Therapeutic Outcome of Stereotactic Body Radiotherapy for Small Hepatocellular Carcinoma Lesions - A Systematic Review and Network Meta-analysis.

Surgical resection, stereotactic body radiotherapy (SBRT) and radiofrequency ablation (RFA) have seldom been compared for small hepatocellular carcinoma (HCC). We explored the treatment outcomes of SBRT for small HCC by conducting a network meta-analysis (NMA). We compared the efficacy and safety of surgical resection, RFA and SBRT for liver-confined small HCC (three or fewer lesions with a diameter ≤5 cm). The study endpoint included the odds ratios of the 1-, 3- and 5-year progression/recurrence/disease-free survival (disease progression-free survival; DPFS) and overall survival rates, as well as severe complications. Forty-five studies included 21 468 patients. In the NMA with comparable data, SBRT had comparable 1-, 3- and 5-year DPFS but significantly worse pooled long-term overall survival (3- and 5-year overall survival) than surgical resection (odds ratio 1.39, 95% confidential interval 1.3-1.89; odds ratio 1.33, 95% confidence interval 1.06-1.69, respectively). SBRT was associated with significantly better pooled 1-year DPFS compared with RFA (odds ratio 0.39, 95% confidence interval 0.15-0.97), with the remaining outcomes being comparable. SBRT had significantly less incidence of severe complications compared with surgical resection (odds ratio 0.62, 95% confidence interval 0.42-0.88) and RFA (odds ratio 0.2, 95% confidence interval 0.03-0.94). In conclusion, for small HCCs (≤5 cm) with one to three nodules, SBRT may be favourable to reduce the risks of severe complications. In terms of DPFS, SBRT may be recommended as an alternative first-line therapy for RFA and surgical resection. The results regarding overall survival should be interpreted with caution, considering the potentially uneliminated bias. There is a clear need for well-designed randomised trials to conclusively identify real differences in efficacy between these treatments, especially SBRT and surgical resection.

Efficient Spin-to-Charge Conversion via Altermagnetic Spin Splitting Effect in Antiferromagnet RuO_{2}.

The relativistic spin Hall effect and inverse spin Hall effect enable the efficient generation and detection of spin current. Recently, a nonrelativistic altermagnetic spin splitting effect (ASSE) has been theoretically and experimentally reported to generate time-reversal-odd spin current with controllable spin polarization in antiferromagnet RuO_{2}. The inverse effect, electrical detection of spin current via ASSE, still remains elusive. Here we show the spin-to-charge conversion stemming from ASSE in RuO_{2} by the spin Seebeck effect measurements. Unconventionally, the spin Seebeck voltage can be detected even when the injected spin current is polarized along the directions of either the voltage channel or the thermal gradient, indicating the successful conversion of x- and z-spin polarizations into the charge current. The crystal axes-dependent conversion efficiency further demonstrates that the nontrivial spin-to-charge conversion in RuO_{2} is ascribed to ASSE, which is distinct from the magnetic or antiferromagnetic inverse spin Hall effects. Our finding not only advances the emerging research landscape of altermagnetism, but also provides a promising pathway for the spin detection.

Susceptibility of Bacillus subtilis to Zinc Oxide Nanoparticles Treatment.

Aim: With the characteristics such as low toxicity, high total surface, ability to inhibit the growth of pathogenic microorganisms, zinc oxide nanoparticles (ZnO NPs), as one of the metallic nanoparticles, have been chosen as an antibacterial agent to treat various skin infections. The present study was aimed to determine the antibacterial potential of ZnO NPs on Bacillus subtilis, the Gram-positive bacterium that can cause skin and wound infections. Methods: B. subtilis was exposed to 5 to 150 µg/mL of ZnO NPs for 24 h. The parameters employed to evaluate the antimicrobial potential of ZnO NPs were the growth inhibitory effect on B. subtilis, the surface interaction of ZnO NPs on the bacterial cell wall, and also the morphological alterations in B. subtilis induced by ZnO NPs. Results: The results demonstrated a significant (p <0.05) inhibition of ZnO NPs on B. subtilis growth and it was in a dose-dependent manner for all the tested concentrations of ZnO NPs from 5 to 150 µg/mL at 24 h. Fourier transformed infrared (FTIR) spectrum confirmed the involvement of polysaccharides and polypeptides of bacterial cell wall in surface binding of ZnO NPs on bacteria. The scanning electron microscopy (SEM) was used to visualize the morphological changes, B. subtilis illustrated several surface alterations such as distortion of cell membrane, roughening of cell surface, aggregation and bending of cells, as well as, the cell rupture upon interacting with ZnO NPs for 24 h. Conclusion: The results indicated the potential of ZnO NPs to be used as an antibacterial agent against B. subtilis. The findings of the present study might bring insights to incorporate ZnO NPs as an antibacterial agent in the topical applications against the infections caused by B. subtilis.

Which of the fibrous layer is more important in the genesis of traumatic temporomanibular joint ankylosis: The mandibular condyle or the glenoid fossa?

INTRODUCTION: The aim of this experimental study was to investigate, under the premise of discectomy, whether damage to either the fibrous layer of the condyle or that of the glenoid fossa, could induce temporomanibular joint (TMJ) ankylosis. And if not, which of the fibrous layer was more important in the genesis of TMJ ankylosis. MATERIALS AND METHODS: Bilateral TMJ surgery was performed in 6 growing Xiao-wei Han sheep. Disk and condylar fibrous layer removal (DCFLR) was performed on the left TMJ, and disk and glenoid fibrous layer removal (DGFLR) was performed on the right TMJ. All animals were sacrificed at 3 months postoperatively. The TMJ complexes were examined by histological evaluation. RESULTS: Partial fibrous ankylosis was achieved on the DCFLR side in the 6 sheep at 3 months after surgery. On the DGFLR side, pathologic characteristics of TMJ osteoarthritis could be seen; however, no evidence of ankylosis was observed. The scores of TMJ ankylosis for the DGFLR side were significantly lower than those for the DCFLR side (P<0.05). CONCLUSION: This study demonstrated that removal of the condylar fibrous layer, not the glenoid fibrous layer, combined with discectomy could lead to traumatic TMJ ankylosis.

Pt nanoparticles decorated heterostructured g-C3N4/Bi2MoO6 microplates with highly enhanced photocatalytic activities under visible light.

Exploring an efficient and photostable heterostructured photocatalyst is a pivotal scientific topic for worldwide energy and environmental concerns. Herein, we reported that Pt decorated g-C3N4/Bi2MoO6 heterostructured composites with enhanced photocatalytic performance under visible light were simply synthesized by one-step hydrothermal method for methylene blue (MB) dye degradation. Results revealed that the synthetic Pt decorated g-C3N4/Bi2MoO6 composites with Bi2MoO6 contents of 20 wt.% (Pt@CN/20%BMO) presented the highest photocatalytic activity, exhibiting 7 and 18 times higher reactivity than the pure g-C3N4 and Bi2MoO6, respectively. Structural analyses showed that Bi2MoO6 microplates were anchored on the wrinkled flower-like g-C3N4 matrix with Pt decoration, leading to a large expansion of specific surface area from 10.79 m2/g for pure Bi2MoO6 to 46.09 m2/g for Pt@CN/20%BMO. In addition, the Pt@CN/20%BMO composites exhibited an improved absorption ability in the visible light region, presenting a promoted photocatalytic MB degradation. Quenching experiments were also conducted to provide solid evidences for the production of hydroxyl radicals (•OH), electrons (e-), holes (h+) and superoxide radicals (•O2-) during dye degradation. The findings in this critical work provide insights into the synthesis of heterostructured photocatalysts with the optimization of band gaps, light response and photocatalytic performance in wastewater remediation.

Development of a new ß Ti alloy with low modulus and favorable plasticity for implant material.

One of the most important development directions of the Ti and its alloys is the applications in medical field. Development of new Ti alloys with low elastic modulus and/or favorable biocompatibility plays an important role for promoting its application in medical field. In this work, a new ß Ti alloy (Ti-31Nb-6Zr-5Mo, wt.%) was designed for implant material using d-electron alloy design method. Microstructure and tensile properties of the designed alloy after hot rolling (HR) and solution followed by aging treatments (SA) were investigated. Results show that the designed alloy is composed of single ß phase. However, microstructural analysis shows that the ß phase in the designed alloy separates into Nb-rich and Nb-poor phase regions. The Nb-rich regions in HR specimen are typical elongated fiber texture, but are equiaxed particles with several micrometers in SA specimen. Tensile results show that the designed alloy has low Young's modulus of 44 GPa for HR specimen and 48 GPa for SA specimen which are very close to the extreme of Young's modulus of bulk titanium alloys. At the same time, the designed alloy has favorable plasticity in term of elongation of 26.7% for HR specimen and 20.6% for SA specimen, and appropriate tensile strength over 700 MPa. In short, the designed alloy has low elastic modulus close to that of bone and favorable plasticity and strength which can be a potential candidate for hard tissue replacements.

Aberrant expression of CXCR4 significantly contributes to metastasis and predicts poor clinical outcome in breast cancer.

Triple negative breast cancer is known for its visceral metastasis. We have found that CXCR4 is overexpressed in triple negative breast cancer and is associated with visceral metastasis. We further investigated whether CXCR4 is a prognostic factor affecting survival following visceral metastasis in breast cancer patients. Our results indicate that increased CXCR4 expression among breast cancer patients with visceral metastasis was positively correlated with poor overall survival (P<0.001). Silencing of CXCR4 was associated with a decrease in the tumorigenic properties of MDA-MB-231 breast cancer cells, caused reversion of EMT and suppression of MMP-9, increased apoptosis, and caused a reduced incidence of tumor lung metastasis in mice. These results are indicative of CXCR4 having a predictive role in patients with visceral metastasis and indicate that shRNA knock down of CXCR4 might be a novel therapeutic strategy to prevent breast cancer metastasis when CXCR4 is overexpressed.

The impact of p53 in predicting clinical outcome of breast cancer patients with visceral metastasis.

In the study, we analyzed role of p53 in predicting outcome in visceral metastasis breast cancer (VMBC) patients. 97 consecutive VMBC patients were studied. P53 positivity rate was 29.9%. In the p53-negative group, median disease free survival (DFS), and time from primary breast cancer diagnosis to death (OS1), time from metastases to death (OS2) were 25, 42.5, and 13.5 months, respectively. In the p53-positive group, they were 10, 22, and 8 months, respectively. Statistically significant differences in DFS and OS1 were detected between the p53-negative and p53-positive subtypes. However, p53 appears to have no influence on OS2. In Cox regression analysis, p53 expression and TNM stage were predictive factors of DFS. In the multivariate analysis, p53 expression and the duration of DFS correlated with OS1, but not for OS2. Taken together, our data indicate p53 showing predicting role in OS1 for VMBC, but not for OS2.

In vitro and in vivo proliferation, differentiation and migration of cardiac endothelial progenitor cells (SCA1+/CD31+ side-population cells).

BACKGROUND: Side-population (SP) cells are a select population identified by a capacity to efflux Hoechst dye and are enriched for stem/progenitor cell activity. Previous studies suggested that cardiac SP (CSP) cells could be divided into SCA1(+)/CD31(-) and SCA1(+)/CD31(+) CSP cells. SCA1(+)/CD31(-) CSP cells have been shown to be cardiac stem/progenitor cells. However, SCA1(+)/CD31(+) CSP cells have not been fully characterized. OBJECTIVE: The aim of the present study was to characterize SCA1(+)/CD31(+) CSP cells in the adult mouse heart, and investigate their abilities to proliferate, differentiate, vascularize and migrate in vitro and in vivo. RESULTS: Using fluorescence-activated cell sorting (FACS), RT-PCR, and assays of cell proliferation, differentiation and migration, and a murine model of myocardial infarction (MI), we showed that SCA1(+)/CD31(+) CSP cells express stem cell and endothelial-specific genes, and reside in the blood vessels. These cells were able to proliferate, differentiate, migrate and vascularize in vitro and in vivo. After MI, SDF-1α and CXCR4 were up-regulated in the damaged myocardium and on SCA1(+)/CD31(+) CSP cells, respectively. Our results further showed that SDF-1α induced migration of these cells in vitro. Importantly, we found that SCA1(+)/CD31(+) CSP cells could migrate into the ischemic region from the non-ischemic area within the myocardium and form a vascular tube-like structure after MI. CONCLUSIONS: Based on the gene expression profile, localization of SCA1(+)/CD31(+) CSP cells, and their ability to proliferate, differentiate, migrate and vascularize in vitro and in vivo, we postulate that SCA1(+)/CD31(+) CSP cells may represent endothelial progenitor cells in the mouse heart.

The effect of potent iron chelators on the regulation of p53: examination of the expression, localization and DNA-binding activity of p53 and the transactivation of WAF1.

Iron (Fe) chelators induce a G1/S arrest and several of these are undergoing clinical trials as anticancer agents. Despite this, little is known concerning the precise function of Fe in cell cycle progression and the role of p53 in this process. The aim of this study was to assess the effect of Fe chelators on p53 and the mechanism involved in the chelator-mediated increase in mRNA levels of the universal cyclin-dependent kinase inhibitor p21CIP1/WAF1. Cells were incubated with the potent Fe chelator 2-hydroxy-1-naphthylaldehyde isonicotinoyl hydrazone (311) and the results compared with those from cells treated with actinomycin D (Act D), which induces p53. Following incubation with 311, a 3- to 5-fold increase in nuclear p53 protein was observed in cells with wild-type p53. In addition, 311 increased p53 DNA-binding activity 2-fold, while Act D increased it 3- to 5-fold in cells with native p53. To determine the role of p53 in WAF1 transcription, a reporter construct was used consisting of a WAF1 promoter containing the p53-binding site. In cells with wild-type p53, chelators had no effect on luciferase activity, while the positive control, Act D, caused a significant increase. Hence, despite increased p53 protein expression and p53 DNA-binding activity following chelation, these latter results suggested it had no role in up-regulating WAF1 mRNA. Our experiments demonstrated: (i) that the elevated WAF1 mRNA expression after Fe chelation was due to increased transcription and also to a post-transcriptional mechanism that was sensitive to cycloheximide; and (ii) that Fe-chelation increased WAF1 expression through a p53-independent pathway.

Spatial distribution and developmental appearance of postjunctional P2X1 receptors on smooth muscle cells of the mouse vas deferens.

P2X1-type purinoceptors have been shown to mediate fast transmission between sympathetic varicosities and smooth muscle cells in the mouse vas deferens but the spatial organization of these receptors on the smooth muscle cells remains inconclusive. Voltage clamp techniques were used to estimate the amplitudes of spontaneous excitatory junction currents (SEJCs) in cells of the vas deferens longitudinal smooth muscle layer. These currents involved the activation of about 6% of the P2X-type channels present on the cell, as compared to whole cell currents produced when isolated smooth muscle cells were exposed to maximal concentrations of either ATP or alpha,beta-MeATP. Immunofluorescence staining of the vas deferens with antibodies against P2X1 receptor showed a diffuse, grainy distribution over the entire membrane of each smooth muscle cell. Anti-P2X1 staining was not markedly clustered beneath anti-SV2-stained sympathetic varicosities. Similar results were obtained for cells in the urinary bladder. During development, P2X1 mRNA was detected as early as embryonic day 15 (E15). Increasing intensities of diffuse immunostaining for P2X1 were observed in the walls of the bladder, tail artery, and aorta from E15 until 6 weeks postnatal. The vas deferens showed increasing intensities of diffuse staining of its smooth muscle layers between 2 and 6 weeks postnatal, consistent with the time-course of development of fast purinergic transmission described previously. Together, the results suggest that the response of smooth muscle of the vas deferens to ATP released from sympathetic varicosities relies on rapidly desensitizing P2X1 receptors, distributed diffusely across the smooth muscle cell surface.

A high-grade primary leiomyosarcoma of the bladder in a survivor of retinoblastoma.

Second nonocular malignancies develop with increased incidence in patients with hereditary retinoblastoma. Osteosarcoma is by far the most common type with an incidence of up to 50%, followed by soft tissue sarcomas. Visceral leiomyosarcoma is extremely rare and only 2 cases have been reported in the past 2 decades, one in the liver and another one in the urinary bladder, both of which developed after cyclophosphamide therapy. Here we report a case of vesical leiomyosarcoma that was diagnosed in a 49-year-old woman 47 years after the diagnosis of a hereditary retinoblastoma. The patient's retinoblastoma was treated with unilateral enucleation without adjuvant radiation or chemotherapy. We believe that this is the first report of vesical leiomyosarcoma occurring in a patient with retinoblastoma without a prior history of radiation or chemotherapy. This report is significant not only because of the rarity of vesical leiomyosarcoma as a second nonocular tumor in retinoblastoma patients, but also because of the infrequency of vesical leiomyosarcoma in general. We also investigated the potential molecular pathogenesis of the leiomyosarcoma.

Structure and chromosome location of the mouse P2X(1) purinoceptor gene (P2rx1).

P2X(1) receptors are ATP-gated cation channels that mediate the fast, purinergic component of sympathetic nerve-smooth muscle neurotransmission in the mouse vas deferens and may serve comparable functions in the urinary bladder and the arteries. The gene for mouse P2X(1) (P2rx1) was cloned and its genomic structure defined by sequencing. The gene spans about 10 kb and consists of 12 exons. All splice sites conformed to the GT-AG motif and the exon-intron boundaries were largely conserved with other members of the P2X gene family so far cloned. A single transcription-starting site was identified by 5' RACE analysis, 233 bp upstream of the translation start site. The P2X(1) gene maps to the central region of mouse chromosome 11.

An immunostaining panel for diagnosis of malignancy in mucinous tumors of the pancreas.

BACKGROUND: The diagnosis of malignancy in pancreatic mucinous cystic tumors depends on demonstrating invasion that may be focal and require extensive sectioning. OBJECTIVE: To explore markers that may indicate malignant potential in mucinous cystic tumors. DESIGN: Routinely processed sections from resected specimens of 12 normal pancreata, 14 pancreata with chronic pancreatitis, 9 mucinous cystic tumors, and 30 invasive adenocarcinomas were immunostained with antibodies to p53, HER-2/neu, epithelial growth factor receptor (EGFR), transforming growth factor alpha (TGF-alpha), and Ki-67. RESULTS: Expression of p53, HER-2/neu, and Ki-67 was significantly more frequent in mucinous tumors than in normal pancreatic tissue and chronic pancreatitis tissue (P =.0003 to.05). Strong expression (more than one third of cells positive) and strong intensity (2+ and 3+) of staining of p53 and EGFR were seen only in carcinomas. Coexpression of p53/HER-2/neu and EGFR/HER-2/neu and a frequency of Ki-67+ nuclei of greater than 5% of cells discriminated between mucinous tumors and normal pancreatic tissue and chronic pancreatitis tissue. p53 expression was significantly more frequent in carcinomas than in mucinous tumor (P =.0326). Coexpression of p53/EGFR discriminated between mucinous tumors and carcinomas; however, TGF-alpha was not discriminative. CONCLUSIONS: The immunostaining panel of p53, HER-2/neu, Ki-67, and EGFR can be helpful in indicating malignant potential in mucinous tumors of pancreas in routine pathology practice.

Development of fast purinergic transmission in the mouse vas deferens.

ATP released by sympathetic varicosities of the mouse vas deferens binds to P2X receptors which activate fast, ligand-gated channels, resulting in depolarisation of smooth muscle cells. We examined the development of fast neuromuscular transmission at surface longitudinal smooth muscle fibres of the mouse vas deferens. Sympathetic varicosities were visualised using DiOC(2)(5)-fluorescence to aid in positioning loose patch electrodes over small sets of sympathetic varicosities to record the nerve terminal impulse (NTI) and excitatory junction currents (EJCs) evoked during nerve stimulation. At the earliest age at which EJCs could be detected, 21 days postnatal (PN), most recording sites rarely showed a detectable EJC over 100 trials, even though NTIs were recorded without failure. The extent of such intermittence in transmitter release progressively declined between 21 and 42 days PN. In addition, the mean amplitude of spontaneous EJCs (SEJCs) and EJCs increased by 2- and 2.4-fold, respectively, between 21 and 42 days PN. The rise time of EJCs varied widely at each age but declined with development (e.g., 7-14 ms at 28 days PN, 3-12 ms at 42 days PN). All EJCs were abolished by suramin (100 microM). Fast rise time EJCs were rapidly abolished by alpha,beta-methylene ATP (20 microM) while some (34%) of the slower rise time EJCs were resistant to rapid desensitisation of this kind. P2X(1) and P2X(2) mRNAs were detected by reverse transcription and polymerase chain reaction (RT-PCR) to determine whether levels of expression of the receptor subunits might explain the increased EJC amplitude. Between 10 and 42 days PN no marked change was observed in the P2X(2) receptor mRNA or beta-actin mRNA (control). In contrast, the intensity of the RT-PCR band for P2X(1) receptor showed a progressive approximately 4.3-fold developmental increase relative to the P2X(2) band. These observations suggest that both prejunctional and postjunctional mechanisms cause the maturation of fast purinergic junctional transmission at the longitudinal muscle of the mouse vas deferens between 21 and 42 days PN.

[High-performance liquid chromatography determination of histamine in nasal mucosa of guinea pig after post-column derivatization].

A rapid and simple method for determining histamine by post-column derivatization liquid chromatography with fluorescent detection was described. SCX weakly acidic cation exchange column was used as an analytical column. Histamine was eluted at 13 min 12 s by 40 mmol.L-1 of trisodium citrate (pH5.50) at flow rate of 1.0 ml.min-1. The recoveries of histamine ranged from 1.0 mumol.L-1 to 100 mumol.L-1 were above 92%. The detection limit for histamine was 50 nmol.L-1 and the linear range for histamine was 50 nmol.L(-1)-500 mumol.L-1.

N-Methyl-5-tert-butyltryptamine: A novel, highly potent 5-HT1D receptor agonist.

It has been observed that reported 5-HT1D receptor agonists have at least one heteroatom (N, O, or S) on the 5-substituent of the indole. This has led to the hypothesis that a 5-substituent capable of participating in hydrogen bonding is critical for conveying high affinity. This article describes the synthesis and biological evaluation of a new series of 5-alkyltryptamine analogues, which does not have a heteroatom in the 5-substituent group. In contrast to the hypothesis, 5-alkyltryptamines all exhibit high binding affinities for the human 5-HT1D receptor. The size of the lipophilic alkyl group at the 5-position of the indole has significant impact on the 5-HT1D binding affinity. Compounds with a tert-butyl group at the 5-position such as 9d, 10, and 11 were identified. These analogues display high binding affinity (Ki < 1 nM) and moderate receptor selectivity in comparison with known antimigraine agents such as sumatriptan, naratriptan, rizatriptan, and VML-251.

Trace element content in drinking water of nasopharyngeal carcinoma patients.

Chinese in the Xiangxi region of Hunan province in China have a high incidence of nasopharyngeal carcinoma (NPC). For analyzing the relation between NPC and trace elements, the concentrations of 7 trace elements in drinking water (well water) of high- and low-incidence areas were measured (75 samples). The results showed that the concentrations of Ni, Zn and Cd in drinking water of high-incidence areas were significantly higher than those in low-incidence areas. Especially, the Ni level in drinking water had a significant positive correlation with NPC mortality. These observations are consistent with earlier studies. We also found a highly positive correlation between Ni/pH value in drinking water and NPC mortality. This suggests that only considering the ion concentration in drinking water is not enough, we should also pay attention to the pH of the drinking water when we study the relation between NPC and trace elements. Because the pH of the medium can strongly affect trace element chemical characteristics and its metabolic state in living systems, the M/pH (M, metal concentration) may be an important factor worthy of further research.