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Objective: To analyze the levels of high mobility group box 1 (HMGB1) protein on different courses of juvenile idiopathic arthritis (JIA)., Methods: In our prospective longitudinal study, children with JIA were included with their blood samples collected at the first visit, 1-month, 3-month, and 6-month follow-up, respectively. Samples were also collected from healthy controls and children with reactive arthritis at the first visit. Levels of HMGB1 were determined using enzyme-linked immunosorbent assays. Clinical disease characteristics and routine laboratory findings were analyzed as well., Results: A total of 64 children were enrolled, of whom 31 (48.4%) were female. The median age at the first visit for participants with JIA was 9.25 years (range, 1.42-15.42) and the median duration of disease was 2.38 months (range, 1.53-49.31). Serum HMGB1 levels at the first visit were significantly elevated in children with systemic JIA compared with other groups, and so were in enthesitis-related arthritis versus healthy controls. Significant correlations were established at the first visit between HMGB1 levels and duration of disease, C-reactive protein, percentage of neutrophils, and ferritin. Data from all samples revealed that serum HMGB1 levels in JIA were significantly associated with erythrocyte sedimentation rates, C-reactive protein, percentage of neutrophils, and disease activity scores., Conclusions: Serum HMGB1 may be associated with clinical disease activity of JIA and specifically increased at the first visit in children with systemic JIA, suggesting its function as a sensitive inflammatory marker. Further large-scale studies are warranted to explore its spectrum in JIA., (© 2021. The Author(s).)

Objective: To explore the clinical characteristics and risk factors of pediatric patients with Wiskott-Aldrich syndrome (WAS). Methods: This was a case-control study. Clinical data of 165 cases of pediatric patients with WAS, who visited the Department of Rheumatology, Children's Hospital of Chongqing Medical University between January 2007 and August 2020 were retrospectively analyzed and divided into death group and survival group (control group) according to the prognosis in the follow-up. Two independent samples t -test, Welch approximate t -test, Mann-Whitney U test, Pearson χ² test, Yates corrected χ² test, or Fisher exact probability test were used for comparison between groups. Risk factors were analyzed by multivariate Logistic regression analysis. Results: A total of 165 patients with Wiskott-Aldrich syndrome were enrolled in this study, including 40 cases in the death group and 125 cases in the survival group. The WAS score was (4.1±0.8) score in the death group and (3.1±1.2) score in the survival group. The age was 19 (9, 28) months in the death group and 60 (36,86) in the survival group. The episode rates of recurrent infection and (or) severe infection, intracranial hemorrhage and eczema in the death group were significantly higher than those in the survival group (95.0% (38/40) vs. 32.0% (40/125),25.0% (10/40) vs. 2.4% (3/125), 90.0% (36/40) vs. 72.0% (90/125), χ²=48.253, 18.325, 5.440, all P <0.05). Infection (22 cases, 55.0%) and intracerebral hemorrhage (15 cases, 37.5%) were the main causes of death, 3 cases (7.5%) died of severe graft-versus-host disease after transplantation. The Logistic regression model indicated that repeated infection and (or) severe infection and non-use of intravenous immunoglobulin (IVIG) replacement therapy were risk factors for death in Chinese WAS patients ( OR values were 8.999 and 2.860, 95% CI were (2.041-39.667) and (1.375-5.950), respectively, all P <0.05). Conclusions: Recurrent and (or) severe infection is the main risk factor of death for WAS patietns. Regular IVIG treatment can improve the survival rate of patients with WAS.

Osteosarcoma (OS) is a lethal bone malignancy. Circular RNAs (circRNAs) have emerged as important regulators of OS development. CircRNA cyclin dependent kinase 14 (circ&#95;CDK14) was reported to be a potential oncogene in OS. However, the mechanistic pathway by which circ&#95;CDK14 functions in OS is largely unknown. The relative expression of circ&#95;CDK14, microRNA (miR)-520a-3p, and GRB2 Associated Binding Protein 1 (GAB1) was evaluated by quantitative real-time PCR and western blot assays. Flow cytometry was employed to monitor cell cycle distribution and apoptosis. Methyl thiazolyl tetrazolium (MTT) and colony formation assays were performed to assess cell viability and colony formation ability, respectively. Western blot assay was also used to detect the expression of apoptosis-related proteins. Transwell assay was carried out to monitor cell migration and invasion. Additionally, the target association between miR-520a-3p and circ&#95;CDK14 or GAB1 was confirmed by a dual-luciferase reporter assay. Xenograft assay was applied to investigate the role of circ&#95;CDK14 in vivo. Circ&#95;CDK14 and GAB1 expression was upregulated, while miR-520a-3p was downregulated in OS tissues and cells. Circ&#95;CDK14 depletion hindered OS cell proliferation, metastasis, and tumorigenesis while facilitated apoptosis, which were all ameliorated by miR-520a-3p inhibition. Circ&#95;CDK14 could sponge miR-520a-3p. miR-520a-3p targeted GAB1 to repress OS cell proliferation and metastasis. Circ&#95;CDK14 knockdown blocked OS tumor growth in vivo. Circ&#95;CDK14 might positively affect OS development by modulating the miR-520a-3p/GAB1 axis.

Objective: To analyze the clinical characteristics of congenital agammaglobulinemia and the efficacy of intravenous immunoglobulin (IVIG) replacement therapy for this disease. Methods: The basic characteristics, clinical manifestations, laboratory examinations, and outcomes of 114 patients with congenital agammaglobulinemia diagnosed in Children's Hospital of Chongqing Medical University from January 1988 to April 2020 were retrospectively analyzed. The efficacy of IVIG in improving the clinical symptoms between regular and irregular treatment groups were compared by χ 2 test. To explore the clinical characteristics associated with delayed diagnosis and treatment, the patients were also stratified into following subgroups: non-cough, short-term cough and long-term cough groups, chronic lung disease and non-chronic lung disease groups, and arthritis and non-arthritis groups. The age at onset, age at diagnosis, time consumed for diagnosis, initial time of immunoglobulin replacement, dose of IVIG, IgG trough level between the above groups were compared by t test, F test or non-parametric test. Results: All the 114 patients were male, with the onset age of (22±18) months. The age at diagnosis was (89±54) months, time consumed in diagnosis was (63±46) months, and the initial time of immunoglobulin replacement was (75±45) months. A total of 66 patients had been followed up to April 2020, with a follow-up period of (54±41) months. Among these children, 42 (63.6%) received regular infusion, whose monthly IVIG dose was (538±105) mg/kg and IgG trough level was (5.8±1.5) g/L, whereas 24 patients (36.4%) were treated irregularly. There was no significant difference in the improvement rate of fever, cough, sinusitis, diarrhea, otitis media and arthritis between regular and irregular IVIG replacement groups (all P >0.05). Sixty-one out of the 66 patients (92.4%) had fever before IVIG treatment, whose fever episodes were significantly decreased after IVIG treatment (5 (2,12) vs . 0 (0, 1) per year, Z =-6.436, P< 0.01). Sixty patients (90.9%) suffered from wet cough before treatment and 36 (54.5%) after treatment. Initial time of immunoglobulin replacement was significantly delayed in the long-term cough (27 cases) and short-term cough groups (9 cases) compared with non-cough group (18 cases) ((97±51) vs . (64±41) vs . (63±42) months, F =3.554, P =0.035). Twenty-nine patients (43.9%) were diagnosed with chronic lung disease, whose initial time of immunoglobulin replacement (103 (75,144) vs . 46 (26,64) months, Z =-4.330, P< 0.01), age at diagnosis (103 (75,142) vs . 47 (31,68) months, Z =-3.486, P< 0.01), and time consumed in diagnosis (91 (55,129) vs . 29 (10,41) months, Z =-4.386, P< 0.01) were significantly later and longer than those in children without chronic lung disease (37 cases). In addition, thirty-two patients(48.5%) were diagnosed with arthritis, whose initial time of immunoglobulin replacement ((98±51) vs . (58±39) months, t =3.420, P =0.001) and time consumed in diagnosis ((74±49) vs . (44±40) months, t =2.600, P =0.010) were also significantly later and longer than those in children without arthritis (34 cases). Conclusions: After immunoglobulin replacement therapy, the clinical symptoms such as fever, sinusitis, diarrhea, and otitis media can be improved more or less. However, long-term wet cough, chronic lung disease, and arthritis are still prominent clinical problems, which could be controlled by standard immunoglobulin replacement therapy in some patients.

Background: Low cardiac output syndrome is the main cause of death after pericardiectomy., Methods: Patients who underwent pericardiectomy for constrictive pericarditis from January 2009 to October 2020 at our hospital were included in the study. Histopathologic studies of pericardium tissue from every patient were performed. All survivors were followed up., Results: Ninety-two consecutive patients underdoing pericardiectomy were included in the study. The incidence of postoperative low cardiac output syndrome was 10.7% (10/92). There were five operative deaths. Mortality and incidence of LCOS in the group with pericardial effusion were significantly higher than those in the group without pericardial effusion. Tuberculosis of the pericardium (60/92, 65.2%) was the most common histopathologic finding in this study. Both univariate and multivariate analyses showed that preoperative pericardial effusion is associated with increased rate of low cardiac output syndrome. Eighty-five survivors were in NYHA class I (85/87, 97.7%), and two were in class II (2/87, 2.3%) at the latest follow up., Conclusions: Preoperative pericardial effusion is associated with low cardiac output syndrome after pericardiectomy. Tuberculosis of the pericardium was the most common histopathologic finding in this study. For constrictive pericarditis caused by tuberculous bacteria, systematic antituberculosis drugs should be given. Preoperative pericardial effusion is associated with increased rate of low cardiac output syndrome. Perfect preoperative preparation is very important to reduce the incidence of postoperative low cardiac output syndrome and mortality. It is very important to use a large dose of diuretics with cardiotonic or vasopressor in a short time after the operation.

Background: MicroRNAs were reported to be involved in the progression of intervertebral disc degeneration (IDD). This study focused on the potential prognostic value and the underlying mechanism of miR-182 in IDD., Methods: The expression level of miR-182 in plasma samples from 60 IDD patients and 60 healthy controls were examined in the present study. Then, the relationship between miR-182 expression and clinical features of IDD patients was analyzed. Moreover, the nucleus pulposus (NP) cells were cultured and transfected with either miR-182 inhibitor, mimics, or NC to explore the effects of miR-182 on cell proliferation and apoptosis. Furthermore, expression levels of proliferation and apoptosis-related proteins Bcl-2, Bax, and Caspase-3 were also evaluated., Results: The expression level of miR-182 was dramatically increased in plasma samples of IDD patients compared with the controls. Moreover, ROC analysis indicated that miR-182 was a feasible diagnostic indicator for the diagnosis of IDD. According to the Japanese Orthopaedic Association (JOA) score, the prognosis of patients with the lower expression levels of miR-182 was better than for those with the higher expression levels of miR-182 in IDD. Furthermore, the miR-182 inhibitor significantly increased the proliferation, decreased the apoptosis of human NP cells, and altered the expression of proliferation and apoptosis-related proteins Bcl-2, Bax, and Caspase-3. On the contrary, miR-182 mimics notably inhibited proliferation but promoted apoptosis of human NP cells and increased Bax and Caspase-3 expressions while reducing the Bcl-2 level., Conclusions: miR-182 was negatively correlated with the prognosis of the IDD patients and affected the proliferation and apoptosis of NP cells in vitro.

Background: Mitral repair has been widely used in the treatment of secondary mitral lesions in recent years. Hemolytic anemia is known to be a rare complication after mitral repair. This study aimed to investigate the diagnosis and treatment of mechanical hemolysis after mitral repair in adults., Methods: In this retrospective study, we reviewed the medical records of patients undergoing mitral repair complicated with mechanical hemolysis at our institution between August 2006 and May 2020., Results: Twenty-four patients undergoing mitral repair complicated with mechanical hemolysis were included in the study. They were divided into two groups: the reoperation group (patients who underwent reoperation; N = 18) and the conservative treatment group (patients who received symptomatic treatments, including blood transfusion, diuresis, alkalization of urine, liver protection, hemodialysis, and oral metoprolol; N = 6. All patients in the reoperation group underwent mitral valve replacement. There were six hospital deaths, all in the conservative treatment group. Seventeen of eighteen patients (94.4%) completed follow up. Fifteen of seventeen survivors (88.2%) were in NYHA class I and 11.8% (2/17) in NYHA class II at the last time follow up., Conclusions: Hemolysis is a sign of failure of mitral repair. Reoperation is the best choice once the hemolysis has been diagnosed. Reoperation should be carried out as soon as possible., (2021 Forum Multimedia Publishing, LLC)

Objective: We conducted a systematic review and network meta-analysis to compare the efficacy and safety of nine non-steroidal anti-inflammatory drugs (NSAIDs) in treating patients with juvenile idiopathic arthritis (JIA)., Methods: Randomized controlled trials (RCTs) of NSAIDs for the treatment in children with JIA were searched systematically by using MEDLINE, EMBASE, and the Cochrane Library for available literature up to January 1, 2019. Bayesian network meta-analysis was used to combine direct and indirect evidence on treatment effectiveness and safety., Results: Eight eligible RCTs involving 1112 patients with JIA were identified, addressing 9 interventions. The ranking probability plot based on the surface under the cumulative ranking curve (SUCRA) indicated that celecoxib (6 mg/kg twice-a-day) had the highest probability of being most effective (SUCRA = 76.4%) among four NSAIDs (celecoxib, rofecoxib, meloxicam, and naproxen). Also, rofecoxib (0.3 mg/kg once-a-day) and piroxicam demonstrated a higher probability of safety in treating children with JIA (SUCRA = 33.0% and 35.5%, respectively), compared with other interventions., Conclusions: The quality of available evidence limits the formation of powerful conclusions regarding the comparative efficacy or safety of NSAIDs used to treat JIA.

Objective: To assess the long-term clinical efficacy of TiRobot-assisted percutaneous cannulated screw fixation in the treatment of femoral neck fractures., Methods: This retrospective study included 50 patients with unilateral femoral neck fractures who were treated with TiRobot-assisted percutaneous cannulated screw fixation from September 2017 to May 2018. After at least 2 years of follow-up, the results of treatment, including operation duration, frequency of fluoroscopy use, intraoperative bleeding, hospital stay, medical expense, screw placement accuracy, rate of fracture healing and necrosis of the femoral head, and Harris hip scores at the last follow up, were recorded and compared with those of 83 matched patients who underwent conventional manual positioning surgery., Results: The TiRobot group had longer operation duration (83.3 ± 31.2 min vs 44.1 ± 14.8 min) and higher medical expenses (28,407.1 ± 7498.0 yuan vs 22,672.3 ± 4130.3 yuan) than the conventional group. The TiRobot group had significantly less intraoperative bleeding (11.3 ± 7.3 mL vs 51.6 ± 40.4 mL) and shorter hospital stay (8.6 ± 2.8 days vs 11.1 ± 3.41 days) than the conventional group. Screw parallelism (1.32° ± 1.85° vs 2.54° ± 2.99° on anteroposterior radiograph; 1.42° ± 2.25° vs 3.09° ± 3.63° on lateral radiograph) and distance between screws (58.44 ± 10.52 mm vs 39.69 ± 12.17 mm) were significantly improved. No significant difference was found between the two groups in terms of the use of fluoroscopy (40.1 ± 28.5 times vs 38.6 ± 21.0 times) and Harris hip scores at the last follow-up (93.2 ± 10.3 points vs 88.4 ± 11.9 points). Two cannulated screws penetrated the femoral head during manual insertion in the conventional group but not in the TiRobot group. The rate of nonunion and necrosis of the femoral head in the TiRobot group was reduced compared with that in the conventional group (0 vs 7.2%; 6.0% vs 24.1%)., Conclusion: TiRobot-assisted percutaneous cannulated screw fixation of femoral neck fractures is accurate and minimally invasive and helps in reducing late complications, particularly necrosis of the femoral head and nonunion of fractures., (© 2021 The Authors. Orthopaedic Surgery published by Chinese Orthopaedic Association and John Wiley & Sons Australia, Ltd.)

As a marker of eosinophilic airway inflammation, fractional exhaled nitric oxide (FeNO) was widely used in clinical practice. NIOX VERO (VERO) and SUNVOU-CA2122 (CA2122) are two commonly used eNO analyzers in China. However, what's the difference and agreement between the two devices and whether the two types of devices can be replaced by each other in the application of common respiratory diseases have not been reported. The purpose of this study was to compare the two types of devices and to evaluate the difference between them in clinical use and whether they could be replaced. FeNO levels in 244 respiratory patients (including asthma, chronic obstructive pulmonary disease, chronic cough) were measured by CA2122 analyzer and VERO analyzer, respectively. The FeNO values obtained by the two devices were compared and the differences were analyzed. The success rate, the number of attempts and the total time required for a successful measurement by CA2122 and VERO were compared. The FeNO values measured by CA2122 online and offline were also compared. FeNO values obtained by CA2122 were slightly higher than those of VERO [median(range): 29.0(9-271) parts per billion (ppb) vs 25.5 (5-263) ppb, P = 0.000]. There was a high correlation between FeNO values measured by the two types of devices ( r = 0.964, P = 0.000). By comparison, there was a high degree of agreement between the FeNO values measured by two devices, in all patients with different respiratory diseases. FeNO values measured online and offline by CA2122 were highly correlated and there was a high degree of agreement between online and offline methods. The success rate of CA2122 was higher than VERO, and the number of attempts (2.1 vs 2.4) and the total time (110.5 ± 35.7 vs 117.5 ± 48.1 s) required for a successful measurement by CA2122 were lower than those of VERO. CA2122 and VERO can be replaced by each other, and FeNO values can be converted if necessary. CA2122 has some advantages in success rate, the mean attempts and time required for successful measurement of FeNO., (Creative Commons Attribution license.)

Objective: To elucidate the relationship between the myositis autoantibodies and clinical phenotypes of juvenile dermatomyositis (JDM) . Methods: A total of 76 JDM patients admitted to the Children's Hospital of Chongqing Medical University from January 2017 to May 2020 were tested for myositis autoantibodies, including myositis-specific autoantibodies (MSAs) and myositis-associated autoantibodies (MAAs). Kruskal-Wallis test and logistic regression were used to analyze the relationship between the antibodies and clinical characteristics. Results: In the 76 cases, 37 were females and 39 males. Forty-three cases (53%) were MSAs positive, among which the most common subtypes were autoantibodies against nuclear matrix protein 2 (NXP2) (15/76, 20%), melanoma differentiation-associated protein 5 (MDA5) (13/76, 17%) and transcription intermediary factor 1 gamma (9/76, 11%). While 20 cases (26%) were positive for MAAs, among which anti-Ro-52 antibody (17/76, 22%) was the most common subtype. Sixteen patients (21%) had both MAAs and MSAs. The incidences of arthritis (9 cases), fever (8 cases), skin ulcers (5 cases) and macrophage activation syndrome (MAS) (1 case) were significantly higher in the patients with anti-MDA5 antibody among the antibody groups. Dysphasia (6 cases) and edema (8 cases) mainly occurred in patients with anti-NXP2 antibody. Children with anti-MDA5 antibody were more likely to develop arthritis ( OR =10.636, 95%CI: 2.770-40.844, P =0.001), skin ulcers ( OR =12.500, 95%CI: 2.498-62.522, P =0.002), fever ( OR =5.600, 95%CI: 1.580-19.849, P =0.008) and interstitial lung disease (ILD) ( OR =23.333, 95%CI: 4.750-114.616, P <0.01). In the patients with different subtypes of MSAs, the creatine kinase value was significantly lower in the anti-MDA5 group than those in the anti-aminoacyl-tRNA synthetase ( P =0.03), anti-NXP2 ( P <0.01), and MSAs-negative group ( P =0.013). Conclusions: Most children with JDM have positive myositis autoantibodies, and will present with different clinical phenotypes based on different autoantibodies. And children with anti-MDA5 antibodies are likely to develop ILD and MAS. Therefore the detection of myositis-specific autoantibodies is important.

Different therapeutically active ingredients, from plants, animals, and mineral sources, are prescribed as traditional Chinese medicines (TCM). TCMs, from animal sources, are rich in proteins and peptides. Different advanced proteomics technologies, such as two-dimensional gel electrophoresis (2-DE), multi-dimensional liquid chromatography (MDLC), matrix-assisted laser desorption/ionization-time of flight mass spectrometry (MALDI-TOF-MS), and isobaric tags for relative and absolute quantitation (iTRAQ), have been applied to analyze TCMs, from animal sources. This paper reviews the common proteomic techniques for analyzing animal - derived TCMs. Various scientific studies have reported the application of proteomics for locating drug targets, identifying active components, and elucidating the mechanisms of action of animal - derived TCMs. However, these researches are still at the preliminary stage. This review has also discussed the existing challenges and future directions in this field of research., Competing Interests: Declaration of Competing Interest The authors report no declarations of interest., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Lessons Learned: Treatment with the Aurora kinase A inhibitor yields often durable disease control, but limited tumor regression, in heavily pretreated patients with unresectable malignant pleural or peritoneal mesothelioma. In a limited sample size, MYC copy-number gain or gene amplification, a candidate predictive biomarker for alisertib, did not correlate with improved response numbers or patient outcomes., Background: Malignant mesothelioma is an aggressive disease for which few effective therapies are available. The Aurora family kinases are critical for mitotic fidelity and highly expressed in mesothelioma, wherein their inhibition leads to growth arrest in vitro. We evaluated the efficacy of alisertib, an Aurora A kinase inhibitor, in relapsed malignant mesothelioma., Methods: Twenty-six patients with previously treated, unresectable pleural or peritoneal mesothelioma were enrolled on a single-arm, single-institution phase II trial of alisertib at a dosage of 50 mg twice daily for 7 of every 21 days. The primary endpoint was 4-month disease control rate. Secondary endpoints included overall response rate, progression free survival, overall survival, safety/toxicity, and correlation of endpoints with MYC copy number., Results: Of the 25 evaluable patients treated on study, 8 (32%) experienced 4-month disease control, surpassing the futility endpoint. There were no confirmed partial or complete responses. Median progression-free and overall survival were 2.8 months and 6.3 months, respectively. No associations between MYC copy number and outcomes were observed., Conclusion: Alisertib has modest activity in this unselected malignant mesothelioma population. Several patients achieved durable disease control. Although the study did meet its prespecified futility endpoint, the sponsor elected to close the trial at the interim analysis., (© 2020 The Authors. The Oncologist published by Wiley Periodicals LLC on behalf of AlphaMed Press.)

DNA methylation has been identified as one of the important causes of tumorigenesis, so it is important to develop some advanced methods for detecting and quantifying DNA methylation. In this study, a label-free and enzyme-free one-step rapid colorimetric detection of DNA methylation based on unmodified Au nanoparticles(Au NPs)has been proposed. This method can quickly, efficiently, economically and easily colorimetric detect methylated DNA only by the color change of unmodified Au NPs solution without the covalent modification of Au NPs in advance or complicated instruments for implementation with practical limitations or expensive biological enzymes or traditional organic dyes during the reaction. The strategy employed the difference in electrostatic attraction of single-stranded DNA and double-stranded DNA against salt-induced aggregation of Au NPs. The method has a DNA methylated detection limit of 8.47 nM and it is distinctly visible to detect methylated DNA with the naked eye as low as 20 nM. Furthermore, the strategy has an ability to detect methylated DNA in the presence of abundant unmethylated DNA with the detection limit of 0.13% and as low as 1% methylated DNA can be distinguished in heterogeneous samples with the naked eye. Also, the stratagem provides a convenient and rapid platform for methylated DNA detection of human serum samples in one step, which displays a huge potential for clinical diagnosis and treatment of oncological diseases., Competing Interests: Declaration of competing interest The author(s) declare that they have no competing interests., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Our aim was to investigate factors predicting blood pressure (BP) variability during diagnostic cerebral angiography and associations between BP variability and clinical outcomes in patients with acute and subacute ischemic stroke and intracranial artery stenosis. 114 patients with ischemic stroke and intracranial artery stenosis (stenosis rate >50%) were recruited. Patients who underwent cerebral angiography within 3 days and 3-14 days of disease onset are referred to be Group A and Group S, respectively. BP variability in Group A was defined as the coefficient of variance (CV) of BP. Univariate and multivariate regression analyses were used to identify predictors of CV of BP and associations between CV of BP and clinical outcomes at discharge. In Group A patients, advanced age was associated with increased CV of SBP and diastolic blood pressure (DBP), and antihypertensive use was associated with lower CV of SBP. Male was associated with lower CV of DBP. In Group S, higher CV of SBP was associated with hypertension and antihypertensive use. Males had lower CV of SBP than females. The calcium channel blocker was associated with lower CV of DBP. Higher scores of the Stroke Scale at admission were significantly associated with poor clinical outcomes for both groups, while BP variability was not. Factors associated with BP variability are significantly different between stroke patients undergoing angiography within 3 days vs. 3-14 days after disease onset. BP variability is not significantly associated with clinical outcomes at discharge., Competing Interests: The authors declare that there are no conflicts of interest., (Copyright © 2020 Hui Pan et al.)

Objectives: The aim of this study was to determine the therapeutic effects of tetrahydropalmatine (Tet) on disseminated intravascular coagulation (DIC) by exploring the role of Tet using a lipopolysaccharide (LPS)-induced DIC model. Methods/Materials: We established a mouse DIC model by injecting LPS. Hematoxylin-eosin (HE) staining was performed to detect liver and kidney damage. Blood samples were obtained to determine liver and kidney injury indexes, coagulation indexes, and inflammatory cytokines. An in vitro cell inflammation model was also established. Tumor necrosis factor-α (TNF-α) levels and nuclear factor kappa B (NF-κB) signaling pathway activation were determined by western blot., Result: Tet ameliorated the damage to organ tissues, improved coagulation indexes, and reduced the inflammatory cytokine production in LPS-induced mouse DIC. Tet also inhibited TNF-α expression by suppressing NF-κB signaling pathway activation in an in vitro LPS model using RAW 264.7 macrophages., Conclusions: Tet has a mitigating and therapeutic effect on the LPS-induced DIC model via anticoagulant and anti-inflammatory effects, showing its potential as an adjunct to DIC treatment.

Aim: Search for a new class of potential antidiabetic agents. Methodology: A series of novel peptidomimetics bearing the p -aminobenzoic acid moiety ( TM3 - TM6 ) were designed and synthesized. For all synthetic target molecules, the peroxisome proliferator response element (PPRE) activated activities have been evaluated and the toxicity were computed. Results & discussion: 46 new p -aminobenzoic acid derivatives have been characterized by 1 H NMR, 13 C NMR and high-resolution mass spectrometry (HRMS). The results of in vitro PPRE-activated activity, molecular docking study and toxicity prediction revealed that these compounds had potential antidiabetic activities and low toxicity. In particular compound 3b had up to 87% PPRE-activated activity compared with pioglitazone. This discovery may provide new insights for finding novel PPRE lead compound.

Objective: To analyze the clinical , immunological and genetic features of a child with BCL11B mutation induced neurodevelopmental disorder. Methods: The clinical data and genetic test of a child with BCL11B mutation hospitalized in the Department of Rheumatology and Immunology in Children's Hospital of Chongqing Medical University in December 2018 were extracted and analyzed. The literature was searched with "BCL11B mutation" and "immunodeficiency 49" as key words in Chinese databases and Pubmed until January 2019 was reviewed. Results: A male patient aged 3 years and 11 months with facial dysmorphisms and delayed language and motor development was admitted due to neurodevelopmental retardation over two years. Laboratory tests showed normal human immunoglobulin (IgG 12.90 g/L, IgA 1.02 g/L, IgM 1.15 g/L, IgE 532 000 U/L), Trec (228) and proliferation of T and B cells. The lymphocyte subsets revealeda reduced percentage of B cells (0.108) but normal absolute numbers (0.574×10(-3)/L), and an increased percentage (0.828) as well as absolute numbers (4.415×10(-3)/L) of T cells. A heterozygous BCL11B mutation was detected by sanger sequencing, showing a de novo frameshift mutation c.1887&#95;c.1893delCGGCGGG in exon 4. Two papers were found which were all in English, with total of 14 patients(13 patients with complete information). Thirteen mutations were reposed, including 7 frameshift, 2 nonsense, 2 missense, and 2 chromosomal rearrangements; Thirteen patients had heterozygous mutations. All patients had delayed language and motor development and facial dysplasia which were mainly hypertelorism, thin eyebrows and small palpebral fissures. Some patients had dental anomalies, ametropia and allergy, and a few were combined with immune impairment, but without overt signs of immunodeficiency. Only one patient had multisystem anomalies and profound immune deficiency. Conclusions: BCL11B is essential for development of the nervous and the immune system. In this study, the de novo mutation of BCL11B gene resulted in neurodevelopmental and immunological disorders.

Background: Juvenile idiopathic arthritis (JIA) is a chronic inflammatory disease that includes seven heterogeneous subgroups with different prognoses. In particular, polyarticular JIA (pJIA) has a longer period of active disease and a poorer prognosis. Tumor necrosis factor (TNF)-alpha inhibitors are effective in patients with pJIA, but the therapeutic regimen remains controversial. Here, we performed a single-center study to determine the potential correlation between TNF-alpha inhibitor (infliximab) therapy and outcomes in these patients., Methods: Clinical data of 40 pJIA patients were collected at our center from January 1, 2010 to January 1, 2018, and patients were grouped according to the timing of infliximab therapy. The erythrocyte sedimentation rate (ESR), the number of joints with active disease, and the 27-point juvenile arthritis disease activity score (JADAS-27) were analyzed., Results: The ESR, the active joint count, and the JADAS-27 decreased significantly in all groups after 3 months (P = 0.041/0.415/0.008, 0.022/0.030/ < 0.001, and 0.05/0.012/ < 0.001, respectively) and 6 months (P = 0.036/0.045/0.041, 0.076/0.037/ < 0.001, and 0.096/0.006/ < 0.001, respectively) of infliximab treatment, although the rates of change of these parameters were similar. However, after 12 months, only patients treated with infliximab within 3 months of disease onset had a stable ESR, active joint count, and JADAS-27, while these parameters increased sharply when infliximab was administered 3 months and especially 1 year after disease onset., Conclusions: TNF-alpha is a pleiotropic pro-inflammatory cytokine of crucial importance in the pathogenesis of JIA. Infliximab can improve the outcomes of patients with pJIA significantly, and should be introduced early during the clinical course.

In order to improve water quality, many urban lakes in China have undergone environmental restoration since the introduction of China's tenth five-year plan. To understand the effectiveness of improvement projects on eutrophic urban lakes, we analyze the changes in water quality of Lihu Lake over the past 30 years, i.e., before and after comprehensive remediation. We use long-term monitoring data from TLLER and from two regional investigations undertaken in 2017. The results were as follows. ① Concentrations of total nitrogen (TN) and total phosphorus (TP), the permanganate index, and chlorophyll-a (Chl-a) in Lihu Lake all increased dramatically since the 1990s and reached the worst levels during the period from 1997 to 2003. After comprehensive improvement measures for the lake undertaken by the local government in 2003, the water quality improved remarkably year by year, but reduced slightly in the past two years assessed here. There was no obvious improvement in water transparency when comparing data from before to after the remediation. ② Before the improvement measures, the water quality fluctuated greatly with season, however, water quality sampled during the winter post remediation was significantly better than during the summer. ③ Spatially, the water quality in the western region of Lihu Lake was significantly better than of that in the eastern region. When comparing government measures in different eutrophic urban lakes, we found that engineering management measures can improve the water quality of urban lakes over a relatively short time period. However, after the water quality has been improved, it is necessary to restore the macrophyte-dominated ecosystem, which should be supplemented by ecological restoration based on biological regulation. By improving species diversity, the aquatic ecosystem can be successfully transformed from being phytoplankton-dominated to macrophyte-dominated, thereby enabling the service functions of a lake ecosystem to be truly restored.

Recurrent spontaneous abortion (RSA) is a common health problem that affects 1-5% of women in reproductive age. Plenty of studies have indicated that microRNAs (miRNAs) are involved in the occurrence of miscarriage. MiR-93 has a wide range of functions in mammalian tissues and plays an important role in many diseases especially for cancers. However, it remains unknown whether miR-93 is associated with human RSA. In this report, clinical samples revealed that miR-93 expression was significantly elevated in the villi tissues of RSA patients. Upregulation of miR-93 inhibited human trophoblast cells HTR-8/SVneo cell proliferation, migration, and invasiveness, but promoted cell apoptosis in vitro. Conversely, the downregulation of miR-93 reversed these effects. Bcl-2 like protein 2 (BCL2L2), a potential target gene of miR-93, was inversely correlated with miR-93 expression in the villi of clinical samples. Furthermore, the luciferase reporter system demonstrated that miR-93 directly downregulated the expression of BCL2L2 by binding a specific sequence of its 3'-untranslated region (3'UTR). Collectively, these data strongly suggest that miR-93 regulates trophoblast cell proliferation, migration, invasive, and apoptosis by targeting BCL2L2 expression and is involved in the pathogenesis of RSA.

Magnolia Officinalis Cortex has been used as a traditional Chinese herb for thousands of years in China. According to Chinese Pharmacopoeia,the processing of Magnolia Officinalis Cortex needs &quot; sweating&quot; or &quot; Fahan&quot;,which was a special drying process and considered to be an important symbol for high quality and genuine medicinal materials. In this unique processing mode,Magnolia Officinalis Cortex&apos;s microbial community structure may be changed,but little is known about microbial diversity during the &quot; sweating&quot;. In this study,to analyze the change and its change rules of microbial community of Magnolia Officinalis Cortex in the whole process of &quot; sweating&quot;,and find out the microbial community that affects the quality of Magnolia Officinalis Cortex in the process of its &quot; sweating&quot;,and provide a basis for further research on the microbial transformation of Magnolia Officinalis Cortex,MiSeq highthroughput sequencing was used to evaluate the microbial diversity of natural &quot; sweating&quot; of Magnolia Officinalis Cortex. In this research,334 genera fungi and 674 genera bacteria were identified. The dominant species weren&apos; t obvious during the early stage of &quot; sweating&quot;. Candida was the dominant fungal species( 45. 01%-71. 93%) during the medium &quot; sweating&quot; stage. Aspergillus is the dominant fungal species( 45. 83%-95. 51%) during the late stage of &quot; sweating&quot;. Moreover,Enterobacter and Klebsiella were the primary bacterial genus( ≥56. 05%) during the middle and late stages of &quot; sweating&quot;. In addition,the predominant bacteria in the process of &quot; sweating&quot; included Bacillus,Deinococcus,Sphingomonas,Hymenobacter and Jatrophihabitans. In conclusion,the microbial diversities and the main dominant fungi and bacteria in the process of &quot; sweating&quot; of Magnolia Officinalis Cortex were initially determined. It was also found that the metabolism of Aspergillus and Candida may be related to the character formation,which were sweet odor and brown inner surface after &quot; sweating&quot;. The results provide a theoretical basis for the study of the influence of different microorganisms on the excellent traits formation of &quot; sweating&quot; Magnolia Officinalis Cortex.

Glycolytic enzyme phosphoglycerate mutase 1 (PGAM1) plays a critical role in cancer metabolism by coordinating glycolysis and biosynthesis. A well-validated PGAM1 inhibitor, however, has not been reported for treating pancreatic ductal adenocarcinoma (PDAC), which is one of the deadliest malignancies worldwide. By uncovering the elevated PGAM1 expressions were statistically related to worse prognosis of PDAC in a cohort of 50 patients, we developed a series of allosteric PGAM1 inhibitors by structure-guided optimization. The compound KH3 significantly suppressed proliferation of various PDAC cells by down-regulating the levels of glycolysis and mitochondrial respiration in correlation with PGAM1 expression. Similar to PGAM1 depletion, KH3 dramatically hampered the canonic pathways highly involved in cancer metabolism and development. Additionally, we observed the shared expression profiles of several signature pathways at 12 h after treatment in multiple PDAC primary cells of which the matched patient-derived xenograft (PDX) models responded similarly to KH3 in the 2 wk treatment. The better responses to KH3 in PDXs were associated with higher expression of PGAM1 and longer/stronger suppressions of cancer metabolic pathways. Taken together, our findings demonstrate a strategy of targeting cancer metabolism by PGAM1 inhibition in PDAC. Also, this work provided "proof of concept" for the potential application of metabolic treatment in clinical practice., Competing Interests: The authors declare no competing interest.

Objective: To investigate the migration and invasion behaviors of Hep-2 after the targeted knockdown of yes-associated protein (YAP). Methods: Hep-2 cells were knock-downed for YAP by shRNA as YAP-shRNA group, Hep-2 treated with non-specific shRNA as YAP-NC group, and Hep-2 with no treatment as control. Glucose uptake and lactate production in the cells were examined to assess Warburg effect. The migration and invasion behaviors of cells in three groups were observed. The expressions of vimentin and E-cadherin were detected by RT-PCR and Western Blot. The statistical software GraphPad Prism 7.0 was used to analyze significance of data. Two tailed Student' s t-tests was used to determine significance when only two groups were compared. P values of less than 0.05 was considered statistically significant. Results: Downregulation of YAP led to a obvious decrease in glucose uptake [(18.51±1.72)%] and lactate production [103.40±8.32] in Hep-2 cells compared with control [(41.20±1.11)% and 743.69±19.49, t= 19.20 and 52.33, respectively, both P< 0.01] and YAP-NC group [(39.60±0.78)% and 705.22±17.20, t= 19.34 and 54.56, respectively, both P< 0.01]. Compared with the control group (78.32±4.04) and YAP-NC group (77.28±3.11), the scratch healing ability of Hep-2 cells was significantly decreased in YAP-shRNA group (44.71±4.68). The P value was less than 0.01 ( t= 9.42 and 10.04). The number of cells with YAP-shRNA (33.30±4.19) passing through compartments was remarkable fewer than the control group (133.71±6.72) and YAP-NC group (126.32±4.21). The P value was less than 0.01 ( t= 21.96 and 27.13). The expression of E-cadherin protein in cells of YAP-shRNA group (6.16±0.11) was up-regulated compared with control (0.97±0.10, t= 35.70, P< 0.01) and YAP-NC group (1.13±0.09, t= 36.28, P< 0.01), while the expression of vimentin protein in cells of YAP-shRNA group (1.08±0.09) was down-regulated compared with control (5.67±0.12, t= 29.91, P< 0.01) and YAP-NC group (5.51±0.12, t= 29.04, P< 0.01). Conclusions: The down-regulation of YAP in Hep-2 inhibits the migration and invasion of cells via suppressing Warburg and EMT program.

Spinal degenerative changes may occur following the rapid growth observed in adolescents, causing a reduced quality of life. The suppressor of cytokine signaling (SOCS) is involved in various degenerative diseases. The current study recruited adolescents with spinal degenerative disease (SDD) to identify the effect of SOCS-3 on leptin and tumor necrosis factor-α (TNF-α) levels in this disorder. From January 2010 to January 2016, 120 adolescents (aged 14 to 25) were enrolled in the current study, with 68 diagnosed with SDD and the remaining 52 treated as controls. Nucleus pulposus cells (NPCs) were extracted and cultured in vitro . TNF-α levels in NPCs were determined using flow cytometry. Degenerative NPCs were then transfected with pCR3.1-SOCS-3 and ELISA was performed to determined TNF-α and leptin levels. RT-qPCR was performed to measure the mRNA level of SOCS-3 and leptin in NPCs and western blotting was utilized to detect the protein level of leptin and the extent of leptin receptor phosphorylation. The results revealed that TNF-α levels in degenerative NPCs were higher than those in normal NPCs. The overexpression of SOCS-3 reduced levels of TNF-α and leptin in degenerative NPCs. In addition, the upregulation of leptin increased SOCS-3 levels in a concentration-dependent manner. Furthermore, the expression of the leptin receptor and phosphorylated leptin receptor gradually decreased with increasing leptin concentrations and the level of phosphorylated leptin receptor negatively correlated with SOCS-3 expression. The inductive effect of leptin on the level of SOCS-3 and the inhibitory effect of SOCS-3 on the activity of leptin were identified. The current study demonstrated that SOCS-3 reduces leptin and TNF-α levels in degenerative NPCs from adolescents, indicating its potential role in the development of novel SDD therapies.

Tendon adhesion is a substantial challenge for tendon repair. Thermal pretreatment (TP) may decrease inflammation by upregulating heat shock proteins (HSPs). The present study intends to identify the function that TP serves when combined with HSP70 overexpression in tendon healing and adhesion in rats. Sprague‑Dawley male rats were used to establish a surgically ablative tendon postoperative suture model, and the positive expression of the HSP70 protein was measured using immunohistochemistry. Changes to the blood vessels and collagenous fiber, in addition to the maximum tensile strength and the tendon sliding distance, were detected under a microscope. Finally, HSP70, tumor growth factor β (TGF‑β), and insulin‑like growth factor 1 (IGF‑1) mRNA and protein levels were all determined by employing reverse transcription‑quantitative polymerase chain reaction and western blot analysis methods. The positive expression of the HSP70 protein increased following TP. Furthermore, TP reduced the infiltration of inflammatory cells and improved the collagenous arrangement, accompanied by an increased maximum tensile force and tendon gliding distance following surgery. In addition, TP increased the mRNA and protein expression levels of HSP70, TGF‑β and IGF‑1. Altogether, TP increases HSP70 expression, thereby reducing postoperative traumatic inflammation and establishing tendon adhesion and promoting tendon healing. Thus, TP may be a potential strategy for the treatment of tendon adhesion.

Severe congenital neutropenia caused by ELANE gene mutation is a rare disease. To date, only four families were reported with mosaicism. Here we examined the morphology and function of granulocytes isolated from two patients and their mosaic fathers. Analysis of granulocytes isolated from the fathers revealed no genetic mutations. DNA extracted from fractionated peripheral blood mononuclear cells (PBMCs) and fingernails obtained from both fathers did harbor the mutation, suggesting mosaicism. Granulocytes isolated from the patients displayed significantly weaker ionomycin-induced intracellular reactive oxygen species (ROS) responses than those isolated from the fathers. Both patients showed increased expression of neutrophil elastase, whereas the mosaic fathers showed normal expression. Taken together, the results suggest that granulocytes from these SCN patients are immunocompromised, whereas those from the mosaic fathers are normal. These findings may provide new insight into disease diagnosis, prognosis, therapy and genetic counseling., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Background: Pulmonary edema is one of the pathological characteristics of acute respiratory distress syndrome (ARDS). The epithelial sodium channel (ENaC) is thought to be the rate-limiting factor for alveolar fluid clearance (AFC) during pulmonary edema. The peroxisome proliferator-activated receptor γ (PPARγ) agonist rosiglitazone was shown to stimulate ENaC-mediated salt absorption in the kidney. However, its role in the lung remains unclear. Here, we investigated the role of the PPARγ agonist in the lung to find out whether it can regulate AFC during acute lung injury (ALI). We also attempted to elucidate the mechanism for this., Methods: Our ALI model was established through intratracheal instillation of lipopolysaccharide (LPS) in C57BL/6 J mice. The mice were randomly divided into 4 groups of 10. The control group underwent a sham operation and received an equal quantity of saline. The three experimental groups underwent intratracheal instillation of 5 mg/kg LPS, followed by intraperitoneal injection of 4 mg/kg rosiglitazone, 4 mg/kg rosiglitazone plus 1 mg/kg GW9662, or only equal quantity of saline. The histological morphology of the lung, the levels of TNF-α and IL-1β in the bronchoalveolar lavage fluid (BALF), the level of AFC, and the expressions of αENaC and serum and glucocorticoid-induced kinase-1 (SGK1) were determined. Type 2 alveolar (AT II) cells were incubated with rosiglitazone (15 μM) with or without GW9662 (10 μM). The expressions of αENaC and SGK1 were determined 24 h later., Results: A mouse model of ALI was successfully established. Rosiglitazone significantly ameliorated the lung injury, decreasing the TNF-α and IL-1β levels in the BALF, enhancing AFC, and promoting the expressions of αENaC and SGK1 in ALI mice, which were abolished by the specific PPARγ blocker GW9662. In vitro, rosiglitazone increased the expressions of αENaC and SGK1. This increase was prevented by GW9662., Conclusions: Rosiglitazone ameliorated the lung injury and promoted ENaC-mediated AFC via a PPARγ/SGK1-dependent signaling pathway, alleviating pulmonary edema in a mouse model of ALI., Competing Interests: Competing interestsThe authors declare that there is no conflict of interest associated with this work.

Background: We previously found that autoantibodies against a panel of six tumor-associated antigens (p53, NY-ESO-1, MMP-7, Hsp70, PRDX6 and Bmi-1) may aid in early detection of esophageal squamous cell carcinoma. Here we aimed to evaluate the diagnostic value of this autoantibody panel in esophagogastric junction adenocarcinoma (EJA) patients., Methods: Serum autoantibody levels were measured by enzyme-linked immunosorbent assay in a training cohort and a validation cohort. We used receiver-operating characteristics (ROC) to calculate diagnostic accuracy., Results: We recruited 169 normal controls and 122 EJA patients to the training cohort, and 80 normal controls and 70 EJA patients to the validation cohort. Detection of the autoantibody panel demonstrated an area under the curve (AUC) of 0.818, sensitivity 59.0% and specificity 90.5% in training cohort, and AUC 0.815, sensitivity 61.4% and specificity 90.0% in validation cohort in the diagnosis of EJA. Measurement of the autoantibody panel could distinguish early stage EJA patients from normal controls (AUC 0.786 and 0.786, sensitivity 50.0% and 56.0%, and specificity 90.5% and 90.0%, for training and validation cohorts, respectively). Moreover, a restricted panel consisting of autoantibodies against p53, NY-ESO-1 and Bmi-1 exhibited similar diagnostic performance for EJA (AUC 0.814 and 0.823, sensitivity 53.5% and 60.0%, and specificity 90.5% and 93.7%, for training and validation cohorts, respectively) and early stage EJA (AUC 0.744 and 0.773, sensitivity 55.6% and 52.0%, and specificity 90.5% and 93.7%, for training and validation cohorts, respectively)., Conclusions: Autoantibodies against an optimized TAA panel as serum biomarkers appear to help identify the present of early stage EJA.

Kif5b-driven anterograde transport and clathrin-mediated endocytosis (CME) are responsible for opposite intracellular trafficking, contributing to plasma membrane homeostasis. However, whether and how the two trafficking processes coordinate remain unclear. Here, we show that Kif5b directly interacts with clathrin heavy chain (CHC) at a region close to that for uncoating catalyst (Hsc70) and preferentially localizes on relatively large clathrin-coated vesicles (CCVs). Uncoating in vitro is decreased for CCVs from the cortex of kif5b conditional knockout (mutant) mouse and facilitated by adding Kif5b fragments containing CHC-binding site, while cell peripheral distribution of CHC or Hsc70 keeps unaffected by Kif5b depletion. Furthermore, cellular entry of vesicular stomatitis virus that internalizes into large CCV is inhibited by Kif5b depletion or introducing a dominant-negative Kif5b fragment. These findings showed a new role of Kif5b in regulating large CCV-mediated CME via affecting CCV uncoating, indicating Kif5b as a molecular knot connecting anterograde transport to CME., Competing Interests: The authors declare that they have no conflict of interest.

Objective: To investigate the effect of microRNA-210 on the spinal cord injury (SCI) and its underlying mechanism., Materials and Methods: The mouse SCI model was established. Mice were randomly assigned into 4 groups, namely the sham operation group (sham group), surgery group (SCI group), surgery+NC group (SCI+NC group) and surgery+microRNA-210 overexpression group (SCI+microRNA-210 mimics group). The mRNA levels of microRNA-210 and the key genes in the JAK-STAT pathway of the four groups were detected by Real-Time Polymerase Chain Reaction (RT-PCR) at different time points. Protein levels of JAK2 and STAT3 in mice of the four groups were detected by Western blot. To investigate the role of microRNA-210 in SCI recovery, changes in the motor function of mice were detected., Results: Grip strengths of right and left forelimbs in mice from the sham group were temporarily decreased at the early stage after surgery, which were gradually recovered to the preoperative levels on the 3rd postoperative day. However, mice in SCI group were unable to complete the grip strength determination at the early stage after surgery. Mice in SCI group were capable of grasping on the 7th postoperative day. Besides, grip strengths of mice in SCI group were remarkably lower than those of sham group until the end-point (on the 50th day). Furthermore, mRNA levels of microRNA-210 in mice of SCI group were decreased in a time-dependent manner (p<0.05). Higher grip strengths were observed in mice of SCI+microRNA-210 mimics group in comparison with those of SCI group and SCI+NC group (p<0.05). In addition, Western blot showed that protein levels of JAK2 and STAT3 in mice of SCI group were increased in a time-dependent manner (p<0.05). Moreover, protein levels of JAK2, STAT3, and MCP-1 in mice of SCI+NC group were remarkably higher than those in the sham group and SCI+microRNA-210 mimics group (p<0.05)., Conclusions: MicroRNA-210 is down-regulated in SCI mice. Grip strengths of SCI mice can be recovered after microRNA-210 overexpression via inhibiting inflammatory response by the JAK-STAT pathway.

Objective: To investigate the clinical, immunological, and molecular manifestations of nuclear factor kappa-B subunit 2 (NFκB2) gene mutation associated common variable immunodeficiency (CVID) . Methods: A 14-month-old boy diagnosed with NFκB2-mutated CVID was admitted into Children's Hospital of Chongqing Medical University in December 2015. The clinical manifestations, biochemical tests, immunological function, molecular features, treatment, and follow-up of the patient were analyzed. The Chinese and PUBMED databases were searched with the key words "NFκB2" and "immune deficiency" and related literatures were reviewed. Results: The patient had 4 episodes of pneumonias and one otitis media since the age of 6 months. The serum immunoglobulin levels were IgG 2.73 g/L, IgA<0.07 g/L, and IgM 0.12 g/L. The percentage of peripheral lymphocyte subsets demonstrated increased CD3(+)T lymphocyte (81.8%), increased CD4(+) naïve T cell (39.1%), normal B cell (14.1%), low switched memory B and plasmablast B (respectively 0.1% and 0), and lightly diminished natural killer(NK) cell (4.13%). Within the peripheral CD4(+)T cells, the percentage of regulatory T cells (1.49% (control 4.08%)), T follicular helper (3.66% (control 11.0%)), and T helper 17 (9.65% (control 15.7%)) were decreased, while the percentage of T helper 2 (60.9% (control 46.5%)) was elevated. T lymphocyte proliferative response and T cell receptor repertoire diversity were normal. NK-cell cytotoxic activity was impaired. The whole-exome sequencing harbored a de novo heterozygous nonsense mutation in exon 22 (c.2557C>T; p. Arg853X) in the C-terminus of NF-κB2. The western blotting confirmed the decreased expression of NF-κB2 (p52) protein. The patient received intravenous immunoglobulin infusion monthly (400-600 mg/kg), followed by improvement of pulmonary infection. After searching the databases, a total of 28 cases (1 Chinese and 27 non-Chinese) were identified. There were 12 cases of nonsense mutation (5 were gain-of-function mutation), and 8 cases of missense and frameshift mutations, respectively. The main clinical manifestation was respiratory infection, followed by autoimmune diseases such as alopecia and trachyonychia. Fifteen cases developed adrenocorticotrophic hormone (ACTH) deficiency. Conclusions: NF-κB2 signaling pathway played an important role in T and B lymphocyte differentiation, and NK-cell cytotoxic activity. NFκB2 mutation should be considered in cases with recurrent infections, hypogammaglobulinemia, and decreased memory B cells and plasma cells, especially when combined with ACTH deficiency.

HPLC analysis was performed on a Phenomenex PS C₁₈（4.6 mm×250 mm, 5 μm）column using methanol -0.2% formic acid (30:70) at a flow rate of 0.8 mL·min⁻¹. The column temperature was 30 °C and the detection wavelength was set at 335 nm. The injection volume was 10 μL. The HPLC fingerprint of Desmodium styracifolium was established with 10 common peaks, and 5 of them were identified as vicenin-1, schaftoside, isoorientin, isoschaftoside and isovitexin, respecivetly. The fingerprints of 21 batches of D. styracifolium samples were analyzed with similarity evaluation, cluster analysis, principal component analysis and partial least squares discriminant analysis. There was no significant difference among the quantitative results of these five ingredients verified by external standard method (ESM) and quantitative analysis of multi-components by single marker (QAMS) method. The application of fingerprint, pattern recognition combined with QAMS can provide more comprehensive references for the quality control and evaluation of D. styracifolium., Competing Interests: The authors of this article and the planning committee members and staff have no relevant financial relationships with commercial interests to disclose., (Copyright© by the Chinese Pharmaceutical Association.)

Agents with multiple modes of tumor cell death can be effective chemotherapeutic drugs. One example of a bimodal chemotherapeutic approach is an agent that can induce both apoptosis and autophagic death. Thus far, no clinical anticancer drug has been shown to simultaneously induce both these pathways. Mono-functional platinum complexes are potent anticancer drug candidates which act through mechanisms distinct from cisplatin. Here, we describe the synthesis and characterize of two mono-functional platinum complexes containing 8-substituted quinoline derivatives as ligands, [PtL 1 Cl]Cl [L 1  = (Z)-1-(pyridin-2-yl)-N-(quinolin-8-ylmethylene) methanamine] (Mon-Pt-1) and [PtL 2 Cl]Cl [L 2  = (Z)-2-(pyridin-2-yl)-N-(quinolin-8-ylmethylene) ethanamine] (Mon-Pt-2). In comparison to cisplatin, Mon-Pt-2 exhibited a greater in vitro cytotoxicity, was more effective in resistant cells and elicited a better anticancer effect. Mechanistic experiments indicate that Mon-Pt-2 mainly accumulates in mitochondria, and stimulates significant TrxR inhibition ROS release and an ER stress response, mediated by mitochondrial dysfunction, ultimately resulting in a simultaneous induction of apoptosis and autophagy. Importantly, compared to cisplatin, Mon-Pt-2 exhibits lower acute toxicity and better anticancer activity in a murine tumor model. To the best of our knowledge, Mon-Pt-2 is the first mono-functional platinum complex inducing pro-death autophagy and apoptosis of cancer cells., (Copyright © 2018 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

Objective: Acute kidney injury (AKI) is common in critically ill patients, and sepsis patients with AKI had a higher mortality rate. The aim of the present study was to determine the potential value of urinary miR-26b in the diagnosis of sepsis-associated AKI., Patients and Methods: Urinary samples were collected from a cohort of 155 sepsis patients (68 AKI patients and 87 non-AKI patients) and 57 patients with non-infectious systemic inflammatory response syndrome (SIRS). The expression levels of urinary miR-26b were measured by RT-qPCR analysis. ROC curve analysis was performed to determine the diagnostic value. Pearson correlation analysis was performed to assess the levels of urinary miR-26b and several clinical parameters. Kaplan-Meier curves were plotted to show the impact of urinary miR-26b on the 28-day survival., Results: Significantly increased urinary miR-26b levels were found in patients with sepsis-associated AKI. Urinary miR-26b had a sensitivity of 90.8% and specificity of 75.0% for distinguishing between AKI sepsis and non-AKI sepsis. Urinary miR-26b levels were closely correlated with clinical parameters reflecting the severity of the disease. Kaplan-Meier analysis revealed that sepsis patients with high urinary miR-26b levels had an elevated mortality rate., Conclusions: Taken together, these findings suggested that urinary miR-26b might be utilized as a potential biomarker for sepsis-associated AKI.

Background and Aims: Vascular peroxidase 1 (VPO1) plays a key role in mediation of cardiovascular oxidative injury. This study aims to determine whether VPO1 can promote programmed necrosis of endothelial cells and the underlying mechanisms., Methods and Results: Human umbilical vein endothelial cells (HUVECs) were incubated with oxidized low-density lipoprotein (ox-LDL, 100 μg/mL) for 48 h to induce cell injury, which showed an elevation in cell necrosis (reflected by the increased propidium iodide (PI) positive-staining cells, LDH release and decreased cell viability), concomitant with an increase in programmed necrosis-relevant proteins including receptor-interacting protein kinase 1/3 (RIPK1/3), p-RIPK3 and mixed lineage kinase domain like (MLKL); these phenomena were attenuated by necrostatin-1(Nec-1) and RIPK3 siRNA. Meanwhile, VPO1 was up-regulated in ox-LDL-treated endothelial cells accompanied by a decrease in GSK-3β activity and p-β-catenin levels, and an elevation of β-catenin levels; these phenomena were reversed in the presence of VPO1 siRNA or hypochlorous acid (HOCl) inhibitor; replacement of ox-LDL with HOCl could also induce endothelial programmed necrosis and activate the β-catenin signaling; β-catenin inhibitor could also suppress ox-LDL-induced RIPK-dependent necrosis. In hyperlipidemic patients, the plasma level of VPO1 was obviously increased concomitant with an elevation in plasma levels of RIPK1, RIPK3 and MLKL, and they were positively correlated., Conclusions: VPO1 plays an important role in promotion of endothelial programmed necrosis under hyperlipidemic conditions through activation of β-catenin signaling. It may serve as a novel therapeutic target for prevention of endothelial dysfunction in hyperlipidemia., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Objective: To explored the clinical application of the three-dimensional finite element model of atlantoaxial complex fracture. Methods: A three-dimensional finite element model of cervical spine (FEM/intact) was established by software of Abaqus6.12.On the basis of this model, a three-dimensional finite element model of four types of atlantoaxial complex fracture was established: C(1) fracture (Jefferson)+ C(2) fracture (type Ⅱfracture), Jefferson+ C(2) fracture(type Ⅲfracture), Jefferson+ C(2) fracture(Hangman), Jefferson+ stable C(2) fracture (FEM/fracture). The range of motion under flexion, extension, lateral bending and axial rotation were measured and compared with the model of cervical spine. Results: The three-dimensional finite element model of four types of atlantoaxial complex fracture had the same similarity and profile.The range of motion (ROM) of different segments had different changes.Compared with those in the normal model, the ROM of C(0/1) and C(1/2) in C(1) combined Ⅱ odontoid fracture model in flexion/extension, lateral bending and rotation increased by 57.45%, 29.34%, 48.09% and 95.49%, 88.52%, 36.71%, respectively.The ROM of C(0/1) and C(1/2) in C(1) combined Ⅲodontoid fracture model in flexion/extension, lateral bending and rotation increased by 47.01%, 27.30%, 45.31% and 90.38%, 27.30%, 30.0%.The ROM of C(0/1) and C(1/2) in C(1) combined Hangman fracture model in flexion/extension, lateral bending and rotation increased by 32.68%, 79.34%, 77.62% and 60.53%, 81.20%, 21.48%, respectively.The ROM of C(0/1) and C(1/2) in C(1) combined axis fracture model in flexion/extension, lateral bending and rotation increased by 15.00%, 29.30%, 8.47% and 37.87%, 75.57%, 8.30%, respectively. Conclusions: The three-dimensional finite element model can be used to simulate the biomechanics of atlantoaxial complex fracture.The ROM of atlantoaxial complex fracture is larger than nomal model, which indicates that surgical treatment should be performed.

Agents inducing both apoptosis and autophagic death can be effective chemotherapeutic drugs. In our present work, we synthesized two organometallic gold(III) complexes harboring C^N ligands that structurally resemble tetrahydroisoquinoline (THIQ): Cyc-Au-1 (AuL 1 Cl 2 , L 1 = 3,4-dimethoxyphenethylamine) and Cyc-Au-2 (AuL 2 Cl 2 , L 2 = methylenedioxyphenethylamine). In screening their in vitro activity, we found both gold complexes exhibited lower toxicity, lower resistance factors, and better anticancer activity than those of cisplatin. The organometallic gold(III) complexes accumulate in mitochondria and induce elevated ROS and an ER stress response through mitochondrial dysfunction. These effects ultimately result in simultaneous apoptosis and autophagy. Importantly, compared to cisplatin, Cyc-Au-2 exhibits lower toxicity and better anticancer activity in a murine tumor model. To the best of our knowledge, Cyc-Au-2 is the first organometallic Au(III) compound that induces apoptosis and autophagic death. On the basis of our results, we believe Cyc-Au-2 to be a promising anticancer agent or lead compound for further anticancer drug development.

Objective: To explore the role of microRNA (miR) 137 in spinal cord injury and its mechanism., Materials and Methods: The model of spinal cord injury in mice was established to detect the recovery differences of grip strength in upper and lower limbs of mice. The expressions of miR-137 and neuronal differentiation 4 (NEUROD4) were detected at the same time. The inflammation level and the oxidative stress response after spinal cord injury were subsequently detected after overexpression of miR-137. Target genes of miR-137 were identified by bioinformatics. Finally, dual-luciferase reporter gene assay was used to identify the target genes of miR-137., Results: By establishing the model of spinal cord injury in mice, the strength of upper and lower limbs recovered after 7 days of injury in mice. The expression of miR-137 in spinal cord injury was found to decrease in a time-dependent manner by quantitative Real-time polymerase chain reaction (qRT-PCR), while the expression of NEUROD4 gradually increased. Inflammation indicators and oxidative stress level were found to be significantly higher after spinal cord injury. However, the inflammation level and oxidative stress were significantly reduced after transfection of miR-137. Finally, we predicted the target gene of miR-137 through bioinformatics website and found that NEUROD4 was a potential target gene of miR-137. Using dual luciferase reporter assays, we found that NEUROD4 bound to miR-137. After overexpression of miR-137, the expression of NEUROD4 was significantly reduced. Overexpression of NEUROD4 could promote spinal cord injury inflammation and oxidative stress. After intracellular transfection of NEUROD4 and miR-137 at the same time, the inflammation level and oxidative stress of spinal cord injury decreased significantly., Conclusions: These results suggested that miR-137 promoted the recovery of spinal cord injury by degrading NEUROD4 to relieve the spinal cord inflammation and the progression of oxidative stress, thus promoting the recovery of spinal cord injury.

Objective: To investigate the effects of Vaspin on lipopolysaccharide (LPS)-induced acute respiratory distress syndrome (ARDS) in mice and explore the possible mechanism., Methods: Forty male C57B/L6 mice were randomized equally into control group, LPS group, Vaspin group and wortmannin group with corresponding treatments. The pathological changes of the lung tissues were evaluated by HE staining, and the severity of pulmonary edema was measured according to the wet/dry ratio (W/D) of the lung tissue. The lung permeability was evaluated by detecting total protein concentrations in the bronchoalveolar lavage fluid (BALF) using bicinchoninic acid (BCA) assay. Myeloperoxidase (MPO) activity in the lung tissue was detected using a MPO assay kit, and the levels of interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α) in the lungs were measured using ELISA. Immunohistochemical staining was performed to detect the expression of vascular cell adhesion molecule-1 (VCAM-1) and Western blotting was used to detect the protein expressions of cleaved caspase-3 and p-Akt in the lung tissues., Results: Compared with the control group, the mice in LPS group displayed typical ARDS pathological changes in the lungs with significantly increased W/D, total protein concentrations in BALF, lung MPO activity, levels of IL-1β and TNF-α, and pulmonary expressions of VCAM-1 and cleaved caspase-3 (P<0.05) but decreased expression of p-Akt (P<0.05). These changes induced by LPS were significantly alleviated by the administration of Vaspin (P<0.05). The protective effects of Vaspin against ARDS were obviously attenuated by the PI3K inhibitor wortmannin (P<0.05)., Conclusion: Vaspin protects against LPS-induced ARDS in mice possibly by inhibiting inflammation and protecting vascular endothelium through upregulation of the PI3K/Akt signal pathway.

Objective: Spinal cord injury (SCI) is a severe trauma to the central nervous system. Long non-coding RNAs have been reported to play essential roles in spinal cord injury. This study mainly explored the role of micro-125 in the regulation of spinal cord injury by regulating STAT3., Materials and Methods: The stable mouse model of cervical spinal cord contusion was established by Infinite Horizon spinal cord striker, and the model mice' motor function was analyzed. Bioinformatics databases were used to screen the target mRNAs of micro-125b. qRT-PCR was performed to detect the expression of micro-125b and its target genes in injury area of mice' spinal cord. Western Blot and ELISA were introduced to detect the expression of inflammation and apoptosis-related proteins in each group. The recovery status of spinal cord after SCI was assessed by motor function scores and axon counts of mice in each group., Results: Micro-125b appeared to be significantly down-regulated over-time after SCI. JAK1 and STAT1, two important neuregulin proteins, were predicted to be the target genes of micro-125b, and overexpression of micro-125b induced the decrease of phosphorylated JAK1 and STAT1. Enhanced micro-125b expression also allowed axons from the injury area of spinal cord to extend into the outer periphery of the damaged area, thus improving the motor function of the injured rats. Besides, overexpression of micro-125b demonstrated significant neuronal protective effects by reducing apoptosis and inflammatory responses in neurons., Conclusions: Our data revealed that micro-125b was down-regulated in injured spinal cord, and overexpression of micro-125b promoted the repair and regeneration following spinal cord injury through the regulation of the JAK/STAT pathway.

Luongo et al. found that the mitochondrial Na + /Ca 2+ exchanger (NCLX) was essential for Ca 2+ homeostasis and viability. Here, we re-analyze their data in terms of fractal self-similarity and quantitative difference (QD). We calculated the 7-dimension data from NCLX conditional loss-of-function mouse models, and the 9-dimension data from NCLX overexpression (NCLX-Tg) models., Results: The 9-dimension data of the NCLX-Tg and its tTA control were partially self-similar to each other, while the 7-dimension data in NCLX knockout models were not., Conclusion: The NCLX may be necessary but is not sufficient for Ca 2+ homeostasis and viability.

Osteosarcoma is the most common and highly aggressive bone neoplasm often occurs among adolescents and young people. In despite of the major advances in the treatment, the overall survival of osteosarcoma patients remains poor. Long non-coding RNAs (lncRNAs) have been identified as key regulators involved in tumorigenesis and progression of osteosarcoma. However, the exact roles and mechanisms of lncRNAs in osteosarcoma remain unclear. In this study, the functions and underlying molecular mechanisms of a novel lncRNA, ITGB2 antisense RNA1 (ITGB2-AS1) were investigated in osteosarcoma. The expression levels of ITGB2-AS1 were up-regulated in osteosarcoma tissue samples and cell lines determined by qRT-PCR assay. Osteosarcoma patients with high ITGB2-AS1 expression had a significantly poor prognosis. In addition, knockdown of ITGB2-AS1 inhibited the proliferation and induced apoptosis of osteosarcoma cells using MTT assay and flow cytometry detection. Furthermore, wound healing and transwell invasion assay revealed that depletion of ITGB2-AS1 suppressed the migration and invasion abilities of osteosarcoma cells. Molecular mechanism study indicated that ITGB2-AS1 inhibition impaired Wnt/β-catenin signalling pathway in osteosarcoma cells. Taken together, our study suggested that ITGB2-AS1 played critical roles in the development and progression of osteosarcoma via Wnt/β-catenin signalling, indicating that ITGB2-AS1 might be a valuable diagnostic biomarker and potential anticancer therapeutic target for osteosarcoma.

Background and Aims: Esophageal squamous cell carcinoma (ESCC), a major histologic subtype of esophageal cancer, is increasing in incidence, but the genetic underpinnings of this disease remain unexplored. The aim of this study is to identify the recurrent genetic changes, elucidate their roles and discover new biomarkers for improving clinical management of ESCC. Methods: Western blotting and immunohistochemistry were performed to detect the expression level of RHCG. Bisulfite genomic sequencing (BGS) and methylation-specific PCR (MSP) were used to study the methylation status in the promoter region of RHCG. The tumor-suppressive effect of RHCG was determined by both in-vitro and in-vivo assays. Affymetrix cDNA microarray was used to identify the underlying molecular mechanism. Results: RHCG was frequently downregulated in ESCCs, which was significantly correlated with poor differentiation ( P = 0.001), invasion ( P = 0.003), lymph node metastasis ( P = 0.038) and poorer prognosis ( P < 0.001). Demethylation treatment and bisulfite genomic sequencing analyses revealed that the downregulation of RHCG in both ESCC cell lines and clinical samples was associated with its promoter hypermethylation. Functional assays demonstrated that RHCG could inhibit clonogenicity, cell motility, tumor formation and metastasis in mice. Further study revealed that RHCG could stabilize IκB by decreasing its phosphorylation, and subsequently inhibit NF-κB/p65 activation by blocking the nuclear translocation of p65, where it acted as a transcription regulator for the upregulation of MMP1 expression. Conclusions: Our results support the notion that RHCG is a novel tumor suppressor gene that plays an important role in the development and progression of ESCC., Competing Interests: Competing Interests: The authors have declared that no competing interest exists.

Objective: To analyze the genetic characteristics of rubella virus isolated from 2012 to 2015 in Guizhou province. Methods: A total of 390 cases of suspected measles were collected from Guizhou measles network laboratory from 2012 to 2015 and 25 cases of rubella cases were diagnosed. Rubella virus isolation was performed using Vero/SLAM cells. The presence of rubella viral RNA was detected using Real-time RT-PCR after RNA extraction from infected tissue culture cells. Fragments of 480 bp and 633 bp nucleotides of E1 genes of the isolates were amplified by RT-PCR and the PCR products were sequenced and spliced. The phylogenetic tree was conducted based on the 739 bp nucleotide sequences of E1 genes and gene characteristic analysis was performed. Results: There were 19 cases of rubella outbreaks and 6 cases of rubella sporadic cases in 25 cases of suspected rubella cases. There were 11 males (44.0%) and 14 females (56.0%). The mean age and standard deviation were (12.3±3.9) years. A total of 10 rubella strains were isolated. The results of phylogenetic analysis showed that 7 strains of rubella virus isolates belonged to genotype 1E and the other belonged to genotype 2B. The nucleotide acid and amino acid homology among 7 strains 1E genotype were 99.0%-100% and 100% respectively. 2B genotype of 3 strains of nucleotide and amino acid homology were 99.4%-100% and 99.5%-100% respectively. Ten strains of rubella virus were not mutated in the E1 glycoprotein gene, Asn 177 and Asn 209 N-type glycosylation sites and E1 antigen epitopes between 213 and 285aa.Among them, 7 strains of 1E genotype had a mutation from leucine to phenylalanine in 338 amino acid, 2 strains of 2B genotype at 377 amino acids from valine to alanine. Conclusion: Rubella virus epidemic was caused by 1E and 2B genotypes in Guizhou from 2012 to 2015.Ten strains of rubella virus were highly conserved in nucleotide and amino acid sequences and there was no variation of important functional sites.