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Background Mutations in the IRF2BPL gene can cause neurodevelopmental disorders. We describe the clinical and genetic characteristics of a Chinese patient with a novel abnormality in this gene, explore the potential pathogenic mechanism and summarize the clinical characteristics of 25 patients with IRF2BPL mutations. Methods We identified the gene mutation sites by whole-exome and Sanger sequencing. The protein-protein interaction network of the IRF2BPL gene was constructed using bioinformatic techniques, and its function was enriched. We conducted a functional experiment to explore the potential pathogenicity of the identified IRF2BPL gene mutation. Results An 8-year-old girl presented with progressive cerebellar ataxia, including involuntary tremor and slurred speech. Electroencephalography and electromyography revealed no abnormalities. Structural cranial MRI was also normal, but genetic analysis identified a truncating de novo variant in IRF2BPL. Bioinformatics predicted that IRF2BPL would be associated with IRF2 and 10 other genes and involved in ubiquitin binding and other pathways. The cellular location of IRF2BPL was altered, and compared to control cells, the level of ubiquitinated proteins was significantly decreased in cells harbouring the mutation. Conclusion In this study, we identified a truncating de novo variant of IRF2BPL as a causative gene in the neurodevelopmental disorder of a Chinese girl. Impairment of the ubiquitin-proteasome pathway caused by this IRF2BPL mutation may play an important role in this neurodevelopmental disorder.

Acute lung injury (ALI) caused by gas explosion is common, and warrants research on the underlying mechanisms. Specifically, the role of abnormalities of coagulation and fibrinolysis in this process has not been defined. It was hypothesized that the abnormal coagulation and fibrinolysis promoted ALI caused by gas explosion. Based on the presence of ALI, 74 cases of gas explosion injury were divided into the ALI and non‐ALI groups. The results of prothrombin time (PT), activated partial thromboplastin time (APTT), fibrinogen (FIB), and platelet count (PLT) were collected within 24 hours and compared between the groups. ALI models caused by gas explosion were established in Sprague Dawley rats, and injuries were evaluated using hematoxylin and eosin (HE) staining and histopathological scoring. Moreover, the bronchoalveolar lavage fluid (BALF) was collected to examine thrombin‐antithrombin complex (TAT), tissue factor (TF), tissue factor pathway inhibitor (TFPI), and plasminogen activator inhibitor‐1 (PAI‐1) levels by enzyme‐linked immunosorbent assay (ELISA). The patients in ALI group had shorter PT and longer APTT, raised concentration of FIB and decreased number of PLT, as compared to the non‐ALI group. In ALI rats, the HE staining revealed red blood cells in alveoli and interstitial thickening within 2 hours which peaked at 72 hours. The levels of TAT/TF in the BALF increased continually until the seventh day, while the PAI‐1 was raised after 24 hours and 7 days. The TFPI was elevated after 2 hours and 24 hours, and then decreased after 72 hours. Abnormalities in coagulation and fibrinolysis in lung tissues play a role in ALI caused by gas explosion.

Objective The cardiotoxicity of doxorubicin (DOX) reduces the quality of life and prognosis of cancer patients, and therefore its clinical application has been largely restricted. This study aimed to assess the effects of cryptotanshione (CPT) on DOX-induced rat cardiac insufficiency. Results CPT treatment significantly suppressed apoptosis in vitro. The oral administration of CPT significantly improved cardiac function in the rat model, reduced collagen production and suppressed apoptosis and the production of reactive oxygen species in the heart tissue. Transcriptomic profiling and its relevant bioinformatics analysis showed that CPT suppressed doxorubicin-induced cardiotoxicity by inhibiting p53 signaling pathway. Conclusion Transcriptomic profiling and bioinformatics analysis can be used to evaluate the cardio-protective effect of CPT through inactivating p53 signaling pathway in the doxorubicin-mediated myocardial damage model. Methods F-actin staining and flow cytometry were used to assess the effects of CPT on cardiomyocytes. In vivo, echocardiography and hemodynamic evaluation were used to assess the effects of CPT on the cardiac dysfunction in rats. Furthermore, transcriptomic profiling and bioinformatics analysis, as well as western blot analysis, were used to determine that CPT induced changes in the signaling pathways in the model.

Accuracy of the fitted surface is of great importance to the performance of deployable antennas utilized in space. This paper proposes a stiffness analysis based fitting accuracy optimization method for achieving the optimal parameters of the parabolic cylindrical deployable antenna mechanism. The stiffness matrix of the proposed cylindrical antenna mechanism is established by assembling the stiffness of beams and tension cables. Structural deformations of the mechanism are calculated where the tensioned cable is substituted by a 2-node truss element and an equivalent force acting on the joint. Consideration of the tensity of tension cables, namely tensioned or slack, is transformed into a typical linear complementarity problem. Comparison between structural deformations of the mechanism fixed at different points is performed. Sensitivities of the geometric and structural parameters on fitting accuracy are investigated. Influence of force of the driven cable on structural deformations of antenna operated in different orbits is conducted. A fitting optimization method is proposed to minimize the structural deformations subject to constraints on volume and mass. Simulation result shows that the fitting accuracy of the antenna mechanism is improved significantly through the optimization. The proposed method can be utilized for the optimal design of other deployable mechanisms constructed by joining rigid links.

Background Recurrence is the major cause of mortality in patients with resected HCC. However, without a standard approach to evaluate prognosis, it is difficult to select candidates for additional therapy. Methods A total of 201 patients with HCC who were followed up for at least 5 years after curative hepatectomy were enrolled in this retrospective, multicentre study. A total of 3144 radiomics features were extracted from preoperative MRI. The random forest method was used for radiomics signature building, and five-fold cross-validation was applied. A radiomics model incorporating the radiomics signature and clinical risk factors was developed. Results Patients were divided into survivor (n = 97) and non-survivor (n = 104) groups based on the 5-year survival after surgery. The 30 most survival-related radiomics features were selected for the radiomics signature. Preoperative AFP and AST were integrated into the model as independent clinical risk factors. The model demonstrated good calibration and satisfactory discrimination, with a mean AUC of 0.9804 and 0.7578 in the training and validation sets, respectively. Conclusions This radiomics model is a valid method to predict 5-year survival in patients with HCC and may be used to identify patients for clinical trials of perioperative therapies and for additional surveillance.

Background: Data on the relationship between the triglyceride glucose (TyG) index and prognosis after off-pump coronary artery bypass grafting (OPCABG) are limited. This retrospective observational study evaluated the association of the TyG index with prognosis in patients with type 2 diabetes mellitus (T2DM) and non-ST-segment elevation acute coronary syndrome (NSTE-ACS) who underwent OPCABG.Methods: A total of 1534 patients with T2DM who underwent OPCABG for NSTE-ACS were enrolled in this study. Patients were divided into lower and higher TyG index groups according to the optimal cutoff value of the TyG index for predicting the primary endpoint. The primary outcomes included the occurrence of major adverse cardiovascular and cerebrovascular events (MACCEs), which were defined as all-cause death, nonfatal myocardial infarction, nonfatal stroke and symptomatic graft stenosis or occlusion. The TyG index was calculated using the following equation: TyG index = ln (fasting triglyceride level [mg/dL] × fasting glucose level [mg/dL]/2).Results: The overall incidence of MACCEs was 10.7% with a median follow-up of 23.1 months. The optimal TyG index cutoff for predicting MACCEs was 9.42 (sensitivity 49.4%; specificity 71.2%; area under the curve 0.631; P < 0.001). The incidence of MACCEs increased with a 1-unit increase in the TyG index [HR 2.218, 95% CI (1.733-2.839), P < 0.001]. A TyG index greater than 9.42 was independently associated with a higher risk of MACCEs [HR 2.092, 95% CI (1.573-2.784), P < 0.001] and each component. Furthermore, the effect of TyG in increasing MACCEs was consistent across groups of age, sex, BMI, hypertension, LDL-C, oral hypoglycemic agents, LIMA, number of grafts and IABP groups, except in patients diagnosed with NSTEMI, treated with statins and prescribed insulin at discharge.Conclusion: The TyG index predicts future MACCEs independently of known cardiovascular risk factors, suggesting that the TyG index may be a useful marker for prognosis in patients with T2DM and NSTE-ACS who underwent OPCABG.

Background De Winter pattern is associated with acute occlusion in the left anterior descending coronary artery combined with upsloping ST-segment depression at the J point in leads V1 through V6 without ST-segment elevation. The ECG changes in this case were illustrated by an up-sloping ST-segment depression in the V1 to V6 leads, followed by tall and symmetrical T waves. Changes from de Winter to ST-segment elevation myocardial infarction (STEMI) are rare. Case presentation Our case illustrated an evolutionary de Winter sign that changed to STEMI; the patient underwent cardiac catheterization in time. Conclusions Patients who have an electrocardiogram showing de Winter changes may require primary percutaneous coronary intervention. Emergency physicians and cardiologists should not ignore these changes.

Objectives: The aim of this study was to investigate the efficacy of combination therapy of caspofungin and TMP/SMZ (trimethoprim/sulfamethoxazole) in moderate to severe pneumocystis jirovecii pneumonia (PJP) in patients without human immunodeficiency virus infection (HIV) and the relationship between therapeutic effect and plasma (1, 3) Beta-d-Glucan (BDG) levels. Methods: We retrospectively reviewed HIV-negative patients with PJP diagnosed in our department, who were treated with combination therapy of caspofungin and TMP/SMZ or monotherapy of TMP/SMZ during a six and a half year period. Results: A total of 126 moderate to severe PJP patients were enrolled in the study. In the multivariate analysis, low lymphocyte counts, high serum lactate dehydrogenase levels at the diagnosis of PJP and progression to shock were significant risk factors for death. In all patients, there was no significant difference in risk of death at 3 months. In the group of BDG ≥ 800 pg/m, patients receiving combination therapy was associated with a significantly decreased risk of death at 3 months, whereas in the group of BDG

Diabetic cardiomyopathy is characterized by diabetes‐induced myocardial abnormalities, accompanied by inflammatory response and alterations in inflammation‐related signalling pathways. Kirenol, isolated from Herba Siegesbeckiae, has potent anti‐inflammatory properties. In this study, we aimed to investigate the cardioprotective effect of kirenol against DCM and underlying the potential mechanisms in a type 2 diabetes mellitus model. Kirenol treatment significantly decreased high glucose‐induced cardiofibroblasts proliferation and increased the cardiomyocytes viability, prevented the loss of mitochondrial membrane potential and further attenuated cardiomyocytes apoptosis, accompanied by a reduction in apoptosis‐related protein expression. Kirenol gavage could affect the expression of pro‐inflammatory cytokines in a dose‐dependent manner but not lower lipid profiles, and only decrease fasting plasma glucose, fasting plasma insulin and mean HbA1c levels in high‐dose kirenol‐treated group at some time‐points. Left ventricular dysfunction, hypertrophy, fibrosis and cell apoptosis, as structural and functional abnormalities, were ameliorated by kirenol administration. Moreover, in diabetic hearts, oral kirenol significantly attenuated activation of mitogen‐activated protein kinase subfamily and nuclear translocation of NF‐κB and Smad2/3 and decreased phosphorylation of IκBα and both fibrosis‐related and apoptosis‐related proteins. In an Electrophoretic mobility shift assay, the binding activities of NF‐κB, Smad3/4, SP1 and AP‐1 in the nucleus of diabetic myocardium were significantly down‐regulated by kirenol treatment. Additionally, high dose significantly enhanced myocardial Akt phosphorylation without intraperitoneal injection of insulin. Kirenol may have potent cardioprotective effects on treating for the established diabetic cardiomyopathy, which involves the inhibition of inflammation and fibrosis‐related signalling pathways and is independent of lowering hyperglycaemia, hyperinsulinemia and lipid profiles.

We studied patients with chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids (CLIPPERS) associated with or without lymphoma and measured risk factors suggestive of an underlying lymphoma and follow-up outcomes.CLIPPERS patients associated with or without lymphoma were included into this study. Clinical presentations were documented, risk factors suggestive of an underlying lymphoma were tested, and prognostic differences in terms of death were compared.Ten patients had a diagnosis of CLIPPERS associated with lymphoma, with 6 B-cell non-Hodgkin lymphoma, 2 T-cell non-Hodgkin lymphoma and 2 Hodgkin lymphoma. Using multivariate logistic analysis, the following 3 independent risk factors were found to be related to a final diagnosis of lymphoma: hyperreflexia (HR 16.56; 95% CI 1.03-265.29; p = 0.032), elevated protein in CSF (HR 11.59; 95% CI 1.24-108.39; p = 0.047), and recurrences between 2 months and 1 year after treatment (HR 29.27; 95% CI 2.09-409.58; p = 0.012). The model calibration was satisfactory (p = 0.392 with the Hosmer-Lemeshow test), and the discrimination power was good (area under the receiver operating characteristic curve 0.921; p 0.001, 95% CI 0.826-1.000). Patients with CLIPPERS associated with lymphoma had higher mortality rate and lymphoma was a significant predictor of total mortality (HR 0.040; 95% CI 0.006-0.262; p = 0.001).Hyperreflexia, elevated protein in CSF and recurrences between 2 months and 1 year after treatment are risk factors suggesting an underlying lymphoma. Relapses during high-dose steroids maintenance therapy can be indicative of lymphoma, too. Patients having CLIPPERS associated with lymphoma have a worse prognosis than those without lymphoma.

To evaluate the correlations between the enhancement pattern of intrahepatic cholangiocarcinoma (ICC) on contrast-enhanced ultrasound (CEUS) and clinicopathologic findings and prognosis, a retrospective study was performed on 197 patients with mass-forming ICC who underwent pre-operative CEUS and surgical resection. The contrast medium we employed in CEUS was SonoVue, which contains microbubbles consisting of sulfur hexafluoride bubbles within a phospholipid shell. This study was approved by the institutional review board with informed consent waived. Patients were classified into an arterial rim-like enhancement group or an arterial non-rim-like enhancement group, and arterial enhancement patterns were correlated with clinicopathologic factors. Overall survival (OS) times were calculated using the Kaplan–Meier method, and differences between groups were compared with the log-rank test. Univariate and multivariate Cox regression models for OS were used to evaluate the independent prognostic factors. The mean and range of ICC tumor size of the arterial rim-like group (59.41 ± 22.09 mm, 20–100 mm) were similar to those of the arterial non-rim-like group (59.82 ± 30.35 mm, 14–162 mm, p = 0.914). Arterial enhancement patterns were correlated with chronic viral hepatitis or cirrhosis, vascular invasion, lymph node metastasis and single/multiple tumors. A total of 78 patients (39.6%) exhibited arterial rim-like enhancement, and the other 119 patients (60.4%) exhibited arterial non-rim-like enhancement. Arterial enhancement pattern (p = 0.045), vascular invasion (p = 0.005), lymph node metastasis (p = 0.000) and number of tumors (p = 0.001) were independent prognostic factors for OS. The arterial non-rim-like enhancement pattern of ICC on CEUS is an independent prognostic factor for better OS and may offer new information for predicting the prognosis of ICC patients before surgical resection.

BACKGROUND Hemangioma of the small intestine is a rare vascular malformation. Before the advent of capsule endoscopy (CE) and balloon-assisted enteroscopy (BAE), preoperative diagnosis of this disease was extremely difficult. CASE SUMMARY In this study, we report a 24-year-old female with a large transmural small bowel cavernous hemangioma, which was diagnosed with CE and BAE preoperatively and removed successfully using minimally invasive surgery. Meanwhile, we perform a literature review of the studies about intestinal hemangiomas published after 2000. Literature review revealed that 91.9% of the lesions were diagnosed preoperatively by CE and/or BAE and 45.9% of them were treated endoscopically, which is a marked improvement compared to before 2000. Therefore, CE and BAE are useful modalities for the preoperative diagnosis of hemangiomas in the small intestine. CONCLUSION Endoscopic treatment of intestinal hemangioma is generally prudent and might be suitable for multiple, relatively small lesions.

Background and Aims: The impact of obstructive sleep apnea (OSA) on perioperative myocardial infarction (PMI) following coronary artery bypass grafting (CABG) remains unclear. Off-pump CABG (OPCABG) has become a common practice for CABG in China. The present study investigated mainly the correlation between OSA and PMI following OPCABG.Methods: In this prospective observational single-center study, consecutive eligible patients listed for elective OPCABG underwent cardiorespiratory polygraphy before surgery between January 2019 and June 2020. OSA was defined as an apnea-hypopnea index (AHI) ≥15 events/h. The primary end point was perioperative myocardial infarction (PMI) following OPCABG (type 5 MI).Results: Patients with OSA accounted for 42.2% (62/147) of the cohort. Twenty-four patients (16.3%) met the protocol criteria for PMI: 17 (27.4%) in the OSA group and 7 (8.2%) in the non-OSA group (P = 0.002). Multivariate logistic regression analysis revealed that AHI (OR = 1.115, 95% CI 1.066 to 1.166, P < 0.001), high-sensitivity c-reactive protein (hs-CRP) (OR = 1.080, 95% CI 1.025 to 1.138, P = 0.004), and SYNTAX score (OR = 1.098, 95% CI 1.056 to 1.141, P < 0.001) were associated with PMI incidence. Furthermore, ROC analysis revealed that the AHI (AUC = 0.766, 95% CI 0.689 to 0.832, P < 0.001) and SYNTAX score (AUC = 0.789, 95% CI 0.715 to 0.852, P < 0.001) had predictive value for PMI. In addition, multiple linear regression analysis showed that the AHI was an independent influencing factor of hs-CRP (B = 0.176, 95% CI 0.090 to 0.263, P < 0.001) and the SYNTAX score (B = 0.553, 95% CI 0.397 to 0.709, P < 0.001).Conclusions: OSA was independently associated with a higher incidence of PMI following OPCABG, and the formation of severe coronary atherosclerotic lesions aggravated by an enhanced inflammatory response might be the potential mechanism. The efficacy of CPAP treatment for improving prognosis after CABG remains to be further investigated.

Background To develop and evaluate a modified four vessel occlusion (4VO) model of global cerebral ischemia-reperfusion (GCI/R) in rats based on the Pulsinelli and Brierley's method. New methods Vertebral arteries (VAs) were isolated and then permanently ligated with 5-0 nylon surgical sutures under visual conditions. A total of 24 h later, GCI was induced by transient clipping of the bilateral common carotid artery for 20 min. Cognitive function and visual perception were then evaluated by behavioral and histopathological approaches. Results There was no significant difference in the survival rates between the groups. The modified 4VO group had a significantly lower body weight at each time point assessed. In the Y-maze test, the percentage of time spent and distance traveled in the III arm was significantly decreased on day 28, suggesting that cognitive function may have been impaired by the modified 4VO model. The modified 4VO procedure induced severe hippocampal damage but did not result in noticeable changes in visual perception, as indicated by the light-dark box test, and analysis of the optic tract and retinal structures. The modified 4VO procedure-induced cognitive deficits were thus likely the result of hippocampal damage, not visual perception. Comparison with existing methods The advantage of this model is the permanent ligation of the bilateral VAs under visual conditions rather than electrocoagulation, which is performed blind. Conclusions This modified 4VO model can mimic the GCI/R method of the Pulsinelli and Brierley and may serve as a valuable tool for studies on GCI/R.

BackgroundCerebrotendinous xanthomatosis (CTX) is an autosomal recessive disorder of bile acid synthesis caused by mutations in the CYP27A1 gene. CTX is an underdiagnosed and potentially treatable disease, thus a detailed appreciation of the phenotypic spectrum and genetic characteristics are crucial for early diagnosis and treatment.Objectives and MethodsFour CTX families with mutations in the CYP27A1 gene were enrolled in our study. We investigated the clinical characteristics and molecular genetic features of the probands with CTX. Genetic analysis was performed for detecting gene variants. Sanger sequencing and segregation analysis were conducted for haplotype analysis.ResultsAll the four probands were compound heterozygote for two CYP27A1 variants, including one mutation in c.1263+1G>A (intron 7) splice site, two novel likely pathogenic mutations (c.255+1G>T and c.1561dupA) and three pathogenic mutations including c.379C>T, c.1263+1G>A and c.1537C>T previously reported. All of the subjects presented with spastic paraparesis. The other common clinical features included ataxia, childhood-onset diarrhea, cataracts, intellectual disability, tendinous xanthomas and dentate nuclei signal alterations at MRI.ConclusionTwo novel likely pathogenic mutations (c.255+1G>T and c.1561dupA) were reported in our study. The 1263+1G>A mutation was commonly seen in Chinese reported case series (7/25, 28%) and could be a latent hotspot for Chinese CTX mutations. Our study expanded the mutation spectrum of CYP27A1 gene and provide an insightful view of the phenotypic spectrum and genetic characteristics to help early diagnosis and treatment with to improve neurologic dysfunction.

Background This study aims to explore the efficacy and safety of prostaglandina E1 (PE1) for the treatment of patients with thrombo-occlusive vasculitis (TOV). Methods Electronic databases (Cochrane Library, PUBMED, EMBASE, Web of Science, Scopus, the Allied and Complementary Medicine Database, Chinese Biomedical Literature Database, and China National Knowledge Infrastructure) will be sought from onset to the March 1, 2020 without language and publication status restrictions. We will include any potential randomized controlled trials that examined the efficacy of PE1 for the treatment of patients with TOV. We will appraise study quality using Cochrane risk of bias tool, and will assess the evidence quality using Grading of Recommendations Assessment Development and Evaluation. We will use RevMan 5.3 Software for statistical analysis. Results A high-quality synthesis of present evidence of PE1 for the treatment of patients with TOV will be provided in this study. Conclusion This study will provide evidence to judge whether PE1 is an effective intervention for TOV. Systematic review registration INPLASY202040081.

Background Neuropathic pain is a debilitating status that is insusceptible to the existing analgesics. It is important to explore the underlying pathophysiological changes and search for new pharmacological approaches. Transient receptor potential canonical 6 (TRPC6) is a mechanosensitive channel that is expressed by dorsal root ganglia and glial cells. It has been demonstrated that this channel in dorsal root ganglia plays essential roles in the formation of mechanical hyperalgesia in neuropathic pain. Recent pharmacological screening suggests that larixyl acetate (LA), a main constituent of larch resin, is able to selectively inhibit TRPC6 function. But whether LA is effective in treating neuropathic pain remains unknown. We investigated the efficacy of LA in rat neuropathic pain model, examined its effects on central neuroinflammation, and explored the possible molecular mechanisms by targeting the spinal dorsal horn. Methods Spared nerve injury (SNI) was conducted in Sprague-Dawley rats. Mechanical hypersensitivity and cold allodynia before and after single and multiple i.t. applications of LA at the dose of 3, 10, and 30 μM were evaluated by von Frey filament and acetone tests, respectively. Western blot, immunohistochemical, and immunocytochemical stainings were employed to examine the level and expression feature of ionized calcium-binding adaptor molecule 1 (Iba-1), glial fibrillary acidic protein (GFAP), TRPC6, and phosphorylated p38 kinase. The changes of cytokine concentrations, including that of TNF-α, IL-1β, IL-6, and IL-10, were also assessed by multiplex analysis. TRPC6 antisense strategy was finally adopted to investigate the action mechanisms of LA. Results Single application of LA on day 5 post injury caused dose-dependent inhibition of mechanical allodynia with the ED50 value of 13.43 μM. Multiple applications of LA at 30 μM not only enhanced the analgesic efficacy but also elongated the effective duration without obvious influences on animal locomotor activities. Single and multiple administrations of LA at 30 μM played similar but weaker inhibitory effects on cold allodynia. In addition to behavioral improvements, multiple applications of LA for 6 days dose-dependently inhibited the upregulation of Iba-1, TNF-α, IL-1β, and IL-6, whereas had no obvious effects on the levels of GFAP and IL-10. Combined Western blot and immunostaining assays revealed that the expression of TRPC6 was significantly increased in both spinal dorsal horn after nerve injury and the cultured microglia challenged by LPS, which was however suppressed by the addition of LA at 30 μM or 10 μM, respectively. Further knockdown of TRPC6 with antisense oligodeoxynucleotide produced prominent analgesic effects in rats with SNI, accompanied by the reduced phosphorylation level of p38 in the microglia. Conclusions These data demonstrate that i.t. applied LA exhibits analgesic and anti-inflammatory action in neuropathic pain. The action of LA involves the suppression of TRPC6 and p38 signaling in the microglia. LA may be thus a promising pharmacological candidate for the treatment of intractable chronic pain.

OBJECTIVE To explore the prevalence of and risk factors for gallstone disease in Shanghai, China. METHODS A population-based cross-sectional study was conducted in Shanghai between 2016 and 2017. Using a three-stage stratified sampling strategy, 4009 participants (1753 men and 2256 women) from 10 districts were enrolled. RESULTS The overall prevalence of gallstones was 6.83% (6.22% for men vs 7.31% for women, P = 0.173). According to the multivariate analysis, individuals aged ≥40 years (odds ratio [OR] 3.058, 95% confidence interval [CI] 2.110-4.433, P

With the extensive application of silver containing materials in industry, the issue of release of silver ions has attracted increasing attention due to toxic effect of silver ions on the human health and environment. Traditionally, silver ions can be detected by atomic absorption spectroscopy, atomic emission spectrometry etc., which needed expensive and elaborate instruments and were high energy consumption. Therefore, economic and convenient methods are required for the effective determination of silver ions. Herein, two types of carbon dots (CDs-1 and CDs-2) have been prepared through a solvothermal synthesis method by using sucrose or citric acid and tris(hydroxymethyl)aminomethane as precursor, respectively. Then, CDs-1 were developed for the detection of silver ions through a colorimetric method. The detection mechanism was based on the reduction of silver ions and the formation of silver nanoparticles, which possess unique surface plasma resonance properties. CDs-1 could both act as reductants and stabilizers during the reaction for determination of silver ions. This CDs-1 based detection system could quantitatively determine silver ions in 3 min with a limit of detection (LOD) of 26 nmol/L (2.81 ppb). Interestingly, this strategy could also realize the detection of silver ions by CDs-2. Furthermore, the sensing assay is applicable to detecting silver ions in lake water and silver sulfadiazine cream samples.

Disease progress and pathological proceeding of functional gastrointestinal disorder (FGID) are considered to be closely related to disordered brain-gut interaction, but only a few researches reported the relationship of functional constipation (FC) and disordered brain-gut interaction. It has been found that FC has a great correlation with emotional problems in clinical patients, but its related mechanisms have not been clearly clarified. In order to explore the molecular pathogenesis of FC related to emotional problem, BGI-500 sequencing technology was used for the first time to study the transcriptomics changes of hippocampus in a rat model. The results showed that the differential expressed genes (DEGs) were mainly involved in the modulation of hemoglobin binding and oxidative stress. These changes could result in changes of hemoglobin content and quality, which could further induce the decreased oxygen-carrying function of erythrocytes. In biological pathway, the disorder of cholinergic system could be speculated through related DEGs. And then, those enriched DEGs were verified by qRTPCR methods As far as the mRNA expressions of Chrna4, Camk2d and Gng13, there were significant difference between the control rats and model rats. These results show that FC could result in side effects on cognitive function, suggesting a new thought for understanding emotional disorder related to cognitive function.

This study aimed to analyze the influence of the cellular differentiation, the tumor size and the underlying hepatic condition on the enhancement pattern of hepatocellular carcinoma (HCC) on contrast-enhanced ultrasound (CEUS). 276 patients with single lesion ≤ 5 cm who underwent CEUS exam and were pathologically confirmed as HCC were retrospectively enrolled. Enhancement patterns, washout patterns, wash-in time and washout time were observed and recorded. During the arterial phase, more poorly differentiated HCCs (42.5%) and lesions > 3 cm (35.2%) performed inhomogeneous enhancement (p 3 cm (97.2 ± 51.3 s) washed out more rapidly than lesions ≤ 3 cm (113.9 ± 53.5 s) (p

Ca2+ signaling is essential for bone metabolism. Fluid shear stress (FSS), which can induce a rapid release of calcium from endoplasmic reticulum (ER) to produce calcium transients, plays a significant role in osteoblast proliferation and differentiation. However, it is still unclear of how calcium transients induced by FSS activating a number of downstream signals which subsequently regulate cell functions. In this study, we performed a group of Ca2+ transients models, which were induced by FSS to investigate the effects of different magnitudes of Ca2+ transients in osteoblast proliferation. Further, we performed a global proteomic profile of MC3T3-E1 cells in different Ca2+ transients models stimulated by FSS. GO enrichment and KEGG pathway analysis revealed that the TCA cycle was activated in the proliferating process. The activation of TCA needed mitochondrial Ca2+ uptake which were influenced by the amplitude of Ca2+ transients induced by FSS. Our work elucidate that osteoblast proliferation induced by FSS was related to the magnitude of calcium transients, which further activated energetic metabolism signaling pathway. This work revealed further understanding the mechanism of osteoblast proliferation induced by mechanic loading and help us to design new methods for osteoporosis therapy.

Autophagy alterations have been observed in a variety of neurological disorders, however, very few studies have focused on autophagy alterations in epilepsy. The ketogenic diet (KD) likely ameliorates neuronal loss in several seizure models. However, whether this neuroprotective function occurs via starvation-induced autophagy and its prevalence in chronic kindled seizures remains unknown. The aim of this study was to determine the role of autophagy following seizure under KD, and the potential mechanism involved. Pentylenetetrazol (PTZ)-kindled rats, which were fed a Normal diet (ND) or KD, were pretreated with intraventricular infusions of saline, autophagy inducer rapamycin (RAP), or inhibitor 3-methyladenine (3-MA). KD alleviated seizure severity, decreased the number of Fluoro-jade B (FJB)-positive cells in the hippocampus of kindled rats. These effects were abolished by 3-MA pretreatment. RAP pretreatment did not affect seizure severity, but decreased the number of FJB-positive cells in ND group. KD decreased the percentage of damaged mitochondria in kindled group. Hippocampal Beclin-1 was increased by KD in vehicle group. The autophagy proteins Atg5, Beclin-1 and the ratio of microtubule-associated protein 1 light chain 3 (LC3) II to LC3-I in kindled KD-fed rats were higher, and the autophagy substrate P62 was lower than those in the kindled ND-fed rats, indicating an increase in autophagy following KD. Pretreatment with RAP increased the level of LC3-II/LC3-I, and pretreatment with 3-MA increased the level of P62 in KD-fed rats. To further clarify the mechanism of autophagy protection, the levels of key mitochondria related molecules were examed. The results showed that mitochondrial cytochrome c was up-regulated, cytosolic cytochrome c and the downstream cleaved caspase-3 was down-regulated in KD-fed rats, indicating a decrease in mitochondrial apoptosis. Taken together, our results indicated that KD activates autophagic pathways and reduces brain injury during PTZ-kindled seizures. The neuroprotective effect of KD is likely exerted via a reduction of mitochondrial cytochrome c release.

St. John’s wort (Hypericum perforatum) is a well-known medicinal plant often used to treat mild to moderate mental depression. In southwest China, four species of Hypericum including H. perforatum, H. hookerianum, H. bellum and H. pseudohenryi have been used as traditional medicines for skin care, such as healing wounds, burns, and snake bites by local people. Hypericum volatile oils of these four species were obtained by supercritical CO2 extraction and analyzed by GC–MS. From H. perforatum, 56 compounds were identified, the amounts of marker components are different between two collection sites. From H. hookerianum, 71 compounds were identified, mainly comprised of alkanes. From H. bellum, 43 compounds were identified, and its essential oil contains mainly oxygenated sesquiterpenoids. From H. pseudohenryi, 57 compounds were identified, and the essential oil has relatively high levels of alkanes. Because Hypericum species are used traditionally to treat depression, wounds, and other skin problems, their volatile oils were evaluated in vitro for neurite outgrowth-promoting, neuroprotective, antimicrobial, and enzyme inhibitory activities. H. bellum and H. perforatum from Wushan demonstrated significant neurite-promoting and neuroprotective activity. The Gram-positive Staphylococcus aureus ssp. aureus was inhibited by most of the tested oils. Sesquiterpenoids and alkanols are the most abundant constituents of H. hookerianum and H. bellum oils which showed strong antibacterial activity and help to explain the observed antimicrobial activity of the oil. H. perforatum collected in Wushan showed tyrosinase inhibition activity. Based on the current results, three Asian Hypericum species and two Chinese H. perforatum populations may be promising ingredients for cosmetics, foods, and pharmaceuticals.

In the past decade, numerous studies have demonstrated the close relationship between gut microbiota and the occurrence and development of Alzheimer's disease (AD). However, the specific mechanism is still unclear. Both the neuroinflammation and systemic inflammation serve as the key hubs to accelerate the process of AD by promoting pathology and damaging neuron. What's more, the gut microbiota is also crucial for the regulation of inflammation. Therefore, this review focused on the role of gut microbiota in AD through inflammatory pathways. Firstly, this review summarized the relationship and interaction among gut microbiota, inflammation, and AD. Secondly, the direct and indirect regulatory effects of gut microbiota on AD through inflammatory pathways were described. These effects were mainly mediated by the component of the gut microbiota (lipopolysaccharides (LPS) and amyloid peptides), the metabolites of bacteria (short-chain fatty acids, branched amino acids, and neurotransmitters) and functional by-products (bile acids). In addition, potential treatments (fecal microbiota transplantation, antibiotics, probiotics, prebiotics, and dietary interventions) for AD were also discussed through these mechanisms. Finally, according to the current research status, the key problems to be solved in the future studies were proposed.

The strong hemolytic toxicity of pulsatilla saponin D (1, HD(50) 6.3 μM) has hampered its clinical development as an injectable anticancer agent. To combat this challenge, 17 new derivatives of 1 with ring C, C-28, or C-3 modifications were synthesized and evaluated for cytotoxicity against several selected human tumor lines, as well as for hemolytic toxicity against rabbit erythrocytes. Structure−activity relationship (SAR) and structure−toxicity relationship (STR) correlations were also elucidated. Compared to the lead compound 1, the hemolytic activity of all 17 derivatives dropped dramatically. Notably, compound 14 exhibited significant cytotoxicity toward A549 human lung cancer cells (IC(50) 2.8 μM) in a dose-dependent manner without hemolytic toxicity (HD(50) > 500 μM). Molecular studies indicated that 14 induced typical G(1) cell cycle arrest and apoptosis in A549 cells, and Western blot assays suggested that both intrinsic and extrinsic apoptosis pathways were activated by 14. Collectively, compound 14 may merit further development as a potential anti-lung cancer agent.

Identifying molecular mechanisms that regulate insulin expression in bone marrow-derived mesenchymal stem cells (bmMSCs) can provide clues on how to stimulate the differentiation of bmMSCs into insulin-producing cells (IPCs), which can be used as a therapeutic approach against type 1 diabetes (T1D). As repression factors may inhibit differentiation, the efficiency of this process is insufficient for cell transplantation. In this study, we used the mouse insulin 2 (Ins2) promoter sequence and performed a DNA affinity precipitation assay combined with liquid chromatography-mass spectrometry to identify the transcription factor, chicken ovalbumin upstream promoter transcriptional factor I (COUP-TFI). Functionally, bmMSCs were reprogrammed into IPCs via COUP-TFI suppression and MafA overexpression. The differentiated cells expressed higher levels of genes specific for islet endocrine cells, and they released C-peptide and insulin in response to glucose stimulation. Transplantation of IPCs into streptozotocin-induced diabetic mice caused a reduction in hyperglycemia. Mechanistically, COUP-TFI bound to the DR1 (direct repeats with 1 spacer) element in the Ins2 promoter, thereby negatively regulating promoter activity. Taken together, the data provide a novel mechanism by which COUP-TFI acts as a negative regulator in the Ins2 promoter. The differentiation of bmMSCs into IPCs could be improved by knockdown of COUP-TFI, which may provide a novel stem cell-based therapy for T1D. Keywords: siRNAs, differentiation, stem cell transplantation, diabetes, mesenchymal stem cells

Members of the Drosophila behavior/human splicing protein family, including splicing factor proline/glutamine rich (SFPQ), non-POU domain-containing octamer-binding protein (NONO), and paraspeckle protein component 1 (PSPC1), are abundantly expressed in testicular Sertoli cells (SCs), but their roles remain obscure. Here, we show that treatment with mono-(2-ethylhexyl) phthalate (MEHP), a well-known SC toxicant, selectively stimulates the expression levels of NONO and PSPC1. Simultaneous inhibition of NONO and PSPC1 expression in SCs enhances MEHP-induced oxidative stress and potentiates SC death. Mechanistically, NONO and PSPC1 transcriptionally activate aldehyde dehydrogenase 1 (Aldh1a1), by synergistically binding to the distinct CCGGAGTC sequence in the Aldh1a1 promoter. Together, the NONO/PSPC1-ALDH1A1 cascade may serve as an indispensable defense mechanism against MEHP insult in SCs.

Background & Aims The EncephalApp Stroop test is a high-sensitivity but low-specificity test that has been used to identify patients with covert hepatic encephalopathy (CHE). We aimed to develop a new strategy to detect CHE, combining EncephalApp Stroop test score with scores from subtests of the psychometric hepatic encephalopathy scoring system (PHES). Methods We performed a survey of 569 adult volunteers (229 men) in 9 communities in Shanghai, China, administering the EncephalApp Stroop test to determine the range of scores in the general population. Data from the standard PHES, including the number connection test-A, number connection test-B (NCT-B), line tracing test, serial dotting test (SDT), and digit symbol test, were used as the reference standard for diagnosis of CHE. A combination of the EncephalApp Stroop with subtests of the PHES was used to establish a new strategy for CHE diagnosis. We validated our findings using data from 160 patients with cirrhosis from 5 centers China. Results We determined the range of EncephalApp Stroop test scores for the volunteers of different decades of age, education levels, and sexes. Age, education level, and sex were independently associated with EncephalApp Stroop test scores. A combination of scores from the EncephalApp Stroop test, the NCT-B, and the SDT identified patients with CHE with the highest level of accuracy, when the standard PHES was used as the reference standard. A combination of scores of 187 sec for the EncephalApp Stroop test and below –1 for the NCT-B or below –1 for the SDT identified patients with CHE with an area under the curve (AUC) of 0.86, 81.0% sensitivity, and 91.9% specificity, and 87.5% accuracy. In the validation cohort, these cutoff scores identified patients with CHE with an AUC of 0.88, 97.1% sensitivity, 79.3% specificity, and 86.9% accuracy. The average time to calculate this score was 374±140 sec, compared 424±115 sec for the entire PHES. Conclusion Scores from the EncephalApp Stroop test, NCT-B, and SDT identify patients with CHE with approximately 87% accuracy, and in a much shorter time than the standard PHES. This score combination could be a valid and convenient method for identifying patients with CHE. chictr.org.cn number, ChiCTR-EDC-17012007, ChiCTR1800019954.

Background Chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids (CLIPPERS) is an inflammatory disorder in the central nervous system (CNS) with distinct clinical, radiological, and pathological characteristics. The pathophysiology of CLIPPERS still remains unclear. Because a few cases about lymphoma mimicking the manifestations of CLIPPERS were reported and the prognosis of lymphoma is much worse, early identification of lymphoma is very important. Case presentation A 31-year-old woman was admitted with 3 months’ history of diplopia, dizziness, gait ataxia, and right facial numbness. The diagnosis of CLIPPERS was established based on the finding of punctate enhancing lesions in the cerebellum, thalamus, pons, medulla, and midbrain region in magnetic resonance imaging (MRI), together with the favorable clinical and radiological responses to corticosteroids. However, she was diagnosed as peripheral T cell lymphoma, not otherwise specified (PTCL-NOS) by the pulmonary nodular and the skin biopsy almost 10 years later, and she got complete remission within 1 year after chemotherapy. Conclusion We report the first case of CLIPPERS developing PTCL-NOS. This case proposes that when brain biopsy was difficult to achieve, biopsies in extra-cerebral lesions under the assisting examination of positron emission tomography-computed tomography (PET-CT) can be helpful in further identification.

Guangyou Duan,1,* Xiaohang Bao,1,* Guiying Yang,1 Jing Peng,1 Zhuoxi Wu,1 Peng Zhao,1 Zhiyi Zuo,2 Hong Li1 1Department of Anesthesiology, Xinqiao Hospital, Third Military Medical University, Chongqing 400037, China; 2Department of Anesthesiology, University of Virginia, Charlottesville, VA, USA *These authors contributed equally to this work Introduction: This study aimed to compare the postoperative analgesic effects of tramadol and hydromorphone for secondary cesarean delivery (CD) as well as their anti-anxiety and anti-depression properties.Methods: A total of 106 patients receiving secondary CD under spinal anesthesia were randomly allocated to the tramadol group (n=53) and the hydromorphone group (n=53). Each group received patient-controlled intravenous analgesia using flurbiprofen 4mg/kg combined with tramadol (4mg/kg) or hydromorphone (0.04mg/kg) immediately after the surgery. Postoperative pain numerical rating scale (NRS) for incision and visceral pain, hospital anxiety and depression scale (HADS), early walking time and length of hospital stay were assessed.Results: Patients in the tramadol and hydromorphone groups exhibited equivalent incision pain NRS at different time points (P>0.05). Visceral pain in the tramadol group was higher than that in the hydromorphone group at postoperative 4 hours (2.9 [1.2] vs 2.3 [1.4], P=0.011) and 8 hours (2.4 [1.1] vs 1.8 [1.1], P=0.028). One week after the surgery, the patients in the tramadol group, as compared to the hydromorphone group, had lower anxiety scores (1.9 [3.5] vs 3.6 [4.1], P=0.033) and depression scores (0.8 [1.3] vs 2.7 [4.1], P=0.023). In addition, early walking time (25.3 [7.0] hours vs 29.3 [9.6] hours, P=0.016) and length of hospital stay (2.9 [0.8] days vs 3.3 [0.8] days, P= 0.008) after the surgery in the tramadol group were less than those in the hydromorphone group.Conclusion: Postoperative intravenous analgesia with tramadol or hydromorphone for secondary CD provides comparable analgesic effects on incision pain. Tramadol is less effective in controlling visceral pain compared to hydromorphone. However, tramadol can help to alleviate anxiety and depression in the early postpartum period, improve patients’ early mobilization and shorten their hospital stay.Clinical trial number and registry URL: No: ChiCTR-IIR-17011043; URL: www.chictr.org.cn. Keywords: anxiety, caesarean section, depression, postoperative pain, tramadol&nbsp

Background Traditional Chinese medicine (TCM) is an integral part of mainstream medicine in China, with theories and practices that are completely different from modern medicine. TCM should not be ignored or confused with modern medicine in the analysis of the Chinese health care system, including the analysis of mobile health (mHealth) apps. To date, differences between TCM apps and modern medicine apps have not be systematically investigated. Objective The aim of this study was to systematically compare the quality of apps for TCM and modern medicine in China. Methods In December 2020, we searched iOS (iTunes) and Android (Tencent, Oppo, and Huawei app stores) platforms for all mHealth apps and then categorized them as TCM or modern medicine apps if they were included in the final analysis. The included apps were downloaded on smartphones and assessed by 2 reviewers on the following 4 aspects: (1) data in the app stores, including user ratings, download counts, cost, target users, and year of last update; (2) functionality; (3) quality of the app content as determined by the Mobile App Rating Scale (MARS); and (4) analysis of the app privacy and security. Results In total, 658 apps were analyzed, including 261 TCM medicine apps and 397 modern medicine apps. The average download count of modern medicine apps (approximately 5 million) was more than 10 times that of TCM apps (approximately 400,000). Regarding functionalities, 64.7% (257/397) of modern medicine apps provided telemedicine (74/261, 28.4% in TCM apps), 62.7% (249/397) provided registration (70/261, 26.8% in TCM apps), and 45.6% (181/397) provided communication (38/261, 14.6% in TCM apps). A larger proportion of TCM apps provided prescription and medication management (144/261, 55.2% in TCM apps versus 168/397, 42.3% in modern medicine apps). The majority of modern medicine apps (329/397, 82.9%) combined ≥3 functionalities compared with one-third of TCM apps (93/261, 34.6%). We then selected 81 top apps for quality and safety assessment (41 TCM apps and 40 modern medicine apps). Of these, the mean overall MARS score of TCM apps (2.7, SD 0.5) was significantly lower than modern medicine apps (3.6, SD 0.4). Almost all modern medicine apps (38/40, 95%) addressed privacy and security by providing a privacy policy and describing how to protect personal data, but less than half of the TCM apps (18/41, 44%) described this information (P Conclusions The different functionalities reflect the distinct innate characteristics of these two medical systems. Although great progress has been made and the Chinese mHealth market size is large, there still exist many opportunities for future development, especially for TCM.

The ketogenic diet (KD) controls seizure and improves cognition in patients with drug refractory epilepsy. However, few experimental models have shown this neuroprotective effect on cognition. In this study, we investigated the cognitive protective effects of KD in pentylenetetrazol (PTZ)-kindled rats. We used two relatively low-stress behavioral assessment methods, the novel object recognition (NOR) task and the novel placement recognition (NPR) task, to reveal impairment in item and spatial memory, respectively. We used the Morris water maze (MWM) test for comparisons amongst memory assessment methods. The KD group had a slower body weight gain and shorter bregma-lambda length than the control normal diet (ND) group. KD did not increase anxiety or decrease motor activities in an open-field test. KD attenuated the decrease in exploration ratio both in NOR and NPR tasks in kindled rats. Compared to the kindled ND rats, kindled KD rats stayed longer in target quarter during the probe trial testing of MWM. However, there were no differences in memory acquisition based on the MWM test results. In conclusion, KD attenuated the spatial and item memory impairment in PTZ-induced seizures.

Background To investigate whether pyruvate-enriched oral rehydration solution (Pyr-ORS), compared with citrate-enriched ORS (Cit-ORS), improves hemodynamics and organ function by alleviating vasopermeability and plasma volume loss during intra-gastric fluid rehydration in dogs with severe burn. Methods Forty dogs subjected to severe burn were randomly divided into four groups ( n = 10): two oral rehydrated groups with Pyr-ORS and Cit-ORS (group PR and group CR), respectively, according to the Parkland formula during the first 24 h after burns. Other two groups were the intravenous (IV) resuscitation (group VR) with lactated Ringer's solution with the same dosage and no fluid rehydration (group NR). During the next 24 h, all groups received the same IV infusion. The hemodynamics, plasma volume, vasopermeability and water contents and function of various organs were determined. Plasma levels of vascular endothelial growth factor (VEGF) and platelet activating factor (PAF) were detected by ELISA. Results Hemodynamics parameters were significantly improved in group PR superior to group CR after burns. Levels of VEGF and PAF were significantly lower in group PR than in group CR. Organ function parameters were also greatly preserved in group PR, relative to groups CR and NR. Lactic acidosis was fully corrected and survival increased in group PR (50.0%), compared to group CR (20.0%). Conclusion Pyr-ORS was more effective than Cit-ORS in improving hemodynamics, visceral blood perfusion and organ function by alleviating vasopermeability-induced visceral edema and plasma volume loss in dogs with severe burn.

Primary hepatic neuroendocrine tumor (PHNET) is an extremely rare liver neoplasm, and its clinical characteristics and imaging features are not well understood. The aim of this study was to analyze the clinical profiles and imaging features of PHNETs on contrast-enhanced ultrasound (CEUS) and computed tomography (CT) METHODS: Patients with PHNET between January 2008 and December 2015 were retrospectively identified, and their demographics, laboratory data, and imaging characteristics on CEUS and CT analyzed.Ten consecutive patients with PHNETs were included (including one G1, seven G2, and two G3 of tumor grades).The median age of patient was 45 years (range: 27-72 years), and 60.0% of patients were male. The most common symptom was abdominal pain (60.0%), and cirrhosis was found in 40.0% of patients. Tumors were confined within the liver in 60.0% of patients, while the remaining patients had extra-hepatic metastasis. The tumors revealed hyperechoic in 60% of patients and mixed echoic in 30% of patients on conventional US, displaying intense arterial enhancement followed by washout in the portal and/or the late phases in 80.0% of patients on CEUS and 60% at CT.Although PHNET is a very rare liver tumor, it should be considered as a possible differential diagnosis in the management of hepatic tumors. Most PHNETs were hyperechoic or mixed echoic on conventional US, showing similar enhancement patterns to that of hepatocellular carcinoma on CEUS.

Many premature newborns develop bronchopulmonary dysplasia (BPD), a chronic lung disease resulting from prolonged mechanical ventilation and hyperoxia. BPD survivors typically suffer long-term injuries not only to the lungs, but also to the brain and retina. However, currently it is not clear whether the brain and retinal injuries in these newborns are related only to their prematurity, or also to BPD. We investigated whether the hyperoxia known to cause histologic changes in the lungs similar to BPD in an animal model also causes brain and retinal injuries. Sprague Dawley rat pups were exposed to hyperoxia (95% O2, ‘BPD’ group) or room air (21% O2, ‘control’ group) from postnatal day 4–14 (P4–14); the rat pups were housed in room air between P14 and P28. At P28, they were sacrificed, and their lungs, brain, and eyes were extracted. Hematoxylin and eosin staining was performed on lung and brain sections; retinas were stained with Toluidine Blue. Hyperoxia exposure resulted in an increased mean linear intercept in the lungs (P, Summary: Our results suggest that the same animal model of chronic neonatal hyperoxia can be used to simultaneously study lung, brain and retinal injuries related to hyperoxia.

The goal of this study was to compare the predictive ability of the Status Epilepticus Severity Score (STESS), the Encephalitis-nonconvulsive status epilepticus (NCSE)-Diazepam resistance-Image abnormalities-Tracheal intubation (END-IT), and the combination of these two scoring tools to predict mortality among inhospital patients with status epilepticus (SE).A retrospective analysis was conducted of adult patients with SE who were admitted to the neurology department, the emergency department, and the intensive care unit from January 2013 to December 2017. The patients were divided into two groups: survivors and nonsurvivors. The STESS data were obtained when the patient arrived at the hospital, and the END-IT data were collected 24 h after patients were initially treated in the hospital. The ability of the scoring tools to predict death in patients with SE, alone or in combination, was evaluated.A total of 123 patients with SE were included in the study, of which 22 died, for a mortality rate of 17.9%. The STESS and END-IT scores of nonsurvivors were both significantly higher than those of survivors (median STESS 4 vs. 2, p = 0.003; median END-IT 3 vs. 1, p 0.001). The area under the receiver operating characteristic curve (AUC) was 0.698 for the STESS and 0.852 for the END-IT, and the cutoff values were 4 and 3, respectively. The AUC of the END-IT with the optimal cutoff value was larger than that of the STESS (p = 0.024). The sensitivity and specificity of combining the STESS and END-IT by the serial method (STESS ≥ 4∩END-IT ≥ 3) were 0.50 and 0.95, respectively, and the specificity was significantly higher than the STESS or END-IT (both p's 0.001). The sensitivity and specificity of combining the STESS and END-IT by the parallel method (STESS ≥ 4⋃END-IT ≥ 3) were 0.91 and 0.53, respectively, and the sensitivity was higher than the STESS was (p = 0.016).Our results indicated that the combined score of the STESS and END-IT systems was a better predictor of survival of patients with SE than the scores of either the STESS system or the END-IT system alone and that combining the scores may be considered to be a new method for early identification of patients for both good and bad outcomes.

There is accumulating evidence that decreased histone acetylation is involved in normal aging and neurodegenerative diseases. Recently, we found that ANP32A, a key component of INHAT (inhibitor of acetyltransferases) that suppresses histone acetylation, increased in aged and cognitively impaired C57 mice and expressing wild-type human full length tau (htau) transgenic mice. Downregulating ANP32A restored cognitive function and synaptic plasticity through upregulation of the expressions of synaptic-related proteins via increasing histone acetylation. However, there is no direct evidence that ANP32A can induce neurodegeneration and memory deficits. In the present study, we overexpressed ANP32A in the hippocampal CA3 region of C57 mice and found that ANP32A overexpression induced cognitive abilities and synaptic plasticity deficits, with decreased synaptic-related protein expression and histone acetylation. Combined with our recent studies, our findings reveal that upregulated ANP32A induced-suppressing histone acetylation may underlie the cognitive decline in neurodegenerative disease, and suppression of ANP32A may represent a promising therapeutic approach for neurodegenerative diseases including Alzheimer's disease.

Our previous studies have demonstrated the protective effects of an edible mushroom Pleurotus eryngii against the colitis in mice. Herein, an itraq-based proteomics analysis has been utilized to es...

Endometriosis is regarded as a hormone-dependent disease. Current therapeutic approaches to treating this common gynecological disorder mainly depend on surgical and hormonal interventions, but the high rate of disease recurrence as well as the side effects related to such therapies make it difficult for patients to recover completely. Molecular evidence has recently suggested that the source of endometriosis can be both hormone-dependent and influenced by the dysregulation of some signaling cascades. In this review, we focus on the non-hormonal triggers of endometriosis and the pre-clinical compounds designed to correct these signaling defects in order to achieve a better understanding of the disease as well as novel approaches to treating it.

We conducted a joint (pooled) analysis of three genome-wide association studies (GWAS) of esophageal squamous cell carcinoma (ESCC) in individuals of Chinese ancestry (5,337 ESCC cases and 5,787 controls) with 9,654 ESCC cases and 10,058 controls for follow-up. In a logistic regression model adjusted for age, sex, study and two eigenvectors, two new loci achieved genome-wide significance, marked by rs7447927 at 5q31.2 (per-allele odds ratio (OR) = 0.85, 95% confidence interval (CI) = 0.82-0.88; P = 7.72 × 10(-20)) and rs1642764 at 17p13.1 (per-allele OR = 0.88, 95% CI = 0.85-0.91; P = 3.10 × 10(-13)). rs7447927 is a synonymous SNP in TMEM173, and rs1642764 is an intronic SNP in ATP1B2, near TP53. Furthermore, a locus in the HLA class II region at 6p21.32 (rs35597309) achieved genome-wide significance in the two populations at highest risk for ESSC (OR = 1.33, 95% CI = 1.22-1.46; P = 1.99 × 10(-10)). Our joint analysis identifies new ESCC susceptibility loci overall as well as a new locus unique to the population in the Taihang Mountain region at high risk of ESCC.