Repeat hepatic resection versus radiofrequency ablation for recurrent hepatocellular carcinoma: retrospective multicentre study.

BACKGROUND: The therapeutic value of repeat hepatic resection (rHR) or radiofrequency ablation (RFA) for recurrent hepatocellular carcinoma (HCC) is unknown. This study aimed to investigate the safety and efficacy of rHR or RFA. METHODS: This was a retrospective multicentre study of patients with recurrent HCC within the Milan criteria who underwent rHR or RFA at nine university hospitals in China and Italy between January 2003 and January 2018. Survival after rHR or RFA was examined in unadjusted analyses and after propensity score matching (1 : 1). RESULTS: Of 847 patients included, 307 and 540 underwent rHR and RFA respectively. Median overall survival was 73.5 and 67.0 months after rHR and RFA respectively (hazard ratio 1.01 (95 per cent c.i. 0.81 to 1.26)). Median recurrence-free survival was longer after rHR versus RFA (23.6 versus 15.2 months; hazard ratio 0.76 (95 per cent c.i. 0.65 to 0.89)). These results were confirmed after propensity score matching. RFA was associated with lower morbidity of grade 3 and above (0.6 versus 6.2 per cent; P < 0.001) and shorter hospital stay (8.0 versus 3.0 days, P < 0.001) than rHR. CONCLUSION: rHR was associated with longer recurrence-free survival but not overall survival compared with RFA.

[Analysis of types and treatment methods of cervical massive hemorrhage].

Objective: To summarize the classification and clinical treatment experience of cervical massive hemorrhage in multiple centers. Methods: From April 2012 to October 2020, clinical data of 42 patients with cervical massive hemorrhage were retrospectively analyzed, including 27 cases from Shanghai Changzheng Hospital, 7 cases from Hunan Provincial People's Hospital, 4 cases from Longkou People's Hospital and 4 cases from Laizhou People's Hospital. According to bleeding position (P), bleeding vessel (V), cerebral blood supply (C), and the presence or absence of associated injury (A), 42 patients were classified as "PVCA", and summarize the methods of pre-hospital emergency and in-hospital treatment based on the "ABC" treatment principles: airway rebuild (A), effective arterial hemostasis and bleeding stop (B), and cerebral blood flow reconstruction within the time window (C). Results: Within the 42 cases of cervical massive hemorrhage, there were 3 cases of type P1 (below cricoid cartilage), 28 cases of type P2 (cricoid cartilage-mandibular angle), 11 cases of type P3 (mandibular angle-skull base); 22 cases of type V1 (arterial hemorrhage), 11 cases of type V2 (main venous hemorrhage), 7 cases of type V3 (simple superficial vein or small artery hemorrhage), 2 cases of type V4 (mixed arteriovenous hemorrhage); 5 cases of type C0 (no symptoms of cerebral ischemia and neurological dysfunction), 33 cases of type C1 (transient cerebral ischemia without sensory disturbance), 4 cases of type C2 (symptoms of cerebral ischemia and neurological dysfunction); 39 cases of type A0 (no other system damage was involved) and 3 cases of type A1 (combined with other system damage). All 42 patients received operations, 25 patients received open surgery of vascular reconstruction+hematoma/foreign body removal (7 cases of vascular ligation, 14 cases of direct suture repair, 4 cases of vascular interposition), 17 patients received hybrid surgery (carotid angiography+covered stent repair+hematoma/foreign body removal). The surgical technique success rate the was 100%. All the hemorrhagic shock was corrected, hematoma compression was relieved, and the symptoms of cephalic ischemia were improved. There were 4 cases of local cranial nerve injury, 1 case of incision hematoma and 6 cases of postoperative hyper perfusion. During the average 14.3 months follow-up, there was no operation related myocardial infarction, stroke or death, no re-rupture or re-dissection, and 50% asymptomatic restenosis was found in 1 case one year after received covered stent endovascular repair. Conclusion: Based on the "PVCA" classification and "ABC" treatment principle, it is safe and effective to rescue cervical massive hemorrhage.

[Predictive value of combined detection tumor markers in the diagnosis of lung cancer].

To evaluate the predictive value of combined five tumor markers (TMs) CEA, NSE, SCCA, CYFRA21-1 and ProGRP in the diagnosis of lung cancer(LC). Total of 305 hospitalized patients with LC were enrolled, 100 healthy subjects and 100 patients with benign lung diseases were selected as the healthy control (HC) group and BLD group, respectively. The levels of TMs in serum were detected by Flow fluorescence technique. Positivity rates were analyzed by using Chi-square test,The differences of tumor marker levels were compared using Mann-Whitney test and Kruskal-Wallis test. The Receiver Operating Characteristics (ROC) curve was performed to analyze the diagnosis efficacy of TMs. The combined detection had a higher positive rate in patients with LC, adenoadenocarcinoma, squamous cell carcinoma and SCLC (70.82%, 64.74%, 76.4% and 81.03%, respectively) than each TM considered individually. The serological levels of CEA, NSE, SCCA, CYFRA21-1 in LC group were higher than HC and BLD group. The differences of them among the three groups were statistically significant (χ²=90.599, 32.802, 8.473, 40.397 respectively, all P values were<0.05), ProGRP level had no remarkable difference (χ²=3.366, P>0.05), whereas ProGRP level in SCLC were significantly higher compared with adenocarcinoma (Z=6.404,P<0.001) and squamous cell carcinoma (Z=5.765,P<0.001) group. The combined detection difference of positive rate between the early stages(stageⅠ and stage Ⅱ)and the advanced stages (stage Ⅲ and stage Ⅳ) were statistically significant(χ²=24.941, P<0.001).The positive rate of combined detection in the diagnosis of lung cancer lymph node metastasis(76.31%) or distant metastasis(78.18%) was significantly higher than that of single detection. Meanwhile, the positive rate of combined detection in patients with lymph node metastasis or distant metastasis was significantly higher than that in patients without metastasis(χ²=24.60, 9.50 respectively, all P values were<0.05).The combined detection had a better sensitivity(70.82%), accuracy(69.10%)and negative predictive value (59.91%)in LC group than each TM considered individually.The ROC curve showed that the AUC of combined detection in the diagnosis of LC, lung adenocarcinoma, lung squamous cell carcinoma and SCLC were 0.769, 0.780, 0.766 and 0.831, respectively.The combined detection of five tumor markers of CEA, NSE, SCCA, CYFRA21-1 and ProGRP by flow fluorescence technique can improve the diagnostic efficiency of lung cancer.

Observational evidence for interhemispheric hydroxyl-radical parity.

The hydroxyl radical (OH) is a key oxidant involved in the removal of air pollutants and greenhouse gases from the atmosphere. The ratio of Northern Hemispheric to Southern Hemispheric (NH/SH) OH concentration is important for our understanding of emission estimates of atmospheric species such as nitrogen oxides and methane. It remains poorly constrained, however, with a range of estimates from 0.85 to 1.4 (refs 4, 7-10). Here we determine the NH/SH ratio of OH with the help of methyl chloroform data (a proxy for OH concentrations) and an atmospheric transport model that accurately describes interhemispheric transport and modelled emissions. We find that for the years 2004-2011 the model predicts an annual mean NH-SH gradient of methyl chloroform that is a tight linear function of the modelled NH/SH ratio in annual mean OH. We estimate a NH/SH OH ratio of 0.97 ± 0.12 during this time period by optimizing global total emissions and mean OH abundance to fit methyl chloroform data from two surface-measurement networks and aircraft campaigns. Our findings suggest that top-down emission estimates of reactive species such as nitrogen oxides in key emitting countries in the NH that are based on a NH/SH OH ratio larger than 1 may be overestimated.

The tumor suppressor NOR1 suppresses cell growth, invasiveness, and tumorigenicity in glioma.

Oxidored-nitro domain-containing protein 1 (NOR1) is a tumor suppressor downregulated in various human cancers, including nasopharyngeal carcinoma (NPC), lung cancer, and testicular cancer. NOR1 protein is highly expressed in the normal brain; however, its role in brain tumors remains unknown. In this study, we demonstrated that the NOR1 protein level was decreased in glioma tissue samples as compared to its normal counterpart. Exogenously expressed NOR1 protein in glioma U251 cells inhibits tumor cell proliferation, migration, and invasion. Re-expression of NOR1 induced cell cycle S to G2 phase arrest and suppressed its tumorigenicity in nude mice. Overexpression of NOR1 in U251 cells also led to a decrease of Ki67 expression in xenografts. Transcriptomic analysis revealed that NOR1 expression altered the expression of genes favored cell proliferation. Among the differentially expressed genes, FOXR2, a member of the FOX gene family, which promotes glioma progression, was decreased in NOR1 expressing cells. The downregulation of FOXR2 by NOR1 was validated in vitro and in vivo. Our findings suggest for the first time that NOR1 suppresses glioma progression via modulating the FOXR2 expression.

[Immune function of myeloid-derived suppressor cells and its mechanism in obstructive sleep apnea syndrome].

Objective: To investigate the immune function of myeloid-derived suppressor cells (MDSC) and its mechanism in obstructive sleep apnea syndrome (OSAS). Methods: Twenty OSAS patients who were diagnosed by polysomnography (Apnea Hyponea Index>30 events/h) from Sleep Disorders Center at First Affiliated Hospital between January 2015 and December 2016 were selected. The percent of CD14(+) low expression or lack of human leukocyte antigen DR (HLA-DR(-/low)) MDSC in the CD14(+) monocyte from both OSAS patients and healthy people were analyzed by flow cytometry. In vitro assay, MDSC from OSAS patients and health people were sorted by flow cytometry and T cells were sorted with negative isolation kit. For T-cell proliferation assays, the carboxyfluorescein diacetate succinimidyl ester (CFSE)-labeled T cells were respectively incubated with autologous MDSC. CFSE fluorescence intensity of T cells was detected by flow cytometry. Enzyme-linked immunosorbent assay (ELISA) and Western blot analysis were used to evaluate the concentrations of interleukin (IL)-6, tumor necrosis factor-α (TNF-α), IL-10, transforming growth factor-ß(1) (TGF-ß(1)), positive rate of programmed death ligand-L1 (PD-L1), relative transcript level of Arginase 1 (Arg1), inducible nitric oxide synthase (iNOS), hypoxic inducible factor-1α (HIF-1α) expressed by MDSC. Results: Comparing to healthy people, the percentage of CD14(+)HLA-DR(-/low) MDSC in CD14(+) monocyte was significantly elevated [(12.5±1.5)% vs (3.5±0.4)%, P<0.05]. In vitro, OSAS patient-derived MDSC exhibited a stronger suppressive effect on T-cell proliferation [(23.2±1.1)% vs (53.7±3.2)%, P<0.05]. Further analysis revealed that OSAS patient-derived MDSC secreted much higher concentrations of IL-6, TNF-α, IL-10 and TGF-ß(1) [(1 316±163) vs (642±72) ng/L, (316±35) vs (167±18) ng/L, (385±42) vs (108±26) ng/L and (44 276±4 589) vs (9 557±1 124) ng/L] (all P<0.05). The percentage of membrane molecule PD-L1-positive cells in OSAS patient-derived MDSC was obviously higher than that in healthy people-derived MDSC [(75.6±7.9)% vs (30.6±2.5)%, P<0.05]. Compared with healthy people-derived MDSC, the relative transcript level of Arg1, iNOS and HIF-1α in OSAS patient-derived MDSC was also increased by (4.6±0.5), (2.8±0.3) and (4.3±0.4) fold, respectively (all P<0.05). Conclusions: OSAS may be capable of inducing the proliferation of MDSC and its expression of immunosuppressive molecules by activating HIF-1α signal, thereby enhancing the immunosuppressive ability of MDSC.

Expression profile analysis of 5-day-old neonatal piglets infected with porcine Deltacoronavirus.

BACKGROUND: Porcine deltacoronavirus (PDCoV) is a novel coronavirus that can cause diarrhea in nursing piglets. This study was aimed to investigate the roles of host differentially expressed genes on metabolic pathways in PDCoV infections. RESULTS: Twenty thousand six hundred seventy-four differentially expressed mRNAs were identified in 5-day-old piglets responded to PDCoV experimental infections. Many of these genes were correlated to the basic metabolism, such as the peroxisome proliferator-activated receptor (PPAR) signaling pathway which plays a critical role in digestion. At the same time, in the PPAR pathway genes of fatty acid-binding protein (FABP) family members were observed with remarkably differential expressions. The differential expressed genes were associated with appetite decrease and weight loss of PDCoV- affected piglets. DISCUSSION: Fatty acid-binding protein 1 (FABP1) and fatty acid-binding protein 3 (FABP3) were found to be regulated by PDCoV. These two genes not only mediate fatty acid transportation to different cell organelles such as mitochondria, peroxisome, endoplasmic reticulum and nucleus, but also modulate fatty acid metabolism and storage as a signaling molecule outside the cell. Therefore, it can be preliminarily concluded that PPAR differential expression caused by PDCoV was mostly associated with weight loss and death from emaciation. CONCLUSIONS: The host differentially expressed genes were associated with infection response, metabolism signaling and organismal systems signaling pathways. The genes of FABP family members in the PPAR signaling pathway were the most highly altered and played important roles in metabolism. Alteration of these genes were most likely the reason of weight loss and other clinical symptoms. Our results provided new insights into the metabolic mechanisms and pathogenesis of PDCoV infection. METHODS: Animal experiment, Determination of viral growth by real-time RT-PCR, Histopathology, Immunohistochemical staining, Microarray analysis.

Systematic review of risk factors of hepatocellular carcinoma after hepatitis B surface antigen seroclearance.

There is no consensus about factors that increase risk of hepatocellular carcinoma (HCC) among patients with chronic hepatitis B who have achieved seroclearance of hepatitis B surface antigen (HBsAg). To assess the available evidence about risk factors for HCC after HBsAg seroclearance, Scopus, EMBASE, PubMed and Cochrane Library databases were systematically searched for relevant studies published through 15 September 2017. A total of 28 studies involving more than 105 411 patients with chronic hepatitis B were included. HBsAg seroclearance occurred spontaneously in 7656, while it occurred after interferon or nucleos(t)ide analogue therapy in 1248. The rate of HBsAg seroclearance was 6.77%. Incidence of HCC was significantly lower among patients who experienced HBsAg seroclearance than among those who remained HBsAg-positive (1.86% vs 6.56%, P < .001). Risk factors of HCC occurrence included cirrhosis (incidence with vs without: 9.51% vs 1.66%), male gender (2.34% vs 0.64%) and age ≥ 50 year at HBsAg seroclearance (2.34% vs 0.63%) (all P < .001). The available evidence suggests that HCC can develop at a low rate after HBsAg seroclearance, so periodic surveillance is recommended, especially for male patients, patients with cirrhosis and patients who experience HBsAg seroclearance when at least 50 years old.

Kaposiform haemangioendothelioma: clinical features, complications and risk factors for Kasabach-Merritt phenomenon.

BACKGROUND: Few studies have reported the clinical features, complications and predictors of Kasabach-Merritt phenomenon (KMP) associated with Kaposiform haemangioendothelioma (KHE). OBJECTIVES: To determine the clinical characteristics present at diagnosis and to identify features that may aid clinicians in managing KHE. METHODS: We conducted a cohort study of 146 patients diagnosed with KHE. RESULTS: KHE precursors or lesions were present at birth in 52·1% of patients. In 91·8% of patients, lesions developed within the first year of life. The median age at diagnosis of KHE was 2·3 months (interquartile range 1·0-6·0). The extremities were the dominant location, representing 50·7% of all KHEs. Among KHEs in the cohort, 63·0% were mixed lesions (cutaneous lesions with deep infiltration). Approximately 70% of patients showed KMP. A KHE diagnosis was delayed by ≥ 1 month in 65·7% of patients with KMP. Patients with KMP were more likely to have major complications than patients without KMP (P = 0·023). Young age (< 6 months), trunk location, large lesion size (> 5·0 cm) and mixed lesion type were associated with KMP in a univariate analysis. In the multivariate analysis, only age [odds ratio (OR) 11·9, 95% confidence interval (CI) 4·07-34·8; P < 0·001], large lesion size (OR 5·08, 95% CI 2·24-11·5; P < 0·001) and mixed lesion type (OR 2·96, 95% CI 1·23-7·13; P = 0·016) were associated with KMP. CONCLUSIONS: Most KHEs appeared before 12 months of age. KHEs are associated with various major complications, which can occur in combination and develop early in the disease process. Young age, large lesion size and mixed lesion type are important predictors of KMP.

Hashimoto's thyroiditis, nodular goiter or follicular adenoma combined with papillary thyroid carcinoma play protective role in patients.

Papillary thyroid carcinoma (PTC) is often combined with other types of thyroid disease, such as Hashimoto's thyroiditis(HT), nodular goiter(NG), Follicular adenoma(FA) and other types. However, the function of these diseases in PTC tumorigenesis and development is not well understood. In this research, 563 PTC patients were recruited and divided into two groups according to pathological diagnosis, namely simple PTC (PTC) and PTC combined with other thyroid diseases (PTC+). Clinicopathological characteristics and BRAFV600E mutation status were compared between PTC and PTC+. Our data showed that there was a statistically significant difference in gender (P=0.007), tumor diameter (5mm, P=0.012; 1cm, P=0.042), lymph node metastasis (P=0.000) and BRAFV600E mutation status (P=0.001) between PTC and PTC+. PTC+ patients have lower lymph node metastasis rate, even if PTC nodule diameter is larger than 5mm (P=0.005) or ≥1cm (P=0.049) or BRAFV600E is mutated (P=0.001). In conclusion, our study suggests that HT, NG and FA, are protective factors of PTC patients, and PTC+ patients have lower lymph node metastasis and BRAFV600E mutation rate compared with simple PTC patients.

Physiologic Changes in the Heart Following Cessation of Mechanical Ventilation in a Porcine Model of Donation After Circulatory Death: Implications for Cardiac Transplantation.

Hearts donated following circulatory death (DCD) may represent an additional source of organs for transplantation; however, the impact of donor extubation on the DCD heart has not been well characterized. We sought to describe the physiologic changes that occur following withdrawal of life-sustaining therapy (WLST) in a porcine model of DCD. Physiologic changes were monitored continuously for 20 min following WLST. Ventricular pressure, volume, and function were recorded using a conductance catheter placed into the right (N = 8) and left (N = 8) ventricles, and using magnetic resonance imaging (MRI, N = 3). Hypoxic pulmonary vasoconstriction occurred following WLST, and was associated with distension of the right ventricle (RV) and reduced cardiac output. A 120-fold increase in epinephrine was subsequently observed that produced a transient hyperdynamic phase; however, progressive RV distension developed during this time. Circulatory arrest occurred 7.6±0.3 min following WLST, at which time MRI demonstrated an 18±7% increase in RV volume and a 12±9% decrease in left ventricular volume compared to baseline. We conclude that hypoxic pulmonary vasoconstriction and a profound catecholamine surge occur following WLST that result in distension of the RV. These changes have important implications on the resuscitation, preservation, and evaluation of DCD hearts prior to transplantation.

Albumin-bilirubin versus Child-Pugh score as a predictor of outcome after liver resection for hepatocellular carcinoma.

BACKGROUND: The Child-Pugh (CP) score is used widely to assess liver function and predict postoperative outcomes in patients with hepatocellular carcinoma (HCC). Recently, the albumin-bilirubin (ALBI) score has been validated as a predictor of overall survival in these patients. This study aimed to compare the ability of the ALBI and CP scores to predict outcomes in patients with HCC after liver resection with curative intent. METHODS: Consecutive patients who underwent liver resection with curative intent for HCC between January 2007 and July 2013 were included in this retrospective study. The performance of the ALBI score in predicting postoperative liver failure (PHLF) and long-term survival was compared with that of the CP score. RESULTS: A total of 1242 patients were enrolled. Of these, 166 (13·4 per cent) experienced PHLF. The area under the receiver operating characteristic (ROC) curve of the ALBI score for predicting PHLF was greater than that of the CP score (0·723 versus 0·607; P < 0·001). Similar to findings for CP grade, the incidence and severity of PHLF increased with increasing ALBI grade. The ALBI grade stratified patients into at least two distinct overall survival cohorts (P < 0·001), whereas the CP grade did not. The ALBI grade also classified patients with CP grade A disease into two distinct overall survival cohorts (P < 0·001), and overall survival rates in the group with poorer survival were similar to those in the majority of patients with CP grade B disease. Both CP and ALBI scores had low power in predicting disease-free survival. CONCLUSION: The ALBI grade predicted PHLF and overall survival in patients with HCC undergoing liver resection with curative intent more accurately than the CP grade.

The CHRM3 gene is implicated in abnormal thalamo-orbital frontal cortex functional connectivity in first-episode treatment-naive patients with schizophrenia.

BACKGROUND: The genetic influences in human brain structure and function and impaired functional connectivities are the hallmarks of the schizophrenic brain. To explore how common genetic variants affect the connectivities in schizophrenia, we applied genome-wide association studies assaying the abnormal neural connectivities in schizophrenia as quantitative traits. METHOD: We recruited 161 first-onset and treatment-naive patients with schizophrenia and 150 healthy controls. All the participants underwent scanning with a 3 T-magnetic resonance imaging scanner to acquire structural and functional imaging data and genotyping using the HumanOmniZhongHua-8 BeadChip. The brain-wide association study approach was employed to account for the inherent modular nature of brain connectivities. RESULTS: We found differences in four abnormal functional connectivities [left rectus to left thalamus (REC.L-THA.L), left rectus to right thalamus (REC.L-THA.R), left superior orbital cortex to left thalamus (ORBsup.L-THA.L) and left superior orbital cortex to right thalamus (ORBsup.L-THA.R)] between the two groups. Univariate single nucleotide polymorphism (SNP)-based association revealed that the SNP rs6800381, located nearest to the CHRM3 (cholinergic receptor, muscarinic 3) gene, reached genomic significance (p = 1.768 × 10-8) using REC.L-THA.R as the phenotype. Multivariate gene-based association revealed that the FAM12A (family with sequence similarity 12, member A) gene nearly reached genomic significance (nominal p = 2.22 × 10-6, corrected p = 0.05). CONCLUSIONS: Overall, we identified the first evidence that the CHRM3 gene plays a role in abnormal thalamo-orbital frontal cortex functional connectivity in first-episode treatment-naive patients with schizophrenia. Identification of these genetic variants using neuroimaging genetics provides insights into the causes of variability in human brain development, and may help us determine the mechanisms of dysfunction in schizophrenia.

[Comparison of the prognosis after hepatic resection for patients with Barcelona Clinical Liver Cancer Stage B hepatocellular carcinoma].

Objective: To compare the efficacy of hepatic resection (HR) in patients with Barcelona Clinical Liver Cancer (BCLC) Stage B hepatocellular carcinoma (HCC) and examine how that efficacy has changed over time in a large medical center. Methods: A consecutive sample of 918 patients with preserved liver function and large and/or multinodular HCC who were treated by initial HR were divided into three groups: those with a single tumor ≥5 cm in diameter (n=582), 2-3 tumors with a maximum diameter>3 cm (n=223), or>3 tumors of any diameter (n=113). Hospital mortality and overall survival (OS) in each group were compared for the years 2001-2007 and 2008-2013. Results: Patients with >3 tumors showed the highest incidence of hospital mortality of all groups (P<0.05). Kaplan-Meier survival analysis showed that OS varied across the three groups as follows: single tumor>2-3 tumors >3+ tumors (all P<0.05). OS rate at 5 years ranged from 24% to 41% in all three groups for the period 2001-2007, and from 35% to 46% for the period 2008-2013. OS was significantly higher during the more recent 6-year period in the entire patient population, those with single tumor, and those with 3+ tumors (all P<0.05). However, in patients with 2-3 tumors, OS was only slightly higher during the more recent 6-year period (P=0.084). Conclusions: Prognosis of three types of HCC was different. Patients with >3 tumors show the highest hospital mortality and lowest OS after HR. OS has been improving for all three types of HCC at our medical center as a consequence of improvements in surgical technique and perioperative management.

The use of propranolol in the treatment of infantile haemangiomas: an update on potential mechanisms of action.

Currently, propranolol is the preferred treatment for problematic proliferating infantile haemangiomas (IHs). The rapid action of propranolol has been shown to be especially dramatic in IHs involving dyspnoea, haemodynamic compromise, palpebral occlusion or ulceration. Another remarkable aspect of propranolol treatment revealed that the growth of the IHs was not only stabilized, but also that the improvement continued until complete involution was achieved, leading to a considerable shortening of the natural course of IH. However, the mechanisms underlying the effects of propranolol have not been fully elucidated. Recent studies have offered evidence of a variety of mechanisms. These include the promotion of pericyte-mediated vasoconstriction, the inhibition of vasculogenesis and catecholamine-induced angiogenesis, the disruption of haemodynamic force-induced cell survival, and the inactivation of the renin-angiotensin system. This review summarizes these mechanisms and the new concepts that are emerging in this area of research. Moreover, several molecular mechanisms by which propranolol may modify neovascularization in IH have also been proposed. The antihaemangioma effect of propranolol may not be attributable to a single mechanism, but rather to a combination of events that have not yet been elucidated or understood. Further studies are needed to evaluate and verify these mechanisms to gain a greater understanding of the effects of the intake of propranolol on haemangioma involution.

The association of cytotoxic T-lymphocyte antigen-4 + 49A/G and CT60 polymorphisms with type 1 diabetes and latent autoimmune diabetes in Chinese adults.

OBJECTIVE: The aim of this study was to investigate the association of cytotoxic T-lymphocyte antigen-4 (CTLA-4) + 49A/G and CT60 polymorphisms with latent autoimmune diabetes in adults (LADA) and the genetic differences between LADA, type 1 diabetes (T1DM), and type 2 diabetes (T2DM) in a Chinese population. SUBJECTS: A total of 231 LADA, 402 T1DM, and 330 T2DM patients as well as 482 nondiabetic controls were recruited in the study. METHODS: CTLA-4 + 49A/G and CT60 polymorphisms were analyzed by polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP). The level of glutamic acid decarboxylase antibodies (GADAs) was detected by a radioligand binding assay. RESULTS: The CTLA-4 + 49A/G risk genotype GG was most frequent in T1DM patients (45.3%), followed by LADA patients (44.2%) and T2DM patients (38.8%). Significantly higher frequencies of the risk genotype GG were observed in the T1DM (OR = 1.532, 95% CI 1.168-2.010, P = 0.002) and LADA patients (OR = 1.464, 95% CI 1.063-2.017, P = 0.019). The frequencies of the CTLA-4 CT60 risk genotype GG were 65.2, 61.9, 58.5, and 56.4% in the T1DM, LADA, T2DM, and control groups, respectively. The CTLA-4 CT60 GG risk genotypes were only associated with T1DM (OR = 1.445, 95% CI 1.1-1.898, P = 0.008). Compared with controls, patients having a high titer of GADA (GADA ≥ 180 IU/ml) had higher frequencies of the GG risk genotype of CTLA-4 + 49 A/G (49.4% vs. 35.1% OR = 1.807, 95% CI 1.125-2.903, P = 0.014), but there was no difference between patients having a low titer of GADA and controls. CONCLUSION: The CTLA-4 + 49 A/G polymorphism confers genetic susceptibility to LADA and T1DM, while the CTLA-4 CT60 polymorphism is only associated with T1DM in Chinese population. The CTLA-4 + 49 A/G genotype distribution in LADA is associated with the GADA level.

PEG-coated irinotecan cationic liposomes improve the therapeutic efficacy of breast cancer in animals.

BACKGROUND: Breast cancer is the most frequently diagnosed cancer and the leading cause of cancer death among females owing. AIM: This study aimed to construct a kind of PEG-coated irinotecan cationic liposomes for investigating its efficacy and mechanism of action in the treatment of breast cancer in preclinical models. MATERIALS AND METHODS: Evaluations were performed on the MDA-MB231 breast cancer cells, the xenografted MDA-MB231 cancer cells in Female nude mice and Sprague-Dawley (SD) rat. The liposomes were characterized through assays of cytotoxicity, intracellular uptake, nuclei morphology, antitumor activities, pharmacokinetics and tissue distribution. RESULTS: The zeta potential of PEG-coated irinotecan cationic liposomes was approximately 23 mV. The PEG-coated irinotecan cationic liposomes were approximately 66nm in diameter, significantly increased the intracellular uptake of irinotecan, and showed strong inhibitory effect on MDA-MB231 breast cancer cells. A significant antitumor efficacy in the xenografted MDA-MB231 breast cancer cells in nude mice was evidenced by intravenous administration of PEG-coated irinotecan cationic liposomes. PEG-coated irinotecan cationic liposomes also improved the irinotecan blood circulation time and showed an enhanced drug concentration in tumor. CONCLUSIONS: PEG-coated irinotecan cationic liposomes had significant inhibitory effect against breast cancer in vitro and in vivo, hence providing a new strategy for treating breast cancer.

Flux focusing with a superconducting nanoneedle for scanning SQUID susceptometry.

A nanofabricated superconducting quantum interference device (nano-SQUID) is a direct and sensitive flux probe used for magnetic imaging of quantum materials and mesoscopic devices. Due to the functionalities of superconductive integrated circuits, nano-SQUIDs fabricated on chips are particularly versatile, but their spatial resolution has been limited by their planar geometries. Here, we use femtosecond laser 3-dimensional (3D) lithography to print a needle onto a nano-SQUID susceptometer to overcome the limits of the planar structure. The nanoneedle coated with a superconducting shell focused the flux from both the field coil and the sample. We performed scanning imaging with such a needle-on-SQUID (NoS) device on superconducting test patterns with topographic feedback. The NoS showed improved spatial resolution in both magnetometry and susceptometry relative to the planarized counterpart. This work serves as a proof-of-principle for integration and inductive coupling between superconducting 3D nanostructures and on-chip Josephson nanodevices.