A HER2-targeted antibody-novel DNA topoisomerase I inhibitor conjugate induces durable adaptive antitumor immunity by activating dendritic cells.

We designed and developed a novel DNA topoisomerase I inhibitor MF-6, which was a more potent cytotoxin and a more potent inducer of immunogenic cell death compared with DXd. To utilize MF-6's ability to induce antitumor immunity, a human epidermal growth factor receptor 2 (HER2)-targeted antibody-drug conjugate (ADC) trastuzumab-L6 that included a cleavable linker and MF-6 was developed. Different from traditional cytotoxic ADC, the antitumor activity of trastuzumab-L6 was assessed by inducing tumor cell immunogenic cell death, activating dendritic cells and cytotoxic CD8+ T cells to acquire durable adaptive immune memory. Tumor cells treated with trastuzumab-L6 were committed to immunogenic cell death, with upregulation of damage-associated molecular patterns and antigen presentation molecules. In a syngeneic tumor model with a mouse cell line that expressed human HER2, immunocompetent mice showed greater antitumor efficacy compared with nude mice. The trastuzumab-L6-cured immunocompetent mice acquired adaptive antitumor memory and rejected subsequent tumor cell challenge. The trastuzumab-L6 efficacy was abrogated when cytotoxic CD8+ T cells were depleted and enhanced when regulatory CD4+ T cells were depleted. The combination of trastuzumab-L6 with immune checkpoint inhibitors significantly increased antitumor efficacy. Enhanced T cell infiltration, dendritic cell activation, and decreased type M2 macrophages in tumor post trastuzumab-L6 administration confirmed the immune-activating responses. In conclusion, trastuzumab-L6 was considered to be an immunostimulatory agent, rather than a traditional cytotoxic ADC, and its antitumor efficacy was enhanced when combined with an anti-PD-L1 and anti-CTLA-4 antibody, which suggested a potential therapeutic strategy.

Muscle synergies for evaluating upper limb in clinical applications: A systematic review.

Introduction: Muscle synergies have been proposed as a strategy employed by the central nervous system to control movements. Muscle synergy analysis is a well-established framework to examine the pathophysiological basis of neurological diseases and has been applied for analysis and assessment in clinical applications in the last decades, even if it has not yet been widely used in clinical diagnosis, rehabilitative treatment and interventions. Even if inconsistencies in the outputs among studies and lack of a normative pipeline including signal processing and synergy analysis limit the progress, common findings and results are identifiable as a basis for future research. Therefore, a literature review that summarizes methods and main findings of previous works on upper limb muscle synergies in clinical environment is needed to i) summarize the main findings so far, ii) highlight the barriers limiting their use in clinical applications, and iii) suggest future research directions needed for facilitating translation of experimental research to clinical scenarios. Methods: Articles in which muscle synergies were used to analyze and assess upper limb function in neurological impairments were reviewed. The literature research was conducted in Scopus, PubMed, and Web of Science. Experimental protocols (e.g., the aim of the study, number and type of participants, number and type of muscles, and tasks), methods (e.g., muscle synergy models and synergy extraction methods, signal processing methods), and the main findings of eligible studies were reported and discussed. Results: 383 articles were screened and 51 were selected, which involved a total of 13 diseases and 748 patients and 1155 participants. Each study investigated on average 15 ± 10 patients. Four to forty-one muscles were included in the muscle synergy analysis. Point-to-point reaching was the most used task. The preprocessing of EMG signals and algorithms for synergy extraction varied among studies, and non-negative matrix factorization was the most used method. Five EMG normalization methods and five methods for identifying the optimal number of synergies were used in the selected papers. Most of the studies report that analyses on synergy number, structure, and activations provide novel insights on the physiopathology of motor control that cannot be gained with standard clinical assessments, and suggest that muscle synergies may be useful to personalize therapies and to develop new therapeutic strategies. However, in the selected studies synergies were used only for assessment; different testing procedures were used and, in general, study-specific modifications of muscle synergies were observed; single session or longitudinal studies mainly aimed at assessing stroke (71% of the studies), even though other pathologies were also investigated. Synergy modifications were either study-specific or were not observed, with few analyses available for temporal coefficients. Thus, several barriers prevent wider adoption of muscle synergy analysis including a lack of standardized experimental protocols, signal processing procedures, and synergy extraction methods. A compromise in the design of the studies must be found to combine the systematicity of motor control studies and the feasibility of clinical studies. There are however several potential developments that might promote the use of muscle synergy analysis in clinical practice, including refined assessments based on synergistic approaches not allowed by other methods and the availability of novel models. Finally, neural substrates of muscle synergies are discussed, and possible future research directions are proposed. Conclusions: This review provides new perspectives about the challenges and open issues that need to be addressed in future work to achieve a better understanding of motor impairments and rehabilitative therapy using muscle synergies. These include the application of the methods on wider scales, standardization of procedures, inclusion of synergies in the clinical decisional process, assessment of temporal coefficients and temporal-based models, extensive work on the algorithms and understanding of the physio-pathological mechanisms of pathology, as well as the application and adaptation of synergy-based approaches to various rehabilitative scenarios for increasing the available evidence.

Nanocarrier of Pin1 inhibitor based on supercritical fluid technology inhibits cancer metastasis by blocking multiple signaling pathways.

Cancer metastasis is the primary cause of all cancer-related deaths due to the lack of effective targeted drugs that simultaneously block multiple signaling pathways that drive the dissemination and growth of cancer cells. The unique proline isomerase Pin1 activates numerous cancer pathways, but its role in cancer metastasis and the inhibitory efficacy of Pin1 inhibitors on cancer metastasis are unknown. Moreover, the applicability of Pin1 inhibitor-all-trans retinoic acid (ATRA) is limited due to its several drawbacks. Herein, uniform ATRA-loaded polylactic acid-polyethylene glycol block copolymer nanoparticles (ATRA-NPs) with high encapsulation efficiency, good cellular uptake, excellent controlled release performance and pharmacokinetics are developed using supercritical carbon dioxide processing combined with an optimized design. ATRA-NPs exhibited excellent biosafety and significant inhibition on the growth and metastasis of hepatocellular carcinoma. Pin1 played a key role in cancer metastasis and was the main target of ATRA-NPs. ATRA-NPs exerted their potent anti-metastatic effect by inhibiting Pin1 and then simultaneously blocking multiple signaling pathways and cancer epithelial-mesenchymal progression. Since ATRA-NPs could effectively couple the inhibition of cancer cell dissemination with cancer growth, it provided a novel therapeutic strategy for efficiently inhibiting cancer metastasis.

Changes in Depression Among Adolescents: A Multiple-Group Latent Profile Transition Analysis.

Background: Depression of adolescents is an important public health problem. Persistent depression will become a huge hidden danger of individual mental health development. It is important to study the change mechanism of adolescents' depression. Methods: A total of 563 males and 739 females aged 11-19 years reported their depression. 1302 adolescents participated in a short-term 6-month longitudinal study. They were contacted every three months for two follow-up tests (T2 and T3). Participants completed internet addiction test, self-rating anxiety scale and self-rating depression scale. Multiple-group latent profile transition analysis (MLPTA) was used to identify meaningful subgroups and transitions between groups across time. Covariates (anxiety and internet addiction) were used to analyze the influencing factors. Results: The results showed that: (1) There are three categories of adolescents' depression, namely no-depression group, low-depression-mountain group and low-depression-hill group. (2) The depression of the subjects showed a trend of improvement, but the proportion of low-depression-mountain group is relatively high at three time points (0.44, 0.59, and 0.30). (3) The transition probability between the low-depression-mountain group and the no-depression group is large, which suggests the low-depression-mountain group can easily convert into the no-depression group, but the transition probability from low-depression-hill group to other groups is relatively low and stable, which suggests the low-depression-hill group is not easily converted into the no-depression group. (4) Both anxiety and internet addiction affect the development of adolescents' depression across three time points. Anxiety played a significant role in affecting female adolescents' depression, while internet addiction played a significant role in affecting male adolescents' depression. Conclusion: This study demonstrated a transition pattern in adolescents' depression. We should pay more attention to the low-depression-mountain group and try to do their mental health well. Adolescents' Depression changes rapidly with anxiety and internet addiction for different genders, which suggests that some interventions are needed.

Biomimetic human eyes in adaptive lenses with conductive gels.

To investigate the imaging effect, adaptive robust lenses are prepared by sealing transparent liquid or gel. Lenses are fabricated using the negative-pressure method, which is a benefit for a stable biconvex shape. Under the action of an electric field, the soft lens deforms following the dielectric elastomer actuator (DEA). DE (dielectric elastomer) membranes expand in the plane perpendicular to the electric field lines. The toroidal driving area leads to a decrease in lens diameter and an increase in convex curvature. Therefore, the focal length of the lens becomes shorter. The experimental measurement utilizes the double focal length method. As a result, the largest focal length change that could be achieved was 44.7% (190 mm→105 mm) of the soft lens using a DEA with carbon grease electrodes. Furthermore, the ECG (electrocardiogram) conductive gel could replace traditional carbon grease for DEA electrodes in optics. This type of transparent electrode is creatively applied to a biomedical lens. Under the same conditions, the electrostriction rate in a DEA with ECG gel was achieved at 33%, which was greater than that of 28% in a DEA coupled with carbon grease electrode. Adaptive lenses have characteristics such as easy fabrication, low cost, and strong operability, and they possess great potential application value in biomedical feild.

Exploiting the size exclusion effect of protein adsorption layers for electrochemical detection of microRNA: A new mechanism for design of E-DNA sensor.

The assay performance of electrochemical DNA (E-DNA) sensors is deeply influenced by the state of DNA probes immobilized on electrode. Moreover, the immobilization procedures for DNA probes are tedious and vary according to the probes and analytes. In this work, we find that the adsorption layers of bovine serum albumin (BSA) on gold electrode (AuE) possess a size exclusion effect to distinguish between single-stranded (-ss) DNA probes and the DNA fragments generated from enzymatic digestion of ssDNA probes. In detail, the BSA layers act as a gatekeeper that hinders the adsorption of a ssDNA probe on AuE but permits the DNA fragments with much smaller sizes to pass through the adsorption layers and adsorb on AuE. This finding is developed into a novel E-DNA sensor for microRNA (miRNA) detection by coupling with duplex-specific nuclease (DSN)-assisted target recycling strategy. The ssDNA probe in solution phase is enzymatically digested during the DSN-assisted target recycling process initiated by target miRNA-21, generating plenty of DNA fragments. The adsorption of these DNA fragment on BSA/AuE is permitted, which arouses electrochemical signals after binding with [Ru(NH3)6]3+ to indicate the recognition of miRNA-21. The developed E-DNA sensor possesses a wide calibration range from 0.001 to 100 pM and a low detection limit of 0.48 fM. Significantly, accurate evaluation of miRNA-21 expression levels in cancer cell lines and non-small-cell lung carcinomas (NSCLC) serum samples are successfully achieved using the developed method. This work provides a new mechanism for constructing sensitive E-DNA sensor without tedious probe immobilization procedures.

Static Analysis with a Realistic Loading Condition on All-Ceramic Crown Prosthesis During Chewing

PURPOSE: To evaluate the stress distribution during chewing in a realistic loading condition on a prosthesis (single-tooth crown) using a static analysis. MATERIALS AND METHODS: An all-ceramic crown in the mandibular first molar was selected as the representative prosthesis. First, three contact states (intrusive state, transition state, and extrusive state) were selected from the parametric chewing trajectory. Then, the distances between the antagonistic molars and the normal vectors of the mandibular first molar were calculated by using an automated contact analysis routine (independently developed). Next, normal and tangential forces were defined based on the contact information and the food property. Finally, the static analysis was executed by applying the force and the fixed boundary condition. RESULTS: The distribution of the occlusal force was nonuniform in the static analysis. Compared to concentrated and uniform loading conditions, the stress distribution of the prosthesis under the nonuniform loading condition revealed new characteristics. CONCLUSION: The generation procedure of the static analysis, based on fundamental contact analysis, was evidence-based. The static analysis with the nonuniform loading condition was more recommended than the other two conditions.

Number of trials and data structure affect the number and components of muscle synergies in upper-limb reaching movements.

Objective.Due to the variability of human movements, muscle activations vary among trials and subjects. However, few studies investigated how data organization methods for addressing variability impact the extracted muscle synergies.Approach.Fifteen healthy subjects performed a large set of upper limb multi-directional point-to-point reaching movements. Then, the study extracted muscle synergies under different data settings and investigated how data structure prior to synergy extraction, namely concatenation, averaging, and single trial, the number of considered trials, and the number of reaching directions affected the number and components of muscle synergies.Main results.The results showed that the number and components of synergies were significantly affected by the data structure. The concatenation method identified the highest number of synergies, and the averaging method usually found a smaller number of synergies. When the concatenated trials or reaching directions was lower than a minimum value, the number of synergies increased with the increase of the number of trials or reaching directions; however, when the number of trials or reaching directions reached a threshold, the number of synergies was usually constant or with less variation even when novel directions and trials were added. Similarity analysis also showed a slight increase when the number of trials or reaching directions was lower than a threshold. This study recommends that at least five trials and four reaching directions and the concatenation method are considered in muscle synergies analysis during upper limb tasks.Significance.This study makes the researchers focus on the variability analysis induced by the diseases rather than the techniques applied for synergies analysis and promotes applications of muscle synergies in clinical scenarios.

Influence of Intellectual-cultural Orientation as Family Culture on Chinese College Students' Subjective Well-being: A Moderation Model.

The well-known mediation-moderation model of subjective well-being has been criticized because it oversimplified the concept of culture. This study aimed to explore whether the family culture, as supplement of social culture, has significant impacts on subjective well-being. The intellectual-cultural orientation subscale (ICO) of family environment scale-CV (FES-CV), Eysenck personality questionnaire for adult (EPQA), and index of well-being (IWB) were used to test 340 college students from China. Results showed that the extraversion and neuroticism of personality traits have great influences on subjective well-being, and intellectual-cultural orientation as family culture, to represent characteristic of family culture, serves as a moderating variable for the 2 components of subjective well-being. And all these findings revealed that the trait of family culture should be considered as a supplement of the social culture and a critical complementary moderating influenced factor for subjective well-being. Together with personality traits, it can explain the variance of subjective well-being to some extent. The family cultural has an important influence on college students' personality and subjective well-being. It is important to provide a high quality family cultural environment for college students.

Evaluation of Methods for the Extraction of Spatial Muscle Synergies.

Muscle synergies have been largely used in many application fields, including motor control studies, prosthesis control, movement classification, rehabilitation, and clinical studies. Due to the complexity of the motor control system, the full repertoire of the underlying synergies has been identified only for some classes of movements and scenarios. Several extraction methods have been used to extract muscle synergies. However, some of these methods may not effectively capture the nonlinear relationship between muscles and impose constraints on input signals or extracted synergies. Moreover, other approaches such as autoencoders (AEs), an unsupervised neural network, were recently introduced to study bioinspired control and movement classification. In this study, we evaluated the performance of five methods for the extraction of spatial muscle synergy, namely, principal component analysis (PCA), independent component analysis (ICA), factor analysis (FA), nonnegative matrix factorization (NMF), and AEs using simulated data and a publicly available database. To analyze the performance of the considered extraction methods with respect to several factors, we generated a comprehensive set of simulated data (ground truth), including spatial synergies and temporal coefficients. The signal-to-noise ratio (SNR) and the number of channels (NoC) varied when generating simulated data to evaluate their effects on ground truth reconstruction. This study also tested the efficacy of each synergy extraction method when coupled with standard classification methods, including K-nearest neighbors (KNN), linear discriminant analysis (LDA), support vector machines (SVM), and Random Forest (RF). The results showed that both SNR and NoC affected the outputs of the muscle synergy analysis. Although AEs showed better performance than FA in variance accounted for and PCA in synergy vector similarity and activation coefficient similarity, NMF and ICA outperformed the other three methods. Classification tasks showed that classification algorithms were sensitive to synergy extraction methods, while KNN and RF outperformed the other two methods for all extraction methods; in general, the classification accuracy of NMF and PCA was higher. Overall, the results suggest selecting suitable methods when performing muscle synergy-related analysis.

Spectrum Analysis Enabled Periodic Feature Reconstruction Based Automatic Defect Detection System for Electroluminescence Images of Photovoltaic Modules.

Electroluminescence (EL) imaging is a widely adopted method in quality assurance of the photovoltaic (PV) manufacturing industry. With the growing demand for high-quality PV products, automatic inspection methods based on machine vision have become an emerging area concern to replace manual inspectors. Therefore, this paper presents an automatic defect-inspection method for multi-cell monocrystalline PV modules with EL images. A processing routine is designed to extract the defect features of the PV module, eliminating the influence of the intrinsic structural features. Spectrum domain analysis is applied to effectively reconstruct an improved PV layout from a defective one by spectrum filtering in a certain direction. The reconstructed image is used to segment the PV module into cells and slices. Based on the segmentation, defect detection is carried out on individual cells or slices to detect cracks, breaks, and speckles. Robust performance has been achieved from experiments on many samples with varying illumination conditions and defect shapes/sizes, which shows the proposed method can efficiently distinguish intrinsic structural features from the defect features, enabling precise and speedy defect detections on multi-cell PV modules.

Intra-Subject and Inter-Subject Movement Variability Quantified with Muscle Synergies in Upper-Limb Reaching Movements.

Quantifying movement variability is a crucial aspect for clinical and laboratory investigations in several contexts. However, very few studies have assessed, in detail, the intra-subject variability across movements and the inter-subject variability. Muscle synergies are a valuable method that can be used to assess such variability. In this study, we assess, in detail, intra-subject and inter-subject variability in a scenario based on a comprehensive dataset, including multiple repetitions of multi-directional reaching movements. The results show that muscle synergies are a valuable tool for quantifying variability at the muscle level and reveal that intra-subject variability is lower than inter-subject variability in synergy modules and related temporal coefficients, and both intra-subject and inter-subject similarity are higher than random synergy matching, confirming shared underlying control structures. The study deepens the available knowledge on muscle synergy-based motor function assessment and rehabilitation applications, discussing their applicability to real scenarios.

Structure and SAXS studies unveiled a novel inhibition mechanism of the Pseudomonas aeruginosa T6SS TseT-TsiT complex.

The bacterial type VI secretion system (T6SS) is a powerful arsenal that fires many toxic effectors into neighboring cells to gain advantage over inter-bacterial competition and eukaryotic host infection. Meanwhile, the cognate immunity proteins of these effectors are employed to protect themselves from the virulence. TseT-TsiT is a newly discovered effector-immunity (E-I) protein pair secreted by T6SS of Pseudomonas aeruginosa. Our group had reported the crystal structure of TsiT before. Here, we report the crystal structure of P. aeruginosa TseT-TsiT complex at 3.1 Å resolution. The interface of TseT-TsiT is characterized in this work. Through structure and small angle X-ray scattering (SAXS) studies, we discover that the long C-terminal helix of TseT may be flexible. Combining the homolog comparison results, we propose that TseT may form an oligomer in favor of its putative nuclease activity. Although TsiT doesn't directly block the putative active-site of TseT, it may hinder the TseT's oligomerization process to neutralize its virulence.

[Design and performance analysis of elastic temporomandibular joint structure of biomimetic masticatory robot].

Masticatory robots have a broad application prospect in the field of denture material tests and mandible rehabilitation. Mechanism type of temporomandibular joint structure is an important factor influencing the performance of the masticatory robot. In view of the wide application of elastic components in the field of the biomimetic robot, an elastic component was adopted to simulate the buffering characteristics of the temporomandibular joint disc and formed the elastic temporomandibular joint structure on the basis of point-contact high pair. Secondly, the influences of the elastic temporomandibular joint structure (on mechanism degree, kinematics, dynamics, etc.) were discussed. The position and velocity of the temporomandibular joint were analyzed based on geometric constraints of the joint surface, and the dynamic analysis based on the Lagrange equation was carried out. Finally, the influence of the preload and stiffness of the elastic component was analyzed by the response surface method. The results showed that the elastic temporomandibular joint structure could effectively guarantee the flexible movement and stable force of the joint. The elastic joint structure proposed in this paper further improves the biomimetic behavior of masticatory robots. It provides new ideas for the biomimetic design of viscoelastic joint discs.

Characterization of the Pseudomonas aeruginosa T6SS PldB immunity proteins PA5086, PA5087 and PA5088 explains a novel stockpiling mechanism.

The bacterial type VI secretion system (T6SS) secretes many toxic effectors to gain advantage in interbacterial competition and for eukaryotic host infection. The cognate immunity proteins of these effectors protect bacteria from their own effectors. PldB is a T6SS trans-kingdom effector in Pseudomonas aeruginosa that can infect both prokaryotic and eukaryotic cells. Three proteins, PA5086, PA5087 and PA5088, are employed to suppress the toxicity of PldB-family proteins. The structures of PA5087 and PA5088 have previously been reported, but the identification of further distinctions between these immunity proteins is needed. Here, the crystal structure of PA5086 is reported at 1.90 Šresolution. A structural comparison of the three PldB immunity proteins showed vast divergences in their electrostatic potential surfaces. This interesting phenomenon provides an explanation of the stockpiling mechanism of T6SS immunity proteins.

Design of realistic chewing trajectory for dynamic analysis of the dental prosthesis.

PURPOSE: The chewing trajectory in the dynamic analysis of dental prosthesis is always defined as a two-segmental straight polyline without enough consideration about chewing force and motion laws. The study was aimed to design a realistic human chewing trajectory for the dynamic analysis based on force and motion planning methods. METHODS: The all-ceramic crown restored in the mandibular first molar was selected as the representative prosthesis. Firstly, a dynamic model containing two molar components and one flat food component was built, and an approximate chewing plane was predefined. According to the desired forces (25 N, 150 N and 25 N), three force planning points were calculated by using tentative trajectories. The motion planning was then executed based on four-segment cubic spline model. Finally, the new trajectory was re-imported into the dynamic model as the displacement load for evaluating its stress influence. RESULTS: The maximum lateral velocity was 26.81 mm/s. Besides, the forces in the three force planning points were 14.11 N, 126.75 N and 13.56 N. The overall repetition rate of chewing force was 77.21%. The force and stress profiles were similar to the sine curve on the whole. The maximum dynamic stress of the crown prosthesis was 398.5 MPa. CONCLUSIONS: The motion law was effectively brought into the chewing trajectory to introduce the dynamic effect. The global force performance was acceptable, and the force profile was more realistic than the traditional chewing trajectory. The additional reliable characteristic feature of the stress distribution of the dental prosthesis was observed.

Modular Organization of Muscle Synergies to Achieve Movement Behaviors.

Muscle synergy has been applied to comprehend how the central nervous system (CNS) controls movements for decades. However, it is not clear about the motion control mechanism and the relationship between motions and muscle synergies. In this paper, we designed two experiments to corroborate the hypothesis: (1) motions can be decomposed to motion primitives, which are driven by muscle synergy primitives and (2) variations of motion primitives in direction and scale are modulated by activation coefficients rather than muscle synergy primitives. Surface electromyographic (EMG) signals were recorded from nine muscles of the upper limb. Nonnegative matrix factorization (NMF) was applied to extract muscle synergy vectors and corresponding activation coefficients. We found that synergy structures of different movement patterns were similar (α=0.05). The motion modulation indexes (MMI) among movement patterns in reaching movements showed apparent differences. Merging coefficients and reconstructed similarity of synergies between simple motions and complex motions were significant. This study revealed the motion control mechanism of the CNS and provided a rehabilitation and evaluation method for patients with motor dysfunction in exercise and neuroscience.

Photodynamic Therapy for Genital Warts Causes Activation of Local Immunity.

BACKGROUND: 5-aminolevulinic acid photodynamic therapy (PDT) for genital warts is effective, safe, and can prevent recurrence. It is believed that PDT can induce immune responses, but the mechanism is not completely understood. OBJECTIVES: The objectives of this article are to confirm the effect of PDT for genital warts on local immunity and to investigate the recruitment and significance of immune cells in tissues. METHODS: Local immune changes in T lymphocytes (CD3+, CD4+, CD8+), plasmacytoid dendritic cells (pDCs) (CD123+), and myeloid dendritic cells (CD1a+) after PDT in patients were evaluated by immunohistochemistry staining. Changes in mRNA levels of IFN-γ, IFN-α, IFN-ß, interferon-stimulated gene 15 kDa (ISG-15), Mx2, Toll-like receptor 9 (TLR9), and interferon regulatory factor 7 (IRF7) were analyzed by real-time quantitative polymerase chain reaction. RESULTS: At 4 hours after PDT, CD4+ increased, accompanied by increased levels of mRNA expression of IFN-γ, but CD4+ and mRNA expression levels of IFN-γ were decreased at 24 hours after PDT. CD123+ pDCs showed an increasing trend. CD1a+ LCs in the epidermis gradually decreased, and DCs in the epidermis gradually increased. CD3+ infiltrated and migrated to the superficial dermis, but CD8+ did not change significantly after PDT. The mRNA expression levels of IFN-α, IFN-ß, ISG-15, Mx2, TLR9, and IRF7 showed an increasing trend after PDT. As compared with the patients without significantly increased IFN-α and IFN-ß after PDT sessions, patients with significant increases needed fewer sessions of PDT for remission. CONCLUSIONS: PDT for genital warts can activate T lymphocyte-mediated, DC-related, and pDC-related immunity. The clinical efficacy of PDT for genital warts may be related to the increased levels of IFN-α and IFN-ß after treatment.

Dosimetric comparison of intensity-modulated radiotherapy and three-dimensional conformal radiotherapy for cerebral malignant gliomas.

PURPOSE: To compare the dose distribution characteristics of tumor target area, normal tissues and organs at risk in patients with malignant gliomas treated with intensity- modulated radiotherapy (IMRT) and three-dimensional conformal radiotherapy (3DCRT). METHODS: Plans of IMRT and 3DCRT were designed for each of the 96 included patients with malignant gliomas. Tumor dose was 60 Gy, and the dose distribution differences between the target area and normal tissues were compared using dose-volume histogram (DVH). RESULTS: Gross tumor volume (GTV) doses for 95% of the volume in the plans of IMRT and 3DCRT were as follows: 59.82±0.43, 57.68±0.62 Gy (p<0.05); clinical target volume (CTV): 58.16±0.48, 54.47±0.28 Gy (p<0.05); and planning treatment volume (PTV): 57.38±0.74, 54.21±0.48 Gy (p<0.05). The conformal index (CI) values of IMRT and 3DCRT plans were 0.92±0.15 and 0.73±0.12, respectively (p<0.05), whereas the homogeneity index (HI) values variability of IMRT and 3DCRT were 0.78±0.12 and 1.13±0.09 respectively (p<0.05). For normal brain tissues pituitary and optic chiasm, the maximum dose (Dmax) and the mean dose (Dmean) of lens exposure differed significantly between thw two plans (p<0.05). CONCLUSION: The target dose distribution of IMRT was superior to that of 3DCRT in terms of rationality, uniformity and conformal nature. IMRT may be better in protecting normal tissue and increasing the tumor radiation dose compared with 3DCRT.