4+ to CD8+ T-cells. The acute rejection group exhibited enhanced desmin expression and reduced α-SMA expression. Compared with the immune tolerance group, the acute rejection group displayed higher galectin-1 expression, a positive expression rate of CD3+ T-cells, and an increased apoptosis rate. Compared with the control1 group, the CCl4 group exhibited higher galectin-1 expression, ALT, AST, TBIL, and Hyp levels, α-SMA expression and CD4+/CD8+ T-cell ratio, in addition to decreased expression of desmin. Compared with the control2 group, UO126 increased galectin-1 expressions, IL-10 and TGF-ß levels and reduced IL-2 levels with inactivated HSCs. CONCLUSIONS: The findings of the current study indicated that the overexpression of galectin-1 promoted the activation of HSCs, which reduced the inflammatory response by exerting immunosuppressive effects and accordingly contributed to immune tolerance in LT.

[The diagnostic value of high-sensitivity C-reactive protein/albumin ratio in evaluating early-onset infection in premature].

OBJECTIVE: To observe the diagnostic value of high-sensitivity C-reactive protein/albumin ratio (hs-CRP/ALB) in early-onset infection in premature and its clinical significance. METHODS: Clinical data of premature patients with high risk factors of intrauterine infection admitted to neonatal intensive care unit (NICU) of Liaocheng People's Hospital in Shandong Province from July 2013 to July 2015 were analyzed retrospectively. They were divided into infection and non-infection groups, as well as survival and death groups according to the outcome of the premature babies. The pre-albumin (PA), ALB, white blood cell count (WBC), platelet count (PLT), and hs-CRP at the moment of NICU admission (0 hour) and 24, 48 and 72 hours after NICU admission were compared. The receiver operating characteristic (ROC) curve was plotted for evaluation of the predictive value of serum hs-CRP/ALB ratio for the babies during hospitalization. RESULTS: A total of 214 cases of premature infants were enrolled, with 102 cases in infection group, and 112 in non-infection group. In infection neonates, 97 of them survived, and 5 died. (1) The level of hs-CRP after NICU admission was increased in infection and non-infection groups, and it was significantly higher at 48 hours in infection group than that of the non-infection group [mg/L: 22.0 (7.6, 40.4) vs. 18.3 (12.9, 23.4),Z = 5.257,P = 0.038]. Then hs-CRP was decreased in non-infection, but it was persistently increased in infection group, and it was significantly higher at 72 hours in infection group than that of the non-infection group [mg/L: 25.5 (9.8, 43.5) vs. 12.2 (1.9, 22.1), Z = 5.879, P = 0.042]. The levels of ALB and WBC in infection group was significantly lower than those of the non-infection group [ALB (g/L): 27.9±2.7 vs. 29.1±2.9, t = 5.178, P = 0.026; WBC (×109/L): 13.7±7.1 vs. 16.1±7.9, t = 4.368, P = 0.037], and at 48 hours hs-CRP/ALB in infection group was significantly higher than that of non-infection group [0.16 (0.08, 0.57) vs. 0.07 (0.00, 0.23), Z = 3.436, P = 0.042]. There was no significant difference in PA and PLT between infection and non-infection groups. (2) In premature patients with infection, ALB in non-survival group was decreased (g/L: 20.4±6.9 vs. 29.6±7.5, t = 7.859, P = 0.003), and 48-hour hs-CRP and hs-CRP/ALB ratio was significantly increased when compared with that of survival group [hs-CRP (mg/L): 25.8 (15.6, 54.8) vs. 18.2 (12.9, 36.2), Z = 4.067, P = 0.043; hs-CRP/ALB: 0.31 (0.28, 0.76) vs. 0.06 (0.00, 0.21), Z = 6.102, P = 0.011].(3) It was shown by ROC curve analysis that the area under ROC curve (AUC) of 48-hour hs-CRP/ALB ratio for evaluating infection was 0.765, when the cut-off of 48-hour hs-CRP/ALB ratio was 0.08, the sensitivity was 84.2%, and the specificity was 76.3%. CONCLUSIONS: The values of hs-CRP and ALB can be used as effective indexes in early diagnosis of intrauterine bacterial infection, and increase in 48-hour hs-CRP/ALB can improve the sensitivity of the diagnosis. Hs-CRP/ALB can be combined to guide rational use of antibiotics.

Exploiting geo-distributed clouds for a e-health monitoring system with minimum service delay and privacy preservation.

In this paper, we propose an e-health monitoring system with minimum service delay and privacy preservation by exploiting geo-distributed clouds. In the system, the resource allocation scheme enables the distributed cloud servers to cooperatively assign the servers to the requested users under the load balance condition. Thus, the service delay for users is minimized. In addition, a traffic-shaping algorithm is proposed. The traffic-shaping algorithm converts the user health data traffic to the nonhealth data traffic such that the capability of traffic analysis attacks is largely reduced. Through the numerical analysis, we show the efficiency of the proposed traffic-shaping algorithm in terms of service delay and privacy preservation. Furthermore, through the simulations, we demonstrate that the proposed resource allocation scheme significantly reduces the service delay compared to two other alternatives using jointly the short queue and distributed control law.

[Application of rhodamine-based fluorescence chemosensor in heavy metal ions and transition metal ions detection].

As one of the fluorescent molecules with high quantum yield, rhodamine was often chosen as the mother molecule in the synthesis of metal ion fluorescence chemosensor. The present paper reviews the applications of rhodamine fluorescence chemosensors in the analysis of heavy metal ions and transition metal ions including the response mechanism, the kinds of targeted ion, scope of application and corresponding detection limit. In addition, the existing challenges and future development directions in the research of rhodamine-based metal ion fluorescence chemosensor are discussed.