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Rib fracture is the most common injury in chest trauma. Most of patients with rib fractures were treated conservatively, but up to 50% of patients, especially those with combined injury such as flail chest, presented chronic pain or chest wall deformities, and more than 30% had long-term disabilities, unable to retain a full-time job. In the past two decades, surgery for rib fractures has achieving good outcomes. However, in clinic, there are still some problems including inconsistency in surgical indications and quality control in medical services. Before the year of 2018, there were 3 guidelines on the management of regional traumatic rib fractures were published at home and abroad, focusing on the guidance of the overall treatment decisions and plans; another clinical guideline about the surgical treatment of rib fractures lacks recent related progress in surgical treatment of rib fractures. The Chinese Society of Traumatology, Chinese Medical Association, and the Chinese College of Trauma Surgeons, Chinese Medical Doctor Association organized experts from cardiothoracic surgery, trauma surgery, acute care surgery, orthopedics and other disciplines to participate together, following the principle of evidence-based medicine and in line with the scientific nature and practicality, formulated the Chinese consensus for surgical treatment of traumatic rib fractures (STTRF 2021). This expert consensus put forward some clear, applicable, and graded recommendations from seven aspects: preoperative imaging evaluation, surgical indications, timing of surgery, surgical methods, rib fracture sites for surgical fixation, internal fixation method and material selection, treatment of combined injuries in rib fractures, in order to provide guidance and reference for surgical treatment of traumatic rib fractures.

Pyridine-based ring systems are one of the most extensively used heterocycles in the field of drug design, primarily due to their profound effect on pharmacological activity, which has led to the discovery of numerous broad-spectrum therapeutic agents. In the US FDA database, there are 95 approved pharmaceuticals that stem from pyridine or dihydropyridine, including isoniazid and ethionamide (tuberculosis), delavirdine (HIV/AIDS), abiraterone acetate (prostate cancer), tacrine (Alzheimer’s), ciclopirox (ringworm and athlete’s foot), crizotinib (cancer), nifedipine (Raynaud’s syndrome and premature birth), piroxicam (NSAID for arthritis), nilvadipine (hypertension), roflumilast (COPD), pyridostigmine (myasthenia gravis), and many more. Their remarkable therapeutic applications have encouraged researchers to prepare a larger number of biologically active compounds decorated with pyridine or dihydropyridine, expandeing the scope of finding a cure for other ailments. It is thus anticipated that myriad new pharmaceuticals containing the two heterocycles will be available in the forthcoming decade. This review examines the prospects of highly potent bioactive molecules to emphasize the advantages of using pyridine and dihydropyridine in drug design. We cover the most recent developments from 2010 to date, highlighting the ever-expanding role of both scaffolds in the field of medicinal chemistry and drug development.

A novel topology to achieve 4:1 voltage step down, aimed at 48 V to 12 V conversion in data center applications, is presented. The so-called dc-transformer topologies have become a very active area of research to improve the overall efficiency of data centers in response to a shift from a 12 Vdc bus architecture to a 48 Vdc bus architecture. In particular, switched-capacitor topologies have been investigated due to their high power density, efficiency, and low reliance on magnetics. However, switched-capacitor topologies have challenges associated with the hard-charging of capacitors and are often forced to make design compromises that reduce their overall performance. The proposed topology maintains many of the advantages of a switched capacitor topology, such as reduced component stresses, and very low reliance on magnetics, while also inherently avoiding any hard-charging of the flying capacitors. This allows the converter to operate at a very low frequency, such as 60 kHz, with a small inductor, such as 100 nH, and use low voltage stress devices to achieve a peak efficiency of more than 99% for 48 V to 12 V conversion and a power density of 800 W/in3.

In this letter, a soft-switching transformerless dc−dc converter with single-input bipolar symmetric outputs (SIBSO) is proposed, which has positive and negative outputs with equal voltage amplitude and can be used in audio amplifier, bipolar symmetric auxiliary power supply application, etc. Based on the proposed bipolar symmetric outputs cells, the SIBSO dc−dc converter only requires two switches forming a half bridge circuit, and zero voltage switching (ZVS) of the two switches can be achieved over full load range. In addition, common ground of input and outputs is realized, which means the floating driver and isolated sensors are not required in the proposed dc−dc converter. The controller and drivers can be powered up by using input power supply through a simple step-down circuit, which reduces not only the cost and volume but also the complexity of the converter. The operation modes and characteristic of the proposed SIBSO dc−dc converter are analyzed. Moreover, parameter design for ZVS operation is presented. Finally, a 60-W 1-MHz switching frequency prototype is built up by using GaN high electron mobility transistors (HEMTs). Experimental results shown that bipolar symmetric outputs are obtained with common ground of input and output, and peak efficiency of 95.8% and power density of 154 W/in3 are achieved.

Conventional half bridge class-D audio amplifier (HB-CDAA) systems typically suffer from serious bus-voltage pumping. Such a bus-voltage pumping increases the device stress and deteriorates the total harmonic distortion and noise (THD+N) of HB-CDAA. To reduce the bus-voltage pumping of HB-CDAA system, large electrolytic capacitors are usually required at the input of downstream HB-CDAA, which seriously affects the power density of HB-CDAA system. In this article, an electrolytic capacitor-free HB-CDAA system without bus-voltage pumping is proposed, which consists of a front-end bipolar-symmetric-outputs (BSO) bidirectional dc–dc converter and a downstream HB-CDAA. By providing a bidirectional current flowing path in the front-end dc–dc converter, the bus-voltage pumping of the HB-CDAA system is eliminated without using large electrolytic capacitors. Zero voltage switching (ZVS) of all switches in the front-end BSO dc–dc converter can be achieved over the full audio load range. Compared with the HB-CDAA system with a unidirectional front-end dc–dc converter, the proposed audio amplifier system benefits from high power density, low-output voltage THD+N, and voltage stress of switches. The bus-voltage pumping problem is identified, the operation of the proposed HB-CDAA system is analyzed, and the design parameters of the converter are derived to ensure ZVS of all switches. Experimental results with a 40-W prototype of the proposed audio amplifier system are presented to verify the design.

Objective To evaluate the effects of calcium supplementation on bone mineral density in children. Methods The PubMed, Embase, and Cochrane library were systematically searched. The retrieve inception date was between October 2001 and October 2019. Two reviewers independently performed the data extraction and assessed methodology quality. Studies were limited to randomized clinical trials comparing calcium supplement with a placebo for bone mineral density in children. A meta-analysis was performed to calculate standard mean difference (SMD) and 95% confidence interval (CI). Results A total of 6 randomized controlled trials involving 408 participants (calcium supplementation group: 198; placebo group: 210) were finally included in this study. The meta-analysis revealed that, compared with placebos, calcium supplementation had no effect on the bone mineral densities [the whole-body: SMD with CI = 0.43 (−0.05–0.91), P=0.08, I 2 = 75%; the 2nd–4th lumbar vertebrae: SMD with 95% CI = 0.27 (−0.17 to 0.70), P = 0.07, I 2 = 0%)]. Sensitivity analysis revealed that the results of the whole-body bone mineral density were unstable and that the bone density of the 2nd–4th lumbar spine was robust. Conclusions The results of this meta-analysis suggested that calcium supplementation did not improve bone mineral density in children. However, there continues to be a need for more high-quality studies to verify this fact in the future.

BACKGROUND Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by systemic involvement and multiple autoantibodies in the serum. Patients with protein C (PC) and protein S (PS) deficiency are prone to thrombosis. In contrast, patients with primary hyperfibrino-lysis tend to bleed. CASE SUMMARY A 52-year-old female patient with bilateral pleural effusion was diagnosed with "tuberculous pleurisy" and treated with anti-tuberculosis drugs and prednisone. The coagulation-related laboratory results showed decreased fibrinogen, PC activity, PS activity, and antithrombin Ш activity. The immune-related laboratory results showed positive antinuclear antibody, anti-Smith antibody, anticardiolipin antibody (ACL), anti-β2-glycoprotein I antibody (aβ2GPI) and direct Coomb’s test and decreased complement 3 and complement 4. Thoracoscopy was performed and bloody pleural fluid was drained. Pathology of the pleural biopsy showed lymphocytes, plasma cells, and a few eosinophils in adipose and fibrous connective tissue. Results of whole exome sequencing of blood showed no genetic mutations suggesting the presence of hereditary hematological diseases. The patient was finally diagnosed with SLE and primary hyperfibrinolysis, and was treated with prednisolone, hydroxychloroquine, and compound cyclophosphamide. CONCLUSION PC and PS deficiency in SLE might be related to ACL and aβ2GPI. SLE and primary hyperfibrinolysis can coexist in one patient, with both a risk of thrombosis and a risk of bleeding.

Dysregulation of matrix metalloproteinase- (MMP-) 9 is implicated in the pathogenesis of acute lung injury (ALI). However, it remains controversial whether MMP-9 improves or deteriorates acute lung injury of different etiologies. The receptor for advanced glycation end products (RAGE) plays a critical role in the pathogenesis of acute lung injury. MMPs are known to mediate RAGE shedding and release of soluble RAGE (sRAGE), which can act as a decoy receptor by competitively inhibiting the binding of RAGE ligands to RAGE. Therefore, this study is aimed at clarifying whether and how pulmonary knockdown of MMP-9 affected sepsis-induced acute lung injury as well as the release of sRAGE in a murine cecal ligation and puncture (CLP) model. The analysis of GEO mouse sepsis datasets GSE15379, GSE52474, and GSE60088 revealed that the mRNA expression of MMP-9 was significantly upregulated in septic mouse lung tissues. Elevation of pulmonary MMP-9 mRNA and protein expressions was confirmed in CLP-induced mouse sepsis model. Intratracheal injection of MMP-9 siRNA resulted in an approximately 60% decrease in pulmonary MMP-9 expression. It was found that pulmonary knockdown of MMP-9 significantly increased mortality of sepsis and exacerbated sepsis-associated acute lung injury. Pulmonary MMP-9 knockdown also decreased sRAGE release and enhanced sepsis-induced activation of the RAGE/nuclear factor-κB (NF-κB) signaling pathway, meanwhile aggravating sepsis-induced oxidative stress and inflammation in lung tissues. In addition, administration of recombinant sRAGE protein suppressed the activation of the RAGE/NF-κB signaling pathway and ameliorated pulmonary oxidative stress, inflammation, and lung injury in CLP-induced septic mice. In conclusion, our data indicate that MMP-9-mediated RAGE shedding limits the severity of sepsis-associated pulmonary edema, inflammation, oxidative stress, and lung injury by suppressing the RAGE/NF-κB signaling pathway via the decoy receptor activities of sRAGE. MMP-9-mediated sRAGE production may serve as a self-limiting mechanism to control and resolve excessive inflammation and oxidative stress in the lung during sepsis.

This article presents a method to design new diplexer-integrated single-pole double-throw (SPDT) switches for composite time division duplexing (TDD) and frequency division duplexing (FDD) requirements. The common fractal stub-loaded resonator (F-SLR) is employed to provide four magnetic coupling paths to introduce the mixed electric and magnetic coupling (MEMC) for every channel. Together with the cross-couplings, the ON-state channel with high selectivity bandpass response can be achieved. As examples, a third-order diplexer-integrated SPDT switch and a fourth-order diplexer-integrated SPDT switch operating at 0.9/1.8 GHz are designed and fabricated. These two diplexer-integrated SPDT switches have three major operating modes, i.e., the 0.9-GHz bandpass filter (BPF)-integrated SPDT switch operating mode, the 1.8-GHz BPF-integrated SPDT switch operating mode, and the 0.9-/1.8-GHz diplexer-integrated SPDT switch operating mode. In the design, the loaded positions of p-i-n diodes on the uniform impedance resonators of 0.9-GHz channel are optimized to improve the OFF-state rejection bandwidth. Measured results also show that these two diplexer-integrated SPDT switches have low ON-state passband insertion loss, high port-to-port isolation, and compact circuit size.

Origin-Destination (OD) prediction which aims to predict the number of passenger’s travel demands from one region to another, is critically important to many real applications including intelligent transportation systems and public safety. The challenges of this problem lie in both the dynamic patterns of the human mobility data and data sparsity in issue in some regions. Thus it is difficult to model the complex spatio-temporal correlations of the human mobility data to predict the OD of their trips. Meanwhile, the crowd flows in different regions of a city and the context features (e.g. holiday, weather and POIs) are potentially useful to alleviate the data sparsity issue and improve the OD prediction, but are largely ignored by existing works. In this paper, we propose a deep spatio-temporal framework which named Auxiliary-tasks Enhanced Spatio-Temporal Network (AEST) to more effectively address the OD prediction problem. AEST trains a model to conduct OD inference via learning crowd flow and external data as auxiliary task. The novel Hierarchical Convolutional LSTM (HC-LSTM) Network is proposed which combines CNN, GCN and LSTM to effectively capture spatiao-temporal correlations. In addition, we design a Contextual Network (ContextNet) which learns representations of contextual information to assist OD prediction. We conduct extensive experiments over bike and taxicab trip datasets in New York. The results show that our method is superior to the state-of-art approaches.

Nanotechnology has prompted the development of hollow inorganic nanomedicine. These medicines are now widely investigated as photothermal-based therapies for various diseases due to their high loading capacity, tuneable wavelength, relatively small size and low density. We begin this review with a brief introduction, followed by a summary of the development of imaging-guided photothermal therapy (PTT) for cancer treatment during the last three years (from 2017 to 2020). We then introduce the antibacterial effects of these medicines on some bacterial infections, in which the pathogenic bacteria can be killed by mild photothermal effects, ions and antibiotic release. Other diseases can also be treated using hollow inorganic photothermal agents. Specifically, we discuss the use of PTT for treating Alzheimer’s disease, obesity and endometriosis. Finally, we share our perspectives on the current challenges and future prospects of using hollow inorganic materials in clinical PTT for various diseases.

Extraskeletal Ewing's Sarcoma (EES) may harbor more than one tumor-specific genetic abnormality, leading to diagnostic difficulties. Case report: We report a nine-year-old boy with recurrent mass o...

Idiopathic rapid eye movement sleep behaviour disorder (RBD) is now recognized as an early manifestation of α-synucleinopathies. Increasing experimental studies demonstrate that manipulative lesion or inactivation of the neurons within the sublaterodorsal tegmental nucleus (also known as the subcoeruleus nucleus in humans) can induce RBD-like behaviours in animals. As current RBD animal models are not established on the basis of α-synucleinopathy, they do not represent the pathological substrate of idiopathic RBD and thus cannot model the phenoconversion to Parkinson’s disease. The purpose of this study was therefore to establish an α-synucleinopathy-based RBD animal model with the potential to convert to parkinsonian disorder. To this end, we first determined the functional neuroanatomical location of the sublaterodorsal tegmental nucleus in wild-type C57BL/6J mice and then validated its function by recapitulating RBD-like behaviours based on this determined nucleus. Next, we injected preformed α-synuclein fibrils into the sublaterodorsal tegmental nucleus and performed regular polysomnographic recordings and parkinsonian behavioural and histopathological studies in these mice. As a result, we recapitulated RBD-like behaviours in the mice and further showed that the α-synucleinopathy and neuron degeneration identified within the sublaterodorsal tegmental nucleus acted as the neuropathological substrates. Subsequent parkinsonian behavioural studies indicated that the α-synucleinopathy-based RBD mouse model were not stationary, but could further progress to display parkinsonian locomotor dysfunction, depression-like disorder, olfactory dysfunction and gastrointestinal dysmotility. Corresponding to that, we determined α-synuclein pathology in the substantia nigra pars compacta, olfactory bulb, enteral neuroplexus and dorsal motor nucleus of vagus nerve, which could underlie the parkinsonian manifestations in mice. In conclusion, we established a novel α-synucleinopathy-based RBD mouse model and further demonstrated the phenoconversion of RBD to Parkinson’s disease in this animal model.

Background. There are distinct results for the relationship between new-onset atrial fibrillation (NOAF) and subsequent incident cancer. To date, no systematic analysis has been conducted on this issue. This study aims to explore the relationship between NOAF and the risk of developing cancer through a meta-analysis with a large sample size. Methods. Electronic databases, such as PubMed and EMBASE, were searched for published relevant studies on NOAF patients diagnosed with cancer after and during follow-ups, including reported records of baseline information and the statistical result of morbidity. Two investigators independently reviewed the articles and extracted the data using uniform standards and definitions. The meta-analysis was conducted using the Cochrane Program Review Manager. Results. This meta-analysis consisted of five cohort studies and one case-control study, which comprised 533,514 participants. The pooled relative risk (RR) for incident cancer was 1.24 (95% CI: 1.10–1.39, P=0.0003). The temporal trend analysis demonstrated that an increased risk of cancer was observed during the initial 90 days (RR: 3.44, 95% CI: 2.29–5.57, P<0.00001), but not after that. Lung cancer (RR: 1.51, 95% CI: 1.47–1.55, P<0.00001) was associated with NOAF, but not colorectal cancer and breast cancer. Conclusion. This meta-analysis provides evidence that NOAF is associated with increased risk of cancer. The risk of incident cancer particularly increases within 90 days after NOAF diagnosis, but not after that.

The tourism industry has the largest scale of economic activities worldwide with the most powerful development momentum but has generated a negative effect on the ecological environment. The development of the tourism industry is a precondition and guarantee of eco-environmental optimization, and a harmonious ecological environment is an important dynamic support for the growth of tourism economy, making them mutually associated with evident coupling characteristic. In this study, related literature regarding the tourism industry and eco-environmental protection of developed countries in Europe and America were first reviewed, and tourism industry-ecological environment coupling model was constructed using Henan Province, China, as a case study. The coupling degrees in Henan Province during 2013-2018 were measured, and a comparative analysis of the spatial changes in tourism industry-ecological environment coupling degrees of 18 prefecture-level cities in Henan in 2013 and 2018 was conducted. Results showed that the order degree of the tourism industry in Henan Province maintained a rising trend during 2013-2018, whereas that of the ecological environment exhibited a fluctuating trend. The overall tourism industry–ecological environment coupling of 18 prefecture-level cities in Henan Province enhanced in 2013 and 2018, where the coupling degrees in Zhengzhou, Nan yang, and Luoyang presented an outward radiation trend from high to low. The study results serve as significant reference values for revealing the spatial-temporal evolution characteristics of the ecological environment and the tourism industry and completing the research regarding the coordinated development of the tourism industry and ecological environment.

Introduction Elderly people are at increased risk of falls, disability and death due to reduced functional reserve, decline in multiple systems functions, which affects their activities of daily living (ADL) and eventually develop into frailty. The ADL assessment is conducive to early detection to avoid further serious situations. Previous studies on patients' activities of daily living with chronic kidney disease (CKD) are mainly focused on dialysis patients. Little information is available on non-dialysis patients. Patients and Methods A total of 303 elderly patients with CKD stage 3-5 who were admitted to our hospital were selected. ADL evaluation was performed on patients at admission, with Barthel index (BI) as the evaluation tool. They were divided into two groups based on BI (≥60 and

Background: The eosinophilic chronic obstructive pulmonary disease (COPD) is known to be more sensitive to corticosteroid. The sputum microbiome has been shown to affect COPD prognosis, but its role in acute exacerbations of eosinophilic COPD is unclear. This study aimed to investigate the dynamic changes of the airway microbiome in patients with acute exacerbations of eosinophilic COPD. Methods: Fifty-seven patients with acute exacerbations of COPD from the First Affiliated Hospital of Guangxi Medical University between June 2017 and June 2018 were divided into two groups. Patients with eosinophils ≥300 cells/μL in the peripheral venous blood were assigned to the eosinophilic group (Eos) and the rest to the non-eosinophilic group (Noneos). All patients received similar treatment including inhaled budesonide according to the guidelines. The induced sputum microbiome was analyzed on the 1st and 7th day of treatment using the 16S ribosomal RNA (rRNA) method. The levels of interleukin (IL)-6 and IL-8 were measured in the plasma and the sensitivity to corticosteroids was determined in isolated peripheral blood mononuclear cells. Quantitative data were compared between the two groups using the independent samples t test or Mann-Whitney U test. Categorical data were evaluated using Chi-squared test or Fisher’s exact test. Results: Twenty-six patients were classified into Eos group and 31 patients were classified into Noneos group. Prior to treatment, the alpha diversity (Shannon index) (2.65 ± 0.63 vs. 2.56 ± 0.54, t = 0.328, P = 0.747) and the structure of the sputum microbiome were similar in the Eos group and the Noneos group. After 7 days of treatment, alpha diversity increased in both groups, while the microbiome richness (Ace index) was significantly lower in the Eos group (561.87 ± 109.13 vs. 767.88 ± 148.48, t = -3.535, P = 0.002). At the same time, IL-6 (12.09 ± 2.85 pg/mL vs. 15.54 ± 2.45 pg/mL, t = -4.913, P < 0.001) and IL-8 (63.64 ± 21.69 pg/mL vs. 78.97 ± 17.13 pg/mL, t = -2.981, P = 0.004) decreased more significantly in the Eos group, and the percentages of inhibition of IL-8 at dexamethasone concentrations 10-8 to 10-6 mol/L were significantly higher in the Eos group than those in the Noneos group (all P < 0.05). Conclusions: The induced sputum microbiome richness decreased more significantly following treatment in the Eos patients compared to the Noneos patients. The lower plasma inflammatory factor levels and the higher percentage of inhibition of IL-8 might be due to higher corticosteroid sensitivity in Eos patients. Key words: Acute exacerbations of chronic obstructive pulmonary disease; Sputum; Microbiome; Eosinophilic; Corticosteroid; Interleukin-8 inhibition

Acetaminophen (APAP)-induced acute liver injury (ALI) is a health issue that has gradually attracted attention, and is often regarded as a model of drug-induced hepatotoxicity. The leaves of Lithocarpus polystachyus Rehd. (named as “sweet tea”, ST) usually serve as tea drink and folk medicine for healthcare in the southwest part of China. In previous reports, it has been proven to protect various animal models, except for APAP-induced liver injury model. Therefore, this study initially explored the protective effect of ST leaf extract (STL-E) on hepatotoxicity induced by APAP in ICR mice. STL-E of 50 and 100 mg kg−1 were given to each group for 7 days. ALI was intraperitoneally induced by APAP treatment (i.p. 250 mg per kg body weight). Biochemical markers, levels of inflammatory factors, histopathological staining and western blotting were used to analyze the inflammation and apoptosis of liver tissues. Interestingly, the treatment with STL-E significantly attenuated APAP-induced liver injury (p < 0.05). Moreover, STL-E partially mitigated APAP-induced liver injury by effectively activating the PI3K/Akt pathway and inhibiting the NF-κB pathway. In a word, STL-E protected liver against APAP-induced hepatotoxicity by inhibiting the PI3K/Akt-mediated apoptosis signal pathway and inhibiting the NF-κB-mediated signaling pathway.

Purpose: Multiple studies have demonstrated an obesity paradox such that obese septic patients have a lower mortality rate and a relatively favorable prognosis. However, less is known on the association between abdominal obesity and short-term mortality in patients with sepsis. We conducted this study to determine whether the obesity-related survival benefit remains among abdominal obese patients.Methods: A retrospective cohort study was conducted using data derived from the Medical Information Mart for Intensive Care IV database. Septic patients (≥18 years) with or without abdominal obesity of first intensive care units (ICU) admission in the database were enrolled. The primary outcome was mortality within 28 days of ICU admission and multivariable logistic regression analyses were employed to assess any association between abdominal obesity and the outcome variable.Results: A total of 21534 patients were enrolled finally, the crude 28-day mortality benefit after ICU admission was not observed in patients with abdominal obesity (15.8% vs. 15.3%, p=0.32). In the extended multivariable logistic models, the odds ratio (OR) of abdominal obesity was significantly inversed after incorporating metabolic variables into the logistic model (OR range 1.094-2.872, p = 0.02). The subgroup analysis showed interaction effects in impaired fasting blood glucose/diabetes and metabolic syndrome subgroups (P = 0.001 and Conclusion: Abdominal obesity was associated with increased risk of adjusted sepsis-related mortality within 28 days after ICU admission and was partially mediated through metabolic syndrome components.

Intrahepatic cholangiocarcinoma (iCCA) is the second most common cancer in liver, with a high recurrence rate after surgery. Recently, we identified a CD11b-CD169-based myeloid response score (MRS), which showed remarkable prognostic potential in hepatocellular carcinoma (HCC). Here, we aimed to verify the prognostic value of the MRS in iCCA and establish an MRS-based nomogram to predict the postoperative prognosis of iCCA patients. From April 2005 to March 2017, a total of 84 patients from the Third Affiliated Hospital of Sun Yat-sen University were enrolled. Preoperative clinical information and surgical specimens of enrolled patients were collected. Among these, tissues from 75 patients passed the clinical data quality control and the staining quality control. The protein expression of CD11b and CD169 in iCCA samples were detected by immunohistochemistry (IHC). Kaplan-Meier analysis and receiver operating characteristic (ROC) curves revealed that the MRS had a high discriminatory ability for predicting the time to recurrence (TTR) of iCCA patients after surgery. Three independent risk factors selected by a Cox proportional hazards regression analysis, namely, the MRS, the tumor size and the status of vascular invasion, were included to construct a nomogram to predict the recurrence of iCCA after resection surgery. ROC curves, calibration analysis and decision curve analysis (DCA) suggested that this nomogram had notable discriminatory power, stability and clinical usefulness in predicting the postoperative recurrence. Together, we explored the prognostic value of the MRS in iCCA, and constructed an MRS-based nomogram which may help to predict postoperative recurrence and aid clinical decisions for iCCA patients.

This paper proposes a new phase-modular three-phase single-stage rectifier based on the LLC resonant converter. The proposed rectifier provides power factor correction, output voltage regulation, and electrical isolation in a single-stage modular-designed approach. The proposed rectifier has minimal switching loss due to the ZVS and ZCS operations of all the switches and diodes. Moreover, the proposed AC-DC converter does not use any bulky passive components and hence is suitable for high power density applications that also require high power conversion efficiency. Design notes and specifications of a single module are provided in this paper. Computer simulation results verified the unity PFC performance and output voltage regulation using a small output capacitance without any low-frequency ripple. Furthermore, the feasibility of the proposed rectifier is validated by the experimental results of a digitally implemented GaN-based laboratory prototype.

The effect of Pulsatilla saponin A (PsA) on acute myocardial infarction (AMI) was unknown. This study targeted to examine the roles of PsA on hypoxia-triggered toxicity to H9c2 cells and reveal the potential mechanism. H9c2 cells were maintained under a hypoxic environment for 12 h to construct the AMI cell model and the cells were pretreated by PsA. Hypoxia triggered toxicity to H9c2 cells and the anti-toxicity effect of PsA was evaluated by CCK8, TUNEL, and Western blot. The levels of miR-24-3p and p16 in H9c2 cells, AMI group tissues, and their respective controls were assessed using qRT-PCR. The dual-luciferase assay was applied to verify the targeting mechanism of miR-24-3p on p16. Then the effects of miR-24-3p inhibitor or/and si-p16 on H9c2 cells treated with PsA under hypoxia were detected by CCK8, TUNEL, and Western blot. Flow cytometry was executed to determine the cell cycle. Hypoxia decreased viability and proliferation and increased apoptosis of H9c2 cells, which were ameliorated by PsA pretreatment. The level of miR-24-3p was diminished, but p16 expression was elevated in hypoxia-treated cells and AMI group tissues. MiR-24-3p could sponge p16 in hypoxia-treated cells. Furthermore, the impact of applying miR-24-3p inhibitor on PsA and hypoxia-treated cells could be reversed by si-p16. PsA relieved hypoxia-triggered cell toxicity via miR-24-3p/p16 axis. These findings provided some fresh insights into the potential therapeutic effects of the application of PsA in AMI.

The switched-capacitor converter (SCC) topology has been gaining attention in recent years because of their advantages of higher power density, switch utilization, and reduced component stress compared to existing converter topologies. However, SCCs have a major drawback in which capacitor charge redistribution results in significant current spikes. One method of addressing charge redistribution is split-phase operation, which accomplishes this by imposing voltage control on the SCC’s flying capacitors. However, an important design consideration was identified regarding the implementation of the split-phase Dickson SCC in high-current applications. Mismatched flying capacitors exhibit uneven charge rates, resulting in incomplete elimination of charge redistribution by split-phase control. This paper presents a discussion of the effects of mismatched flying capacitors on the operation of the split-phase Dickson SCC. Furthermore, design processes and test results of a prototype high-current split-phase Dickson SCC will be presented.

The sperm quality of some males is in a critical state, making it hard for clinicians to choose the suitable fertilisation methods. This study aimed to develop an intelligent nomogram for predicting fertilisation rate of infertile males with borderline semen. 160 males underwent in vitro fertilisation (IVF), 58 of whom received rescue ICSI (R‐ICSI) due to fertilisation failure (fertilisation rate of IVF ≤30%). A least absolute shrinkage and selection operator (LASSO) regression analysis identified sperm concentration, progressively motile spermatozoa (PMS), seminal plasma anti‐Müllerian hormone (spAMH), seminal plasma inhibin (spINHB), serum AMH (serAMH) and serum INHB (serINHB) as significant predictors. The nomogram was plotted by multivariable logistic regression. This nomogram‐illustrated model showed good discrimination, calibration and clinical value. The area under the receiver operating characteristic curve (AUC) of the nomogram was 0.762 (p

The TM-doped Si-based semiconductor clusters have aroused increased attention in a lot of fields. Here, we have performed a structural search of the global minimum for neutral and anionic Sin and L...

Although a single-stage off-line power light-emitting diode (LED) driver can achieve low cost and high efficiency, the notorious double-line-frequency flicker issue with a single-stage LED driver limits its usage in high-quality lighting applications. To solve lighting flicker, as well as maintain a low cost and high efficiency, a multiplexing ripple cancellation (MRC) LED driver is proposed in this paper. One switching cycle is divided into two intervals. During the first interval, the proposed LED driver operates as a conventional LED driver that transfers energy from the ac input to LED output, performs power factor correction, and generates the main output voltage. The main output voltage has a double-line-frequency ripple like in a conventional design. During the second interval, the proposed LED driver transfers energy from the ac input again to generate an opposite ripple voltage to cancel the ripple voltage from the main output. In this way, the voltage across the LED load is a dc to achieve flicker-free LED driving performance. More than 99% of the output power goes through one-time power conversion, while less than 1% goes through two-time power conversion. A 7.5-W experimental prototype is built and tested to verify the design concept.

A soft switching symmetric bipolar outputs dc-transformer (DCX) for eliminating power supply pumping of half-bridge class-D audio amplifiers is proposed in this paper. Compared with the traditional unidirectional front-end dc–dc converter in the half-bridge class-D audio amplifier, output capacitances of the proposed DCX and voltage stress of the half-bridge class-D audio amplifier are significantly reduced. Soft switching of the proposed DCX can be achieved when the load current of half-bridge class-D audio amplifier is positive or negative. Thus, the efficiency and power density of the proposed audio amplifier system can be improved. In addition, the proposed DCX has smoothing transition between the positive load current and the negative load current with a simple open-loop controller. The operating principle of the proposed DCX is analyzed and a 200-W prototype is built up. Experimental results show that power supply pumping is reduced with small DCX output capacitors, symmetric bipolar outputs are obtained and peak efficiency of 96.3% is achieved.

Parkinson's disease (PD) is a common neurodegenerative disease, featured by motor deficits and non-motor symptoms such as cognitive impairment, and malfunction of gamma-aminobutyric acid (GABA) mediated inhibitory transmission plays an important role in PD pathogenesis. The ginsenoside Rb1 molecule, a major constituent of the extract from the Ginseng root, has been demonstrated to ameliorate motor deficits and prevent dopaminergic neuron death in PD. However, whether Rb1 can regulate GABAergic transmission in PD-associated deficits and its underlying mechanisms are still unclear. In this study, we explored the effects of Rb1 on the GABAergic synaptic transmission in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) mouse model of PD. We demonstrated that Rb1 can bind with GABAARα1 and increase its expression in the SH-SY5Y cells and in the prefrontal cortex (PFC) of MPTP model in vitro and in vivo. Furthermore, Rb1 can promote prefrontal cortical GABA level and GABAergic transmission in MPTP-treated mice. We also revealed that Rb1 may suppress presynaptic GABABR1 to enhance GABA release and GABAA receptor-mediated inhibitory transmission. In addition, Rb1 attenuated MPTP-induced dysfunctional gait dynamic and cognitive impairment, and this neuroprotective mechanism possibly involved regulating prefrontal cortical GABAergic transmission. Thus, Rb1 may serve as a potential drug candidate for the treatment of PD.

AC-connected light emitting diode (LED) drivers experience imbalanced energy between input and output in a half-line cycle. To achieve the flicker-free operation, the imbalanced energy needs to be buffered, often by energy-dense electrolytic capacitors. However, electrolytic capacitors are also well-known for their short lifespan. These capacitors are the limiting factor of an LED drivers’ lifespan. High voltage film capacitors and a buck converter have been used in the proposed LED driver to buffer the imbalanced energy. When P in > P LED, the extra energy is transferred from the ac input directly to the high voltage film capacitors. When P in P LED, the energy is transferred from the high voltage film capacitors to the output by the buck converter. The imbalanced energy goes through two power conversion steps in the proposed LED driver, which is one time less than other comparable electrolytic capacitor-less designs, enabling a higher efficiency to be achieved. A 28 W flyback topology based experimental prototype had been built and tested to verify the proposed design.

The structural resilience of a steel frame with posttensioned (PT) connections under a column-removal scenario is numerically investigated. Four high-fidelity PT connections finite element (FE) models are developed and compared with the experimental results in the literature, and the developed models describe the behavior of the connections accurately. A method to evaluate middle column removal scenario in a one-story, two-bay frame with PT connections is proposed. The corresponding resisting mechanisms are quantitatively evaluated, which consists of beam mechanism contributed mainly by beam arching action and strand catenary mechanism. A three-dimensional FE model of beam-column substructure with PT connections are developed considering the effect of increasing vertical displacement. Vertical responses associated with different working cases are assessed and the influences of strands, beams and top-seat angles are investigated. In addition, a quantitative evaluation index of the structural resilience under a column-removal scenario for a PT steel frame is proposed based on vertical response displacement. A resilience-based design approach is proposed for the practical engineering design.

PURPOSE To retrospectively evaluate the role of intraoperative ultrasonography (IOUS) and contrast-enhanced IOUS (CE-IOUS) for the patients with hepatocellular carcinoma (HCC) undergoing hepatic resection (HR). METHODS Twenty-one consecutive patients who had undergone HR for HCC were included in this study. The patients were subject to preoperative imaging modalities including preoperative ultrasonography (Pre-US) and preoperative contrast-enhanced ultrasonography (Pre-CEUS). All the patients then underwent intraoperative ultrasonography (IOUS) and contrast-enhanced intraoperative ultrasonography (CE-IOUS) during surgery. The visualization of primary HCC and additional lesions of all patients were analyzed. RESULTS Twenty-one HCCs were detected during Pre-US and the remaining six lesions (28.6%) were detected during IOUS and CE-IOUS. Thus the treatment plan was changed in 28.6% of patients. Twenty-one HCCs (diameter, 0.6-3.0 cm; mean±SD, 1.98±0.85 cm) were measured on Pre-US and remeasured on IOUS (diameter, 0.9-3.3 cm; mean±SD, 2.19±0.84 cm) (p

OBJECTIVE We aimed to test the association of polymorphisms in HTR2A, TPH1, and TPH2 genes with attempted suicide in rural China. PARTICIPANTS AND METHODS On the basis of a case-control study, we recruited 1200 pairs of participants from Shandong Province, China. The blood samples of 712 suicide attempters and 739 nonsuicide attempters were collected finally. We tested seven single nucleotide polymorphisms: rs6313 and rs6311 in HTR2A, rs4537731, rs1800532, and rs1799913 in TPH1, and rs4448731 and rs4641527 in TPH2. RESULTS In univariate analysis, allele C of rs4537731 was associated negatively with attempted suicide among total and male samples; however, the association was not statistically significant in multivariate analysis after adjusting for other potential confounding factors. No association between other six single nucleotide polymorphisms and attempted suicide was found in the total, male, or female samples. CONCLUSION This study did not support the effect of these seven serotonergic gene polymorphisms on attempted suicide in rural China.

Efficient and accurate control of incoming inter-domain traffic is critically important for Autonomous Systems (ASes). However, it is extremely difficult for two neighboring ASes to efficiently control incoming traffic over multiple inter-domain links in the current Internet. By contrast, Information-Centric Networking (ICN) is a novel network paradigm and has many inherent features, which can support finer granularity of routing policies and provide more opportunities to realize Traffic Engineering (TE). In this paper, we explore the potentials of ICN in controlling incoming inter-domain traffic between neighboring ASes who have multiple inter-domain links. We present a heuristic algorithm and extend it with different information on network status and content metadata. We implement them in a real prototype and compare them with a classic inter-domain TE approach in the current Internet (i.e., the IP-prefixes negotiation approach, IPN) in three scenarios. Three interesting conclusions are drawn from extensive experiments on the prototype. First, ICN makes it easier to control inter-domain traffic compared with IPN. In particular, ICN approaches have shorter negotiation delay and lower negotiation overhead. Second, content metadata (e.g., content size) in ICN is quite beneficial to control traffic since it can help estimate traffic volumes so as to achieve more accurate control of traffic. Third, ICN can efficiently handle the bursty traffic and link failures compared with IPN.

Background and Aims. Hydrotalcite plays an important role in the therapy of gastric ulcer induced by nonsteroidal anti-inflammatory drugs (NSAIDs), but little is known about the mechanism. We designed two experiments to study the preventive and curative effects of hydrotalcite on NSAIDs-related gastric injury in rats and to investigate the relationship between the protective and curative mechanism of hydrotalcite and the secretion of epidermal growth factor (EGF)/prostaglandin E2 (PGE2).Methods. Two experiments were separately designed to evaluate the preventive and curative effects of hydrotalcite. A total of 25 male rats and 25 female rats were randomly divided into five groups (vehicle group, model group, omeprazole group, hydrotalcite group, and ranitidine group) in each experiment. Rats were treated with indomethacin by gavage to build the model of acute gastric mucosal injury. The concentrations of EGF and PGE2 in blood specimens and mucosal injury indexes by gross inspection were measured and an immunohistochemical technique was also employed to test the levels of EGF, cyclooxygenase-1 (COX-1), and cyclooxygenase-2 (COX-2) in gastric mucosa.Results. Comparing with model group in both preventive and curative experiments, hydrotalcite decreased the gastric injury in the mucosa of stomach significantly (7±4.5 vs. 16±11.25, 1.5±2 vs. 2.5±6;P, PPPP, PConclusions. Hydrotalcite promotes gastric protection and healing via several mechanisms, including increased levels of PGE2 in blood serum, activation of EGF, and antagonising the inhibition of cyclooxygenase (COX) caused by NSAIDs.

In data center and telecommunication power supplies, the front-end dc–dc stage is required to operate with a wide input voltage range to provide hold-up time when ac input fails. Conventional LLC converter serving as the dc–dc stage is not suitable for this requirement, as the normal operation efficiency (at 400 V input) will be penalized once the converter is designed to achieve high peak gain (wide input voltage range). This paper examined the operation of the LCLC converter and revealed that the LCLC converter could be essentially equivalent to a set of LLC converters with different magnetizing inductors that are automatically adjusted for different input voltages. In nominal 400 V input operation, the LCLC converter behaves like an LLC converter with large magnetizing inductor, thus the resonant current is small. In the hold-up period, when the input voltage reduces, the equivalent magnetizing inductor will reduce together with switching frequency reducing, thus the converter achieves high peak gain. In this paper, a new design methodology is also proposed to achieve optimal utilization of the two resonant capacitors for high power application. To verify the effectiveness of the LCLC converter for hold-up operation, comprehensive analysis has been conducted; a detailed step by step design example based on capacitor voltage stress is introduced; an experimental LCLC prototype optimized at 400 V, with input voltage range of 250–400 V and 12 V/500 W as output has been presented.

Inflammation is associated with skeletal muscle dysfunction and atrophy in patients with chronic obstructive pulmonary disease (COPD). Theophylline has an anti-inflammatory role in COPD. However, the effects of theophylline on inflammation in skeletal muscle in COPD have rarely been reported. The aims of this study were to explore whether theophylline has an anti-inflammatory effect on skeletal muscle in a mouse model of emphysema and to investigate the molecular mechanism underlying this effect. In mice, cigarette smoke (CS) exposure for 28 wk resulted in atrophy of the gastrocnemius muscle. Histone deacetylase 2 (HDAC2) and nuclear factor-κBp65 (NF-κBp65) mRNA and protein levels were significantly decreased and increased, respectively, in gastrocnemius muscle. This effect was revered by aminophylline. The exposure of murine skeletal muscle C2C12 cells to CS extract (CSE) significantly increased IL-8 and TNF-α levels as well as NF-κBp65 mRNA and protein levels and NF-κBp65 activity. This effect was reversed by theophylline. HDAC2 knockdown enhanced the activity of NF-κBp65 and increased IL-8 and TNF-α levels in C2C12 cells. CSE significantly increased the interaction of HDAC2 with NF-κBp65 in C2C12 cells. These data suggest that theophylline has an anti-inflammatory effect on skeletal muscle in a mouse model of emphysema by upregulating HDAC2 expression and decreasing NF-κBp65 activation.

UV radiometers are used in many areas. There are many kinds of UV light sources with different peak wavelength and different wavelength range. The broadband UV radiometers are wildly used due to easy to use and low cost. However, there are some obvious disadvantages for the broadband radiometers. They cannot distinguish the spectral characteristics of UV sources. That will cause the spectral mismatch measurement error for the UV broadband radiometers calibration. Recently, the fiber spectroradiometer plays a more and more important role in this area. The fiber spectroradiometer is more portable and low cost compared to the double grating spectroradiometer. We can obtain the spectral characteristics and any UV irradiance using the fiber spectroradiometer. However, for most fiber spectroradiometers, we cannot use them to replace the UV broadband radiometers for the absolute irradiance measurement. There are four key effects for that. The first one is the stray light. Stray light effect is obvious for the fiber spectroradiometer, especially in the UV wavelength range. The second one is the temperature effect. The third one is the non-linearity effect. The fourth one is the bandwidth effect. This effect will cause the measurement error for the spectral distribution of the UV source. In this paper, we research the four factors that reduce the measurement accuracy of the fiber spectroradiometer in UV wavelength range.

More than ten thousand peer-reviewed studies have assessed the role of fibroblast growth factors (FGFs) and their receptors (FGFRs) in cancer, but few patients have yet benefited from drugs targeting this molecular family. Strategizing how best to use FGFR-targeted drugs is complicated by multiple variables, including RNA splicing events that alter the affinity of ligands for FGFRs and hence change the outcomes of stromal-epithelial interactions. The effects of splicing are most relevant to FGFR2; expression of the FGFR2b splice isoform can restore apoptotic sensitivity to cancer cells, whereas switching to FGFR2c may drive tumor progression by triggering epithelial-mesenchymal transition. The differentiating and regulatory actions of wild-type FGFR2b contrast with the proliferative actions of FGFR1 and FGFR3, and may be converted to mitogenicity either by splice switching or by silencing of tumor suppressor genes such as CDH1 or PTEN. Exclusive use of small-molecule pan-FGFR inhibitors may thus cause nonselective blockade of FGFR2 isoforms with opposing actions, undermining the rationale of FGFR2 drug targeting. This splice-dependent ability of FGFR2 to switch between tumor-suppressing and -driving functions highlights an unmet oncologic need for isoform-specific drug targeting, e.g., by antibody inhibition of ligand-FGFR2c binding, as well as for more nuanced molecular pathology prediction of FGFR2 actions in different stromal-tumor contexts.

Background: Pressure ulcers (PU) are a chronic wound for elderly populations. Previous works have shown that exosomes from stem cells contain cytokines and growth factors that play a role in tissue repair and can represent a therapeutic strategy for wound healing. Thus, as a new cell-free treatment model, fully understanding the extraction of exosomes and its mechanism of action can help promote the management of clinically chronic refractory wound healing. Material and Methods: In this study, we initially isolated exosomes from human umbilical cord mesenchymal stem cells (hucMSC-Exo) and examined their roles in wound healing. Different time points were evaluated for 15 mice which were randomly divided into three groups to serve three I-R circles and took different dose of hucMSC-Exo. Quantitative real-time polymerase chain reaction (qRT-PCR) was applied to analyze collagen mRNA levels in tissue samples. HMGB1 content was explored by western blot and immunohistochemistry. Comparing α-SAM, CD34, HMGB1 were used to investigate the potential mechanisms.Results: We found that hucMSC-Exo could be taken up by fibroblasts and significantly regulate and improve fibroblast fibrotic status and in-vivo PU wound healing. Further, we observed that hucMSC-Exo treatment of PU wound was able to downregulate the expression of HMGB1 previously shown to have a deleterious role in the wound healing process. Conclusion: Our study indicates that hucMSC-Exo regulates the repair of pressure ulcer wounds in part by inhibiting HMGB1. Exosome treatment has opened up a new perspective in regenerative medicine and trauma management.

Background:To explore the application effect of multicenter transitional nursing in patients post-TIPS.Methods:A total of 368 patients who underwent TIPS were randomly allocated to the control or intervention group. Patients in the control group received conventional care, and patients in the intervention group received conventional care combined with transitional care. The Child-Pugh scores, blood ammonia levels, compliance behavior, medication compliance, and adverse event incidence rates in the two groups were compared at 1, 3, 6, 9 and 12 months post-TIPS.Results:Repeated measures analysis of variance showed significant group effects 1, 3, 6, 9 and 12 months post-TIPS in the compliance behavior scores of the two groups. The intervention group had significantly higher compliance behavior scores than the control group 1, 3, 6, 9 and 12 months post-TIPS. The incidence of postoperative adverse events in the intervention group was significantly lower than that in the control group 12 months after TIPS. The group effects, time effects and group*time interaction revealed significant differences in the Child-Pugh scores 1, 3, 6, 9 and 12 months post-TIPS between the two groups and significant differences in blood ammonia levels 9 months after TIPS.Conclusions:Post-TIPS transitional care interventions increased patients’access to scientifically informed nursing, significantly improved patients’compliance behavior and health, and decreased the incidence of postoperative adverse events.