Combination immunotherapy of glioblastoma with dendritic cell cancer vaccines, anti-PD-1 and poly I:C.

Glioblastoma (GBM) is a lethal cancer with limited therapeutic options. Dendritic cell (DC)-based cancer vaccines provide a promising approach for GBM treatment. Clinical studies suggest that other immunotherapeutic agents may be combined with DC vaccines to further enhance antitumor activity. Here, we report a GBM case with combination immunotherapy consisting of DC vaccines, anti-programmed death-1 (anti-PD-1) and poly I:C as well as the chemotherapeutic agent cyclophosphamide that was integrated with standard chemoradiation therapy, and the patient remained disease-free for 69 months. The patient received DC vaccines loaded with multiple forms of tumor antigens, including mRNA-tumor associated antigens (TAA), mRNA-neoantigens, and hypochlorous acid (HOCl)-oxidized tumor lysates. Furthermore, mRNA-TAAs were modified with a novel TriVac technology that fuses TAAs with a destabilization domain and inserts TAAs into full-length lysosomal associated membrane protein-1 to enhance major histocompatibility complex (MHC) class I and II antigen presentation. The treatment consisted of 42 DC cancer vaccine infusions, 26 anti-PD-1 antibody nivolumab administrations and 126 poly I:C injections for DC infusions. The patient also received 28 doses of cyclophosphamide for depletion of regulatory T cells. No immunotherapy-related adverse events were observed during the treatment. Robust antitumor CD4+ and CD8+ T-cell responses were detected. The patient remains free of disease progression. This is the first case report on the combination of the above three agents to treat glioblastoma patients. Our results suggest that integrated combination immunotherapy is safe and feasible for long-term treatment in this patient. A large-scale trial to validate these findings is warranted.

O-GlcNAcylation in cancer development and immunotherapy.

O-linked ß-D-N-acetylglucosamine (O-GlcNAc), as a posttranslational modification (PTM), is a reversible reaction that attaches ß-N-GlcNAc to Ser/Thr residues on specific proteins by O-GlcNAc transferase (OGT). O-GlcNAcase (OGA) removes the O-GlcNAc from O-GlcNAcylated proteins. O-GlcNAcylation regulates numerous cellular processes, including signal transduction, the cell cycle, metabolism, and energy homeostasis. Dysregulation of O-GlcNAcylation contributes to the development of various diseases, including cancers. Accumulating evidence has revealed that higher expression levels of OGT and hyper-O-GlcNAcylation are detected in many cancer types and governs glucose metabolism, proliferation, metastasis, invasion, angiogenesis, migration and drug resistance. In this review, we describe the biological functions and molecular mechanisms of OGT- or O-GlcNAcylation-mediated tumorigenesis. Moreover, we discuss the potential role of O-GlcNAcylation in tumor immunotherapy. Furthermore, we highlight that compounds can target O-GlcNAcylation by regulating OGT to suppress oncogenesis. Taken together, targeting protein O-GlcNAcylation might be a promising strategy for the treatment of human malignancies.

[Comparison of curative effect between Tianji robot assisted screw placement and traditional cannulated screw internal fixation for femoral neck fracture].

OBJECTIVE: To investigate the clinical efficacy and advantages of Tianji orthopedic robot assisted cannulated screw internal fixation for femoral neck fracture. METHODS: The clinical data of 41 patients with femoral neck fracture who underwent internal fixation with cannulated screws from January 2019 to January 2022 were retrospectively analyzed. According to different surgical methods, they were divided into Tianji robot group and traditional cannulated screw fixation group (traditional operation group). Among them, there were 18 patients in Tianji robot group including 8 males and 10 females with age of (56.00±4.22) years old, Garden typeⅠ (4 cases), type Ⅱ (11 cases), type Ⅲ (2 cases), and type Ⅳ (1 case). There were 23 patients in the traditional operation group, including 10 males and 13 females, aged (54.87±4.81) years old;there were 5 cases of Garden typeⅠ, 14 cases of type Ⅱ, 3 cases of type Ⅲ and 1 case of type Ⅳ. The operation time, intraoperative blood loss, fluoroscopy times, guide needle placement times, operation costs and other indicators were observed and compared between two groups. Harris score was used to evaluate hip joint function 12 months after operation. RESULTS: The wounds of all patients healed in Grade A without complications. There were significant differences between two groups in terms of operation time, times of intraoperative fluoroscopy, times of guide needle placement, amount of intraoperative bleeding, and operation cost (P<0.05). All 41 patients were followed up for at least 12 months. The fractures of both groups were healed. There was no infection, screw loosening, fracture displacement and femoral head necrosis in Tianji robot group during follow-up;Screw loosening occurred in 2 patients in the traditional operation group during follow-up. At 12 months after operation, Harris hip joint function score of Tianji robot group was higher than that of traditional operation group in daily activity, lameness, joint activity score and total score (P<0.05). CONCLUSION: Tianji robot assisted nail placement is a better method for the treatment of femoral neck fracture, which improves the surgical efficiency, is more accurate, has higher success rate of one-time nail placement, shorter operation time, less radiation, and has better hip joint function recovery after surgery.

Two new antimicrobial monoterpenoid indole alkaloids from the roots of Rauvolfia yunnanensis.

Two new monoterpenoid indole alkaloids 3-hydroxylochnerine (1) and 10-hydroxyvinorine (2) were isolated from the roots of Rauvolfia yunnanensis. Their structures were elucidated based on the analysis of spectroscopic data and ECD calculation. Both compounds exhibited potent antimicrobial activity against Bacillus subtilis and Escherichia coli, and their activities were comparable to the well-known antibacterial drug berberine.

Rapid Recovery of Postoperative Pulmonary Function in Patients With Lung Cancer and Influencing Factors.

Among malignant tumors, lung cancer has the highest morbidity and mortality worldwide. Surgery is the first-line treatment for early-stage lung cancers, and has gradually advanced from conventional open-chest surgery to video-assisted thoracic surgery (VATS). Additionally, increasingly smaller surgical incisions and less surgical trauma have resulted in reduced pulmonary function damage. Previous studies have found that the level of pulmonary function loss and recovery is significantly correlated with postoperative complications and the quality of life. Thus, an accurate assessment of the preoperative pulmonary function and effective rehabilitation of postoperative pulmonary function are highly important for patients undergoing lung surgery. In addition, pulmonary function assessment after pulmonary rehabilitation serves as an objective indicator of the postoperative pulmonary rehabilitation status and is crucial to facilitating pulmonary function recovery. Furthermore, a complete preoperative assessment and effective rehabilitation are especially critical in elderly patients with pulmonary tumors, poor basic physiological functions, comorbid lung diseases, and other underlying diseases. In this review, we summarize the clinical significance of pulmonary function assessment in patients undergoing lung cancer surgery, postoperative changes in pulmonary function, effective pulmonary function rehabilitation, and the influencing factors of pulmonary function rehabilitation.

Mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS) syndrome mimicking herpes simplex encephalitis: A case report.

Mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes (MELAS) syndrome presents with the features of herpes simplex encephalitis (HSE), which is rare and has been described in only a few case reports. Our case describes a 17-year-old female with no significant previous medical history presenting with an acute onset of fever, headache, and epilepsy, similar to HSE. Computed tomography of the brain showed bilateral basal ganglia calcification. Magnetic resonance imaging demonstrated gyriform restricted diffusion with T2-weighted images prolongation. Further investigation showed elevated blood lactate concentration at rest. Hence, MELAS was suspected and the diagnosis was confirmed by the presence of a nucleotide 3243 A→G mutation in the mitochondrial DNA. The clinical presentation and imaging studies of MELAS are variable and may mimic those of HSE. Infection may have also precipitated MELAS manifestation in this patient. Laboratory features, such as elevated lactate, basal ganglia calcification, and gyriform restricted diffusion may be helpful in identifying patients with MELAS.

Association of Increased Remnant Cholesterol and the Risk of Coronary Artery Disease: A Retrospective Study.

Background and Aims: Low-density lipoprotein cholesterol (LDL-C) is the primary target of lipid-lowering therapy in coronary artery disease (CAD). But some patients with the normal levels of LDL-C still suffer from CAD progression and malignant outcomes (e.g., major adverse cardiovascular events [MACEs]), and the mechanism is unclear. The previous prospective studies demonstrated that the remnant cholesterol (RC) and non-high-density lipoprotein cholesterol (non-HDL-C) were capable to predict the risk of CAD. This study evaluated the association between RC and non-HDL-C with the risk of CAD. Methods: In our study, 12,563 patients were enrolled. We categorized patients into four concordance/discordance groups according to the median of RC, LDL-C, and non-HDL-C. Then, we performed a propensity score matching (PSM) strategy. The unadjusted and adjusted multivariate logistic regression models were used to evaluate the relationship between the lipid concentrations. Results: In this study, 8,658 (68.9%) patients were male with a median age of 61 (54 and 67) years. The multivariate logistic regression showed the odds ratio (OR) of RC was 1.952 (CI = 1.276-2.988, p = 0.002). The OR of the low RC/high LDL-C group was 0.626 (CI = 0.504-0.778, p < 0.001) and the OR of the low RC/high non-HDL-C group was 0.574 (CI = 0.462-0.714, p < 0.001). The p-values for interaction between the RC and hypertension, diabetes were both < 0.001. Conclusion: Our study showed a significant association between the RC and CAD. The level of RC was more capable to reflect the risk of CAD than LDL-C and non-HDL-C. There was an interaction relationship between RC and age, gender, hypertension, diabetes, in CAD. But we did not find whether there was a relationship between the non-HDL-C and CAD.

Autoimmune diseases in HIV-negative cryptococcal meningitis.

Aim: The purpose of our study was to assess the differences between HIV-negative cryptococcal meningitis (CM) patients with and without autoimmune diseases. Methods: A total of 43 CM patients with autoimmune diseases and 67 without autoimmune diseases were enrolled for analysis. Results: CM patients with autoimmune diseases had higher fever, modified Rankin Scale scores, C-reactive protein and erythrocyte sedimentation rate, but had lower rates of visual and hearing symptoms, ventriculoperitoneal shunts, MRI meningeal enhancement and amphotericin B treatment, as well as lower cerebrospinal fluid pressure and fungal counts. When divided according to gender, each group had lower intracranial pressure and higher inflammation indicators. No differences in outcomes, sequelae and mortality hazard were found. Fluconazole treatment was a prognostic factor for CM without autoimmune diseases. Conclusions: Both antifungal and anti-inflammatory therapy should be considered in CM patients with autoimmune diseases.

Epidemiological and numerical simulation of rabies spreading from canines to various human populations in mainland China.

BACKGROUND: The mortality of humans due to rabies in China has been declining in recent years, but it is still a significant public health problem. According to the global framework, China strives to achieve the goal of eliminating human rabies before 2030. METHODS: We reviewed the epidemiology of human deaths from rabies in mainland China from 2004 to 2018. We identified high risk regions, age and occupational groups, and used a continuous deterministic susceptibility-exposure-infection-recovery (SEIR) model with periodic transmission rate to explore seasonal rabies prevalence in different human populations. The SEIR model was used to simulate the data of human deaths from rabies reported by the Chinese Center for Disease Control and Prevention (China CDC). We calculated the relative transmission intensity of rabies from canines to different human groups, and they provided a reliable epidemiological basis for further control and prevention of human rabies. RESULTS: Results showed that human deaths from rabies exhibited regional differences and seasonal characteristics in mainland China. The annual human death from rabies in different regions, age groups and occupational groups decreased steadily across time. Nevertheless, the decreasing rates and the calculated R0s of canines of various human groups were different. The transmission intensity of rabies from canines to human populations was the highest in the central regions of China, in people over 45 years old, and in farmers. CONCLUSIONS: Although the annual cases of human deaths from rabies have decreased steadily since 2007, the proportion of human deaths from rabies varies with region, age, gender, and occupation. Further enhancement of public awareness and immunization status in high-risk population groups and blocking the transmission routes of rabies from canines to humans are necessary. The concept of One Health should be abided and human, animal, and environmental health should be considered simultaneously to achieve the goal of eradicating human rabies before 2030.

Discovery of the EL-0052 as a potential anesthetic drug.

As a γ-aminobutyric acid A receptor (GABAAR) inhibitor, etomidate fulfills several characteristics of an ideal anesthetic agent, such as rapid onset with rapid clearance and high potency, along with cardiovascular stability. Unfortunately, etomidate has been reported to inhibit CYP11B1 at hypnotic doses, which is associated with a marked increase in patient deaths due to this unexpected off-target effect. In this study, molecular docking was used to simulate the binding mode of etomidate with GABAAR and CYP11B1. Based on the in-depth analysis of the binding mode, strong electron-withdrawing group on the C4 position of the imidazole ring was introduced to reduce the charge density of the nitrogen, which is beneficial in reducing the coordination bond between the imidazole nitrogen and heme iron in CYP11B1, as well as in reducing the adrenocortical suppression. Based on the results of ADMET property prediction, MEP analysis, and molecular docking simulation, 4-fluoroetomidate (EL-0052) was designed and synthesized. In vivo studies in rats and mice confirmed that EL-0052 had the efficacy similar to etomidate, but without adrenocortical suppression. These findings suggested that EL-0052 was superior to etomidate and support the continued development of EL-0052 as a preclinical candidate as an anesthetic.

Large-area rainbow holographic diffraction gratings on a curved surface using transferred photopolymer films.

We report the fabrication of large-area holographic diffraction gratings on a curved surface from transferred photopolymer films by introducing a water-soluble interlayer. The holographic gratings on a curved surface have a diffraction efficiency of ∼63%, which is ∼80% of the recorded holographic film on a flat surface. By transferring a recorded holographic grating to a flat substrate, we obtained rainbow holographic gratings under white light illumination. This can be explained by the deformation of the holographic gratings. Our result provides a low-cost method for fabricating diffraction optical elements on a curved surface for optical systems.

Red yeast rice prevents atherosclerosis through regulating inflammatory signaling pathways.

OBJECTIVE: To observe the effects of red yeast rice (RYR) on blood lipid levels, aortic atherosclerosis (AS), and plaque stability in apolipoprotein E gene knockout (ApoE-/-) mice. METHODS: Twenty-four ApoE-/- mice were fed with a high-fat diet starting from 6 weeks of age. Mice were randomized into three groups (n = 8 in each group): model group (ApoE-/- group), RYR group (ApoE-/- + RYR group), and simvastatin group (ApoE-/- + simvastatin group). Eight 6-week-old C57BL/6 mice were assigned as the control group and fed with a basic diet. After 36 weeks, plasma lipids and inflflammatory factors were measured. Aortic atherosclerotic lesions by microscope, scanning electron microscope and transmission electron microscope were observed. Plasma levels of interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) were measured with enzyme-linked immunosorbent assay. The level of high sensitivity C-reaction protein (Hs-CRP) was detected by the scattering immunoturbidimetric assay. Protein expression of matrix metalloproteinase-9 (MMP-9) and nuclear factor κB (NF-κB) in aorta were tested by immunohistochemistry. RESULTS: Compared with the model group, treatment with RYR significantly decreased the levels of total cholesterol, triglyceride, low-density lipoprotein cholesterol, lipoprotein (a), and apolipoprotein B100 in ApoE-/- mice (P<0.01). Compared with the model group, treatment with RYR decreased the levels of Hs-CRP, IL-6, and TNF-α (P<0.01). RYR also reduced the protein levels of NF-κB and MMP-9 of the aorta. CONCLUSIONS: RYR has the anti-atherosclerotic and stabilizing unstable plaque effects. The mechanism might be related to the inflflammatory signaling pathways.

In Situ Fabrication of Halide Perovskite Nanocrystal-Embedded Polymer Composite Films with Enhanced Photoluminescence for Display Backlights.

A simple and versatile in situ fabrication of MAPbX3 nanocrystal-embedded polymer composite films is developed by controlling the crystallization process from precursor solutions. The composite films exhibit enhanced photoluminescence properties, improved stability, and excellent piezoelectric and mechanical properties. Applications of these composite films as color converters in liquid-crystal-display backlights are demonstrated, showing bright potential in display technology.

Low-Rank Decomposition-Based Restoration of Compressed Images via Adaptive Noise Estimation.

Images coded at low bit rates in real-world applications usually suffer from significant compression noise, which significantly degrades the visual quality. Traditional denoising methods are not suitable for the content-dependent compression noise, which usually assume that noise is independent and with identical distribution. In this paper, we propose a unified framework of content-adaptive estimation and reduction for compression noise via low-rank decomposition of similar image patches. We first formulate the framework of compression noise reduction based upon low-rank decomposition. Compression noises are removed by soft thresholding the singular values in singular value decomposition of every group of similar image patches. For each group of similar patches, the thresholds are adaptively determined according to compression noise levels and singular values. We analyze the relationship of image statistical characteristics in spatial and transform domains, and estimate compression noise level for every group of similar patches from statistics in both domains jointly with quantization steps. Finally, quantization constraint is applied to estimated images to avoid over-smoothing. Extensive experimental results show that the proposed method not only improves the quality of compressed images obviously for post-processing, but are also helpful for computer vision tasks as a pre-processing method.

Ambient-Temperature Spin-State Switching Achieved by Protonation of the Amino Group in [Fe(H2Bpz2)2(bipy-NH2)].

Magnetism of a complex [Fe(H2Bpz2)2(bipy-NH2)] (H2Bpz2 = dihydrobis(1-pyrazolyl)borate, bipy-NH2 = 4,4'-diamino-2,2'-bipyridine) has been altered from paramagnetic to spin-crossover (SCO) behavior, through protonation of one amino group of bipy-NH2 with CF3SO3H. Complete SCO transition, both in solid state and in solution, occurs at ambient temperature.

Compressive Sampling-Based Image Coding for Resource-Deficient Visual Communication.

In this paper, a new compressive sampling-based image coding scheme is developed to achieve competitive coding efficiency at lower encoder computational complexity, while supporting error resilience. This technique is particularly suitable for visual communication with resource-deficient devices. At the encoder, compact image representation is produced, which is a polyphase down-sampled version of the input image; but the conventional low-pass filter prior to down-sampling is replaced by a local random binary convolution kernel. The pixels of the resulting down-sampled pre-filtered image are local random measurements and placed in the original spatial configuration. The advantages of the local random measurements are two folds: 1) preserve high-frequency image features that are otherwise discarded by low-pass filtering and 2) remain a conventional image and can therefore be coded by any standardized codec to remove the statistical redundancy of larger scales. Moreover, measurements generated by different kernels can be considered as the multiple descriptions of the original image and therefore the proposed scheme has the advantage of multiple description coding. At the decoder, a unified sparsity-based soft-decoding technique is developed to recover the original image from received measurements in a framework of compressive sensing. Experimental results demonstrate that the proposed scheme is competitive compared with existing methods, with a unique strength of recovering fine details and sharp edges at low bit-rates.

Analysis of Decorrelation Transform Gain for Uncoded Wireless Image and Video Communication.

An uncoded transmission scheme called SoftCast has recently shown great potential for wireless video transmission. Unlike conventional approaches, SoftCast processes input images only by a series of transformations and modulates the coefficients directly to a dense constellation for transmission. The transmission is uncoded and lossy in nature, with its noise level commensurate with the channel condition. This paper presents a theoretical analysis for an uncoded visual communication, focusing on developing a quantitative measurements for the efficiency of decorrelation transform in a generalized uncoded transmission framework. Our analysis reveals that the energy distribution among signal elements is critical for the efficiency of uncoded transmission. A decorrelation transform can potentially bring a significant performance gain by boosting the energy diversity in signal representation. Numerical results on Markov random process and real image and video signals are reported to evaluate the performance gain of using different transforms in uncoded transmission. The analysis presented in this paper is verified by simulated SoftCast transmissions. This provide guidelines for designing efficient uncoded video transmission schemes.

Quality of Life Among Breast Cancer Survivors 2 Years After Diagnosis: The Relationship With Adverse Childhood Events and Posttraumatic Growth.

BACKGROUND: Quality of life (QoL) is an important patient outcome in oncology. Many breast cancer survivors report difficulties with QoL. Adverse childhood events (ACEs) and posttraumatic growth (PTG) may influence QoL in breast cancer survivors after diagnosis. OBJECTIVE: The aim of this study was to determine the association of QoL with ACEs and PTG among breast cancer survivors 2 years after diagnosis. METHODS: This was a cross-sectional study, conducted on 93 Chinese breast cancer survivors diagnosed at least 2 years prior to the study. Measures included a self-reported demographic questionnaire, the Adverse Childhood Experiences questionnaires, the Posttraumatic Growth Inventory, and the Functional Assessment of Cancer Therapy-Breast Cancer QoL questionnaire. RESULTS: Among the 93 participants, more than one-third (34.4%) experienced childhood adversity. We found a negative relationship between ACEs and QoL and a positive relationship between PTG and QoL. CONCLUSIONS: The findings suggest that childhood adversity and PTG are important predictors of QoL among breast cancer survivors at least 2 years after diagnosis. Women who had experienced ACEs had poorer health-related QoL than did those who did not. Individuals who experienced PTG following a cancer diagnosis also reported better QoL than did those who did not. IMPLICATIONS FOR PRACTICE: A better understanding of how ACE and PTG contribute to breast cancer survivors' QoL will help in tailoring and therefore enhancing the efficacy of interventions aimed at improving QoL.

Image Denoising via Bandwise Adaptive Modeling and Regularization Exploiting Nonlocal Similarity.

This paper proposes a new image denoising algorithm based on adaptive signal modeling and regularization. It improves the quality of images by regularizing each image patch using bandwise distribution modeling in transform domain. Instead of using a global model for all the patches in an image, it employs content-dependent adaptive models to address the non-stationarity of image signals and also the diversity among different transform bands. The distribution model is adaptively estimated for each patch individually. It varies from one patch location to another and also varies for different bands. In particular, we consider the estimated distribution to have non-zero expectation. To estimate the expectation and variance parameters for every band of a particular patch, we exploit the nonlocal correlation in image to collect a set of highly similar patches as the data samples to form the distribution. Irrelevant patches are excluded so that such adaptively learned model is more accurate than a global one. The image is ultimately restored via bandwise adaptive soft-thresholding, based on a Laplacian approximation of the distribution of similar-patch group transform coefficients. Experimental results demonstrate that the proposed scheme outperforms several state-of-the-art denoising methods in both the objective and the perceptual qualities.

[Clinical study on treatment of carotid atherosclerosis with extraction of polygoni cuspidati rhizoma et radix and crataegi fructus: a randomized controlled trial].

OBJECTIVE: To observe the effect of detoxifying and blood circulation activating Chinese herb extraction of polygonum cuspidatum and hawthorn on carotid intima-media thickness (IMT), plaque integral and plaque stability related serum indexes of patients with carotid atherosclerosis. METHOD: Sixty and four cases of carotid artery atherosclerosis patients were assigned randomly to 2 groups: detoxifying and blood circulation activating treatment group (treatment group, 32 cases) and control group (32 cases). Patients in treatment group were treated with capsules of extraction of polygonum cuspidatum and hawthorn, 1 pill po, bid (dosage of administration: polygonum cuspidatum extraction 5.33 mg x kg(-1) x d(-1), hawthorn extraction 5.0 mg x kg(-1) x d(-1)); patients in control group were treated with lovastatin 20 mg po, qd (dosage of administration: 0.33 mg x kg(-1) x d(-1)). The course of treatment was six months. To observe changes of IMT, plaque integral, and detect the level of plaque stability related serum indexes such as Hs-CRP, MMP-1 and TIMP-1. RESULT: After 6 months of treatment, in control group one patient quit the clinical trial because of liver dysfunction and one patient was rejected because of having not followed the therapeutic regimen. 32 cases in treatment group and 30 cases in control group were analyzed. The results showed that IMT and plaque integral of treatment group decreased significantly after the treatment (P < 0.05, P < 0.01), and there was no significant difference compared with control grope. Serum Hs-CRP, MMP-1 and MMP-1/TIMP-1 decreased after the treatment (P < 0.05, P < 0.01), and the treatment group was superior to control group in decreasing serum Hs-CRP (P < 0.05). CONCLUSION: Detoxifying and blood circulation activating Chinese herb extraction of polygonum cuspidatum and hawthorn has good effect of anti-atherosclerosis and promoting plaque stability. Its mechanism might be related with anti-inflammation and inhibiting degradation of extracellular matrix, and deserves further studies.