Author Correction: The dual role of anti-viral therapy in the treatment of Coronavirus disease 2019.

Correction to: European Review for Medical and Pharmacological Sciences 2020; 24 (22): 11939-11944-DOI: 10.26355/eurrev_202011_23854-PMID: 33275267, published online 30 November, 2020. The authors state that "Figures 3 and 4 were used twice due to a careless mistake during the preparation of Figures". There are amendments to this paper.  The Publisher apologizes for any inconvenience this may cause. https://www.europeanreview.org/article/23854.

The dual role of anti-viral therapy in the treatment of Coronavirus disease 2019.

OBJECTIVE: Coronavirus disease 2019 (COVID-19) has become a worldwide public health emergency; unfortunately, there is currently no treatment for improving outcomes or reducing viral-clearance times in infected patients. The aim of the present study was to evaluate the efficacy of interferon (IFN) with or without lopinavir and ritonavir as antiviral therapeutic option for treating COVID-19 infection. PATIENTS AND METHODS: The present study enrolled 148 patients that received either standard care, treatment with IFN alfa-2b, or IFN alfa-2b combined with lopinavir plus ritonavir. Viral testing was performed using Reverse-Transcription Polymerase Chain Reaction (RT-PCR). RESULTS: There was no significant difference in the viral-clearance time at 28 days after treatment between patients receiving standard care and those receiving anti-viral treatments. However, the average viral-clearance time of patients receiving standard care (14 days) was shorter than that for patients receiving IFN alfa-2b or IFN alfa-2b combined with lopinavir plus ritonavir (15.5 or 17.5 days) (p<0.05). Patients treated with IFN alfa-2b within five days or IFN alfa-2b combined with lopinavir plus ritonavir after three days of symptoms exhibited shorter viral-clearance times than the other groups (p<0.05). Moreover, viral-clearance times were significantly longer in patients receiving standard care or anti-viral treatment 5 days after symptoms appeared than those of patients who received these treatments within five days of symptom onset (p<0.05). CONCLUSIONS: Early symptomatic treatment is most critical for maximizing amelioration of COVID-19 infection. Anti-viral treatment might have complicated effect on viral-clearance.

MiR-429-5p attenuates the migration and invasion of malignant melanoma by targeting LIMK1.

OBJECTIVE: To investigate the potential effects of microRNA-429-5p (miR-429-5p) on the development of malignant melanoma (MM) and the relevant mechanism. PATIENTS AND METHODS: Quantitative Real Time-Polymerase Chain Reaction (qRT-PCR) was used to detect the differential expression of miR-429-5p in MM tissues. The relationship between miR-429-5p expression and clinical pathological data of MM patients was analyzed. LIM kinase 1 (LIMK1) was verified as a downstream target of miR-429-5p by online prediction software, and the interaction between LIMK1 and miR-429-5p was verified by Dual-Luciferase reporter assay. RESULTS: Compared with normal skin tissues, miR-429-5p was downregulated in MM tissues. MiR-429-5p expression was correlated with tumor size and stage of MM. Upregulation of miR-429-5p significantly inhibited protein expression of LIMK1 and reduced migration and invasion ability of MM cells. LIMK1 was involved in MM progression regulated by miR-429-5p. CONCLUSIONS: MiR-429-5p attenuates migration and invasion in MM by targeting LIMK1. Hence, miR-429-5p/LIMK1 axis might be a potential therapeutic target for the treatment of MM.

Expression and clinical significance of aquaporin-1 and ET-1 in urine of children with congenital hydronephrosis.

OBJECTIVE: Congenital hydronephrosis is induced by congenital obstruction of uretero pelvic junction, bladder vesicoureteral reflux, posterior urethral valve, stricture of ureter end and ureterocyst, which is extremely apt to cause end-stage renal failure in children. It becomes significant to explore the expression profile and clinical significance of aquaporin-1 (AQP-1) and ET-1 (endothelin-1) in the urine of children with congenital hydronephrosis. PATIENTS AND METHODS: 80 cases of children with congenital hydronephrosis were selected to be the observation group and another 40 cases of children with other diseases were served as control group. Pre-operative morning urine, intra-operative renal pelvis urine and morning urine at the 7th day after the operation of all the children were collected for the detection of the level of ET-1, Cr level and AQP1 in the urine. Urine various indexes of different diseases stages in children of both groups were compared. RESULTS: There was no significant difference between children with mild and children in control group (p > 0.05). In the observation group, the AQP-1 level during the operation was significantly lower than that before operation, but it was significantly higher in post-operation than that during the operation, which was still lower than that in control group (p < 0.05). Urine ET-1 level in observation group and its positive rate were significantly higher than that in control group (p < 0.05). Serum stress indexes in each stage of the observation group were significantly higher than that in control group (p < 0.05). CONCLUSIONS: The expression levels of urine AQP-1 and ET-1 of children with congenital hydronephrosis were obviously increased. The AQP-1 level during the operation was lower than that before operation. This post-operation level was significantly higher than before the operation. The expression of AQP-1 and ET-1 could be used as important indexes for clinical diagnosis.

Prognostic significance of preoperative albumin-to-globulin ratio in patients with cholangiocarcinoma.

BACKGROUND: This study aimed to assess the prognostic value of the serum albumin to globulin ratio (AGR) in cholangiocarcinoma patients after surgery. METHODS: We retrospectively enrolled 123 cholangiocarcinoma patients who underwent surgical treatment between June 2003 and September2014 at the Third Affiliated Hospital of Sun Yat-sen University. Univariate and multivariate analyses using the Cox regression model were performed to determine the prognostic value of AGR. RESULTS: Univariate analysis suggested that AGR was a predictive factor for (overall survival) OS but not for recurrence free survival (RFS). After adjustment for other risk factors, multivariate analysis showed that AGR remained independently associated with OS. The optimal cut-off point for AGR was determined to be 1.44. Kaplan-Meier curves showed that there was a significantly lower mean survival time in the low AGR group compared to the high AGR group. A low AGR was found to be significantly associated with high alkaline phosphatase, gamma-glutamyl transpeptidase, total bilirubin levels and an advanced American Joint Committee on Cancer TNM stage, but a low hemoglobin level. CONCLUSION: In summary, patients with higher AGRs have better outcomes than those with lower AGRs. Preoperative AGR can be a reliable marker for evaluating the prognosis of cholangiocarcinoma patients.

Effect of serum high molecular weight adiponectin level on the occurrence of eclampsia during subsequent pregnancy in patients with primary pregnancy induced hypertension.

OBJECTIVE: To analyze the effect of serum levels of high molecular weight adiponectin (HMWA) on the occurrence of eclampsia during subsequent pregnancy in patients with primary pregnancy-induced hypertension (PIH). PATIENTS AND METHODS: Thirty patients with primary PIH (observation group) and sixty patients without primary PIH (control group) were consecutively selected. ELISA was used to measure the serum levels of HMWA. The differences in the occurrence of eclampsia during subsequent pregnancy between the two groups were compared. RESULTS: The serum levels of HMWA in the observation group were significantly lower than in the control group, and they decreased with increased severity of PIH (p < 0.05). In the observation group, the gestational age was lower than that of the control group, and the occurrence of cesarean section and maternal complications were increased. The neonatal weight and Apgar scores were lower than those of the control group, and the occurrence of neonatal complications was increased. The difference was statistically significant (p < 0.05). There were no differences in the time intervals between pregnancies in the two groups. The occurrence of PIH and eclampsia during subsequent pregnancy in the observation group was significantly higher than that in the control group (p < 0.05). According to receiver operating curve analysis, the sensitivity, specificity, and accuracy of serum HMWA level in predicting the occurrence of eclampsia during subsequent pregnancy were 85.6%, 74.8%, and 0.824 (95% CI = 0.811-0.936, p = 0.015), respectively. The critical value was 2.4 mg/l. CONCLUSIONS: Decreases of serum levels of HMWA in patients with primary PIH are closely related to the severity of PIH and the outcome of pregnancy, which has important predictive value for the occurrence of eclampsia during subsequent pregnancy.

Study on quality standards for Chimonanthus nitens.

Chimonanthus nitens Oliv. is a commonly used traditional Chinese medicine. Terpenoids, flavonoids, and coumarins are usually considered its main bioactive ingredients. Thus, qualitative and quantitative analyses of these compounds are crucial in quality control studies of Chimonanthus nitens. In this study, five compounds were identified by double-development thin layer chromatography (TLC) and the content of four compounds was determined by high performance liquid chromatography; the detection wavelength was set to 344 nm and the column temperature was 40°C. All calibration curves showed good linear regression (R2 > 0.9995). The average recoveries ranged from 97.06 to 104.44%. The RSD was below 4.2%. Four compounds remained stable over 24 h and the relative standard deviation (RSD) of the precision of their measurement was less than 1.5%. The developed method was reproducible, sensitive, and simple, and could be used for quality control of Chimonanthus nitens.

Eosinophil differentiation in the bone marrow is promoted by protein tyrosine phosphatase SHP2.

SHP2 participates in multiple signaling events by mediating T-cell development and function, and regulates cytokine-dependent granulopoiesis. To explore whether and how SHP2 can regulate bone-marrow eosinophil differentiation, we investigate the contribution of SHP2 in the bone-marrow eosinophil development in allergic mice. Blockade of SHP2 function by SHP2 inhibitor PHPS-1 or conditional shp2 knockdown by adenovirus-inhibited bone-marrow-derived eosinophil differentiation in vitro, with no detectable effects on the apoptosis of eosinophils. Furthermore, SHP2 induced eosinophil differentiation via regulation of the extracellular signal-regulated kinase pathway. Myeloid shp2 conditional knockout mice (LysM(cre)shp2(flox/flox)) failed to induce eosinophilia as well as airway hyper-responsiveness. The SHP2 inhibitor PHPS-1 also alleviated eosinophilic airway inflammation and airway hyper-responsiveness, accompanied by significantly reduced levels of systemic eosinophils and eosinophil lineage-committed progenitors in allergic mice. We demonstrate that inhibition of eosinophil development is SHP2-dependent and SHP2 is sufficient to promote eosinophil formation in vivo. Our data reveal SHP2 as a critical regulator of eosinophil differentiation, and inhibition of SHP2 specifically in myeloid cells alleviates allergic airway inflammation.

LZTFL1 suppresses lung tumorigenesis by maintaining differentiation of lung epithelial cells.

Lung cancer is the leading cause of cancer-related death in the United States, and metastatic behavior is largely responsible for this mortality. Mutations in multiple 'driver' oncogenes and tumor suppressors are known to contribute to the lung tumorigenesis and in some cases represent therapeutic targets. Leucine Zipper Transcription Factor-like 1 (LZTFL1) is located in the chromosome region 3p21.3 where allelic loss and genetic alterations occur early and frequently in lung cancers. Previously, we found that LZTFL1 is downregulated in epithelial tumors, including lung cancer, and functions as a tumor suppressor in gastric cancers. However, the functional role of LZTFL1 in lung oncogenesis is undefined. We show here that downregulation of LZTFL1 expression in non-small cell lung cancer is associated with recurrence and poor survival, whereas re-expression of LZTFL1 in lung tumor cells inhibited extravasation/colonization of circulating tumor cells to the lung and inhibited tumor growth in vivo. Mechanistically, we found that LZTFL1 is expressed in ciliated human bronchial epithelial cells (HBECs) and its expression correlates with HBEC differentiation. LZTFL1 inhibits transforming growth factor ß-activated mitogen-activated protein kinase and hedgehog signaling. Alteration of intracellular levels of LZTFL1 resulted in changes of expression of genes associated with epithelial-to-mesenchymal transition (EMT). We conclude that LZTFL1 inhibits lung tumorigenesis, possibly by maintaining epithelial cell differentiation and/or inhibition of signalings that lead to EMT and suggest that reactivation of LZTFL1 expression in tumor cells may be a novel lung cancer therapeutic approach.

Epigenetic changes of the Klotho gene in age-related cataracts.

OBJECTIVE: To determine the mRNA and protein expression, and methylation levels of the Klotho in lens epithelial cells (LECs) of normal transparent lenses and age-related cataracts (ARCs), and to explore the role of epigenetic changes of the Klotho gene in regulating the development of ARCs. PATIENTS AND METHODS: A total of 90 subjects were divided into three groups: a young adult group with normal transparent lenses aging from18 to30 years, a middle-aged group with ARC aging from 40 to 49 years, and an elderly group with ARC aging from 67 to 85 years. The LECs were collected through curvilinear capsulorhexis. The mRNA expression of the Klotho gene was determined using the reverse transcription polymerase chain reaction (RT-PCR). Protein expression of the Klotho gene in LECs was detected using immunohistochemical (IHC) staining. The methylation specific polymerase chain reaction (MSP) was used to detect the methylation level of the target gene. RESULTS: Decreased mRNA expression of the Klotho gene was reversely correlated with age. IHC results showed that the Klotho was mainly expressed in the cell membrane and cytoplasm of LECs. It was strongly positive in the young adult group (100.0%), with even distribution; weakly positive in the middle-aged group (36.7%), with expression distributed 4-5 mm away from the center of the anterior lens capsule; and negative in the elderly group (0.0%). MSP results showed that the Klotho gene was highly methylated in the elderly group (93.3%) and weakly methylated (56.7%) in the middle-aged group, but barely methylated in the young adult group (3.3%). CONCLUSIONS: Klotho were positively expressed in the LECs of normal individuals at the mRNA and protein level. Its promoter showed increased methylation as age increased, resulting in Klotho gene silencing as well as down-regulated expression or no expression of the Klotho protein. These epigenetic changes could affect the biological activities of LECs, which provided the basis for further studies of the association between the Klotho gene and ARC.

Lack of estrogen down-regulates CXCR4 expression on Treg cells and reduces Treg cell population in bone marrow in OVX mice.

Postmenopausal osteoporosis (PMO) is the most common metabolic bone disease in women after menopausal. Recent works focused on cross—talk between immune regulation and bone metabolism pathways and suggested Treg cells suppressed bone resorption and osteoclasts (OC) differentiation in bone marrow via cell—cell contact interaction and/or secreting of IL—10 and TGF—beta. In this study, we investigated the impact of estrogen on regulatory T cells (Treg cells) trafficking and staying in bone marrow and we found that a significant reduction of Treg cell population in bone marrow in estrogen deficiency ovariectomied (OVX) mice. We then studied the expressions of chemokines CXCL12/CXCR4 axes, which were critical to Treg cells migration and our data show the expression of CXCR4 on Treg cells was relative with oestrogen in vivo, however, the expression of CXCL12 was not. Furthermore, the loss of trafficking ability of Treg cells in OVX mice was recoverable in our system. These findings may mechanistically explain why Treg cells lose their suppressive functions on the regulation of OC cells and demonstrate a previously unappreciated role for estrogen, which may be critical to the novel therapy in clinical practice of PMO patients.

Germline mutations of DICER1 in Chinese women with BRCA1/BRCA2-negative familial breast cancer.

Germline mutations in identified breast cancer susceptibility genes account for less than 20% of Chinese familial breast cancers. Dicer is an essential component of the microRNA-producing machinery; germline mutations of DICER1 have been confirmed in familial pleuropulmonary blastoma, ovarian sex cord-stromal tumors, and other cancers. Low expression of DICER1 is frequently detected in breast cancer. However, whether germline mutations of DICER1 occur in familial breast cancers remain unknown. Sixty-five breast cancer probands from BRCA1/BRCA2-negative Chinese breast cancer families were screened for germline mutations in DICER1. In addition, 100 unrelated healthy females were enrolled as controls. A polymerase chain reaction sequencing assay was used to screen for mutations in coding regions and at the exon-intron boundaries of DICER1. All variants in introns were evaluated using the NNSplice software to determine the potential splicing effect. A total of 12 germline variants were found, including 11 variants in introns and 1 variant in the 3'-non-coding region. Four variants (IVS8-205 C>T, IVS11+131 delGAAA, IVS16+42 delTA, and IVS19+160 T>C) were novel. Three variants (IVS11+105 C>T, IVS16+42 delTA, and 6095 T>A) may affect splice sites. None of the observed variants appeared to be disease-related, suggesting that germline mutations in DICER1 are rare or absent in familial breast cancer patients.

Pemetrexed versus gefitinib as a second-line treatment in advanced nonsquamous nonsmall-cell lung cancer patients harboring wild-type EGFR (CTONG0806): a multicenter randomized trial.

BACKGROUND: CTONG0806 assessed the efficacy of pemetrexed versus gefitinib as second-line treatment in advanced nonsquamous nonsmall-cell lung cancer (NSCLC) harboring wild-type epidermal growth factor receptor (EGFR). PATIENTS AND METHODS: Patients with locally advanced or metastatic nonsquamous NSCLC harboring wild-type EGFR, detected by direct sequencing, and previously treated with platinum-based chemotherapy were randomized to receive gefitinib (250 mg/day) orally or pemetrexed (500 mg/m(2)) i.v. on day 1 of a 21-day cycle until disease progression or unacceptable toxicity. The primary end point was progression-free survival (PFS). The Independent Review Committee (IRC) evaluated all pictorial data. RESULTS: From February 2009 to August 2012, 161 patients were enrolled, and 157 were assessable (81 in the gefitinib arm, 76 in the pemetrexed arm). Baseline characteristics were balanced between the two arms. The median PFSs were 4.8 versus 1.6 months in the pemetrexed and gefitinib arms, respectively [hazard ratio (HR) 0.54, 95% confidence interval (CI) 0.40-0.75, P < 0.001] as confirmed by IRC evaluation (5.6versus 1.7 months, HR 0.53, 95% CI 0.38-0.75, P < 0.001). The median overall survival (OS) showed a trend of superiority in the pemetrexed arm (12.4 versus 9.6 months, HR 0.72, 95% CI 0.49-1.04, P = 0.077). Quality-of-life assessment showed no marked difference between the arms. No unexpected adverse events were found. Of 108 patients with sufficient DNA samples, EGFR mutation status was re-tested by Scorpion amplification refractory mutation system (ARMS); 32 (29.6%) tested positive (19 in the pemetrexed arm, 13 in the gefitinib arm; median PFS: 8.1 versus 7.0 months, HR 0.94, 95% CI 0.43-2.08, P = 0.877). CONCLUSIONS: CTONG0806 is the first trial to show significant improvement in PFS and an improved OS trend with pemetrexed compared with gefitinib as second-line setting treatment of EGFR wild-type advanced nonsquamous NSCLC. ARMS is superior to direct sequencing in excluding false-negative patients. CLINICALTRIALSGOV IDENTIFIER: NCT00891579.

EIF5A2 predicts outcome in localised invasive bladder cancer and promotes bladder cancer cell aggressiveness in vitro and in vivo.

BACKGROUND: EIF5A2, eukaryotic translation initiation factor 5A2, is associated with several human cancers. In this study, we investigated the role of EIF5A2 in the metastatic potential of localised invasive bladder cancer (BC) and its underlying molecular mechanisms were explored. METHODS: The expression pattern of EIF5A2 in localised invasive BC was determined by immunohistochemistry. In addition, the function of EIF5A2 in BC and its underlying mechanisms were elucidated with a series of in vitro and in vivo assays. RESULTS: Overexpression of EIF5A2 was an independent predictor for poor metastasis-free survival of localised invasive BC patients treated with radical cystectomy. Knockdown of EIF5A2 inhibited BC cell migratory and invasive capacities in vitro and metastatic potential in vivo and reversed epithelial-mesenchymal transition (EMT), whereas overexpression of EIF5A2 promoted BC cells motility and invasiveness in vitro and metastatic potential in vivo and induced EMT. In addition, we found that EIF5A2 might activate TGF-ß1 expression to induce EMT and drive aggressiveness in BC cells. EIF5A2 stabilized STAT3 and stimulated nuclear localisation of STAT3, which resulted in increasing enrichment of STAT3 onto TGF-ß1 promoter to enhance the transcription of TGF-ß1. CONCLUSIONS: EIF5A2 overexpression predicts tumour metastatic potential in patients with localised invasive BC treated with radical cystectomy. Furthermore, EIF5A2 elevated TGF-ß1 expression through STAT3 to induce EMT and promotes aggressiveness in BC.

AIB1 predicts bladder cancer outcome and promotes bladder cancer cell proliferation through AKT and E2F1.

BACKGROUND: We previously demonstrated that AIB1 overexpression is an independent molecular marker for shortened survival of bladder cancer (BC) patients. In this study, we characterised the role and molecular mechanisms of AIB1 in BC tumorigenicity. METHODS: AIB1 expression was measured by immunohistochemistry in non-muscle-invasive BC tissue and adjacent normal bladder tissue. In addition, the tumorigenicity of AIB1 was assessed with in vitro and in vivo functional assays. RESULTS: Overexpression of AIB1 was observed in tissues from 46 out of 146 patients with non-muscle-invasive BC and was an independent predictor for poor progression-free survival. Lentivirus-mediated AIB1 knockdown inhibited cell proliferation both in vitro and in vivo, whereas AIB1 overexpression promoted cell proliferation in vitro. The growth-inhibitory effect induced by AIB1 knockdown was mediated by G1 arrest, which was caused by reduced expression of key cell-cycle regulatory proteins through the AKT pathway and E2F1. CONCLUSION: Our results suggest that AIB1 promotes BC cell proliferation through the AKT pathway and E2F1. Furthermore, AIB1 overexpression predicts tumour progression in patients with non-muscle-invasive BC.

cDNA cloning and analysis of polymorphism of GFI1B gene in GuiZhou white goat.

This study mainly aimed to research the CDS sequence (coding sequence), polymorphisms of exon 1, exon 2 and part of exon 8 of GFI1B in GuiZhou white goat of indigenous Chinese goat. The cDNA of GFI1B was analysed through bioinformatics which was obtained by the reverse transcription PCR (RT-PCR). The polymorphisms of GFI1B gene exons region was identified whose association with growth traits was analysed by GuiZhou white goat. The results revealed that the cDNA of GFI1B which contained a complete open reading frame (ORF) was 996 bp in full length. The accession numbers on GenBank was JX627316. One new mutation sites of C347A had been determined in the eighth intron. Our results could lay the foundation for the further investigation on the role of GFI1B gene in goat growth traits.

Prognostic significance of cyclinD1 amplification and the co-alteration of cyclinD1/pRb/ppRb in patients with esophageal squamous cell carcinoma.

CyclinD1/pRb/ppRb is one of the most important pathways regulating the cell cycle, and related with the development of many cancers. However, the co-alteration of CyclinD1/pRb/ppRb in esophageal squamous cell carcinomas is less understood. This study aims to analyze the combined prognostic significance of cyclinD1 (CCND1) DNA amplification and the co-alteration of CCND1/pRb/ppRB in patients with esophageal squamous cell carcinoma. CCND1 DNA amplification and the protein expression of CCND1, pRb, and ppRb on 100 tumor specimens and 11 normal tissues were detected using real-time quantitative reverse transcription polymerase chain reaction and immunohistochemistry, respectively. Their prognosis significance was analyzed by Kaplan-Meier method. We found that 41% of the patients had CCND1 DNA amplification, which had a short survival time compared with the patients without CCND1 amplification (25.63 months vs. not reached, P=0.007). The patients with the co-alternation of CCND1(+) /pRb(-) /ppRb(+) protein expression levels have a poorer overall survival than the others (11.4 vs. 43.4 months, P=0.001). Cox regression analysis showed that the co-alternation of CCND1/pRb/ppRb and CyclinD1 amplification were the two most independent prognosis factors of patients with esophageal cancer. These findings suggested that CCND1 amplification and co-alternation of CCND1(+) /pRb(-) /ppRb(+) may play a crucial role in the prognostic evaluation of patients with esophageal cancer, and the patients with CCND1(+) /pRb(-) /ppRb(+) have the worst prognosis in all the patients. The results also indicated that the patients with CCND1 amplification or co-alternation of CyclinD1(+) /pRb(-) /ppRb(+) might be the preponderant people for therapy targeting the CCND1/pRb/ppRb pathway in the future.

Anti-gamma chain and anti-IL-2Rbeta mAbs in combination with donor splenocyte transfusion induce H-Y skin graft acceptance in murine model.

BACKGROUND: The common cytokine receptor gamma chain signals regulate proliferation, differentiation, and apoptosis of peripheral T cells. OBJECTIVE: To investigate whether simultaneous blockade of IL-2Rbeta and gamma chain signaling in combination with donor splenocyte transfusion (DST) induces transplant tolerance. MATERIALS AND METHODS: C57BL/6 (H-2b) mice were randomly divided into 5 groups. In group 1, female mice received only H-Y skin grafts. In group 2, female mice received transfused splenocytes (5 x 10(6) cells) from syngeneic male mice on day 7 before H-Y skin grafting. In group 3, on days 2 and 4 after DST, female mice received intraperitoneal injections of a mixture of anti-IL-2Rbeta monoclonal antibody (mAb) and anti-gamma chain mAbs (4G3, 3E12, and TUGm2; 0.5 mg). After DST, group 4 received an intraperitoneal injection of the mixture of anti-gamma chain mAbs, and group 5 received intraperitoneal injection of anti-IL-2Rbeta mAb (TM-beta1). On day 7, H-Y skin grafting was performed. RESULTS: Group 3 recipients accepted H-Y skin grafts for more than 100 days compared with group 1 (mean survival time [MST], 33.42 days), group 2 (MST, 14.71 days), group 4 (MST, 58.71 days), and group 5 (MST, 17.29 days). Statistical differences (P < .05) were observed between any 2 groups except groups 2 and 5. CONCLUSION: Blockade of gamma chain signaling rather than IL-2Rbeta signaling combined with DST prolongs H-Y skin graft survival. Simultaneous blockade of IL-2Rbeta and gamma chain signaling may strengthen this effect.

Effects of diagnostic contrast-enhanced ultrasound on permeability of placental barrier: a primary study.

OBJECTIVE: To evaluate the effects of contrast-enhanced ultrasound (CEU) on the permeability of placental barrier primarily. METHODS: A total of 60 pregnant Sprague Dawley (SD) rats were divided into 10 groups, including six groups of microbubbles-enhanced ultrasound (varied mechanical index (MI) of 0.13, 1.0 and 1.4 with continuous and intermittent insonation respectively) (US+MB), two groups of ultrasound insonation only (continuous and intermittent insonation respectively) (US), the group of microbubbles only (MB) and the control group. Evans blue (EB), as the tracer, was intravenously injected before treatment. The EB in placenta and fetus was observed under fluorescence microscope and analyzed quantitatively. The EB amount was compared between groups and between placenta and fetus. Lanthanum nitrate-tracing transmission electron microscope examination was performed to observe the distribution of lanthanum in the placenta and fetus. RESULTS: Observed by naked eye, the plancenta was dyed into deep blue while there was no sign of dyeing to the fetus in all groups. Under fluorescence microscope, the red fluorescence radiated by EB was observed in placenta but not in fetus. The EB amount in placenta, insonated by microbubbles-enhanced ultrasound of varied MI, was higher significantly than that in MB, US and control group (all P<0.01) while there was no difference between the latter three groups. And in each group, EB amount was much higher in placenta than that in fetus (P<0.01). The lanthanum particles deposited in the intercellular space in the syntrophoblast while there was no lanthanum presented in the cytotrophoblast in all groups. CONCLUSION: Our findings suggest that diagnostic CEU with SonoVue will not increase the permeability of placenta to the macromolecules larger than albumin, although it may affect placenta.

Improvement of monocyte function and immune homeostasis by high volume continuous venovenous hemofiltration in patients with severe acute pancreatitis.

BACKGROUND: Continuous renal replacement therapy (CRRT) showed promising results in the management of critically ill patients with systemic inflammatory response syndrome (SIRS)/sepsis. However, the underlying mechanism is still not very clear. A change of immune homeostasis in critically ill patients during CRRT was observed only to a smaller degree. OBJECTIVE: The purpose of this study was to test the hypothesis that high-volume continuous venovenous hemofiltration (HV-CVVH) treatment could improve monocyte function and restore immune homeostasis in patients with severe acute pancreatitis (SAP). METHODS: This was a prospective clinical trial in the surgical intensive care unit of a teaching hospital. Subjects were 16 patients with severe acute pancreatitis: sepsis group (n=7): positive culture result and in the late phase of disease (from onset of SAP to receiving CVVH therapy: more than 3 days); and nonseptic group (n=9): negative culture result and early phase of disease (less than 3 days). Patients received 72 hours of HV-CVVH. We measured the change in mean arterial pressure, APACHE II score, monocyte functions (including antigen-presenting and cytokine production ability), and plasma cytokines. RESULTS: Mean arterial pressure were stable accompanied with APACHE II score improvements. HLA-DR expression on monocytes (antigen-presenting ability) were markedly decreased (p<0.0001) in all patients. Lipopolysaccharide (LPS)-induced TNF-alpha, interleukin-6 (IL-6), and IL-10 production from patients' monocytes markedly decreased in septic patients, but significantly increased in nonseptic patients. During HV-CVVH treatment, HLA-DR expression was markedly increased in nonseptic patients in 24 hours (p<0.05), and in septic patients in 72 hours (p<0.05). LPS-induced cytokine production was decreased in nonseptic patients, but not significantly changed in septic patients. The change of plasma cytokines showed the same trend. CONCLUSIONS: In patients with SAP, HV-CVVH was associated with improved hemodynamics. HV-CVVH restores monocytes functions, especially in patients in the early phase of the disease and without sepsis. These findings suggest a potential role for HV-CVVH in the treatment of SAP.