Search

The development of safe and effective vaccines to respond to COVID-19 pandemic/endemic remains a priority. We developed a novel subunit protein-peptide COVID-19 vaccine candidate (UB-612) composed of: (i) receptor binding domain of SARS-CoV-2 spike protein fused to a modified single-chain human IgG1 Fc; (ii) five synthetic peptides incorporating conserved helper and cytotoxic T lymphocyte (Th/CTL) epitopes derived from SARS-CoV-2 structural proteins (three from S2 subunit, one from membrane and one from nucleocapsid), and one universal Th peptide; (iii) aluminum phosphate as adjuvant. The immunogenicity and protective immunity induced by UB-612 vaccine were evaluated in four animal models: Sprague–Dawley rats, AAV-hACE2 transduced BALB/c mice, rhesus and cynomolgus macaques. UB-612 vaccine induced high levels of neutralizing antibody and T-cell responses, in all animals. The immune sera from vaccinated animals neutralized the SARS-CoV-2 original wild-type strains and multiple variants of concern, including Delta and Omicron. The vaccination significantly reduced viral loads, lung pathology scores, and disease progression after intranasal and intratracheal challenge with SARS-CoV-2 in mice, rhesus and cynomolgus macaques. UB-612 has been tested in primary regimens in Phase 1 and Phase 2 clinical studies and is currently being evaluated in a global pivotal Phase 3 clinical study as a single dose heterologous booster.

To investigate the predictors of clinical outcomes in unresponsive patients with acquired brain injuries.Patients with coma or disorders of consciousness were enrolled from August 2019 to March 2021. A retrospective analysis of demographics, etiology, clinical score, diagnosis, electroencephalography (EEG), and event-related potential (ERP) data from 1 week to 2 months after coma onset was conducted. Findings were assessed for predicting favorable outcomes at 6 months post-coma, and functional outcomes were determined using the Glasgow Outcome Scale-Extended (GOS-E).Of 68 patients, 22 patients had a good neurological outcome at 6 months, while 11 died. Univariate analysis showed that motor response (Motor-R; p 0.001), EEG pattern (p = 0.015), sleep spindles (p = 0.018), EEG reactivity (EEG-R; p 0.001), mismatch negativity (MMN) amplitude at electrode Fz (FzMMNA; p = 0.001), P3a latency (p = 0.044), and P3a amplitude at electrode Cz (CzP3aA; p 0.001) were significantly correlated with patient prognosis. Multivariable logistic regression analysis showed that FzMMNA, CzP3aA, EEG-R, and Motor-R were significant independent predictors of a favorable outcome. The sensitivity and specificity of FzMMNA (dichotomized at 1.16 μV) were 86.4% and 58.5%, and of CzP3aA (cut-off value 2.76 μV) were 90.9% and 70.7%, respectively. ERP amplitude (ERP-A), a combination of FzMMNA and CzP3aA, improved prediction accuracy, with an area under the receiver operating characteristic curve (AUC) of 0.884. A model incorporating Motor-R, EEG-R, and ERP-A yielded an outstanding predictive performance (AUC=0.921) for a favorable outcome.ERP-A and the prognostic model resulted in the efficient prediction of a favorable outcome in unresponsive patients.

BackgroundInfection and rejection are the two most common complications after lung transplantation (LT) and are associated with increased morbidity and mortality. The differential diagnosis of infection and rejection is sometimes difficult due to similar clinical manifestations. However, few studies have investigated the airway microbiota between lung transplant recipients (LTRs) with infection and rejection. ResultsA total of 181 sputum samples (event-free, n=47; infection, n=103; rejection, n=31) were collected from 59 LTRs. A distinct airway microbiota was observed among clinically stable (or event-free) recipients and those with infection or acute rejection after LT. Alpha and beta diversity were significantly different between event-free and rejection recipients and between infection and rejection recipients. Ten differential genera were identified by linear discriminant analysis effect size (LEfSe), with Corynebacterium, unclassified Enterococcaceae and unclassified Lactobacillales enriched in recipients with infection, and Rothia, Granulicatella, Neisseria, Actinomyces, Leptotrichia, Lactobacillus and unclassified Aerococcaceae more abundant in LTRs with acute rejection. Random forest analyses indicated that the combination of the 10 microbiota constituents and procalcitonin (PCT) and T-lymphocyte levels showed AUCs of 0.894, 0.955 and 0.913 to differentiate between event-free and infection, event-free and rejection, and infection and rejection recipients, respectively. ConclusionsOur study is the first to compare the airway microbiota between LTRs with infection and acute rejection. The airway microbiota, especially combined with PCT and T-lymphocyte levels, showed satisfactory predictive efficiency in discriminating among clinically stable recipients and those with infection and acute rejection, suggesting that the airway microbiota was an indicator to differentiate between infection and acute rejection after LT.

Long noncoding RNA (lncRNA) nuclear enriched abundant transcript 1 (NEAT1) is nuclear-located and transcribed from chromatin 11. To date, little is known about the cellular functions and regulatory mechanisms of NEAT1 in prostate cancer (PCa). In this study, whole-genome RNA sequencing data were downloaded from TCGA and GEO databases. Biological information was used to analyze the different expressions of NEAT1. In situ hybridization (ISH) was performed to detect the expression of NEAT1 in PCa and paracarcinoma clinical samples. Then, NEAT1 was knocked down in PC3 cells through lentiviral infection with a plasmid construct. Bioinformatics and integrative analytical approaches were utilized to identify the relationships of NEAT1 with specific cancer-related gene sets. Cell proliferation assay and colony formation assay were performed to evaluate the cell proliferative ability. Glycolysis stress test, metabolism assay, and infiltrating T-cell function analysis were implemented to assess the changes in metabolism and immune microenvironment of PCa. We found that the expression of NEAT1 was higher in PCa than in non-neoplastic tissues. The cell proliferative capability of PCa cells was significantly reduced in the NEAT1 knockdown group. PCR array and bioinformatics analysis revealed that the enrichment of acidic substance-related gene sets was associated with NEAT1 expression. NEAT1 depletion inhibited PCa cell aerobic glycolysis accompanied by the reduction of lactate levels in the medium. Further, we found that lactate dehydrogenase A (LDHA) expression was positively regulated by NEAT1. At last, co-culture systems indicated that NEAT1 or LDHA knockdown promoted the secretion of CD8+ T-lymphocyte factors, including TNF-α, IFN-γ, and Granzyme B, and enhanced the antitumor effects.

Thyroid tumors with abundant adipose tissue component are rare, reportedly accounting for 0.98-2.8% of all thyroid nodules, and include entities such as thyroid lipoadenoma and thyroid carcinoma with lipomatous stroma (TCLS). They may be encountered on fine-needle aspiration biopsy (FNAB), which is widely used in evaluation of thyroid nodules. However, due to their relative rarity, adipose elements rarely are recognized preoperatively in these tumors. Herein, we report two cases of thyroid tumors with abundant adipose tissue, along with cytologic, histologic, and ultrasonographic features. Although an intermixture of adipose tissue and thyroid follicular cells is the key cytologic feature of thyroid tumors with adipose stroma, other cytologic findings, such as abundant fat droplets or isolated fragments of adipose tissue, also should raise the possibility of a fat-containing tumor, particularly when a biopsy is performed by a cytopathologist under ultrasonographic guidance and adequate radiologic-pathologic correlation. Cytopathologists should be aware that overlooking lesional adipose tissue within a thyroid neoplasm might give the false impression of a non-diagnostic or sparsely cellular FNAB specimen.

Our objective was to assess the impact of hs-cTnT elevation on functional outcome and mortality in AIS patients with large vessel occlusion (LVO) in the anterior circulation 3 months after ET and explore factors affecting hs-cTnT elevation. A total of 143 consecutive AIS patients with large vessel occlusion (LVO) in the anterior circulation following ET in a single stroke center were enrolled between January 2015 and November 2017. Hs-cTnT was quantitated on admission. Demographic characteristics, clinical data, functional outcome and all-cause mortality were compared between patients with elevated hs-cTnT levels (14 ng/L) and those with normal hs-cTnT levels (≤14 ng/L). 58/143(40.6%) patients showed elevated hs-cTnT levels before ET. Factors independently associated with hs-cTnT elevation were admission NIHSS score (OR = 1.08, 95% CI 1.01-1.16, p = 0.032), coronary heart disease (OR = 4.89, 95% CI 1.82-13.11, p = 0.002) and congestive heart failure (OR = 4.10, 95% CI 1.07-15.68, p = 0.039). In the univariate analysis, patients with elevated hs-cTnT levels were at significantly higher risk of 3-month poor outcome (p = 0.029) and mortality (p 0.001) than those with normal hs-cTnT levels. After multivariable analysis, hs-cTnT elevation remained an independent predictor of 3-month mortality (OR = 4.49, 95% CI 1.68-11.98, p = 0.003). In this cohort of AIS patients with LVO in the anterior circulation undergoing ET, hs-cTnT elevation is an independent predictor of 3-month mortality. Admission NIHSS score, coronary heart disease and congestive heart failure are independently associated with elevated hs-cTnT levels.

BackgroundPrevious studies suggest that recurrence of hemoptysis after arterial embolization is associated with the underlying pulmonary disease.PurposeTo compare the baseline information and imagi...

To investigate the factors influencing the positive rate of prostate biopsy and its relationship with the prostate volume and inflammatory cell infiltration (ICI).We retrospectively analyzed the clinical data on 230 cases of double-plane transrectal ultrasound-guided prostate biopsy in our Department of Urology, including the patients' age, body mass index (BMI), serum total prostate-specific antigen (tPSA), PSA density (PSAD), prostate volume, and ICI in the prostate tissue. We also investigated the relationship of the above factors with the pathological results of prostate biopsy by binary logistic regression analysis.The positive rate of prostate biopsy was 38.7% (89/230) in the total number of cases, 28.57% (n = 56) in the 196 cases with tPSA100 μg/L, and 97.06% (n = 33) in the 34 cases with tPSA ≥ 100 μg/L. Binary logistic regression analysis showed that the positive rate of prostate biopsy in those with tPSA100 μg/L was correlated positively with age (P0.01, OR = 1.09), tPSA (P0.01, OR = 1.04) and PSAD (P0.01, OR = 10.04), negatively with the prostate volume (P0.01, OR = 0.98) and ICI (P0.01, OR = 0.22), but not with BMI (P0.05). As a predictor of positive prostate biopsy, tPSA10 μg/L exhibited a sensitivity of 82.14% and a specificity of 35.71%, while PSAD0.26 showed a sensitivity of 78.57% and a specificity of 71.43%.Non-specific elevation of the tPSA level induced by increased prostate volume and inflammatory cell infiltration may lead to unnecessary biopsies in some patients. As a predictor of positive prostate biopsy, PSAD0.26 has a higher clinical application value than tPSA10 μg/L.

Background: Diabetic gastroparesis (DG) is a common autonomic neuropathy which impacts on nutritional state and quality of life in diabetic patients, and it also adversely affects glycemic control in diabetes. The prevalence of DG is growing with the number of patients with diabetes continues to increase. However, there is no definitive answer as to which of the current therapies is the best for the clinical treatment of the different manifestations of DG. The subject of this study is to answer the following question: what is the best intervention for diabetic patients with gastroparesis? Methods: Comprehensive searches of the Cochrane Library, PubMed, Embase, Medline, Central and Web of Science, and 4 Chinese databases, including China National Knowledge Infrastructure, VIP Database for Chinese Technical Periodicals, Chinese Biomedical Literature Database, and WanFang will be completed using the following keywords DG and therapies and related entry terms. Studies will be included, according to the eligibility criteria (randomized controlled trials and controlled clinical trials, considering specific outcome measures for DG). The reference lists of included studies will be manual searched. Relevant data will be extracted from included studies using a specially designed data extraction sheet. Risk of bias of the included studies will be assessed, and the overall strength of the evidence will be summarized through GRADE. A random effects model will be used for all pairwise meta-analyses (with a 95% confidence interval). A Bayesian network meta-analysis will explore the relative benefits between the various therapies. The review will be reported using the Preferred Reporting Items for Systematic Reviews incorporating Network Meta-Analyses statement. Network meta-analysis will be performed using a Bayesian framework through the Winbugs software. Results: This network meta-analysis will identify the best effective therapy for DG. Conclusion: This study will compare and evaluate current therapies for DG, and find the best treatment of DG.

The design and synthesis of novel coumarin-thiazolyl ester derivatives of potent DNA gyrase inhibitory activity were the main aims of this study. All the novel synthesized compounds were examined for their antibacterial activity against Staphylococcus aureus, Listeria monocytogenes, Escherichia coli and Salmonella. Compound 8p exhibited excellent antibacterial activity against four bacteria strains with MIC values of 0.05, 0.05, 8, and 0.05 μg/mL, respectively. In vitro drug-resistant bacterial inhibition experiments indicated that compound 8p exhibited the best bacteriostatic effect in the selected compounds and four positive control drugs with MIC values of 4 μg/mL. In vitro enzyme inhibitory assay showed that compound 8p exhibited potent inhibition against DNA gyrase with IC50 values of 0.13 μM. The molecular docking model indicated that compounds 8p can bind well to the DNA gyrase by interacting with amino acid residues. This study demonstrated that the compound 8p can act as the most potent DNA gyrase inhibitor in the reported series of compounds and provide valuable information for the commercial DNA gyrase inhibiting bactericides.

Objective To identify the risk factors for early and late relapse of haemoptysis after bronchial artery embolisation (BAE). Design We performed a retrospective study of 255 patients with haemoptysis who underwent BAE from January 2009 to June 2016 at the First Affiliated Hospital of Nanjing Medical University, Nanjing, China. Using a Cox regression model, risk factors contributing to early (within the first month) and late (>1 month) recurrence were analysed. We censored recurrence-free patients at 1 month and patients without rebleeding after 1 month. Results The cumulative recurrence rate at 1, 6, 12, 24 and 48 months was respectively 14.9%, 16.9%, 20.6%, 31.0% and 39.9%, with a median follow-up of 574 days. Early relapse occurred in 38 of 255 patients, while late recurrence was found in 45 of the remaining 217 patients. The risk factors related to early recurrence were lung destruction on computed tomography of the chest and involvement of non-bronchial systemic arteries. The risk factors associated with late recurrence were tuberculosis sequelae, the presence of shunts and the use of gelfoam as an embolisation material. Conclusions The variables related to incomplete embolisation were the risk factors for early rebleeding. The variables associated with same-vessel recanalisation and formation of a new collateral circulation influenced late recurrence.

Background/Aims: Metal stent insertion is a common palliative treatment for distal malignant biliary obstruction (MBO) but whether placement across the sphincter of Oddi (SO) causes more complications or shorter survival is in question. The aim of this study was to compare the clinical outcomes of percutaneous uncovered self-expandable metal stent placement above and across the SO in patients with distal MBO. Patients and Methods: We retrospectively studied 59 patients who underwent uncovered metal stent placement for distal MBO between January 2012 and March 2016. Stents were placed above the SO for 22 subjects (group A) and across the SO for 37 subjects (group B). Early cholangitis, stent occlusion, and overall survival time were compared between the two groups. Results: Clinical success was 90.9 and 86.5% for groups A and B, respectively. Early cholangitis occurred in 2 patients (9.1%) in group A and in 6 patients (16.2%) in group B (P = 0.645). Median stent patency and median survival time was 105 and 140 days for group A, 120 and 160 days for group B, respectively. The stent occlusion (31.8% in group A and 21.6% in group B, P = 0.454) and the cumulative stent patency times (P = 0.886) did not differ between the two groups. There was no significant difference in cumulative patient survival between the two groups (P = 0.810). Conclusion: Uncovered metal stent placement across the SO did not significantly affect early cholangitis, stent patency, or patient survival.

Objectives: Congenital renal arteriovenous malformations (rAVMs) represent rare vascular diseases. The heterogeneous vascular architecture of each rAVM determines the endovascular treatment techniques employed. We reported our experience with the endovascular treatment of a series of rAVMs. Materials: This retrospective study consisted of 12 patients with 12 rAVMs who underwent renal arterial embolization (RAE) in our hospital. Embolic materials, including particles, liquid embolic agents (n-butyl 2-cyanoacrylate, Onyx, and ethanol), and coils, were selectively used based on the decisions of interventional radiologists. Technical success was defined as the complete occlusion of the feeding arteries and nidus on postprocedure renal arteriography. Clinical success was defined as the resolution of hematuria or the disappearance of rAVM-relevant symptoms. Results: The median follow-up period was 13.5 months (range: 4-72). The technical success based on 12 procedures in 12 patients was 83.3% (10 of 12). In the 2 procedures that technically failed, the existence of multiple fine feeding arteries arising from the proximal portion of different segmental renal arteries explains the incomplete embolization. One of the 2 patients achieved clinical success without additional RAE. The other patient had recurrent hematuria 25 months after initial treatment, which was successfully managed conservatively with hemostatic agents. Thus, the clinical success was 91.7% (11 of 12). Conclusions: Renal artery embolization with the selective use of various embolic materials is an effective treatment for patients with rAVMs. The existence of multiple fine feeding vessels arising from the proximal portion of different segmental renal arteries is likely to affect the technical success of treatment.

Oculomotor nerve palsy (ONP) may result from Posterior communicating artery (Pcom) aneurysms. Endovascular treatment of ruptured Pcom aneurysms generally is a safe procedure, but the effect of this therapy on ONP is incompletely elucidated. This retrospective study evaluates outcomes of ONP after endovascular treatment for ruptured Pcom aneurysm and with the intention to clarify predictors of recovery. From May 2010 to October 2015, 210 patients with Pcom aneurysms underwent endovascular treatment at our institution. Among them, 34 patients with ruptured aneurysms and either complete or incomplete ONP were identified. The outcomes and predictors of ONP recovery were analyzed. At the last available clinical follow-up, ONP resolution was complete in 21 (61.8%) patients and incomplete in 8 (23.5%) patients. The mean resolution time after embolization was 24.5 days. Five patients showed no signs of ONP recovery. In no case was an initial incomplete ONP observed to worsen. There was a statistically insignificant trend toward complete recovery among patients with initial incomplete ONP (OR = 4.17; 95% CI, 0.75–23.18; P = 0.103). Endovascular treatment appears to be an effective treatment modality for ruptured Pcom aneurysm and related ONP. The initial incomplete ONP might encourage complete ONP recovery after endovascular treatment.

The study aimed to compare the tumor response to and complications of doxorubicin-eluting CalliSphere bead-transarterial chemoembolization (DEB-TACE) using small- and medium-sized beads in patients with hepatocellular carcinoma (HCC) who underwent multiple rounds of oncology therapies. Sixty patients with intermediate stage HCC who had previously received multiple oncology therapies underwent DEB-TACE with CalliSpheres of 100–300 μm (small bead group, n = 34) or 300–500 μm (medium bead group, n = 26) in diameter between October 2016 and December 2018. Adverse events and the response rate of the index tumor based on the modified Response Evaluation Criteria in Solid Tumors at 3 months post-TACE were compared between the groups. The rates of complete response, partial response, stable disease, and progressive disease were 35.4%, 29.4%, 17.6%, and 17.6%, respectively, for the small bead group and 33.1%, 23.1%, 20.8%, and 23.0%, respectively, for the medium bead group, showing no significant between-group differences (P > 0.05). Common Terminology Criteria for Adverse Events version 4.0 grade 3/4 adverse events were reported in 8 patients in the small bead group and in no patients in the medium bead group, showing a significant group difference (P

Mammalian target of rapamycin (mTOR) is an intracellular signaling pathway molecule which regulates various fundamental physiological processes. The mTOR signaling pathway plays an important role in synaptic plasticity, information transmission and processing, and neuroregulation. Dysregulation of the mTOR signaling pathway is generally considered to be related to the pathogenesis of autism spectrum disorder (ASD); meanwhile, the mTOR inhibitor can ameliorate the symptoms of ASD. The role of mTOR in the pathogenesis of ASD is summarized in this article to provide a theoretical basis for targeted therapy of ASD.

Guo Xia He,1,2,* Ning Li,1,3,* Lei Ren,2,4,* Hong Hua Shen,2 Ning Liao,5 Jian Jun Wen,6 Yi Min Xu,2 Jing Wang,4 Qing Yun Li1,3 1Department of Pulmonary and Critical Care Medicine, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200025, People’s Republic of China; 2Department of Respiratory Rehabilitation, The Fourth Rehabilitation Hospital of Shanghai (Shanghai Jingan Geriatric Hospital), Shanghai 200042, People’s Republic of China; 3Institute of Respiratory Disease, Shanghai Jiaotong University School of Medicine, Shanghai 200025, People’s Republic of China; 4Department of Respiratory Medicine, The Second Affiliated Hospital of Suzhou University, Jiangsu 215004, People’s Republic of China; 5West-Nanjing Road Community Health-care Center of Shanghai, Shanghai 200040, People’s Republic of China; 6Caojiadu Community Health Service of Shanghai, Shanghai 200042, People’s Republic of China*These authors contributed equally to this workCorrespondence: Qing Yun LiDepartment of Pulmonary and Critical Care Medicine, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, No. 197 Ruijin 2nd Road, Shanghai 200025, People’s Republic of ChinaTel +86 1 350 173 8686Fax +86 215 764 3271Email liqingyun68@hotmail.comPurpose: Pulmonary rehabilitation (PR) is essential to manage patients with COPD. The aim of this study was to investigate the appropriate intensity of PR exercise training for patients with moderate-to-severe COPD.Patients and methods: A prospective multicenter randomized controlled trial was conducted from January 2014 to October 2018. The subjects were randomly assigned to three groups with different intensities of PR, according to their maximum oxygen uptake percentage determined by cardiopulmonary exercise testing. After 20 weeks of exercise training, the effects of low-, moderate-, and high-intensity exercise interventions on patients were compared to determine the most appropriate PR prescription.Results: For patients with moderate COPD, all the measured parameters were significantly improved in the moderate- and high-intensity PR groups (P0.05).Conclusion: High-intensity PR exercise is helpful for patients with moderate to severe COPD. Moderate COPD patients need to receive intensive PR training; the improvement degrees from PR intervention were higher than those of the severe COPD patients. For patients with severe COPD, high-intensity PR exercise may be more beneficial if patients can tolerate it.Keywords: chronic obstructive pulmonary disease, cardiopulmonary exercise testing, exercise therapy, pulmonary rehabilitation

Background College students with suicidal ideation (SI) are at high risk of suicide. Adverse childhood experiences (ACEs) are important risk factors for suicidal behavior. Most research in this area has been restricted to 10 conventional ACEs and suggests negative long-term developmental effects from other common childhood adversities such as peer victimization, peer isolation/rejection, exposure to community violence, and low socioeconomic status. Objective To test the unique and cumulative associations of 14 different ACEs with SI among young adults. Participants and Setting Participants were 989 college students from two universities in China’s provincial-leveled Hui Autonomous Region. Methods Associations between ACEs and SI were analyzed by logistic regression. A Chi-square trend test was used to examine the association between cumulative ACEs and SI. Results The rates of suicidal ideation, plans, and attempts among the cohort were 11.9%, 3.7%, and 1.6%, respectively; 43.9% had experienced at least one ACE. The strongest predictor of SI in adulthood was peer isolation/rejection, followed by emotional neglect, then low socioeconomic status. There was a cumulative effect of ACEs and SI, whereby the greater the number of ACEs, the greater the likelihood of SI. Conclusion Peer isolation/rejection, emotional neglect, and low socioeconomic status were associated with increased risk of SI in adulthood. Two (peer isolation/rejection and low socioeconomic status) of the three factors that emerged from the analysis are not typically included in ACEs research. There was a cumulative effect of 14 kinds of ACEs on SI among young adults. Early recognition of risk factors is therefore important.

Rationale: X-linked lymphoproliferative syndromes (XLPs) are rare, yet often fatal primary immunodeficiency diseases, which rarely manifest as Langerhans cell histiocytosis (LCH) complicated with hemophagocytic lymphohistiocytosis (HLH). Clinical data of a case of XLP-2 manifesting as LCH complicated with HLH was retrospectively analyzed to determine the etiology and causal gene. Patient concerns and diagnosis: The diagnosis of multisystem LCH was confirmed by skin biopsy and other examinations in a 13-month boy with recurrent ear discharge, fever and hemorrhagic papules for 3 months. A good therapeutic response to LCH-III protocol-directed induction chemotherapy was achieved but unremitting HLH developed 6 weeks after the initiation of induction chemotherapy. To identify possible underlying genetic causes, gene mutation analysis was undertaken. A novel XIAP gene mutation (c.99delT, p.F33fsX37) was documented. Interventions: After the diagnosis of HLH had been confirmed, HLH-2004-directed chemotherapy was instituted. Outcomes: The clinical condition of the patient had become progressively deteriorating after 8-week chemotherapy of HLH-2004 protocol, requiring frequent infusions of RBC suspensions and apheresis platelets. His parents decided to receive no further therapy, and the patient died soon after discharge. Lessons: Meticulous laboratory investigations including genetic studies should be undertaken in young children with LCH complicated with HLH and poor therapeutic response.

Background and objective Accurate dose of compression imposed by functional compression garments, such as medical compression stockings, is critical for medical treatment or rehabilitation. To evaluate or provide fitted compression stockings for individuals, the real curved calf shapes other than just anthropometric parameters are required. Methods This paper proposes and verifies a simple 3D parametric model of human calf that can fast and efficiently construct representative calves for evaluation or size-design purposes. Instead of selecting feature points, shape parameters were used to characterize the real calves. Results Based on principal component analysis and a database of 220 scanned Chinese subjects, the proposed parametric model was found as capable of largely reducing the data complexity to only the 1st order principal component with a major variance percentage of as high as 96%. A methodological framework of parametric modeling was then proposed. Results show that the proposed parametric model and method can fast produce valid representative shapes of patients’ calves, with which commercial stockings can be evaluated and customized stockings can be designed. Conclusions It can be concluded that the proposed parametric model and method can highly boost evaluation/size customization of MCSs, and will also inspire the research on customization of other compression garments.

Gastric cancer is one of the most common malignancies in the world. A number of miRNAs are aberrantly expressed during the progression of gastric cancer. In this study, we aimed to investigate the role of miR-203 in the invasion and metastasis of gastric cancer and the potential mechanism of the effect of miR-203 on the tumor progression of gastric cancer. Our results showed that miR-203 was significantly downregulated in gastric cancer tissues and cells, while ataxia telangiectasia mutated kinase (ATM) was upregulated in gastric cancer tissues and cells and was directly regulated by miR-203. Ectopic overexpression of miR-203 inhibited the colony formation, migration, and invasion of gastric cancer cells. In addition, miR-203 overexpression significantly suppressed the protein level of Snail and obviously promoted the protein level of E-cadherin in gastric cancer cells. ATM knockdown phenocopied the effect of miR-203 overexpression. These results suggested that miR-203 suppressed the migration and invasion of gastric cancer through regulating the level of ATM-mediated-Snail and E-cadherin. MiR-203 might be a novel therapeutic strategy for the treatment of gastric cancer.

Transarterial embolization (TAE) appears to be a safe and effective treatment for patients with intractable epistaxis, despite different etiologies or angiography findings. Idiopathic epistaxis is prone to present with negative angiographic findings.To retrospectively evaluate the safety and effectiveness of TAE for intractable epistaxis, and focus on the factors of etiology and angiographic findings.From March 2008 to December 2014, the data of 43 patients with intractable bleeding undergoing TAE were reviewed. The outcomes of interventional therapy were assessed according to different etiology (malignant or benign disease) and angiographic finding (positive or negative angiogram).Positive angiographic findings were found in 11 of 12 cases with malignant diseases and 22 of 31 cases with benign diseases, respectively (p = 0.237). Among the 10 cases with negative angiographic findings, the negative angiography rate of idiopathic epistaxis was higher than that of epistaxis with definite etiology (p = 0.003). Bleeding was controlled successfully in all of the 43 patients after embolization. During the mean follow-up period of 24.0 ± 16.7 months, five patients relapsed. No significant difference was found in recurrence rates between malignant and benign diseases or between positive and negative angiography (p = 0.241, p = 0.704, respectively).

Setting Tertiary referral centre. Objective To retrospectively observe the characteristics of bronchial angiograms in the setting of systemic artery-pulmonary circulation shunts (SPS), and to evaluate the safety and effectiveness of bronchial artery embolisation (BAE) for these patients with life-threatening haemoptysis. Design The records of life-threatening haemoptysis patients with SPS who presented to a tertiary referral centre from January 2009 to March 2014 were reviewed. Results SPS consisted of bronchial artery-pulmonary artery shunt (AAS) in 30 cases, bronchial artery-pulmonary vein shunt (AVS) in 4 cases, non-bronchial systemic artery-pulmonary circulation shunt (n-BPS) in 7 cases and more than one type of SPS in 4 cases (AAS and AVS in 3 cases, three types of SPS in 1 case). BAE using polyvinyl alcohol (PVA) was successful in 97.8% (44/45) of the patients. Cumulative rates of freedom from recurrence at 1 month, 1 year and 2 years were respectively 97.8%, 93.2% and 85.4%. No major procedure-related complications occurred. No significant differences were found in recurrence rates or cumulative haemoptysis control rates among patients with different types of SPS complications (P = 0.55 and 0.46, respectively). Conclusion BAE with PVA was safe and effective for life-threatening haemoptysis complicated by SPS.

Pendred syndrome is an autosomal recessive disorder characterized by hearing loss and goiter and is caused by bi-allelic mutations (homozygous or compound heterozygous) of the PDS (SLC26A4) gene. The incidence of Pendred syndrome is 7.5-10/100,000 in the general population, and it carries a 1 % risk of developing thyroid carcinoma. Herein, we report a case of a patient with Pendred syndrome who developed a follicular variant of papillary thyroid carcinoma (FVPTC)-that is approximately at an odd of 1/1,000,000. Targeted next-generation sequencing with ThyroSeq v2 was performed on the tumor, and only a TP53 mutation (TP53 p.R175H) was identified. The mutation was limited to the tumor nodule of FVPTC as shown by immunohistochemistry. This report represents the first extensive molecular study of a Pendred syndrome-associated thyroid carcinoma. The evidences support that thyroid carcinomas arising from dyshormonogenetic goiter require additional genetic alteration in addition to the purported thyroid-stimulating hormone (TSH) overstimulation. It is intrigue to note that the mutant p53 is involved in the development of a low-grade malignant thyroid tumor as FVPTC in this patient.

Ankylosing spondylitis (AS) is a common inherited autoimmune disease. Copy number variation (CNV) of DNA segments has been found to be an important part of genetic variation, and the FCGR3A and FCGR3B gene CNVs have been associated with various autoimmune disorders. The aim of the study was to determine whether CNVs of FCGR3A and FCGR3B were also associated with the susceptibility of AS. A total of 801 individuals including 402 AS patients and 399 healthy controls were enrolled in this study. The copy numbers of FCGR3 gene (two fragments, included FCGR3A and FCGR3B) were measured by AccuCopy™ methods. Chi-square test and logistic regression model were used to evaluate association between FCGR3 gene CNVs and AS susceptibility. P values, odds ratio, and 95% confidence intervals (CIs) were used to estimate the effects of risk. Significantly, difference in the frequencies of FCGR3A and FCGR3B gene CNVs was founded between the patients with AS and controls. For the FCGR3A gene, a low (≤3) copy number was significantly associated with AS [for ≤3 copies versus 4 copies, (OR 2.17, 95% CI (1.41, 3.34), P < 0.001, adjusted OR 2.22, 95% CI (1.44, 3.43), P < 0.001)]. A low FCGR3B copy number was also significantly associated with increasing risk of AS [for ≤3 copies versus 4 copies, (OR 1.87, 95% CI (1.25, 2.79), P = 0.002, adjusted OR 1.94, 95% CI (1.29, 2.91), P = 0.001)]; however, both the high FCGR3A and FCGR3B copy numbers (≥5) were not significantly associated with the risk of AS (≥5 copies versus 4 copies). The lower copy numbers (≤3) of FCGR3A and FCGR3B genes confer a risk factor for AS susceptibility.

Background: Non-alcoholic fatty liver disease (NAFLD), especially non-alcoholic steatohepatitis, which is considered as the hepatic manifestation of metabolic syndrome, has a great prevalence all over the world. New drugs are urgently needed for the treatment of NAFLD. This review will be to assess the efficacy and safety of omega-3 polyunsaturated fatty acids (n-3 PUFAs) on liver-related outcomes (liver histology and liver enzymes) in patients with NAFLD. Methods: We will search 5 databases for relative studies: Medline, the Cochrane Library, EMBASE, Web of Science, and ClinicalTrials.gov and identified all reports of randomized controlled trials published prior to July 2020. Two authors will independently scan the articles searched, extract the data from articles included, and assess the risk of bias by Cochrane tool of risk of bias. Disagreements will be resolved by discussion among authors. All analysis will be performed based on the Cochrane Handbook for Systematic Reviews of Interventions. Fixed-effects model or random-effects model will be used to calculate pooled estimates of weighted mean difference with 95% confidence intervals. Results: This systematic review aims to examine the effect of n-3 PUFAs on liver histology and liver enzymes in patients with NAFLD. Conclusions: These findings will provide guidance to clinicians and patients on the use of n-3 PUFAs for NAFLD. Ethics and dissemination: This study is a protocol for a systematic review of n-3 PUFAs as a treatment of NAFLD patients. This review will be published in a journal and disseminated in print by peer-review. Systematic review registration: INPLASY202050008.

To identify the key genes and pathways in the development of hepatocellular carcinoma (HCC) from hepatitis B virus (HBV)-positive liver cirrhosis, differentially expressed genes (DEGs) between HCC and liver cirrhosis tissue samples from the {"type":"entrez-geo","attrs":{"text":"GSE17548","term_id":"17548"}}GSE17548 gene expression profile dataset were screened. A total of 1,845 DEGs were identified, including 1,803 upregulated and 42 downregulated genes. Gene Ontology, Kyoto Encyclopedia of Genes and Genomes (KEGG) and protein-protein interaction (PPI) network analyses were performed. It was identified that the ‘cell cycle’ and ‘progesterone-mediated oocyte maturation’ KEGG pathways were significantly enriched in the DEGs. In addition, the high expression of the hub genes from the PPI network (including cyclin dependent kinase 1, cyclin B1, cyclin B2, mitotic arrest deficient 2 like 1, BUB1 mitotic checkpoint serine/threonine kinase and cyclin A2; P=0.00116, 0.00021, 0.04889, 0.00222, 0.00015 and 0.00647, respectively) was associated with a decrease in overall survival for patients with HCC as identified using survival and expression data from The Cancer Genome Atlas. The identified hub genes and pathways may help to elucidate the molecular mechanisms of HCC progression from HBV-positive liver cirrhosis. Additionally, they may be useful as therapeutic targets or serve as novel biomarkers for HCC prognosis prediction.

Ultra-weak bioluminescence (UWL) is a physiological phenomenon widely existing in all the biological activities including human, animals, plants, etc., which reflects the energy metabolism of the organism. Since the last century, ultra-weak photon emission (UPE) has been applied to the study of the essence of meridians and acupoints of traditional Chinese medicine and obtained some results as the higher luminescence characteristics, but many problems remain unsolved due to the limitation of detection technology. In recent years, along with the development of bioluminescence signal acquiring system and imaging system, we are able to further explore the characteristics and biological mechanisms of UWL of acupuncture points and meridians in the human body. We proposed to study changes of ultra-weak luminous intensity of acupuncture points and meridians before and after needling stimulation, and the delayed effect of UPE phenomenon, etc., trying to reveal their regularities and essence. In this paper, the prospect of application of UPE to acupuncture research is also discussed by combining newly acquired results of some biological substances of acupoints in experimental studies.

To evaluate the effectiveness and safety of simultaneous placement of a self-expandable metallic stents (SEMS) and iodine-125 seed strand in the management of malignant obstructive jaundice (MOJ). This study included 132 patients with MOJ treated from November 2015 to October 2017. Forty-five patients underwent insertion of SEMS with iodine-125 seed strands (Seeds group); the remaining 87 patients underwent SEMS placement alone (Control group). Technical success was defined as accurate, successful deployment of SEMS with or without iodine-125 seed strand; clinical success was defined as 20% reduction in serum bilirubin within 1 week after the procedure, compared with baseline. Complications, duration of primary stent patency, and overall survival were evaluated. Technical success was achieved in all patients in both groups. In the Seeds group, an average of 14 seeds (range 8–22) were implanted in the bile duct as a strand. Clinical success rates were similar between the groups (Seeds group, 93.3%; Control group, 95.4%). Major complications occurred in only one patient, in the Control group. The median period of primary stent patency was significantly longer in the Seeds group (194 days) than in the Control group (86 days; P = 0.049). The median overall survival was also significantly longer in the Seeds group (194 days) than in the Control group (96 days; P = 0.031). SEMS combined with iodine-125 seed strands is effective and safe in the management of MOJ and can improve stent patency and patient survival.

Rationale: Blue rubber bleb nevus syndrome (BRBNS) is a rare vascular disorder consisting of multifocal venous malformations. Delayed diagnosis or misdiagnosis frequently occurs in patients without typical cutaneous lesions or gastrointestinal bleeding symptoms. This article reports a 10-year case of delayed diagnosis of BRBNS detected by capsule endoscopy. Patient concerns and diagnosis: A 15-year-old girl presented with refractory iron-deficiency anemia (IDA) for 10 years, without any hemorrhagic signs or noticeable cutaneous lesions, which led to her obvious physical growth retardation. Capsule endoscopic examination revealed dozens of vascular blebs distributed from the jejunum to the ileum and a site of active bleeding. Hence, she was diagnosed with BRBNS. Interventions: Laparotomy was performed with resection of the small bowel lesions, and iron supplementation was prescribed for 3 months. Postoperatively, the patient had an uncomplicated course. Outcomes: On follow-up after 3 years, IDA in this patient was cured and she did not require further blood transfusion and showed excellent vigor. Lessons: A high index of suspicion for BRBNS and adequate endoscopy examination will help to identify the origin of refractory IDA in older children, particularly in patients with vascular lesions of the skin.

OBJECTIVE To evaluate the ability of contrast-enhanced transrectal ultrasound (CETRUS) scanning for prostate cancer detection in different area, compared with conventional transrectal ultrasound (TRUS). METHODS 228 patients underwent TRUS-guided prostate biopsy after examinations of TRUS and CETRUS scanning. Cancer detection between CETRUS and TRUS were compared by patient and by site in different areas (right, left; base, mid-gland, apex). The receiver operating characteristic (ROC) curve was plotted to evaluate the diagnostic performance of CETRUS. RESULTS 89 patients were malignant and 48 patients were significant cancer. Compared with TRUS, CETRUS could increase the detection rates of overall and significant cancer (P = 0.008; P = 0.031). CETRUS had higher sensitivity, specificity (except right lobe), accuracy, positive predictive value (PPV) and negative predictive value (NPV) in total, right and left lobe (P

Background Renal arteriovenous malformation is an aberrant vascular connection between the renal artery and vein. Acquired renal arteriovenous malformation (arteriovenous fistulae) accounts for approximately 70% of renal arteriovenous abnormalities. Congenital renal arteriovenous malformation, relatively rare, can result in significant hematuria which may require arterial embolization or nephrectomy. Case presentation A 64-year-old Asian man presented to the Urology department in our hospital with gradual left scrotal swelling for 2 years. Ultrasound and computed tomography showed an irregular mass in the upper pole of his left kidney. Digital subtraction angiography confirmed cirsoid-type left renal arteriovenous malformation combined with left renal vein ostial stenosis. After digital subtraction angiography and selective segmental renal artery embolization, the varicocele was obviously alleviated. Conclusions The etiology diagnosis of varicocele is not always straightforward, and renal arteriovenous malformation should be considered in the differential diagnosis of varicocele and renal mass. Renal arteriovenous malformation is difficult to distinguish from renal tumor according to varicocele and computed tomography presentation, while magnetic resonance imaging and digital subtraction angiography help to make a definite diagnosis and selective renal angiographic embolization is one of the best treatments for renal arteriovenous malformation.

Clear cell follicular carcinoma is a rare type of thyroid cancer and some with aggressive biological behavior. The cytoplasmic clearing of the neoplastic cells has been attributed to the accumulation of various substances, such as glycogen, lipid, mucin, and thyroglobulin, or distension of mitochondria or endoplasmic reticulum. However, the molecular mechanisms responsible for the characteristic appearance of the cell cytoplasm and the biological behavior remain unknown. We report here a case of aggressive clear cell follicular carcinoma of the thyroid with molecular profile using targeted next generation sequencing (NGS) that presented as a metastatic tumor in a woman with a history of breast carcinoma. The NGS data revealed the coexisting of a well-characterized loss-of-function TP53 R248Q mutation and a putative gain-of-function mutation of TSHR L272V, which was suggested by the overexpression of thyroglobulin and SLC5A5 (NIS) genes in this tumor. TP53 mutations are usually related with dedifferentiation, progression, and metastasis of thyroid carcinomas. Identification of TP53 R248Q in this tumor correlated with its aggressive clinical behavior. Gain-of-function mutation of TSHR can overstimulate the thyroid follicular cells as the elevated level of TSH does and might have contributed to the development of clear cell morphology in this tumor. This report represents the first case of clear cell follicular carcinoma of the thyroid with NGS analysis and more molecular characterization is needed to elucidate the pathogenesis and provide more prognosis-relevant information for this uncommon variant of thyroid carcinomas.

The relationship between the endoplasmic reticulum aminopeptidase 1 (ERAP1) polymorphisms and ankylosing spondylitis (AS) was inconsistent in the recent literatures, a meta-analysis was therefore performed.A total of 25 independent studies with 24,271 AS patients and 42,666 controls were included after searching electronic databases for studies published before June 2014. The pooled and individual odds ratios (ORs) with 95% confidence intervals (CIs) were presented to assess the associations between ERAP1 polymorphisms and AS in different ethnicities.This meta-analysis includes 25 studies that investigate 8 single nucleotide polymorphisms (SNPs; rs17482078, rs30187, rs2287987, rs27044, rs26653, rs10050860, rs27037, and rs27434) in ERAP1 gene. Overall, six SNPs were associated with AS; two SNPs (rs27044 and rs26653) were not when all studies were pooled into the meta-analysis (rs27044 G vs. C, OR = 1.058, 95% CI = 0.827-1.354; rs26653 C vs. G, OR = 1.154, 95% CI = 0.937-1.422). In Caucasians, all the 8 SNPs were significantly associated with AS. But 5 SNPs (rs17482078, rs2287987, rs27044, rs26653, and rs10050860) did not show statistical association with the risk of AS in Asians.ERAP1 polymorphisms were associated with AS in Caucasians, but their association with AS in Asians needs further exploration.

Carcinosarcomas (malignant mixed Mullerian tumors or MMMT) are rare malignant tumors in the female genital tract composed of both malignant epithelial and malignant mesenchymal components. They comprise

Danshen (Salvia miltiorrhiza) preparations such as Danhong injection, Danshen injection, Salvianolate injection, compound Danshen injection and Sodium Tanshinone IIA Sulfonate (STS) injection are widely used in China to treat stable angina (angina pectoris) caused by coronary heart disease. In this study we compared the network pharmacological mechanisms of the 5 Danshen preparations. Following a literature search performed in PubMed, EMBASE, Cochrane Library, China National Knowledge Infrastructure (CNKI) database, China Biology Medicine (CBM) database, China Conference Paper Database, Wanfang Database, VIP Database and Conference Proceedings Citation Index (through January 2015), 444 randomized controlled trial publications detailing the use of the 5 Danshen-based injections for treating stable angina were identified, and their combined data were analyzed using a network meta-analysis. All of the 5 Danshen-based preparations were effective in treating stable angina with clinical improvement rates of 72.4%-91.6% and electrocardiogram (ECG) improvement rates of 54.5%-71.6%. According to both clinical improvement and ECG improvement, the 5 Danshen-based preparations were ranked as follows: Danhong injection > Salvianolate injection > STS injection > compound Danshen injection > Danshen injection. There were no significant differences among the safety profiles of the 5 Danshen preparations. The meta-analysis results were further examined using a network pharmacology approach and functional enrichment analysis, which revealed that Danshen and Danhong injections affected 4 and 15 signaling pathways, respectively, and that the 4 signaling pathways affected by Danshen were a subset of those influenced by Danhong. Therefore, Danhong injection affected some unique signaling pathways that might regulate lipoprotein metabolism, oxidation, and inflammation, and protect vascular endothelia, reflecting the multi-component and multi-target characteristics of this traditional formula and its strengths in treating complex diseases.

Metastatic carcinoma to the pancreas is uncommon and head and neck squamous carcinoma metastatic to the pancreas is extremely rare. Metastatic squamous cell carcinoma to the pancreas presents a unique diagnostic challenge: in addition to mimicking the rare primary squamous cell carcinoma of the pancreas based on cytologic, histologic, and immunohistochemical features, it may be mistaken for a cystic neoplasm of the pancreas because of its high predilection for cystic degeneration in metastatic sites. Herein, we report a case of tonsillar squamous cell carcinoma with a cystic pancreatic metastasis diagnosed by ultrasound-guided fine needle aspiration biopsy (EUS-FNA). This represents a third reported case of metastatic squamous cell carcinoma to the pancreas from the head and neck region. Metastatic squamous cell carcinoma should be considered in the differential diagnosis of EUS-FNA during evaluation of pancreatic cystic lesion.

Background The management of breakthrough pain in cancer patients is always a challenge for medical professions. Occurring in 80% of cancer patients with advanced disease, breakthrough pain significantly decreases both patient’s and caregiver’s quality of life. The aim of this study is to assess the analgesic efficacy of a fixed inhaled nitrous oxide/oxygen mixture for adult cancer patients with breakthrough pain. Methods/design This is a randomized, placebo-controlled, double-blind study; it will be conducted in the General Hospital of Ningxia Medical University. The target study subjects are at least 18 years old, and are hospitalized cancer patients who are receiving routine opioids to control cancer-related pain but still experience breakthrough pain. A total of 240 patients will be recruited and randomly allocated between three treatment groups (A, B, C) and a control group (group D) in a ratio of 3:1. All treatment groups (A, B, C) will receive standard pain treatment (oral immediate-release morphine) plus a pre-prepared nitrous oxide/oxygen mixture, and the control group (D) will receive the standard pain treatment plus oxygen. Patients, doctors, nurses, and data collectors are all blind to the experiment. Assessments will be taken before treatment (T0), at 5 min (T1) and 15 min (T2) during treatment, and at 5 min after treatment (T3). The primary endpoint measures will be the percentage of patients whose pain is relieved at T1, T2, and T3. Secondary outcome measures will include the safety of treatment, adverse events, and satisfaction from both health professionals and patients. Discussion This study aims to provide an effective and practical intervention for a fast breakthrough pain relief and to improve cancer patients’ quality of life significantly. The Evidence-Based Medicine Working Group claim that a randomized, double-blind, placebo-controlled experimental intervention is the most appropriate design to demonstrate its efficacy, so this study could give a new approach to controlling breakthrough pain episodes. Trial registration ChiCTR-INC-16008075. Registered on 8 March 2016. Electronic supplementary material The online version of this article (doi:10.1186/s13063-016-1739-9) contains supplementary material, which is available to authorized users.

Combinations of chemotherapeutic drugs with nucleic acid has shown great promise in cancer therapy. In the present study, paclitaxel (PTX) and DNA were co-loaded in the hyaluronic acid (HA) and folate (FA)-modified liposomes (HA/FA/PPD), to obtain the dual targeting biomimetic nanovector. The prepared HA/FA/PPD exhibited nanosized structure and narrow size distributions (247.4 ± 4.2 nm) with appropriate negative charge of −25.40 ± 2.7 mV. HA/FA/PD (PTX free HA/FA/PPD) showed almost no toxicity on murine malignant melanoma cell line (B16) and human hepatocellular carcinoma cell line (HepG2) (higher than 80% cell viability), demonstrating the safety of the blank nanovector. In comparison with the FA-modified PTX/DNA co-loaded liposomes (FA/PPD), HA/FA/PPD showed significant superiority in protecting the nanoparticles from aggregation in the presence of plasma and degradation by DNase I. Moreover, HA/FA/PPD could also significantly improve the transfection efficiency and cellular internalization rates on B16 cells comparing to that of FA/PPD (p < 0.05) and PPD (p < 0.01), demonstrating the great advantages of dual targeting properties. Furthermore, fluorescence microscope and flow cytometry results showed that PTX and DNA could be effectively co-delivered into the same tumor cell via HA/FA/PPD, contributing to PTX/DNA combination cancer treatment. In conclusion, the obtained HA/FA/PPD in the study could effectively target tumor cells, enhance transfection efficiency and subsequently achieve the co-delivery of PTX and DNA, displaying great potential for optimal combination therapy.

Previous studies have found that serum levels of interleukin (IL)-33 are elevated in patients with ankylosing spondylitis (AS). The aim of this study was to determine whether the single nucleotide polymorphisms (SNPs) in the IL-33 gene are associated with susceptibility to AS in a Chinese population.Eight SNPs in the IL-33 gene (rs1891385, rs16924144, rs2210463, rs16924159, rs10118795, rs1929992, rs10975519, and rs1048274) were genotyped by the improved multiplex ligase detection reaction (iMLDR) method in 400 patients with AS and 395 geographically and ethnically matched healthy controls. Haplotypes were constructed after linkage disequilibrium (LD) analysis.There were statistically significant differences at SNPs rs1891385, rs2210463, rs10118795, rs1929992, rs10975519, and rs1048274 in the IL-33 gene between cases and controls. The A allele frequency of rs1891385 was lower in the patient group than in the controls [odds ratio (OR) 0.762] whereas the A allele frequency of rs2210463 and the C allele frequency of rs10118795 and rs1929992 were higher in the patient group than in the controls (OR 1.265, 1.305, and 1.248, respectively). However, there were no differences in the genotype distribution and allele frequencies of rs16924144 and rs16924159 between the patients and controls (p0.05). Four SNPs (rs10118795, rs1929992, rs10975519, and rs1048274) were in strong LD and were included in four haplotypes: ht1 (CCCG), ht2 (CCTA), ht3 (CTCG), and ht4 (TTCG). Haplotype ht4 was associated with a decreased risk of AS [OR 0.766, 95% confidence interval (CI) 0.626-0.937, χ(2) = 6.761, p = 0.009].The results suggest that SNPs and the TTCG haplotype of the IL-33 gene are associated with the development of AS in a Chinese Han population.

Published association studies of killer cell immunoglobulin-like receptors (KIRs) and ankylosing spondylitis (AS) in populations are inconsistent. The aim of this study is to determine whether the KIR polymorphisms confer susceptibility to AS in populations by conducting a meta-analysis.A computer search was carried out up to August 2013 for literature pertaining to AS and KIR polymorphisms. Publications addressing the association between the KIR polymorphisms and susceptibility to AS in populations were selected from the Pubmed, Elsevier Science Direct, China National Knowledge Infrastructure (CNKI) and Chinese Biomedical Literature Database (CBM) databases. The odds ratio (OR) with 95% confidence interval (95%CI) was calculated.A total of 13 case-control studies in 9 articles were included in this meta-analysis. Meta-analysis results identified two positive associations of 2DS4 and 3DS1 with susceptibility to AS in populations. In subgroup analysis, there was a positive association between 2DS4 and susceptibility to AS in Asians, but not in Caucasians. And there were associations between 3DL1, 3DS1 and susceptibility to AS in Caucasians, but not in Asians. Results of subgroup analysis also showed that there were associations between 2DL5, 2DS4, 2DS5, 3DL1, 3DS1 and susceptibility to AS in HLA-B*27-positive patients and HLA-B*27-positive healthy controls.This meta-analysis confirms that 2DS4 and 3DS1 might be potential risk factors for AS in populations.

Background: Breakthrough pain is an extremely painful symptom that impairs quality of life in cancer patients. It negatively impacts their emotional wellbeing, physical function, and mental health. The aim of this study is to use a qualitative methodology to examine the perception of cancer patients with breakthrough pain in the Northwest of China. Methods: A semi-structured, face-to-face interview was conducted with nine cancer patients who experienced breakthrough pain; and a qualitative content analysis was performed. Results: Five themes were generated: (1) sufferings from breakthrough cancer pain, (2) hopelessness and helplessness, (3) perception of breakthrough cancer pain and analgesia, (4) strong as a Chinese, and (5) support needed from health care system. Conclusion: Although certain traditional cultural worldviews increase patients' acceptance of pain, healthcare providers need proper treatment guidelines to improve the quality of cancer patient care in Northwest China. We recommend that healthcare workers and hospital managers place cancer pain management in higher priority. Relevant pain management education programs should be provided to both healthcare providers and patients to improve their knowledge in these area. Healthcare professionals need to establish a mutual communication channel between patients and healthcare workers to meet patients' needs during breakthrough pain episodes in order to improve pain management. Nevertheless, the government and the healthcare system need to recognize the importance and urgency of palliative care services.

The purpose of this study was to evaluate the influence of the serum prostate-specific antigen (PSA) level, prostate volume, and PSA density on prostate cancer detection with contrast-enhanced sonography using contrast-tuned imaging technology compared with baseline imaging (combination of grayscale and power Doppler imaging).In all, 161 patients were evaluated with grayscale, power Doppler, and contrast-tuned imaging. Biopsy was performed at 10 sites in each patient. When an abnormality was shown on any of these examinations, the biopsy was directed toward the abnormality. Cancer detection between contrast-tuned imaging and baseline imaging was compared for different subgroups according to PSA level (4-10, 10-20, and20 ng/mL), prostate volume (35, 35-50, 50-65, and65 mL), and PSA density (0.15, 0.15-0.30, 0.30-0.50, and0.50).In total, 413 sites were malignant in 78 patients. By biopsy site, the accuracy was greater for contrast-tuned imaging than for baseline imaging in all PSA level, prostate volume, and PSA density subgroups except 0.30 to 0.50 (all P.05). Contrast-tuned imaging had significantly higher sensitivity in the subgroups with PSA levels between 4 and 20 ng/mL, prostate volumes between 35 and 65 mL, and PSA densities between 0.15 and 0.50 than baseline imaging (all P.05); it also had significantly higher specificity for all PSA level subgroups except 10 to 20 ng/mL, all prostate volume subgroups except 35 to 50 mL, and all PSA density subgroups except 0.30 to 0.50 (all P.05).Contrast-tuned imaging could improve cancer detection over baseline imaging in patients with different PSA levels, prostate volumes, and PSA densities.

Gemcitabine has been increasingly prescribed for the treatment of gallbladder cancer. However, the response rate is low. The aim of this study is to determine whether icariin, a flavonoid isolated from Epimedi herba, could potentiate the antitumor activity of gemcitabine in gallbladder cancer.Human gallbladder carcinoma cell lines GBC-SD and SGC-996 were tested. Cell proliferation and apoptosis were analyzed using MTT assay and flow cytometry, respectively. The expression of apoptosis- and proliferation-related molecules was detected with Western blotting. Caspase-3 activity was analyzed using colorimetric assay, and NF-κB activity was measured with ELISA. A gallbladder cancer xenograft model was established in female BALB/c (nu/nu) mice. The mice were intraperitoneally administered gemcitabine (125 mg/kg) in combination with icariin (40 mg/kg) for 2 weeks.Icariin (40-160 μg/mL) dose-dependently suppressed cell proliferation and induced apoptosis in both GBC-SD and SGC-996 cells, with SGC-996 cells being less sensitive to the drug. Icariin (40 μg/mL) significantly enhanced the antitumor activity of gemcitabine (0.5 μmol/L) in both GBC-SD and SGC-996 cells. The mice bearing gallbladder cancer xenograft treated with gemcitabine in combination with icariin exhibited significantly smaller tumor size than the mice treated with either drug alone. In GBC-SD cells, icariin significantly inhibited both the constitutive and gemcitabine-induced NF-κB activity, enhanced caspase-3 activity, induced G(0)-G(1) phase arrest, and suppressed the expression of Bcl-2, Bcl-xL and surviving proteins.Icariin, by suppressing NF-κB activity, exerts antitumor activity, and potentiates the antitumor activity of gemcitabine in gallbladder cancer. Combined administration of gemcitabine and icariin may offer a better therapeutic option for the patients with gallbladder cancer.

To evaluate the efficacy and safety of cyanoacrylate glue embolization in the treatment of severe arterioportal shunt (APS) presenting with hepatofugal portal venous flow in hepatocellular carcinoma (HCC) patients. Between July 2000 and January 2010, 27 HCC patients with severe APS presenting with hepatofugal portal venous flow underwent transarterial angiography and treatment. Among them, four patients were excluded from the study. Twelve patients underwent transarterial chemoperfusion and embolization of APS with cyanoacrylate glue between January 2006 and January 2010 (Emb group), and the other 11 patients undergoing only transarterial chemoperfusion without embolization of APS between July 2000 and December 2005 served as a control group (non-Emb group). The change of APS, survival rates, and procedure related complications were analyzed. In the Emb group, APS was improved in all of the 12 patients after initial glue embolization; long-term APS improvement with hepatopetal portal flow was achieved in 80 % (8 of 10) patients who underwent follow-up angiography. Survival rates in the Emb group were 67 % at 6 months, 33 % at 1 year, and 8 % at 2 years, whereas those in the non-Emb group were 0 % at 6 months (P

Background In recent years, with social and economic development and lifestyle changes, the incidence of gastric cancer as well as the surgical results and prognoses of patients with gastric cancer have changed significantly in southeast China. Methods A total of 1,451 patients were divided into 2 groups according to admission time periods. Trends in clinicopathologic characteristics and operative outcomes of these patients were analyzed retrospectively. Results The numbers of old and young patients were significantly increased in period 2 compared with period 1. Tumors located in the proximal stomach increased from 20.26% to 36.83%. The incidence of early gastric cancer was significantly increased from period 1 to period 2. Lymph node metastasis was seen more prevalently in period 2 than in period 1. The rate of operation-related major complications decreased from 5.23% to 1.43%. Operative mortality was .49% in period 1 and .24% in period 2. The 5-year survival rate increased from 38.40% to 53.99%. Conclusions Early diagnosis, standardized surgical treatment including pertinent lymph node dissection, and better perioperative care notably improve the outcomes of patients with gastric cancer.

Osteoarthritis is a degenerative joint disease, in which matrix metalloproteinase (MMP)-13 plays an important role. This study aimed to investigate miRNA-140-mediated negative regulation of MMP-13 expression in interleukin-1β (IL-1β)-stimulated human cartilage cells.The human cartilage cell line C28/I2 was cultured in the presence of IL-1β to mimic an osteoarthritic environment. Expression of miRNA-140 and MMP-13 was analyzed after 48 h by real-time RT-PCR and western blot analyses. MiRNA-140 mediated regulation of MMP-13 expression was analyzed by luciferase reporter assays and anti-miRNA-140 oligonucleotide transfection. Furthermore, miRNA-140 and MMP-13 expression was analyzed following DHMEQ treatment.Expression of miRNA-140 and MMP-13 was elevated in IL-1β-stimulated C28/I2 cells. Bioinformatic prediction showed that the 3'-UTR of MMP-13 mRNA contained a potential binding miRNA-140 site and luciferase mRNA fused with 3'-UTR of MMP-13 mRNA was shown to be repressed by miRNA-140 in reporter assays. Expression of MMP-13 was elevated in IL-1β-stimulated C28/I2 cells following anti-miRNA-140 oligonucleotide transfection. NF-κB activity was inhibited in DHMEQ treated IL-1β-stimulated C28/I2 cells and was associated with decreased miRNA-140 and MMP-13 expression.Expression of miRNA-140 and MMP-13 was induced by IL-1β. Expression of miRNA-140 inhibited MMP-13 in C28/I2 cells. Expression of miRNA-140 and MMP-13 was shown to be NF-κB-dependent.

We prospectively compared clinical response and penile color duplex ultrasound results of oral tadalafil 20 mg plus low dose intracavernous injection of vasoactive agents with those of intracavernous injection and oral tadalafil 20 mg alone. We also observed the best approach to facilitate penile color duplex ultrasound and that most preferred by patients.All 56 patients with erectile dysfunction underwent penile color duplex ultrasound 3 times at an interval of at least 1 week using different pharmacological induction methods, including tadalafil mode (20 mg tadalafil), intracavernous injection mode (30 to 60 mg papaverine) and mixed mode (15 mg papaverine plus 20 mg tadalafil). Ultrasound parameters included peak systolic and end diastolic velocity, resistance index and acceleration time. Clinical response was assessed by the erection hardness score. Patient preference was determined when all tests were finished.For penile color duplex ultrasound parameters no significant difference was observed between intracavernous injection and mixed modes. However, for tadalafil mode peak systolic velocity of the 2 cavernous arteries measured 15 minutes after induction were significantly lower than for intracavernous injection and mixed modes. Also, acceleration time of the right cavernous artery measured 5 minutes after induction and left cavernous artery measured 15 minutes after induction in tadalafil mode were significantly shorter than those in intracavernous injection and mixed modes. No severe side effect occurred in tadalafil and mixed modes but 2 patients experienced priapism in intracavernous injection mode. Of the patients 55.4% preferred tadalafil mode, an incidence significantly higher than intracavernous injection (16.1%) and mixed (28.5%) modes.Oral tadalafil plus low dose vasodilator led to a significantly better clinical response than high dose vasodilator. Penile color duplex ultrasound parameters showed no difference between the 2 modes. Thus, this mixed mode emerges as a possible alternative to high dose vasodilator injection.

Spleen tyrosine kinase (Syk) is reported to be involved in the suppression of proliferation and invasion of breast cancer. Methylation-mediated Syk gene silencing is found in a subset of breast cancer. In this study, we used a DNA methyltransferase inhibitor, 5-aza-2-deoxycytidine (AZA), to restore Syk expression of breast cancer cells. Surprisingly, we found that AZA treatment could reestablish the expression of Syk, but not affect the proliferation of breast cancer cells. Moreover, tumor formation in situ by MDA-MB-435s treated with (+) or without (-) AZA in a nude mice MFP (Mammary fat pad) model did not show significant difference, too. Interestingly, pulmonary metastasis was still significantly suppressed in MDA-MB-435s(+) group (1/9 vs. 7/9). Our findings suggested Syk may be more correlated to metastasis rather than proliferation. This study implied a potential use of Syk methylation as a valuable biomarker to detect high metastatic potential cancerous lesions and the prospect of AZA to join the arsenal of drug candidates to be developed as a new reagent for management of advanced breast cancer.