[Effect of sorafenib and prophylactic TACE for prevention of postoperative relapse in patients with liver cancer combined with microvascular invasion].

Objective: To study the effect of sorafenib and prophylactic transarterial chemoembolization (TACE) for prevention of postoperative relapse in patients with liver cancer combined with microvascular invasion (MVI) after using radical hepatectomy. Methods: A retrospective analysis was performed on 137 cases that underwent radical hepatectomy at the First Affiliated Hospital of Zhengzhou University from August 2015 to January 2018. Clinical data of liver cancer patients with MVI were diagnosed by postoperative pathology. General data of the three groups were analyzed. Kaplan-Meier was used to calculate the tumor-free survival rate. COX proportional hazards-model was used to analyze the independent risk factors for postoperative recurrence of liver cancer with MVI recurrence. Counting data was compared by x(2) test between groups, and log-rank test was used to compare the tumor-free survival rates. Results: A, B, and C groups had 49, 36, and 52 cases, respectively. General clinicopathological data of the three groups were not statistically significant. The postoperative tumor-free survival rates at 1-, 2-, and 3-years were 71.4%, 51.0%, 38.8%, 86.1%, 75.0%, 66.7%, and 82.7%, 75.0%, and 59.6% respectively in A, B, and C groups. Multivariate Cox proportional-hazards regression model showed that patients' age (HR = 0.622, P = 0.046), maximum tumor diameter (HR = 1.661, P = 0.033), prophylactic TACE (HR = 0.544, P = 0.019), and postoperative use of sorafenib (HR = 0.419, 0.222, 0.791, P = 0.007) were independent risk factors for postoperative recurrence of liver cancer with MVI. Conclusion: Sorafenib or prophylactic TACE use can significantly reduce the recurrence rate within 3 years after radical surgery in patients with liver cancer who were confirmed to have MVI by postoperative pathology.

MicroRNA-337-5p participates in the development and progression of osteosarcoma via ERBB, MAPK and VEGF pathways.

OBJECTIVE: To investigate the role of microRNA-337-5p in osteosarcoma (OS) and its underlying mechanism. PATIENTS AND METHODS: The microRNA (microRNA-337-5p) that may be related to OS development was screened out by GEO (Gene Expression Omnibus) database. Survival analysis and ROC curve were performed according to microRNA-337-5p expressions in OA patients. Besides, the correlation between microRNA-337-5p expression and clinical parameters was evaluated by Chi-square analysis. Cox regression analysis was performed to detect the relationship between the overall survival and clinical parameters of OA patients. Subsequently, enriched functions and pathways of microRNA-337-5p were predicted by GESA (gene enrichment sets analysis). MicroRNA-337-5p expression was detected in 65 OS tissue samples and 30 normal tissue samples by qRT-PCR (quantitative Real-Time Polymerase Chain Reaction). For in vitro experiments, after microRNA-337-5p mimics or microRNA-337-5p inhibitor was transfected into OS cells, proliferative and invasive abilities were detected by CCK-8 (Cell Counting Kit-8) and transwell assay, respectively. Finally, Western blot was used to explore the underlying mechanism of microRNA-337-5p in regulating OS. RESULTS: MicroRNA-337-5p was overexpressed in serum and tissue samples of OS patients, which was valuable in diagnosing OS. Besides, microRNA-337-5p expression was correlated with the overall survival and necrosis range of OA patients, whereas not correlated with age and sex. GESA indicated that microRNA-337-5p was enriched in ERBB, MAPK, and VEGF pathways. In vitro experiments indicated elevated proliferative and invasive abilities in MG63 and U2OS cells after microRNA-337-5p overexpression. Furthermore, increased expressions of ERBB2, Erk1/2, and VEGF121 were observed in OS cells after microRNA-337-5p overexpression. CONCLUSIONS: MicroRNA-337-5p is upregulated in OS tissues, which is an independent prognostic factor in OS. Overexpressed microRNA-337-5p can promote proliferative and invasive abilities of OS cells via activating ERBB, MAPK, and VEGF pathways.

[Effect of simplified and traditional Chinese character on accommodative microfluctuation in young adult myopes and emmetropes].

Objective: This study investigates the effect of simplified and traditional Chinese character on accommodative microfluctuation in young adult myopes and emmetropes. Methods: Prospective cohort study. Based on refractive errors, Young adult candidates (18-28 years) were classified into two groups based on their spherical equivalent degrees: emmetropes (n=18), myopes (n=18). Four different reading targets (12pt size simplified and traditional Chinese characters, and 8pt size simplified and traditional Chinese characters) were displayed on computer screen collectively for 135s. The accommodative microfluctuation of the candidates were measured using the free space Grand-Seiko WAM-5500 autorefractor. Results: The results indicated that the type of character (simplified and traditional) had significant influence on accommodative microfluctuation. For myopic candidates, the accommodative microfluctuation for traditional Chinese character was greater than that for simplified Chinese character [traditional Chinese character: (0.35±0.17) D, vs. simplified Chinese character: (0.29±0.11) D, t=2.556, P=0.017], however as for emmetropic candidates, the difference between the accommodative microflucuation for the two types of characters was of no statistical significance [traditional Chinese character: (0.24±0.11) D, vs. simplified Chinese character: (0.24±0.12) D, t=0.004, P=0.996]. There was a difference between emmetropic and myopic candidates in terms of accommodative microfluctuation for traditional Chinese character, myopes had greater accommodative microfluctuation than emmetropes (t=3.140, P=0.02). However the difference between emmetropic and myopic candidates in terms of accommodative microfluctuation for simplified Chinese character was of no statistical significance (t=1.866, P=0.066). Conclusions: The results of the study indicated that myopes were more susceptible than emmetropic in accommodative microfluctuation when reading traditional Chinese character of high spatial frequency. (Chin J Ophthalmol, 2018, 54: 288-293).

[Study on the difference of binocular accommodative response between atients with intermittent exotropia under different viewing condition].

Objective: To evaluate the accommodative response of patients with intermittent exotropia (IXT) objectively, and study the changes of accommodative response of intermittent exotropia patients when maintaining binocular fusion. Methods: The prospective cohort study was used in this study. Twenty-four patients diagnosed with basic intermittent exotropia who visited the eye hospital of Wenzhou Medical University during October 2016 through January 2017 together with 24 normal volunteers were included, the 48 participants aged from 10 to 27 years old. The participants were divided into the case group and the control group. There were 11 males and 13 females in the case group, and 7 males and 17 females in the control group. The Open-filed autorefractor WAM-5500 (Grand Seiko, Japan) was used to measure the accommodative response of each eye under binocular and monocular viewing conditions at 5 m and 40 cm respectively. During the measurement, patients wore full correction spectacles to achieve distant best-corrected visual acuity of both eyes. The accommodative responses of each eye under binocular and monocular viewing conditions at distance or near between fellow eyes and groups were compared. Results: Under near fixation (40cm) binocular viewing conditions, the accommodative response of the fixating eye (-1.915±0.301)D was different from the deviating eye -1.649(-2.020, -0.304)D in the case group (Z=-3.714, P<0.001). Under near fixation monocular viewing conditions, the accommodative response of the fixating eye (-1.653±0.271)D was also different from the deviating eye -1.565 (-2.031, -0.667)D in the case group (Z=-2.971, P=0.003). During binocular viewing, the asymmetric value of the accommodative response between both eyes of the case group was 0.389(0.102, 1.458)D which was more significant than the normal controls' 0.155(0.009, 0.573)D (Z=-3.505, P<0.001), but during monocular viewing, there was no significant difference between the groups (Z=-1.908, P=0.056). Under near viewing conditions, the variation value of the fixating eyes of the case group was -0.228(-0.796, 0.382)D, which was greater than the variation value -0.086(-0.606, 0.628)D of the right eye of the normal controls, such difference is of statistical significance (Z=-2.279, P=0.023). Under distance viewing conditions, there was no significant difference in the accommodative response between fixating eyes and deviating eyes in case group neither during monocular viewing nor binocular viewing (t=-1.525, -1.729, P>0.05). Besides, the asymmetric values of accommodative response between groups were not significantly different (Z=-1.433, P=0.152. Z=-0.938, P=0.348). Under distance viewing conditions, the changes in accommodative response of each eye during both monocular viewing and binocular viewing were not significantly different between case group and normal controls (Z=-0.041, P=0.967. Z=-1.433, P=0.152). Conclusions: The accommodative responses of the fixating eye and deviating eye of patients with intermittent exotropia were asymmetric under near fixation binocular viewing conditions, and the accommodative response of the deviating eye tends to decrease. Besides, the change of accommodative response of the patients with intermittent exotropia when maintaining binocular fusion is more significant than that of the normal controls. (Chin J Ophthalmol, 2018, 54: 55-61).

Oncogenic MCT-1 activation promotes YY1-EGFR-MnSOD signaling and tumor progression.

Tumor cells often produce high levels of reactive oxygen species (ROS) and display an increased ROS scavenging system. However, the molecular mechanism that balances antioxidative and oxidative stress in cancer cells is unclear. Here, we determined that oncogenic multiple copies in T-cell malignancy 1 (MCT-1) activity promotes the generation of intracellular ROS and mitochondrial superoxide. Overexpression of MCT-1 suppresses p53 accumulation but elevates the manganese-dependent superoxide dismutase (MnSOD) level via the YY1-EGFR signaling cascade, which protects cells against oxidative damage. Conversely, restricting ROS generation and/or targeting YY1 in lung cancer cells effectively inhibits the EGFR-MnSOD signaling pathway and cell invasiveness induced by MCT-1. Significantly, MCT-1 overexpression in lung cancer cells promotes tumor progression, necrosis and angiogenesis, and increases the number of tumor-promoting M2 macrophages and cancer-associated fibroblasts in the microenvironment. Clinical evidence further confirms that high expression of MCT-1 is associated with an increase in YY1, EGFR and MnSOD expression, accompanied by tumor recurrence, poor overall survival and EGFR mutation status in patients with lung cancers. Together, these data indicate that the MCT-1 oncogenic pathway is implicated in oxidative metabolism and lung carcinogenesis.

TC10ß/CDC42 GTPase activating protein is required for the growth of cortical neuron dendrites.

Neuronal morphogenesis plays an important role in neuronal development. TC10ß/CDC42 GTPase-activating protein (TCGAP) is known to be a brain-enriched multiple domain protein, but its role in neuronal development process remains poorly understood. In the present study, we showed that TCGAP positively regulated dendritic outgrowth and spine formation in developing cortical neurons. Knocking down TCGAP by RNA interference led to a decrease in the overall length of dendrite arbors and the number of dendrite branches both in vitro and in vivo. Overexpressing TCGAP in cultured cortical neurons increased dendritic outgrowth and branching. Moreover, overexpressing TCGAP lead to an increase of spine density while knocking-down TCGAP decreased spine density in vivo. The defect by downregulating TCGAP could be rescued by expressing a knock-down resistant form of TCGAP both in vivo and in vitro. In contrast, neither downregulating nor overexpressing TCGAP had any effect on axonal morphogenesis in primary cortical neuron cultures. Together, our findings suggest that TCGAP regulates neuronal morphogenesis in developing cortical neurons at both early and late stage.

T helper cells promote disease progression of osteoarthritis by inducing macrophage inflammatory protein-1γ.

OBJECTIVE: Immune cells are involved in the pathogenesis of osteoarthritis (OA). We examined the effects of T helper (Th) cells, which induce the expression of macrophage inflammatory protein (MIP-1γ), on the progression of OA. DESIGN: Using anterior cruciate ligament-transection (ACLT), we induced OA in one hind-leg knee joint of B6 mice. The CD4(+) T cells from splenocytes and synovium were flow-cytometrically and immunochemically evaluated, respectively. The knee joints were histologically assessed for manifestations of OA. MIP-1γ levels and nuclear factor-κB (NF-κB) in the knee joints were measured using enzyme-linked immunosorbent and immunoblotting assays, respectively; osteoclastogenesis was detected by tartrate-resistant acid phosphatase (TRAP) staining. The inflammatory responses and MIP-1γ expression were examined using immunohistochemistry. RESULTS: The number of CD4(+) T cells and the expression of interferon-γ (IFN-γ) increased during OA onset (30 days after ACLT) and then decreased at a later stage of OA (90 days after ACLT). Tissue damage induced by CD4(+) T cells was evident at the later stage. The activation of CD4(+) T cells induced the expression of MIP-1γ and NF-κB. The expression of MIP-1γ can be detected in synovium which CD4(+) T cells were infiltrated. The increased MIP-1γ expression caused an increase in the number of osteoclasts in joints. The regulation of CD4(+) T cells was accompanied by increased macrophage infiltration and matrix metalloproteinase (MMP)-9 expression. Histopathological examinations revealed that CD4(+) T cell knockout (CD4(-/-)) mice had less expression of MIP-1γ and slower cartilage degeneration than control mice had. CONCLUSIONS: CD4(+) T cells were activated during the onset of OA, but cartilage damage was more prominent at a later stage. CD4(+) T cells were involved in the pathogenesis of OA: they induced MIP-1γ expression and subsequent osteoclast formation.

Enucleation after fusion and activation enhances the development of reconstructed bovine embryos.

Effects of enucleation timing on enucleation rates, development and methylation levels of reconstructed bovine embryos were investigated. However, the enucleation rate of reconstructed embryos produced by the enucleation before fusion and activation (EBFA) was higher than that by the enucleation after fusion and activation (EAFA) procedure (80.7% vs. 59.1%, P<0.05). The blastocyst rate of reconstructed embryos cloned with ear fibroblasts in EBFA group was reduced (P<0.05) in comparison with that of EAFA group (24.6% vs. 34.4%). Two out of 11 recipients were pregnant and gave birth to two viable calves after transfer of 20 reconstructed EBFA embryos. Two out of seven recipients were pregnant and also gave birth to two calves, with one surviving, after transfer of 12 reconstructed embryos produced by EAFA procedure. Finally, the methylation level of satellite I gene of donor cells (69.8%) and reconstructed embryos in EBFA group (64.7%) were similar, which were both higher (P<0.05) than that of the reconstructed embryos in EAFA group (44.4%). The methylation level of satellite I gene of the reconstructed embryos in the IVF embryos (31.9%) was lower (P<0.05) than those in all other treatments. In conclusion, the reconstructed bovine embryos produced by the EAFA procedure revealed a better developmental competence with a lower methylation rate of satellite I gene than those produced by the EBFA procedure.

Differential thermal sensitivity between the recipient ooplasm and the donor nucleus in Holstein and Taiwan native yellow cattle.

The objective of this study was to compare thermal sensitivity of recipient ooplasm and donor nucleus from Holstein and Taiwan native yellow (TY) cows. Oocytes and cumulus cells from each breed were incubated at 43 °C (heat shock) or 38.5 °C (control) for 1 h prior to nucleus transplantation. Reconstructed embryos cloned by transfer of non-heated Holstein donor cells to heat-shocked Holstein ooplasm (Ho(+)-Hd⁻) had a lower (P < 0.05) blastocyst rate than those cloned from non-heated Holstein ooplasm receiving heated (Ho⁻-Hd(+)) or non-heated (Ho⁻-Hd⁻) Holstein donor cells (11.3 vs. 34.3 or 36.8%). Heat-shocked donor cells from either Holstein or TY cows did not significantly affect blastocyst rates of reconstructed embryos produced from Holstein ooplasm (30.6-32.9%). In contrast, blastocyst rates of reconstructed embryos generated with heat-shocked Holstein ooplasm were lower (P < 0.05) than that with heat-shocked TY ooplasm (11.2 vs 45.2%). Without heat shock, embryos reconstructed by transferring donor cells to ooplasm of Holstein or TY cows had similar (P > 0.05) blastocyst rates (28.9-33.3%). Transplantation of reconstructed embryos (n = 30) to recipients (n = 23) resulted in three live calves, derived from embryos cloned with TY ooplasm and donor nuclei from either Holstein (n = 2) or TY cows (n = 1). In conclusion, ooplasm of TY cattle was more resistant to heat stress than that derived from Holsteins; therefore, ooplasm may be a major determinant for thermal sensitivity in bovine oocytes and embryos.

An ultrasonographic and anatomical study of carpal tunnel, with special emphasis on the safe zones in percutaneous release.

We examined 40 wrists of 12 embalmed and eight fresh cadavers and defined the relative position of the flexor retinaculum to the neurovascular structure, ultrasonographic markers and safe zones by ultrasonography and anatomical dissection. Both longitudinal and transverse ultrasonographic sections clearly depicted the flexor retinaculum, neurovascular bundles, median nerve, flexor tendons and bony boundaries of the underlying joints. Topographic measurement showed [i] good correlation between the actual extent of the flexor retinaculum and the ultrasonographically determined distance between bony landmarks in all hands, and [ii] the widths and lengths of well-defined safe zones. A comparison study confirmed the accuracy of ultrasonography. We conclude that these ultrasonographic landmarks can locate the flexor retinaculum and facilitate safe and complete carpal tunnel release with open or minimally invasive techniques.

The assessment of the ulnar nerve at the elbow by ultrasonography in children.

We evaluated the morphological changes to the ulnar nerve of both elbows in the cubital tunnel by sonography in a total of 237 children, of whom 117 were aged between six and seven years, 66 between eight and nine years, and 54 between ten and 11 years. We first scanned longitudinally in the extended elbow and then transversely at the medial epicondyle with the elbow extended to 0 degrees . We repeated the scans with the elbow flexed at 45 degrees , 90 degrees , and 120 degrees . There were no significant differences in the area of the ulnar nerve, but the diameter increased as the elbow moved from extension to flexion in all groups. More importantly, the ulnar nerve was subluxated anteriorly on to the medial epicondyle by 1.5% to 1.9% in extended elbows, by 5.9% to 7.9% in those flexed to 45 degrees , by 40.0% to 44% in those flexed to 90 degrees , and by 57.4% to 58.1% in those flexed to 120 degrees , depending on the age group. Sonography clearly and accurately showed the ulnar nerve and was useful for localising the nerve before placing a medial pin. Because the ulnar nerve may translate anteriorly onto the medial epicondyle when the elbow is flexed to 90 degrees or more, it should never be overlooked during percutaneous medial pinning.

The effect of activation treatments on the development of reconstructed bovine oocytes.

The purpose of this study was to investigate the effect of different activation treatments on the development of IVM-derived and cloned bovine embryos. The effect of oocyte age (20h versus 24h after IVM) on the blastocyst rate was also investigated. No differences in the percentage of blastocyst development were observed between the oocytes matured for 20 and 24h (15% versus 27%, p>0.05). Reconstructed oocytes activated 4h after fusion (fusion before activation, FBA) had a higher blastocyst rate than those oocytes activated immediately after electrofusion (fusion and activation simultaneously, FAS) (26% versus 5%, p<0.01). Blastocyst rates were significantly greater (p<0.01) for the reconstructed oocytes activated by calcium ionophore (A23187) combined with 6-dimethylaminopurine (6-DMAP) (51.6%) than for those activated with cycloheximide (CHX) plus cytochalasin B (CB) treatment (1h, 8.2%; 5h, 14.3%). However, the blastocyst rates were similar among reconstructed oocytes activated by electric pulses and A23187 (30.5% versus 42.2%) or by A23187 and ionomycin (36.7% versus 33.3%) combined with 6-DMAP, respectively. Blastocysts that developed from reconstructed oocytes activated by A23187 and 6-DMAP resulted in three pregnancies (3/9) and one live birth from 18 embryos transferred to recipient cows. Genotypic analysis of six bovine microsatellite markers by polymerase chain reaction confirmed that the cloned calf was genetically identical to the nuclear donor. In conclusion, reconstructed oocytes that derived from oocytes exposed to activation treatment 4h after electrofusion are more likely to develop to the blastocyst stage. The best treatment to activate reconstructed bovine oocytes in this study was A23187 combined with 6-DMAP.

The effect of electrical field strength on activation and development of cloned caprine embryos.

The activation procedure used in nuclear transfer (NT) is one of the critical factors affecting the efficiency of animal cloning. The purpose of this study was to compare the effect of two electrical field strengths (EFS) for activation on the developmental competence of caprine NT embryos reconstructed from ear skin fibroblasts of adult Alpine does. The NT embryos were obtained by transfer of the quiescent fibroblasts at the fourth passage into the enucleated metaphase II (M II) oocytes. Four to five hours after electrical fusion, the NT-embryos were activated by EFS either at 1.67 or at 2.33 kV/cm and immediately incubated in 6-DMAP (2 mM) for 4 h. The cleavage rate of the NT-embryos activated with 2.33 kV/cm was greater than that activated with 1.67 kV/cm after in vitro culture for 18 h (65.6% versus 19.6%, p < 0.001). No pregnancy was found in 14 recipient does after transferring 51 NT embryos at 1-2 cell stages activated with 1.67 kV/cm. In contrast, two of the seven recipients were pregnant and gave birth to three kids after transferring 61 NT embryos at 1-2 cell stages activated by 2.33 kV/cm. The birth weights of three cloned kids were within the normal range of Alpine goats. However, one kid died 1h after birth while the remaining two are still healthy. DNA analysis by polymerase chain reaction (single-strand conformation polymorphism, SSCP) confirmed that the three kids were genetically identical to the nuclear donor.

Diagnostic efficacy of non-breath-hold magnetic resonance cholangiopancreatography.

Magnetic resonance cholangiopancreatography (MRCP) is an emerging imaging technique for direct visualization of biliary and pancreatic ducts without the need for an invasive procedure, ionizing radiation, or iodine contrast media administration. The purpose of this study was to evaluate the efficacy of non-breath-hold MRCP in depicting normal and diseased biliary and pancreatic ducts. A retrospective analysis of 162 patients who underwent MRCP was performed, and a comparison between MRCP and direct cholangiography was made. The overall accuracy of MRCP in diagnosing malignant and benign pancreaticobiliary diseases was also calculated. MRCP depicted more than three hepatic segments in 99% of patients with dilated intrahepatic ducts and in 63% of patients with nondilated intrahepatic ducts. MRCP demonstrated the main hepatic duct, gallbladder, and cystic duct in 100%, 89%, and 72% of patients, respectively. The dilated extrahepatic duct, nondilated extrahepatic duct, dilated pancreatic duct, and nondilated pancreatic duct were visualized in 100%, 98%, 95%, and 77% of patients, respectively. The accuracy of MRCP in diagnosing hepatolithiasis, cholecystolithiasis, and choledocholithiasis was 96%, 97%, and 96%, respectively. The obstruction levels and characteristics determined by MRCP were in agreement with those determined from direct cholangiography in 98% of malignant obstructions and 89% of benign obstructions. The overall accuracy of a combination of MRCP and conventional magnetic resonance imaging in diagnosing pancreaticobiliary diseases was 81% for malignant diseases, 86% for benign diseases, and 82% for stone diseases. We conclude that non-breath-hold MRCP can reliably depict normal and diseased pancreaticobiliary ducts except for cystic ducts and nondilated pancreatic ducts.