[Effect of TFF3 on tight junction protein in eosinophilic chronic sinusitis and its related mechanism].

Objective: To study the effect of trefoil factor family (TFF) 3 on the expression of tight junctions (TJs) in the nasal mucosa epithelium of eosinophilic chronic rhinosinusitis (eCRS) and its mechanism. Methods: From September to December 2020, eligible patients from the Department of Otorhinolaryngology of the First Affiliated Hospital of Nanchang University were recruited, including 11 control patients and 37 patients with chronic rhinosinusitis with nasal polyps (CRSwNP), from whom nasal mucosa and nasal polyp tissue samples were collected. Immunohistochemistry (IHC) was used to detect the localization and expression intensity of TFFs (TFF1, TFF2 and TFF3) and TJs (occudin, claudin-1 and ZO-1) in nasal mucosa. Real-time fluorescence quantitative polymerase chain reaction (RT-qPCR) and western blot (WB) were used to detect the mRNA and protein expression. A cell model of tight junction injury in human nasal epithelial cells (HNECs) through stimulation with interleukin (IL)-13 was also established. The optimal modeling concentration and time for HNECs were determined, which were subsequently treated with TFF3 and/or a phosphoinositide 3-kinase (PI3K)-specific inhibitor (LY294002). Finally, RT-qPCR and WB were used to assess the effects of TFF3 on tight junctions and the PI3K/serine/threonine kinase (Akt) signaling pathway. Data were analyzed statistically using GraphPad Prism 7 software. Results: IHC results showed that the expression of TFF1 and TFF3 in nasal mucosa of eCRS group was significantly higher than that of control group (t=4.62, P=0.002; t=5.89, P<0.001), respectively, mainly expressed in goblet cell. The expression of occludin, claudin-1 and ZO-1 in the nasal mucosa of the eCRS group was lower than that of the control group (occludin t=3.98, P=0.019; claudin-1 t=5.15, P=0.002; ZO-1 t=5.42, P=0.001), respectively. WB results showed that the expression of TFF3 in non-eosinophilic chronic sinusitis (Non-eCRS) group and eCRS group was higher than that in the control group (t=3.62, P=0.036; t=5.93, P<0.001). The expression of occludin, claudin-1 and ZO-1 in eCRS group was lower than that in the control group (occludin t=5.14, P=0.002; claudin-1 t=6.35, P<0.001; ZO-1 t=6.64, P<0.001), respectively. The RT-qPCR results showed that compared with the control group, the levels of TFF1 and TFF3 mRNA were increased in the nasal mucosal epithelium of the Non-eCRS and eCRS groups (TFF1 t=3.98, P=0.046, t=4.89, P=0.002; TFF3 t=3.50, P=0.044, t=6.78, P<0.001). There was no statistically significant difference in TFF2 mRNA levels between the Non-eCRS and eCRS groups (t=1.34, P=0.061; t=3.37, P=0.055). Compared with the control group, Non-eCRS and eCRS groups showed a decrease in the mRNA levels of occludin, claudin-1 and ZO-1 (occludin t=4.27, P=0.011, t=5.61, P=0.007; claudin-1 t=3.62, P=0.036, t=6.80, P<0.001; ZO-1 t=3.47, P=0.047, t=7.86, P<0.001). The mRNA levels of TFF3 and TJs in eCRS nasal mucosa tissue showed a moderate positive correlation (occludin r=0.661, claudin-1 r=0.614, ZO-1 r=0.548, all P<0.001); TFF1 showed a low degree of positive correlation with the expression of occludin, claudin-1 and ZO-1 (occludin r=0.467, P=0.040; claudin-1 r=0.362, P=0.012; ZO-1 r=0.425, P=0.025). The establishment of cell models showed that compared with normal HNECs, the mRNA expression of TFF3 was most significantly increased at a concentration of 50 ng/ml stimulated by IL-13 (t=3.72, P=0.013); The mRNA expression of occludin, claudin-1 and ZO-1 decreased (occludin t=3.18, P=0.031; claudin-1 t=3.86, P=0.010; ZO-1 t=5.16, P=0.002). The expression of TFF3 mRNA increased most significantly after 15 hours of IL-13 stimulation (t=3.14, P=0.034); The mRNA expression of occludin, claudin-1 and ZO-1 decreased (occludin t=3.97, P=0.010; claudin-1 t=4.78, P=0.004; ZO-1 t=5.16, P=0.004). TJs damage model could be established by treating HNECs with 50 ng/ml IL-13 for 15 hours. Intervention experiments showed that compared with the IL-13 group, the IL-13+TFF3 group showed an increase in TJs mRNA expression (occludin t=6.10, P=0.009; claudin-1 t=5.90, P=0.013; ZO-1 t=9.44, P=0.007). Compared with the IL-13 group, the expression of TJs protein in the IL-13+TFF3 group increased (occludin t=3.23, P=0.013; claudin-1 t=9.40, P=0.017; ZO-1 t=2.23, P=0.032); The expression of TJs protein decreased in the IL-13+TFF3+LY294002 group (occludin t=4.73, claudin-1 t=8.77, ZO-1 t=3.51, all P<0.001). Compared with the IL-13+TFF3 group, the IL-3+TFF3+LY294002 group showed a decrease in PI3K and p-Akt/Akt protein expression (PI3K t=13.29, p-Akt/Akt t=10.30, all P<0.001). The increased mRNA and protein expression of occludin, claudin-1 and ZO-1 induced by TFF3 were also inhibited by LY294002. Conclusion: TFF3 can up-regulate the expression of occludin, claudin-1, and ZO-1 through PI3K/Akt pathway, and has a certain protective effect on the nasal mucosal epithelial barrier, providing a new idea for treating eCRS.

[Clinicopathological and gene mutation characteristics of uterine carcinosarcoma].

To explore the clinicopathological characteristics, immunophenotype, diagnosis and differential diagnosis of uterine carcinosarcoma (UCS), and to explore the gene mutation characteristics and tumor mutation burden (TMB) of UCS. The clinical imaging, pathomorphological data and immunohistochemical expression of 4 cases of UCS, which were archived in the Department of Pathology of the Second Affiliated Hospital of Soochow University from January 2021 to May 2022 were retrospectively analyzed. All exon groups of 4 cases of UCS were sequenced. All the 4 patients were female, aged 47-81 years. The maximum diameter of the tumor was 4.0-13.0 cm, and the boundary was unclear. Microscopically, the tumor was composed of malignant epithelium and sarcoma. Immunohistochemistry showed that the epithelial components of 4 patients expressed broad-spectrum cytokeratin (AE1/E3), the sarcoma components expressed Vimentin, PAX8, ER, PR were expressed to varying degrees, and Ki-67 positive index was high (60%-90%). There were 3 p53 missense mutations, 1 nonsense mutation, 4 MLH1, PMS2, MSH2, MSH6 were positive and PD-L1 was negative. The sequencing results of the whole exon group of 4 UCS patients showed that TP53, BCL9L, BRD4, CLTCLI, PSMD1I, PLEC genes showed a high mutation ratio, which was 3/4, 2/4, 2/4, 2/4, 2/4, 2/4, respectively. TMB analysis showed that the TMB of 4 cases of UCS was<5 mut/Mb. UCS is a rare and highly malignant endometrial tumor. The sequencing results of the whole exon group suggested that TP53, BCL9L, BRD4 and other genes had high mutation rates, suggesting that the occurrence and development of UCS may be closely related to Wnt signaling pathway. Molecular typing indicated that 3 cases of UCS were of high copy number type/p53 mutation type, and 1 case had POLD1 mutation. Microsatellite stability, low PD-L1 expression and TMB results suggested that UCS patients have no obvious advantage in immunotherapy.

[CT perfusion combined with energy spectrum imaging to evaluate the short-term efficacy of bronchial arterial chemoembolization for lung cancer].

Objective: To evaluate the clinical value of dynamic volumetric CT perfusion combined with energy spectrum imaging in bronchial arterial chemoembolization (BACE) in patients with lung cancer. Methods: The data of 31 patients with lung cancer confirmed by pathology and treated with BACE in Lishui Central Hospital from January 2018 to February 2022 were retrospectively collected, including 23 men and 8 women, aged 31-84 (67) years. All patients received perfusion scans of lesion sites within 1 week before surgery and 1 month after surgery. We collected and compared the changes in preoperative and postoperative perfusion parameters such as blood flow (BF), blood volume (BV), mean through time (MTT), permeability surface (PS) and energy spectrum parameters including arterial phase CT value (CTA), venous phase CT value (CTV), arterial phase iodine concentration (ICA), venous phase of iodine concentration (ICV), arterial standardization iodine concentration (NICA), and intravenous standardized iodine concentration (NICV) to confirm the significance of these parameters in evaluating the short-term efficacy of BACE in the treatment of advanced lung cancer. Data normality was tested using the Kolmogorov-Smirnov test and normally distributed measurement data are expressed here as mean ± standard deviation; the independent-samples t-test was used for comparisons between two groups. The measurement data that were not normally distributed are expressed as median (interquartile interval) [M (Q1, Q3)], and the comparison between the two groups used the Kruskal-Wallis test. Count data are expressed as cases (%), and comparisons between groups used the χ2 test. Results: The objective response rate (ORR) and disease control rate (DCR) at 1 month after BACE were 54.8% (17/31) and 96.8% (30/31), respectively. CT perfusion parameters and energy spectrum parameters of patients before and after BACE treatment were compared. The results showed that BF, BV, MTT, ICA, ICV and NICV were significantly decreased after BACE treatment compared with before treatment, and the differences were statistically significant[58.06 (40.47,87.22) vs.23.57(10.92, 36.24) ml·min-1·100g-1,3.33(2.86,6.09) vs.2.12(1.96,3.61)ml/100g,2.70(2.19,3.88) vs.1.53 (1.12,2.25)s, 3.51 (3.11,4.14)vs.1.74 (1.26,2.50)mg/ml,2.00 (1.30,2.45) vs.1.32(0.92,1.76)mg/ml,0.51(0.42,0.57) vs.0.33(0.23,0.39)](all P<0.05). At the same time, compared with the non-remission group, the study results showed that the difference of parameters in remission group before and after BACE was more obvious, including ΔBF, ΔBV, ΔMTT, ΔPS, ΔCTA, ΔCTV, ΔICA, ΔICV, ΔNICA, ΔNICV were significantly increased, and the difference was statistically significant [36.82(32.38, 45.34) vs.9.50(-1.43, 12.34) ml·min-1·100g-1,4.46(2.52, 5.79) vs.0.22(-0.76, 4.09) ml/100g,4.22(2.25, 6.77) vs.0.43(-2.53, 1.88) s,10.07 (2.89, 13.13) vs.-2.01(-6.77, 4.28) ml·min-1·100g-1,14.22(11.88, 20.57) vs.4.18(-5.25, 6.37) HU, 34.6(14.88, 43.15) vs.11.60(0.26, 25.05) HU,0.95(0.54, 1.47) vs.0.11(0.20, 0.59) mg/ml,1.57(1.10, 2.38) vs. 0.26(-0.21, 0.63) mg/ml,0.05(0.03, 0.08) vs.-0.02(-0.04, 0.01),0.18(0.13, 0.21)vs. 0.11(-0.06, 0.16)](all P<0.05). Conclusions: CT perfusion combined with spectral imaging could effectively evaluate the changes in tumor vascular perfusion in patients with advanced lung cancer before and after BACE treatment, which has important value in judging the short-term efficacy after treatment.

[Fontan-associated liver disease current status and transplantation consideration].

Fontan-associated liver disease (FALD) is one of the main complications after the Fontan procedure, manifesting mostly as liver fibrosis and even cirrhosis, with a high incidence rate and a lack of typical clinical symptoms that seriously affect patient prognosis. The specific cause is unknown, although it is considered to be associated with long-term elevated central venous pressure, impaired hepatic artery blood flow, and other relevant factors. The absence of association between laboratory tests, imaging data, and the severity of liver fibrosis makes clinical diagnosis and monitoring difficult. A liver biopsy is the gold standard for diagnosing and staging liver fibrosis. The most important risk factor for FALD is time following the Fontan procedure; therefore, it is recommended to do a liver biopsy 10 years after the Fontan procedure and to be cautious for the presence of hepatocellular carcinoma. Combined heart-liver transplantation is a recommended choice with favorable outcomes for patients with Fontan circulatory failure and severe hepatic fibrosis.

[Clinical effects of island posterior femoral composite tissue flaps in the repair of sinus cavity pressure ulcers in the areas of ischial tuberosity and greater trochanter].

Objective: To explore the clinical effects of island posterior femoral composite tissue flaps in the repair of sinus cavity pressure ulcers in the areas of ischial tuberosity and greater trochanter. Methods: The retrospective observational study was conducted. From December 2018 to December 2021, 23 patients with sinus cavity pressure ulcers in the areas of ischial tuberosity and greater trochanter who met the inclusion criteria were admitted to Ganzhou People's Hospital, including 16 males and 7 females, aged 45 to 86 years. The size of pressure ulcers in ischial tuberosity ranged from 1.5 cm×1.0 cm to 8.0 cm×5.0 cm, and the size of pressure ulcers in greater trochanter ranged from 4.0 cm×3.0 cm to 20.0 cm×10.0 cm before debridement. After treatment of underlying diseases, debridement and vacuum sealing drainage for 5 to 14 days were performed. All the wounds were repaired by island posterior femoral composite tissue flaps, with area of 4.5 cm×3.0 cm-24.0 cm×12.0 cm, pedicle width of 3-5 cm, pedicle length of 5-8 cm, and rotation radius of 30-40 cm. Most of the donor site wounds were sutured directly, and only 4 donor site wounds were repaired by intermediate thickness skin graft from the contralateral thigh. The survival of composite tissue flaps, wound healing of the donor and recipient sites and the complications were observed. The recurrence of pressure ulcers, and the appearance and texture of flaps were observed during follow-up. Results: A total of 32 wounds in 23 patients were repaired by island posterior femoral composite tissue flaps (including 3 fascio subcutaneous flaps, 24 fascial flaps+fascio subcutaneous flaps, 2 fascial flaps+fascial dermal flaps, 2 fascial flaps+fascio subcutaneous flaps+femoral biceps flaps, and one fascial flap+fascio subcutaneous flap+gracilis muscle flap). Among them, 31 composite tissue flaps survived well, and a small portion of necrosis occurred in one fascial flap+fascio subcutaneous flap post surgery. The survival rate of composite tissue flap post surgery was 96.9% (31/32). Twenty-nine wounds in the recipient sites were healed, and 2 wounds were torn at the flap pedicle due to improper postural changes, and healed one week after bedside debridement. One wound was partially necrotic due to the flap bruising, and healed 10 days after re-debridement. Thirty-one wounds in the donor sites (including 4 skin graft areas) were healed, and one wound in the donor site was torn due to improper handling at discharge, and healed 15 days after re-debridement and suture. The complication rate was 12.5% (4/32), mainly the incision dehiscence of the flap pedicle and the donor sites (3 wounds), followed by venous congestion at the distal end of flap (one wound). During the follow-up of 3 to 24 months, the pressure ulcers did not recur and the flaps had good appearance and soft texture. Conclusions: The island posterior femoral composite tissue flaps has good blood circulation, large rotation radius, and sufficient tissue volume. It has a high survival rate, good wound healing, low skin grafting rate in the donor site, few postoperative complications, and good long-term effect in the repair of sinus cavity pressure ulcers in the areas of ischial tuberosity and greater trochanter.

Discovery and insights from DSX mission's high-power VLF wave transmission experiments in the radiation belts.

Space weather phenomena can threaten space technologies. A hazard among these is the population of relativistic electrons in the Van Allen radiation belts. To reduce the threat, artificial processes can be introduced by transmitting very-low-frequency (VLF) waves into the belts. The resulting wave-particle interactions may deplete these harmful electrons. However, when transmitting VLF waves in space plasma, the antenna, plasma, and waves interact in a manner that is not well-understood. We conducted a series of VLF transmission experiments in the radiation belts and measured the power and radiation impedance under various frequencies and conditions. The results demonstrate the critical role played by the plasma-antenna-wave interaction around high-voltage space antennae and open the possibility to transmit high power in space. The physical insight obtained in this study can provide guidance to future high-power space-borne VLF transmitter developments, laboratory whistler-mode wave injection experiments, and the interpretation of various astrophysical and optical phenomena.

[Clinicopathological features of diffuse leptomeningeal glioneuronal tumor].

Objective: To investigate the clinicopathological features, diagnosis and prognosis of diffuse leptomeningeal glioneuronal tumor (DLGNT). Methods: Five cases of DLGNT diagnosed from January 2016 to January 2020 were collected from Xuanwu Hospital, Capital Medical University. The clinical features, histopathologic characteristics, immunohistochemical and molecular genetic findings and prognosis were analyzed and the relevant literature was reviewed. Results: The five patients (two males and three females) were aged 2 to 52 years (median 11 years), and had history of increased intracranial pressure (headache and vomiting) or limb weakness. Three of them were younger than 16 years of age. The imaging studies showed diffuse intracranial and intraspinal nodular leptomeningeal thickening and enhancement, with or without parenchymal involvement. At times there were associated small cyst-like lesions. Imaging interpretations were inflammatory lesions in three cases and space occupying lesions in two. Microscopically, in three cases the tumors showed low to moderate cellularity, consisting of relatively monomorphous oligodendrocyte-like cells arranged in small nests or diffusely distribution. No mitosis and necrosis were observed. In two cases there were increased cellularity with a diffuse honeycomb pattern. The tumor showed mild to moderate polymorphism with hyperchromatic nuclei. Mitosis, endothelial vascular proliferation and glomeruloid vessels were seen. Necrosis was absent. The tumor cells in all five cases were positive for synaptophysin,Olig2 and negative for IDH1 and H3 K27M. GFAP was focally positive in four cases and only one case expressed NeuN partly. The Ki-67 labeling index was 1%-35%. BRAF fusion was detected in four cases. Genetic analysis showed solitary 1p deletion in two cases (2/5), while all cases were negative for 1p/19q co-deletion (0/5). The five patients were followed up for 13 to 28 months (median 15 month). One patient died after 27 months. There was no evidence of tumor progression in the remaining four patients. Conclusions: DLGNT is rare and easily confused with other central nervous system tumors and inflammatory lesions. Therefore, the diagnosis of DLGNT should be made based on comprehensive information including imaging, morphologic and corresponding immunohistochemical examinations and molecular genetics to avoid misdiagnosis and delay in management.

CircRNA ZFR stimulates the proliferation of hepatocellular carcinoma through upregulating MAP2K1.

OBJECTIVE: The aim of the study was to illustrate the function of circRNA ZFR in aggravating the development of hepatocellular carcinoma (HCC) by upregulating MAP2K1. PATIENTS AND METHODS: CircRNA ZFR levels in 62 paired HCC and paracancerous species were detected. The influence of circRNA ZFR on clinical data of HCC patients was analyzed. After the overexpression or knockdown of circRNA ZFR, changes in viability and clonality of Bel-7402 and Hep3B cells were assessed, respectively. The involvement of circRNA ZFR/MAP2K1 axis in the development of HCC was explored through Luciferase assay and rescue experiments. RESULTS: CircRNA ZFR was highly expressed in HCC species than the paracancerous ones. Higher level of circRNA ZFR predicted more advanced tumor grading of HCC. The knockdown of circRNA ZFR attenuated the proliferative ability of HCC cells, while the overexpression of circRNA ZFR obtained opposite results. MAP2K1 level was positively correlated to that of circRNA ZFR. Luciferase assay uncovered that circRNA ZFR can be targeted by MAP2K1 through specific binding sites. In addition, the overexpression of MAP2K1 could reverse the influence of silenced circRNA ZFR on proliferative ability of HCC cells. CONCLUSIONS: CircRNA ZFR is upregulated in HCC and closely linked to tumor grading. It promotes proliferative ability in HCC by upregulating MAP2K1.

Using an Online Vaccination Registry to Confirm Tetanus Status in Children with Tetanus-prone Wounds.

INTRODUCTION: Tetanus vaccination status is an important consideration for emergency physicians managing patients with tetanus-prone wounds. Physicians must identify at-risk patients, but vaccination histories are often unknown and commonly lack documentation. The study objective was to determine the potential impact of an online immunization registry (Florida SHOTS - State Health Online Tracking System) on the appropriate administration of tetanus prophylaxis for pediatric patients managed in the emergency department (ED). METHODS: We conducted a retrospective review of all patients less than 18 years old who received ED tetanus prophylaxis at two separate sites between January 2011-May 2015. The Florida SHOTS database was accessed to determine vaccination status for each patient in the study group at the time of the encounter. We compared vaccination status for each patient, as documented in the electronic health record (EHR), with Florida SHOTS data to determine whether tetanus prophylaxis was indicated. The proportion of patients receiving tetanus prophylaxis in the ED, who were subsequently identified as up to date with tetanus vaccination per Florida SHOTS, was determined. RESULTS: We identified 743 patients who received ED tetanus prophylaxis. Forty-three (6%) were listed as "up to date" on the EHR and 656 (93%) were listed as "not up to date." In comparison, 209 (30%) of the study group were identified as "up to date" via Florida SHOTS, and 477 (70%) were not. We accessed the Florida SHOTS record retrospectively to determine whether the vaccine was required. It was determined that 174 (25%) of the patients received tetanus prophylaxis unnecessarily as they were already up to date per Florida SHOTS documentation. CONCLUSION: Twenty-five percent of patients vaccinated for tetanus in the ED could have been spared if Florida SHOTS data had been used by providers at the time of the encounter. Access to Florida SHOTS provides valuable information regarding vaccination status that impacts patient care and resource utilization in the ED.

MED27 promotes malignant behavior of cells by affecting Sp1 in breast cancer.

OBJECTIVE: The aim of this study was to investigate the expression of mediator complex subunit 27 (MED27) in breast cancer (BC) and explore its effects on the proliferation and apoptosis of BC cells. PATIENTS AND METHODS: The expression of MED27 in 60 BC tissues and para-cancer tissues was detected. Based on the significantly high expression level of MED27 in tumors, the tumor samples were divided into high-expression group and low-expression group according to the median standard, with 30 samples in each group. Then, the association between MED27 expression and clinicopathological features of patients was analyzed. The correlation between MED27 expression and survival time of patients was estimated using the Kaplan-Meier method. Next, the expression level of MED27 in cells was also measured using qRT-PCR assay. In vitro study, si-MED27 was designed to interfere with the expression of MED27 in MDA-MB-231 cells. To further explore the mechanism of MED27 in BC, the expression level of SP1 in cells was examined after different treatments. RESULTS: In quantitative reverse transcription-polymerase chain reaction (qRT-PCR) assay, MED27 was found to be highly expressed in both BC tissues and cells. Then, the relationship between MED27 expression and clinical pathological data was statistically analyzed, and it was found that MED27 expression was correlated with tumor size and grade. In the 60-month follow-up and Kaplan-Meier analysis, patients with high expression of MED27 had a poor prognosis. In in vitro study, MED27 expression in cells was down-regulated by transfection with si-MED27. Western blot (WB) analysis suggested that si-MED27 could effectively reduce the protein expression level of MED27 in cells, and the specificity protein 1 (Sp1) expression was also limited. In CCK-8, clone formation and flow cytometry experiments, the proliferation of cells with low MED27/Sp1 expression was suppressed, while cell apoptosis was promoted. CONCLUSIONS: MED27 acted as an oncogene in BC. By affecting Sp1, MED27 could be a new therapeutic target for the treatment of BC.

[Differential population screening and efficacy analysis of (125)I implantation after radiofrequency ablation of primary liver cancer].

Objective: To investigate the clinical efficacy radiofrequency ablation (RFA) combined with (125)I radioactive seed implantation in treatment of hepatocellular carcinoma HCC with the tumor diameter 3-5 cm. Methods: One hundred patients with HCC diagnosed clinically or pathologically with Barcelona staging of B or C in Lishui Central Hospital from February 2012 to September 2017 were retrospectively analyzed. Of the included 100 cases, 89 were males and 11 were females with the mean age of 18-80 (57±11) years old.According to the treatment modality, the subjects were divided into control group (RFA, n=67) and combined group (RFA+(125)I, n=33). Patients in control group were only received RFA and cases in combined group received RFA plus sequenced with (125)I implantation therapy. The prognosis of progression free survival (PFS) and overall survival (OS) between the two groups were compared through the Kaplan-Meier curve and Log-rank test. Results: The median follow-up time period was 6-55 months in the last follow-up time point of Dec 30, 2017. The median PFS were 4-55 (23.0±4.7) and 1-53 (12.0±1.6) months for combined and control groups respectively with significant statistical difference (P=0.015). The median OS were 6-55 (42.0±7.9) and 2-55 (38.0±2.8) months for combined and control groups with the trend of improvement in combined group, but without statistical difference (P=0.444). Subgroup analysis further indicated that the PFS was significant improved in patients with residual tumor lesions who received the combined treatment (PFS: 18 vs 9 months, P=0.025). However, there was no statistical difference for PFS between the control and combined treatment groups for cases without residual tumor lesions after RAF treatment(P=0.685). Conclusions: PFS was obviously increased in HCC patients(tumor diameter 3-5 cm) who received(125)I implantation after radiofrequency ablation, especially for cases with residual tumor lesions.

Sodium-rich manganese oxide porous microcubes with polypyrrole coating as a superior cathode for sodium ion full batteries.

Highly conductive cathode material with enhanced Na+ diffusion kinetics is of great importance in the exploration of sodium ion batteries. In this work, Na0.91MnO2 porous microcube which is coated with highly conductive polypyrrole (PPy) is obtained. The high Na content in the layered sodium manganate oxide brings about wider interlayer distance resulting in high capacity and electrochemical kinetics. The higher sodium content of Na0.91MO2 makes capacity increase up to 50 mAh g-1 compared with Na0.7MnO2.05. Furthermore, the well-designed combination between porous structure and conductive PPy coating exhibits fast ion/electron transfer inside the electrode and high cycling stability. The PPy coated Na0.91MnO2 delivers a high initial capacity of 208 mAh g-1, encouraging capacity retention and rate capability. Based on the porous Na0.91MnO2@PPy cathode, the sodium ion full cells with puffed millet porous carbon anode show remarkably stable cycling and high-rate performances.

Effect of alprostadil on myocardial fibrosis in rats with diabetes mellitus via TGF-ß1/Smad signaling pathway.

OBJECTIVE: To observe the influence of alprostadil on myocardial fibrosis in rats with diabetes mellitus (DM) through the transforming growth factor beta-1 (TGF-ß1)/Smad signaling pathway. MATERIALS AND METHODS: Wistar rats were employed to induce models of DM (DM group), and alprostadil treatment group (ALPR group) and control group (NC group) were set up. After successful modeling, blood and myocardial tissues were collected from rats. Next, blood glucose level, liver function, and myocardial function were detected. In addition, hematoxylin-eosin (HE) assay was performed to determine pathological changes. The enzyme-linked immunosorbent assay (ELISA) was carried out to measure serum interleukin-6 (IL-6) and cardiac function indexes such as ejection fraction (EF), Reverse Transcription-Polymerase Chain Reaction (RT-PCR) and Western blotting, which were applied to measure the gene and protein expression levels of important molecules in the proliferation and differentiation of myocardial fibroblasts [including checkpoint kinase 1 (Chek1) and alpha-smooth muscle actin (α-SMA)] and the relevant pathway TGF-ß1/Smad2. RESULTS: The blood glucose level was increased in DM group (p<0.01), suggesting that modeling is successful. The tumor necrosis factor-alpha (TNF-α), IL⁃6, and IL-1 levels were higher in DM group than in NC group. DM group had significantly elevated serum content of alkaline phosphatase (ALP), alanine aminotransferase (ALT), and creatine kinase (CK), as well as left ventricular end-diastolic dimension (LVEDd) and left ventricular end-systolic dimension (LVESd), but it clearly decreased fractional shortening (FS) and EF in comparison with NC group. Besides, myocardial cells were orderly arranged in NC group, while myocardial fibrosis was observed in DM group. The results of RT-PCR showed that the levels of Collagen, Chek1, α-SMA, TGF-ß1, and Smad2 in myocardial fibroblasts were notably lowered in ALPR group, but evidently increased in DM group (p<0.05). According to Western blotting, there were evident decreases in the levels of TGF-ß1 and Smad2 in myocardial fibroblasts in ALPR group (p<0.05). The above results suggest that alprostadil represses the expression of the TGF-ß1/Smad2 signaling pathway and its relevant molecules, thus further suppressing the fibrosis of myocardial cells. CONCLUSIONS: Alprostadil treats myocardial fibrosis in DM rats by inhibiting the TGF-ß1/Smad2 signaling pathway.

Effect of feeding grape seed Proanthocyanidin extract on production performance, metabolic and anti-oxidative status of dairy cattle / Efeito da alimentação do extrato de semente de uva Proanthocyanidin sobre o desempenho da produção e o status metabólico e antioxidante de gado leiteiro

Aims to investigate the effects of grape seed proanthocyanidin extract (GSPE) on production performance, metabolism, and anti-oxidative status of Holstein dairy cattle in early lactation. Forty-eight multiparous Holstein dairy cattle were assigned to four groups (CON, G20, G40 and G80) and supplied with 0, 20, 40, and 80mg GSPE/kg of body weight/day. G20 significantly increased milk yield compared with other groups. Milk protein and non-fat-solids were increased in G20, G40 and G80 groups compared with the control group only at the 7th day during the experiment. No significant difference was observed in milk fat and somatic cell count, nor on parameters of energy metabolism in blood, liver function and kidney function between the four groups. There was no significant difference in glutathione peroxidase, superoxide dismutase, total antioxidant capacity, and hydrogen peroxide between the groups; but the malondialdehyde content of G20 significantly increased at day 14 in comparison with CON, and tended to increase at the 28th day. In conclusion, feeding 20mg GSPE/kg of body weight/day was associated with a significant increase in milk yield without detrimental effects on liver or kidney function and with substantial energy metabolism and antioxidant parameters improvement in early lactation dairy cattle.(AU)

O presente trabalho visa investigar os efeitos do extrato de semente de uva Proanthocyanidin (GSPE) sobre o desempenho da produção, o metabolismo e o status antioxidante de gado leiteiro Holstein em lactação precoce. Quarenta e oito vacas leiteiras multíparas Holstein foram divididas em quatro grupos (CON, G20, G40 e G80) e receberam 0, 20, 40 e 80mg de GSPE/kg de peso corporal/dia, respectivamente. O G20 aumentou significativamente o rendimento do leite em comparação com os outros grupos. A proteína e os sólidos não gordurosos do leite foram aumentados nos grupos G20, G40 e G80 somente no sétimo dia durante a experiência. Não foi observada diferença significativa na gordura do leite e na contagem de células somáticas, bem como nos parâmetros de metabolismo energético no sangue, na função hepática e na função renal entre os grupos em relação ao grupo controle. Não houve diferença significativa na glutationa peroxidase, na dimutase de superóxido, na capacidade antioxidante total e no peróxido de hidrogênio entre os grupos, mas o conteúdo malondialdeído do G20 aumentou significativamente no dia 14 em comparação com o CON, e tendia a aumentar no dia 28. Em conclusão, a alimentação de 20mg de GSPE/kg de peso corporal/dia foi associada a um aumento significativo no rendimento do leite, sem efeitos nocivos sobre a função hepática ou a renal, com o metabolismo de energia substancial e a melhoria dos parâmetros antioxidantes de gado leiteiro no início da lactação.(AU)

Disruption of glucocorticoid signalling in osteoblasts attenuates age-related surgically induced osteoarthritis.

OBJECTIVE: Aging is a major risk factor for osteoarthritis (OA). Skeletal expression and activity of the glucocorticoid-activating enzyme 11ß-hydroxysteroid-dehydrogenase type 1 increases progressively with age in humans and rodents. Here we investigated the role of endogenous osteocytic and osteoblastic glucocorticoid (GC) signalling in the development of osteoarthritic bone and cartilage damage in mice. METHODS: We utilized transgenic (tg) mice in which glucocorticoid signalling is disrupted in osteoblasts and osteocytes via overexpression of the glucocorticoid-inactivating enzyme, 11ß-hydroxysteroid-dehydrogenase type 2. Osteoarthritis was induced in 10- and 22-week-old male transgenic mice (tg-OA, n = 6/group) and their wildtype littermates (WT-OA, n = 7-8/group) by surgical destabilization of the medial meniscus (DMM). Sham-operated mice served as controls (WT- & tg-Sham, n = 3-5 and 6-8/group at 10- and 22-weeks of age, respectively). RESULTS: Sixteen weeks after DMM surgery, mice developed features of cartilage degradation, subchondral bone sclerosis and osteophyte formation. These changes did not differ between WT and tg mice when OA was induced at 10-weeks of age. However, when OA was induced at 22-weeks of age, cartilage erosion was significantly attenuated in tg-OA mice compared to WT-OA littermates. Similarly, subchondral bone volume (-5.2%, 95% confidence intervals (CI) -9.1 to -1.2%, P = 0.014) and osteophyte size (-4.0 mm2, 95% CI -7.5 to -0.5 mm2, P = 0.029) were significantly reduced in tg-OA compared to WT-OA mice. CONCLUSION: Glucocorticoid signalling in cells of the osteoblast lineage promotes the development of surgically-induced osteoarthritis in older, but not younger, male mice. These data implicate osteoblasts and osteocytes in the progression of DMM-OA, via a glucocorticoid-dependent and age-related pathway.

[Application of virtual reality in surgical treatment of complex head and neck carcinoma].

Objective: To investigate the application of virtual reality technology in the preoperative evaluation of complex head and neck carcinoma and he value of virtual reality technology in surgical treatment of head and neck carcinoma. Methods: The image data of eight patients with complex head and neck carcinoma treated from December 2016 to May 2017 was acquired. The data were put into virtual reality system to built the three-dimensional anatomical model of carcinoma and to created the surgical scene. The process of surgery was stimulated by recognizing the relationship between tumor and surrounding important structures. Finally all patients were treated with surgery. And two typical cases were reported. Results: With the help of virtual reality, surgeons could adequately assess the condition of carcinoma and the security of operation and ensured the safety of operations. Conclusions: Virtual reality can provide the surgeons with the sensory experience in virtual surgery scenes and achieve the man-computer cooperation and stereoscopic assessment, which will ensure the safety of surgery. Virtual reality has a huge impact on guiding the traditional surgical procedure of head and neck carcinoma.

Farnesyltransferase inhibitor FTI-277 inhibits PD-L1 expression on septic spleen lymphocytes and promotes spleen lymphocyte activation.

Farnesyltransferase inhibitors have been tested in clinical trials for the treatment of tumours. In sepsis, the binding of programmed death 1 (PD-1) to programmed death ligand 1 (PD-L1) promotes lymphocyte apoptosis and decreases cytokine expression, thus affecting survival rates. The PD-1/PD-L1 pathway plays an important role in chronic viral infection, bacterial infection and sepsis. However, the precise immunosuppressive and anti-inflammatory functions of this pathway remain poorly understood. In our previous study, the induction of sepsis by caecal ligation and puncture (CLP) resulted in increased farnesyltransferase activity and farnesylated protein levels in the spleen relative to sham treatment. However, the effect of inhibition of farnesyltransferase activity on overall survival rates in patients with sepsis and the specific signalling pathway involved remain to be investigated. In this study, mice with CLP-induced sepsis were treated with farnesyltransferase inhibitor (FTI-277), and PD-L1 expression on septic spleen lymphocytes was examined. Flow cytometric analysis revealed that PD-L1 is expressed constitutively on lymphocytes and that PD-L1 protein expression was up-regulated strongly following CLP. FTI-277 down-regulated PD-L1 mRNA and protein expression on septic spleen lymphocytes in a dose-dependent manner. This effect was associated closely with nuclear factor kappa B (NF-κB). In addition, the significant damping effect of FTI-277 on the PD-L1 signal promoted interferon (IFN)-γ secretion, interleukin (IL)-2 production and splenocyte proliferation in response to anti-CD3+ CD28+ antibodies in mice. Furthermore, FTI-277 reduced spleen lymphocyte apoptosis in septic mice. Therefore, FTI-277 regulates spleen lymphocyte activity via the PD-L1 signalling pathway, with significant anti-inflammatory effects attributable to suppression of the NF-κB pathway. Farnesyltransferase represents a valuable therapeutic target for the treatment of sepsis.