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Background: Cancer testis antigens (CTAs) are an extensive gene family with a unique expression pattern restricted to testis tissues, but aberrantly high expressed in a variety of cancer tissues. In view of this, CTAs are typically considered as efficient biomarkers and targets of immunotherapy. However, limited information is available regarding CTAs as immunotherapeutic targets for gastric cancer (GC) patients. Herein, we evaluated the expression levels of CTAs in both Eastern and Western GC patients and elucidate the expression pattern and functions of a novel CTAs. Method: Four independent GC and two human normal tissues retrospective cohorts were applied to detect expression patterns and clinical characteristics of CTAs. We identified the association between ZNF165 expression and tumor-infiltrated immune cells by using ESTIMATE, CIBERSORT algorithm and immunohistochemistry (IHC) staining. Functional enrichment analysis of ZNF165 were identified by using transcriptome sequencing. ZNF165 overexpression and knockdown in vitro and in vivo were used to assess the roles of ZNF165 in the cell cycle pathway. Results: ZNF165 expression significantly increased in GC tissues, especially in the intestinal type, MSI type, epithelial phenotype, and was associated with poor overall survival and disease-free survival for GC patients who received fluorouracil-based chemoradiation and radical gastrectomy. Little or no expression of ZNF165 was observed in human normal tissues, except for testis and placenta. Furthermore, ZNF165 was positively associated with pro-inflammatory tumor-infiltrating immune cells and tumor mutational burden (TMB). Enrichment analysis, in vivo and in vitro assays showed that ZNF165 could promote GC cell proliferation by regulating cell cycle. Conclusions: By demonstrating the expression pattern, clinical features, prognostic values and cellular functions of ZNF165 in GC, this study suggests that ZNF165 could serve as a potential novel immunotherapeutic target for GC patients.

Combination therapy is a common approach for clinical treatment of type 2 diabetes mellitus, especially for patients with poor monotherapy. Meta-analysis suggested that omarigliptin, a long-acting DPP-4 inhibitor, combined with pioglitazone might improve the side effects of pioglitazone. However, little is known about the pharmacokinetic properties after a coadministration. In this study, a rapid and reliable method for the simultaneous determination of the pioglitazone and omarigliptin in rat plasma by UHPLC-MS/MS was established and validated for the first time. An exsil mono C18 column (2.0 × 50 mm, 3 μm) was used to separate the analytes and the column temperature was kept at 30°C. Sitagliptin was selected as the internal standard. 0.02% formic acid aqueous solution (A) and methanol-acetonitrile (B) were used as mobile phases with gradient elution at a flow rate of 0.3 mL/min. The elution procedure was as follows: 20%B (0–0.1 min), 80%B (0.1–0.3 min), 80%B (0.3–2.0 min), and 20%B (2.1–3.0 min). A multiple reaction monitor (MRM) was used under positive ionization mode with electrospray ion source to detect pioglitazone (357.1 ⟶ 134.1), omarigliptin (399.2 ⟶ 153.0), and sitagliptin (408.2 ⟶ 235.0). The linear ranges of pioglitazone and omarigliptin were 5–2000 ng/mL and 10–4000 ng/mL, respectively. Good linear relationships were exhibited in the corresponding linear ranges (r ≥ 0.9944). The bioanalytical method was validated, and the selectivity, linearity, sensitivity, accuracy, precision, stability, recovery, and matrix effect were acceptable. The validated method was then successfully applied to pharmacokinetic study of pioglitazone combined with omarigliptin in rats. Results suggested that the combination of the two drugs had little effect on the pharmacokinetic parameters of each other in rats.

There are few studies regarding imaging markers for predicting postoperative rebleeding after stereotactic minimally invasive surgery (MIS) for hypertensive intracerebral haemorrhage (ICH), and little is known about the relationship between satellite sign on computed tomography (CT) scans and postoperative rebleeding after MIS. This study aimed to determine the value of the CT satellite sign in predicting postoperative rebleeding in patients with hypertensive ICH who undergo stereotactic MIS. We retrospectively examined and analysed 105 patients with hypertensive ICH who underwent standard stereotactic MIS for hematoma evacuation within 72 h following admission. Postoperative rebleeding occurred in 14 of 65 (21.5%) patients with the satellite sign on baseline CT, and in 5 of the 40 (12.5%) patients without the satellite sign. This difference was statistically significant. Positive and negative values of the satellite sign for predicting postoperative rebleeding were 21.5% and 87.5%, respectively. Multivariate logistic regression analysis verified that baseline ICH volume and intraventricular rupture were independent predictors of postoperative rebleeding. In conclusion, the satellite sign on baseline CT scans may not predict postoperative rebleeding following stereotactic MIS for hypertensive ICH.

To investigate the impact of the COVID-19 outbreak on the behaviours, mental health and seizure control of adult patients with epilepsy (PWE) and to identify the correlation of seizure increase and the COVID-19 outbreak to guide the medical care of individuals with epilepsy during a public health crisis.This study was conducted at 28 centres from February 2020 to April 2020. Participants filled out a 62-item online survey including sociodemographic, COVID-19-related, epilepsy-related and psychological variables and were divided into two groups based on whether their seizure frequency increased during the COVID-19 pandemic. Chi-square tests and t-tests were used to test differences in significant characteristics. Multiple logistic regression analyses were used to identify risk factors for seizure worsening.A total of 1,237 adult PWE were enrolled for analysis. Of this sample, 31 (8.33%) patients experienced an increase in seizures during the pandemic. Multivariate logistic regression suggested that feeling nervous about the pandemic (P0.05), poor quality of life (P = 0.001), drug reduction/withdrawal (P = 0.032), moderate anxiety during the COVID-19 outbreak (P = 0.046) and non-seizure free before the COVID-19 outbreak (P0.05) were independently related to seizure increase during the pandemic.During the COVID-19 pandemic, PWE with poor quality of life and mental status, as well as AED reduction/withdrawal, were more likely to experience seizure increase. This observation highlights the importance of early identification of the population at high risk of seizure worsening and implementation of preventive strategies during the pandemic.

Background Ovarian cancer is the most lethal gynecological cancer worldwide. Since the early clinical symptoms are not obvious, most patients with ovarian cancer are already in an advanced clinical stage when they are diagnosed. HGSOC accounts for the greatest number of ovarian cancer deaths and shows an association between an enhanced immune response and prolonged patient survival. Methods 88 normal ovarian samples from TCGA and 149 ovarian cancer patients from GTEx were used to analyze gene expression, proteins and pathways associated with INPP4B in HGSOC, LGSOC and ovarian cancer. The correlation between INPP4B gene and immune factors was analyzed by TIMER website. The expression of INPP4B was verified by immunohistochemistry and Western Blotting. MTT assay, flow cytometry, and scratch assay were used to verify the effects of INPP4B on proliferation, apoptosis and migration. Tumor formation experiment to verify the effect of INPP4B on tumor formation. Results In this study, we performed data mining analysis of HGSOC and LGSOC samples. We first identified 25 tumor suppressor genes associated with poor prognosis and survival in HGSOC. Further immune infiltration analysis of these 25 genes with the TIMER web tool showed that among the 25 genes, INPP4B had the most pronounced effect on CD8 + T-cell infiltration. In addition, detection of INPP4B expression by IHC staining in clinical samples indicated that the INPP4B level was significantly lower in ovarian cancer tissues and negatively related to patient survival. Moreover, knockdown of INPP4B accelerated ovarian cancer cell growth and migration in vitro and vivo. Finally, the genes related to INPP4B in ovarian cancer were mainly enriched in the immune response and inflammatory response. Conclusions INPP4B plays an important role in cell proliferation, cell growth, cell migration, apoptosis and immune infiltration in OC. The INPP4B gene, as a potential tumor suppressor gene, may become a biomarker and therapeutic target for ovarian cancer.

Objective—Intracerebral hemorrhage (ICH) is the second most common subtype of stroke with higher mortality and morbidity, and it lacks effective 6-month prognostic markers,especially in young patients.The aim of this research is to construct a newly valuable prognostic nomogram model incorporating hemoglobin level for young patients with ICH.Method—Patients aged between 18 and 50 years with first-ever intracerebral hemorrhageselected from Tongji Hospital affiliated to Tongji Medical College of Huazhong University of Science and Technology from January1,2012 to December 31,2018.We retrospectively analyzed 565 young patients with ICH. The independent factors of prognosis were identified by univariate and multivariate logistic regression analysis. Then，based on independent risk factors,a new nomogram model was further constructed and validated. Its clinical value was subsequently explored utilizing decision curve analysis and clinical impact curve.Results—A total of 565 patients were enrolled in this study.There were 117 patients (20.7%) who developed unfavourable prognosis. Infratentorial lesion(adjusted odds ratio [aOR]=3.708,95%confidence interval [CI],1.490-9.227; P=0.005)was most significant with unfavourable outcome.Age([aOR]=1.054;95%CI,1.014-1.096;P=0.008),hematoma volume(aOR=1.014,95%CI,1.002-1.027;P=0.024),hemoglobin(aOR=0.981,95% CI,0.969-0.993;P=0.002),blood glucose(aOR=1.135,95%CI,1.037-1.241; P=0.005)and NIHSS(aOR=1.105,95%CI,1.069-1.141;PConclusion—The hemoglobin level at admission may be an easily overlooked factor in clinical work.This new nnomogram model could be a promising and convient tool to predict the early functional prognosis of in young people with ICH.In addition, more prospective multicenter studies are needed to cestimate these findings.

This study presents both experimental and theoretical investigations about gas transport in shales. Gas apparent permeability coefficients and Klinkenberg slippage factors were determined on Longma...

Yanting Lu, Shu Zhu, Xiaoyan Wang, Juhai Liu, Yingying Li, Wei Wang, Shijun Wang, Furong Wang College of TCM, Shandong University of Traditional Chinese Medicine, Jinan, 250355, People’s Republic of ChinaCorrespondence: Shijun Wang; Furong Wang Email wsj@sdutcm.edu.cn; 15168888786@163.comBackground and Purpose: ShengMai-San (SMS) is traditionally used to treat ischemic cardiovascular and cerebrovascular diseases. Recently, several studies have reported the cardioprotective effects of SMS in diabetic animals. However, the potential mechanisms have not yet been fully elucidated. In this study, we investigated whether SMS exerts a beneficial effect in diabetic cardiomyopathy (DCM) by alleviating NADPH oxidase (NOX)-mediated oxidative stress.Methods: SD rats were randomly divided into a negative controlgroup (NC), diabetes mellitus group (DM) and SMS-treated group (SMS). The myocardial structure alterations, apoptosis and biomarkers of oxidative stress were observed. Moreover, to explore the protective mechanism of SMS, the activation of AMPKα, expression and translocation of NOX-related proteins were assessed.Results: Diabetes led to excessive collagen content, fibrosis, and apoptosis in the myocardium. Oxidative stress in diabetic hearts was indicated by low levels of T-AOC, high levels of 8-iso-PGF2α and 8-OHdG, inactivation of AMPKα, elevated expression of NOX2 and NOX4 and translocation of NOX isoforms p47phox and p67phox. Treatment with SMS for 10 weeks resulted in the alleviation of diabetes-associated myocardial structure abnormalities and apoptosis. Additionally, SMS attenuated the accumulation of oxidative stress markers in myocardial tissue. Further investigation showed that SMS was able to reverse the levels of oxidative stress-associated proteins NOX2 and NOX4 in the DM rats. Moreover, SMS treatment blunted the translocation of NADPH oxidase isoforms p47phox and p67phox as well. Furthermore, SMS promoted the activation of AMPK in the cardiac tissue of diabetic rats.Conclusion: These findings indicate that SMS exhibits therapeutic properties against diabetic cardiomyopathy by attenuating myocardial oxidative damage via activation of AMPKα and inhibition of NOX signaling.Keywords: diabetes, myocardium, ShengMai-San, oxidative stress, AMPK, NOX

The parameter estimation of multiple frequency-hopping (multiple FH) signals with frequency-switching time is a great challenge under conditions in which the number of signals is unknown. Due to the increasing mobility of devices such as unmanned aerial vehicles (UAVs), speed of parameter estimation is even more demanding. To solve this problem, an algorithm for estimating parameters of multiple FH signals based on compressed spectrum sensing and maximum likelihood (CSML) theory is proposed in this paper. First, the received signal is split into segments of the same length, and the frequencies contained in each segment are extracted using compressed spectrum sensing and kurtosis threshold. Next, the frequencies contained in adjacent segments are compared to find the signal segment in which frequency hopping occurs and its corresponding frequency. Finally, a hopping-time fast estimation algorithm based on the maximum likelihood theory is used to estimate the hopping time. Simulation results show that the algorithm proposed in this paper can estimate the parameters of multiple FH signals quickly and accurately when the number of signals is unknown and that it is equally effective for multiple FH signals with frequency-switching time.