We conducted a meta-analysis of relevant cohort studies to investigate the relationships between cyclooxygenase-2 (COX-2) protein and the prognosis of pancreatic cancer. The following electronic ...databases were searched without language restrictions: MEDLINE (1966∼2013), the Library Database (Issue 12, 2013), EMBASE (1980∼2013), CINAHL (1982∼2013), Web of Science (1945∼2013), and the Chinese Biomedical Database (CBM) (1982∼2013). Meta-analysis was performed using the STATA statistical software. Six cohort studies with a total of 712 pancreatic cancer patients were involved in this meta-analysis. Our findings showed that COX-2-positive patients were significantly associated with a shorter overall survival (OS) than COX-2-negative patients (hazard ratio (HR) = 1.48, 95 % confidence interval (95%CI) = 1.12∼1.85,
P
< 0.001). A subgroup analysis by ethnicity also revealed that pancreatic cancer patients with an abnormal COX-2 expression exhibited a worse OS than COX-2-negative patients among both Asians and Caucasians (Asians: HR = 1.40, 95%CI = −0.09∼2.89,
P
= 0.066; Caucasians: HR = 1.49, 95%CI = 1.11∼1.87,
P
< 0.001, respectively). Our findings provide empirical evidence that abnormal COX-2 expression may be strongly correlated with poor prognosis for patients with pancreatic cancer. Thus, COX-2 protein may be a useful biomarker for pancreatic cancer.
In this paper, a chiral metamaterial consisting of bi-layered metasurface with double F-shaped resonators is investigated. We experimentally demonstrate that this new structure can realize multi-band ...asymmetric transmission of a linearly polarized wave in the microwave region. The simulated results also show that the structure can achieve multi-band 90° polarization rotator for a y-polarized wave. The mechanisms of coupling modes are analyzed by the current distribution at different resonant frequencies, which indicates that the cross-polarized transmission is due to both the electric coupling and the magnetic coupling. Furthermore, the polarization conversion ratios (PCRs) with more than 90 % conversion efficiency of x-polarized and y-polarized waves are also studied based on the optical activity and electric field distributions.
We evaluated the SGP-1 protein composition of 368 Chinese wheat landraces using SDS-PAGE. The SGP-D1 null type was identified in three accessions (Xiaoqingmang, Pushanbamai, and P119). An 18-bp ...deletion and 9-bp variation were found at the junction region of the 7th intron and 8th exon, leading to deletion of the intron–exon junction recognition site AG when aligned the 8261-bp DNA sequence of TaSSIIa-D in Pushanbamai with that of Chinese Spring. Four cDNA types with mis-spliced isoforms were subsequently detected through amplification of TaSSIIa-D cDNAs. Among these, nine type II cDNAs with a 16-bp deletion in the 8th exon were detected, indicating that the major transcriptional pattern of TaSSIIa in Pushanbamai is type II. In the type IV cDNA, a 97-bp sequence remains undeleted in the end of the 5th exon. The amylose content in Pushanbamai was significantly higher than that in all control lines under field conditions, which suggested that deletion of SGP-D1 has an efficient impact on amylose content. As the TaSSIIa gene plays an important role in regulating the content of amylose, it is anticipated that these natural variants of TaSSIIa-D will provide useful resources for quality improvement in wheat.
T-cells play an important role in promoting mucosal immunity against pathogens, but the mechanistic basis for their homeostasis in the intestine is still poorly understood. We report here that ...T-cell-specific deletion of mTOR results in dramatically decreased CD4 and CD8 T-cell numbers in the lamina propria of both small and large intestines under both steady-state and inflammatory conditions. These defects result in defective host resistance against a murine enteropathogen, Citrobacter rodentium, leading to the death of the animals. We further demonstrated that mTOR deficiency reduces the generation of gut-homing effector T-cells in both mesenteric lymph nodes and Peyer's patches without obviously affecting expression of gut-homing molecules on those effector T-cells. Using mice with T-cell-specific ablation of Raptor/mTORC1 or Rictor/mTORC2, we revealed that both mTORC1 and, to a lesser extent, mTORC2 contribute to both CD4 and CD8 T-cell accumulation in the gastrointestinal (GI) tract. Additionally, mTORC1 but not mTORC2 plays an important role regulating the proliferative renewal of both CD4 and CD8 T-cells in the intestines. Our data thus reveal that mTOR is crucial for T-cell accumulation in the GI tract and for establishing local adaptive immunity against pathogens.
Excessive inflammation and increased apoptosis of macrophages contribute to organ damage and poor prognosis of sepsis. Ginkgolic acid (GA) is a natural constituent extracted from the leaves of
, that ...can regulate inflammation and apoptosis. The present study aims to investigate the potential effect of GA in treating sepsis and its possible mechanisms.
Here, a classic septic mice model and a lipopolysaccharide (LPS)-induced RAW 264.7 inflammation model were established. Cytokines in serum and culture supernatant were detected by ELISA, and the mRNA levels of them were examined by PCR. Hematoxylin and eosin (H&E) staining was performed to determine histopathological changes in liver, lung and kidney. Bacterial burden in the blood, peritoneal lavage fluids (PLFs) and organs were observed on Luria-Bertani agar medium. Flow cytometry and western blotting was used to detect apoptosis and the expression level of apoptosis related molecules, respectively. Moreover, the levels of SUMOylation were detected by western blotting. The activity of NF-κB p65 was assessed by immunofluorescence staining and western blotting.
The result showed that GA promoted inflammatory responses, reduced bacterial clearance, aggravated organ damage, and increased mortality in septic mice. GA increased apoptosis in peritoneal macrophages (PMs) and RAW 264.7 cells. Meanwhile, GA inhibited SUMOylation and increased the nuclear translocation of NF-κB p65 as well as its phosphorylation level.
Collectively, GA promotes inflammation and macrophage apoptosis in sepsis, which may be mediated by inhibiting the SUMOylation process and increasing NF-κB p65 activity.
Background. Evidence regarding the nonlinear relationship between serum uric acid (SUA) and blood lipids in Chinese population with hypertension is limited. Therefore, the present study aimed to ...investigate whether there is a nonlinear association between SUA and lipids in Chinese hypertensive population with an estimated glomerular filtration rate (eGFR) ≥30 ml/min/1.73 m2. Methods. A total of 13,355 hypertensive participants with eGFR ≥30 ml/min/1.73 m2 were selected from the Chinese Hypertension Registry Study. Multivariate linear regression was used to examine the linear relationship between SUA and lipids. Smooth curve fitting (penalized spline method) and threshold saturation effects were used to analyze the nonlinear association between SUA and lipids. Results. In the fully adjusted model, the results showed a positive correlation between SUA and TG (β = 0.15; 95% CI: 0.14, 0.16) and LDL-C (β = 0.06; 95% CI: 0.05, 0.07), respectively. However, the relationship between SUA and HDL-C was nonlinear. The inflection point of SUA was 7.24 mg/dL. On the left side of the inflection point (<7.24 mg/dL), SUA was negatively associated with HDL-C (β = −0.02; 95% CI −0.02, −0.01). On the right side of the inflection point (≥7.24 mg/dL), SUA was not related to HDL-C (β = 0.01; 95% CI −0.01, 0.02). Conclusion. After adjusting for all covariates, SUA was positively associated with TG and LDL-C. The relationship between SUA and HDL-C was nonlinear. The negative correlation between SUA and HDL-C only existed when the SUA was less than 7.24 mg/dL in a hypertensive population with eGFR ≥30 ml/min/1.73 m2.
Treatment options for patients with recurrent/metastatic nasopharyngeal carcinoma (RM-NPC) are not clear after progression on previous treatment with PD-(L)1 inhibitor; critical gaps in evidence ...remain for such cases. Immunotherapy combined with antiangiogenic therapy has been reported to have synergistic antitumor activity. Therefore, we evaluated the efficacy and safety of camrelizumab plus famitinib in patients with RM-NPC who failed treatment with PD-1 inhibitor-containing regimens.
This multicenter, adaptive Simon minimax two-stage, phase II study enrolled patients with RM-NPC refractory to at least one line of systemic platinum-containing chemotherapy and anti-PD-(L)1 immunotherapy. The patient received camrelizumab 200 mg every 3 weeks and famitinib 20 mg once per day. The primary endpoint was objective response rate (ORR), and the study could be stopped early as criterion for efficacy was met (>5 responses). Key secondary endpoints included time to response (TTR), disease control rate (DCR), progression-free survival (PFS), duration of response (DoR), overall survival (OS), and safety. This trial was registered with ClinicalTrials.gov, NCT04346381.
Between October 12, 2020, and December 6, 2021, a total of 18 patients were enrolled since six responses were observed. The ORR was 33.3% (90% CI, 15.6–55.4) and the DCR was 77.8% (90% CI, 56.1–92.0). The median TTR was 2.1 months, the median DoR was 4.2 months (90% CI, 3.0–not reach), and the median PFS was 7.2 months (90% CI, 4.4–13.3), with a median follow-up duration of 16.7 months. Treatment-related adverse events (TRAEs) of grade ≥3 were reported in eight (44.4%) patients, with the most common being decreased platelet count and/or neutropenia (n = 4, 22.2%). Treatment-related serious AEs occurred in six (33.3%) patients, and no deaths occurred due to TRAEs. Four patients developed grade ≥3 nasopharyngeal necrosis; two of them developed grade 3–4 major epistaxis, and they were cured by nasal packing and vascular embolization.
Camrelizumab plus famitinib exhibited encouraging efficacy and tolerable safety profiles in patients with RM-NPC who failed frontline immunotherapy. Further studies are needed to confirm and expand these findings.
Jiangsu Hengrui Pharmaceutical Co., Ltd.
Highlights • The CTL responses to pancreatic cancer induced by DCs in vitro. • DCs were loaded with 2 pancreatic tumor-associated antigens, MUC4 and survivin. • DC encoding 2 pancreatic TAA mRNAs ...induced a more potent CTL response toward PC. • The antigen-specific CTL response is restricted by MHC class I antigen presentation. • It is a prerequisite for DC vaccines encoding multiple pancreatic TAA epitopes.
The microstructural evolutions of 5Mn steel during various heat treatments have been investigated by in-situ transmission electron microscopy (TEM). The specimen of 5Mn steel was prepared using ...focused ion beam (FIB) milling, which allowed the selection of specific morphology of interest prior to the in-situ observation. The complete austenization at 800 °C was verified at the atomic scale by minimizing thermal expansion and sample drift in a heating holder based on micro-electro-mechanical-systems. During annealing at 650 °C, the formation of reverted austenite was dynamically observed, while the morphologies of austenite laths of 5Mn steel after in-situ heating were quite similar to that after ex-situ intercritical annealing. During annealing at 500 °C, the morphological evolution of cementite and associated Mn diffusion were investigated. It was demonstrated that a combination of FIB sampling and high temperature in-situ TEM enables us to probe the morphological evolution and elemental diffusion of specific areas of interest in steel at high spatial resolution.
► The strength and toughness of continuous CNT fibers are studied at multi-scale levels. ► Fibers consist of two load-bearing materials, namely CNT bundles and CNT threads. ► Bundles and threads play ...different roles at different stages of the fiber deformation. ► Constitutive equation is developed to characterize mechanical properties of fibers. ► Strength and toughness of fibers can be enhanced by controlling structural parameters.
The control mechanisms of the strength and toughness of carbon nanotube (CNT) fibers are revealed by analyzing the load-bearing and deformation characteristics of multi-scale structures in the fiber under tensile loading. A theoretical model is established to investigate the effect of the multi-scale structures on the strength and toughness of CNT fibers. Based on our previous experimental results on tension with in situ micro-Raman monitoring Li et al., Nanotechnology 22, 2011, the macro- and micro-mechanical behaviors of the fiber are analyzed. The tensile behaviors of the fiber are correlated with the load-bearing and deformation processes involved in the multi-scale structures in the fiber, such as the nanotube bundle and the thread in microscopic scale, and the CNT in nanoscale. The CNT fiber exhibits high strength and toughness simultaneously depending on the multi-scale structure of the material, the differences in the properties between bundles and threads, and the unique interfaces formed by the tabular geometric configuration of double-walled CNTs. A constitutive relationship for CNT fiber materials is developed to provide information on the role of multi-scale structures on the strength and toughness of fibers. Both strength and toughness of CNT fibers can be enhanced by increasing the volume ratio of bundles to threads, the interfacial shear strength, and the interface slippage friction resistive force among the CNTs.
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