Purkinje cells of vestibulocerebellum play an important role in acute vestibular migraine.

Both the central and peripheral vestibular systems contribute to the pathogenesis of vestibular migraine, although the mechanism of vestibular migraine remains unclear. To assess central and peripheral vestibular system damage in vestibular migraine and explore the underlying mechanism we performed vestibular function tests, including a caloric test, spontaneous, gaze-evoked nystagmus and saccadic, pursuit and optokinetic eye movements to evaluate the involvement of the central and/or peripheral vestibular system in subjects with acute vestibular migraine episodes. It was found that both peripheral and central vestibular systems were damaged in vestibular migraine patients with the number of subjects with central deficits significantly larger than those with peripheral deficits. The cerebellum, especially the vestibule cerebellum, is the most important part of the central vestibular system. Locculus and paraflocculus are essential structures of cerebellar circuitry controlling vestibular nuclei and oculomotor functions and are anatomically linked with the "migraine pathway". Purkinje cells are the only source of cerebellar output and it innervates inhibitory action. Therefore, we examined the effect of the electric stimulation on paraflocculus Purkinje cells by using a specific electrical stimulation of trigeminal ganglia to induce a migraine-like phenomenon in animal part. Moreover, electrophysiological recordings showed that parafloccular Purkinje cells of rats underwent electrical stimulation of trigeminal ganglia resulted in partial inhibition. It is suggested that Purkinje cells in the paraflocculus could be inhibited after the occurrence of migraine episode and this inhibition may be an important factor leading to vestibular migraine.

Tumor apelin, not serum apelin, is associated with the clinical features and prognosis of gastric cancer.

BACKGROUND: To study the association between Apelin expression and the clinical features and postoperative prognosis in patients with gastric cancer (Int J Cancer 136:2388-2401, 2015). METHODS: Tumor samples and matched adjacent normal tissues were collected from 270 patients with GC receiving surgical resection. The tumor and serum Apelin levels were determined by immunohistochemistry and ELISA methods, respectively. GC cell lines were cultured for migration and invasive assays. RESULTS: Our data showed that tumor Apelin expression status, instead of serum Apelin level, was closely associated with more advance clinical features including tumor differentiation, lymph node and distant metastases. Moreover, patients with high tumor Apelin level had a significantly shorter overall survival period compared to those with low Apelin expression and those with or negative Apelin staining. Our in vitro study revealed that the Apelin regulated the migration and invasion abilities of GC cell lines, accompanied by up-regulations of a variety of cytokines associated with tumor invasiveness. CONCLUSION: Our data suggest that tumor Apelin can be used as a marker to evaluate clinical characteristics and predict prognosis in GC patients.

Automated interventricular septum segmentation for black-blood myocardial T2* measurement in thalassemia.

PURPOSE: To develop and validate an automated segmentation method that extracts the interventricular septum (IS) from myocardial black-blood images for the T2* measurement in thalassemia patients. MATERIALS AND METHODS: A total of 144 thalassemia major patients (age range, 11-51 years; 73 males) were scanned with a black-blood multi-echo gradient-echo sequence using a 1.5 Tesla Siemens Sonata system (flip angle 20°, sampling bandwidth 810 Hz/pixel, voxel size 1.56 × 1.56 × 10 mm(3) and variable fields of view (20-30) × 40 cm(2) depending on patient size). The improved Chan-Vese model with an automated initialization by the circular Hough transformation was implemented to segment the endocardial and epicardial margins of the left ventricle (LV). Consequently, the IS was extracted by analyzing the anatomical relation between the LV and the blood pool of the right ventricle, identified by intensity thresholding. The proposed automated IS segmentation (AISS) method was compared with the conventional manual method by using the Bland-Altman analysis and the coefficient of variation (CoV). RESULTS: The T2* measurements using the AISS method were in good agreement with those manually measured by experienced observers with a mean difference of 1.71% and a CoV of 4.15% (P < 0.001). CONCLUSION: Black-blood myocardial T2* measurement can be fully automated with the proposed AISS method.

Improved pixel-by-pixel MRI R2* relaxometry by nonlocal means.

PURPOSE: To investigate the feasibility of improving MRI R2* mapping by filtering the images before curve-fitting. METHODS: Pixel-by-pixel curve-fitting for the quantification of MRI relaxometry remains a challenge for low signal-to-noise ratio images. By computing the weighted mean of spatially adjacent pixels, the low-pass Gaussian (LPG) filter can suppress the noise but at the expense of blurring. By assigning high weights to pixels with similar neighborhood patches, the nonlocal means (NLM) algorithm can reduce noise while retaining intrinsic signals, however, its potential has not been explored in pixel-by-pixel MRI relaxometry, and in this study, we aimed to investigate the impact of the LPG and the NLM filtering on decay signals and MRI R2* mapping. These two filtering methods were compared on both simulated and in vivo data. RESULTS: Both LPG and NLM algorithms produces R2* maps with decreased root-mean-square-errors. The LPG filter blurs edges of R2* maps while the NLM algorithm preserves details well. The NLM consistently yields R2* mapping with smaller errors than the LPG filtering in all cases. CONCLUSION: Pixel-by-pixel fitting can skew MRI relaxometry. The NLM outperforms the conventional LPG filter and has the potential to provide more accurate pixel-by-pixel MRI relaxometry for improved tissue characterization.

A novel semiautomatic parenchyma extraction method for improved MRI R2* relaxometry of iron loaded liver.

PURPOSE: To propose and evaluate an automatic method of extracting parenchyma from a manually delineated whole liver for the R2* measurement of iron load. MATERIALS AND METHODS: In all, 108 transfusion-dependent patients with a wide range of hepatic iron content were scanned with a multiecho gradient-echo sequence. The R2* was measured by fitting the average signal of liver parenchyma, extracted by the proposed semiautomatic parenchyma extraction (SAPE), traditional manually delineated multiple regions-of-interest (mROIs), and T2* thresholding methods to the noise-corrected monoexponential model. The R2* measurement accuracy of the SAPE method was evaluated through simulation; the intra- and interobserver reproducibility of SAPE, mROI, and T2* thresholding were assessed from the in vivo data using coefficient of variation (CoV). RESULTS: In the simulation, the mean absolute percentage error of R2* measurement using SAPE was 0.23% (range 0.01%-1.09%). In vivo study, the CoVs of intra- and interobserver reproducibility were 0.83%, 1.39% for SAPE, 3.63%, 6.28% for mROI, and 1.62%, 2.66% for T2* thresholding, respectively. CONCLUSION: The SAPE method provides an accurate and reliable approach to assessing the overall hepatic iron content. The improved magnetic resonance imaging (MRI) R2* reproducibility using the SAPE method may lead to more accurate tissue characterization and increased diagnostic confidence.

A dataset of endorheic basins on detailed delineation and classification for the Qinghai-Tibet Plateau.

Endorheic basins are important geomorphological and ecological units on the Qinghai-Tibet Plateau (QTP), which is undergoing a rapid evolution of its lake system structure and drainage reorganization that is threatening local ecology, infrastructures and residuals owing to climate change. This dataset provides a detailed delineation and classification of endorheic basins on the QTP for understanding the complex dynamics under climate changes. A newly-developed algorithm, namely the Joint Elevation-Area Threshold (JEAT) algorithm (Liu et al, 2024), is applied for delineating endorheic basins based on digital elevation model (DEM). A total of 184 endorheic basins were divided, of which the permanent divide lines were characterized. All the endorheic basins were further categorized into five groups based on the hydraulic connectivity attributes, which have been commonly observed since 2000. The dataset also includes basic information such as drainage area, water surface area, and water storage volume of each endorheic basin. It is particularly beneficial for digital watershed analysis towards ecological restoration and water resource management on the environmentally vulnerable QTP.

Microstructures and Properties of NbC-Reinforced Ni-Based Coatings Synthesized In Situ by Ultrasonic Vibration-Assisted Laser Cladding.

This paper aims to explore the mechanism of an ultrasonic applied field on the microstructures and properties of coatings, and clarify the evolution of the molten pool under different ultrasonic frequencies. The Taguchi experimental design method was adopted in this paper. NbC-reinforced Ni-based coatings were in situ synthesized by laser cladding to investigate the effects of ultrasonic vibration process parameters on the microstructure, pore area, microhardness, and wear resistance of the cladding layer. The results show that the pore area decreases first and then increases as ultrasonic power increases from 600 to 900 W and ultrasonic frequency from 23 to 40 kHz. On the contrary, the hardness and wear resistance increase at first and then decrease. The pore area is minimized at 800 W ultrasonic power and 32 kHz ultrasonic frequency, and the hardness is maximized at 600 W ultrasonic power and 40 kHz ultrasonic frequency. Meanwhile, the highest wear resistance can be obtained when ultrasonic power is 700 W and ultrasonic frequency is 32 kHz. Based on the phase structure analysis, the cladding layer mainly consists of FeNi3, NbC, B4C, and CrB2. Ultrasonic vibration will not change the phase composition of the layer. Combined with the varying G/R value and cooling rate, the reasons for the change in grain morphology in different areas were analyzed to reveal the evolution mechanism of the molten pool under the influence of ultrasound.

Case report: 10-year survival of a patient with a primary hepatic gastrointestinal stromal tumor.

Background: Gastrointestinal stromal tumors (GISTs) are mesenchymal tumors of the gastrointestinal tract. Extra-gastrointestinal stromal tumors (EGISTs) predominantly arise outside the gastrointestinal tract, although primary hepatic GISTs are extremely rare. GISTs are highly aggressive; they often grow to a large size. Here, we report the 10-year survival of a patient with a primary hepatic GIST following sequential response therapy. Case presentation: A 50-year-old Chinese man complained of fatigue and slight abdominal pain, and presented with a large lump in the liver, which was detected by computed tomography (CT). He was subsequently diagnosed with a primary hepatic GIST, based on CT-guided fine needle aspiration cytology and immunohistochemistry analyses. The presence of GIST or EGIST metastases was excluded using CT, esophagogastroduodenoscopy, colonoscopy, and ultrasound. Cytological examination showed that the tumor was composed of epithelioid and spindle cells. Immunohistochemistry analysis revealed positive staining for CD117 (KIT) and DOG1, and negative staining for CD34, S-100, and α-smooth muscle actin (SMA). Following tumor ablation with argon-helium cryosurgery, the patient received imatinib mesylate for 61 months. However, this treatment was discontinued because of disease progression, at which point interventional therapy was administered once. One month later, sunitinib malate was administered for 71 months. The patient achieved long-term survival for 135 months. Conclusions: EGISTs can be easily misdiagnosed as other types of tumors because they have no specific characteristics to distinguish them during imaging examinations. However, our case study demonstrates that the long-term survival of patients with EGISTs can be achieved with molecular targeted therapy.

Circ_0075804 Regulates the Expression of LASP1 by Targeting miR-1287-5p and Thus Affects the Biological Process of Retinoblastoma.

PURPOSE: Increasing evidence reveals that circular RNA (circRNA) dysregulation is involved in retinoblastoma (RB) pathogenesis. To further realize the development of RB, we investigated the role and regulatory mechanism of circ_0075804 in RB. METHODS: Real-time quantitative PCR (RT-qPCR) and western blot were employed for expression analysis. CCK-8 assay, EdU assay, colony formation assay, flow cytometry assay and transwell assay were performed to monitor cell phenotypes. Xenograft models were established to monitor the role of circ_0075804 on tumor growth. Tumor growth was assessed by the expression of Ki67, N-cadherin, MMP2 and MMP9 via IHC assay. The predicted binding sites between miR-1287-5p and circ_0075804 or LIM and SH3 protein 1 (LASP1) were validated by dual-luciferase reporter assay. RESULTS: Upregulation of circ_0075804 and LASP1, and downregulation of miR-1287-5p were shown in RB tissues and cells. Circ_0075804 knockdown repressed RB cell growth, invasion and survival, and hindered tumor development in vivo. MiR-1287-5p was targeted by circ_0075804, and its repression largely reversed the functional effects of circ_0075804 knockdown. LASP1 was a functional target of miR-1287-5p. The inhibition of miR-1287-5p upregulation on RB cell proliferation, survival and invasion was reversed by LASP1 overexpression. Moreover, circ_0075804 knockdown weakened LASP1 expression via increasing miR-1287-5p. CONCLUSION: Circ_0075804 promotes LASP1 expression by targeting miR-1287-5p, thus acting as a contributor to RB carcinogenesis.HighlightsCirc_0075804 is overexpressed in RB.Circ_0075804 knockdown inhibits RB cell malignant phenotypes and tumor growth in vivo.Circ_0075804 regulates RB cell behaviors by targeting miR-1287-5p.MiR-1287-5p affects RB cell behaviors by binding to LASP1.Circ_0075804 regulates LASP1 expression via targeting miR-1287-5p.

Synergistic effects of epigallocatechin gallate and l-theanine in nerve repair and regeneration by anti-amyloid damage, promoting metabolism, and nourishing nerve cells.

Green tea has significant protective activity on nerve cells, but the mechanism of action is unclear. Epigallocatechin gallate (EGCG) and N-ethyl-L-glutamine (L-theanine) are the representative functional components of green tea (Camellia sinensis). In this study, an AD model of Aß25-35-induced differentiated neural cell line PC12 cells was established to study the synergistic effect of EGCG and L-theanine in protecting neural cells. The results showed that under Aß25-35 stress conditions, mitochondria and axons degenerated, and the expression of cyclins was up-regulated, showing the gene and protein characteristics of cellular hyperfunction. EGCG + L-theanine inhibited inflammation and aggregate formation pathways, significantly increased the percentage of G0/G1 in the cell cycle, downregulated the expression of proteins such as p-mTOR, Cyclin D1, and Cyclin B1, upregulated the expression of GAP43, Klotho, p-AMPK, and other proteins, promoted mitochondrial activity and energy metabolism, and had repair and regeneration effects on differentiated nerve cells. The synergistic mechanism study showed that under the premise that EGCG inhibits amyloid stress and inflammation and promotes metabolism, L-theanine could play a nourish nerve effect. EGCG + L-theanine keeps differentiated nerve cells in a quiescent state, which is beneficial to the repair and regeneration of nerve cells. In addition, EGCG + L-theanine maintains the high-fidelity structure of cellular proteins. This study revealed for the first time that the synergistic effect of EGCG with L-theanine may be an effective way to promote nerve cell repair and regeneration and slow down the progression of AD. Our findings provide a new scientific basis for the relationship between tea drinking and brain protection.

MicroRNA-375 is a therapeutic target for castration-resistant prostate cancer through the PTPN4/STAT3 axis.

The functional role of microRNA-375 (miR-375) in the development of prostate cancer (PCa) remains controversial. Previously, we found that plasma exosomal miR-375 is significantly elevated in castration-resistant PCa (CRPC) patients compared with castration-sensitive PCa patients. Here, we aimed to determine how miR-375 modulates CRPC progression and thereafter to evaluate the therapeutic potential of human umbilical cord mesenchymal stem cell (hucMSC)-derived exosomes loaded with miR-375 antisense oligonucleotides (e-375i). We used miRNA in situ hybridization technique to evaluate miR-375 expression in PCa tissues, gain- and loss-of-function experiments to determine miR-375 function, and bioinformatic methods, dual-luciferase reporter assay, qPCR, IHC and western blotting to determine and validate the target as well as the effects of miR-375 at the molecular level. Then, e-375i complexes were assessed for their antagonizing effects against miR-375. We found that the expression of miR-375 was elevated in PCa tissues and cancer exosomes, correlating with the Gleason score. Forced expression of miR-375 enhanced the expression of EMT markers and AR but suppressed apoptosis markers, leading to enhanced proliferation, migration, invasion, and enzalutamide resistance and decreased apoptosis of PCa cells. These effects could be reversed by miR-375 silencing. Mechanistically, miR-375 directly interfered with the expression of phosphatase nonreceptor type 4 (PTPN4), which in turn stabilized phosphorylated STAT3. Application of e-375i could inhibit miR-375, upregulate PTPN4 and downregulate p-STAT3, eventually repressing the growth of PCa. Collectively, we identified a novel miR-375 target, PTPN4, that functions upstream of STAT3, and targeting miR-375 may be an alternative therapeutic for PCa, especially for CRPC with high AR levels.

[Assess correlation between bleb morphology at long-term intraocular pressure effect in primary angle-closure glaucoma following trabeculectomy].

OBJECTIVE: To evaluate the correlation between morphologic appearance of blebs at 3 month and long-term intraocular pressure (IOP) effect in patients with primary angle-closure glaucoma (PACG) after trabeculectomy. METHODS: Multi-centered cases series. Data were collected from 176 patients aged ≥ 40 years with PACG who were participated in a randomized clinical trial that aimed at addressing the efficacy of augmented releasable sutures after trabeculectomy. The bleb morphology was graded using the Modified Indian Bleb Appearance Grading Scale (IBAGS) based on standard photos at 3 month after trabeculectomy. IOPs were measured with Goldmann applanation tonometer. The correlation between bleb components and other selected testing influencing factors and long-term IOP was tested by linear Logistic regression analysis. RESULTS: 150 patients (85.7%) completed 18 months of follow up. IOP was (15.6 ± 5.4) mm Hg at 18 month of post-operation. 135 eyes had an IOP ≤ 21 mm Hg without additional medications, 10 eyes ≥ 21 mm Hg, and the remaining 5 eyes required one or two medications to maintain normal IOP. Using IBAGS system, bleb was graded in 142 eyes as follows: H(0) in 3 eyes, H(1) in 45 eyes, H(2) in 90 eyes, and H(3) in 4 eyes, while V(0) was observed in 66 eyes, V(1-3) in 76 eyes. IOP at 18 months in bleb with microcysts was 2.77 mm Hg lower (ß = -2.77, 95%CI = -0.46 to -5.08) than those without microcysts and in bleb with non-vascular was 2.07 mm Hg lower (ß = -2.07, 95%CI = -0.15 to -3.98) than those with vascular at 3 months after surgery. IOP was significantly (ß = -1.20, 95%CI: -0.00 to -2.40) decreased by 1.2 mm Hg with 10 years of age increase (P < 0.05). CONCLUSIONS: Early filtering bleb with microcysts, vascular, and age are identified as important factors to predict long-term IOP effect in patients with PACG after trabeculectomy but not early morphological appearance of filtering bleb.

Molecular Mediators of Estrogen Reduction-induced Otolith Shedding.

OBJECTIVE: Previous study suggested that estradiol (E2) plays an important role in otolith shedding by regulating the expression of otoconin 90 (OC90). The purpose of this article is to provide further data on the effect and mechanism of E2 on the morphology of otolith. METHODS: The rats receiving bilateral ovariectomy (OVX) were used as animal models. Co-immunoprecipitation was used to observe the relationship between estrogen receptor (ER) and estrogen-related receptor α (ERRα). The morphology of otolith was observed under the scanning electron microscopy. Western blotting and qPCR were used for quantitative analysis of the roles of ER and ERRα in regulating OC90 expression. RESULTS: The looser otoliths were observed in rats receiving bilateral OVX, which could be reversed by supplementation with E2. The level of ERRα was decreased in bilateral OVX rats. ER and ERRα interacted with each other on the regulation of the expression of OC90. CONCLUSION: Our results suggest ER and ERRα are both important downstream receptors involved in regulating OC90 expression in utricles of rats, and ERRα probably functions by interacting with ER. This provides evidence for the mechanism of otolith shedding. And it may be significant for future studies of targeted prevention and therapies for benign paroxysmal positional vertigo.

Inhibitory Effects of Six Types of Tea on Aging and High-Fat Diet-Related Amyloid Formation Activities.

Aging and lipid metabolism disorders promote the formation and accumulation of amyloid with ß-sheet structure, closely related to cardiovascular disease, senile dementia, type 2 diabetes, and other senile degenerative diseases. In this study, five representative teas were selected from each of the six types of tea, and a total of 30 teas were selected to evaluate the inhibitory activities on the formation of aging-related amyloid in vitro. The results showed that the 30 teas had a significant inhibitory effect on the formation activity on aging-related amyloid at the protein level in vitro. Although the content of catechins is relatively low, black tea and dark tea still have significant antioxidant activity and inhibit the formation of amyloid. A high-fat diet established the model of lipid metabolism disorder in premature aging SAMP8 mice, and these mice were gavaged different tea water extracts. The results showed that different tea types have a significant inhibitory effect on the formation of ß-amyloid and Aß42 mediated by age-related lipid metabolism disorders, and the in vivo activity of fully fermented teas was better than that of green tea. The action mechanism was related to antioxidation, anti-inflammatory, and improving lipid metabolism.

Anti-damage effect of theaflavin-3'-gallate from black tea on UVB-irradiated HaCaT cells by photoprotection and maintaining cell homeostasis.

Keratinocytes are rich in lipids and are the main sensitive cells to ultraviolet (UV) rays. Theaflavins are the core functional components of black tea and are known as the "soft gold" in tea. In this study, ultraviolet-B (UVB) irradiation caused apoptosis and necrosis of human epidermal keratinocytes (HaCaT). EGCG and the four theaflavins had anti-UVB damage activity, among which theaflavin-3'-gallate (TF3'G) had the best activity. The results of biophysical and molecular biology experiments showed that TF3'G has anti-damage effects on UVB-irradiated HaCaT cells through the dual effects of photoprotection and maintenance of cell homeostasis. That is, TF3'G preincubation could absorb UV rays, reduce the accumulation of aging-related heterochromatin (SAHF) formation, increase mitochondrial membrane potential, downregulate NF-κB inflammation pathways, inhibit the formation of cytotoxic aggregates, and protect biological macromolecules Structure, etc. The accumulation of conjugated π bonds and the balance benzoquinone are the core functional structure of TF3'G with high efficiency and low toxicity. The study indicates that TF3'G has the potential to inhibit the photoaging and intrinsic aging of skin cells.

Research progress on the potential delaying skin aging effect and mechanism of tea for oral and external use.

Skin aging is characterized by the gradual loss of elasticity, the formation of wrinkles and various color spots, the degradation of extracellular matrix proteins, and the structural changes of the dermis. With the increasingly prominent problems of environmental pollution, social pressure, ozone layer thinning and food safety, skin problems have become more and more complex. The skin can reflect the overall health of the body. Skincare products for external use alone cannot fundamentally solve skin problems; it needs to improve the overall health of the body. Based on the literature review in recent 20 years, this paper systematically reviewed the potential delaying effect of tea and its active ingredients on skin aging by oral and external use. Tea is the second-largest health drink after water. It is rich in tea polyphenols, l-theanine, tea pigments, caffeine, tea saponins, tea polysaccharides and other secondary metabolites. Tea and its active substances have whitening, nourishing, anti-wrinkle, removing spots and other skincare effects. Its mechanism of action is ultraviolet absorption, antioxidant, anti-inflammatory, inhibition of extracellular matrix aging, inhibiting the accumulation of melanin and toxic oxidation products, balancing intestinal and skin microorganisms, and improving mood and sleep, among other effects. At present, tea elements skincare products are deeply loved by consumers. This paper provides a scientific theoretical basis for tea-assisted beauty and the high-end application of tea in skincare products.

Research progress of epigallocatechin-3-gallate (EGCG) on anti-pathogenic microbes and immune regulation activities.

At the end of 2019, the COVID-19 virus spread worldwide, infecting millions of people. Infectious diseases induced by pathogenic microorganisms such as the influenza virus, hepatitis virus, and Mycobacterium tuberculosis are also a major threat to public health. The high mortality caused by infectious pathogenic microorganisms is due to their strong virulence, which leads to the excessive counterattack by the host immune system and severe inflammatory damage of the immune system. This paper reviews the efficacy, mechanism and related immune regulation of epigallocatechin-3-gallate (EGCG) as an anti-pathogenic microorganism drug. EGCG mainly shows both direct and indirect anti-infection effects. EGCG directly inhibits early infection by interfering with the adsorption on host cells, inhibiting virus replication and reducing bacterial biofilm formation and toxin release; EGCG indirectly inhibits infection by regulating immune inflammation and antioxidation. At the same time, we reviewed the bioavailability and safety of EGCG in vivo. At present, the bioavailability of EGCG can be improved to some extent using nanostructured drug delivery systems and molecular modification technology in combination with other drugs. This study provides a theoretical basis for the development of EGCG as an adjuvant drug for anti-pathogenic microorganisms.

Long Non-coding RNA JHDM1D-AS1 Interacts with DHX15 Protein to Enhance Non-Small-Cell Lung Cancer Growth and Metastasis.

JHDM1D antisense 1 (JHDM1D-AS1), a long non-coding RNA (lncRNA), has been shown to promote pancreatic cancer growth by inducing an angiogenic response. However, its biological and clinical significance in non-small-cell lung cancer (NSCLC) is still unclear. In this study, we examined the expression and prognostic significance of JHDM1D-AS1 in NSCLC. The effects of JHDM1D-AS1 knockdown or overexpression on NSCLC growth and metastasis were investigated. We show that JHDM1D-AS1 is upregulated in NSCLC relative to adjacent normal lung tissues. High JHDM1D-AS1 expression is significantly correlated with advanced tumor, node, and metastasis (TNM) stage and lymph node metastasis. JHDM1D-AS1 expression serves as an independent prognostic factor for overall survival of patients with NSCLC. Functionally, JHDM1D-AS1 knockdown inhibits NSCLC cell aggressiveness both in vitro and in vivo, which is rescued by ectopic expression of JHDM1D-AS1. JHDM1D-AS1 binding stabilizes DHX15 protein in NSCLC cells. DHX15 overexpression enhances NSCLC cell proliferation and invasion, whereas knockdown of DHX15 exerts opposite effects. JHDM1D-AS1-mediated aggressive phenotype is impaired when DHX15 is silenced. Ectopic expression of DHX15 restores the defects in proliferation and invasion of JHDM1D-AS1-depleted NSCLC cells. Collectively, the interaction between JHDM1D-AS1 and DHX15 accounts for NSCLC growth and metastasis. This work provides potential additional therapeutic targets for treatment of NSCLC.

Establishment of cancer/testis antigen profiling based on clinicopathological characteristics in resected pathological stage III non-small cell lung cancer.

BACKGROUND: Cancer/testis antigen (CTA) expression was found to be highly heterogeneous in previous studies. We aimed to establish a precision CTA profiling in resected stage III non-small cell lung cancer (NSCLC) and demonstrate the best CTA combination covering the widest range of NSCLC cases. MATERIALS AND METHODS: The expression of 10 CTAs was evaluated in 200 resected stage III NSCLC tissue specimens at protein level. Hierarchical clustering and python programming language analyses was used to demonstrate CTA expression and coverage. RESULTS: The most commonly expressed CTAs for total cases were MAGEA1 (60.0%), MAGEA10 (50.0%), and KK-LC-1 (47.5%). CTA expression was histology dependent, and concurrent expression was common. The best 2, 3, and 4 CTA combination covered 72.0%, 76.5%, and 79.5% of total cases, respectively. Stratified analysis based on variable clinicopathological characteristics achieved the maximum coverage of 92.3% with only 2 CTA combination in patients with features of male sex, positive smoking history, and adenocarcinoma, compared with a 85.0% coverage when 10 CTAs were assessed. Selected CTA expression was correlated with prognosis based on subgroup analysis. No significant difference was found between CTA expression and epidermal growth factor receptor mutant status. CONCLUSION: We established an individualized CTA profiling in resected stage III NSCLC based on 10 CTA expression. With the help of computer programming language, the goal of the maximum CTA expression coverage was reached by using the least CTA combination based on sex, smoking history, and histology. These results were significant for the further study of CTA-specific T-cell immunotherapy.

Lymphocyte-to-monocyte ratio is associated with prognosis of diffuse large B-cell lymphoma: correlation with CD163 positive M2 type tumor-associated macrophages, not PD-1 positive tumor-infiltrating lymphocytes.

The research aims to examine the prognostic value of the lymphocyte-to-monocyte ratio (LMR), neutrophil-to- lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) in diffuse large B-cell lymphoma (DLBCL). The relation of these hematologic indicators to poor antitumor immunity and prognosis must be investigated. Clinicopathologic data and survival information of 355 patients with DLBCL was retrospectively analyzed. Univariate analysis revealed that lower LMR (<2.71), higher NLR (≥2.81), CD163+ M2 tumor-associated macrophages (TAM) content ≥9.5% and programmed cell death 1 (PD-1)+ tumor-infiltrating lymphocytes (TILs) content < 4.5 cells per high power field(HPF) were significantly related to unfavorable overall survival (OS) and progression free survival (PFS). When considering the prognostic indexes of IPI, multivariate analysis confirmed that LMR of <2.71 and CD163+ M2 TAM content ≥9.5% significantly affected the prognosis of DLBCL. Spearman correlation test showed LMR was negatively correlated with CD163+ M2 TAM content. However, there were no correlation was found between LMR and PD-1+ TIL as well as between NLR and PD-1+ TIL content. These results indicated that decreased LMR lead to a weak anti-tumor immunity and could be used as a bad prognosis biomarker of DLBCL.