Search

Abstract Objective To analyze primary angle closure suspect (PACS) patients’ anatomical characteristics of anterior chamber configuration, and to establish artificial intelligence (AI)-aided diagnostic system for PACS screening. Methods A total of 1668 scans of 839 patients were included in this cross-sectional study. The subjects were divided into two groups: PACS group and normal group. With anterior segment optical coherence tomography scans, the anatomical diversity between two groups was compared, and anterior segment structure features of PACS were extracted. Then, AI-aided diagnostic system was constructed, which based different algorithms such as classification and regression tree (CART), random forest (RF), logistic regression (LR), VGG-16 and Alexnet. Then the diagnostic efficiencies of different algorithms were evaluated, and compared with junior physicians and experienced ophthalmologists. Results RF [sensitivity (Se) = 0.84; specificity (Sp) = 0.92; positive predict value (PPV) = 0.82; negative predict value (NPV) = 0.95; area under the curve (AUC) = 0.90] and CART (Se = 0.76, Sp = 0.93, PPV = 0.85, NPV = 0.92, AUC = 0.90) showed better performance than LR (Se = 0.68, Sp = 0.91, PPV = 0.79, NPV = 0.90, AUC = 0.86). In convolutional neural networks (CNN), Alexnet (Se = 0.83, Sp = 0.95, PPV = 0.92, NPV = 0.87, AUC = 0.85) was better than VGG-16 (Se = 0.84, Sp = 0.90, PPV = 0.85, NPV = 0.90, AUC = 0.79). The performance of 2 CNN algorithms was better than 5 junior physicians, and the mean value of diagnostic indicators of 2 CNN algorithm was similar to experienced ophthalmologists. Conclusion PACS patients have distinct anatomical characteristics compared with health controls. AI models for PACS screening are reliable and powerful, equivalent to experienced ophthalmologists.

Abstract This paper investigates an intelligent reflecting surface (IRS) assisted downlink short packet transmission system, where an access point sends short packets to multiple devices with the help of an IRS. Specifically, a performance comparison between the frequency division multiple access and time division multiple access is conducted for the considered system, from the perspective of average age of information (AoI). To minimize the maximum average AoI among all devices, the resource allocation and passive beamforming are jointly optimized. However, the formulated problem is difficult to solve due to the non‐convex objective function and coupled variables. Thus, an alternating optimization based algorithm is proposed by exploiting the semidefinite relaxation and bisection search techniques. Simulation results show that time division multiple access can achieve lower AoI by exploiting the time‐selective passive beamforming of IRS for maximizing the signal to noise ratio of each device consecutively. Moreover, it also shows that as the length of information bits becomes sufficiently large as compared to the available bandwidth, the proposed frequency division multiple access transmission scheme becomes more favourable due to more flexible power allocation.

Abstract The increasing prevalence of wearable devices has sparked a growing interest in real‐time health monitoring and physiological parameter tracking. This study focuses on the development of a cost‐effective sweat analysis device, utilizing microfluidic technology and selective electrochemical electrodes for non‐invasive monitoring of glucose and potassium ions. The device, through real‐time monitoring of glucose and potassium ion levels in sweat during physical activity, issues a warning signal when reaching experimentally set thresholds (K+ concentration at 7.5 mM, glucose concentrations at 60 μM and 120 μM). This alerts users to potential dehydration and hypoglycemic conditions. Through the integration of microfluidic devices and precise electrochemical analysis techniques, the device enables accurate and real‐time monitoring of glucose and potassium ions in sweat. This advancement in wearable technology holds significant potential for personalized health management and preventive care, promoting overall well‐being, and optimizing performance during physical activities.

Abstract Background There are various recommendations for third-line treatment in mCRC, however, there is no consensus on who is more suitable for particular strategy. Chemotherapy re-use in third-line setting is a common option in clinical practice. This study aimed to investigate the efficacy of third-line chemotherapy re-use by the comparison with that of anti-angiogenic monotherapy, and further find the population more suitable for third-line chemotherapy. Methods Using electronic medical records of patients with mCRC, a retrospective cohort study was conducted. A total of 143 patients receiving chemotherapy and 40 patients receiving anti-angiogenic monotherapy in third-line setting as control group were retrospectively collected. Baseline characteristics were analyzed using the χ² test or the Fisher’s exact test. ROC curve and surv_cutpoint function of ‘survminer’ package in R software were used to calculate the cut-off value. Survival curves were plotted with the Kaplan-Meier method and were compared using the log-rank test. The Cox proportional hazard regression model was used to analyze the potential risk factors. Results A total of 143 patients receiving chemotherapy and 40 patients receiving anti-angiogenic monotherapy in third-line setting were retrospectively collected. Chemotherapy rechallenge was recorded in 93 patients (93/143, 65.0%), and the remaining patients chose new chemotherapeutic drugs that had not been previously used, including irinotecan-based (22/50), oxaliplatin-based (9/50), raltitrexed (9/50), gemcitabine (5/50) and other agents (5/50). The ORR and DCR of third-line chemotherapy reached 8.8%, 61.3%, respectively (anti-angiogenic monotherapy group: ORR 2.6%, DCR 47.4%). The mPFS and mOS of patients receiving chemotherapy were 4.9 and 12.0 m, respectively (anti-angiogenic monotherapy group: mPFS 2.7 m, mOS 5.2 m). Subgroup analyses found that patients with RAS/RAF mutation, longer PFS (greater than 10.6 m) in front-line treatment or larger tumor burden had better prognosis with third-line chemotherapy rather than anti-angiogenic monotherapy. Conclusions Third-line chemotherapy re-use was effective in mCRC. Those with more aggressive characteristics (RAS/RAF mutant, larger tumor burden) or better efficacy of previous chemotherapy (longer PFS) were more appropriate for third-line chemotherapy, rather than anti-angiogenic monotherapy.

Abstract Background Increasing evidence has showed that inflammatory biomarkers, including neutrophil to lymphocyte ratio (NLR), platelet to lymphocyte ratio (PLR) and fibrinogen can be used as predictors in the prognosis of esophageal squamous cell carcinoma (ESCC). The aim of this study was to explore prognostic value of these biomarkers and evaluate the clinicopathological and prognostic significance of combined score based on plasma fibrinogen and platelet-lymphocyte ratio (F-PLR score). Methods A total of 506 patients with ESCC were enrolled in this study. Harrell’s concordance index (c-index) was used to determine the optimal cut-off values of these markers and evaluate their prognostic significance. The relationship between factors with survival rates (including overall survival [OS] and disease-free survival [DFS]) was explored by Kaplan-Meier curve, univariate analysis and multivariate cox hazard analysis. Results Our result indicated that high F-PLR score was significantly associated with longer tumor length and deeper depth of tumor invasion (p

Abstract Background The prognosis of patients with previously treated advanced gastric or gastroesophageal junction (GEJ) cancer remains poor. Given the robust development of immunotherapy and targeted therapy during the last decades, we aimed to investigate if the combination of traditional second-line chemotherapy with sintilimab and apatinib could bring survival benefits for these patients. Methods In this single-center, single-arm, phase II trial, patients with previously treated advanced gastric or GEJ adenocarcinoma received specific dose level of intravenous paclitaxel or irinotecan (investigator’s choice), 200 mg intravenous sintilimab on day 1, and 250 mg oral apatinib once daily continuously in each cycle until disease progression, intolerable toxicity, or withdrawal of consent. The primary endpoints were objective response rate and progression-free survival. The secondary endpoints were mainly overall survival and safety. Results From May 2019 to May 2021, 30 patients were enrolled. At the data cutoff date (March 19, 2022), the median follow-up duration was 12.3 months and 53.6% (95% CI, 33.9–72.5%) patients achieved objective response. The median progression-free survival and overall survival were 8.5 months (95% CI, 5.4–11.5) and 12.5 months (95% CI, 3.7–21.3), respectively. Grade 3–4 adverse events included hematological toxicities, elevated alanine aminotransferase, elevated aspartate aminotransferase, elevated alkaline phosphatase, elevated gamma-glutamyl transpeptidase, hyperbilirubinemia and proteinuria. The most frequent grade 3–4 adverse event was neutropenia (13.3%). No serious treatment-related adverse events or treatment-related deaths occurred. Conclusion Sintilimab plus apatinib and chemotherapy demonstrates promising anti-tumor activity with manageable safety profile in patients with previously treated advanced gastric or GEJ cancer. Trial registration ClinicalTrials.gov: NCT05025033, 27/08/2021.

Background: There are multiple recommendations on the third-line therapy of metastatic colorectal cancer (mCRC); however, no consensus has been reached. Objectives: This study aimed to explore the patient demographics and the real-world third-line treatment landscape of mCRC. Design: A retrospective real-world cohort study. Methods: Electronic medical records of mCRC patients from Tianjin Medical University Cancer Institute and Hospital between 2013 and 2020 were collected. Upon descriptive, comparative, and survival analyses, a retrospective study was conducted to describe demographics and clinical outcomes of mCRC patients receiving third-line treatment. Results: Among 218 mCRC patients receiving third-line therapy, 65.5% received chemotherapy combined with or without targeted drugs, followed by anti-angiogenic monotherapy (18.4%), anti-epidermal growth factor receptor drugs (6.9%) and immunotherapy (6.4%). The overall response rate and disease control rate reached 10.2% and 59.2%, respectively; and median progression-free survival (PFS) and overall survival were 4.0 m and 10.7 m, respectively. After Cox multivariate analysis, we found that therapeutic regime was an independent prognostic factor. Compared to patients receiving anti-angiogenic monotherapy, those receiving chemotherapy combined with or without targeted drugs exhibited better prognosis. For patients whose PFS were longer in the front-line treatment, the PFS of third-line therapy was also relatively longer ( p = 0.023). Multiple types of therapies (>3, p = 0.002) or multiple drugs (>5, p = 0.024) in the whole-course management of mCRC are indicators of longer survival. Conclusion: Chemotherapy combined with or without targeted therapy remained dominated third-line choice and showed favorable efficacy compared with anti-angiogenic monotherapy. With the application of more types and quantities of effective drugs, patients would achieve better survival.

The global energy crisis and growing environmental concerns provide a strong impetus for the development of fuel-efficient hydraulic excavators (HEs). The boom potential energy of a conventional HE is consumed by throttling in a lowering process, which is a major reason for energy inefficiency. To solve the issue, this paper presents a flywheel-based boom energy regeneration system for HEs using load-sensing systems. The otherwise wasted boom potential energy is regenerated by a pump/motor and stored in a flywheel. The recaptured energy is reused in the form of pressure energy released to the pump outlet. The energy efficiencies of a conventional load-sensing system and the proposed system were analyzed. A control strategy was proposed to optimize the energy-saving procedure. To obtain a more reliable simulation model, a coasting experiment of the flywheel was carried out to obtain the key parameters related to the friction of the flywheel. A 4-t HE in our laboratory was selected as a study case to investigate the energy-saving effect of the flywheel-based boom energy regeneration system. Numeric simulations showed that compared with a conventional load-sensing system, the energy-saving rate was about 32.7% in a typical digging and dumping cycle. These findings indicated that the flywheel-based boom energy regeneration system is promising for developing energy-efficient HEs.

Background: Neurodegenerative diseases, including age-related macular degeneration (AMD), may be linked to mitochondrial dysfunction and endoplasmic reticulum (ER) stress. We examined whether Pigment epithelium-derived factor (PEDF) could prevent changes in the structure and function of these organelles by accelerating by rotenone (ROT), a mitochondrial inhibitor, in human retinal pigment epithelium (RPE) cells of chronological age. Methods: RPE cells from 9–20, 50–55, 60–70, and >70-year-old donors were isolated, grown as primary cultures, harvested, and treated with ROT and PEDF for electron microscope (EM), western blot analysis, and polymerase chain reaction (PCR). Reactive oxygen species (ROS) and cytoplasmic calcium [Ca2+]c and mitochondrial calcium [Ca2+]m levels were measured by flow cytometry using 2′,7′-dichlorodihydrofluorescin diacetate (H2-DCF-DA), fluo-3/AM, and Rhod-2/AM, and ATP levels were measured using a luciferin/luciferase-based assay. Mitochondrial membrane potential (ΔΨm) was detected using 5,5′,6,6′-tetrachloro1,1′,3,3′-tetraethylbenzimid azolocarbocyanine iodide (JC-1), and susceptibility of the cells to ROT toxicity and PEDF-protective effect was determined by propidium iodide (PI) staining and lactate dehydrogenase (LDH) assay. The expression of ER stress-related genes was detected using real-time (RT)-PCR. Results: We observed decay in the mitochondria of aged RPE cells, including matrix abnormalities, elongation, loss of cristae, and disruption of membrane integrity after ROT treatment. We also observed lower [Ca2+]c, higher ROS and [Ca2+]m levels, decreased ΔΨm after ROT treatment, and greater susceptibility to ROT toxicity in aged RPE cells. PEDF can protect the cristae and integrity of the mitochondrial membrane, increase ATP levels and ΔΨm, and lower ROS, [Ca2+]c, and [Ca2+]m in aged RPE cells induced by ROT. In addition, there was an increase in RDH expression in RPE cells with increasing age after PEDF treatment. Similarly, PEDF decreased the expression of ROT-induced ER stress-related genes. Conclusions: Our study provides evidence that PEDF can reduce bioenergetic deficiencies, mitochondrial decay, and ER stress in aging RPE, a condition that may trigger the onset of retinal diseases such as AMD.

Abstract Background Betahistine is a clinical medication for the treatment of benign paroxysmal positional vertigo (BPPV). Otolin, a secreted glycoprotein with a C-terminal globular domain homologous to the immune complement C1q, has been identified as a biomarker for BPPV. However, the role of complement C1q/TNF-related proteins (CTRPs) with a C-terminal globular domain in BPPV is unclear, so we explored the change of CTRPs in betahistine treated BPPV. Methods We treated BPPV patients with Betahistine (12 mg/time, 3 times/day) for 4 weeks and observed the clinical efficacy and the expression of CTRP family members in BPPV patients. Then, we constructed a vertigo mice model of vestibular dysfunction with gentamicin (150 mg/Kg) and a BPPV model of Slc26a4 loop/loop mutant mice. Adenoviral vectors for CTRP expression vector and small interfering RNA were injected via the intratympanic injection into mice and detected the expression of CTRP family members, phosphorylation levels of ERK and AKT and the expression of PPARγ. In addition, we treated mice of vestibular dysfunction with Betahistine (10 mg/Kg) and/or ERK inhibitor of SCH772984 (12 mg/Kg) and/or and PPARγ antagonist GW9662 (1 mg/Kg) for 15 days, and evaluated the accuracy of air righting reflex, the time of contact righting reflex and the scores of head tilt and swimming behavior. Results After treatment with Betahistine, the residual dizziness duration and the score of the evaluation were reduced, and the expression of CTRP1, 3, 6, 9 and 12 were significantly increased in BPPV patients. We also found that Betahistine improved the accuracy of air righting reflex, reduced the time of contact righting reflex and the scores of head tilt and swimming behavior in gentamicin-treated mice and Slc26a4 loop/loop mutant mice. The expression levels of CTRP1, 3, 6, 9 and 12, phosphorylation levels of ERK and AKT, and PPARγ expression were significantly increased, and the scores of head tilt and swimming behavior were decreased in vestibular dysfunction mice with overexpression of CTRPs. Silencing CTRPs has the opposite effect. SCH772984 reversed the effect of Betahistine in mice with vestibular dysfunction. Conclusion Betahistine alleviates BPPV through inducing production of multiple CTRP family members and activating the ERK1/2-AKT/PPARy pathway.

BackgroundEsophageal squamous carcinoma (ESCC) is a highly lethal malignancy with poor prognosis. The effect of transcriptome characteristics of patient immune microenvironment (TME) on the efficacy of immunosuppressive agents is still poorly understood.MethodsHere we extracted and isolated immune cells from peripheral blood of patients with PD-1 monoclonal antibody sensitivity and resistance, and conducted deep single-cell RNA sequencing to describe the baseline landscape of the composition, lineage, and functional status of infiltrating immune cells in peripheral blood of patients with esophageal cancer.ResultsThe transcriptome characteristics of immune cells were comprehensively analyzed, and the dynamic changes of cell percentage, heterogeneity of cell subtypes and interactions between cells were explained. Co-expression and pedigree tracking based on T-cell antigen receptors revealed a significant proportion of highly migratory intertissue-effector T cells. GO and KEGG enrichment pathway Analysis of CD8+ effect-T cells ESCC_S group and ESCC_D1,2 group, found that in the up-regulated enrichment pathway, ESCC_S group enriched more PD-L1 and PD-1 checkpoint pathways expressed in tumors (JUN/NFKBIA/FOS/KRAS/IFNG), which also exist in T cell receptor signaling pathways. MT2A, MT1X and MT1E were differentially expressed in ESCC patients with PD-1 monoclonal antibody resistance, which may be related to the resistance of PD-1 mMAB.ConclusionsThis study has an in-depth understanding of the influence of peripheral immune cell infiltration on the sensitivity of monoclonal antibody PD-1 in patients with esophageal cancer, which is helpful to promote the immunotherapy of patients with esophageal cancer.

Objective: To analyze the effects of twirling reinforcing and reducing manipulations on protein expression in parietal cortex of spontaneously hypertensive rats (SHRs), and elucidate the main mechanisms and differences between two manipulations in hypertension treatment. Methods: Rats were randomly divided into the control, model, twirling reinforcing manipulation (TRFM), and twirling reducing manipulation (TRDM) groups. The control and model groups received catch and fixation stimulations once a day for 14 days. The TRFM and TRDM groups were intervened once a day for 20 min for 14 days. On days 0, 2, 6, 10, and 14 after acupuncture, rat systolic blood pressures (SBPs) were measured. Differential protein (DP) expression in the rat parietal cortices was detected. Thereafter, GO functional significance and KEGG pathway enrichment analyses were performed. Results: Compared with the model group, SBP of rats in the TRDM and TRFM groups decreased on days 6 and 10 of acupuncture, respectively (P = .009; P

Abstract The quiescent/slow‐cycling state preserves the self‐renewal capacity of cancer stem cells (CSCs) and leads to the therapy resistance of CSCs. The mechanisms maintaining CSCs quiescence remain largely unknown. Here, it is demonstrated that lower expression of MAN1A1 in glioma stem cell (GSC) resulted in the formation of high‐mannose type N‐glycan on CD133. Furthermore, the high‐mannose type N‐glycan of CD133 is necessary for its interaction with DNMT1. Activation of p21 and p27 by the CD133–DNMT1 interaction maintains the slow‐cycling state of GSC, and promotes chemotherapy resistance and tumorigenesis of GSCs. Elimination of the CD133–DNMT1 interaction by a cell‐penetrating peptide or MAN1A1 overexpression inhibits the tumorigenesis of GSCs and increases the sensitivity of GSCs to temozolomide. Analysis of glioma samples reveals that the levels of high‐mannose type N‐glycan are correlated with glioma recurrence. Collectively, the high mannose CD133–DNMT1 interaction maintains the slow‐cycling state and tumorigenic potential of GSC, providing a potential strategy to eliminate quiescent GSCs.

ObjectiveFor patients with drug–resistant focal epilepsy, intracranial monitoring remains the gold standard for surgical intervention. Focal cortical dysplasia (FCD) is the most common cause of pharmacoresistant focal epilepsy in pediatric patients who usually develop seizures in early childhood. Timely removal of the epileptogenic zone (EZ) is necessary to achieve lasting seizure freedom and favorable developmental and cognitive outcomes to improve the quality of life. We applied brain network analysis to investigate potential biomarkers for the diagnosis of EZ that will aid in the resection for pediatric focal epilepsy patients with FCD type II.MethodsTen pediatric patients with focal epilepsy diagnosed as FCD type II and that had a follow–up after resection surgery (Engel class I [n = 9] and Engel class II [n = 1]) were retrospectively included. Time–frequency analysis of phase transfer entropy, graph theory analysis, and power spectrum compensation were combined to calculate brain network parameters based on interictal epileptiform discharges from ECoG.ResultsClustering coefficient, local efficiency, node out–degree, and node out–strength with higher values are the most reliable biomarkers for the delineation of EZ, and the differences between EZ and margin zone (MZ), and EZ and normal zone (NZ) were significant (p < 0.05; Mann–Whitney U-test, two–tailed). In particular, the difference between MZ and NZ was significant for patients with frontal FCD (MZ > NZ; p < 0.05) but was not significant for patients with extra–frontal FCD.ConclusionsBrain network analysis, based on the combination of time–frequency analysis of phase transfer entropy, graph theory analysis, and power spectrum compensation, can aid in the diagnosis of EZ for pediatric focal epilepsy patients with FCD type II.

Abstract Background Ferroptosis is a novel mode of non-apoptotic cell death induced by build-up of toxic lipid peroxides (lipid-ROS) in an iron dependent manner. Cancer-associated fibroblasts (CAFs) support tumor progression and drug resistance by secreting various bioactive substances, including exosomes. Yet, the role of CAFs in regulating lipid metabolism as well as ferroptosis of cancer cells is still unexplored and remains enigmatic. Methods Ferroptosis-related genes in gastric cancer (GC) were screened by using mass spectrum; exosomes were isolated by ultra-centrifugation and CAF secreted miRNAs were determined by RT-qPCR. Erastin was used to induce ferroptosis, and ferroptosis levels were evaluated by measuring lipid-ROS, cell viability and mitochondrial membrane potential. Results Here, we provide clinical evidence to show that arachidonate lipoxygenase 15 (ALOX15) is closely related with lipid-ROS production in gastric cancer, and that exosome-miR-522 serves as a potential inhibitor of ALOX15. By using primary stromal cells and cancer cells, we prove that exosome-miR-522 is mainly derived from CAFs in tumor microenvironment. Moreover, heterogeneous nuclear ribonucleoprotein A1 (hnRNPA1) was found to mediate miR-522 packing into exosomes, and ubiquitin-specific protease 7 (USP7) stabilizes hnRNPA1 through de-ubiquitination. Importantly, cisplatin and paclitaxel promote miR-522 secretion from CAFs by activating USP7/hnRNPA1 axis, leading to ALOX15 suppression and decreased lipid-ROS accumulation in cancer cells, and ultimately result in decreased chemo-sensitivity. Conclusions The present study demonstrates that CAFs secrete exosomal miR-522 to inhibit ferroptosis in cancer cells by targeting ALOX15 and blocking lipid-ROS accumulation. The intercellular pathway, comprising USP7, hnRNPA1, exo-miR-522 and ALOX15, reveals new mechanism of acquired chemo-resistance in GC. Graphical abstract

This paper studies the anti-jamming problem of unmanned aerial vehicle (UAV)-enabled Internet of Things (IoT) communication networks in the presence of a jammer under the accurate probabilistic line-of-sight (LoS) model. Our goal is to maximize the information collection throughput of the system under the assumption that only the jammer’s approximate location is known. To this end, we formulate a throughput maximization problem by optimizing the UAV trajectory, the IoT devices’ transmit power, and communication scheduling under the accurate real-time probabilistic LoS channel. However, the proposed optimization problem is non-convex and coupled, and hence intractable to be solved. In order to tackle the problem, a robust iterative algorithm is proposed by leveraging the block coordinate descent (BCD) method, the successive convex approximation (SCA) technology, the difference of convex (D.C) programming approach, and the S-procedure. Extensive simulation results show that our proposed algorithm significantly improves the system throughput while achieving a practical anti-jamming effect compared with the benchmark algorithms.

In this paper, we proposed a novel expectation–maximization-based simultaneous localization and mapping (SLAM) algorithm for millimeter-wave (mmW) communication systems. By fully exploiting the geometric relationship among the access point (AP) positions, the angle difference of arrival (ADOA) from the APs and the mobile terminal (MT) position, and regarding the MT positions as the latent variable of the AP positions, the proposed algorithm first reformulates the SLAM problem as the maximum likelihood joint estimation over both the AP positions and the MT positions in a latent variable model. Then, it employs a feasible stochastic approximation expectation–maximization (EM) method to estimate the AP positions. Specifically, the stochastic Monte Carlo approximation is employed to obtain the intractable expectation of the MT positions’ posterior probability in the E-step, and the gradient descent-based optimization is used as a viable substitute for estimating the high-dimensional AP positions in the M-step. Further, it estimates the MT positions and constructs the indoor map based on the estimated AP topology. Due to the efficient processing capability of the stochastic approximation EM method and taking full advantage of the abundant spatial information in the crowd-sourcing ADOA data, the proposed method can achieve a better positioning and mapping performance than the existing geometry-based mmW SLAM method, which usually has to compromise between the computation complexity and the estimation performance. The simulation results confirm the effectiveness of the proposed algorithm.

Abstract Background Immune checkpoint inhibitors (ICIs) were approved to have a significant antitumor activity in various tumor types. In practice, some patients do not seem to benefit from ICIs but rather to have accelerating disease. The aim of this study was to evaluate hyperprogression in patients with malignant tumors of digestive system treated with ICIs. Methods Medical records from consecutive patients with malignant tumors of digestive system treated with ICIs in Peking University Cancer Hospital were retrospectively collected. Tumor growth kinetics (TGK) on immunotherapy and TGK pre-immunotherapy were collected and TGK ratio (TGKR) was calculated. Hyperprogression was defined as TGKR≥2. Results From August 2016 to May 2017, 25 evaluable patients were identified from 45 patients with malignant tumors of digestive system. Five patients were considered as having hyperprogression. Three of 5 were neuroendocrine carcinomas (NECs) and the other 2 were adenocarcinomas. Four of 5 were treated with programmed cell death ligand 1 (PD-L1) inhibitor, the other one was treated with PD-L1 inhibitor combined with cytotoxic T lymphocyte associated antigen-4 (CTLA-4) inhibitor. Pseudoprogression was observed in 2 patients. Conclusions Hyperprogression was observed in a fraction of patients with malignant tumors of digestive system treated with ICIs. Further investigation is urgently needed.

AIM: To analyze the expression of uncoupling protein 2 (UCP2) in retinal pigment epithelium (RPE) cells at the different human age, further explore the possible new target of RPE cells protection. METHODS: Adult retinal pigment epithelial-19 (ARPE-19) cells and the primary RPE cells at the different age (9-20y, RESULTS: Cells from the donors more than 60y are larger and more fibroblastic in appearance compared to ARPE-19 cells and those primary cultures obtained from the younger individuals by using phase-contrast micrographs. Results of RT-PCR, Western blot and confocal microscopy all showed that UCP2 was highly expressed in ARPE-19 cells and in the younger primary cultured human RPE cells at the age of 9-20y and 50-55y, whereas lower expression of UCP2 was measured in the older primary cultured human RPE cells at the age more than 60y. CONCLUSION: Expression of UCP2 gene is decreased in aged RPE cells, promoting the lower ability of anti-oxidation in these cells. It is indicated that UCP2 gene might be a new target for protecting the cells from oxidative stress damage.

In this paper, we investigate the position problem of limit cycles for a class of Liénard-type differential systems. By considering the upper bound of the amplitude of limit cycles on $\{(x,y)\in\mathbb{R}^2: x0\}$ respectively, we provide a criterion concerning an explicit upper bound for the amplitude of the unique limit cycle of the Liénard-type system on the plane. Here the amplitude of a limit cycle on $\{(x,y)\in\mathbb{R}^2: x0\}$) is defined as the minimum (resp. maximum) value of the $x$-coordinate on such a limit cycle. Finally, we give two examples including an application to predator-prey system model to illustrate the obtained theoretical result, and Matlab simulations are presented to show the agreement between our theoretical result with the simulation analysis.

Purpose: To report a case of surgical interventions for a patient with relapsing polychondritis who presented with late ocular complications. Observations: A 44-year-old male was diagnosed to have relapsing polychondritis on the basis of recurrent acute auricular chondritis, deformity of the ear, saddle nose deformity and painful nasal chondritis, acute ocular inflammation with conjunctivitis, episcleritis and keratouveitis, laryngotracheal chondritis, erythema nodosum in the skin, a history of polyarthritis, and abnormal blood examination findings. The acute ocular and auricular inflammation was resolved with oral corticosteroid treatment. Intraocular pressure (IOP) of the left eye was 60 mmHg as measured by Goldmann applanation tonometer. Gonioscopic observation revealed the presence of peripheral anterior synechiae and plateau iris configuration. Express drainage screw implantation was applied to the left eye, because topical and systemic medicines failed to decrease the IOP. After 12 months, complicated cataract aggravated in the right eye, and phacoemulsification operation was performed with corticosteroids administered during the perioperative period. His corrected visual acuity was 20/20 for the right eye, and the IOP remained below 21 mmHg for the left eye. The patient has been healthy, without any recurrence, for 36 months. Conclusions and importance: The present case of relapsing polychondritis is the first to be reported wherein late ocular complications were alleviated by surgical interventions. Routine use of corticosteroids is necessary for successful anti-glaucoma and phacoemulsification operations.

Objective: To explore the protective effect of acupuncture against myocardial injury in rats with stress-induced prehypertension (SIPH) by observing the genetic expression of myocardial endothelin-1 (ET-1) and atrial natriuretic peptide (ANP). Methods: Thirty-six Wistar rats were randomized into three groups: the control group, model group, and model + acupuncture (AP) group (n = 12 rats per group). During the 11-day modeling period, the model group and the model + AP group experienced plantar electric stimulation in combination with noise exposure, and daily acupuncture intervention was applied simultaneously in the model + AP group; the control group did not experience modeling or acupuncture. Systolic pressure (SP) was measured the day before modeling began, and on the 3rd, 5th, 7th, 9th, and 11th day after modeling initiation. On the 12th day, histopathological observation of the left ventricle was made with hematoxylin-eosin staining and quantitative genetic expression of myocardial ET-1, and ANP was tested by quantitative real-time polymerase chain reaction (PCR). Results: SP was higher in the model group than the control group on the 3rd, 5th, 7th, 9th, and 11th days (all P

Serum α-fetoprotein- (AFP-) elevated gastric cancer is a rare tumor that has a poor prognosis due to high incidence of liver metastasis. This study sought to investigate the optimal treatment modality. A total of 319 gastric cancer patients with liver metastasis (GCLM) whose serum AFP levels were tested before treatment were enrolled in this study. They were classified as the serum AFP ≥ 20 ng/ml group (n=74) and the AFP

Understanding users’ continued usage intentions for online learning applications is significant for online education. In this paper, we explore a scale to measure users’ usage intentions of online learning applications and empirically investigate the factors that influence users’ continued usage intentions of online learning applications based on 275 participant data. Using the extended Technology Acceptance Model (TAM) and the Structural Equation Modelling (SEM), the results show that males or users off campus are more likely to use online learning applications; that system characteristics (SC), social influence (SI), and perceived ease of use (PEOU) positively affect the perceived usefulness (PU), with coefficients of 0.74, 0.23, and 0.04, which imply that SC is the most significant to the PU of online learning applications; that facilitating conditions (FC) and individual differences (ID) positively affect the PEOU, with coefficients of 0.72 and 0.37, which suggest that FC is more important to the PEOU of online learning applications; and that both PEOU and PU positively affect the behavioral intention (BI), with coefficients of 0.83 and 0.51, which indicate that PEOU is more influential than PU to users’ continued usage intentions of online learning applications. In particular, the output quality, perceived enjoyment, and objective usability are critical to the users’ continued usage intentions of online learning applications. This study contributes to the technology acceptance research field with a fast growing market named online learning applications. Our methods and results would benefit both academics and managers with useful suggestions for research directions and user-centered strategies for the design of online learning applications.

Silicon insert is a promising tool for microinjection moulding (MIM). However, its fracture problem induced by impact in MIM creates a bottleneck for application. The purpose of this paper is to investigate the impact behaviour in MIM and the effect on the fracture of silicon inserts. The finite element method is utilised to calculate the crack propagation of silicon inserts with pressure load and thermal load in the MIM process. The simulation result shows that the crack propagation is more easily induced by the increase of pressure load, while the temperature change has little effect on the crack propagation. An experimental platform, including a novel rotatable insert mould, is developed to investigate the dynamic pressure in the MIM process. The result shows that both the maximum pressure and the maximum loading rate occur in the initial period of MIM process. It indicates that the silicon insert is more prone to fracture at the beginning of the MIM process, and spatial pressure peaks are observed in the cavity as well. The nearly consistent distribution between the peak positions and the insert fracture zones shows that the pressure distribution is quite relevant to the fracture of the silicon insert. The result is helpful because it reveals the fracture phenomenon of silicon inserts.

Piper motuoense X.W.Qin, F.Su & C.Y.Hao, a new species of Piperaceae from Xizang, China, is described and illustrated in this paper. The new species resembles P. yinkiangense and P. anisotis, but it can be readily distinguished from the compared species by several characteristics. Gonophyll leaves are chartaceous and the leaf secondary vein count is 7–9, with the outermost pair being very weak when there are nine veins. Additionally, the apical pair arises 2–4 cm above the base and the leaf base is asymmetrical, with bilateral petioles that cling and heal together. Pistillate floral bracts are sessile, with 3, 4 or 5 stigmas. The description of the new species includes photographs, detailed descriptions, notes on etymology, distribution and habitat, as well as comparisons with morphologically similar species. [ABSTRACT FROM AUTHOR]