Causal relationship between linoleic acid and type 2 diabetes and glycemic traits: a bidirectional Mendelian randomization study.

Objective: To investigate the causal relationships between linoleic acid and type 2 diabetes, and between linoleic acid and glycemic traits in European populations. Methods: This study employed a two-sample Mendelian randomization approach to infer causality between linoleic acid and type 2 diabetes, as well as between linoleic acid and glycemic traits, leveraging genetic variations. Data were sourced from genome-wide association study summary datasets. Random-effects inverse-variance weighted, weighted median, and MR-Egger methods were used for the two-sample Mendelian randomization analyses. Results were presented as odds ratios with a 95% confidence interval. Multiple sensitivity analyses were conducted to assess result robustness. Results: MR findings indicated a correlation between linoleic acid levels and the risk of type 2 diabetes, fasting blood glucose, and glycated hemoglobin (HbA1c), but not with fasting insulin. Specifically: type 2 diabetes (OR: 0.811, 95% CI: 0.688-0.956, P=0.013<0.05),fasting blood glucose (ß_IVW): -0.056, 95% CI: (-0.091,-0.021), P=0.002< 0.0125), glycated hemoglobin (ß_IVW: -0.032, 95% CI: (-0.048,-0.015), P=0.0002< 0.0125) and Fasting insulin (ß_IVW: -0.024, 95% CI: (-0.056,-0.008), P=0.136 >0.05).Reverse MR analyses showed a correlation between type 2 diabetes and reduced levels of linoleic acid (ß_IVW: -0.033, 95% CI: (-0.059,-0.006), P=0.014<0.05). Multiple sensitivity analyses also detected study heterogeneity but found no evidence of horizontal pleiotropy. Conclusion: High levels linoleic acid can reduce the risk of type 2 diabetes, fasting blood glucose, and glycated hemoglobin, but has no significant relation with fasting insulin. Type 2 diabetes can lower linoleic acid levels; however, no significant causal relationship was observed between the three glycemic traits and reduced levels of linoleic acid.

Shenmai Injection Alleviates Acute Lung Injury in a Severe Acute Pancreatitis Rat Model via Heme Oxygenase-1 Upregulation.

BACKGROUND: One of the serious complications of severe acute pancreatitis (SAP) is acute lung injury (ALI). Suppressing inflammation is a feasible treatment strategy for SAP-induced ALI. Shenmai injection (SMI), which is a Traditional Chinese Medicine (TCM treatment, can suppress inflammation. Therefore, this study used an established SAP rat model to determine the effect of SMI on ALI induced by SAP. METHODS: A total of 40 male Sprague-Dawley (SD) rats were assigned to one of four groups: the SAP group, the sham surgery (SS) group, the SAP + SMI group and the SAP + SMI + zinc protoporphyrin (ZnPP) group. Rats in the SAP group were intravenously injected with 1.6 ml/kg saline 30 minutes after induction of SAP models, rats in the SAP + SMI group were intravenously injected with 1.6 ml/kg SMI, while rats in the SAP + SMI + ZnPP group were intravenously injected with 1.6 ml/kg SMI and 30 mg/kg ZnPP via intraperitoneal injection. The rates were sacrificed 24 hours after SAP induction. Excised lung tissues were histologically examined, protein concentration in bronchoalveolar lavage fluid (BALF) was measured and lung wet-to-dry (W/D) weight ratio was calculated. The protein and mRNA levels of tumor necrosis factor (TNF)-α, heme oxygenase (HO)-1 and interleukin (IL)-10 in blood and tissue samples were measured. RESULTS: SMI treatment attenuated SAP-induced ALI as evidenced by lower lung damage scores compared with the untreated SAP group (P < .05). SMI also abolished the SAP-induced rise in BALF and W/D ratio protein concentrations (P < .05). Moreover, SMI treatment increased HO-1 and IL-10 levels but decreased TNF-α levels in serum and tissue samples (P < .05). However, inhibition of HO-1 expression by ZnPP led to significant inhibition of all the changes. CONCLUSION: SMI can alleviate SAP-induced ALI through HO-1 upregulation.

[Analysis of Predictive Value of Laboratory Indexes for Malignant Lymphoma Patients with Bone Marrow Involvement].

OBJECTIVE: To analyze the influence of bone marrow involvement (BMI) in patients with malignant lymphoma (ML) on laboratory indexes, and evaluate the laboratory markers that can be used to predict/diagnose BMI. METHODS: The clinical characteristics and laboratory indexes of 137 ML patients were analyzed retrospectively, from which the indexes of BMI in ML patients was studied. The logistic regression analysis and receiver operating curve (ROC) were used to evaluate independent risk factors and predictors of BMI diagnosis in ML patients. RESULTS: Compared with non-BMI group, the red blood cell distribution width, C-reactive protein, erythrocyte sedimentation rate, D-dimer, lactate dehydrogenase, alkaline phosphatase, ß2-microglobulin, transferrin, CA153, CA125, and soluble interleukin-2 receptor (sIL-2R) levels were increased while platelet (PLT) count was decreased in BMI group, and the difference was statistically significant (P<0.05). The blood indexes related to BMI and the statistically significant indexes in the univariate regression analysis were corrected by multivariate logistic regression analysis. The corrected results showed that T cell-related non-Hodgkin lymphoma (adjusted OR=2.18, 95%CI: 1.48-4.90, P＜0.001), clinical stage Ⅲ-Ⅳ (adjusted OR=3.32, 95%CI: 2.16-5.83, P＜0.001), sIL-2R (adjusted OR=4.26, 95%CI: 2.95-12.85, P＜0.001) were the risk factors for ML patients with BMI, while PLT (adjusted OR=0.89, 95%CI: 0.55-0.96, P= 0.003) was a protective factor. ROC analysis showed that the areas under the ROC curve of PLT and sIL-2R predicting BMI in ML patients was 0.712 (95%CI: 0.646-0.776, P<0.001) and 0.796 (95%CI: 0.739-0.853, P<0.001), respectively. The best cut-off point of PLT and sIL-2R was 160×109/L and 2 568 U/ml, respectively. The diagnostic specificities of the two indexes here were both greater than 80%. CONCLUSION: PLT and sIL2R show good diagnostic value for ML patients with BMI.

Shenmai Injection Upregulates Heme Oxygenase-1 to Confer Protection Against Severe Acute Pancreatitis.

BACKGROUND: To explore the mechanism of Shenmai injection (SMI) on severe acute pancreatitis (SAP) through heme oxygenase-1 (HO-1) signaling. METHODS: A total of 40 male Sprague-Dawley (SD) rats (220-260 g) were grouped into the following four categories (n = 10): SAP + SMI + Zinc protoporphyrin (ZnPP), SAP + SMI, SAP, and sham surgery groups. ZnPP is a specific inhibitor of HO-1. Four percent of sodium taurocholate (1 mL/kg) was retrogradely injected via the pancreatic duct to induce the SAP model. The SAP group rats received 1.6 mL/kg saline by intravenous injection 30 min after the induction of SAP. The SAP + SMI group rats received 1.6 mL/kg SMI by intravenous injection 30 min after the induction of SAP. The SAP + SMI + ZnPP group rats received an intravenous injection of 1.6 mL/kg SMI and intraperitoneal administration of 30 mg/kg ZnPP 30 min after the SAP induction. Twenty-four hours after the SAP induction, blood samples were collected for the measurement of amylase, lipase, creatinine, myeloperoxidase, interleukin-10 (IL-10), tumor necrosis factor-α (TNF-α), and HO-1 level, while tissue specimens were harvested for the determination of HO-1, TNF-α, and IL-10 mRNA level. Meanwhile, histopathological changes in organs (pancreas, lung, and kidney) were stored. RESULTS: The serum concentration of amylase, lipase, creatinine, and myeloperoxidase was higher in the SAP group than in the SAP + SMI group. Treatment with SMI increased HO-1 and IL-10 level and reduced TNF-α level in serum and tissues compared to the SAP group (P < 0.05). Treatment with SMI abolished the organ-damaging effects of SAP (P < 0.05). Furthermore, suppression of HO-1 expression by ZnPP canceled the aforementioned effects. CONCLUSIONS: SMI confers protection against the SAP-induced systemic inflammatory response and multiple organs damage via HO-1 upregulation.

Effect of Shen-Fu Injection () on Hemodynamics in Early Volume Resuscitation Treated Septic Shock Patients.

OBJECTIVE: To investigate the hemodynamic effect of Shen-Fu Injection (, SFI) in early volume resuscitation treated septic shock patients by monitoring pulse indicator continuous cardiac output (PICCO). METHODS: All septic shock patients admitted in the Intensive Care Unit of the Affiliated Hospital of Shandong University of Traditional Chinese Medicine from January 1st, 2014 to December 31th, 2015, were reviewed, and totally 65 were enrolled in this study. They were assigned to SFI group (33 cases) and control group (32 cases). All 65 patients underwent conventional treatment mainly including volume resuscitation, antibiotics and vasoactive drugs therapy. The patients of the SFI group received additional 100 mL of SFI intravenously every 12 h. In all 65 patients, the PICCO arterial catheter and vein catheter were implanted within 1 h after the diagnosis of septic shock. In the course of early volume resuscitation, hemodynamic data of patients were recorded by PICCO monitor at 0, 12, and 24 h after the catheter implantation. RESULTS: The hemodynamic indices of the two groups showed no significant differences at the beginning of 0 h (P>0.05). At 12 and 24 h, the hemodynamic indices of SFI group were significantly improved in comparison with the control group (P<0.05), including cardiac index (CI), global end diastolic volume index (GEDI), mean arterial pressure (MAP) and heart rate (HR). In addition, there was no significant change of extra-vascular lung water index between the two groups (P>0.05). CONCLUSION: SFI significantly improved hemodynamic indices such as CI, GEDI, MAP and HR in early volume resuscitation treated septic shock patients.

High-Contrast SEM Imaging of Supported Few-Layer Graphene for Differentiating Distinct Layers and Resolving Fine Features: There is Plenty of Room at the Bottom.

For supported graphene, reliable differentiation and clear visualization of distinct graphene layers and fine features such as wrinkles are essential for revealing the structure-property relationships for graphene and graphene-based devices. Scanning electron microscopy (SEM) has been frequently used for this purpose where high-quality image contrast is critical. However, it is surprising that the effect of key imaging parameters on the image contrast has been seriously undermined by the graphene community. Here, superior image contrast of secondary electron (SE) images for few-layer graphene supported on SiC and SiO2 /Si is realized through simultaneously tuning two key parameters-acceleration voltage (Vacc ) and working distance (WD). The overlooked role of WD in characterizing graphene is highlighted and clearly demonstrated. A unified model of Vacc and WD dependence of three types of SE collected by the standard side-attached Everhart-Thornley (E-T) SE detector is conceptually developed for mechanistically understanding the improved mass thickness contrast for supported few-layer graphene. The findings reported here will have important implications for effective characterizations of atomically thick 2D materials and devices.

LncRNA FEZF1-AS1 enhances epithelial-mesenchymal transition (EMT) through suppressing E-cadherin and regulating WNT pathway in non-small cell lung cancer (NSCLC).

OBJECTIVE: Recent discoveries verify that long non-coding RNAs (lncRNAs) are important functional regulators involved in non-small cell lung cancer (NSCLC) progression. However, long non-coding RNA FEZF1-AS1 was not been investigated in NSCLC so for. METHODS: We applied the quantitative real time polymerase chain reaction (qRT-PCR) assays to detect the expression of lncRNA FEZF1-AS1 in NSCLC tissues and adjacent normal tissues. Cell proliferation and invasion capacities were evaluated by MTT, colony formation, and cell invasion assays. Chromatin immunoprecipitation (ChIP) and RNA immunoprecipitation (RIP) methods demonstrated the association between lncRNA FEZF1-AS1 expression and E-cadherin. The relative protein expression levels were analyzed by western blot analysis. RESULTS: LncRNA FEZF1-AS1 was significantly up-regulated in NSCLC tissues compared with adjacent normal tissues. Higher lncRNA FEZF1-AS1 expression levels associated with lymph node metastasis, poor differentiation grade and advanced TNM stage. In vitro, we revealed that down-regulation of lncRNA FEZF1-AS1 inhibited cell proliferation and cell invasion capacities in NSCLC. Moreover, down-regulation of lncRNA FEZF1-AS1 suppressed cell epithelial-mesenchymal transition (EMT) process by increasing the expression of E-cadherin and ZO-1, whereas, decreasing the expression of Slug, Twist and Vimentin in NSCLC cells. Furthermore, we demonstrated lncRNA FEZF1-AS1 could epigenetically repress the expression of E-cadherin via binding with LSD1 and EZH2 in NSCLC cells. We also revealed that knockdown of lncRNA FEZF1-AS1 suppressed Wnt/ß-catenin signaling in NSCLC. CONCLUSION: These results demonstrated that lncRNA FEZF1-AS1 could function as a tumor promoting regulator in NSCLC, which may provide a target of treatment in NSCLC.

Protective effects of heme oxygenase-1 against severe acute pancreatitis via inhibition of tumor necrosis factor-α and augmentation of interleukin-10.

BACKGROUND: Heme oxygenase-1 (HO-1) is an inducible defense gene which plays a significant role in inflammation. HO-1 protects cells and tissues through the mechanism of anti-oxidation, maintaining microcirculation and anti-inflammation. The aim of the current study is to investigate the role of HO-1 on systemic inflammatory response in severe acute pancreatitis (SAP). METHODS: Forty male Sprague-Dawley (SD) rats were randomly assigned into four groups: control group (n = 10); SAP group (n = 10), SAP model was induced by retrograde injection of 3% sodium taurocholate through pancreatic duct; HO-1 stimulation group (n = 10), SD rats were injected 75 µg/kg hemin intraperitoneally 30 min after induction of SAP; HO-1 inhibition group (n = 10), SD rats were injected 20 µg/kg Zinc porphyrin (Zn-PP) intraperitoneally 30 min after induction of SAP. After 24 h of SAP establishment, tissues were collected for HO-1, tumor necrosis factor-α (TNF-α) and interleukin-10 (IL-10) mRNA expression, and blood samples were collected for cytokines and biochemical measurements. Meanwhile, the histopathological changes of pancreas and liver tissues were observed. RESULTS: The expression of HO-1 mRNA and protein were significantly induced by SAP in rat pancreas and liver. Hemin treatment significantly decreased oxidative stress and TNF-α in plasma and tissues, while the IL-10 was significantly increased. Pancreas and liver injury induced by SAP was markedly attenuated by Hemin treatment. Moreover, inhibition of HO-1 expression by Zn-PP administration aggravated the injury caused by SAP. CONCLUSIONS: Induction of HO-1 in early SAP may modulate systemic inflammatory response and prevent pancreas and nearby organs such as liver injury through inhibition of TNF-α and augmentation of IL-10.

Relationship between asperity-mediated surface forces and topography alteration of silica microspheres sliding on mica, sapphire, and glass substrates under ambient conditions: atomic force microscopy and theoretical studies.

Contact geometry significantly influences adhesive force measurements and modeling for adhesion/friction studies where an AFM colloidal probe technique has been extensively employed. Here we present a systematic study on the topography alteration of silica microspheres sliding on mica, sapphire, and glass substrates under ambient conditions at a relative humidity of 30-55% and the consequential adhesion behaviors of worn microspheres through AFM direct force measurements and theoretical modeling. The wearing of microspheres creates a truncated platform, which is largest for sliding on glass substrates. On the platform are nanoasperities consisting of wear debris and airborne particulate contaminants. Variations in adhesive forces with sliding time and testing modes as well as the effect of surface roughness of substrates are explained within the theoretical framework of nanoasperity-mediated capillary and van der Waals forces. The drawbacks of the present reverse-imaging method for microsphere topography examination, and numerous sources of errors associated with the extraction of key parameters for force modeling, are discussed in detail. The results will also have important implications for more reliable AFM colloidal probe technique and its application in adhesion and tribological studies.