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Abstract Background Cachexia is a complicated metabolic disorder that is characterize by progressive atrophy of skeletal muscle. Cathepsin K (CTSK) is a widely expressed cysteine protease that has garnered attention because of its enzymatic and non‐enzymatic functions in signalling in various pathological conditions. Here, we examined whether CTSK participates in cancer‐induced skeletal muscle loss and dysfunction, focusing on protein metabolic imbalance. Methods Male 9‐week‐old wild‐type (CTSK+/+, n = 10) and CTSK‐knockout (CTSK−/−, n = 10) mice were injected subcutaneously with Lewis lung carcinoma cells (LLC; 5 × 105) or saline, respectively. The mice were then subjected to muscle mass and muscle function measurements. HE staining, immunostaining, quantitative polymerase chain reaction, enzyme‐linked immunosorbent assay, and western blotting were used to explore the CTSK expression and IRS1/Akt pathway in the gastrocnemius muscle at various time points. In vitro measurements included CTSK expression, IRS1/Akt pathway‐related target molecule expressions, and the diameter of C2C12 myotubes with or without LLC‐conditioned medium (LCM). An IRS1 ubiquitin assay, and truncation, co‐immunoprecipitation, and co‐localization experiments were also performed. Results CTSK+/+ cachectic animals exhibited loss of skeletal muscle mass (muscle weight loss of 15%, n = 10, P 15%, n = 10, P 30%, n = 5, P

Abstract This retrospective study investigated the association between the pattern of disease progression and molecular mechanism of acquired resistance in a large cohort of 49 patients with ROS1-rearranged advanced non-small-cell lung cancer treated with first-line crizotinib. We found that treatment-emergent ROS1 point mutations were the major molecular mechanism of crizotinib resistance, particularly for patients who developed extracranial-only disease progression. Our findings highlight the importance of rebiopsy and gene testing for subsequent-line therapeutic management.

Summary: The precise sequence control of polymer chain is an important research topic of polymer chemistry. Although some methods such as iterative synthesis and supramolecular polymerization have been developed to fabricate sequence-controllable polymer, it is still a great challenge to consecutively prepare multiple supramolecular polymers with different sequence structures. In this work, through the reasonable utilization of assembly motifs, we integrated multiple host-guest recognitions and metal coordination interactions to prepare different sequence-controlled supramolecular polymers by a multistep assembly strategy. This research provides inspiration for the design and preparation of supramolecular polymers with different sequence structures.

Importance: Brain–computer interface (BCI) decodes and converts brain signals into machine instructions to interoperate with the external world. However, limited by the implantation risks of invasive BCIs and the operational complexity of conventional noninvasive BCIs, applications of BCIs are mainly used in laboratory or clinical environments, which are not conducive to the daily use of BCI devices. With the increasing demand for intelligent medical care, the development of wearable BCI systems is necessary. Highlights: Based on the scalp-electroencephalogram (EEG), forehead-EEG, and ear-EEG, the state-of-the-art wearable BCI devices for disease management and patient assistance are reviewed. This paper focuses on the EEG acquisition equipment of the novel wearable BCI devices and summarizes the development direction of wearable EEG-based BCI devices. Conclusions: BCI devices play an essential role in the medical field. This review briefly summarizes novel wearable EEG-based BCIs applied in the medical field and the latest progress in related technologies, emphasizing its potential to help doctors, patients, and caregivers better understand and utilize BCI devices.

BackgroundThe unmet needs in treating acute myeloid leukemia(AML) promote us to look for more effective and less toxic therapies. In this study, we discovered that Yinzhihuang injection(YZHI), a traditional Chinese patent medicine for hepatitis treatment, suppressed the growth of AML cells.MethodAnti-proliferative activities of YZHI were measured by CCK-8 assay. Cell cycle arrest was evaluated by PI staining, and apoptosis was evaluated by annexin V/PI staining. To explore the cell cycle arrest and cell death mechanism induced by YZHI, we assessed a series of assays, including measurements of the protein expression and cellular ATP. The anti-tumor activity was further demonstrated in nude mice.ResultsFlow cytometric and biochemical analysis revealed that YZHI caused cell cycle arrest and induced apoptosis in the AML HL-60 cells. Mechanistically, YZHI activated AMPK by promoting phosphorylation of the kinase. The active AMPK negatively regulated the downstream target mTORC1, leading to the inhibition of cell proliferation and induction of apoptosis. Pretreatment with the AMPK inhibitor compound C rescued YZHI induced apoptosis and partially restored cell proliferation of HL-60. Consistent with the data in vitro, YZHI obviously suppressed subcutaneous xenograft growth in nude mice.ConclusionsIn a word, our data suggest that YZHI can be repurposed for the treatment of AML, which is worthy of further clinical evaluation.

Online reviews of consumers after purchasing drugs online reflect the factors affecting their satisfaction. How to understand customer satisfaction through online reviews and tapping their needs to improve satisfaction has become an urgent issue facing pharmaceutical e-commerce companies. Based on the online reviews of Alibaba Health Pharmacy, six representative OTC online medicines were selected for this study, including the following categories: tonics, anti-cold drugs, rheumatism and orthopaedic drugs, skin drugs, gastrointestinal drugs, vitamins, and calcium. By training and testing the LDA topic model, five potential topics are extracted as factors affecting customer satisfaction, including drug efficacy, drug cost performance, online customer service, logistics and transportation, and packaging. In this paper, Sentiment Analysis is used to process the review text to quantify the sentiment tendency of the review, and determine the evaluation scale value. Then, the random dominance among various drug factors is determined based on the Stochastic Dominance Rules. Finally, the PROMETHEE–Ⅱ method is used to determine the ranking value of the importance of each factor. The results suggest that the factors in different types of OTC drugs rank differently, which is also rationalized in this paper. This study provides a significant reference for improving customer satisfaction with pharmaceutical e-commerce.

The research on the recycling of discarded drugs has become an important direction of the green supply chain in China. Faced with the great challenge of recycling discarded drugs in China, it is necessary to make clear the behavior choice of each recycling subject. This paper constructs an evolutionary game model among government, drugs recycling companies and consumers, describes the evolutionary game process, and analyzes the influence of the gain of government, drug recycling enterprises and consumers on the evolutionary stable strategy trend. By using Matlab simulation software to simulate the evolution of tripartite behavior, the final result is obtained: The government's choice of a strong regulatory strategy has an important positive role in guiding the entire discarded drug recovery market. Consumer's choice of active participation strategy and enterprise's choice of active participation strategy are most beneficial to the healthy development of the discarded drug recovery market. This study provides some valuable theoretical support and reference for the national decision-making of discarded drug recovery, helps to solve the problem of discarded drug recovery, and provides theoretical support and policy-making recommendations for the ultimate achievement of sustainable development goals.

Three-phase separator is an important device used in the development of offshore oil and gas fields to separate the oil, gas and water, for which proper pressure setting value is very critical. Herein, three-phase separators of A and B offshore platforms were taken as the object of research, and a dynamic simulation model of process was established based on the field operation conditions with K-Spice software. Specifically, the internal pressure change of the separators was simulated under two conditions, i.e. the gas outlet pipeline blocked and the control valve on the gas outlet pipeline of the separators stuck, and comparison was also made with the pressure setting value recommended by the domestic and foreign industry specifications. The results indicate that: For the setting value of high-high pressure for shutdown is low, the sticking of control valve at the gas outlet of separator may result in the shutdown of oil fields, and under the condition that the gas outlet is blocked, the problem concerning the non-independence of primary protection measure(close the shutoff valve)and the secondary protection measure(open the safety valve for pressure relief) may occur. Therefore, a new method of pressure setting was proposed, that is, to determine the minimum setting value of high-high pressure for shutdown according to the fluctuation value of internal pressure of the separator with the control valve on the gas outlet pipeline stuck, and to determine the minimum value of the setting pressure of the safety valve according to the pressure change of separator with the gas outlet blocked. The new method for pressure setting of three-phase separators can avoid the problem of "production shutdown" caused by the sticking of control valve of the separator and ensure the independence of the primary and secondary protection measures of separators.

Abstract Background An angiomyolipoma usually occurs in the kidneys and rarely in the liver. Hepatic epithelioid angiomyolipoma (HEAML), a rare variant of angiomyolipoma, possesses malignant potential and mimics the imaging features of hepatocellular carcinoma. Sonazoid® (perfluorobutane microbubbles), a new contrast agent that facilitates hepatic parenchyma-specific Kupffer phase imaging on contrast-enhanced ultrasonography (CEUS), is useful for the detection and characterization of focal liver lesions. Case presentation A 30-year-old man with HEAML underwent CEUS using Sonazoid®, in which new concepts for ultrasonography-based differentiation between HEAML and hepatocellular carcinoma were applied. Conclusions This case report provides clinicians and radiologists with a reference for distinguishing HEAML from hepatocellular carcinoma based on CEUS using Sonazoid®.

BackgroundSynchronous multiple primary malignant neoplasms occurring at the same time (SMPMNS) are not currently uncommon in clinical oncological practice; however, the diagnostic performance of 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) for SMPMNS needs further elucidation.PurposeThis study aimed to evaluate the application of 18F-FDG PET/CT in patients with SMPMNS.Materials and methodsThe clinical and imaging data of 37 patients with SMPMNS who had undergone 18F-FDG PET/CT from October 2010 to December 2020 were retrospectively analyzed. The kappa consistency test was applied to evaluate the consistency of the diagnostic performance between PET/CT and conventional imaging (CI). The sensitivity, specificity, and accuracy of PET/CT and CI in the detection of metastatic lesions were compared.ResultsThis retrospective diagnostic study included 74 lesions identified in 37 patients with SMPMNS, with 94.6% of patients having double primary tumors. Of the incidences of SMPMNS, 18.9% occurred in the same organ system, with respiratory tumors being the most common type of neoplasm (43.2%) and the lung being the most common primary site (40.5%). The overall survival of SMPMNS patients without metastases was longer than that of those with metastases (χ2 = 12.627, p = 0.000). The maximum standardized uptake value (SUVmax), the SUVmax ratio (larger SUVmax/smaller SUVmax), and the difference index of SUVmax (DISUVmax) [(larger SUVmax − smaller SUVmax)/larger SUVmax] of the primary lesions ranged from 0.9 to 41.7 (average = 12.3 ± 7.9), from 0.3 to 26.7 (average = 4.4 ± 6.9), and from 0.0% to 96.3% (average = 50.3% ± 29.3%), respectively. With regard to diagnostic accuracy, PET/CT and CI showed poor consistency (κ = 0.096, p = 0.173). For the diagnosis of primary lesions (diagnosed and misdiagnosed), PET/CT and CI also showed poor consistency (κ = 0.277, p = 0.000), but the diagnostic performance of PET/CT was better than that of CI. In the diagnosis of metastases, the patient-based sensitivity, specificity, and accuracy of PET/CT were 100.0%, 81.8%, and 89.2%, respectively, while those of CI were 73.3%, 100.0%, 89.2%, respectively. The sensitivity and specificity values were significantly different, with PET/CT having higher sensitivity (p = 0.02) and CI showing higher specificity (p = 0.02).Conclusions18F-FDG PET/CT improves the diagnostic performance for SMPMNS and is a good imaging modality for patients with SMPMNS.

There are technical obstacles in the safety evaluation of traditional Chinese medicine (TCM) injections due to their complex chemical nature and the lack of rapid and accurate in vitro methods. Here, we established a dual in vitro mitochondrial toxicity approach combing the conventional “glucose/galactose” assay in HepG2 cells with the cytotoxic assay in mitochondrial respiration deficient cells. Using this dual in vitro approach, for the first time, we systematically assessed the mitochondrial toxicity of TCM injections. Four of the 35 TCM injections, including Xiyanping, Dengzhanhuasu, Shuanghuanglian, and Yinzhihuang, significantly reduced cellular ATP production in galactose medium in the first assay, and presented less cytotoxic in the respiration deficient cells in the second assay, indicating that they have mitochondrial toxicity. Furthermore, we identified scutellarin, rutin, phillyrin, and baicalin could be the potential mitochondrial toxic ingredients in the 4 TCM injections by combining molecular docking analysis with experimental validation. Collectively, the dual in vitro approach is worth applying to the safety evaluation of more TCM products, and mitochondrial toxic TCM injections and ingredients found in this study deserve more attention.

BackgroundChemotherapy combined with immunotherapy or anti-vascular therapy is both recommended by guidelines for first-line treatment of lung adenocarcinoma. However, no head-to-head clinical trial has ever compared which strategy is the optimal choice. This real-world retrospective study was done to compare the efficacy and treatment-related adverse events of immunotherapy and bevacizumab in combination with chemotherapy.Patients and methodsFrom January 2018 to March 2021, we retrospectively collected 276 patients with advanced lung adenocarcinoma managed with chemotherapy combined with bevacizumab or PD-1 inhibitors at our center. Among them, 139 patients were treated with chemotherapy combined with bevacizumab, while 137 patients were treated with chemotherapy combined with PD-1 inhibitors. After receiving four cycles of combination therapy, all patients received maintenance therapy until disease progression. Progression‐free survival (PFS), overall response rate (ORR), overall survival (OS), disease control rate (DCR), and adverse events (AE) were analyzed between the two groups.ResultsCompared to patients who received anti-vascular therapy, patients who underwent immunotherapy achieved better PFS (7.3 months vs. 10 months, p = 0.002) while ORR (40.9% vs. 51.1%, p = 0.093), as well as OS (18 months vs. 24 months, p = 0.060), had no statistical difference between the two groups. In the PD-L1-negative population, there was no statistical difference in PFS and OS between the two groups. (8.0 months VS. 6.0 months, p = 0.738; and 19 months vs. 13 months, p = 0.274). In the PD-L1-positive population, there was a significant benefit in PFS in the population receiving immunotherapy (7.0 months vs. 10.0 months, p = 0.009). Proteinuria and hypertension occurred more frequently in the bevacizumab-treated group (p = 0.001 and p = 0.002), whereas immune-related pneumonia and hypothyroidism occurred more frequently in the immunotherapy-treated group (p = 0.007 and p = 0.030).ConclusionsThe addition of a PD-1 inhibitor was superior to bevacizumab in terms of PFS among patients with advanced lung adenocarcinoma. PD-L1-positive patients appeared to exhibit better PFS, OS, and ORR. Toxic reactions were manageable in both groups.

Introduction: IDegLira (brand name Xultophy) is a novel fixed ratio combination of insulin degludec and liraglutide for type 2 diabetes (T2D) patients. This study aimed to investigate the lifetime cost-effective value of IDegLira compared with its single component (Degludec or Liraglutide) and to explore the suitable annual cost of IDegLira if necessary.Methods: UKPDS OM2 was applied to determine the long-term quality-adjusted life years (QALYs) and total costs. The efficacy data that were inputted into the model were synthesized from 6 randomized clinical trials (RCTs) that directly assessed the clinical benefit of IDegLira and its components in the treatment of uncontrolled T2D patients. The economic results were examined by one-way sensitivity analysis (OSA) and probabilistic sensitivity analysis (PSA). Further price reduction of IDegLira was investigated by binary search.Results: The IDegLira, IDeg, and Lira yielded 11.79 QALYs, 11.62 QALYs, and 11.73 QALYs and total cost of $20281.61, $3726.76, and $11941.26, respectively. The incremental cost-utility ratio (ICUR) of IDegLira versus IDeg was $99464.12/QALYs, and the ICUR of IDegLira versus Lira was $143348.26/QALYs, which indicated that IDegLira was not a cost-effective therapy for T2D patients compared with its components at the current price from a Chinese national healthcare system perspective. Base case results were robust to OSA and PSA. A further binary search showed that IDegLira appears to only be cost-effective if the annual cost of IDegLira is decreased by 58% when IDeg is considered as a reference, or by 30.57% when Lira is considered as a reference.Conclusion: In conclusion, IDegLira appears to not be cost-effective when compared with the current prices of IDeg or Lira for T2D patients in China. However, after the binary search, IDegLira appears to only be cost-effective if the annual cost of IDegLira is decreased 58% when IDeg is considered as a reference, or by 30.57% when Lira is considered as a reference.

Polypropylene has been used for applications requiring high mechanical properties, good adhesion, chemical stability and insulation. Whereas, Polypropylene itself is flammable, and its limiting oxygen index (LOI) is low, which cannot pass the UL-94 combustion test. Therefore, extensive use will cause a serious threat to human life and property. With the wide application of thermoplastic polypropylene in industry, the development of environmentally friendly flame retardant materials has become an important research direction. For the past dozen years, researchers have been exploring flame retardants with high flame retardant efficiency, low toxicity, less smoke or other excellent performance flame retardants. This paper reviews the research progress of some phosphorus-containing flame retardants on the flame retardant properties of polypropylene in recent years. Phosphorus flame retardant is a flame retardant with high flame retardant efficiency, good stability and wide application. The types and flame retardant properties of phosphorus flame retardant will be introduced, and the future research of phosphorus flame retardant is summarized, direction and development opportunities.

The information security has an irreplaceable position in the smart grid (SG). In order to avoid the malicious attack and ensure the information security, the cryptographic techniques are essential. This paper focuses on the encryption techniques to ensure the information security of SG. Firstly, an unusual 7-dimensional complex chaotic system (7D-CCS) combined with the cubic memristor is introduced. Besides its phase portraits, Lyapunov exponent, 0–1 test, complexity, and bifurcation diagram are investigated. Then, with the proposed 7D-CCS, we design a data encryption algorithm to ensure the encryption security. Finally, the data and monitoring images in SG are encrypted by the designed encryption scheme. Besides, the encryption performance is given in detailed. The experimental results show that the proposed encryption scheme has quite good encryption performance. Therefore, it can ensure the information security of SG.

This study investigated the effects of different ultrasonic power and ultrasonic time on the structure and emulsifying properties of pea protein isolate (PPI)–arabinose conjugates. An examination of the absorbance and color development of PPI-d-arabinose (Ara) conjugates found that compared with traditional heating, the degree of glycosylation of protein reached the maximum when the ultrasonic treatment power was 150 and the treatment time was 30 min. Structural analysis revealed that the content of disordered structures (β-turn and random coil) of the protein conjugates increased, the maximum emission wavelength of the fluorescence spectrum was red-shifted, and the UV second-order derivative values decreased. The protein structure unfolded, exposing more hydrophobic groups on the molecular surface. Ultrasonic treatment improved the emulsification of protein conjugates. The emulsifying activity index (EAI) increased to 19.7 and 19.3 m2/g, and the emulsifying stability index (ESI) also increased. The contact angle and zeta potential also demonstrate that ultrasonic power has a positive effect on emulsion stability. Based on examining the thermal stability of the emulsion, the ultrasonic treatment increased the thermal denaturation resistance of the protein. This result confirms that mild sonication can increase the degree of glycosylation reaction and improve the emulsification properties of protein–Ara conjugates, providing a theoretical basis for developing foods with excellent emulsification properties.

Background: It has been demonstrated that scutellarin, a natural flavone compound from Scutellaria lateriflora and Scutellaria barbata, exerts selective cytotoxicity against a range of cancer cells. However, the underlining mechanism of scutellarin on acute myeloid leukemia (AML) remains elusive.Methods: In this study, the combination of network pharmacology and experimental verification was performed to identify the pharmacological mechanisms of scutellarin for AML therapy. The public databases, such as PharmMapper, UniProt, OMIM, GeneCards, DrugBank and PharmGkb database, were used to sceen the potential targets of scutellarin and AML. The protein-protein interaction (PPI), gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis were conducted to uncover the mechanism of scutellarin in the treatment of AML. Finally, the network pharmacological results were further confirmed by in vitro and in vivo experiments.Results: First and foremost, we totally obtained 289 target genes for scutellarin and 10998 disease targets for AML. 253 overlapping genes were preliminarily considered the potential targets of scutellarin for AML treatment. The results of PPI network analysis, GO analysis and KEGG pathway enrichment demonstrated that the anti-AML effect of scutellarin may focused on MAPK signaling pathway. Furthermore, the cytologic tests suggested that scutellarin can inhibit AML cells proliferation through the mediation of JNK/Caspase-3 pathway. Meanwhile, pretreatment with the JNK inhibitor SP600125 rescued scutellarin-induced apoptosis. Similarly, scutellarin obviously suppressed subcutaneous xenograft growth in nude mice via regulating the JNK/Caspase-3 signaling pathway.Conclusion: In this study, we integrated network pharmacology-based prediction and experimental validation and revealed the importance of the JNK pathway in scutellarin-mediated AML treatment.

Cyber mimic defense is designed to ensure endogenous security, effectively countering unknown vulnerabilities and backdoors, thereby addressing a significant challenge in cyberspace. However, the immense scale of real-world networks and their intricate topology pose challenges for measuring the efficacy of cyber mimic defense. To capture and quantify defense performance within specific segments of these expansive networks, we embrace a partitioning approach that subdivides large networks into smaller regions. Metrics are then established within an objective space constructed on these smaller regions. This approach enables the establishment of several fine-grained metrics that offer a more nuanced measurement of cyber mimic defense deployed in complex networks. For example, the common-mode index is introduced to highlight shared vulnerabilities among diverse nodes, the transfer probability computes the likelihood of risk propagation among nodes, and the failure risk assesses the likelihood of cyber mimic defense technology failure within individual nodes or entire communities. Furthermore, we provide proof of the convergence of the transfer probability. A multitude of simulations are conducted to validate the reliability and applicability of the proposed metrics.

To provide scientific guidance for the use of foamed concrete (FC) in construction engineering, a thermal conductivity calculation method, based on the fractal model of FC, has been developed. The thermal conductivity (TC) of FC has been tested by the transient planar heat source method in order to verify the reliability of the proposed calculation model. The FC was made of cement, fly ash, and ore powder, and cured under natural conditions for 7 d, 14 d, 28 d, and 42 d, respectively. The TC of FC gradually decreases with the increase in age. The fractal dimension of FC can be determined by both the box-counting method and compressive strength test, and the dimensions determined by both methods are similar. The TC of FC at different porosities and curing ages can be calculated by the fractal dimension, and the estimated values are basically consistent with the test data.

Abstract Background Inconsistent associations between egg consumption and cardiovascular disease (CVD) risk have been observed in previous studies. This study aims to longitudinally investigate the association between egg consumption and altered risk of arterial stiffness, a major pre-clinical pathogenic change of CVD, which was assessed by brachial-ankle pulse wave velocity (baPWV). Methods A total of 7315 Chinese participants from the Kailuan Study, free of CVD and cancer were included in this study. Egg consumption was assessed by a semi-quantitative validated food frequency questionnaire in 2014. baPWV was repeatedly measured at baseline and during follow-up (mean follow-up: 3.41 years). General linear regression was used to calculate means of baPWV change rate across different egg consumption groups, adjusting for age, sex, baseline baPWV, healthy eating index, total energy, social-economic status, blood pressure, obesity, smoking, lipid profiles, and fasting glucose concentrations. Results Compared to the annual baPWV change rate in participants with 0–1.9 eggs/wk. (adjusted mean: 35.9 ± 11.2 cm/s/y), those consuming 3–3.9 eggs/wk. (adjusted mean: 0.2 ± 11.4 cm/s/y) had the lowest increase in baPWV during follow-up (P-difference = 0.002). Individuals with low (0–1.9 eggs/wk) vs. high (5+ eggs /wk) egg intake showed similar changes in baPWV. Conclusions In this large-scale longitudinal analysis, we did not find a significant difference in arterial stiffness, as assessed by baPWV level, between low and high egg consumption groups. However, moderate egg consumption (3–3.9 eggs/wk) appeared to have beneficial effects on arterial stiffness.

Abstract Background The risk of stroke in individuals with very low low-density lipoprotein cholesterol (LDL-C) concentrations remains high. We sought to prioritize predictive risk factors for stroke in Chinese participants with LDL-C concentrations

Abstract Rising temperature will cause the changes of pore characteristics and strength property in rock. This research takes the limestone produced in Taihang Mountains as the research object, and performs high-temperature treatment within 25–1000 °C. The high-resolution X-ray computed tomography (CT) scanning test method is used to visually reconstruct the three-dimensional image of the sample, and obtain the spatial distribution status of the mesoscopic parameters of the bones, pores/cracks, etc. The results show that when the temperature exceeded 700 °C, the samples appeared milky white in appearance and as the temperature increased, the color gradually turned white, macroscopic cracks began to appear on the surface, while the meso-pores connected rapidly, reflecting a typical progressive destruction process from inside to outside. The change law of volume porosity with temperature has a consistent trend with that of the apparent morphology of the sample. Similarly, the mechanical test results suggest that 700 °C is also the turning temperature for strength deterioration and brittle-plastic transformation of sample. Based on the results of high-temperature test, CT test and mechanical test, there are enough evidences to show that, for the limestone sample, 700 °C is probably to be the mutation temperature of physical–mechanical behavior.

BackgroundThe long-term survival prognosis of patients with high-grade (Hunt-Hess grade IV–V or World Federation of Neurosurgical Societies grade IV–V) aneurysmal subarachnoid hemorrhage (aSAH) is generally poor, and the association between endovascular treatment timing and the prognosis of high-grade aSAH has not been explored in depth. This retrospective cohort study aimed to determine whether endovascular treatment within 24 h of high-grade aSAH is associated with a better prognosis.MethodsWe retrospectively analyzed the clinical data of patients with high-grade aSAH who were admitted to our institution between January 2018 and January 2021. The Modified Rankin Scale score was used to assess the 6-month prognosis of patients. Univariate and multivariate logistic regression analyses were used to identify the factors associated with prognosis. The area under the receiver operating characteristic (ROC) curve was used to assess the model's discriminatory ability.ResultsEighty-six patients were included in the study. In the multivariate analysis, the timing of endovascular treatment (odds ratio = 7.003 [1.800–27.242], P = 0.005) was an independent risk factor for prognosis. The ROC curve showed that the predictive power of the timing of endovascular treatment was 0.744, the best cut-off value was 12.5 h, and the corresponding sensitivity and specificity were 71.4 and 70.5%, respectively. Hydrocephalus (P = 0.005) and pulmonary infection (P = 0.029) were also associated with prognosis. In addition, cerebrospinal fluid drainage immediately after endovascular treatment had a significant effect on reducing hydrocephalus formation.ConclusionsEndovascular therapy within 24 h is feasible and improves the prognosis of patients with high-grade aSAH.

Abstract Fundamental understanding and control of the electronic structure evolution in rare‐earth nickelates is a fascinating and meaningful issue, as well as being helpful to understand the mechanism of recently discovered superconductivity. Here the dimensionality effect on the ground electronic state in high‐quality (NdNiO3) m/(SrTiO3)1 superlattices is systematically studied through transport and soft X‐ray absorption spectroscopy. The metal‐to‐insulator transition temperature decreases with the thickness of the NdNiO3 slab decreasing from bulk to 7 unit cells, then increases gradually as m further reduces to 1 unit cell. Spectral evidence demonstrates that the stabilization of insulating phase can be attributed to the increase of the charge‐transfer energy between O 2p and Ni 3d bands. The prominent multiplet feature on the Ni L3 edge develops with the decrease of NdNiO3 slab thickness, suggesting the strengthening of the charge disproportionate state under the dimensional confinement. This work provides convincing evidence that dimensionality is an effective knob to modulate the charge‐transfer energy and thus the collective ground state in nickelates.

Cervical cancer is one of the most common gynecologic malignancies and one of the leading causes of cancer-related deaths in women worldwide. There are more than 30 categories of human papillomavirus infections in the genital tract. The recently discovered immune checkpoint suppression is a potential approach to improve clinical outcomes in these patients by altering immune cell function. However, many questions remain unanswered in terms of this method. For example, the proportion of responders is limited and the exact mechanism of action is uncertain. The tumor microenvironment (TME) has long been regarded as having nonnegligible influence on effectiveness of immunotherapy. The programmed cell death protein 1 (PD-1) pathway has received much attention due to its involvement in activating T-cell immune checkpoint responses. Since tumor cells may evade immune detection and become highly resistant to conventional treatments, anti-PD-1/PD-L1 antibodies are preferred as a kind of cancer treatment and many have just been licensed. To provide a theoretical basis for the development of new therapies, investigating the effect of tumor microenvironment on the prognosis of cervical cancer is necessary. In this work, immunological scores obtained from the ESTIMATE algorithm were used to differentiate between patients with high and low immune cell infiltration. We identified 11 immunologically significant differentially expressed genes (DEGs). For example, CXCR3 was found to be an important factor in CD8+ T cell recruitment and tumor immunological infiltration in cervical cancer. These results may lead to novel directions of understanding complex interactions between cancer cells and the tumor microenvironment, as well as new treatment options for cervical cancer.

Precast concrete block slope protection is widely used due to its advantages of easy detection and laying, ease of organization, and the limited time required for construction. In order to prevent the soil or gravel bedding of precast concrete from being subjected to wind and wave pressures, the joints between precast concrete blocks are usually filled with mortar. However, the existing standards do not specify the width or material of the joints. Furthermore, excessively wide mortar joints or shrinkage of the mortar can result in loss, a hollowed-out cushion, and damage to the slope, thus compromising the quality of slope protection engineering. To establish standards for controlling the quality of slope protection seams, this paper designed and conducted a physical model test of precast concrete block revetment seams. By embedding pore water pressure sensors in the cushion layer, changes in the pore water pressure were observed under varying conditions, including different water pore pressure sensor locations, water levels in front of the embankment, and different joint widths. Based on the test results, design standards for joint widths and recommendations for the treatment of joint mortar materials were proposed. After adding different amounts of a calcium oxide–calcium sulfoaluminate composite expansion agent (HME) into a joint mortar material, the paper also carried out a shear test on the contact surface between the joint mortar and the slope protection concrete after adding varying amounts of a calcium oxide-calcium sulfoaluminate composite expansion agent (HME) to the joint mortar material. Following a microporous structure test, recommendations for joint mortar construction treatment were proposed. The results indicate that the pore water pressure of the precast concrete slope protection cushion is closely related to the position of the cushion, the water level in front of the embankment, and the width of the paving seam. When the masonry seam width increased from 0.5 mm to 1 mm and from 1 mm to 1.5 mm, the variation ranges of the pore water pressure were 40–80% and 6–20%, respectively, with the latter being significantly lower than the former. Therefore, in practical engineering, joint treatment should take into account the impact of the cushion position, the water level in front of the dike, and the joint mortar width. Mortar shedding within the range of wave climbing height should be addressed promptly, and joint width should be controlled to below 1 cm as much as possible to effectively prevent damage to the cushion surface. The addition of an expansion agent can improve the bond strength of the concrete and mortar to a certain extent. The study found that an 8% content of the expansion agent resulted in the best mortar bond strength and the densest microstructure. These research findings can serve as a basis for the development of quality control standards for precast concrete slope protection.

Spiroaromatic compounds are advantageous platforms for designing expanded aromatic systems. Herein, the authors present a tris‐spiro metalla‐aromatic Vanadium compound which forms a 40π Craig‐Möbius aromatic system.

Background and Aims Many previous studies comparing liver resection versus thermal ablation for colorectal cancer liver metastases (CRCLM) are subject to severe selection bias. This study aimed to compare the long-term clinical efficacy of ultrasonography-guided percutaneous microwave ablation (PMWA) with resection for CRCLM using propensity score analysis to reduce confounding by indication. Methods This retrospective study included 184 patients with CRCLM from January 2012 to June 2017. Treatment effect was estimated after propensity score matching, Descriptive, regression and survival statistics were applied. Results A lower American Society of Anesthesiologists classification score and higher performance status were found positively associated with resection (p

A microRNA (miRNA) often regulates the expression of hundreds of target genes. A fundamental question in the field of miRNA research is whether a miRNA exerts its biological function through regulating a small number of key targets or through small changes in the expression of hundreds of target genes. We addressed this issue by performing functional analysis of target genes regulated by miR-148a. We previously identified miR-148a as a critical regulator of B cell central tolerance and found 119 target genes that may mediate its function. We selected 4 of them for validation and demonstrated a regulatory role for Bim, Pten, and Gadd45a in this process. In this study, we performed functional analysis of the other miR-148a target genes in in vitro and in vivo models of B cell central tolerance. Our results show that those additional target genes play a minimal role, if any, in miR-148a-mediated control of B cell central tolerance, suggesting that the function of miRNAs is mediated by a few key target genes. These findings have advanced our understanding of molecular mechanisms underlying miRNA regulation of gene expression and B cell central tolerance.

Colorectal cancer (CRC), a leading cause of cancer-related mortalities globally, results from the accumulation of multiple genetic and epigenetic alterations in the normal colonic and rectum epithelium, leading to the progression from colorectal adenomas to invasive carcinomas. Almost half of CRC patients will develop metastases in the course of the disease and most patients with metastatic CRC are incurable. Particularly, the 5-year survival rate of patients with stage 4 CRC at diagnosis is less than 10%. Although genetic understanding of these CRC tumors and paired metastases has led to major advances in elucidating early driver genes responsible for carcinogenesis and metastasis, the pathophysiological contribution of transcriptional and epigenetic aberrations in this malignancy which influence many central signaling pathways have attracted attention recently. Therefore, treatments that could affect several different molecular pathways may have pivotal implications for their efficacy. In this review, we summarize our current knowledge on the molecular network of CRC, including cellular signaling pathways, CRC microenvironment modulation, epigenetic changes, and CRC biomarkers for diagnosis and predictive/prognostic use. We also provide an overview of opportunities for the treatment and prevention strategies in this field.

Abstract Background Several previously healthy young adults have developed Coronavirus Disease 2019 (COVID-19), and a few of them progressed to the severe stage. However, the factors are not yet determined. Method We retrospectively analyzed 123 previously healthy young adults diagnosed with COVID-19 from January to March 2020 in a tertiary hospital in Wuhan. Patients were classified as having mild or severe COVID-19 based on their respiratory rate, SpO2, and PaO2/FiO2 levels. Patients’ symptoms, computer tomography (CT) images, preadmission drugs received, and the serum biochemical examination on admission were compared between the mild and severe groups. Significant variables were enrolled into logistic regression model to predict the factors affecting disease severity. A receiver operating characteristic (ROC) curve was applied to validate the predictive value of predictors. Result Age; temperature; anorexia; and white blood cell count, neutrophil percentage, platelet count, lymphocyte count, C-reactive protein, aspartate transaminase, creatine kinase, albumin, and fibrinogen values were significantly different between patients with mild and severe COVID-19 (P

The hinge region of immunoglobulin G1 (IgG1) is used as a common linker for Fc-fusion therapeutic proteins. With the advances of high-resolution mass spectrometry and sample treatment strategies, unexpected O-linked glycosylation has been observed in the linker. However, the molecular mechanism involved in this unusual posttranslational modification is unknown. In this study, we applied site-direct mutagenesis, mass spectrometry, analytical chromatography, and computational modeling to investigate O-glycosylation processes in a clinically used CTLA4 Fc-fusion protein and its impacts on protein quality attributes. Surprisingly, O-glycans could be formed at new sites when an initial O-glycosylation site was eliminated, and continued to occur until all potential O-glycosylation sites were nulled. Site-preference of O-glycosylation initiation was attributed to the complex formation between the linker peptide and glycan transferase whereas the O-glycosylating efficiency and the linker flexibility were correlated using molecular modeling and simulations. As predicted, O-glycan-free CTLA4 Fc-fusion proteins were more homogenous for sialylation, and interestingly less prone to protein aggregation. Attenuating protein aggregation was a desirable effect, and could be related to the reduced presence of linker O-glycans that hindered inter-chain disulfide bond reformation. Findings from this study shed light on new therapeutic protein design and development.

Synergetic innovation between pharmaceutical enterprises and scientific research institutions is extremely important for the development of innovative drugs. However, it is unstable in the pharmaceutical industry, which seriously hinders the development of innovative drugs in the World. China is the country with the biggest population, and therefore problems in this country are ones of the most important. In this context, we studied the influence of strengthening correlation degree on synergetic innovation between pharmaceutical enterprises and scientific research institutions by using quantum game. Through the establishment of quantum game model, we obtain the optimal strategy of both players in different case. The results show that the quantum game can solve the problem of “prisoner's dilemma” existing in the game between pharmaceutical enterprises and scientific research institutions; it is easier for the two players to choose complete synergy when they are entangled state and quantum strategy has been adopted; when pharmaceutical enterprises and scientific research institutions are not in a state of entanglement, the quantum game has no difference with classical game in this case.

In order to develop the biomedical industry, government subsidy of biosimilars is an incentive policy which has been used by the government. Different government subsidy strategies have an impact on drug price, consumer surplus, social welfare, the income of biosimilars enterprises and the demand of biosimilars, which have been deeply analyzed through backward induction of the dynamic game theory. The analysis shows that the price coefficient and the influence of the subsidy on demand will affect the choice of government subsidy strategies. It is concluded that under different subsidy strategies, consumer surplus, social welfare and the income of biosimilars enterprises are positively correlated with the amount of subsidy per unit product. This paper provides a decision-making basis for developing government subsidy strategies scientifically.

CAPTCHA, a short form of “Completely Automated Public Turing test to Tell Computers and Humans Apart”, is a computer program that can generate and grade tests that most humans can pass, but current computer programs cannot. This paper advances research on image-based CAPTCHA by incorporating the object segment collages. We first collect object segments from thousands of images by using our self-developed collection tool. Then, we create an image collage that compiles randomly selected object segments. To increase the difficulty for computer detection algorithms, we embed some features such as noisy background, object segment occlusion and object segment orientation update. We also develop a practical application using the newly proposed Object Segment Collage CAPTCHA. For the evaluation, we measure the accuracy performance of computer vs. human in solving CAPTCHA questions. In addition, we also conduct a user study over different CAPTCHA methods.

The rapidly increasing number of digital images requires effective retrieval. Meanwhile, the dominant color descriptor has been widely used in image processing. Due to the influence of lighting and other factors, the same color in nature may have some different changes. The human eye is usually more sensitive to zones of consistent color, often identifying objects by zones of consistency. Therefore, the proposed method in this paper first applies the texton template to detect and extract the consistent zone of an image, and calculates the dominant color descriptor feature on the pixels in this consistent zone. Besides, the translation and rotation invariance of the Hu moments feature is applied to extract the shape information in the same consistent zone of the image. Finally, the combination of the dominant dolor descriptor and the Hu moments is used for content-based image retrieval. The algorithm proposed in this paper is tested on three data sets: Corel-1k, Corel-5k and Corel-10k, and the experimental results show that it is superior to the current content-based image retrieval methods.

This paper studies the pharmaceutical production supply chain system composed of upstream and downstream pharmaceutical enterprises, and explores the impact of government subsidy strategies on the new drug research and development (R&D) decision variables and profits of pharmaceutical enterprises as well as social welfare, when considering both the horizontal spillover effects within the industry and the vertical spillover effects between industries. Comparing and analyzing the impact of these strategies including non-government subsidy strategy, pharmaceutical enterprise innovation input subsidy strategy, pharmaceutical enterprise innovative product subsidy strategy, patient price subsidy strategy, and patient medical insurance subsidy strategy. By establishing a four-stage Cournot duopoly model incorporating spillover effects, the equilibrium solutions are obtained by backward induction, and the impact of spillover effects on decision variables is investigated accordingly. Studies have shown that: (a) Government subsidy strategies can promote pharmaceutical enterprises' R&D investment and have a positive incentive effect on the pharmaceutical enterprises' profits and social welfare. (b) The patient medical insurance subsidy strategy is the optimal subsidy strategy, which can generate higher profits for pharmaceutical enterprises and higher social welfare.

Arbuscular mycorrhizal fungi (AMF) form mutualistic symbiotic relationships with many land plants and play a key role in nitrogen (N) acquisition. NO3−-N and NH4+-N are the main sources of soil mineral N, but how extraradical mycelial transfer affects the different N forms and levels available to tomato plants is not clear. In the present study, we set up hyphal compartments (HCs) to study the efficiency of N transfer from the extramycelium to tomato plants treated with different N forms and levels of fertilization. Labeled 15NO3−-N or 15NH4+-N was placed in hyphal compartments under high and low N application levels. 15N accumulation in shoots and the expression of LeNRT2.3, LeAMT1.1, and LeAMT1.2 in the roots of tomato were measured. According to our results, both 15NO3−-N and 15NH4+-N were transported via extraradical mycelia to the shoots of plants. 15N accumulation in shoots was similar, regardless of the N form, while a higher 15N concentration was found in shoots with low N application. Compared with the control, inoculation with AMF significantly increased the expression of LeAMT1.1 under high N and LeNRT2.3 under low N. The expression of LeAMT1.1 under high N was significantly increased when NO3—N was added, while the expression of LeNRT2.3 was significantly increased when NH4+-N was added under low N. Taken together, our results suggest that the N transfer by extraradical mycelia is crucial for the acquisition of both NO3−-N and NH4+-N by the tomato plant; however, partial N accumulation in plant tissue is more important with N deficiency compared with a higher N supply. The expression of N transporters was influenced by both the form and level of N supply.

ObjectiveThe goal of this study was to systematically summarize and categorize the syndrome differentiation, medication rules, and acupoint therapy in the domestic traditional Chinese medicine (TCM) literature on type 2 diabetes mellitus (T2DM), such that guidelines and new insights can be provided for future practitioners and researchers.MethodsTaking randomized controlled trials (RCTs) on the treatment of T2DM in TCM as the research theme, we searched for full-text literature in three major clinical databases, including CNKI, Wan Fang, and VIP, published between 1990 and 2020. We then conducted frequency statistics, cluster analysis, association rules extraction, and topic modeling based on a corpus of medical academic words extracted from 3,654 research articles.ResultsThe TCM syndrome types, subjective symptoms, objective indicators, Chinese herbal medicine, acupuncture points, and TCM prescriptions for T2DM were compiled based on invigorating the kidney and Qi, nourishing Yin, and strengthening the spleen. Most TCM syndrome differentiation for T2DM was identified as “Zhongxiao” (the lesion in the spleen and stomach) and “Xiaxiao” (the lesion in the kidney) deficiency syndromes, and most medications and acupoint therapies were focused on the “Spleen Channel” and “Kidney Channel.” However, stagnation of liver Qi was mentioned less when compared with other syndromes, which did not have symptomatic medicines.ConclusionThis study provides an in-depth perspective for the TCM syndrome differentiation, medication rules, and acupoint therapy for T2DM and provides practitioners and researchers with valuable information about the current status and frontier trends of TCM research on T2DM in terms of both diagnosis and treatment.

Sugarcane molasses vinasse is the residue of the fermentation of molasses and the water and soil environmental pollutants from distilleries. However, its recycling value has been neglected. The chemical analysis of the molasses vinasse led to the isolation of a new benzoyl chloride called 2,3,4-trihydroxy-5-methoxy benzoyl chloride, as well as thirteen known compounds, including six benzoic acids. The structure of the new benzoyl chloride was elucidated on the basis of extensive spectroscopic analysis. The antioxidant activity of all isolated compounds was measured using the ORAC assay. Moreover, we compared the cellular antioxidant activity (CAA) and inhibitory activity against α-amylase and α-glucosidase for structure–activity analysis. The results showed that only vanillic acid had CAA (8.64 μmol QE/100 μmol in the no PBS wash protocol and 6.18 μmol QE/100 μmol in the PBS wash protocol), although other benzoic acid derivatives had high ORAC values ranging between 1879.9 and 32,648.1 μmol TE/g. Additional methoxy groups at the ortho-positions of the p-hydroxy group of benzoic acids enhanced the inhibition of α-glucosidase but reduced the ORAC activity unless at the para-position. This work indicated that phenolics, especially phenolic acids in the sugarcane molasses vinasse, possessed potential antioxidant and antihyperglycemic activity, which improved the utilization rate of resources and reduced the discharge of pollutants.

Introduction We aimed to investigate the individual and combined effects of age-specific and sex-specific pulse pressure (PP) and brachial-ankle pulse wave velocity (baPWV) on the incidence of new-onset diabetes mellitus.Research design and methods Participants in the Kailuan study cohort who were ≥20 years old, participated in follow-up assessments and underwent baPWV measurements in 2010–2011, 2012–2013, and 2014–2015 were studied. The participants were allocated to four groups according to their PP and baPWV status, each categorized as high or normal, according to age-specific and sex-specific median values. Cox proportional hazards models were used to explore the individual and combined effects of PP and baPWV on the incidence of diabetes mellitus.Results There were 18 619 participants who were followed for 4.27±1.91 years. A total of 877 new cases of diabetes were identified, and the incidence density was 11.03/1000 per year. Using the normal PP and normal baPWV group as the reference group, the multivariable-adjusted HRs and 95% CIs for diabetes mellitus in the high PP and high baPWV groups were 1.08 (0.93 to 1.25) and 1.64 (1.41 to 1.90), respectively. Compared with the normal PP/baPWV group, the HR and 95% CI for diabetes in the normal PP/high baPWV, the high PP/normal baPWV, and high PP/baPWV groups were 1.66 (1.35 to 2.05), 1.09 (0.86 to 1.37), and 1.74 (1.43 to 2.13), respectively.Conclusions High baPWV was independently associated with a higher risk of diabetes mellitus, and individuals with both high baPWV and high PP were at a still higher risk of diabetes mellitus.

Abstract Background Fibrous hamartoma of infancy(FHI) is a rare benign lesion most frequently occurring within the first year of life. So far, just over 200 cases have been reported in the English literature, in which the radiologic findings of FHI have not been fully described. Herein, 2 adult cases of FHI receiving treatment in our hospital and the published cases searched on PubMed are reviewed, with the emphasis on the discussion of the spectrum of MR findings and their histologic correlation. Case presentation We present two adult cases who aged 47 years and 19 years with slow growing masses beginning from their childhood in the posterior craniocervical area. On CT and MR imaging, the tumours showed as the superficially located lesions with ill-defined margins that involved the subcutaneous layer and its underlying muscles. The size of the lesions were 21.3 × 16.7 × 16 cm in case 1 and 20.2 × 19.3 × 13.6 cm in case 2. The tumours demonstrated heterogeneous intensities/signals with the adipose tissue presenting as the disperse strands or small focus of fatty intensity/signal. Parallel or whirling appearance, and dilated vessels were delineated in the cases. Contrast enhancement was administered in case 1 and marked enhancement was found. Conclusions The usually observed manifestation of FHI on CT and/or MR imaging is the strands of adipose/fibrous intensities traversing the lesions, with the characteristic parallel or whirling appearance in some cases. The tumours with ill-defined margins have the tendency to involve the underlying muscles. Some fibroblastic and adipocytic tumours should be ruled out in differential diagnosis.

Network externality is an important feature of the era of network economy. The competition between online and offline retail pharmacies caused by network externality is getting fiercer and fiercer. In this context, we studied the long-term market competition evolution of two-channel retail pharmacies under the network external environment, in order to obtain higher profits, two-channel retail pharmacies prefer to choose profit maximization marketing strategy or market share maximization marketing strategy. Using evolutionary game theory, an evolutionary game model of two-channel retail pharmacies was established. Through the establishment of the model, obtain the payment matrix of different marketing strategies selected by the two-channel retail pharmacies and the evolution and stability of the selection of marketing strategies. The results show that when the strength of the network externality is within a certain range, the traditional retail pharmacies with higher marketing cost choose to pursue the profit maximization strategy, while online pharmacy with lower marketing costs choose market share maximization strategy to achieve greater profits; when the network externality is large, in order to maintain a certain market share in the long-term market evolution, the traditional retail pharmacy with high marketing cost chooses to pursue the market share maximization marketing strategy in order to obtain greater profits, while the online pharmacy with low marketing cost chooses to profit from the profit maximization marketing strategy.

Government subsidies can supplement R&D investment within pharmaceutical firms and strengthen industry knowledge spillovers effectively. Based on the inter-firm spillovers, a differential game model is established to investigate the government subsidy strategies under the different innovative drug R&D strategies of pharmaceutical firms. With the Hamilton-Jacobi-Bellman equitation, the optimal R&D investment, the pharmaceutical technical levels, and the optimal benefits are obtained under the strategies of no pharmaceutical firms conduct R&D innovation, one side innovates alone and R&D cooperation. It can be concluded that the R&D investment of pharmaceutical firms and the effort level of the government is positively related to the technical level and their comprehensive benefits, while it is a negative correlation to the cost coefficient. In addition, an increase in spillover coefficient produces an increase in government subsidy. Furthermore, when the spillovers are low, the government should give a higher subsidy to the strategy of R&D cooperation. As the spillovers increase, the government should allocate more subsidies to pharmaceutical firm who conduct independent R&D of innovative drugs.

AimThe aim of this study was to assess the clinical efficacy and safety of Tripterygium-derived glycosides (TG) after 3-month and 6-month of treatments of diabetic nephropathy (DN) and to resolve the conflict between medicine guidance and clinical practice for TG application.MethodsWe conducted a systematic review and meta-analysis of randomized controlled trials involving TG application in treating DN. We extensively searched PubMed, Cochrane Library, CNKI, VIP, Wan-Fang, CBM, Chinese Clinical Trial Registry, and WHO International Clinical Trial Registration Platform till November 2020, along with grey literature for diabetes and all other relevant publications to gather eligible studies. Based on the preset inclusion and exclusion criteria, document screening, quality assessment of methodology, and data extraction was conducted by two researchers independently. The methodological quality was assessed by the Cochrane risk test from the Cochrane Handbook 5.2, and then analyses were performed by Review Manager 5.3 (Rev Man 5.3). The quality of output evidence was classified by GRADE.ResultsThirty-one eligible studies (2764 patients) were included for this meta-analysis. Our study results showed a comparable significant decrease in the 24 h-UTP and blood creatinine levels in DN patients from both 3-month and 6-month TG treatment groups, compared with the routine symptomatic treatment alone. To the contrary of the findings from the included studies, our results showed that the occurrence of serious adverse reaction events was significantly higher in the TG treated group with 6 months of treatment duration compared to that of 3 months of the treatment course. However, the total AR ratio was slightly varied while increasing the percent of severe adverse events. GRADE assessment indicated that the quality of evidence investigating TG-induced adverse reactions was moderate and that for 24 h-UTP and blood creatinine indicators were considerably low.ConclusionCombinatorial treatment regimen including TG can significantly decrease the pathological indicators for DN progression, while it can also simultaneously predispose the patient to a higher risk for developing severe adverse events, as the medicine guidance indicates. Notably, even in 3-month of course duration smaller percent of severe adverse events can get to a fatal high percent and is likely to increase proportionally as the TG treatment continues. This suggests that TG-mediated DN treatment duration should be optimized to even less than 3 continuous months to avoid adverse event onset-associated further medical complications in DN patients. In clinical practice, serious attention should be paid to these severe side-effects even in a course normally considered safe, and importantly more high-quality studies are urgently warranted to obtain detailed insights into the balance between the efficacy and safety profiles of TG application in treating DN.

Adipose tissue (AT) is a highly heterogeneous and dynamic organ that plays important roles in regulating energy metabolism and insulin sensitivity. In addition to its classical roles in nutrient sensing and energy storage/dissipation, AT secretes a large number of bioactive molecules (termed adipokines) participating in immune responses and metabolic regulation through their paracrine and/or endocrine actions. Adipose-derived extracellular vesicles (ADEVs), including exosomes, microvesicles (MVs), and apoptotic bodies, have recently emerged as a novel class of signal messengers, mediating intercellular communications and inter-organ crosstalk. In AT, ADEVs derived from adipocytes, immune cells, mesenchymal stem cells, endothelial cells are actively involved in modulation of immune microenvironment, adipogenesis, browing of white adipose tissue, adipokine release and tissue remodeling. Furthermore, ADEVs exert their metabolic actions in distal organs (such as liver, skeletal muscle, pancreas and brain) by sending genetic information (mainly in the form of microRNAs) to their target cells for regulation of gene expression. Here, we provide an updated summary on the nature and composition of ADEVs, and their pathophysiological functions in regulating immune responses, whole-body insulin sensitivity and metabolism. Furthermore, we highlight the latest clinical evidence supporting aberrant production and/or function of ADEVs as a contributor to obesity-related chronic inflammation and metabolic complications and discuss the opportunities and challenges in developing novel therapies by targeting ADEVs.

Geographic pattern of dengue fever is changing due to the global environmental and climate changes in the 21st century. Evidence of community's knowledge, mosquito bite patterns and protective behavior practices in non-endemic regions is limited. This study examined the knowledge of dengue, mosquito bite patterns, protective behavior practices and their associated factors in Hong Kong, a non-endemic subtropical city. A population-based random telephone survey (n = 590) was conducted three weeks after the government announcement of a local dengue outbreak in August 2018. Sociodemographic status, awareness, knowledge, protective measures, bite patterns of mosquito were collected. Results indicated high level of community awareness of the local outbreak (95.2%), symptom identification (84.0%) and adoption of at least one mosquito protective measures (nearly 80%). About 40% of respondents reported that they were bitten by mosquitoes during the study period, a high mosquito season in Hong Kong. Mosquito bites were prevalent near grassy area (63.4%), at home (42.6%) and at public transportation waiting spots (39.6%). Younger people (< 25 years old), female, those who lived on lower floors (≤the 6th) and near grassy area were at higher risk of mosquito bites at home. Respondents perceived higher threat of dengue to society were more likely to practice mosquito prevention. While residential factors affected their indoor prevention, other socio-demographic factors affected the outdoor prevention. Practicing prevention behaviors were associated with self-reported mosquito bite at home. Furthermore, the general prevention uptake rate unchanged after the announcement of local dengue outbreak. Although the uptake rate of protective measures during August was high, 40% participants reported they were bitten. Also public locations are more common area for bites, which suggested stronger mosquito prevention and control on public environments and more personal protective behaviors should be advocated.

Background. We recently demonstrated that proliferin-1 (PLF-1) functions as an apoptotic cell-derived growth factor and plays an important role in vascular pathobiology. We therefore investigated its role in muscle regeneration in response to cardiotoxin injury. Methods and Results. To determine the effects of PLF-1 on muscle regeneration, we used a CTX-induced skeletal muscle injury model in 9-week-old male mice that were administered with the recombinant PLF-1 (rPLF-1) or neutralizing PLF-1 antibody. The injured muscles exhibited increased levels of PLF-1 gene expression in a time-dependent manner. On day 14 after injury, rPLF-1 supplementation ameliorated CTX-induced alterations in muscle fiber size, interstitial fibrosis, muscle regeneration capacity, and muscle performance. On day 3 postinjury, rPLF-1 increased the levels of proteins or genes for p-Akt, p-mTOR, p-GSK3α/β, p-Erk1/2, p-p38MAPK, interleukin-10, Pax7, MyoD, and Cyclin B1, and it increased the numbers of CD34+/integrin-α7+ muscle stem cells and proliferating cells in the muscles and/or bone marrow of CTX mice. An enzyme-linked immunosorbent assay revealed that rPLF-1 suppressed the levels of plasma tumor necrosis factor-α and interleukin-1β in CTX mice. PLF-1 blocking accelerated CTX-related muscle damage and dysfunction. In C2C12 myoblasts, rPLF-1 increased the levels of proteins for p-Akt, p-mTOR, p-GSK3α/β, p-Erk1/2, and p-p38MAPK as well as cellular functions; and these effects were diminished by the depletion of PLF-1 or silencing of its mannose-6-phosphate receptor. Conclusions. These findings demonstrated that PLF-1 can improve skeletal muscle repair in response to injury, possibly via the modulation of inflammation and proliferation and regeneration, suggesting a novel therapeutic strategy for the management of skeletal muscle diseases.