[Treatment of New Daily Persistent Headache With Esketamine: Report of One Case].

New daily persistent headache (NDPH) is a kind of persistent headache that patients can identify the exact date of the sudden onset.It is one of the rare primary headaches difficult to be cured and may lead to disability,seriously affecting the daily life and work.The exact pathogenesis of NDPH remains unclear,which makes the treatment difficult.Here we report a case of refractory NDPH treated by intravenous injection of esketamine at a sub-anesthetic dose.

Incorporating body mass index into esophageal manometry metrics and mean nocturnal baseline impedance for the evaluation of gastro-esophageal reflux disease.

This study aims to enhance the effectiveness of high resolution manometry (HRM) and pH-impedance monitoring metrics in distinguishing between gastro-esophageal reflux disease (GERD) and non-GERD. A retrospective propensity score matching (PSM) study was conducted on 643 patients with GERD symptoms. PSM matched 134 GERD patients with 134 non-GERD controls. Body mass index (BMI), intra-esophageal pressure (IEP) and intra-gastric pressure (IGP) were significantly higher in the GERD group compared to the non-GERD group. BMI was correlated with IEP and IGP positively. IGP was positively correlated with esophagogastric (EGJ) pressure (EGJ-P) in participants with EGJ type 1 and 2, but not in participants with EGJ type 3. BMI was correlated with distal MNBI negatively. Logistic regression showed BMI as an independent risk factor for GERD. Receiver operating characteristic curve (ROC) and decision curve analysis (DCA) showed that BMI adjusted EGJ contractile integral (EGJ-CI) and BMI adjusted MNBI were superior to the corresponding original ones in predicting GERD susceptibility. According to the findings, BMI and IGP are the main factors contributing to the development of GERD. BMI affects IEP through the adaptive response of EGJ-P to IGP. Incorporating BMI into the calculations of EGJ-CI and MNBI can improve their ability in predicting GERD susceptibility.

Association Between Different Metabolic Obesity Phenotypes and Erosive Esophagitis: A Retrospective Study.

Background and Aim: Obesity is association with elevated risks of erosive esophagitis (EE), and metabolic abnormalities play crucial roles in its development. The aim of the study was to assess the association between metabolic obesity phenotypes and the risk of EE. Methods: This retrospective study enrolled 11,599 subjects who had undergone upper gastrointestinal endoscopy at the First Affiliated Hospital of Dalian Medical University from January 1, 2008, to December 31, 2023. The enrolled individuals were grouped into four cohorts based on their metabolic health and obesity profiles, namely, metabolically healthy non-obesity (MHNO; n=2134, 18.4%), metabolically healthy obesity (MHO; n=1736, 15.0%), metabolically unhealthy non-obesity (MUNO; n=4290, 37.0%), and metabolically unhealthy obesity (MUO; n=3439, 29.6%). The relationships of the different phenotypes of metabolic obesity with the risks of developing EE in the different sexes and age groups were investigated by multivariate logistic regression analysis. Results: The MUNO, MHO, and MUO cohorts exhibited elevated risks of developing EE than the MHNO cohort. The confounding factors were adjusted for, and the findings revealed that the MUO cohort exhibited the greatest risk of EE, with odds ratios (ORs) of 5.473 (95% CI: 4.181-7.165) and 7.566 (95% CI: 5.718-10.010) for males and females, respectively. The frequency of occurrence of EE increased following an increase in proportion of metabolic risk factors. Subgroup analyses showed that the individuals under and over 60 years of age in the MHO, MUNO, and MUO cohorts exhibited elevated risks of developing EE. Further analysis suggested that obesity has a stronger influence on the risks of developing EE compared to metabolic disorders. Conclusion: Metabolic disorders and obesity are both related with an elevated risk of EE, in which obesity has a potentially stronger influence. Clinical interventions should target both obesity and metabolic disorders to reduce EE risk.

[Network Meta-analysis of Chinese patent medicines in treatment of coronary heart disease complicated with heart failure].

The efficacy and safety of different Chinese patent medicines in the treatment of coronary heart disease complicated with heart failure were evaluated by network Meta-analysis. The randomized controlled trial(RCT) of Chinese patent medicines for coronary heart disease complicated with heart failure was retrieved from CNKI, Wanfang, VIP, SinoMed, PubMed, Web of Science, EMbase, and Cochrane Library with the time interval from inception to July 5, 2023. The quality of the included RCT was evaluated by the Cochrane's risk of bias assessment tool, and a network Meta-analysis was performed in Stata 16.0. Finally, a total of 82 RCTs were included, involving 9 298 patients and 11 Chinese patent medicines. Network Meta-analysis yielded the following results based on the surface under the cumulative ranking curve(SUCRA).(1)In terms of improving the clinical response rate, the top three interventions were Qishen Yiqi Dripping Pills + conventional western medicine, Zhenyuan Capsules + conventional western medicine, and Tongxinluo Capsules + conventional western medicine.(2) In terms of increasing left ventricular ejection fraction(LVEF), the top three interventions were Shexiang Baoxin Pills + conventional western medicine, Compound Danshen Dripping Pills + conventional western medicine, and Tongxinluo Capsules + conventional western medicine.(3) In terms of reducing left ventricular end-diastolic diameter(LVEDD), the top three interventions were Shexiang Tongxin Dripping Pills + conventional western medicine, Tongxinluo Capsules + conventional western medicine, and Shexiang Baoxin Pills + conventional western medicine.(4) In terms of reducing N-terminal pro-brain natriuretic peptide(NT-proBNP), the top three interventions were Shexiang Baoxin Pills + conventional western medicine, Qi-shen Yiqi Dripping Pills + conventional western medicine, and Compound Danshen Dripping Pills + conventional western medicine.(5) In terms of reducing hyper-sensitive C-reactive protein(hs-CRP), the top three interventions were Naoxintong Capsules + conventional western medicine, Shexiang Baoxin Pills + conventional western medicine, and Compound Danshen Dripping Pills + conventional western medicine.(6) In terms of increasing the distance of the six-minute walking trail(6MWT), the top three interventions were Zhen-yuan Capsules + conventional western medicine, Qili Qiangxin Capsules + conventional western medicine, and Qishen Yiqi Dripping Pills + conventional western medicine. The results showed that Chinese patent medicines combined with conventional western medicine can effectively improve the clinical response rate, LVEF, and 6MWT and reduce LVEDD, NT-proBNP, and hs-CRP. However, due to the overall low quality of the articles included and the few articles of some Chinese patent medicines, direct comparison between diffe-rent Chinese patent medicines remains to be carried out and the results need to be further verified.

[Outcome indicators in clinical trials on traditional Chinese medicine treatment of microvascular angina].

This study reviewed the current status of the use of outcome indicators in randomized controlled trial(RCT) on traditional Chinese medicine(TCM) treatment of microvascular angina(MVA) and analyzed the existing problems and possible solutions, aiming to provide a basis for the design of high-quality RCT and the establishment of core outcome sets for MVA. CNKI, Wanfang, VIP, SinoMed, PubMed, EMbase, Cochrane Library, Web of Science, and 2 clinical trial registries were searched for the RCT on TCM treatment of MVA according to pre-defined criteria. The Cochrane's risk of bias assessment tool was used to evaluate the methodological quality of the included RCT and the use of outcome indicators was summarized. A total of 69 RCTs were included, from which 100 outcome indicators were extracted, with the frequency of 430. The extracted outcome indicators belonged to 8 domains: response rate, symptoms and signs, physical and chemical examinations, TCM efficacy, safety, quality of life, economic evaluation, and long-term prognosis. The indicators of physical and chemical examinations were the most(70 indicators with the frequency of 211), followed by those of response rate(7 indicators with the frequency of 73) and symptoms and signs(7 indicators with the frequency of 54). The outcome indicators with higher frequency were adverse reactions, angina attack frequency, clinical efficacy, endothelin-1, total duration of treadmill exercise, and hypersensitive C-reactive protein. The RCT on TCM treatment of MVA had the following problems: irregular reporting of adverse reactions, diverse indicators with low frequency, lack of attention to the application of endpoint indicators, insufficient use of TCM differentiation and efficacy indicators, non-standard evaluation criteria and failure to reflect the basic characteristics of TCM. A unified MVA syndrome differentiation standard should be established, on the basis of which an MVA treatment efficacy evaluation system and core outcome indicator set that highlights the characteristics of TCM with patient-reported outcomes as the starting point should be established to improve the clinical research and research value.

Proximal interruption of the pulmonary artery: A review of radiological findings.

Objectives: Proximal interruption of the pulmonary artery (PIPA) has various clinical manifestations. This review focused on and summarized the clinical and radiological features of PIPA, based on relevant literature studies. Methods: The study included a total of 25 PIPA cases in the Guangzhou Women and Children's Medical Center between January 2015 and December 2021. Conventional chest photographs and chest computed tomography angiography (CCTA) of patients with PIPA were analyzed and summarized. Results: The radiological results showed that 17 cases were right-sided and 8 cases were left-sided PIPA. Additionally, the percentage of pulmonary hypoplasia on the affected side was 44%, 36% for pulmonary hypertension, 28% for the mosaic sign, 20% for subpleural cystic lucency shadow, 20% for subpleural serrated shadow, 20% for collateral vessel thickening, 16% for subpleural band-like parenchyma, 12% for pneumonia, and 56% for patent ductus arteriosus. Conclusion: The clinical manifestations of PIPA are non-specific. Awareness of this anomaly, based on radiological manifestations, particularly those observed on CCTA images, is important for ruling out alternative diagnoses and implementing appropriate management.

[Effect of Organic Material Amendments on Soil Respiration in Tobacco Fields of Central Henan].

A field experiment was conducted to study the effects of different organic material amendments on soil respiration in a flue-cured tobacco field. Five treatments were set up:no fertilizer (NF), chemical fertilizer (NPK), chemical fertilizer+ryegrass (NPKG), chemical fertilizer+wheat straw (NPKS), and chemical fertilizer+tobacco straw biochar (NPKB). The results showed that:① Compared with that under NPK, NPKG and NPKS decreased the temperature sensitivity (Q10) of total soil respiration and heterotrophic respiration, whereas NPKB increased the Q10 of heterotrophic respiration. The two-factor fitting model of soil respiration and soil hydrothermal factors accounted for 50%-80% of the variation in soil respiration. ② The addition of organic materials significantly increased the content of soil soluble organic carbon (DOC) and root dry matter. Soil heterotrophic respiration(Rh) was significantly positively correlated with DOC content, and soil autotrophic respiration(Ra) was significantly parabolically correlated with root biomass, with an R2 of 0.327-0.634. ③ Soil respiration increased first and then decreased during the tobacco growth period. Compared with that under the NF treatment, the NPK treatment significantly promoted soil respiration and its components. Compared with those of the NPK treatment, Rsrates were significantly increased by 20.08%, 10.32%, and 9.88% under the NPKG, NPKS, and NPKB treatments, respectively; Rh rate increased by 24.21%, 16.51%, and 11.68% respectively, and Ra rate was increased by 15.12% in the NPKG treatment. In summary, straw returning and biochar addition significantly increased Rh by increasing soil DOC, thereby promoting Rs. Incorporation of ryegrass not only increased the Rh but also increased Ra by promoting the growth and development of roots and therefore the Rs.

Pharmacokinetics of treprostinil in children with functional single-ventricle pulmonary arterial hypertension: a randomized controlled trial.

BACKGROUND: Application of Treprostinil (TRE) in the patients with single ventricle (SV) physiology is very limited, and the optimal dose for children has not been determined. In this study, we aimed to analyze plasma samples to assess the attainment of clinically therapeutic concentrations of TRE and its efficacy and safety in the treatment of pediatric functional SV pulmonary arterial hypertension (FSV-PAH).. METHODS: Pediatric patients with FSV-PAH were recruited in this study. IV TRE at an initial rate of 5 ng/kg/min was administered through the femoral vein with an increase in rate to 10 ng/kg/min every 30 minuntil the aiming dose of 80 ng/kg/min had been reached. The drug was gradually discontinued after 12 h of treatment at a stable dose. The mean postoperative pulmonary artery pressure (mPAP), pulmonary-to-systemic arterial pressure ratio (Pp/Ps), and the ratio between arterial oxygen partial pressure and inhaled oxygen concentration (PaO2/FiO2) were used to evaluate the efficacy of TRE treatment. A multiple linear regression model was used to explore the relevant factors associated with TRE blood concentration. RESULTS: A total of eight patients were enrolled in the investigation, with an age range of 2.5-9.9 years. The median stable dose of TRE was 70 ng/kg/min with a range of 55-75 ng/kg/min. The median subliminal dose was 55 ng/kg/min with a range of 25-75 ng/kg/min. A linear relationship was established between the TRE dose and the plasma concentration. TRE blood concentrations were associated with dose and patient height. After TRE treatment, mPAP, Pp/Ps, and PaO2/FiO2 were significantly improved (P<0.05). CONCLUSIONS: A linear relationship was found between the blood concentration of TRE and its dose. IV TRE was an effective therapy without serious side effects in pediatric patients with FSV-PAH. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02865733.

Brain imaging features of children with Hoyeraal-Hreidarsson syndrome.

OBJECTIVE: This study aimed to summarize the magnetic resonance imaging (MRI) and computed tomography (CT) features of the central nervous system (CNS) in children with Hoyeraal-Hreidarsson syndrome. METHODS: The imaging and clinical data of four children diagnosed with Hoyeraal-Hreidarsson syndrome by clinical and laboratory tests in the Guangzhou Women and Children's Medical Center were gathered and analyzed retrospectively. The clinical manifestations and CNS imaging features of Hoyeraal-Hreidarsson syndrome were summarized based on our results and a literature review. RESULTS: Our results showed that delayed development, skin pigmentation, nail/toenail dystrophy, thrombocytopenia, and anemia are the most observed clinical presentations of Hoyeraal-Hreidarsson syndrome. Important findings on CNS imaging showed that all patients had cerebellar hypoplasia, delayed myelination, hydrocephalus, brain atrophy, and calcification. The gene mutations in all cases were consistent with those of dyskeratosis congenita, including TINF2 mutations in three cases and DKC1 mutations in one case. CONCLUSION: Hoyeraal-Hreidarsson syndrome is a severe variant of dyskeratosis congenita. Both DKC1 and TINF2 mutations can lead to the phenotypes of Hoyeraal-Hreidarsson syndrome. In our study, CNS imaging revealed that cerebellar hypoplasia has an important diagnostic value for Hoyeraal-Hreidarsson syndrome while delayed myelination, calcification of the parenchyma, brain atrophy, and hydrocephalus are also important findings on CNS imaging. Combining imaging features with clinical and laboratory indicators can assist the diagnosis of Hoyeraal-Hreidarsson syndrome.

Safety and efficacy of allogeneic natural killer cell immunotherapy on human immunodeficiency virus type 1 immunological non-responders: a brief report.

BACKGROUND: Allogeneic natural killer (NK) cell immunotherapy is recognized as a promising anti-tumor strategy, but whether it plays a role in poor CD4 recovery among human immunodeficiency virus type 1 (HIV-1) infected patients is unknown. This study aimed to investigate the safety and effectiveness of allogeneic NK cells immunotherapy on HIV-1 immunological non-responders (INRs) receiving antiretroviral therapy (ART). METHODS: From February to April 2018, a prospective, randomized, controlled, open-label clinical trial, which enrolled 20 HIV-1 INRs following specific inclusion criteria, was conducted at Nankai University Second People's Hospital. Participants were randomly allocated (simple randomization 1:1) to either the combined treatment (NK + ART) group (n = 10) or the control (ART) group (n = 10). The allogenic highly activated NK cells from killer cell immunoglobulin-like receptor (KIR)/human leukocyte antigen (HLA)-Cw mismatched healthy donor were prepared (10 cells in each injection) and intravenously infused to each recruited patient of NK+ART group in three courses. Key immune parameters (CD4 count, CD8 count, CD4/CD8 ratio), laboratory tests (count of blood cells, biochemistry panel) and symptoms at baseline and at month 1, 3, 6, 9, 12, and 24 were measured/collected to analyze the safety and efficacy of the therapy. Comparisons were between the seven time-points of both groups using repeated measurement analysis of variance (ANOVA) test. Generalized estimating equations (GEE) model was performed to evaluate the overall effect of the NK+ART group vs. the ART group. RESULTS: From baseline to 24 months, we noted a mean CD4 count augmentation (139 to 243 cells/µL) in the NK + ART group and (144 to 176 cells/µL) in the ART group (difference, 67; 95% CI, 10 to 124; P = 0.024). Our estimations revealed that NK+ART group could improve CD4 level (ß = 54.59, P = 0.006) and CD8 level (ß = 322.47, P = 0.010) on average among the six measurements compared with the ART group. Only two (2/10, 20%) participants in the NK+ART group developed a transient mild fever after the first course. CONCLUSIONS: This preliminary study informs that HIV-1 INRs, allogenic NK cells immunotherapy is safe and could significantly improve CD4 recovery but not CD4/CD8 ratio. The practical effects, however, need long-term follow-up observations. Further study on the potential underlying mechanism is warranted. REGISTRATION INFO:: www.chictr.org.cn/showproj.aspx?proj=34912 (No. ChiCTR1900020634).

The Nutritional Status of Pediatric Patients with Single Ventricle Undergoing a Bidirectional Glenn Procedure.

Single ventricle (SV) physiology is associated with growth retardation in children. The nutritional status of pediatric patients with SV undergoing a bidirectional Glenn (BDG) procedure vitally affects the feasibility of the next operation stages. To explore the nutritional status and to identify specific anthropometric parameters relevant to short-term surgical outcomes in children with SV after the BDG procedure, this study included 151 patients who underwent the BDG procedure. Anthropometric assessments and Infant and Child Feeding Index (ICFI) scores were used to evaluate nutritional status. There was a significant statistical correlation between ICFI and malnutrition in both the height-for-age Z-score (HAZ) and weight-for-age Z-score (WAZ) groups (P < 0.05). The clinical data, including ventilation time, nosocomial infection presence, pressure injury presence, peritoneal dialysis status, and total intensive care unit days, after BDG surgery were significantly different among the HAZ groups (P < 0.05), while nosocomial infection was different among the WAZ groups (P < 0.05). Children after BDG procedure had a high incidence of malnutrition, in addition to disease factors, the type and frequency of dietary intake were also important factors leading to worse clinical outcomes during hospitalization. Therefore, it is vital to maintain an optimal nutritional status in infants with SV who are undergoing a series of surgical procedures.

Corynebacterium striatum meningitis combined with suspected brain and lung abscesses: a case report and review.

BACKGROUND: Intracranial infections with Corynebacterium striatum (C. striatum) have been described sporadically in the literature over the last two decades. However, C. striatum meningitis combined with multiple abscesses has not been published before. CASE PRESENTATION: In this report, we describe the clinical and imaging findings in a 54-year-old woman with meningitis caused by C. striatum and combined with suspected brain and lung abscesses. This patient who underwent multiple fractures and a recent cut presented with headache and paraphasia. C. striatum was isolated in cerebrospinal fluid and supposedly transmitted from the skin purulent wound through blood. The patient was treated with intravenous vancomycin and had a transient improvement, but died finally. Multiple abscesses, especially in the brain, could be a reason to explain her conditions were deteriorating rapidly. CONCLUSIONS: Note that C. striatum can cause life-threatening infections. Early identification and diagnosis, early administration of antibiotics to which the bacterium is susceptible, and treatment of complications will be beneficial in patients with C. striatum-related infection.

[Study on protective effect of vanillic acid from Astragalus membranaceus on hypertensive cardiac remodeling based on network pharmacology screen].

To identify and verify the active ingredients from Astragalus membranaceus on hypertensive cardiac remodeling based on network pharmacology and heart RNA-sequencing data. The monomers of A. membranaceus and their intervention target database were established by using network pharmacology. The genes associated to cardiac remodeling were then screened by analyzing cardiac RNA-sequencing data. An overlap between genes related to cardiac remodeling and targets of ingredients form A. membranaceus was collected to obtain monomers with protective effect on hypertensive cardiac remodeling. Angiotensin Ⅱ(AngⅡ)-induced mouse cardiac remodeling model was used to validate the protective effect of active ingredients from A. membranaceus on hypertensive cardiac remodeling. Finally, a total of 81 monomers and 1 197 targets were enrolled in our database. Mouse RNA-sequencing data showed that 983 genes were significantly up-regulated and 465 genes were down-regulation in myocardial tissues of the cardiac remodeling mice as compared with blank group mice, respectively. Ninety-two genes were found via overlapping between genes related to cardiac remodeling and targets, involving 59 monomers from A. membranaceus. Further research found that vanillic acid(VA) could intervene 27 genes associated with hypertensive cardiac remodeling, ranking top 1. Meanwhile, VA could significantly inhibit AngⅡ-induced increase in ratio of heart weight to body weight and heart weight to tibial length, ANP and BNP mRNA levels in myocardial tissues, myocardial tissue damage, cardiac fibrosis level and cardiac hypertrophy level in vivo. Those results showed that network pharmacology screen-based VA has protective effect on AngⅡ-induced cardiac remodeling.

Pseudodominant inheritance of autosomal recessive congenital stationary night blindness in one family with three co-segregating deleterious GRM6 variants identified by next-generation sequencing.

BACKGROUND: The congenital stationary night blindness (CSNB) affects the patients' dim light vision or dark adaption by impairing the normal function of retina. It is a clinically and genetically heterogeneous disorder and can be inherited in an X-linked, autosomal dominant or autosomal recessive pattern. Several genetic alterations to the genes involved in visual signal transduction of photoreceptors and/or bipolar cells underlie its pathogenesis. METHODS: In this study, we used Sanger sequencing and next-generation sequencing (NGS)-based gene panel screening to investigate a family of three patients with CSNB inherited in an apparent autosomal dominant pattern. We expected to find out the disease-causing gene defects carried by this family. RESULTS: We found that the patients in this family did not carry the RHO, GNAT1, or PDE6B mutation, but carried compound heterozygotes mutations of GRM6. Three deleterious GRM6 variants, p.Arg621Ter, p.Gly51Val, and p.Gly464Arg, were found to be co-segregating with the disease, causing a pseudodominant inheritance of GRM6-related autosomal recessive complete CSNB. CONCLUSION: This study presents a rare case of autosomal recessive CSNB (arCSNB) pseudodominant inheritance, which potentially leads us to expand our gene candidate list in future genetic testing for apparent dominant pedigrees. The discovery of the two novel likely pathogenic variants p.Gly51Val and p.Gly464Arg could broaden our knowledge about the genetics of CSNB and provide insights into the structure and function of the GRM6 protein.

Clinical significance of USP7 and EZH2 in predicting prognosis of laryngeal squamous cell carcinoma and their possible functional mechanism.

BACKGROUND: Laryngeal squamous cell carcinoma (LSCC) is one of the most prevalent cancer types in the world. The ubiquitin specific protease 7 (USP7), a kind of deubiquitylating enzyme, has been reported to play multifaceted roles in different tumor types. EZH2 has been found to be highly expressed in various malignantcells and high expression of EZH2 is closely related to tumor growth infiltration, lymph node involvement, clinical stage, and poor prognosis. The aim of this study was to investigate the expression and function of USP7 and EZH2 in LSCC. CASE PRESENTATION: Immunohistochemical staining and histochemical staining were performed to explore the expression of USP7 and EZH2 in both LSCC tissues and adjacent normal laryngeal tissues. Chi-square test, univariate analysis, and multivariate analysis were conducted to statistically evaluate the clinical significance of USP7 and EZH2. CONCLUSIONS: USP7and EZH2 affects LSCC evolution; USP7 and EZH2 were upregulated in LSCC tissues, which can serve as independent prognostic predictors, and potential therapeutic targets for LSCC.

TLR4 mediates high-fat diet induced physiological changes in mice via attenuating PPARγ/ABCG1 signaling pathway.

High-fat diet (HFD) is known to promote atherosclerosis which accelerates the development of atherosclerotic cardiovascular diseases. Vascular dysfunction characterized by inflammation and lipid accumulation is common in atherosclerosis caused by HFD. The specific effects of HFD on blood vessels and the underlying mechanisms need to be further clarified. Toll-like receptor 4 (TLR4) is a key contributing factor in atherosclerosis and TLR4 deficiency protects vascular smooth muscle cells against inflammatory responses and lipid accumulation in vitro. However, the physiological significance of TLR4 signaling in HFD-induced changes is unknown. In this study, we observed that HFD feeding increased body weight, circulating inflammatory cytokines and lipid accumulation in the aorta of wild-type mice but apart from increasing body weight, did not affect the TLR4 knockout mice. TLR4 expression increased significantly in the arterial walls after receiving HFD treatment, while that of the co-localizing PPARγ and ABCG1 markedly decreased. TLR4 deficiency reversed the HFD-induced attenuation of PPARγ and ABCG1. In conclusion, TLR4 mediates HFD induced increase in body weight, inflammation and aortic lipid accumulation through, at least partly, the PPARγ/ABCG1 signaling pathway. Therefore, interfering with TLR4 signaling is a viable therapeutic option in diet induced atherosclerosis.

Asparaginyl endopeptidase enhances pancreatic ductal adenocarcinoma cell invasion in an exosome-dependent manner and correlates with poor prognosis.

Pancreatic cancer is one of the most lethal types of cancer; owing to low early detection rates and high metastasis rates, it is associated with an extremely poor prognosis. Therefore, a better understanding of the molecular mechanisms that underlie its metastasis and the identification of potential prognostic biomarkers are urgently required. Although high expression levels of asparaginyl endopeptidase (AEP) have been detected in various types of solid tumor, the expression and functions of AEP in pancreatic carcinomas have yet to be determined. The present study aimed to examine the putative functions of AEP in pancreatic carcinoma. Immunohistochemical analysis revealed that AEP was highly expressed in pancreatic cancer tissues compared with adjacent normal tissues. Patients with high AEP expression exhibited a significantly shorter overall survival time. Results from multivariate Cox regression analysis revealed that AEP was an independent prognostic factor for overall survival. Gain- and loss-of-function experiments demonstrated that knockdown of AEP expression significantly reduced the invasive ability of pancreatic cancer cells, whereas overexpression of AEP increased the invasive ability. In addition, AEP was detected in exosomes that were derived from cultured pancreatic ductal adenocarcinoma cells (PDACs) and in the serum from patients with PDAC. The Matrigel-Transwell invasion assay revealed that exosomes enriched with AEP were able to enhance the invasive ability of PDAC cells, whereas exosomes lacking AEP decreased the invasive ability. Furthermore, results from the present study suggested that AEP may be crucial for activation of the phosphoinositide 3-kinase/RAC­α serine/threonine-protein kinase signaling pathway in PDAC cells. The present study data indicated that high AEP expression may be important for pancreatic carcinoma progression in an exosome-dependent manner, and that AEP may be an independent indicator of poor prognosis in patients with PDAC and may be a novel prognostic biomarker or therapeutic target in pancreatic carcinoma.

Circulating tumor cell as a biomarker for evaluating allogenic NK cell immunotherapy on stage IV non-small cell lung cancer.

In this study, we determined the number of peripheral blood circulating tumor cells (CTCs) pre- and post-NK in patients with stage IV non- small cell lung cancer (NSCLC) as a reference for understanding the relevance of any changes to the efficacy of NK cells therapy. The patients were given one to three courses of immunotherapy. CTC numbers and CTC-related gene expression were measured in the peripheral blood of 31 patients with stage IV NSCLC at 1day before and 7 and 30d after NK cells therapy using magnetic activated cell sorting (MACS) and fluorescence activated cell sorting (FACS) combined with real-time quantitative PCR (RT-qPCR). Throughout the research, fever was the most common reaction (34.6%). The number of CTCs was 18.11±5.813, 15.13±5.984 and 10.32±5.623, respectively, and this decreased significantly over time. ΔCt values for the CTC-related genes CEA, MAGE-3 and CK18 increased significantly after NK cells infusion. The expression of CEA, CK18 and MAGE-3 decreased significantly with time after NK. CTC was a useful biomarker for evaluating the efficacy of NK cells therapy on stage IV NSCLC.

[Differentiation of Cultivated CD45-/CD31+ Mouse Lung Side Population Cells into Vascular Smooth Muscle Cells in vitro].

OBJECTIVES: To investigate the characteristics of differentiation of lung side population cells (LSP cells)in vitro. METHODS: CD45-/CD31+ LSP cells sorted by flow cytometry were taken from mouse lung tissues and cultured for 14 d. The cultured LSP cells were observed with colony formation assay and flow cytometryin vitro. The mRNA expressions of ATP-binding cassette transporter G2 (ABCG2), smooth muscle actin (SMA) and α-smooth muscle tropomyosin (α-SMT) in both freshly isolated LSP cells and cultured LSP cells were examined. The expressions of ABCG2 and stem cell antigen 1 (Sca1) in LSP cells were detected using immunofluorescence. RT-PCR tests were performed to detect the expressions of ABCG2, SMA and α-SMT in LSP cells. RESULTS: The isolated CD45-/CD31+ lung side population cells expressed ABCG2, SMA and Sca1, but not α-SMT. A large number of LSP in aggregated state were observed after 14 d of culture. Before induction of differentiation, the CD45-/CD31+ LSP cells expressed ABCG2 and SMA, but not α-SMT. After induction of differentiation, the CD45-/CD31+ lung side population cells expressed α-SMT and SMA, but not ABCG2. CONCLUSIONS: CD45-/CD31+ LSP cells might be progenitor cells of vascular smooth muscle cells, possessing the characteristics of stem cell differentiations.

Clinical efficacy of percutaneous cryoablation combined with allogenic NK cell immunotherapy for advanced non-small cell lung cancer.

In this study, the safety and clinical efficacy of cryosurgery combined with allogenic NK cell immunotherapy for the treatment of advanced non-small cell lung cancer (NSCLC) were evaluated. From July 2016 to March 2017, we enrolled 60 patients who met the enrollment criteria and divided them into two groups: (1) the simple cryoablation group (n = 30) and (2) the cryoablation combined with allogenic NK cell group (n = 30). The changes in immune function, quality of life, and clinical response were evaluated. We found that allogenic NK cells combined with cryosurgical treatment for advanced NSCLC have a synergistic effect, which not only enhancing the immune function of patients, improving the quality of life, and significantly increasing the response rate (RR) and disease control rate (DCR) compared to cryoablation group. This study is the first clinical trial of allogenic NK cells combined with cryosurgery for the treatment of advanced NSCLC and preliminaily its safety and efficacy.