Cepharanthine induces the proliferation of human dermal papilla cells and stimulates vascular endothelial growth factor expression through increased intracellular calcium mobilization and hypoxia-inducible factor activation.

BACKGROUND: Cepharanthine (CEP), a compound extracted from the vine Stephania cephalantha, is commonly prescribed to treat alopecia areata; however, the scientific evidence for its efficacy is limited. AIM: To investigate the effect of CEP and its structural analogues on human hair growth in vitro. METHODS: The effects of CEP and three of its structural analogues on the proliferation of human dermal papilla cells (hDPCs) and human outer root sheath cells (hORSCs) were investigated. Their effects on vascular endothelial growth factor (VEGF) expression were also assessed by real-time PCR. Activation of pathways leading to VEGF expression, such as intracellular Ca2+ mobilization and hypoxia-inducible factor (HIF) expression, was also characterized. RESULTS: CEP and two of its structural analogues significantly stimulated the growth of hDPCs but not hORSCs. Moreover, CEP and all three structural analogues significantly induced the expression of VEGF in hDPCs. CEP increased the intracellular Ca2+ concentration in hDPCs. CEP also increased the expression of HIF-1α and HIF-2α and induced the expression of HIF-responsive genes in hDPCs, even under normoxia. CONCLUSIONS: These results suggest that CEP and its structural analogues have the potential to restore hair growth by promoting the proliferation of hDPCs and increasing their expression of VEGF.

A clinical comparison between dedifferentiated low-grade osteosarcoma and conventional osteosarcoma.

AIMS: The purpose of this study was to clarify the clinical behaviour, prognosis, and optimum treatment of dedifferentiated low-grade osteosarcoma (DLOS) diagnosed based on molecular pathology. PATIENTS AND METHODS: We retrospectively reviewed 13 DLOS patients (six men, seven women; median age 32 years (interquartile range (IQR) 27 to 38)) diagnosed using the following criteria: the histological coexistence of low-grade and high-grade osteosarcoma components in the lesion, and positive immunohistochemistry of mouse double minute 2 homolog (MDM2) and cyclin-dependent kinase 4 (CDK4) associated with MDM2 amplification. These patients were then compared with 51 age-matched consecutive conventional osteosarcoma (COS) patients (33 men, 18 women; median age 25 years (IQR 20 to 38)) regarding their clinicopathological features. RESULTS: The five-year overall survival (OAS) rates in the DLOS and COS patients were 85.7% and 77.1% (p = 0.728), respectively, and the five-year progression-free survival (PFS) rates were 57.7% and 44.9% (p = 0.368), respectively. A total of 12 DLOS patients received chemotherapy largely according to regimens for COS. Among the nine cases with a histological evaluation after chemotherapy, eight showed a poor response, and seven of these had a necrosis rate of < 50%. One DLOS patient developed local recurrence and five developed distant metastases. CONCLUSION: Based on our study of 13 DLOS cases that were strictly defined by histological and molecular means, DLOS showed a poorer response to a standard chemotherapy regimen than COS, while the clinical outcomes were not markedly different. Cite this article: Bone Joint J 2019;101-B:745-752.

Burst intensification by singularity emitting radiation in multi-stream flows.

Burst Intensification by Singularity Emitting Radiation (BISER) is proposed. Singularities in multi-stream flows of emitting media cause constructive interference of emitted travelling waves, forming extremely localized sources of bright coherent emission. Here we for the first time demonstrate this extreme localization of BISER by direct observation of nano-scale coherent x-ray sources in a laser plasma. The energy emitted into the spectral range from 60 to 100 eV is up to ~100 nJ, corresponding to ~1010 photons. Simulations reveal that these sources emit trains of attosecond x-ray pulses. Our findings establish a new class of bright laboratory sources of electromagnetic radiation. Furthermore, being applicable to travelling waves of any nature (e.g. electromagnetic, gravitational or acoustic), BISER provides a novel framework for creating new emitters and for interpreting observations in many fields of science.

Scintillator-based transverse proton beam profiler for laser-plasma ion sources.

A high repetition rate scintillator-based transverse beam profile diagnostic for laser-plasma accelerated proton beams has been designed and commissioned. The proton beam profiler uses differential filtering to provide coarse energy resolution and a flexible design to allow optimisation for expected beam energy range and trade-off between spatial and energy resolution depending on the application. A plastic scintillator detector, imaged with a standard 12-bit scientific camera, allows data to be taken at a high repetition rate. An algorithm encompassing the scintillator non-linearity is described to estimate the proton spectrum at different spatial locations.

Abnormal neutrophil scattergram obtained using Pentra MS CRP in the patients with myelodysplastic syndrome showing dysgranulopoiesis.

INTRODUCTION: Pentra MS CRP is an automated hematology analyzer capable of cytochemistry using Chlorazol black E, a lipid-staining agent, for white blood cell (WBC) differentials. Pentra MS CRP displays a WBC scattergram according to the cell volume obtained using flow impedance and light absorbance reflecting the Chlorazol black E (CBE)-positive lipid content. METHOD: Neutrophil scattergrams obtained using Pentra MS CRP were compared between 5 patients with myelodysplastic syndrome (MDS) and normal controls. Sudan black B (SBB)-staining patterns of peripheral blood neutrophils were subdivided into four types (types I, II, III, and VI) based on their staining intensity and scored by counting 200 cells. Such SBB scores were also compared between the two groups. RESULTS: Neutrophil scattergrams deviated downward in the MDS group, suggesting the decreased CBE positivity that seemed reflect the reduction of the lipid content in dysplastic neutrophils. SBB scores determined in this study were also decreased in the MDS group when compared with those in normal controls. CONCLUSION: Pentra MS CRP might rapidly generate useful information on dysplastic neutrophils in patients with MDS based on its cytochemistry for WBC differentials during routine laboratory hematology.

Carcinosarcoma of the fallopian tube with disappearance of carcinoma cells by neoadjuvant chemotherapy: case study.

The authors report a case of carcinosarcoma (CS) of the fimbria of the fallopian tube in which carcinoma cells disappeared with neoadjuvant chemotherapy (NAC). A 74-year-old woman visited the present hospital with a large pelvic mass and pleural effusion. A magnetic resonance image of the tumor was highly suggestive of ovarian carcinoma. Due to the presence of both serous.adenocarcinoma cells in pleural effusion and pulmonary thrombosis, the patient was given NAC consisting of carboplatin plus paclitaxel (TC) and anticoagulant therapy with warfarin potassium. With six courses of NAC, the pleural effusion and pulmonary thrombosis disappeared, and the tumor decreased 36.2% in greatest diameter. Maximum debulking surgery was then performed. The tumor was found to be located in the fimbria of the right fallopian tube. Hysterectomy and bilateral salpingo-oophorectomy were performed, and histologic examination revealed chondrosarcoma with the presence of necrotic epithelial cells. The necrotic areas were interspersed with papillary structures, and immunohistochemical study showed positivity for CK7 and negativity for CK20, p53, and estrogen receptor (ER), indicating serous adenocarcinoma. Thus, heterologous CS with disappearance of viable carcinoma cells by NAC was diagnosed. The patient was given adjuvant chemotherapy consisting of three courses of TC, and there has been no evidence of disease for 20 months. The authors' experience in this case of gynecologic CS indicates that a serous adenocarcinomatous component of tubal CS can be well cured by TC-based NAC.

Nonlinear increase of X-ray intensities from thin foils irradiated with a 200 TW femtosecond laser.

We report, for the first time, that the energy of femtosecond optical laser pulses, E, with relativistic intensities I > 10(21) W/cm(2) is efficiently converted to X-ray radiation, which is emitted by "hot" electron component in collision-less processes and heats the solid density plasma periphery. As shown by direct high-resolution spectroscopic measurements X-ray radiation from plasma periphery exhibits unusual non-linear growth ~E(4-5) of its power. The non-linear power growth occurs far earlier than the known regime when the radiation reaction dominates particle motion (RDR). Nevertheless, the radiation is shown to dominate the kinetics of the plasma periphery, changing in this regime (now labeled RDKR) the physical picture of the laser plasma interaction. Although in the experiments reported here we demonstrated by observation of KK hollow ions that X-ray intensities in the keV range exceeds ~10(17) W/cm(2), there is no theoretical limit of the radiation power. Therefore, such powerful X-ray sources can produce and probe exotic material states with high densities and multiple inner-shell electron excitations even for higher Z elements. Femtosecond laser-produced plasmas may thus provide unique ultra-bright X-ray sources, for future studies of matter in extreme conditions, material science studies, and radiography of biological systems.

Measurements of electron-induced neutrons as a tool for determination of electron temperature of fast electrons in the task of optimization laser-produced plasma ions acceleration.

High intensity laser-plasma interaction has attracted considerable interest for a number of years. The laser-plasma interaction is accompanied by generation of various charged particle beams, such as high-energy proton and ions with high charge to mass ratio (Q/M; same as multi-charged ions). Results of simultaneous novel measurements of electron-induced photonuclear neutrons (photoneutron), which are a diagnostic of the laser-plasma interaction, are proposed to use for optimization of the laser-plasma ion generation. The proposed method is demonstrated by the laser irradiation with the intensity of 1 × 10(21) W/cm(2) on the metal foil target. The photoneutrons are measured by using NE213 liquid scintillation detectors. Heavy-ion signal is registered with the CR-39 track detector simultaneously. The measured signals of the electron-induced photoneutrons are well reproduced by using the Particle and Heavy Ion Transport code System. The results obtained provide useful approach for analyzing the various laser based ion beams.

Multi-charged heavy ion acceleration from the ultra-intense short pulse laser system interacting with the metal target.

Experimental demonstration of multi-charged heavy ion acceleration from the interaction between the ultra-intense short pulse laser system and the metal target is presented. Al ions are accelerated up to 12 MeV/u (324 MeV total energy). To our knowledge, this is far the highest energy ever reported for the case of acceleration of the heavy ions produced by the <10 J laser energy of 200 TW class Ti:sapphire laser system. Adding to that, thanks to the extraordinary high intensity laser field of ∼10(21) W cm(-2), the accelerated ions are almost fully stripped, having high charge to mass ratio (Q/M).

Insertable pulse cleaning module with a saturable absorber pair and a compensating amplifier for high-intensity ultrashort-pulse lasers.

We demonstrate the performance of an efficient insertable pulse cleaning module (IPCM) that uses a saturable absorber (SA) pair with a compensating multi-pass amplifier. IPCM consists of a first SA, a grating compressor, a second SA, a stretcher and a compensating Ti:sapphire amplifier. It is implemented with a conventional chirped pulse amplification (CPA) Ti:sapphire laser system, resulting in a double CPA system architecture, and suppresses the amplified spontaneous emission (ASE) level of the pulse pedestal by about three orders of magnitude while preserving the output pulse energy and repetition-rate of the overall laser system. The duration of recompressed cleaned pulses is comparable to that obtained without the cleaning module. The effectiveness of the cleaning module is confirmed in laser-driven proton acceleration experiments. At the 10(9) W/cm2 pedestal level, the surface structure and electrical resistivity of an insulator target (100 nm silicon nitride) are preserved prior to the arrival of the intense ultrashort pulse.

Immediate soft-tissue reconstruction using a rectus abdominis myocutaneous flap following wide resection of malignant bone tumours of the pelvis.

Resection of malignant bony tumours of the pelvis creates large bone and soft-tissue defects, and is frequently associated with complications such as wound dehiscence and deep infection. We present the results of six patients in whom a rectus abdominis myocutaneous (RAM) flap was used following resection of a malignant tumour of the pelvis. Bony reconstruction was performed using a constrained hip tumour prosthesis in three patients, vascularised fibular graft in two and frozen autograft in one. At a mean follow-up of 63 months (16 to 115), no patients had a problem with the wound. Immediate reconstruction using a RAM flap may be used after resection of a malignant tumour of the pelvis to provide an adequate volume of tissue to eliminate the dead space, cover the exposed bone or implants with well-vascularised soft tissue and to reduce the risk of complications.

Successful treatment for Cronkhite-Canada syndrome with endoscopic mucosal resection and salazosulfapyridine.

A 79-year-old woman was referred to our hospital because numerous polyps were found in her stomach and large intestine at an ambulatory clinic. Although there were no characteristic symptoms or signs of Cronkhite-Canada syndrome (CCS), endoscopic and pathological findings indicated CCS. Moreover, colonoscopy showed two polypoid lesions (Is type), which appeared neoplastic by magnifying observation with image-enhanced endoscopy (IEE), in the ascending colon. Histologically, the resected specimens revealed tubular adenomas arising in the CCS inflammatory polyps. Remarkable remission of the polyps and edematous mucosa in the stomach and colon was seen after 8 months of administration of salazosulfapyridine (SASP) (3 g/day). Another adenoma was detected and removed endoscopically in the sigmoid colon. This is the first report to describe an asymptomatic case of CCS probably detected in the early phase of the disease, by magnifying IEE which enabled detection and treatment for associated colonic adenomas. SASP was effective in eradication of the inflammatory polyposis, and an additional adenoma was successfully found and removed by surveillance colonoscopy thereafter.

The role of osteocytes in bone resorption during orthodontic tooth movement.

We investigated the roles of osteocytes in osteoclastic bone resorption during orthodontic tooth movement using the transgenic mice in which osteocytes can be specifically ablated. Because these transgenic mice express the receptor for diphtheria toxin on the cell surfaces of osteocytes, the injection of diphtheria toxin can ablate their osteocytes in vivo. Injection of diphtheria toxin into the transgenic mice significantly increased the number of ablated osteocytes in alveolar bone compared with that in wild-type mice with or without diphtheria toxin injection. Increased numbers of ablated osteocytes were observed from day 4 to day 12 after the injection in alveolar bones as well as in cortical bone of the tibiae. We applied the orthodontic force 4 days after the injection of diphtheria toxin, and the distance of tooth movement on day 12 was significantly smaller in transgenic mice than that in control mice. The numbers of osteoclasts and the quantity of eroded bone surface at the compression site were significantly reduced in the transgenic mice injected with diphtheria toxin than in control mice. These results provide in vivo demonstration of osteocyte involvement in osteoclastic bone resorption during orthodontic tooth movement.

Quantitative measurement of hard x-ray spectra for high intensity laser produced plasma.

X-ray line spectra ranging from 17 to 77 keV were quantitatively measured with a Laue spectrometer, composed of a cylindrically curved crystal and a detector. Either a visible CCD detector coupled with a CsI phosphor screen or an imaging plate can be chosen, depending on the signal intensities and exposure times. The absolute sensitivity of the spectrometer system was calibrated using pre-characterized laser-produced x-ray sources and radioisotopes. The integrated reflectivity for the crystal is in good agreement with predictions by an open code for x-ray diffraction. The energy transfer efficiency from incident laser beams to hot electrons, as the energy transfer agency for specific x-ray line emissions, is derived as a consequence of this work.

Soft-x-ray harmonic comb from relativistic electron spikes.

We demonstrate a new high-order harmonic generation mechanism reaching the "water window" spectral region in experiments with multiterawatt femtosecond lasers irradiating gas jets. A few hundred harmonic orders are resolved, giving µJ/sr pulses. Harmonics are collectively emitted by an oscillating electron spike formed at the joint of the boundaries of a cavity and bow wave created by a relativistically self-focusing laser in underdense plasma. The spike sharpness and stability are explained by catastrophe theory. The mechanism is corroborated by particle-in-cell simulations.

Endoscopic full-thickness resection of a lateral spreading rectal tumor after unplanned injection of dilute hyaluronic acid into the subserosal layer (with video).

A 74-year-old woman underwent colonoscopy for investigation of a liver tumor. A lateral spreading tumor of the non-granular type (LST-NG), 25 mm in diameter, was detected at the rectosigmoid junction. As magnifying image-enhanced colonoscopy suggested a tubulovillous adenoma, endoscopic mucosal resection (EMR) was chosen for removal of the LST-NG. The lesion was effectively and evenly lifted after injection of 0.4% hyaluronic acid diluted with glycerol in the ratio of 1:1. A small amount of indigo-carmine dye was also added for coloration of the plane of resection. The lesion was completely removed en bloc. Although a blue-colored layer was identified in the resection defect, a small amount of a whitish layer was detected above the blue layer. The muscle layer was clearly located on the underside of the resected polyp. A total of 14 endoclips were used to close the defect completely. The patient was successfully treated conservatively without surgery. Histology of the resected specimen showed that it contained a tubulovillous adenoma with the submucosal layer and both layers of the muscularis propria. The surgical margin was free of neoplastic change horizontally and vertically. To the best of our knowledge, this is the first case report of full-thickness resection associated with EMR after unplanned injection of dilute hyaluronic acid into the subserosal layer rather than the intended submucosal layer. We describe how to promptly recognize this complication during colonoscopy, in order to achieve immediate closure of the defect, with the identification of a "mirror target sign" on the colonic wall.

Response to air insufflation in patients with non-erosive gastro-oesophageal reflux disease (NERD).

This study compared changes in intragastric pressure (IGP) in response to a gastric distension stimulus caused by air insufflation in 25 patients with non-erosive gastro-oesophageal reflux disease (NERD) and 34 healthy volunteers (controls). In four NERD patients, IGP responses were also measured before and after oral treatment with 10 mg rabeprazole daily for 2 weeks. The rate of increase in IGP at the start of insufflation was significantly higher in NERD patients than in controls. The time to appearance of symptoms (i.e. time to threshold) was significantly shorter in NERD patients than in controls. Direct measurement of IGP showed that visceral hypersensitivity and impaired fundal relaxation are both characteristic of NERD. Administration of rabeprazole led to a marked prolonging of time to threshold, indicating that treatment could alleviate this hypersensitivity.

Efficient multi-keV x-ray generation from a high-Z target irradiated with a clean ultra-short laser pulse.

Kα line emissions from Mo and Ag plates were experimentally studied using clean, ultrahigh-intensity femtosecond laser pulses. The absolute yields of Kα x-rays at 17 keV from Mo and 22 keV from Ag were measured as a function of the laser pulse contrast ratio and irradiation intensity. Significantly enhanced Kα yields were obtained for both Mo and Ag by employing high contrast ratios and irradiances. Conversion efficiencies of 4.28×10⁻5/sr for Mo and 4.84×10⁻5/sr for Ag, the highest values obtained to date, were demonstrated with contrast ratios in the range 10⁻¹° to 10⁻¹¹.

Energy increase in multi-MeV ion acceleration in the interaction of a short pulse laser with a cluster-gas target.

An approach for accelerating ions, with the use of a cluster-gas target and an ultrashort pulse laser of 150-mJ energy and 40-fs duration, is presented. Ions with energy 10-20 MeV per nucleon having a small divergence (full angle) of 3.4 degrees are generated in the forward direction, corresponding to approximately tenfold increase in the ion energies compared to previous experiments using solid targets. It is inferred from a particle-in-cell simulation that the high energy ions are generated at the rear side of the target due to the formation of a strong dipole vortex structure in subcritical density plasmas.