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BACKGROUND Acute lung injury (ALI) is a common and life-threatening complication of severe acute pancreatitis (SAP). There are currently limited effective treatment options for SAP and associated ALI. Calycosin (Cal), a bioactive constituent extracted from the medicinal herb Radix Astragali exhibits potent anti-inflammatory properties, but its effect on SAP and associated ALI has yet to be determined. AIM To identify the roles of Cal in SAP-ALI and the underlying mechanism. METHODS SAP was induced via two intraperitoneal injections of L-arg (4 g/kg) and Cal (25 or 50 mg/kg) were injected 1 h prior to the first L-arg challenge. Mice were sacrificed 72 h after the induction of SAP and associated ALI was examined histologically and biochemically. An in vitro model of lipopolysaccharide (LPS)-induced ALI was established using A549 cells. Immunofluorescence analysis and western blot were evaluated in cells. Molecular docking analyses were conducted to examine the interaction of Cal with HMGB1. RESULTS Cal treatment substantially reduced the serum amylase levels and alleviated histopathological injury associated with SAP and ALI. Neutrophil infiltration and lung tissue levels of neutrophil mediator myeloperoxidase were reduced in line with protective effects of Cal against ALI in SAP. Cal treatment also attenuated the serum levels and mRNA expression of pro-inflammatory cytokines tumor necrosis factor-α, interleukin-6, IL-1β, HMGB1 and chemokine (CXC motif) ligand 1 in lung tissue. Immunofluorescence and western blot analyses showed that Cal treatment markedly suppressed the expression of HMGB1 and phosphorylated nuclear factor-kappa B (NF-κB) p65 in lung tissues and an in vitro model of LPS-induced ALI in A549 cells suggesting a role for HGMB1 in the pathogenesis of ALI. Furthermore, molecular docking analysis provided evidence for the direct interaction of Cal with HGMB1. CONCLUSION Cal protects mice against L-arg-induced SAP and associated ALI by attenuating local and systemic neutrophil infiltration and inflammatory response via inhibition of HGMB1 and the NF-κB signaling pathway.

Background Acute pancreatitis (AP) is an inflammatory disease in which the regulatory pathway is complex and not well understood. Soluble suppression of tumorigenicity 2 (sST2) protein receptor functions as a decoy receptor for interleukin (IL)-33 to prevent IL-33/suppression of tumorigenicity 2L (ST2L)-pathway-mediated T helper (Th)2 immune responses. Aim To investigate the role of sST2 in AP. Methods We assessed the association between sST2 and severity of AP in 123 patients enrolled in this study. The serum levels of sST2, C-reactive protein (CRP) and Th1- and Th2-related cytokines, including interferon (IFN)-γ, tumor necrosis factor (TNF)-α, IL-2, IL-4, IL-5 and IL-13, were measured by highly sensitive ELISA, and the severity of AP in patients was evaluated by the 2012 Atlanta Classification Criteria. Results Serum sST2 levels were significantly increased in AP patients, and further, these levels were significantly elevated in severe AP (SAP) patients compared to moderately severe AP (MSAP) and mild AP (MAP) patients. Logistic regression showed sST2 was a predictor of SAP [odds ratio (OR): 1.003 (1.001-1.006), P = 0.000]. sST2 cutoff point was 1190 pg/mL, and sST2 above this cutoff was associated with SAP. sST2 was also a predictor of any organ failure and mortality during AP [OR: 1.006 (1.003-1.009), P = 0.000, OR: 1.002 (1.001-1.004), P = 0.012, respectively]. Additionally, the Th1-related cytokines IFN-γ and TNF-α in the SAP group were higher and the Th2-related cytokine IL-4 in the SAP group was significantly lower than those in MSAP and MAP groups. Conclusion sST2 may be used as a novel inflammatory marker in predicting AP severity and may regulate the function and differentiation of IL-33/ST2-mediated Th1 and Th2 Lymphocytes in AP homeostasis.

Injury or disease in the somatosensory nervous system may cause broad molecular changes and lead to neuropathic pain. Excitatory synaptic transmission in somatosensory pathways conveys the somatosensory information from the peripheral to the central nervous system. Long-term effects of excitatory synaptic transmission on the pain pathway contribute to neuropathic pain hypersensitivity. Synaptic strength is dynamically regulated and undergoes bidirectional changes, manifested by two primary forms of synaptic plasticity, long-term potentiation and long-term depression (LTD), which are mediated by insertion and endocytosis of amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors (AMPARs), respectively. Molecular mechanisms of LTP have been extensively studied; on the other hand, the role of AMPAR endocytosis in the pain-related synaptic enhancement is less well known. Recent research in the anterior cingulate cortex reveals that loss of LTD contributes to the maintenance of neuropathic pain, which provides the novel perspective of the mechanism of LTD also being critical for maintaining neuropathic pain. More importantly, exploring the molecular mechanism of LTD may help with the development of novel analgesic strategies to manage neuropathic pain.

Steroid receptor coactivator 1 (SRC-1) is one of the coactivators recruited by the nuclear receptors (NRs) when NRs are activated by steroid hormones, such as glucocorticoid. SRC-1 is abundant in hippocampus and hypothalamus and is also related to some major risk factors for depression, implicated by its reduced expression after stress and its effect on hypothalamus-pituitary-adrenal gland axis function. However, whether SRC-1 is involved in the formation of depression remains unclear. In this study, we firstly established chronic unpredictable stress (CUS) to induce depressive-like behaviors in mice and found that SRC-1 expression was reduced by CUS. A large number of studies have shown that neuroinflammation is associated with stress-induced depression and lipopolysaccharide (LPS) injection can lead to neuroinflammation and depressive-like behaviors in mice. Our result indicated that LPS treatment also decreased SRC-1 expression in mouse brain, implying the involvement of SRC-1 in the process of inflammation and depression. Next, we showed that the chronic unpredictable mild stress (CUMS) failed to elicit the depressive-like behaviors and dramatically promoted the expression of SRC-1 in brain of wild type mice. What's more, the SRC-1 knockout mice were more susceptible to CUMS to develop depressive-like behaviors and presented the changed expression of glucocorticoid receptor. However, SRC-1 deficiency did not affect the microglia activation induced by CUMS. Altogether, these results indicate a correlation between SRC-1 level and depressive-like behaviors, suggesting that SRC-1 might be involved in the development of depression induced by stress.

Background Galactose-deficient IgA1 plays a key role in the pathogenesis of IgA nephropathy, the most common primary GN worldwide. Although serum levels of galactose-deficient IgA1 have a strong genetic component, the genetic link between this molecule and IgA nephropathy has not yet been clearly established. Methods To identify novel loci associated with galactose-deficient IgA1, we performed a quantitative genome-wide association study for serum galactose-deficient IgA1 levels, on the basis of two different genome-wide association study panels conducted in 1127 patients with IgA nephropathy. To test genetic associations with susceptibility to IgA nephropathy, we also enrolled 2352 patients with biopsy-diagnosed IgA nephropathy and 2632 healthy controls. Peripheral blood samples from 59 patients and 27 healthy controls were also collected for gene expression analysis. Results We discovered two loci, in C1GALT1 and GALNT12, that achieved genome-wide significance, explaining about 3.7% and 3.4% of variance in serum galactose-deficient IgA1 levels, respectively. We confirmed the previously reported association of C1GALT1 with serum galactose-deficient IgA1 levels, but with a different lead single-nucleotide polymorphism (rs10238682; β=0.26, P=1.20×10-9); the locus we identified at GALNT12 (rs7856182; β=0.73, P=2.38×10-9) was novel. Of more interest, we found that GALNT12 exhibits genetic interactions with C1GALT1 in both galactose-deficient IgA1 levels (P=1.40×10-2) and disease risk (P=6.55×10-3). GALNT12 mRNA expression in patients with IgA nephropathy was significantly lower compared with healthy controls. Conclusions Our data identify GALNT12 as a novel gene associated with galactose-deficient IgA1 and suggest novel genetic interactions. These findings support a key role of genetically conferred dysregulation of galactose-deficient IgA1 in the development of IgA nephropathy.

Background and objectives IgA nephropathy is the most common form of primary GN worldwide. The evidence of geographic and ethnic differences, as well as familial aggregation of the disease, supports a strong genetic contribution to IgA nephropathy. Evidence for genetic factors in IgA nephropathy comes also from genome-wide association patient-control studies. However, few studies have systematically evaluated the contribution of coding variation in IgA nephropathy. Design, setting, participants, & measurements We performed a two-stage exome chip–based association study in 13,242 samples, including 3363 patients with IgA nephropathy and 9879 healthy controls of Han Chinese ancestry. Common variant functional annotation, gene-based low-frequency variants analysis, differential mRNA expression, and gene network integration were also explored. Results We identified three non-HLA gene regions (FBXL21, CCR6, and STAT3) and one HLA gene region (GABBR1) with suggestive significance (Pmeta Conclusions Five novel gene regions with suggestive significance for IgA nephropathy were identified and shed new light for further mechanism investigation.

The suboptimal carrier dynamics at the perovskite/electron transport layer has largely limited the further performance enhancement of the state-of-the-art inverted p-i-n structured perovskite solar cells. Herein, we discovered that a simple surface modification of the perovskite film by a trivalent metal halide salt, InBr3, could convert the doping levels of the top surface to be more n-type, which spontaneously formed an intriguing n/n+ homojunction between the bulk (weak n type (n) component) and the surface (more n-type (n+) component) in a monolithic perovskite film. This brought about synergistic advantages of the enlarged built-in electric field for facilitated charge separation, as well as optimized electronic energy level alignment and minimized electron injection barrier at the perovskite/C60 interface, leading to both accelerated charge extraction and suppressed interfacial charge recombination. Blade-coated inverted PSCs with n/n+ homojunctions achieved a high power conversion efficiency (PCE) of up to 22.2%, narrowing the efficiency gap with their conventional n-i-p counterparts. The InBr3 surface treatment also improved the operational stability to >1000 hours under light with 93% initial efficiency retained.

MicroRNAs (miRNAs) are short (19–24 nucleotides in length) noncoding RNAs that have a profound effect on gene expression. By completely or almost perfectly base-pairing with their individual target mRNAs they cause mRNA cleavage or repression of translation. As important regulators, miRNAs plays an important role in the regulation of fruit quality. Extensive studies have been reported in fruits, however current studies are mostly focused on the identification of miRNAs and the prediction and validation of target genes. This review summarizes research progress on the role of miRNAs in regulating fruit ripening and senescence and quality characteristics, such as coloration, flavor metabolism, and texture for providing information for future research.

Background The discovery and use of antibiotics have produced tremendous benefits for human society, however, with the large-scale use of antibiotics in medicine, animal husbandry and other fields, more and more antibiotic-resistant bacteria have emerged. Since diseases caused by such antibiotic-resistant bacteria could require more drastic measures to treat, the emergence of such resistant bacteria in food has attracted much concern. Scope and approach In this review, we summarized the interplay between antibiotic resistance and food-associated stress tolerance, and the hypothesized molecular mechanisms for the cross protection in bacteria. Key findings and conclusions In this review, we found that some common food-associated stresses, such as cold, acid, osmosis and sanitizers could provide cross protection for bacteria against antibiotics. In turn, antibiotic resistance could also render bacteria more tolerant to food-associated stresses. Meanwhile, novel nonthermal technologies may more likely result in little or no difference in bacterial antibiotic resistance, and this can be an advantage over traditional sterilization methods. Several molecular mechanisms for the cross protection between antibiotics and food-associated stresses have been discussed in this review. General stress response (e.g., sigma factors and two-component system), SOS response, mutations, and other mechanisms have been proposed as strategies for bacteria acquisition of cross protection.

The purpose of this study was to investigate the diagnostic performance of the automated breast ultrasound system (ABUS) compared with hand-held ultrasonography (HHUS) and mammography (MG) for breast cancer in women aged 40 y or older. A total of 594 breasts in 385 patients were enrolled in the study. HHUS, ABUS and MG exams were performed for these patients. Follow-up and pathologic findings were used as the reference standard. Based on the reference standard, 519 units were benign or normal and 75 were malignant. The sensitivity, specificity, accuracy and Youden index were 97.33%, 89.79%, 90.74% and 0.87 for HHUS; 90.67%, 92.49%, 92.26% and 0.83 for ABUS; 84.00%, 92.87%, 91.75% and 0.77 for MG, respectively. The specificity of ABUS was significantly superior to that of HHUS (p = 0.024). The area under the receiver operating characteristic curve was 0.936 for HHUS, which was the highest, followed by 0.916 for ABUS and 0.884 for MG. However, the difference was not statistically significant (p > 0.05). In conclusion, the diagnostic performance of ABUS for breast cancer was equivalent to HHUS and MG and potentially can be used as an alternative method for breast cancer diagnosis.

Background The N-terminal fragment of proB-type natriuretic peptide (NT-proBNP) is an established predictive marker for sepsis-related mortality in adult. This retrospective study aimed to determine age-stratified cut-off values for serum levels of NT-proBNP and mortality from sepsis in children under 18 years. Material/Methods Patients were stratified by age as follows

Glaucoma is a disease involving impaired visual function accompanied by degeneration and necrosis of the optic nerve. Epigallocatechin-3-gallate (EGCG) exerts a neuroprotective effect against the degeneration of retinal ganglion cells. However, whether EGCG can relieve glaucoma and the possible mechanisms remain unclear. In order to determine the function of EGCG in glaucoma, an acute glaucoma rat model was established. Optic neuropathology was examined by haematoxylin-eosin staining and immunofluorescence staining for class III-β tubulin. The levels of inflammation-associated cytokines, such as interleukin (IL)-4, IL-6, TNF-α, IL-1β, IL-13 and IFN-γ were measured by flow cytometry. T cell proliferation was assessed by the carboxyfluorescein diacetate succinimidyl ester method. Finally, the functional role of EGCG in glaucoma was explored. The levels of the inflammation-associated proteins p-IκBα and p-p65 were measured by western blot analysis. The results showed that optic nerve injury occurred, and elevated levels of the inflammatory cytokines IL-4, IL-6, TNF-α, IL-1β, IL-13 and IFN-γ were observed in the rat model of acute glaucoma. In addition, an increased T lymphocyte proliferation rate and imbalance of Th1/Th2 cytokines were present in the models. Importantly, treatment with EGCG significantly alleviated optic nerve injury. At the molecular level, EGCG decreased the levels of inflammation-associated cytokines, decreased the proliferation rate of T lymphocyte cells, and repaired the imbalance of Th1/Th2 cytokines. Moreover, EGCG inhibited the increase in the phosphorylation of IκBα and p65 caused by modelling and thus suppressed the activation of the nuclear factor (NF)-κB signalling pathway. The findings of the present study indicate that EGCG could attenuate the symptoms of glaucoma and inhibit inflammatory responses by suppressing the NF-κB signalling pathway in a rat glaucoma model.

Object: The fluid management strategy in ARDS is not very clear. A secondary analysis of RCT data was conducted to identify patients with ARDS benefitting from a conservative strategy of fluid management.Methods: The data of this study were downloaded from the ARDS network series of randomized controlled trials (Conservative Strategy vs. Liberal Strategy in 2006). Based on the clinical feature of patients, within the first 24 h after admission, clustering was performed using the k-means clustering algorithm to identify the phenotypes of ARDS. Survival was analyzed using the Kaplan-Meier survival analysis to assess the effect of the two fluid management strategies on the 90-day cumulative mortality. Categorical/dichotomic variables were analyzed by the chi-square test. Continuous variables were expressed as the mean and standard deviation and evaluated through a one-way ANOVA. A P-value < 0.05 was defined as the statistically significant cut-off value.Results: A total of 1,000 ARDS patients were enrolled in this unsupervised clustering research study, of which 503 patients were treated with a conservative fluid-management strategy, and 497 patients were treated with a liberal fluid-management strategy. The first 7-day cumulative fluid balance in patients with the conservative strategy and liberal strategy were −136 ± 491 ml and 6,992 ± 502 ml, respectively (P < 0.001). Four phenotypes were found, and the conservative fluid-management strategy significantly improved the 90-day cumulative mortality compared with the liberal fluid-management strategy (HR = 0.532, P = 0.024) in patients classified as “hyperinflammatory anasarca” phenotype (phenotype II). The characteristics of this phenotype exhibited a higher WBC count (20487.51 ± 7223.86/mm3) with a higher incidence of anasarca (8.3%) and incidence of shock (26.6%) at baseline. The furthermore analysis found that the conservative fluid management strategy was superior to the liberal fluid management strategy in avoiding superinfection (10.10 vs. 14.40%, P = 0.037) and returned to assisted breathing (4.60 vs. 16.20%, P = 0.030) in patients classified as “hyperinflammatory anasarca” phenotype. In addition, patients with other phenotypes given the different fluid management strategies did not show significant differences in clinical outcomes.Conclusion: Patients exhibiting a “hyperinflammatory anasarca” phenotype could benefit from a conservative fluid management strategy.

Severe acute pancreatitis (SAP) is often associated with pulmonary inflammation leading to acute lung injury. Daphnetin, a natural coumarin derivative, has been reported to exert anti-inflammatory effects. Here, we explored the effect and possible mechanism of daphnetin in a mouse model of SAP-associated lung injury induced by an intraperitoneal injection of l-arginine. The severity of pancreatic and lung injury is determined by histology and its score. Immunostaining of inflammatory and apoptotic cells was used to demonstrate lung tissue inflammation and apoptosis; ELISA analysis of serum and tissue cytokine levels; and western blotting and immunohistochemical staining for the activated Janus kinase 2 (JAK2)–signal transducer and activator of transcription protein 3 (STAT3) signalling pathway in lung tissues. Daphnetin pretreatment significantly reduced SAP-induced pancreatic and lung tissue damage, reduced interleukin-6 and tumour necrosis factor-α concentrations in both serum and lung tissues, reduced serum amylase and myeloperoxidase activities, and reduced macrophage (CD11b) and neutrophil (Ly6G) infiltration and cell apoptosis in the lung tissue. Moreover, SAP-induced phosphorylation of JAK2 and STAT3 in the lung tissue was also significantly diminished by the daphnetin pretreatment. These results indicated that daphnetin reduces SAP-associated lung tissue damage, likely by inhibiting the activation of JAK2–STAT3 signalling.

Exposure to chronic stress can influence nociception and further induce hyperalgesia. Whether stress modulation of pain in female animals occurs in an estrous cycle-specific manner is still unclear. We profiled the changes in nociception (thermal, mechanical, formalin-evoked acute and inflammatory pain) of female Sprague-Dawley rats after treatment with chronic unpredictable mild stress (CUMS) and investigated whether these changes occur in an estrous cycle-dependent manner. The results showed that CUMS female rats exhibited a lower mechanical withdrawal threshold in proestrus and estrus, a longer formalin-evoked licking time in metestrus and diestrus, but no changes in the latency time on the tail-flick test. The present study findings suggest that chronic stress induces mechanical and formalin-evoked acute hyperalgesia of female rats in an estrous cycle-dependent manner.SUMMARYOur studies showed that chronic stress increased nociceptive sensitivity of female rats. Furthermore females had different stress-induced pain responses in different estrous phases: mechanical hyperalgesia in proestrus and estrus, formalin-evoked acute hyperalgesia in metestrus and diestrus.

Background: Cytidine deaminase (CDA) polymorphisms may affect the response to gemcitabine/cisplatin chemotherapy in patients with non-small cell lung cancer (NSCLC). This study is designed to investigate the associations of CDA-79A>C and 208G>A polymorphisms and gemcitabine/cisplatin chemotherapy effectiveness in Xinjiang Uyghur and Han patients. Methods: This prospective cohort study enrolled consecutive patients with stage IIIb/IV NSCLC administered gemcitabine/cisplatin chemotherapy at the First Affiliated Hospital, Medical College of Shihezi University and the First People’s Hospital, Kashgar Region. CDA-A79C and CDA-G208A polymorphisms were detected by direct sequencing. Progression-free survival was analyzed by the Kaplan-Meier method. Associations of A79C and G208A polymorphisms with treatment effectiveness and progression-free survival were analyzed using logistic regression and multivariate Cox regression analyses. Subgroup analyses based on ethnicity were performed. Results: The study enrolled 120 patients. A79C and G208A polymorphisms followed the Hardy-Weinberg equilibrium. The frequencies of the AA, AC, and CC genotypes and the A and C alleles of A79C were 52.2%, 29.9%, 17.9%, 67.2%, and 32.8%, respectively, in Han patients and 75.4%, 18.9%, 5.7%, 84.9%, and 5.1%, respectively, in Uyghur patients. Uyghur patients had lower frequencies of A79C-AC/CC genotypes, A79C-C allele, G208A-GA genotype, and G208A-A allele ( PConclusion: For Uyghur and Han ethnic groups, A79C and G208A polymorphisms can be used as a promising biomarker for the chemotherapy efficacy and prognosis of NSCLC.

Objective We reported an outbreak of human parainfluenza virus type 1 (HPIV1) in a kindergarten and explored the genetic characteristics of HPIV1 hemagglutinin-neuraminidase (HN) and fusion (F) genes to provide more evidence about HPIV1 outbreaks. Methods Suspected cases were the children with an influenza-like illness during June 20 to 26, 2018. Nasopharyngeal swabs were collected and screened to determine the presence of respiratory pathogens by real-time fluorescent quantitative polymerase chain reaction. The HN and F gene sequences of HPIV-positive samples were further amplified and sequenced to confirm the HPIV genotype and identify genetic characteristics. A phylogenetic tree, based on the HN and F genes, was reconstructed by maximum likelihood method. Results Fourteen children in the outbreak were diagnosed as upper respiratory tract infection. The most common symptom was cough (10/14), followed by rhinorrhea (5/14), sore throat (4/14), headache (1/14), and abdominal pain (1/14). Eight patients were positive for HPIV1 and negative for other pathogens. Phylogenetic tree demonstrated that the eight strains from the year 2018 in our study located in the clade 2.3. Two specific substitutions (N333S and I509M) in the amino acids of the F protein and two substitutions (V19A and L436I) in the HN protein were different from other strains in the clade 2. Conclusion HPIV1 was attributed to the outbreak, which may be related to the genetic variations of HPIV1.

Our aim was to investigate the diagnostic potential of an automated breast ultrasound (ABUS) system in differentiating benign and malignant breast masses compared with handheld ultrasound (HHUS).Women were randomly and proportionally selected from outpatients and underwent both HHUS and ABUS examinations. Masses with final American College of Radiology Breast Imaging Reporting and Data System categories 2 and 3 were considered benign. Masses with final Breast Imaging Reporting and Data System categories 4 and 5 were considered malignant. The diagnosis was confirmed by pathologic results or at least a 1-year follow-up. Automated breast US and HHUS were compared on the basis of their sensitivity, specificity, positive predictive value, negative predictive value, and accuracy. Diagnostic consistency and areas under the receiver operating characteristic curves were analyzed. The maximum diameters of masses were compared among HHUS, ABUS, and pathologic results.A total of 599 masses in 398 women were confirmed by pathologic results or at least a 1-year follow-up; 103 of 599 masses were malignant, and 496 were benign. There were no significant differences between ABUS and HHUS in terms of diagnostic accuracy (80.1% versus 80.6%), specificity (77.62% versus 80.24%), positive predictive value (46.12% versus 46.46%), and negative predictive value (97.96% versus 95.67%). There were significant differences in sensitivity (92.23% versus 82.52%; P .01) and areas under the curve (0.85 versus 0.81; P .05) between ABUS and HHUS. The correlation of the maximum diameter was slightly higher between ABUS and pathologic results (r = 0.885) than between HHUS and pathologic results (r = 0.855), but the difference was not significant (P .05).Automated breast US is better than HHUS in differentiating benign and malignant breast masses, especially with respect to specificity.

BACKGROUND Cardiac remote ischemic conditioning (RIC) is a noninvasive cardioprotective method in ischemia-reperfusion injury and acute myocardial infarction (AMI). The aims of this study were to investigate the effects of RIC in a rat model of AMI. MATERIAL AND METHODS Adult male Sprague-Dawley rats included the AMI group that underwent ligation of the left anterior descending (LAD) coronary artery (n=24), the RIC group that consisted the AMI rat model treated with RIC once daily in the left hind limb until days 1, 7 and 14 (n=24), and the sham group (n=24). Myocardial infarct size was measured by routine histology with triphenyltetrazolium chloride (TTC) and Masson's trichrome histochemical staining for myocardial necrosis and fibrosis, respectively. Serum levels of Bcl-2, Bax, caspase-3, and inducible nitric oxide synthase (iNOS) were measured by enzyme-linked immunosorbent assay (ELISA). The apoptosis index was detected using the TUNEL assay. Spectrophotometry of the myocardium was used to identify mitochondrial complexes and myocardial ATP. RESULTS The RIC group showed improved cardiac hemodynamics, reduced the size of the myocardial infarction, upregulated expression of Bcl-2, and down-regulation of the levels of Bax, caspase-3, and iNOS, and reduced cardiac myocyte apoptosis and inhibited the opening of the mitochondrial permeability transition pore (MPTP). CONCLUSIONS In a rat model of AMI, RIC improved the hemodynamic index, reduce the levels of apoptosis and myocardial injury, and improved mitochondrial function.

BACKGROUND A floating shoulder may be associated with catastrophic neurovascular injury and requires a multidisciplinary approach for its management. To maximize the likelihood of good patient outcomes, this unique injury pattern should be recognized in patients as early as possible. This can be difficult to achieve, however, as there are currently few reports of floating shoulder in the literature, meaning that associated neurovascular injuries may be overlooked. CASE SUMMARY We present here a rare case of floating shoulder with axillary artery injury in a 34-year-old woman. The patient complained of pain and numbness of her left upper limb after losing control of her motorcycle on a highway and falling from the vehicle 2 h ago. No blood pressure reading could be obtained from her left upper limb and no blood oxygen readings could be obtained from any of her left fingers. Computed tomography angiography and duplex ultrasonography revealed interruption of blood flow through the axillary artery, with distal flow being maintained through collateral arteries. The clinical diagnosis including fracture of the left proximal humerus, the left clavicle, and the left scapula, left axillary artery rupture, and left brachial plexus injury. We successfully performed open reduction and internal fixation of the fracture and vascular repair. The patient showed satisfactory recovery that was observed during 4-mo follow-up. CONCLUSION Emergency surgery can be an effective therapeutic option for the closed floating shoulder with catastrophic axillary artery injury.

Continuous chromatography is a promising technology for downstream processing of biopharmaceuticals. The operation of continuous processes is significantly different to batch-mode chromatography and needs comprehensive evaluation. In this work, the performances of four Protein A affinity resins were studied systematically for twin-column continuous capture processes. A model-based approach was used to evaluate the process performance (productivity and capacity utilization) under varying operation conditions, and the objective was to reveal the crucial resin properties for continuous capture. The trade-off between productivity and capacity utilization was found, and it is necessary to select appropriate resins for different feedstock and operation conditions. The capacity utilization heavily depends on mass transfer, and steep breakthrough curves are favorable for high capacity utilization. The productivity is determined by both equilibrium binding capacity and mass transfer, and the balance of feed amount and feed time is critical. Moreover, the influence of binding capacity and mass transfer on process productivity and parameter sensitivity with two important resin properties (equilibrium binding capacity qmax and effective pore diffusion coefficient De) were assessed by the model, and suitable resin parameter ranges for twin-column continuous capture were determined. The model-based approach is an effective and useful tool to evaluate the complex performance of different resins and guide the design of next-generation resins for continuous processes.

Traditional methods to determine whether the work of electric vehicle charging equipment is abnormal is limited to in-lab confirmation and on-site the abnormal over- limit attribute of single threshold, which have such problems as long time, low quality, easy development of defects, and easy to make mistakes. Breakthrough the limitation of laboratory and field conditions, in this paper, an effective abnormal prediction method for electric vehicle charging equipment is established by comparing various machine learning technologies and combining with the working mechanism of EV charging equipment components based on multi-scale massive data accumulated in time and space during the operation of EV charging equipment. The results show that the XGboost algorithm has a high accuracy in the abnormal prediction of EV charging equipment components and their characteristics, and the accuracy of anomaly prediction reaches 90.34%, which has an absolute advantage.

Background Ramsay Hunt syndrome (RHS) is caused by a reactivation of varicella-zoster virus (VZV) infection, and it is characterized by the symptoms of facial paralysis, otalgia, auricular rash, and/or an oral lesion. Elderly patients or immunocompromised patients, deep pain at the initial visit and no prompt treatment are significant predictors of postherpetic neuralgia (PHN). When PHN occurs, especially involved cranial polyneuropathy, multiple modalities should be administered for patients with the intractable PHN. The use of thermography in the follow-up of PHN secondary to RHS with multicranial nerve involvement has not yet been described yet in the literature. Case presentation The patient was a 78-year-old man with the chief complaint of a 3-month history of PHN secondary to RHS with polycranial nerve (V, VII, VIII, and IX) involvement. Multimodality therapy with oral gabapentin, pulsed radiofrequency (PRF) application to the Gasserian ganglion for pain in the trigeminal nerve region, linear-polarized near-infrared light irradiation for pain in the facial nerve region, and 2% lidocaine spray for pain in the glossopharyngeal nerve region was used to the treat patient, and follow-up evaluations included thermography. This comprehensive treatment obviously improved the quality of life, resulting in considerable pain relief, as indicated by a decrease in the numerical rating scale (NRS) score from 9 to 3 and a decrease in thermal imaging temperature from higher to average temperature on the ipsilateral side compared with the contralateral side. Lidocaine spray on the tonsillar branches of the glossopharyngeal nerve resulted in an improvement in odynophagia, and the NRS score decreased from 9 to 0 for glossopharyngeal neuralgia after three applications. Conclusion Although the use of thermography in the follow-up of RHS with multiple cranial nerve (V, VII, VIII, and IX) involvement is very rare, in this patient, thermal imaging showed the efficacy of combination therapy (oral gabapentin, 2% lidocaine sprayed, PRF application and linear-polarized near-infrared light irradiation) and that is a good option for treatment.

Background Acute kidney injury (AKI) is an important complication of severe acute pancreatitis (SAP) with a poor prognosis. The methyl ester of (S,R)-3-(4-hydroxyphenyl)-4,5-dihydro-5-isoxazole acetic acid (ISO-1), an inhibitor of macrophage migration inhibitory factor (MIF), has protective effects against many diseases. Our previous study confirmed MIF inhibition alleviated SAP. Here, we explored the effects of ISO-1 in an experimental mouse model of SAP-associated AKI induced by l -arginine. Methods Mice were randomly divided into four treatment groups (n = 6 each): control (CON), SAP, SAP + ISO-1, and ISO-1. Histopathologic examination was used to observe damage in pancreatic and renal tissues. Biochemical and enzyme-linked immunosorbent assays (ELISA) kits were used to measure the serologic indicators amylase, lipase, creatinine, uric acid, interleukin (IL)-6, and tumor necrosis factor (TNF)-α. Immunohistochemistry was used to detect protein expression of NLRP3, ASC and caspase-1, and the infiltration of myeloperoxidase (MPO)-positive neutrophils in kidney tissue. Western blotting was used to detect NLRP3, ASC and caspase-1 and IL-1β protein expression, and real-time PCR was used to measure MIF, IL-6, TNF-α, IL-1β and IL-18 mRNA levels in kidney tissue. Results ISO-1 treatment alleviated pathological damage in pancreatic and renal tissues, and reduced the serum levels of amylase, lipase, creatinine, uric acid, IL-6 and TNF-α. ISO-1 also reduced protein expression of NLRP3, ASC, caspase-1 and IL-1β, mRNA expression of MIF, IL-6, TNF-α, IL-1β and IL-18, and the infiltration of MPO-positive neutrophils in kidney tissue. Conclusion ISO-1 has a protective effect against experimental SAP-associated AKI. And the mechanism may be associated with ISO-1 inhibiting NLRP3 inflammasome signaling pathway.

Background Liver injury is one of the most common complications during sepsis. Macrophage migration inhibitory factor (MIF) is an important proinflammatory cytokine. This study explored the role of MIF in the lipopolysaccharide (LPS)-induced liver injury through genetically manipulated mouse strains. Methods The model of LPS-induced liver injury was established in wild-type and Mif-knockout C57/BL6 mice. Serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), and total bilirubin (TBil) were detected, and the expressions of MIF, tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) were measured. Liver histopathology was conducted to assess liver injury. Moreover, the inhibitions of MIF with (S,R)-3-(4-hydroxyphenyl)-4,5-dihydro-5-isoxazole acetic acid methyl ester (ISO-1) and 4-iodo-6-phenylpyrimidine (4-IPP) were used to evaluate their therapeutic potential of liver injury. Results Compared with wild-type mice, the liver function indices and inflammation factors presented no significant difference in the Mif−/− mice. After 72 h of the LPS-induced liver injury, serum levels of ALT, AST, and TBil as well as TNF-α and IL-1β were significantly increased, but the knockout of Mif attenuated liver injury and inflammatory response. In liver tissue, mRNA levels of TNF-α, IL-1β and NF-κB p65 were remarkably elevated in LPS-induced liver injury, while the knockout of Mif reduced these levels. Moreover, in LPS-induced liver injury, the inhibitions of MIF with ISO-1 and 4-IPP alleviated liver injury and slightly attenuated inflammatory response. Importantly, compared to mice with LPS-induced liver injury, Mif knockout or MIF inhibitions significantly prolonged the survival of the mice. Conclusions In LPS-induced liver injury, the knockout of Mif or MIF inhibitions alleviated liver injury and slightly attenuated inflammatory response, thereby prolonged the survival of the mice. Targeting MIF may be an important strategy to protect the liver from injury during sepsis.

Insulin resistance promotes the occurrence of liver cancer and decreases its chemosensitivity. Rosiglitazone (ROSI), a thiazolidinedione insulin sensitiser, could be used for diabetes with insulin resistance and has been reported to show anticancer effects on human malignant cells. In this paper, we investigated the combination of ROSI and chemotherapeutics on the growth and metastasis of insulin-resistant hepatoma. In vitro assay, ROSI significantly enhanced the inhibitory effects of adriamycin (ADR) on the proliferation, autophagy and migration of insulin-resistant hepatoma HepG2/IR cells via downregulation of EGFR/ERK and AKT/mTOR signalling pathway. In addition, ROSI promoted the apoptosis of HepG2/IR cells induced by ADR. In vivo assay, high fat and glucose diet and streptozotocin (STZ) induced insulin resistance in mice by increasing the body weight, fasting blood glucose (FBG) level, oral glucose tolerance, fasting insulin level and insulin resistance index. Both the growth of mouse liver cancer hepatoma H22 cells and serum FBG level in insulin resistant mice were significantly inhibited by combination of ROSI and ADR. Thus, ROSI and ADR in combination showed a stronger anti-tumour effect in insulin resistant hepatoma cells accompanying with glucose reduction and might represent an effective therapeutic strategy for liver cancer accompanied with insulin resistant diabetes.

BackgroundHerpangina is a highly infectious disease, which is usually prevalent in preschool children.MethodsThis study analyzed the clinical and pathogenic characteristics of herpangina children to demonstrate the epidemiology of herpangina. Clinical manifestations, laboratory indicators and pharyngeal swabs were collected from children with herpangina who were monitored by Tongzhou Center for Disease Control and Prevention in Beijing, 2008. Utilizing pharyngeal swabs, virus extraction and amplification were performed for nucleotide identification and sequencing. The phylogenetic analysis was conducted based on all sequences amplified in this study and strains retrieved from GenBank.ResultsAmong 190 children with herpangina, 69.0% (131/190) were positive for enterovirus. Eight genotypes were identified, mainly including CV-A6 (39/131), CV-A4 (25/131), CV-A10 (24/131). The phylogenetic analysis showed one CV-A6 strain of Tongzhou was imported from Japan. CV-A10 strains were clustered into five groups (A-E). The dominant cluster of CV-A10 was Group E6 between 2009 and 2013, and converted to Group E5 after 2013. CV-A6 was the predominant pathogen causing herpangina in Tongzhou in 2018, followed by CV-A4 and CV-A10.ConclusionsThe circulation of coxsackievirus had spatiotemporal cluster. In controlling the transmission of herpangina, the surveillance and reporting system should be enhanced.

PurposeBiomechanical comparison of wedge and biconcave deformity of different height restoration after augmentation of osteoporotic vertebral compression fractures was analyzed by three-dimensional finite element analysis (FEA).MethodsThree-dimensional finite element model (FEM) of T11-L2 segment was constructed from CT scan of elderly osteoporosis patient. The von Mises stresses of vertebrae, intervertebral disc, facet joints, displacement, and range of motion (ROM) of wedge and biconcave deformity were compared at four different heights (Genant 0–3 grade) after T12 vertebral augmentation.ResultsIn wedge deformity, the stress of T12 decreased as the vertebral height in neutral position, flexion, extension, and left axial rotation, whereas increased sharply in bending at Genant 0; L1 and L2 decreased in all positions excluding flexion of L2, and T11 increased in neutral position, flexion, extension, and right axial rotation at Genant 0. No significant changes in biconcave deformity. The stress of T11-T12, T12-L1, and L1-L2 intervertebral disc gradually increased or decreased under other positions in wedge fracture, whereas L1-L2 no significant change in biconcave fracture. The utmost overall facet joint stress is at Genant 3, whereas there is no significant change under the same position in biconcave fracture. The displacement and ROM of the wedge fracture had ups and downs, while a decline in all positions excluding extension in biconcave fracture.ConclusionsThe vertebral restoration height after augmentation to Genant 0 affects the von Mises stress, displacement, and ROM in wedge deformity, which may increase the risk of fracture, whereas restored or not in biconcave deformity.

Qian-Kun Yang,1,* Yan-Na Su,2,* Wei Wang,1,* Nan Wang,3 Zhong-Xiang Yao,4,* Xiao-Jing Zhang1 1Department of Bone and Soft Tissue Surgery, Cancer Hospital of China Medical University, Liaoning Cancer Hospital and Institute, Shenyang, Liaoning 110042, People’s Republic of China; 2Clinical Laboratory, The First Affiliated Hospital of China Medical University, Shenyang, Liaoning 110042, People’s Republic of China; 3Department of Radiotherapy, Cancer Hospital of China Medical University, Liaoning Cancer Hospital and Institute, Shenyang, Liaoning 110042, People’s Republic of China; 4Department of Physiology, Army Medical University, Chongqing 400038, People’s Republic of China*These authors contributed equally to this workCorrespondence: Xiao-Jing ZhangDepartment of Bone and Soft Tissue Surgery, Cancer Hospital of China Medical University, Liaoning Cancer Hospital and Institute, Shenyang, Liaoning 110042, People’s Republic of ChinaEmail zhangxiaojing@cancerhosp-ln-cmu.comBackground: Nutritional and immune status is paramount for the overall survival (OS) of patients with advanced osteosarcoma. Comprehensive prognostic predictors based on the two indices are scarce. This study aimed to construct and validate individualized web dynamic nomograms based on CONUT score or/and peripheral blood CD4+/CD8+ ratio for OS in patients with advanced osteosarcoma.Materials and Methods: The clinical data of 376 advanced osteosarcoma patients from January 2000 to December 2019 were retrospectively collected. Data from the 301 patients (diagnosed in the first 15 years) were used as the development set and data from the remaining 75 patients were assigned as the validation set. Multivariate Cox regression analyses were conducted and three prediction models were constructed, namely, CD4+/CD8+ ratio univariate model (model 1), CONUT score univariate model (model 2), and CD4+/CD8+ ratio plus CONUT score (model 3). These models were visualized by conventional nomograms and individualized web dynamic nomograms, and their performances were further evaluated by C-index, calibration curve, receiver operating characteristic (ROC) curve, and decision curve analysis (DCA), respectively.Results: In multivariate Cox analysis, age, metastasis, ALP, CD4+/CD8+ ratio, chemotherapy, and CONUT score were identified as independent prognostic factors for OS. The calibration curves of the three models all showed good agreement between the actual observation and nomogram prediction for 1-year overall survival. In the development set, the C-index and area under the curve (AUC) of model 3 (0.837, 0.848) were higher than that of model 1 (0.765, 0.773) and model 2 (0.712, 0.749). Similar trends were observed in the validation set. The net benefits of model 3 were better than the other two models within the threshold probability of 36– 80% in DCA.Conclusion: CONUT score and peripheral CD4+/CD8+ ratio are easily available, reliable, and economical prognostic predictors for survival prediction and stratification in patients with advanced osteosarcoma, but the two predictors combined can establish a better prognosis prediction model.Keywords: CONUT score, osteosarcoma, survival, nomogram

Multi-column continuous chromatography has advantages of high resin capacity utilization and productivity, low buffer consumption and small footprint. Experimental optimization is often time-consuming and inefficient due to the complexity of continuous processes. In this study, a model-based approach was investigated to improve process development of twin-column continuous capture with Protein A affinity resin MabSelect PrismA. Breakthrough curves under various conditions, productivity and capacity utilization (CU) of the continuous processes under varying operating conditions were predicted. Effects of three key operating parameters (feed concentration (c0), interconnected feed residence time (RT) and breakthrough percentage control of the first column during interconnected feeding (s)) on the productivity and CU were evaluated. A recommended working window can be determined directly from contour maps to balance the trade-off between productivity and CU. The model-optimized operating conditions at varying feed concentrations were verified by experiments, which indicated that the model-based approach was feasible and reliable. The results showed that the suitable RT was 1~2 min and suitable s was 0.6~0.75 for the continuous IgG capture with MabSelect PrismA. The maximum productivity varied from 14 to 47 g/L/h with the feed IgG concentrations at the range of 1 to 10 mg/mL. The results indicated that model-based approach could assist process development efficiently and promote target-orientated process design for continuous processes.

Management of chronic pain is still hard, and new analgesic drugs are needed. Evodiamine (Evo) and rutaecarpine (Rut) are two major active components of Evodia rutaecarpa, a Chinese traditional medicine that has been used as an analgesic for a long time. However, their effects on peripheral hypersensitivity remain unknown. Similar to capsaicin, the Evo and Rut were docked to the transient receptor potential cation channel subfamily V member 1 (TRPV1) in molecular simulation experiments. Moreover, Evo (10 µM) and Rut (50 µM) activated TRPV1 on human embryonic kidney 293 (HEK293) cells in electrophysiological recording experiments. Behaviorally, the application of Evo and Rut reduced peripheral hypersensitivity in a dose-dependent manner, which was blocked by capsazepine (a selective inhibitor of TRPV1). Furthermore, both Evo and Rut increased time in the open arms of the elevated plus maze on mice with nerve injury. These observations suggested that Evo and Rut reduced peripheral hypersensitivity and anxiety in mice with nerve injury or inflammation via TRPV1.

To evaluate the association between congenital missing of maxillary lateral incisor (MLI) with cervical vertebral body fusions, posterior arch deficiency, and both anomalies. A total of 64 subjects (24 males and 40 females; mean age 16 ± 4.5 years) were detected to have congenital missing of MLI and selected as a study group. Two hundred and fifty-six subjects (87 males and 169 females, mean age 18.1 ± 3.2 years) were assigned to the control group. In the congenital absence of MLI, 53.7% revealed cervical column body fusion, 11.1% indicated a posterior arch deficiency, and 9.3% showed cervical column body fusion with posterior arch deficiency. Morphological deviations of the cervical column showed significant associations with congenital absence of MLI compared to control group (p 0.05). Subjects with congenial MLI tend to have an increased frequency of cervical anomaly.

Microvesicles (MVs) have been shown to be involved in pathophysiology of ischemic heart diseases. However, the underlying mechanisms are still unclear. Here we investigated the effects of MVs derived from ischemic preconditioning (IPC-MVs) on myocardial ischemic/reperfusion (I/R) injury in rats. Myocardial IPC model was elicited by three cycles of ischemia and reperfusion of the left anterior descending (LAD) coronary artery. IPC-MVs from the peripheral blood of the above animal model were isolated by ultracentrifugation and characterized by flow cytometry and transmission electron microscopy. IPC-MVs were administered intravenously (7 mg/kg) at 5 min before reperfusion procedure in I/R injury model which was induced by 30-min ischemia and 120-min reperfusion of LAD in rats. We found that total IPC-MVs and different phenotypes, including platelet-derived MVs (PMVs), endothelial cell-derived MVs (EMVs), leucocyte-derived MVs and erythrocyte-derived MVs (RMVs) were all isolated which were identified membrane vesicles (

A new type of graphene oxide (GO) is successfully prepared using an improved modified Hummers method. The Raman shift, X-ray diffraction (XRD), and scanning electron microscope (SEM) measurement techniques are used to characterize the GO. An efficient and compact Q-switched green laser based on Nd:YVO 4 /PPLN is demonstrated with a few-layered GO as the saturable absorber. Our experimental results show that such a few-layered GO saturable absorber allows for the generation of a stable Q-switched laser pulse centered at 532.1 nm with a 3 dB spectral bandwidth of 2.78 nm, a repetition rate of 71.4 kHz, and a pulse duration of 98 ns. The maximum average output power of 536 mW is obtained at the absorbed pump power of 5.16 W, corresponding to an optical conversion efficiency of 10.3%.

We investigate the optical amplification of the output field and fast-slow light effect in a three-mode cavity optomechanical system without rotating wave approximation and discuss two ways of realizing the optical amplification effect. Resorting to the Coulomb coupling between the nanomechanical resonators, the asymmetric double optomechanically induced amplification effect can be achieved by utilizing the counterrotating term. Moreover, we find a remarkable optical amplification effect and observe the prominent fast-slow light effect at the singular point since the introduction of mechanical gain. Meanwhile, the transmission rate of the output field is increased by four orders of magnitude and the group delay time can reach in the order of 105μs. Our work is of great significance for the potential applications of optomechanically induced amplification in quantum information processing and quantum precision measurement.

Tyrosine kinase inhibitors (TKIs) are an effective treatment strategy for non-small cell lung cancer (NSCLC) patients harboring mutations that result in constitutive activation of the epidermal growth factor receptor (EGFR). However, most patients eventually develop resistance to TKIs. This occurs due to additional EGFR mutations or the activation of bypass signaling pathways. In our previous work, we demonstrated that Marsdenia tenacissima extract (MTE) restored gefitinib sensitivity in resistant NSCLC cells with EGFR T790M or K-ras mutations. However, the potential efficacy of MTE in NSCLC cells with resistance mediated by Axl and c-Met, and the related molecular mechanisms need to be elucidated. In this study we evaluated the ability of MTE to restore erlotinib/gefitinib sensitivity in TKI resistant HCC827/ER cells and xenograft mice models. Our results demonstrate that MTE overcomes erlotinib and gefitinib resistance driven by Axl and c-Met in vitro and in vivo. Combination therapy significantly suppressed EGFR downstream molecules and the c-Met and Axl activated bypass signaling pathways. Moreover, we observed that MTE is more efficient at restoring resistance to erlotinib than gefitinib. As the Axl and c-Met mediated bypass pathways share the same downstream signaling cascade as EGFR, simultaneous targeting of these pathways is a promising strategy to overcome acquired resistance of TKIs. Our results demonstrate that MTE treatment attenuates Axl phosphorylation and the associated epithelial-mesenchymal transition, suggesting MTE treatment may be a potential therapeutic strategy for overcoming erlotinib and gefitinib cross-resistance in NSCLC, especially for erlotinib resistance.

// Yao Wang 1 , Su Wei 1 , Yi-Lu Wang 1 , Miao Liu 1 , Man Shang 1 , Qi Zhang 4 , Yan-Na Wu 1 , Ming-Lin Liu 2, 3 , Jun-Qiu Song 1 and Yan-Xia Liu 1 1 Department of Pharmacology, School of Basic Medical Sciences, Tianjin Medical University, Tianjin 300070, China 2 Section of Endocrinology, Department of Medicine, Temple University School of Medicine, Philadelphia, PA19140, USA 3 Section of Endocrinology, Department of Medicine, Temple University School of Medicine, Philadelphia, PA 19140, USA 4 Department of Dermatology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA Correspondence to: Yan-Xia Liu, email: liu_yanxia126@126.com Jun-Qiu Song, email: song_junqiu@126.com Keywords: microvesicles, ischemia/reperfusion, apoptosis, Bcl-2/Bax, GRP78 Received: October 17, 2016 Accepted: March 28, 2017 Published: April 26, 2017 ABSTRACT Objective: To investigate the effects of circulating microvesicles derived from myocardial ischemia (I-MVs) on apoptosis in myocardial ischemia/reperfusion (I/R) injury in rats. Methods: I-MVs from rats undergoing myocardial left anterior descending (LAD) coronary artery ligation were isolated by ultracentrifugation from circulating blood and characterized by flow cytometry. I-MVs were administered intravenously (4.8 mg/kg) at 5 min before reperfusion procedure in I/R injury model which was induced by 30-min of ischemia and 120-min of reperfusion of LAD in rats. Results: Treatment with I-MVssignificantly reduced the size of myocardial infarction, the activities of serum CK-MB and LDH, and the number of apoptotic cardiomyocytes. The activities of caspase 3, caspase 9 and caspase 12 in myocardium were also decreased significantly with I-MVs treatment. Moreover, the expression of Bax was decreased but Bcl-2 was increased. The expression of glucose regulated protein 78 (GRP78), sarco/endoplasmic reticulum Ca 2+ -ATPase 2 (SERCA2) and phosphorylated phospholamban (p-PLB) were increased after being treated with I-MVs. Conclusion: I-MVs could protect hearts from I/R injury in rats through SERCA2 and p-PLB of calcium regulatory proteins to alleviate intrinsic myocardial apoptosis including mitochondrial and endoplasmic reticulum pathways.

This letter presents a wideband digital power amplifier (DPA) with Class-G technique to enhance back-off efficiency for Internet-of-Things (IoT) applications. The switched-capacitor power amplifier topology is adopted for high linearity performance. A wideband matching network is proposed to achieve 0.54–0.95-GHz frequency coverage for 802.11ah and narrowband IoT standards. The measurement results demonstrate a flat frequency response with only 0.5-dB power deviation over 0.54–0.95 GHz. The DPA achieves the peak output power of 23.5 dBm with 42.7% peak PAE and 32.8% PAE at 6-dB back off. When amplifying an 8-MHz 64 quadratic-amplitude modulation 802.11ah signal at 800 MHz, it obtains −28.4-dB error vector magnitude and 30.1% average PAE at 16.5-dBm average output power.

Understanding secular trends of thyroid cancer is critical to plan strategies for cancer prevention and control. Our aim was to estimate the incidence and mortality trends of thyroid cancer in China during 2005–2015. A retrospective cohort evaluation of thyroid cancer cases and deaths during 2005–2015 was performed using population-based data from the Chinese Cancer Registry Annual Report. The incidence and mortality rates of thyroid cancer were stratified by gender, age group (0, 1–4, 5–9, 10–14…80–84, 85–), and area (urban or rural). A Joinpoint regression model was used to examine secular trends. In China, the age-standardized incidence was 3.21/105 in 2005, and increased to 9.61/105 in 2015. Besides, a significant increase incidence rate was observed with the average annual percent change (AAPC) of 12.4% (95% CI: 10.5%–14.4%) in the period 2005–2015. The age-standardized mortality was 0.30/105 in 2005 and 0.35/105 in 2015, and the AAPC was 2.9% (95% CI: 1.3%–4.5%). For both incidence and mortality, the rates of thyroid cancer were much higher in females than in males, and in urban areas rather than rural areas; however, the rates of increasing trends showed no significant differences. With respect to the highest age-specific rates, it appeared in the age group of 50–54 years old for incidence and in the age group of 80–84 years old for mortality. Notably, the rate of increasing incidence trend was lower in older age groups, especially for people aged 70–79 years old. A rapid increase in incidence and a moderate increase in mortality of thyroid cancer were observed from 2005 to 2015 in our study. Effective measures and tailored programs should be taken to curb the growth trend and reduce the disease burden.

Objectives: The objective of this systematic review was to assess the analgesic efficacy of duloxetine (DLX) for fibromyalgia (FM) and find out which dosage between 60 mg/d DLX and 120 mg/d...

Background Macrophage migration inhibitory factor (MIF) is an important pro-inflammatory cytokine implicated in sepsis, rheumatoid arthritis and other diseases. However, the role of MIF in acute pancreatitis (AP) remains unclear. This study aims to explore the role of MIF in the pathogenesis of AP using MIF−/− mice (referred to as KO) and the biological effects of pharmacological inhibition of MIF in l -arginine induced AP. Methods AP was induced in C57BL/6 wild-type (referred to as WT) and KO mice by administration of l -arginine. The severity of AP was assessed by serum analysis of amylase and lipase, and of these pro-inflammatory cytokines TNF-α and IL-1β. Histological hematoxylin and eosin (H&E) and immunohistochemical staining of pancreatic tissues were examined for inflammation and expression of pro-inflammatory mediators. We also investigated the biological effects of pharmacological inhibition of MIF activity using ISO-1((S,R)-3-(4-hydroxyphenyl)-4,5-dihydro-5-isoxazole acetic acid methyl ester). Results At 72 h after the induction of AP with l -arginine, significantly lower levels of serum amylase, lipase, TNF-α, and IL-1β were observed in KO mice when compared with WT controls. Histological examination further showed protective effects against pancreatic tissue damage and inflammation, with pancreatic expression of TNF-α, IL-1β and NF-κB p65 markedly reduced. Pharmacological inhibition of MIF activity with ISO-1 markedly mirrored the protective effect seen in the KO AP model providing further evidence that MIF is involved in the pathogenesis of AP. Conclusion Our data provided strong evidence for the participation of MIF in the pathogenesis of AP and subsequent inflammatory response. The genetic ablation of MIF or its inhibition with pharmacological agents significantly ameliorated the severity of AP.

MicroRNAs (miRNAs) play an important role in drug resistance, and it is reported that miR-27a-3p regulated the sensitivity of cisplatin in breast cancer, lung cancer and ovarian cancer. However, the relationship between miR-27a-3p and chemosensitivity of cisplatin in hepatocellular carcinoma (HCC) was unclear, especially the underlying mechanism was unknown. In the present study, we analyzed miR-27a-3p expression levels in 372 tumor tissues and 49 adjacent tissues in HCC samples from TCGA database, and found that the miR-27a-3p was down-regulated in HCC tissues. The level of miR-27a-3p was associated with metastasis, Child–Pugh grade and race. MiR-27a-3p was regarded as a favorable prognosis indicator for HCC patients. Then, miR-27a-3p was overexpressed in HepG2 cell, and was knocked down in PLC cell. Next, we conducted a series of in vitro assays, including MTT, apoptosis and cell cycle assays to observe the biological changes. Further, inhibitor rate and apoptosis rate were detected with pre- and post-cisplatin treatment in HCC. The results showed that overexpression of miR-27a-3p repressed the cell viability, promoted apoptosis and increased the percentage of cells in G0/G1 phase. Importantly, overexpression of miR-27a-3p significantly increased the inhibitor rate and apoptosis rate with cisplatin intervention. Besides, we found that miR-27a-3p added cisplatin sensitivity potentially through regulating PI3K/Akt signaling pathway. Taken together, miR-27a-3p acted as a tumor suppressor gene in HCC cells, and it could be useful for modulating cisplatin sensitivity in chemotherapy.

Stress plays an important role in reproductive health and likely is one of the psychological factors affecting ART success. This study was designed to examine the relationship between the stress level as inferred from the amount of the enzyme alpha-amylase secreted in saliva (SAA) and pregnancy outcome in infertile couples undergoing in vitro fertilization and embryo transplantation (IVF-ET). A prospective cohort study was conducted in the Reproductive Medicine Centre of Zhengzhou University Hospital in Henan, China. Four hundred fifty-seven infertile couples undergoing in vitro fertilization and embryo transplantation (IVF-ET) for the first time participated in the study. Couples collected saliva samples the morning before the start of their first treatment cycle for the measurement of SAA. We found that the level of SAA (and hence, the amount of stress) in female partners, male partners, and couples analyzed together significantly affected IVF-ET outcome. Cutoff levels of SAA that predicted pregnancy failure were 136 μmol/L, 149 μmol/L, and 288 μmol/L in female partners, male partners, and couples, respectively. Female partners, male partners, and couples with high SAA levels had increased risk of pregnancy failure compared to those with low SAA levels. The SAA level directly correlated with the follicle-stimulating hormone level and was inversely proportional to the anti-Müllerian hormone level and endometrial thickness. Some semen parameters of male partners, such as density, survival rate, sperm rapid progressive motility (A%), and progressive motility [(A + B)%], were significantly lower in the high-SAA than in the low-SAA group. Furthermore, couples in the high SAA group had fewer transferable and high-quality embryos. We concluded that a high SAA level, known to be an objective indicator of high stress, increases the risk of pregnancy failure in infertile couples undergoing IVF-ET. Lay summary To explore the relationship between stress, as measured by the levels of the stress biomarker salivary alpha-amylase (SAA), and pregnancy outcome in infertile couples undergoing in vitro fertilization, a prospective cohort study was conducted in the Reproductive Medicine Centre of Zhengzhou University Hospital in Henan, China. Four hundred fifty-seven infertile couples undergoing IVF-ET collected saliva samples the morning before the start of their first treatment cycle for the measurement of SAA. Results of this study demonstrated that a high SAA level, known to be an objective indicator of high stress, increases the risk of pregnancy failure in infertile couples undergoing IVF-ET.

In theory, the key step of traditional Harsanyi transformation is “Nature” assigns types to real players according to certain probability distributions. In big data era, it is still a challenge to obtain the probability distributions in practice, partly because the history type data of a new player is still private. Considering it is easy to access some feature data of a new player as well as to obtain both the feature and type data of massive other players, this paper introduces the statistical learning method eXtreme Gradient Boosting (XGBoost) to propose an XGBoost-driven Harsanyi transformation, where XGBoost is used to predict a new player’s type distribution indirectly. To test the effect of XGBoost-driven Harsanyi transformation, an incomplete information Internet loan credit game (3ILCG) is modeled and analyzed. When the loan interest rate r = 0.2, the empirical analysis is executed on 24,000 training data and 6,000 testing data. The experiment shows the accuracy (A) and harmonic mean (F1) of the enterprise loan decision based on pxgb on 6,000 testing data are 0.900833 and 0.945864 respectively. The test experiment demonstrates the XGBoost-driven Harsanyi transformation can help the lending platform to make loan decisions scientifically in practice and improve the practice value of game theory.

Perovskite solar cells (PSCs) have been rapidly crowded into the emerging photovoltaic technology, exhibiting continuously boosted power conversion efficiencies (PCEs) over 25%. Despite the high PCE, the voltage loss (Vloss) of PSCs still need to be further reduced to achieve higher open-circuit voltage (Voc) and thus approaching its Shockley–Queisser limit. Great effort on minimizing the Vloss has been made by mainly suppressing non-radiative recombination in perovskite and/or relevant interface, maximizing initial radiative efficiency, and modifying energy level alignment in PSCs. However, a timely overview of the lowest Vloss values achieved and the strategies of suppressing Vloss for the PSCs based on the most prevalent perovskite compositions is still lacking. In this review, the definition and determining factors of Vloss are elucidated, and the state-of-the-art low Vloss values of PSCs based on various types of prevailing perovskites with variable bandgaps are comprehensively discussed. The strategies for suppressing Vloss of PSCs are highlighted, aiming to boost the fundamental understanding of related Vloss mechanisms. Finally, an insightful perspective on further suppressing the Vloss in PSCs is provided, targeting on achieving new record PCEs in PSCs.

Speed up robust features (SURF) image geometrical registration algorithm available tends to have a one-to-many association problem in feature association. One feature point in an image is associated with multiple feature points in another image, of which some or even all are mismatching points. Coordinates of these mismatching points are used to compute transformation matrix, making it difficult to obtain desirable registration. To solve this problem of SURF algorithm, super-SURF image geometrical registration algorithm is proposed, in which information richness areas are selected to detect feature points and to implement feature points association. The degree of closeness of multiple feature points from the one-to-many feature point pairs is analysed in order to remove feature point pairs with larger errors and retain those with smaller errors. Transformation matrix is then determined with coordinates of feature point pairs retained. Registration image can be obtained after transformation of floating image. Experimental results indicate that super-SURF image geometrical registration algorithm is of higher matching accuracy with less running time than SURF algorithm.

Slightly acidic electrolyzed water (SAEW) has been recognized as an effective bactericidal agent with free chlorine, but its limitations include its instability and its great dependence on equipment. Newly developed circulating electrolyzed water (CEW) with a higher available chlorine concentration (ACC) could successfully overcome these limitations. In this study, SAEW (ACC of 20 mg/L), CEW1 (ACC of 200 mg/L), and CEW2 (ACC of 20 mg/L) were evaluated for changes in properties (pH, oxidization reduction potential [ORP], and ACC) during storage in open or closed glass bottles under light or dark conditions at room temperature (approximately 20 °C) and after washing pork and lettuce. Additionally, the washed pork and lettuce were evaluated for total viable counts, pH and general appearance. The results showed that CEW1 with a higher ACC has better stability than SAEW with a lower ACC for the storage and washing experiments, and CEW still remained stable after dilution with distilled water. The property indices of EW were greatly affected for the pork-washing experiments compared with the lettuce-washing experiments, probably due to the existence of alkaline and organic materials on the surface of pork. Furthermore, EWs were more effective for inactivating microbes in lettuce than in pork, while there was no significant difference in tissue pH and the general appearance of pork and lettuce. These findings indicated that CEW with a higher ACC shows potential for reducing foodborne pathogens on pork and lettuce without effects on their physicochemical characteristics, and it can be applied in a diluted form.

"Internet +" is the core feature of the current development of information technology. It has been achieved that the Internet and China's logistics industry recombined profoundly using information and communication technologies and Internet platforms. We can grasp more accurate and comprehensive the relationship between supply and demand through online real-time monitoring of procurement and distribution data, and minimize commodity inventory, reduce operating costs, simultaneously we can open up multiple sales channels, explore actively logistics innovation and development countermeasures in order to create a new model of diversified logistics management.