Tunable and mode-locked Tm,Ho:GdScO3 laser.

A novel, to the best of our knowledge, Tm,Ho:GdScO3 crystal grown using the Czochralski method was investigated for its polarized spectroscopic properties and laser performance in both tunable continuous-wave (CW) and mode-locked regimes. The crystal's multisite structure (Gd3+/Sc3+ site) and Tm3+/Ho3+ dopants contributed to spectral broadening, enabling a tunable laser operation from 1914 to 2125 nm (with a broad range of 215 nm). Additionally, a pulse duration of 72 fs was achieved for E || b polarization. These results demonstrate the potential of the Tm,Ho:GdScO3 perovskite crystal as a promising gain material for ultrafast lasers operating around 2 µm.

Miniaturized and Portable Laser Gas Sensor for Standoff Methane Detection With Non-Cooperative Targets.

A standoff methane (CH4) sensor with actual hard topographic targets (usually called non-cooperative targets) is essential for natural gas pipeline leakage inspection and many other practical applications. To address this requirement, a miniaturized and low-power-consumption gas sensor was developed based on tunable diode laser absorption spectroscopy for standoff CH4 detection with a non-cooperative target. Wavelength modulation spectroscopy with a 1f normalized 2f detection method was employed for calibration-free CH4 measurement. A Kalman filter algorithm was used to improve the precision of the detection. The performance of the standoff CH4 sensor was evaluated comprehensively under various conditions, including different incident angles, different hard topographic targets, and different standoff distances. The results show that the measurement precision is 0.107% and the sensitivity is 4.08 parts per million per meter (ppm·m) with a time resolution of 1 s and a standoff distance of 40 m. The detection limit can achieve 1.24 ppm·m at an optimal integration time of 70 s. This sensor can be easily integrated into mobile platforms, which lays the foundation for intelligent leak inspection.

Association of Neutrophil and Albumin With Mortality Risk in Patients Receiving Peritoneal Dialysis.

OBJECTIVE: Inflammation and nutrition have been recognized as predicting mortality in patients receiving peritoneal dialysis (PD). Serum neutrophil and albumin are crucial factors in inflammation and nutrition status. Up until now, the synergistic effect of neutrophil and albumin on mortality prediction in PD patients is still being determined. Our study sought to assess the effect of the interaction between neutrophils and albumin on the risk of all-cause mortality and cardiovascular disease (CVD) mortality patients receiving PD. METHODS: A total of 1229 PD patients were recruited and divided into three categories in this cohort study. Their relationships with all-cause mortality and CVD mortality were analyzed in multivariable COX regression models adjusted for confounding factors. RESULTS: During the median follow-up of 34.2 months, 222 (18.1%) patients died, and 115 (51.8%) suffered from cardiovascular events. Patients with high neutrophil percentage-to-albumin ratio (NPAR) showed increased all-cause mortality and CVD mortality, with adjusted hazard ratios of 1.490 (95% confidence interval, 1.070-2.074, P = .018) and 1.633 (95% confidence interval, 1.041-2.561, P = .033), respectively, compared with those with low NPAR. Competitive risk models and sensitivity analyses further confirmed this association. In the receiver operating characteristic curve analysis, however, there was little evidence that NPAR is a better indicator than albumin and neutrophil count. CONCLUSIONS: Having a high NPAR is linked to a higher risk of mortality, especially when both high neutrophil and low albumin are present.

The Utility of ctDNA in Lung Cancer Clinical Research and Practice: A Systematic Review and Meta-Analysis of Clinical Studies.

This systematic review with embedded meta-analysis aimed to evaluate the clinical utility of circulating tumor DNA (ctDNA) in lung cancer. After screening and review of the Embase database search, 111 studies from 2015 to 2020 demonstrated ctDNA's value in prognostication/monitoring disease progression, mainly in patients with advanced/metastatic disease and non-small cell lung cancer. ctDNA positivity/detection at any time point was associated with shorter progression-free survival and overall survival, whereas ctDNA clearance/decrease during treatment was associated with a lower risk of progression and death. Validating these findings and addressing challenges regarding ctDNA testing integration into clinical practice will require further research.

Sarm1 Regulates Circadian Rhythm Disorder in Alzheimer's Disease in Mice.

BACKGROUND: Sarm1 (Sterile alpha and TIR motif-containing 1) is a key protein that regulates neurodegenerative pathologies. Alzheimer's disease (AD) is highly associated with neurodegenerative lesions and biorhythmic disturbances. OBJECTIVE: This study aims to decipher the role of Sarm1 in AD-induced circadian rhythm disturbances and AD progression. METHODS: Open field and water maze tests were used to assess the cognitive function of mice. Thioflavin-S staining was used to assess amyloid-ß (Aß) plaque deposition in the hippocampus and cortex. Rhythmic waveform of home cage activity and temperature was recorded to evaluate circadian rhythm. Expression of clock molecules including Bmal1 and Per2 in the hippocampus were analyzed using western blot and real-time PCR. Further, HT22 cells with Sam1 knockout were treated with Aß31-35 treatment to initiate circadian rhythm disorder in the cellular level to assess the changes in Bmal1 and Per2. RESULTS: Our data suggested that Sarm1 deficiency rescued cognitive disorder, decreased Aß plaque deposition in the hippocampus and cortex, inhibited astrocyte activation, improved circadian rhythm, altered clock molecule expression in the cortex and hippocampus in APP/PS1 mice. CONCLUSION: Sarm1 attenuates circadian rhythm disturbances and reduces AD progression. These data support the potential use of Sarm1 as a therapeutic target to improve circadian rhythm to impede AD progression.

Characterization and Modeling of a Pt-In2O3 Resistive Sensor for Hydrogen Detection at Room Temperature.

Sensitive H2 sensors at low concentrations and room temperature are desired for the early warning and control of hydrogen leakage. In this paper, a resistive sensor based on Pt-doped In2O3 nanoparticles was fabricated using inkjet printing process. The H2 sensing performance of the sensor was evaluated at low concentrations below 1% at room temperature. It exhibited a relative high response of 42.34% to 0.6% H2. As the relative humidity of 0.5% H2 decreased from 34% to 23%, the response decreased slightly from 34% to 23%. The sensing principle and the humidity effect were discussed. A dynamic current sensing model for dry H2 detection was proposed based on Wolkenstein theory and experimentally verified to be able to predict the sensing behavior of the sensor. The H2 concentration can be calculated within a short measurement time using the model without waiting for the saturation of the response, which significantly reduces the sensing and recovery time of the sensor. The sensor is expected to be a promising candidate for room-temperature H2 detection, and the proposed model could be very helpful in promoting the application of the sensor for real-time H2 leakage monitoring.

Proton pump inhibitor usage associates with higher risk of first episodes of pneumonia and peritonitis in peritoneal dialysis patients.

BACKGROUND: A large number of studies have shown that proton pump inhibitors (PPIs) are associated with infection events. Therefore, we retrospectively evaluated the association of PPI therapy with the occurrence of first pneumonia and peritoneal dialysis(PD)-related peritonitis events in the maintenance PD patients. METHODS: We collected PD patients in two large hospitals from January 1, 2012 to December 31, 2016, and divided them into the PPI group and the non-PPI group. Multivariate Cox proportional hazards models were applied to evaluate the cumulative incidence and hazard ratios (HRs). Inverse probability of treatment weight (IPTW) method was used to adjust for covariate imbalance between the two groups and further confirm our findings. RESULTS: Finally, 656 PD patients were included for data analysis, and the results showed that PPI usage was associated with an increased risk of pneumonia [HR 1.71; 95% CI 1.06-2.76; p = 0.027] and peritonitis [HR 1.73; 95% CI 1.24-2.40; p = 0.001]. IPTW-adjusted HRs for the association of PPIs with pneumonia and peritonitis were 1.58 (95% CI:1.18-2.12; p = 0.002) and 2.33 (95% CI:1.91-2.85; p < 0.001), respectively. Moreover, the competitive risk model proved that under the conditions of competition for other events(including transfer to hemodialysis therapy, kidney transplant, transfer from our research center, loss to follow-up, and death), the differences in endpoints events between the two groups were still statistically significant (p = 0.009, p < 0.001, respectively). CONCLUSIONS: PPIs was associated with an increased risk of first pneumonia and PD-related peritonitis events in PD patients, which reminds clinicians to be cautious when prescribing acid-suppressing drugs for PD patients.

Imaging simulation of the AMCW ToF camera based on path tracking.

The time-of-flight (ToF) camera suffers from many error factors, such as multiple reflection or multipath interference and electronic and optical shot noise, making it difficult to simulate its imaging process. Aiming to test the ToF camera algorithm, it is important to obtain a depth image affected by these error factors. In order to model the light propagation behavior and the sensor effect in the imaging process of the ToF camera, an amplitude modulated continuous-wave (AMCW) ToF camera imaging simulation method based on path tracking is presented by deducing the path tracking algorithm model in the AMCW ToF camera theoretically and by realizing the physically based simulation by introducing the infrared bidirectional reflectance distribution function (BRDF) data of the actual materials. According to the constructed error evaluation indexes, the correctness of the imaging simulation method is verified based on the ground experiment. The mean absolute error (MAE) and root mean square error (RMSE) are 10.32 mm and 15.12 mm, respectively, which are less than the error results of the other two comparative simulation methods. The results show that the proposed method is reasonable and can provide reliable data support for AMCW ToF hardware development and algorithm testing.

Parthenolide alleviates peritoneal fibrosis by inhibiting inflammation via the NF-κB/ TGF-ß/Smad signaling axis.

Peritoneal fibrosis is a common complication of peritoneal dialysis (PD) with a complicated pathogenesis and limited treatments. Parthenolide (PTL), a recognized nuclear factor-κB (NF-κB) inhibitor extracted from Tanacetum balsamita, has been widely used to treat various inflammatory diseases and has been proven to improve peritoneal fibrosis in PD mice by selectively inhibiting the phosphorylation of Smad2/3. Transforming growth factor-ß1 (TGF-ß1), via Smad-dependent signaling, has a pivotal role in promoting pathogenic of fibrosis. To investigate whether PTL can inhibit peritoneal fibrosis, we affected the interaction between NF-κB and the TGF-ß/Smad2/3 pathway. Long dwell peritoneal dialysis fluid (PDF) and peritoneum tissues were collected from continuous ambulatory peritoneal dialysis (CAPD) patients. PTL was administered intragastrically into a PD mouse model by daily infusion of 4.25% dextrose-containing PDF. Treated HMrSV5 cells or rat peritoneal mesothelial cells (RPMCs) were treated with high glucose(138 mM) at the same concentration as 2.5% dextrose-containing PDF and PTL. PD-related peritoneal fibrosis samples indicated an increase in inflammation, and PTL decreased the levels of inflammatory cytokines (L-6, TNF-α, and MCP-1). PTL inhibited high glucose-induced mesothelial-to-mesenchymal transition (MMT), as indicated by a reduced expression of fibrosis markers (fibronectin, collagen I, and α-SMA) and increased expression of the epithelial marker E-cadherin. PTL also significantly decreased TGF-ß1 expression and the phosphorylation of IκBα and NF-κBp65. The changes in the levels of TGF-ß1 expression and p-p65 or p65 showed similar trends according to western blot, immunohistochemistry, and immunofluorescence assays in vitro and in vivo. Chromatin immunoprecipitation (ChIP) and luciferase reporter assays were used to confirm that PTL regulates the transcription of TGF-ß1 induced by high glucose through NF-κBp65. In summary, PTL induces a therapeutic effect in peritoneal fibrosis by inhibiting inflammation via the NF-κB/ TGF-ß/Smad signaling axis.

Biochemical Process and Microbial Evolution in the Conversion of Corn Straw Combined with Coal to Biogas.

The combined anaerobic fermentation of coal and straw can increase the production of biogas. To explore the mechanism of adding corn straw to increase methane production, coal with different metamorphic degrees and corn straw were collected for biogas production simulation experiments under different substrate ratios. The changes in liquid products, the structure of lignocellulose in corn straw, and microbial evolution were monitored. The results showed that the combined fermentation of bituminous coal A with corn straw and bituminous coal C with corn straw at a mass ratio of 2:1 each ((AC-2) and (CC-2)) and that of bituminous coal B and corn straw at a mass ratio of 3:1 (BC-3) had the best gas production, and methane yields reached 17.28, 12.51, and 14.88 mL/g, respectively. The fermentation liquid had organic matter with more types and higher contents during the early and peak stages of gas production, and fewer types of organic matter were detected in the terminal stage. The degradation of lignocelluloses in the corn straw of AC-2 was higher. With the increase in fermentation time, the carbohydrates in the fermentation system increased and the degradation rate of cellulose decreased gradually. The abundance of genes related to nitrate reduction gradually increased, while that of sulfate reduction was on the contrary. Bacteria in the cofermentation system mainly metabolized carbohydrates. During cofermentation with high metamorphic coal, corn straw would be preferentially degraded. The structure of the archaea community changed from Methanosarcina and Methanothrix to Methanobacterium.

Neutrophil to high-density lipoprotein ratio associates with higher all-cause mortality and new onset cardiovascular events in peritoneal dialysis patients.

BACKGROUND: Neutrophil to high-density lipoprotein ratio (NHR), a new inflammatory marker, is associated with poor clinical prognosis. However, the correlation of NHR and adverse outcomes in peritoneal dialysis (PD) patients remains unclear. METHODS: In this retrospective cohort study, a total of 1051 PD patients were recruited from three centers during Jan 1, 2009 to Dec 31, 2017. Eligible patients were distributed according to quartiles of the NHR. Kaplan-Meier cumulative incidence curves, multivariate COX regression, competitive risk analysis and restricted cubic spline (RCS) were applied to analyze the relationship between NHR and all-cause mortality as well as cardiovascular events (CVE). In addition, forest plots were used to calculate the interaction between different subgroups. RESULTS: During follow-up, a total of 240 all-cause mortality and 157 new-onset CVE were recorded. The all-cause mortality in the highest quartile of NHR (> 5.43) were higher than those in the other groups. RCS showed a non-linear relationship between NHR and adverse outcomes. Multivariate COX regression indicated elevated NHR was an independent risk factor for all-cause mortality. Compared to the highest quartile, hazard ratio (HR) of new-onset CVE equals to 0.522 (95% CI 0.321-0.849) in the secondary quartile (2.43 < NHR ≤ 3.57), and the HR of all-cause mortality analysis is 0.551 (95% CI 0.378-0.803) in the third quartile (3.57 < NHR ≤ 5.43). Kaplan-Meier analysis suggested there were significant differences in all-cause mortality and new-onset CVE among four NHR groups. CONCLUSIONS: NHR was a new independent risk factor for all-cause mortality in PD patients.

Proton pump inhibitor usage is associated with higher all-cause mortality and CV events in peritoneal dialysis patients.

OBJECTIVES: A long period of inappropriate proton pump inhibitors (PPI) treatment has been proved to be associated with adverse prognosis in general population and hemodialysis patients. This study was conducted to clarify the impact of PPI usage on mortality and adverse cardiovascular (CV) events in peritoneal dialysis (PD) patients. METHODS AND DESIGN: This is a retrospective study. A total of 905 patients were enrolled from two PD centers, including 211 patients on PPI treatment and 618 patients not on PPIs. Kaplan-Meier curves were used to identify the incidence of adverse outcomes. Multivariate Cox regression models and inverse probability of treatment weighting (IPTW) were applied to analyze hazard ratios (HRs) for adverse outcomes. RESULTS: During follow-up, 162 deaths and 102 CV events were recorded. Kaplan-Meier curve demonstrated all-cause mortality (log-rank test p = .018) and CV events (log-rank test p = .024) were significantly higher in PPI usage group. Multivariate Cox regression models and IPTW showed that PPI usage was an indicator for all-cause mortality (HR = 1.35, 95%CI = 1.09-1.67, p = .006) and CV events (HR = 1.78, 95%CI = 1.35-2.32, p < .001). CONCLUSIONS: PPI usage is associated with higher all-cause mortality and CV events in PD patients. Clinicians are supposed to be more careful when using PPI and need to master the indications more rigorously in patients receiving PD treatment.

ACEi/ARBs associate with lower incidence of gastrointestinal bleeding in peritoneal dialysis patients.

BACKGROUND: Gastrointestinal bleeding (GIB) is widespread in patients with impaired renal function. Whether angiotensin-converting enzyme inhibitors/angiotensin II receptor blockers (ACEi/ARBs) potentially take a crucial role in avoiding GIB incidence among peritoneal dialysis (PD) patients is unknown. METHODS: Overall, 734 PD patients were enrolled after using propensity score matching. Kaplan-Meier analysis and COX regression were used to explore correlation between ACEi/ARBs and GIB. Competitive risk model was aimed to identify whether other events were confounding factors. Forest plot was applied to assess the influence of ACEI/ARBs on GIB incidence in different groups. RESULTS: During 8-year follow-up, 89 (12.13%) cases of GIB were recorded. Kaplan-Meier analysis revealed that the incidence of GIB among patients taking ACEi/ARBs was lower than those subjects who had not (log rank = 6.442, P = 0.011). After adjusted different confounding factors, administration of ACEi/ARBs was associated with lowered GIB incidence (adjusted HR = 0.49, 95% CI 0.32-0.77, P = 0.002). In competitive risk model, considering of other events, the incidence of GIB in two groups was still statistically significant (P = 0.010). Subgroup analysis showed ACEi/ARBs taking impeded GIB in the ≥ 60 age group (HR = 0.52, 95% CI 0.28-0.98, P = 0.040). CONCLUSION: PD patients who were submitted to ACEi/ARBs inclined to have a lower risk for GIB. In this regard, ACEi/ARBs offered a promising choice to GIB.

Ad hoc Analysis of the Phase III ENGOT-OV16/NOVA Study: Niraparib Efficacy in Germline BRCA Wild-type Recurrent Ovarian Cancer with Homologous Recombination Repair Defects.

In this analysis, we examined the relationship between progression-free survival (PFS) and mutation status of 18 homologous recombination repair (HRR) genes in patients in the non-germline BRCA-mutated (non-gBRCAm) cohort of the ENGOT-OV16/NOVA trial (NCT01847274), which evaluated niraparib maintenance therapy for patients with recurrent ovarian cancer. This post hoc exploratory biomarker analysis was performed using tumor samples collected from 331 patients enrolled in the phase III ENGOT-OV16/NOVA trial's non-gBRCAm cohort. Niraparib demonstrated PFS benefit in patients with either somatic BRCA-mutated (sBRCAm; HR, 0.27; 95% confidence interval, CI, 0.08-0.88) or BRCA wild-type (BRCAwt; HR, 0.47; 95% CI, 0.34-0.64) tumors. Patients with BRCAwt tumors with other non-BRCA HRR mutations also derived benefit from niraparib (HR, 0.31; 95% CI, 0.13-0.77), as did patients with BRCAwt/HRRwt (HRR wild-type) tumors (HR, 0.49; 95% CI, 0.35-0.70). When patients with BRCAwt/HRRwt tumors were further categorized by genomic instability score (GIS), clinical benefit was observed in patients with homologous recombination-deficient (GIS ≥ 42; HR, 0.33; 95% CI, 0.18-0.61) and in patients with homologous recombination-proficient (HRp; GIS < 42; HR, 0.60; 95% CI, 0.36-0.99) disease. Although patients with sBRCAm, other non-BRCA HRR mutations, or GIS ≥ 42 benefited the most from niraparib treatment, PFS benefit was also seen in HRp (GIS < 42) patients without HRR mutations. These results support the use of niraparib in patients with recurrent ovarian cancer regardless of BRCA/HRR mutation status or myChoice CDx GIS. Significance: We retrospectively evaluated the mutational profile of HRR genes in tumor samples from 331 patients from the non-germline BRCA-mutated cohort of the phase III NOVA trial of patients with platinum-sensitive high-grade serous ovarian cancer. Patients with non-BRCA HRR mutations generally benefited from second-line maintenance treatment with niraparib compared with placebo.

Preclinical characterization of dostarlimab, a therapeutic anti-PD-1 antibody with potent activity to enhance immune function in in vitro cellular assays and in vivo animal models.

Inhibitors of programmed cell death protein 1 (PD-1) and its ligand (PD-L1) have dramatically changed the treatment landscape for patients with cancer. Clinical activity of anti-PD-(L)1 antibodies has resulted in increased median overall survival and durable responses in patients across selected tumor types. To date, 6 PD-1 and PD-L1, here collectively referred to as PD-(L)1, pathway inhibitors are approved by the US Food and Drug Administration for clinical use. The availability of multiple anti-PD-(L)1 antibodies provides treatment and dosing regimen choice for patients with cancer. Here, we describe the nonclinical characterization of dostarlimab (TSR-042), a humanized anti-PD-1 antibody, which binds with high affinity to human PD-1 and effectively inhibits its interaction with its ligands, PD-L1 and PD-L2. Dostarlimab enhanced effector T-cell functions, including cytokine production, in vitro. Since dostarlimab does not bind mouse PD-1, its single-agent antitumor activity was evaluated using humanized mouse models. In this model system, dostarlimab demonstrated antitumor activity as assessed by tumor growth inhibition, which was associated with increased infiltration of immune cells. Single-dose and 4-week repeat-dose toxicology studies in cynomolgus monkeys indicated that dostarlimab was well tolerated. In a clinical setting, based on data from the GARNET trial, dostarlimab (Jemperli) was approved for the treatment of adult patients with mismatch repair-deficient recurrent or advanced endometrial cancer that had progressed on or following prior treatment with a platinum-containing regimen. Taken together, these data demonstrate that dostarlimab is a potent anti-PD-1 receptor antagonist, with properties that support its continued clinical investigation in patients with cancer.

High Neutrophil/Lymphocyte Ratio as an Independent Risk Factor for the First Occurrence of Stroke in Peritoneal Dialysis Patients.

INTRODUCTION: Though neutrophil/lymphocyte ratio (NLR) level appears to be related with stroke events in general population, its relationship with stroke in peritoneal dialysis (PD) patients is still uncertain. This study aims to investigate the association between NLR and the first occurrence of stroke in PD patients. METHODS: In this retrospective cohort study, 1507 PD patients were enrolled from four centers in China and stratified into tertiles of NLR levels. The incidence of the first occurrence of stroke was analyzed by Kaplan-Meier cumulative incidence curve among different NLR tertiles, competing risk analysis was used to calculate the incidence of the first occurrence of stroke in the presence of competing risk of other events, multivariable COX regression analysis was performed to estimate the hazard ratios (HRs) for the first occurrence of stroke, as well as forest plot was utilized to describe the relationship between NLR and the first occurrence of stroke in different subgroups. RESULTS: During follow-up, 84 new-onset stroke events were recorded. Kaplan-Meier cumulative incidence curves showed significant differences in the incidence of the first occurrence of stroke among three groups (log-rank test: P < .001). In competing risk analysis, the cumulative incidence curves for tertiles of NLR levels were highly significant for the first occurrence of stroke (P < .001), but they were not statistically different for the occurrence of other events. Compared to the lowest tertile of NLR level, the highest tertile was associated with increased risk of the first occurrence of stroke in the adjusted Cox model (HR = 2.39, 95% CI: 1.37 to 4.15; P < .05). As for forest plot, there was no interaction in all subgroups. CONCLUSION: High NLR was an independent risk factor for the first occurrence of stroke in PD patients.

Neutrophil to Lymphocyte Ratio Predicts Adverse Cardiovascular Outcome in Peritoneal Dialysis Patients Younger than 60 Years Old.

BACKGROUND: Neutrophil to lymphocyte ratio (NLR) is a new inflammatory marker; the relationship between NLR and adverse cardiovascular (CV) prognosis has been gradually emphasized in the general population. However, their association in peritoneal dialysis (PD) patients remains unclear. METHODS: From January 1, 2010, to May 31, 2017, a total of 1652 patients were recruited. NLR was categorized in triplicates: NLR ≤ 2.74, 2.74 < NLR ≤ 3.96, and NLR > 3.96. Kaplan-Meier cumulative incidence curve and multivariable COX regression analysis were used to determine the relationship between NLR and the incidence of adverse CV outcome, while a competitive risk model was applied to assess the effects of other outcomes on adverse CV prognosis. Besides, forest plot was investigated to analyze the adverse CV prognosis in different subgroups. RESULTS: During follow-up, 213 new-onset CV events and 153 CV disease (CVD) deaths were recorded. Multivariable COX regression models showed that the highest tertile of NLR level was associated with increased risk of CV events (HR = 1.39, 95%CI = 1.01-1.93, P = 0.046) and CVD mortality (HR = 1.81, 95%CI = 1.22-2.69, P = 0.003), while compared to the lowest tertile. Competitive risk models showed that the differences in CV event (P < 0.001) and CVD mortality (P = 0.004) among different NLR groups were still significant while excluding the effects of other outcomes. In subgroups, with each 1 increased in the NLR level, adjusted HR of new-onset CV event was 2.02 (95%CI = 1.26 - 3.23, P = 0.003) and CVD mortality was 2.98 (95%CI = 1.58 - 5.62, P = 0.001) in the younger group (age < 60 years). CONCLUSIONS: NLR is an independent risk factor for adverse CV prognosis in PD patients younger than 60 years old.

High Mean Platelet Volume Associates with In-Hospital Mortality in Severe Pneumonia Patients.

BACKGROUND: Although mean platelet volume (MPV) appears to be associated with poor outcome of pneumonia, the relationship between MPV and in-hospital mortality is unclear in severe pneumonia (SP) patients. METHODS: In this retrospective cohort study, 115 SP patients from June 1st, 2016, to September 29th, 2019, were included and divided into two groups. The primary outcome was in-hospital mortality. The receiver operating characteristic (ROC) curve was performed to assess the predictive ability for in-hospital mortality. Kaplan-Meier cumulative incidence curves were applied to observe the incidence of mortality. Multivariable Cox regression analyses were used to evaluate the hazard ratios (HRs). Besides, a formal test for interaction was investigated to analyze the relationship between MPV and sex. RESULTS: During the course of hospitalization, 63 cases of mortality were recorded. ROC analysis suggested that MPV had a modest power for predicting in-hospital mortality (AUC = 0.723, 95% CI: 0.628-0.818, P < 0.001). Yet the cutoff value of MPV was 10.5 (sensitivity = 73.02%; specificity = 73.08%). Compared to the low-MPV group, the high-MPV group had significantly increased in-hospital mortality (log-rank test = 13.501, P < 0.001), while the adjusted Cox model indicated that the high-MPV group was associated with an elevated risk of in-hospital mortality (HR: 2.267, 95% CI: 1.166-4.406, P = 0.016). Moreover, analyses of in-hospital mortality suggested a significant interaction between optimal MPV level and sex (P = 0.011). In a multivariate Cox model which included females only, a high MPV level was associated with increased risk of in-hospital mortality (HR: 11.387, 95% CI: 1.767-73.380, P = 0.011). CONCLUSION: High MPV level is an independent risk factor for in-hospital mortality in patients with SP.

The relationship between neutrophil-to-lymphocyte ratio and the first occurrence of pneumonia in peritoneal dialysis patients.

BACKGROUND: Although neutrophil-to-lymphocyte ratio (NLR) is closely associated with pneumonia in the general population, its relationship is unclear in peritoneal dialysis (PD) patients. METHODS: This is a cohort study consisting of 739 PD patients and dividing into two groups. Kaplan-Meier curves were applied to observe the incidence of the first occurrence of pneumonia, competitive risk analysis was conducted to compare whether there was a significant difference in each NLR group in the presence of other competing events, multivariable COX regression analysis was used to evaluate the hazard ratios (HRs), as well as forest plot was used to analyze the relationship between NLR and the first occurrence of pneumonia in different subgroups. RESULTS: Of all the patients, 116 cases of first-time pneumonia were recorded. The first-time pneumonia incidence rate was 71.67/1000 patient-years in high NLR group, which was markedly higher than that of 45.81/1000 patient-years in low NLR group. Kaplan-Meier curves indicated significant differences in the incidence of the first occurrence of pneumonia between two groups (log-rank test p = 0.015). The competitive risk model suggested a significant difference in the cumulative incidence of first pneumonia between the two groups (p = 0.032). Compared to low NLR group, adjusted Cox model showed that high NLR group was associated with increased risk of pneumonia incidence (HR, 1.51; 95% CI 1.04-2.21; p = 0.031). Forest plot showed no interaction was found in subgroups. CONCLUSIONS: The risk of pneumonia was significantly increasing in PD patients with high NLR, which may have a certain guiding significance for the clinic.

Cabin1 involves in renal tubular epithelial cells mitochondrial dysfunction through SIRT1/p53 pathway.

Background: Angiotensin II (AngII) induced Calcineurin binding protein 1 (Cabin1) protein expression significantly increased during Renal tubular epithelial cells (RTEC) injury. However, the detailed function of Cabin1 protein in RTEC was not characterized well. In this study, we aimed to explore the downstream target of Cabin1 in vitro model.Methods: Rat kidney epithelial cells were cultured and stimulated with AngII. Electron microscopy was performed to observe mitochondrial morphology change. Immunofluorescence staining was detected to observe the distribution of cytoskeleton and Cabin1. Mitochondrial morphology change and protein expression were detected by electrical microscopy and western blot.Results: AngII induced the disruption of cytoskeleton at 24 and 48 h. Western blot analysis showed AngII significantly induced the overexpression of Cabin1. AngII induced a great deal of small, long and irregular mitochondria in RTEC, aspect ratio which reflects the length-to-width ratio of mitochondria remarkably increased at 12 and 24 h. Knocking down Cabin1 aggravated mitochondrial morphological abnormality in AngII treated RTEC. In comparison with control, Cabin1, p53 and cyto C level were significantly increased in AngII treated cells, while SIRT1 level was obviously decreased. Knocked down Cabin1 plus AngII stimulated, SIRT1 was further decreased, while p53 and cyto C were significantly increased.Conclusions: Cabin1 involves in RTEC mitochondrial dysfunction through SIRT1/p53 pathway. Cabin1 may be used as a new marker for the mechanisms of RTEC injury.