Stable pulsed operation of Lissajous structured beams by Nd:YVO4/Cr4+:YAG laser in a concave-convex resonator.

A Nd:YVO4/Cr4+:YAG laser with a symmetric concave-convex cavity ensuring strong intracavity beam focusing on the absorber is designed for stable pulsed operation of Lissajous structured modes with transverse patterns as Lissajous figures. Setting the cavity length to fulfill the criterion for efficient passive Q switching (PQS), as well as to meet the accidental degenerate conditions, Lissajous pulsed beams with well-defined structures and good temporal stability are created under two-dimensional off-axis pumping. Although the multi-transverse-mode oscillation inevitably induces asynchronous pulsation and leads the short-term pulse profiles to reveal parasitic effects, the overall long-term behavior of Lissajous pulses can be kept regular with amplitude fluctuations ≤15% and pulse-to-pulse timing jitter ≤5%. With the maximum peak power exceeding 500 W at a pump power of 4.5 W, the PQS Lissajous modes are further transformed into trochoidal pulsed beams to realize high-order and high-peak power structured vortex fields.

[Attention should be paid to glaucoma following pediatric cataract surgery].

Glaucoma following cataract surgery is one of the common complications after pediatric cataract surgery, and it is the main cause of "second blindness" in children. Since this atypical disease is difficult to diagnose and evaluate, it has been gradually paid more attention by clinicians. There are still some controversies and challenges related to the characteristics of the disease, diagnostic criteria, and treatment options. This article discusses the definition, diagnostic criteria, related risk factors, treatment strategies, follow-up, and prognoses of glaucoma following cataract surgery. Establishment of a diagnosis and treatment system can better improve the visual rehabilitation of pediatric cataract children.

[Reflections on surgical treatment of congenital cataract].

Congenital cataract is the first main cause of avoidable blindness in children. The manifestations of congenital cataract are diverse and complex, often associated with other ocular structural abnormalities. The infantile eyeballs are in the growth and development stage, the structure of eyeball wall is fragile, and the blood-ocular barrier is immature. Therefore, congenital cataract surgery features relatively higher surgical technical requirements with higher postoperative complications occurrence. Congenital cataract is not a miniature version of age-related cataract, which has its own unique surgical principles. In this article, issues including the preoperative characteristics of congenital cataract, surgical timing and techniques, and follow-up treatment, were discussed based on expert clinical experiences of Zhongshan Ophthalmic Center and relevant literatures. (Chin J Ophthalmol, 2021, 57: 11-16).

[Clinical characteristics and surgical effect observation of congenital aniridia combined with cataract].

Objective: To analyze the clinical manifestations, surgical approaches and postoperative prognosis for the cases of congenital aniridia combined with cataract. Methods: In this retrospective case series, 26 patients diagnosed with congenital aniridia combined with cataract were collected from Zhongshan Ophthalmic Center from February 2002 to August 2016. The Clinical data were collected to analyze the clinical features, surgical approaches and postoperative prognosis. T-test was used for statistical analysis. Results: Twenty-six bilateral congenital aniridia patients were included in the case series, with 50% male cases. The average age for the first visit was (8.72±8.06) years old. Hereditary patients constitutes 30.8% (8/26) of the total number. The proportions for bilateral and unilateral cataracts were 88.5% (23/26) and 11.5% (3/26) respectively, and 49 eyes suffering from both congenital aniridia and cataract were therefore included in the final analysis. The most common morphology cataract subtypes were lamellar cataract (24.5%, 12/49), posterior subcapsular cataract (22.4%, 11/49), and total cataract (18.4%,9/49). The observed ocular comorbidities included nystagmus (36.7%, 18/49), vitreous opacity (28.6%, 14/49), foveal hypoplasia (20.4%, 10/49), ametropia (12.2%, 6/49), exotropia (12.2%, 6/49), congenital glaucoma (12.2%, 6/49), esotropia (4.1%, 2/49), congenital ptosis (4.1%, 2/49), lens ectopia (4.1%, 2/49), scleral staphyloma (2.0%, 1/49) and pigmentary degeneration of retina (2.0%, 1/49). 30.6% (15/49) eyes were performed the cataract extraction surgery. The percentage of postoperative best corrected visual acuity (BCVA) for ≥0.1 and ≥0.3 were 93.3% (14/15) and 20.0% (3/15) respectively. Evaluated ocular pressure (33.3%, 5/15), severe posterior capsular opacification (PCO) (13.3%, 2/15) and choroidal hemorrhage combined with choroidal detachment (6.7%, 1/15) were detected as the postoperative complications. Followed by cataract extraction, 80.0% (12/15) eyes were sequentially performed the intraocular lens implantation, while, 20.0% (3/12) eyes remained aphakia due to ocular comorbidities. Conclusions: Congenital aniridia combined with cataract are rare diseases, calling for the precious retrospective researches. This disorder tended to affect both eyes and occurred hereditary. The clinical courses of the cases presented progressive features. Ocular comorbidities were the crucial factors to influence the surgical approaches and postoperative prognosis. (Chin J Ophthalmol, 2017, 53: 821-827).

Suppression of lentivirus-mediated transgenic dendritic cells in graft-versus-host disease after allogeneic bone marrow transplantation in mice.

We determined whether genetically engineered immature dendritic cells (imDCs) mediated by lentiviral vectors alleviate acute graft-versus-host disease (GVHD) after allogeneic bone marrow transplantation (allo-BMT) in mice. We introduced the mouse chemokine receptor 7 (Ccr7) gene into the bone marrow-derived imDCs of C57BL/6 mice to construct genetically engineered imDCs. A 1:1 mixture of bone marrow and spleen cells from the donors was injected into the recipients, which were divided into four groups: radiation, transplantation, empty vector, and transgenic imDC groups. Symptoms, clinical scores, GVHD pathological changes, and survival times and rates of recipients were recorded; secretion of IFN-γ and IL-4, and allogeneic chimerism rates were detected. The survival time of the transgenic imDC group (27.5 ± 7.55 days) was significantly longer than in the other three groups (P < 0.01). The GVHD score of the imDC group mice was significantly lower than in the transplantation and empty vector groups (P < 0.05), which meant that mice in the transgenic imDC group had the lightest pathology damage in the target organs. In the transplantation group, IFN-γ increased while IL-4 decreased. In contrast, IFN-γ decreased and IL-4 increased in both empty vector and trans-imDC groups, and the difference was significant in the latter (P < 0.01). Thirty days or more following transplantation, the allogeneic chimerism rate was still 95-100%, suggesting complete donor type implantation. Ccr7 transfection into imDCs suppressed occurrence and severity of acute GVHD after allo-BMT in mice; the mechanism might be associated with IFN-γ decrease and IL-4 increase.

Forward and backward propagation of dendritic impulses and their synaptic control in mitral cells.

The site of impulse initiation is crucial for the integrative actions of mammalian central neurons, but this question is currently controversial. Some recent studies support classical evidence that the impulse always arises in the soma-axon hillock region, with back-propagation through excitable dendrites, whereas others indicate that the dendrites are sufficiently excitable to initiate impulses that propagate forward along the dendrite to the soma-axon hillock. This issue has been addressed in the olfactory mitral cell, in which excitatory synaptic input is restricted to the distal tuft of a single primary dendrite. In rat olfactory bulb slices, dual whole cell recordings were made at or near the soma and from distal sites on the primary dendrite. The results show that the impulse can be initiated in either the soma-axon hillock or in the distal primary dendrite, and that the initiation site is controlled physiologically by the excitatory synaptic inputs to the distal tuft and inhibitory synaptic inputs near the soma.

Analysis of relations between NMDA receptors and GABA release at olfactory bulb reciprocal synapses.

In the mammalian olfactory bulb, signal processing is mediated by synaptic interactions between dendrites. Glutamate released from mitral cell dendrites excites dendritic spines of granule cells, which in turn release GABA back onto the mitral cell dendrites, forming a reciprocal synaptic pair. This feedback synaptic circuit was shown to be mediated predominantly by NMDA receptors. We further utilized caged Ca2+ compounds to obtain insight into the mechanism that couples NMDA receptor activation to GABA release. Feedback inhibition elicited by photo-release of caged Ca2+ in mitral cell secondary dendrites persisted when voltage-gated Ca2+ channels were blocked by cadmium (Cd2+) and nickel (Ni2+). These results indicate that Ca2+ influx through NMDA receptors can directly trigger presynaptic GABA release for local dendrodendritic feedback inhibition.

[Study on the immune functions of dendritic cells regulated by histone deacetylase inhibitor Belinostat].

Objective: To explore effects of histone deacetylase inhibitor Belinostat on the immunologic function of dendritic cells (DC) and its possible mechanism. Methods: Cultured mouse bone marrow-derived DC from C57BL/6 mouse in vitro. The experiments were divided into 0, 50, 100 nmol/L Belinostat + immature DC (imDC) group, and 0, 50, 100 nmol/L Belinostat mature DC (mDC). The changes of the ultrastructure of DC were observed by transmission electron microscope (TEM). Immunophenotype and CCR7 expression rate were detected by FCM, and the migration rate was observed by chemotaxis assay. The proliferation of lymphocytes stimulated by different DC was detected by mixed lymphocyte culture reaction. The cytokines in the culture supernatant, including TNF-α, IL-12 and IL-10, were examined by ELISA. RQ-PCR was used to examine the relative expression of mRNA in RelB. Results: Successful cultured and identified the qualified imDC and mDC. Belinostat decreased the expression of CCR7 on imDC [(25.82±7.25)% vs (50.44±5.61)% and (18.71±2.00)% vs (50.44±5.61)%], meanwhile increased the rate on mDC [(71.14±1.96)% vs (64.90±1.47)%]. Chemotaxis assay showed that the migration rate of Belinostat+imDC and Belinostat+mDC group were both decreased, but the difference in imDC was not significant. T lymphocyte proliferation rate stimulated by 100 nmol/L Belinostat+imDC group was lower than imDC group in condition irritation cell∶reaction cell=1∶2 [(227.09±13.49)% vs (309.49±53.69)%]. Belinostat significantly suppressed the secretion of cytokines TNF-α, IL-12 and IL-10 (all P<0.01). The relative expression of mRNA in RelB was slightly decreased in Belinostat+imDC and Belinostat+mDC group (all P<0.05). Conclusion: Belinostat could effectly suppress DC maturation and regulate immune tolerance of DC, which may be due to the down-regulation of mRNA level of RelB in DC.

Antitumor immunity induced by laser immunotherapy and its adoptive transfer.

The ideal cancer treatment modality should not only cause tumor regression and eradication but also induce a systemic antitumor immunity, which is essential for control of metastatic tumors and for long-term tumor resistance. Laser immunotherapy using a laser, a laser-absorbing dye, and an immunoadjuvant has induced such long-term immunity in treatment of a mammary metastatic tumor. The successfully treated rats established total resistance to multiple subsequent tumor challenges. To further study the mechanisms of the antitumor immunity induced by this novel treatment modality, passive adoptive transfer was performed using splenocytes as immune cells. The spleen cells that were harvested from successfully treated tumor-bearing rats provided 100% immunity in the naive recipients. The passively protected first cohort rats were immune to tumor challenge with an increased tumor dose; their splenocytes also prevented the establishment of tumor in the second cohort of naive recipient rats. This immunity transfer was accomplished without the usually required T-cell suppression in recipients.

Laser-photosensitizer assisted immunotherapy: a novel modality for cancer treatment.

Photosensitizer-enhanced laser treatment, where dyes are activated in situ by lasers of appropriate wavelengths, provides highly selective tissue destruction, both spatially and temporally, through photophysical reactions. Although laser-sensitizer treatment for cancer can achieve a controlled local tumor cell destruction on a large scale, total tumor eradication may not be accomplished because of the incomplete local tumor killing or the presence of tumor metastases, or both. The long-term control of cancer depends on the host immune surveillance and defense systems in which both cell-mediated and humoral responses are critical. In this study we report a novel minimally invasive cancer treatment combining the laser photophysical effects with the photobiological effects. Irradiation of a rat mammary tumor by an 805 nm diode laser, after an intratumor administration of a specific photosensitizer, indocyanine green in a glycated chitosan gel, caused immediate photothermal destruction of neoplastic cells. Concomitantly this treatment stimulated the immunological defense system against residual and metastatic tumor cells. Increases in survival rate and in the eradication of tumor burden, both primary and metastatic, were observed after this treatment. Furthermore, the resistance of successfully treated rats to tumor rechallenge demonstrated a long-lasting systemic effect of the treatment. These findings indicate that our treatment has triggered a specific humoral immune response in the tumor-bearing rats.

Chromophore-enhanced in vivo tumor cell destruction using an 808-nm diode laser.

Rat mammary tumors were treated using an 808-nm diode laser in a power range of 3-15 W. Photothermolysis was selectively enhanced by the chromophore indocyanine green (ICG), which has an absorption peak corresponding to the laser wavelength. ICG, injected into neoplastic tissues 24 h before laser exposure, was retained in sufficient quantity to produce a strong photothermal reaction. With appropriate laser power and adequate irradiation duration, laser energy could inflict severe photothermal damage to the entire targeted tumor tissue while leaving the skin and other interdicted tissue undamaged. Higher laser powers (10-15 W) produced more surface damage that limited light transmission and as a result gave rise to reduced regions of thermal destruction. Post-treatment observation revealed the survival of numerous tumor cells. This finding questions the long term efficacy of the photothermal effect of a single treatment using the combination of the ICG and the diode laser, particularly in the absence of other modalities.

Photothermal effects on murine mammary tumors using indocyanine green and an 808-nm diode laser: an in vivo efficacy study.

Murine mammary tumors were treated using indocyanine green and an 808 nm diode laser, and the in vivo chromophore-enhanced photothermal effects on the tumor burden and on tumor rat survival were investigated. The power of the laser was selected in the range of 5-10 W, and irradiation duration 3-5 min. One percent aqueous indocyanine green solution in a volume of 100-200 microliters was administered in situ, either acutely or 24 h prior to the treatment. The photothermal interaction was apparent under all our treatment conditions with a well-defined spatial containment in this study and the tumor growth was slowed after treatment. The post-treatment observation showed tumor recurrence and metastasis; no long-term survival was achieved with the single application of laser in conjunction with indocyanine green. Our results pose a question on the efficacy of the photothermal interaction even though tumor cell destruction can be achieved in a large and controlled scale. However, this highly selective photothermal impact on the tumor tissue did suggest that this method be applied repeatedly to be more effective and be used as the precursor of other modalities, such as chemotherapy, radiation therapy, immunotherapy, and surgery.

Chromophore-enhanced laser-tumor tissue photothermal interaction using an 808-nm diode laser.

A diode laser was used to irradiate tumor tissue, with indocyanine green as the chromophore. The 808-nm wavelength radiation falls within the absorption peak of the chromophore (about 780 nm). The preliminary results in this report revealed clear and significant coupling of this laser and indocyanine green in laser-tissue photothermal interaction. The chromophore targeted tissue showed laser damage while peripheral tissues remained intact. Without the chromophore, this laser inflicted no apparent tissue damage in the non-contact mode with irradiance up to 1755 J/cm2.

Survival of albumin, IgG, IgM, and complement (C3) in human blood after ingestion by Aedes albopictus and Phlebotomus papatasi.

The levels of albumin, IgG, IgM, and complement (C3) were determined by enzyme-linked immunosorbent assay in Aedes albopictus and Phlebotomus papatasi at regular intervals after feeding on human blood. Albumin disappeared most rapidly; by 48 hr, detectable levels of albumin had decreased 100-fold. In contrast, IgG and IgM survived longer and were still detectable at low levels several days after ingestion. C3 was intermediate in its rate of degradation. In general, serum protein disappearance occurred more rapidly in Ae. albopictus than in Ph. papatasi, despite a larger volume of blood ingested by the former.

A new genotype of Japanese encephalitis virus from Indonesia.

Primer-extension sequencing of the RNA template of polio, dengue, Rift Valley fever, and Japanese encephalitis (JE) viruses has provided new information on their geographic distribution, origin, and evolution. In a previous study of 46 diverse JE virus strains, we demonstrated the existence of three distinct JE genotypes in Asia. We now report the occurrence of a fourth genotype. In the present study, 19 JE virus isolates, representing various geographic regions of Asia and a 50-year time span, were compared with each other and with Murray Valley encephalitis, West Nile, and Kunjin viruses. Twelve of the JE strains from the Indonesian Archipelago and the Philippines had not been previously examined; the remainder were representatives of the three previously identified genotypes. Two hundred forty nucleotides from the pre-M gene region of the virus were used in these comparisons. Using 12% divergence as a cut-off point, the 19 JE strains fell into four distinct genotypic groups; maximum divergence across the comparison region was 21%. The newly recognized fourth genotype was comprised of five Indonesian isolates that were 7% divergent from the rest of the JE viruses.

Electrophysiological characterization of rat and mouse olfactory receptor neurons from an intact epithelial preparation.

To understand the coding mechanisms underlying olfactory discrimination, it is necessary to characterize odor response properties of olfactory receptor neurons (ORNs). In contrast with rapid progress in molecular biology, there is little physiological data from ORNs in rodent. To facilitate acquisition of such data, we have developed an intact olfactory epithelial preparation from both rat and mouse. We have carried out initial studies of this preparation by monitoring odor responses by patch-clamping directly on the ORN dendritic knobs, a subcellular site very close to the locus of olfactory signal transduction. Our results show that rat and mouse ORNs have similar intrinsic membrane properties. Most cells fired spontaneously at a low frequency (f) and about one half fired repetitively in response to current (I) injection with a linear f/I relation. About one third of rat and mouse ORNs responded to a mixture of four odors in a dose-dependent manner and about 60% of them responded to IBMX, a potent inhibitor of phosphodiesterase. The results suggest that this intact preparation offers the advantage of approximating in vivo physiological conditions, while furnishing an opportunity to map single neuron responses in the epithelium in a spatially-defined manner, using electrophysiological or cell imaging methods.

Membrane and synaptic properties of mitral cells in slices of rat olfactory bulb.

We have investigated the membrane properties and excitatory synaptic transmission of mitral cells in a slice preparation of rat olfactory bulb. In response to intracellular injection of depolarizing current, most mitral cells showed several distinct membrane properties: (1) delayed onset of firing (suggesting the presence of a type of potassium A current); (2) subthreshold oscillation of the membrane potential; and (3) repetitive firing of clustered action potentials during prolonged threshold stimulation. Olfactory nerve (ON) stimulation evoked a long-lasting EPSP in most of the mitral cells. This long EPSP was completely blocked by combined application of NMDA and non-NMDA receptor antagonists (20 microM CNQX and 100 microM APV), confirming that glutamate is the neurotransmitter at the synapses from ON to mitral cells. The ON-evoked EPSP was preceded by a prespike, which was resistant to membrane potential hyperpolarization at the soma. This fast prepotential may be indicative of an active response in the primary dendritic tufts of the mitral cells. Stimulation of the lateral olfactory tract evoked an antidromic pulse followed by a short EPSP, which could also be elicited independently of an antidromic spike in the recorded cell. Since the asymmetrical synapses so far observed on the mitral cells are all form the ON, this antidromically evoked EPSP may reflect self-excitation of a mitral cell by glutamate released from its own dendrites by antidromic impulse invasion, or/and lateral excitation by neighboring invaded dendrites.

Measurement of x-ray attenuation coefficients of aqueous solutions of indocyanine green and glycated chitosan.

We report our experimental results of measurements of x-ray attenuation coefficients of aqueous solutions of a light absorbing dye, indocyanine green, and an immunoadjuvant, glycated chitosan. In the treatment of metastatic tumors in rats using a novel laser immunotherapy these solutions were administered in situ. The x-ray attenuation data of the solutions are essential to development of an x-ray digital imaging system for monitoring the administration of the solution, as well as for the distribution and the diffusion of the solution in tumors and in surrounding tissue. The composition of the solutions, the measurement system configuration, and the technique used to determine the attenuation coefficients are described. The experimental results show that glycated chitosan has a higher attenuation coefficient compared to indocyanine green and water. Our experimental data proved that, even at low concentrations, the x-ray attenuation through these aqueous solutions could be differentiated. Therefore, a digital x-ray imaging technique can be used effectively in monitoring and controlling the intratumor diffusion and distributions of these solutions.

Lens distortion in optically coupled digital x-ray imaging.

UNLABELLED: The objectives of this research are to analyze geometrical distortions introduced by relay lenses in optically coupled digital x-ray imaging systems and to introduce an algorithm to correct such distortions. METHODS: The radial and tangential errors introduced by a relay lens in digital x-ray imaging were experimentally measured, using a lens-coupled CCD (charge coupled device) prototype. An algorithm was introduced to correct these distortions. Based on an x-ray image of a standard calibration grid, the algorithm first identified the location of the optical axis, then corrected the radial and tangential distortions using polynomial transformation technique. RESULTS: Lens distortions were classified and both radial and tangential distortions introduced by lenses were corrected using polynomial transformation. For the specific lens-CCD prototype investigated, the mean positional error caused by the relay lens was reduced by the correction algorithm from about eight pixels (0.69 mm) to less than 1.8 pixels (0.15 mm). Our investigation also shows that the fourth order of polynomial for the correction algorithm provided the best correction result. CONCLUSIONS: Lens distortions should be considered in position-dependent, quantitative x-ray imaging and such distortions can be minimized in CCD x-ray imaging by appropriate algorithm, as demonstrated in this paper.

The influence of the extent of target organs on sensitivities of methods for screening rodent carcinogens.

Two hundred and thirty-three rodent carcinogens from the Carcinogenic Potency Database (CPDB) were analyzed with CASE (Computer Automated Structure Evaluation), and a comparison of the extents of target organs with the sensitivities for long-term carcinogenic bioassays in rats and mice, Salmonella assay (Sty), electrophilic substructure alert analysis (ESAA) and CASE was made. The carcinogenicity of 233 chemicals was evaluated in both rat and mouse bioassays. The present study showed that the sensitivities of the five methods for screening carcinogens were related to the extents of target organs of carcinogens. Among the carcinogens that did not induce tumors (extent = 0) in rats, the sensitivities of Sty and ESAA were 46 and 53, respectively. Among the carcinogens which induced tumors at a single organ (extent = 1) in rats, the sensitivities were 57 and 64 respectively; and 71 and 80 at multiple organs (extent > 1) respectively. The sensitivities of CASE were 76, 82, and 89 respectively at these three different extents. Similar results were obtained with these carcinogens in mice. The results indicate that mutagenic or electrophilic carcinogens are more likely to induce tumors at multiple target organs; in contrast, most carcinogens which induced tumors at only a single target organ in one species are rarely mutagenic or electrophilic. The sensitivities of Sty and ESAA were lower than that of the CASE method in these carcinogens. CASE analyzed chemical structures of many carcinogens and non-carcinogens and then established a database of key fragments, and its parameters are not only based on mutagenicity or electrophilicity of chemicals, and this resulted in a more exact detection of the carcinogenicity of chemicals with the CASE method.