Expression pattern of serum interleukin-7 in elderly septic patients and its prognostic value for predicting short-term mortality.

BACKGROUND: The identification of novel prognostic biomarkers in elderly septic patients are essential for the improvement of mortality in sepsis in the context of precision medicine. The purpose of this study was to explore the expression pattern and prognostic value of serum interleukin-7 (IL-7) in predicting 28-day mortality in elderly patients with sepsis. METHODS: Patients were retrospectively enrolled according to the sepsis-3.0 diagnostic criteria and divided into the survival group and non-survival group based on the clinical outcome at the 28-day interval. The baseline characteristic data, samples for the laboratory tests, and the SOFA, Acute Physiology and Chronic Health Evaluation (APACHE II), as well as Glasgow coma scale (GCS) scores, were recorded within 24 h after admission to the emergency department. Serum levels of IL-7 and TNF-α of the patients were quantified by the Luminex assay. Spearman correlation analysis, logistic regressive analysis and receiver operating characteristic curve (ROC) analysis were performed, respectively. RESULTS: Totally, 220 elderly patients with sepsis were enrolled, 151 of whom died in a 28-day period. Albumin (ALB), high-density lipoprotein (HDL), systolic pressure (SBP), and platelet (PLT) were found to be significantly higher in the survival group (p < 0.05). IL-7 was shown to be correlated with TNF-α in the non-survival group (p = 0.030) but not in the survival group (p = 0.194). No correlation was shown between IL-7 and other factors (p > 0.05). IL-7 and TNF-α were found to be independent risk factors associated with the 28-day mortality (OR = 1.215, 1.420). Combination of IL-7, SOFA and ALB can make an AUROC of 0.874 with the specificity of 90.77 %. Combination of IL-7 and TNF-α can make an AUROC of 0.901 with the sensitivity of 90.41 % while the combination of IL-7, TNF-α, and ALB can make an AUROC of 0.898 with the sensitivity of 94.52 %. CONCLUSIONS: This study highlights the importance of monitoring the serum level of IL-7 and TNF-α in elderly septic patients as well as evaluating the combinations with other routine risk factors which can be potentially used for the identification of elderly septic patients with higher risk of mortality.

Effectiveness of Different Telerehabilitation Strategies on Pain and Physical Function in Patients With Knee Osteoarthritis: Systematic Review and Meta-Analysis.

BACKGROUND: Knee osteoarthritis (OA) is a chronic, degenerative bone and joint disease. It can lead to major pressure to the quality of life and mental health of patients, and also brings a serious economic burden to society. However, it is difficult for patients with knee OA to access rehabilitation when discharging from the hospital. Internet-based rehabilitation is one of the promising telemedicine strategies for the improvement of knee OA, but the effect of different telerehabilitation strategies on knee OA is not clear. OBJECTIVE: The aim of this systematic review and meta-analysis was to identify telerehabilitation strategies attributing to the improvement of pain and physical function outcomes in patients with knee OA. METHODS: We reviewed and analyzed telerehabilitation strategies from randomized controlled trials (RCTs) comparing telerehabilitation with conventional treatment or usual care. For each strategy, we examined whether RCTs that applied the telerehabilitation strategy resulted in a significant improvement in pain or physical function compared with conventional treatment or usual care. RESULTS: We included 6 RCTs (n=734) incorporating 8 different telerehabilitation strategies. The duration of the interventions ranged from 1 to 48 weeks, and sample sizes ranged from 20 to 350 patients. The results showed that RCTs that provided telerehabilitation were found to be more effective than conventional treatments for improving pain (P=.003; standardized mean difference [SMD] -0.21, 95% CI -0.35 to -0.07), but not physical function (P=.24; SMD -0.09, 95% CI -0.25 to 0.06). Furthermore, this systematic review and meta-analysis indicated that there is no significant correlation between different telerehabilitation strategies and the pain and physical function of patients with knee OA. CONCLUSIONS: This systematic review and meta-analysis showed that telerehabilitation programs could relieve pain but not improve physical function for patients with knee OA. These results indicated that telerehabilitation is beneficial for the implementation of home rehabilitation exercises for patients with knee OA, thereby reducing the economic burden of health. However, there were limitations in terms of the number of search results and the number of studies that were eligible for this review and meta-analysis. Therefore, the results need to be interpreted with caution, and more high-quality studies with large samples are needed to focus on the long-term outcomes of telerehabilitation for patients with knee OA to address this limitation.

miR-448-3p controls intracranial aneurysm by regulating KLF5 expression.

microRNAs (miRNAs) control several processes known to be involved in progression of aneurysm. Here, intracranial aneurysms (IAs) were surgically induced in Sprague-Dawley rats, and we found that miR-448-3p was downregulated and KLF5 was upregulated in IA rats. We identified Klf5 as a direct target of miR-448-3p in smooth muscle cells (SMCs). In addition, aneurysms size and the lumen area of the aneurysms were smaller 4 weeks after IA induction in the miR-448-3p-treated group. miR-448-3p treatment protected the wall thickness ratio and suppressed macrophage infiltration after IA induction. IAs caused a significant increase in KLF5 expression and were alleviated by miR-448-3p. Moreover, the anti-inflammatory effect of miR-448-3p was verified in lipopolysaccharide -stimulated RAW 264.7 macrophage cells. The expression levels of KLF5, MMP2, and MMP9 levels were elevated by LPS, and were attenuated by miR-448-3p. These data suggest that miR-448-3p plays the inhibitory role in IA progression, indicating that miR-448-3p overexpression is crucial for preventing the development of IA through downregulation of macrophage-mediated inflammation.

Improvement of cerebral blood perfusion in certain cerebral regions after cranioplasty could be monitored via tympanic membrane temperature changes.

OBJECTIVE: Delayed neurological deficit was often observed in patients underwent craniectomy, which could be improved by cranioplasty. Little is known about hemodynamic improvement before and after cranioplasty. METHODS: Cerebral blood perfusion, tympanic membrane temperature (TMT), neuropsychological and cognitive function were assessed in eleven craniectomy patients before and after cranioplasty. RESULTS: Before cranioplasty, the cerebral blood volume (CBV) on the decompressed side was significantly lower than that of the contralateral side. The cranioplasty led to instant improvement (7 days after cranioplasty) of cerebral perfusion at the cranioplasty side in the frontal lobe, parietal lobe, temporal lobe, mesencephalon, basal ganglia and thalamus, but not the occipital lobe and epencephalon. Interestingly, CBV of the thalamus and basal ganglia gradually decreased to pre-surgical status 6 months later while the frontal lobe, parietal lobe, temporal lobe, mesencephalon remained well perfused. Meanwhile, the TMT changes acquired positive correlation with the perfusion of temporal lobe and mesencephalon as well as the GCS and MMSE score. CONCLUSION: The cranioplasty remarkably improves neurological and cognitive function by ameliorating cerebral perfusion in certain regions. The TMT could be used as a non-invasive method to monitor the cerebral perfusion improvement after the cranioplasty.

Use of CRB-65 and quick Sepsis-related Organ Failure Assessment to predict site of care and mortality in pneumonia patients in the emergency department: a retrospective study.

BACKGROUND: The quick Sepsis-related Organ Failure Assessment (qSOFA) is a new screening system for sepsis that has prognostic performance equal to the full SOFA for patients with suspected infection outside the intensive care unit (ICU). The predictive value of qSOFA for mortality and site of care in patients with pneumonia is not clear. The present study was designed to investigate the predictive performance of qSOFA, CRB-65 (confusion, respiratory rate ≥30/minute, systolic blood pressure <90 mmHg or diastolic blood pressure ≤60 mmHg, age ≥65 years) and CRB (confusion, respiratory rate ≥30/minute, systolic blood pressure <90 mmHg or diastolic blood pressure ≤60 mmHg) for mortality, hospitalisation and ICU admission in patients with pneumonia in the emergency department (ED). METHODS: Retrospective analyses of published data on adult patients with pneumonia presenting between January 2012 and May 2014 were undertaken. The prevalence of 28-day mortality, hospitalisation and ICU admission were compared with regard to qSOFA, CRB and CRB-65 scores. The performance of these three systems for predicting outcomes was compared. RESULTS: Of 1641 patients, 861 (53 %) were hospitalised (38 % in a general ward, 15 % in the ICU), and the remaining 780 (47 %) were treated as outpatients or were observed in the ED. Within 28 days, 547 (33 %) of 1641 patients died. CRB-65, CRB and qSOFA scores of patients who died, were hospitalised and admitted to the ICU than those who survived and were not hospitalised or admitted to the ICU (P < 0.001). AUC values of qSOFA for prediction of 28-day mortality, hospitalisation and ICU admission were similar to those for CRB-65 and CRB. Patients with qSOFA scores of 0, 1, 2 and 3 were associated with, respectively, mortality of 16.3 %, 24.4 %, 48.2 % and 68.4 %; prevalence of hospitalisation of 37.2 %, 47.4 %, 61.6 % and 73.7 %; and prevalence of ICU admission of 9.3 %, 9.1 %, 22.4 % and 45.3 %. Patients with qSOFA scores of 2 and 3 had a significantly higher prevalence of mortality and ICU admission than patients with identical CRB-65 scores. CONCLUSIONS: qSOFA is better than CRB-65 for identification of a high risk of mortality and requirement of ICU admission.

Predictive performance of quick Sepsis-related Organ Failure Assessment for mortality and ICU admission in patients with infection at the ED.

OBJECTIVE: The objectives of this study are to investigate the performance of the quick Sepsis-related Organ Failure Assessment (qSOFA) in predicting mortality and intensive care unit (ICU) admission in patients with clinically diagnosed infection and to compare its performance with that of Mortality in Emergency Department Sepsis (MEDS), Acute Physiology and Chronic Health Evaluation (APACHE) II, and Sepsis-related Organ Failure Assessment (SOFA). METHODS: From July to December 2015, we retrospectively analyzed 477 patients clinically diagnosed with infection in the emergency department. We compared the performance of SOFA, MEDS, APACHE II, and qSOFA in predicting ICU admission and 28-day mortality. RESULTS: All scores were higher in nonsurvivors and ICU patients than in survivors and non-ICU patients (P< .001). The area under the receiver operating characteristic curve of qSOFA was lower than that of MEDS (0.666 vs 0.751; P< .05) and similar to that of SOFA (0.729) and APACHE II (0.732) in predicting 28-day mortality. The areas under the receiver operating characteristic curve of qSOFA, SOFA, MEDS, and APACHE II in predicting ICU admission were 0.636, 0.682, 0.661, and 0.640, respectively. There were no significant differences among the score systems. In patients with qSOFA scores less than 2 and greater than or equal to 2, 28-day mortality rates were 17.4% and 42.9% (P< .001), and ICU admission rates were 16.0% and 33.3% (P< .001). CONCLUSIONS: Quick SOFA predicted ICU admission with similar performance to that of SOFA, MEDS, and APACHE II. Its prognostic ability was similar to that of SOFA and APACHE II but slightly inferior to that of MEDS.

Ubiquitin-specific protease 2a stabilizes MDM4 and facilitates the p53-mediated intrinsic apoptotic pathway in glioblastoma.

The mouse double minute 4 (MDM4) oncoprotein may inhibit tumorigenesis by regulating the apoptotic mediator p53. Ubiquitin-specific protease 2a (USP2a) is a deubiquitinating enzyme that protects MDM4 against degradation, so USP2-MDM4 interaction may be a key determinant of the malignant potential of human cancers. MDM4 and USP2a, as well as the MDM4-USP2a complex, were more highly expressed in glioblastoma multiforme tissue samples from patients with good prognosis compared with patients with poor prognosis. Analysis of the prognostic parameters indicated that MDM4 expression was positively correlated with an increased likelihood for survival. Compared with the poor prognosis patients, mitochondria from good prognosis glioma patients contained higher levels of both MDM4 and the proapoptotic protein p53Ser46(P). In U87MG glioma cell line, the overexpression of MDM4 enhanced ultraviolet (UV)-induced cytochrome c release and apoptosis. In contrast, MDM4 knockdown decreased mitochondrial p53Ser46(P) levels and rescued cells from UV-induced apoptosis. The expression of MDM4 and USP2a were positively correlated with each other. MDM4-USP2a complexes were found only in the cytoplasmic fraction, whereas the mitochondrial fraction contained MDM4-p53Ser46(P) and MDM4-Bcl-2 complexes. Overexpression of USP2a increased p53 and p53Ser46(P) levels in the mitochondria, whereas simultaneous MDM4 knockdown completely reversed this effect. UV-induced apoptosis was reduced by USP2a knockdown but restored by the simultaneous overexpression of MDM4. This apoptotic response was reduced by knockdown of p53 but not p21. Our results suggest that USP2a binds to and stabilizes MDM4; thus in turn, it enhances the mitochondrial localization of p53 and promotes apoptosis in glioma cells.

[Change in soil enzymes activities after adding biochar or straw by fluorescent microplate method].

The present work was aimed to study soil a-glucosidase and beta-glucosidase activities of and red soils based on fluorescence detection method combined with 96 microplates with TECAN Infinite 200 Multi-Mode Microplate Reader. We added biochar or straw (2.5 g air dry sample/50g air dry soil sample) into and red soils and the test was carried under fixed temperature and humidity condition (25 degrees C, 20% soil moisture content). The results showed that straw addition enhances soil alpha-glucosidase and beta-glucosidase activities, beta-glucosidase activity stimulated by rice straw treatment was higher than that of corn straw treatment, and activity still maintains strong after 40 days, accounting for increasing soil carbon transformation with straw inputting. Straw inputting increased soil nutrients contents and may promote microbial activity, which also lead to the increase oin enzyme Straw inputting increased soil nutrients contents and may promote microbial activity, which also lead to the increase oin enzyme activities. Different effects of straw kinds may be related to material source that needs further research. However, biochar inputting has little effect on soil alpha-glucosidase and beta-glucosidase activity. Biochar contains less available nutrients than straw and have degradation-resistant characteristics. Compared with the conventional spectrophotometric method, fluorescence microplate method is more sensitive to soil enzyme activities in suspension liquid, which can be used in a large number of samples. In brief, fluorescence microplate method is fast, accurate, and simple to determine soil enzymes activities.

RLIP76 is overexpressed in human glioblastomas and is required for proliferation, tumorigenesis and suppression of apoptosis.

The guanosine triphosphatase-activating protein RLIP76 is overexpressed in many malignant tumor cells, but it is unclear if RLIP76 overexpression contributes to the high proliferative potential of glioma cells. We demonstrate that RLIP76 messenger RNA and protein expression are positively correlated with glioma grade and that higher RLIP76 expression correlates with shorter patient survival. Immunohistochemical staining revealed that RLIP76 expression was positively correlated with the expression of Ki-67, a biomarker for cell proliferation. Inhibition of RLIP76 expression in U87 and U251 glioma cell lines by stable transfection of a targeted siRNA suppressed anchorage-independent growth and enhanced apoptosis in vitro. Conversely, overexpression of RLIP76 in SW1088 and U251 cell lines enhanced proliferation and reduced apoptosis. Inhibition of RLIP76 in U251 cells also significantly suppressed tumorigenicity and induced apoptosis in an endotopic xenograft mouse model. Moreover, we demonstrate that knockdown of RLIP76 increases apoptosis in different human gliomas independently of p53 status. In addition, a constitutively active Rac1 reversed both the suppression of proliferation and the promotion of apoptosis induced by the RLIP76-targeted siRNA, indicating that RLIP76 is an upstream activator of Rac1. Rac1-mediated suppression of apoptosis and promotion of proliferation were dependent on intact c-jun N-terminal kinase (JNK) signaling. Furthermore, we demonstrate that RLIP76 promotes proliferation and suppresses glioma cell apoptosis through a mechanism independent of Rho-selective GTPase-activating protein. Instead, we found that the adenosine triphosphatase function of Rlip76 modulates Rac1 activity by regulating Rac1 protein ubiquitylation and degradation. These data demonstrate that RLIP76 may suppress apoptosis and promote the proliferation of glioma cells by direct adenosine triphosphate-dependent xenobiotic transport and by activating the Rac1-JNK signaling pathway. Inhibition of RLIP76 signaling is a potential treatment for malignant glioma.

The relation between persistent coma and brain ischemia after severe brain injury.

AIM: To investigate the relation between brain ischemia and persistent vegetative state after severe traumatic brain injury. METHODS: The 66 patients with severe brain injury were divided into two groups: The persistent coma group (coma duration ≥10 d) included 51 patients who had an admission Glasgow Coma Scale (GCS) of 5-8 and were unconscious for more than 10 d. There were 15 patients in the control group, their admission GCS was 5-8, and were unconscious for less than 10 d. The brain areas, including frontal, parietal, temporal, occipital lobes and thalamus, were measured by Single Photon Emission Computed Tomography (SPECT). RESULTS: In the first SPECT scan, multiple areas of cerebral ischemia were documented in all patients in both groups, whereas bilateral thalamic ischemia were presented in all patients in the persistent coma group and were absented in the control group. In the second SPECT scan taken during the period of analepsia, with an indication that unilateral thalamic ischemia were persisted in 28 of 41 patients in persistent coma group(28/41,68.29%). CONCLUSION: Persistent coma after severe brain injury is associated with bilateral thalamic ischemia.

Valve repair after infective endocarditis secondary to perforation caused by Streptococcus gordonii: A case report.

BACKGROUND: We report a case of infective endocarditis (IE) in a patient with congenital heart valve lesions accompanied by IE, which was diagnosed based on blood culture analysis that revealed the presence of a gram-negative bacterium, Streptococcus gordonii. CASE SUMMARY: The patient had a history of precordial valve disease diagnosed by cardiac ultrasound, as well as a 4-mo history of fever. He was subjected to comprehensive anti-infection and anti-heart failure treatment in the internal medicine department. Further examination revealed sudden dislodgement from and perforation through the aortic valve by the superfluous organisms, as well as occurrence of bacterial emboli dislodgement, which caused bacteremia and infectious shock. He recovered and was discharged from the hospital after surgical and postoperative anti-infection treatments. CONCLUSION: We review the treatment process and highlight inspirations and reflections from this case; suggest possible future changes in treatment modalities.

Low serum thyroid-stimulating hormone levels may be an early predictor of sepsis.

OBJECTIVE: This study aimed to explore whether thyroid-stimulating hormone (TSH) plays an early warning role in detecting progression of bacterial infection to sepsis and can serve as a novel marker for the diagnosis of sepsis. METHOD: This was a prospective study of patients treated for 'bacterial infection' in the emergency department of Beijing Chaoyang Hospital from 1 January 2021 to 31 August 2021. Subjects were divided into a sepsis group (SG) and a non-SG (NSG), according to whether their condition had progressed to sepsis within 72 hours of admission. Routine blood test results as well as biochemical and thyroid function indices (T4, FT4, T3, FT3) were recorded at the time of admission. TSH, Acute Physiology and Chronic Health Evaluation II scores and Sequential Organ Failure Assessment scores were likewise documented. RESULTS: A total of 62 patients were enrolled, the SG and the NSG showed significant differences in their levels of TSH. The results indicate that TSH is an early warning marker for sepsis. CONCLUSIONS: TSH plays an early warning role in the diagnosis of bacterial infection progressing to sepsis, having a strong predictive value.

Predictive Value of Heart-Type Fatty Acid-Binding Protein for Mortality Risk in Critically Ill Patients.

Objective: Our study assessed the predictive value of heart-type fatty acid-binding protein (H-FABP) for critically ill patients. Methods: 150 critically ill patients admitted to the emergency department of Beijing Chaoyang Hospital, Capital Medical University, were included in our study from August 2021 to April 2022. Serum H-FABP, procalcitonin (PCT), lactate (LAC), and other markers were determined within 1 h after admission. The Sequential Organ Failure Assessment (SOFA) score and the Acute Physiology and Chronic Health Evaluation II (APACHE II) were calculated. The independent predictors of 28-day mortality in critically ill patients were analyzed by logistic regression, and the receiver operating characteristic curve (ROC) was used to analyze the predictive value for 28-day mortality in critically ill patients. Results: Age, APACHE II, SOFA, GCS, LAC, H-FABP, IL-6, Scr, and D-dimer were significantly different in the nonsurvivor vs. survivor groups (P < 0.05), with H-FABP correlating with cTNI, Scr, PCT, and SOFA scores (P < 0.05). Logistic regression analysis showed that H-FABP, APACHE II, LAC, and age were independent predictors for 28-day mortality in critically ill patients (P < 0.05). The AUC of ROC curve in H-FABP was 0.709 (sensitivity 72.9%, specificity 66.1%, and cut-off 4.35), which was slightly lower than AUC of ROC curve in LAC (AUC 0.750, sensitivity 58.3%, specificity 76.1%, and cut-off 1.95) and APACHE II (AUC 0.731, sensitivity 77.1%, specificity 58.7%, and cut-off 12.5). However, statistically, there was no difference in the diagnostic value of H-FABP compared with the other two indicators (Z 1 = 0.669, P = 0.504; Z 2 = 0.383, P = 0.702). But H-FABP (72.9%) has higher sensitivity than LAC (58.3%). The combined evaluation of H-FABP+APACHE II score (AUC 0.801, sensitivity 71.7%, and specificity 78.2%; Z = 2.612, P = 0.009) had better diagnostic value than H-FABP alone and had high sensitivity (71.7%) and specificity (78.2%). Conclusion: H-FABP, LAC, APACHE II, and age can be used as independent risk factors affecting the prognosis of critically ill patients. Compared with using the above indicators alone, the H-FABP+APACHE II has a high diagnostic value, and the early and rapid evaluation is particularly important for the adjustment of treatment plans and prognosis.

A rare Von Hippel-Lindau disease that mimics acute myelitis: case report and review of the literature.

Von Hippel-Lindau disease (VHL) comprises a series of complicated clinical manifestations. We hereby report one unique case of VHL with a natural history that mimics acute myelitis. MRI and biopsy in this patient showed multiple solid hemangioblastomas of the central nervous system and kidney. This study further confirmed that VHL is of highly clinical, imaging, and pathological heterogeneity. Diagnosis for VHL should be based on combination of clinical, radiological, pathological, and genetic data.

Acute pancreatitis with hypercalcemia caused by primary hyperparathyroidism associated with paraneoplastic syndrome: A case report and review of literature.

BACKGROUND: Although acute pancreatitis associated with hyperparathyroidism has occasionally been reported, acute pancreatitis with metabolic encephalopathy caused by hyperparathyroidism combined with paraneoplastic syndrome is an extremely rare entity and poorly described in the literature. CASE SUMMARY: We present a case of a 56-year-old female with upper abdominal discomfort and intermittent nausea and vomiting for 1 wk, without apparent abdominal pain or bloating, no jaundice and decreased blood pressure at the outset. The patient was ultimately diagnosed with moderately severe acute pancreatitis (according to the revised Atlanta classification of acute pancreatitis) combined with metabolic encephalopathy secondary to hypercalcemia caused by primary hyperparathyroidism associated with paraneoplastic syndrome. After active treatment of acute pancreatitis, massive fluid resuscitation, resection of parathyroid and uterine malignant tumors, neoadjuvant chemotherapy and other treatments, her serum calcium eventually returned to the normal level. The patient was successfully discharged from hospital. CONCLUSION: This is the first case of acute pancreatitis caused by primary hyperparathyroidism associated with paraneoplastic syndrome.

[Effect of sand-stabilization engineering on soil humus and components by analysis by several spectroscopy methods].

After the potassium bichromate-strong sulfuric acid hot process, the ultraviolet spectrophotometer was used on the contrast with the traditional titrimetric method to analyze soil (51 years, 43 year, 32 year, 20 year vegetations restores in the Tenggeli sand) humus and the humus components content. At the same time, the infrared spectrum was used to discuss their structure change during restoring process. The result indicated that using the visible spectroscopy method for the determination of the humus and the humus component is feasible. The spectroscopy method determination of organic matter is better (coefficient of variation at most is 7.26%) than the traditional titrimetric method, as it is accurate, fast and simple, and favors large quantities. The result indicated that humus content presents increasing tendency along with restoring ages. Change is big in early restore time, and tends to be stable in the later period. Infrared spectrum shape is similar, but the characteristic peak intensity has obvious difference. Compared with the wind-drift sand, little molecule saccharides decrease and aryl-groups increase.

Sonochemical preparation of carbon nanosheets supporting cuprous oxide architecture for high-performance and non-enzymatic electrochemical sensor in biological samples.

Copper (Cu) based metal oxides have high electrocatalytic ability. In this work, we are synthesized stone-like cuprous oxide particles (Cu2O SNPs) covered on acid functionalized graphene oxide (GOS) sheets using ultrasonic process (50 kHz and 100 W). Besides, the chemical structural and crystalline analyses of Cu2O SNPs@GOS composites were characterized by transmission electron microscopy, X-ray crystallography and energy-dispersive X-ray spectroscopy. The Cu2O SNPs@GOS nanomaterials were tested towards detection of 8-hydroxydeoxyguanosine (8-OHdG) in biological samples. As expected Cu2O SNPs@GOS catalyst modified electrodes performed an outstanding catalytic ability on 8-hydroxydeoxyguanosine oxidation. 8-OHdG is oxidative stress biomarker. Further, it is noted that the detection performance of Cu2O SNPs@GOS coated electrodes and it's highly enhanced due to the synergistic effect of Cu2O SNPs and GOS. Besides, the modified materials provide more electro-active faces and as well as rapid electron transport pathway and shorten diffusion. Moreover, oxidation of 8-OHdG sensor is exploring a long linear or working range of 0.02-1465 µM and high sensitivity (8.75 nM). The viability of the Cu2O SNPs@GOS proposed electrochemical methods have tested, to find out 8-OHdG concentrations in biological fluids (blood serum and urine) with a satisfying recovery ranges.

Continuous fluoxetine administration prevents recurrence of pulmonary arterial hypertension and prolongs survival in rats.

1. The serotonin transporter (SERT) is strongly implicated in the pathogenesis of pulmonary arterial hypertension (PAH) in patients and animal models. Inhibitors of SERT have been reported to attenuate or reverse experimental PAH, which makes them potential therapeutic options for the treatment of PAH in humans. However, little is known about pathophysiological features after reversal or attenuation of PAH; moreover, the long-term therapeutic effects of SERT inhibitors on PAH remain undetermined. Thus, the aim of the present study was to investigate the short- and long-term effects of fluoxetine on monocrotaline (MCT)-induced PAH and associated pathophysiological changes in PAH models. 2. Rats were randomly divided into four groups as follows: (i) an M + F group, in which rats received a single injection of MCT (60 mg/kg, s.c.) and then after 3 weeks were given fluoxetine (10 mg/kg) once daily by gavage from Week 4 to Week 12; (ii) an M/F group, in which 3 weeks after a single MCT (60 mg/kg, s.c.) injection, rats were given fluoxetine (10 mg/kg) by daily gavage from Week 4 to Week 6 and were then given an equivalent volume of saline once daily by gavage from Week 7 to Week 12; (iii) an MCT group, in which 3 weeks after a single MCT (60 mg/kg, s.c.) injection rats were given an equivalent volume of saline by gavage from Week 4 to Week 12; and (iv) a saline group, in which rats received an equivalent volume of saline injection or gavage over the 12 week treatment period. Morphometric changes, pulmonary arterial pressure, percentage wall thickness, right ventricular hypertrophy index and SERT expression were detected at various times during the 12 week treatment period. Survival analysis was performed in each group. 3. After 12 weeks treatment, it was found that even through fluoxetine treatment resulted in complete reversal of PAH, PAH recurred after fluoxetine withdrawal. In contrast, continuous administration of fluoxetine prevented the recurrence of PAH and prolonged survival. Analysis of SERT protein levels in rat lung indicated that, compared with values obtained at Week 0, SERT protein increased significantly after discontinuation of fluoxetine but continuous fluoxetine administration inhibited this increase. 4. In conclusion, SERT overexpression correlates with the recurrence of PAH after withdrawal of fluoxetine in rats. Continuous fluoxetine administration prevents recurrence of PAH and prolongs survival.

Assessing the efficacy of mammalian target of rapamycin inhibitors by phosphorylation of p70S6K in CD4-positive cells of liver transplant patients.

The activity of p70S6 kinase located downstream of the mammalian target of rapamycin (mTOR) pathway is sensitive to mTOR inhibitors. However, the methods of assessing p70S6 kinase activity are still unclear. This study aimed to investigate p70S6 kinase activity in CD4-positive cells of liver transplant patients.Liver transplant patients treated with mTOR inhibitors were recruited from Beijing Chaoyang Hospital between October 2014 and October 2016. The influence of mycophenolic acid (MPA) derivatives and prednisone on p70S6 kinase phosphorylation in CD4-positive cells was examined in liver transplant patients and healthy controls (HCs). The phosphorylation of p70S6K in CD4 + CD25 regulatory T cells (Treg cells) and CD4 + CD25- T effector cells was analyzed by phospho-flow cytometry.The phospho-flow technique detected a significant loss of p70S6 kinase phosphorylation in CD4-positive cells of patients treated with mTOR inhibitors compared with HCs. MPA derivatives and prednisone did not affect p70S6 kinase phosphorylation significantly. No significant difference in p70S6 kinase phosphorylation was observed when the whole blood was stored within 3 hours at room temperature. The phosphorylation of p70S6K was significantly lower in CD4 + CD25 Treg cells than in CD4 + CD25-T effector cells in HCs. After liver transplant patients were treated with mTOR inhibitors, p70S6K phosphorylation was more reduced in CD4 + CD25-T effector cells than in CD4 + CD25 Treg cells.The presence of phosphorylation of p70S6 kinase in CD4-positive cells was reduced in liver transplant patients who were treated by mTOR inhibitors.