Bendtsenringgaard8537

To evaluate PJP infection risk in patients with SLE in Taiwan.

We identified 24,367 patients with SLE from the National Health Insurance research database between 1997 and 2012 and compared the PJP incidence rates (IRs) with those in 243,670 age- and sex-matched non-SLE controls. PJP risk in the patients was evaluated using a Cox multivariate proportional hazards model.

The patients exhibited a significantly higher PJP risk than the controls, with an IR of 2.63 per 10,000 person-years and IR ratio of 27.65 (95% CI 17.2-45.3, p < 0.001). Male sex (hazard ratio [HR] 2.42, p < 0.01), end-stage renal disease (ESRD; HR 1.74, p = 0.01), recent use of mycofenolate mofetil (MMF; HR 4.43, P < 0.001), intravenous steroid pulse therapy (HR 108.73, p < 0.001), and average oral dose of >7.5 mg/day prednisolone or equivalent (HR 4.83, p < 0.001) were associated with PJP in SLE, whereas hydroxychloroquine use reduced its risk (HR 0.51, p = 0.01). Of note, cyclophosphamide was not associated with PJP infection in the multivariate Cox proportional hazard model.

Patients with SLE have a considerably high PJP risk. Cyclophosphamide does not increase PJP risk. Male sex, ESRD, MMF use, intravenous steroid pulse therapy, oral prednisolone or equivalent (>7.5 mg/day) are risk factors for PJP, whereas hydroxychloroquine use reduces PJP risk.

7.5 mg/day) are risk factors for PJP, whereas hydroxychloroquine use reduces PJP risk.Ageing population is a tough task worldwide, and the aggravating trend of ageing population in China brings enormous pressure to healthcare system. Chinese acupuncture has shown definite anti-ageing effect as arthralgia relief, movement improvement, energy increase and immunity enhancement; however, the mechanisms underlying are far away from illumination. Increasing literature has highlighted the role of alterations in mitochondrial function as a potential central regulator in ageing biology; mitophagy plays a critical role in mitochondrial quality control. In the present study, we demonstrated that acupoint catgut embedding treatment ameliorated ageing-related alterations in appearance, muscle function and spatial memory in rats, reduced degenerated cells in hippocampus, and maintained relatively normal structures in the hippocampus tissue and neurons. Topoisomerase inhibitor These changes were proved to be associated with the regulation of mitochondrial function and autophagic activity. Furthermore, we investigated part of the molecular mechanisms and demonstrated that the PINK1 other than PINK1-Parkin signalling pathway involved in the effects of acupoint catgut embedding, and the imbalancement between mitochondrial fusion and fission and stimulation of mitochondrial biogenesis may aggravate or compensate for impaired mitochondria. The factors act downstream PINK, and the interaction between them for mitochondrial homeostasis in this process remains to be identified.Owing to their ability to rapidly proliferate in specific niches and their amenability to genetic manipulation, bacteria are frequently studied as potential diagnostic or therapeutic bioagents in a range of pathological contexts. A sustained oxygen supply within solid tumors is essential in order to achieve positive radiotherapy (RT) outcomes, as these intratumoral oxygen levels are necessary to facilitate RT-induced reactive oxygen species (ROS) generation. In this study, a genetically engineered variant of the tumor-targeting probiotic E. coli Nissle 1917 bacteria that secret catalase is utilized to alleviate intratumoral hypoxia and to thereby enhance tumor radiosensitivity. These engineered bacteria are able to facilitate robust O2 evolution and consequent ROS generation in response to X-ray irradiation both in vitro and in vivo, significantly inhibiting tumor growth. Overall, the study highlights a novel and practical approach to enhance the efficacy of tumor RT, underscoring the value of future research in the field of probiotic medicine.

PTPRZ1-MET (ZM) is a critical genetic alteration driving the progression of lower-grade glioma. Glioma patients harboring ZM could benefit from MET inhibitors. According to the remarkable role of ZM as a driver of glioma progression and indicator of MET inhibitor sensitivity, it is necessary to detect this alteration even when it presents in glioma with relatively fewer copies.

Herein, we proposed that ZM could be detected with a high-sensitive method of reverse transcriptase PCR with 50 amplification cycles. Via this newly proposed detection method, we depicted the incidence preference of ZM fusion in a cohort of 485 glioma patients. To further explore the oncogenic nature of ZM, we predicated the protein structure alteration of MET kinase brought by its fusion partner.

The incidence of ZM fusions was much higher than previous report. ZM fusions exhibited a striking preference in lower-grade glioma and secondary glioblastoma. By contrast, none of patients with primary glioblastoma was detected harborinverse transcriptase PCR. The hyperactivations of MET signaling driving glioma progression might be contributed by a ligand-independent activation enabled by the protein structure modification of extracellular domain of MET in ZM fusions.

Intracerebral hemorrhage (ICH) is a catastrophic cerebrovascular disease with high morbidity and mortality. Evidence demonstrated that sphingosine-1-phosphate receptor (S1PR) plays a vital role in inflammatory damage via the upregulation of CCL2 expression. However, whether S1PR3 is involved in blood-brain barrier (BBB) breakdown via CCL2 activation after ICH has not been described.

We investigated the expression profiles of all S1PRs using high-throughput RNA-seq analysis and RT-PCR. The potential role of S1PR3 and interaction between S1PR3 and CCL2 were evaluated via Western blotting, immunofluorescence, and flow cytometry. BBB disruption was examined via magnetic resonance imaging, transmission electron microscopy, and Evans blue extravasation. Microglial activation, proliferation, and polarization were assessed via histopathological analysis. The expression levels of CCL2, p-p38 MAPK, ICAM-1, and ZO-1 were examined in vitro and in vivo.

The present results showed that the levels of S1PR3 and its ligthis is the first demonstration of the neuroprotective role of S1PR3 modulation in maintaining BBB integrity by inhibiting the S1PR3-CCL2 axis after ICH, providing a novel treatment for ICH by targeting S1PR3.The complement receptor of the immunoglobulin superfamily (CRIg, encoded by the VSIG4 gene) is a macrophage receptor involved in the clearance of immune complexes and autologous cells. Our results suggest that the VSIG4 rs1044165T allele is a risk factor for severe functional status of rheumatoid arthritis in women, possibly by affecting VSIG4 gene expression.Extensive cytocompatibility testing of 2D nanocarbon materials including graphene oxide (GO) has been performed, but results remain contradictory. Literature has yet to account for settling-although sedimentation is visible to the eye and physics suggests that even individual graphenic flakes will settle. To investigate settling, a series of functional graphenic materials (FGMs) with differing oxidation levels, functionalities, and physical dimensions are synthesized. Though zeta potential indicates colloidal stability, significant gravitational settling of the FGMs is theoretically and experimentally demonstrated. By creating a setup to culture cells in traditional and inverted orientations in the same well, a "blanket effect" is demonstrated in which FGMs settle out of solution and cover cells at the bottom of the well, ultimately reducing viability. Inverted cells protected from the blanket effect are unaffected. Therefore, these results demonstrate that settling is a crucial factor that must be considered for FGM cytocompatibility experiments.A 57-year-old female presented with progressive swelling of both calves (Fig.1A), associated with dull-aching pain on exertion for last 6 months. She underwent L5-S1 discectomy in 2006 for right lower limb radicular pain and L4-L5 laminectomy with discectomy in 2008 for recurrence of symptoms. Investigations revealed normal hemogram, liver and kidney function tests, thyroid profile, and inflammatory markers. Creatine phosphokinase was 542U/L (Normal less then 145) and lactate dehydrogenase was 948U/L (Normal less then 480).Radiotherapy (RT) is a popular clinical therapy method for extending cancer patient survival, but is hampered by severe side effects and the weak therapy effect. Herein, responsive degradable selenium (Se) theranostic agents (Se@SiO2 @Bi nanocomposites (NCs)) are fabricated, which combine computed tomography (CT) imaging and simultaneously enhance the therapeutic effects of photothermal therapy (PTT) and RT, while reducing the side effects of radiation. The Se@SiO2 @Bi theranostic agents can accumulate at the tumor site, and responsively decompose to releease Se, avoiding systemic toxicity by the element. Se enhances the effect of PTT/RT, simultaneously reducing the side effects of RT. The Se@SiO2 @Bi NCs as CT agents also exhibit significantly enhanced contrast imaging performance due to the high atomic number of Bi. More importantly, the Se@SiO2 @Bi NCs can be rapidly excreted without long-term toxicity, owing to responsive degradation into ultrasmall particles ( less then 5 nm) at the tumor site. In vitro and in vivo results show that the Se@SiO2 @Bi NCs can remarkably inhibit tumor cells, without causing appreciable toxicity during the treatment. This study opens a new perspective in rationally designing responsive degradable theranostic agents for future tumor therapy with enhanced therapeutic efficacy and lesser side effects.

Histology represents the major source of information to define a usual interstitial pneumonia (UIP) pattern. However, the procedure is associated with significant morbidity and mortality. The aim of this study was to evaluate morbidity and mortality of surgical lung biopsy (SLB) in diagnosing UIP.

Patients undergoing SLB with the ultimate diagnosis of UIP were studied. Clinical data concerning medical history, histology, pulmonary functions, radiology, length of hospital stay (LOS), morbidity and mortality status were retrospectively recruited from four hospitals.

The study included consecutive 93 patients with a SLB diagnosis of UIP. Mean age was 61 ± 8 years, with one third of the patients were ≥65 years. In 58 cases (62.4%), the biopsy was performed by video-assisted thoracoscopic surgery, in 35 (37.7%) by limited thoracotomy. Eighty patients (86%) had possible UIP, 12 (12.9%) had inconsistent with UIP and one (1.1%) had UIP pattern on high-resolution computed tomography. The mean LOS was 5.47 ± 3.16 days. LOS was associated with smoking status (P = 0.024), type of biopsy (P = 0.00), 6-min walk test (P = 0.00) and number of biopsy (P = 0.00). There was no in-hospital and 30-day mortality in our cohort, and 90-day mortality rate was 1.1%. In seven patients (7.5%), we observed postoperative morbidities, predominantly prolonged air leakage (7.5% of all cases). Postoperative morbidity was only associated with the type of SLB. Patients with limited thoracotomy showed greater morbidity rates (17.1% versus 1.7%, P = 0.011).

SLB is a relatively safe procedure in the diagnosis of UIP and can be performed in suitable patients with suspected UIP/idiopathic pulmonary fibrosis.

SLB is a relatively safe procedure in the diagnosis of UIP and can be performed in suitable patients with suspected UIP/idiopathic pulmonary fibrosis.