Lipid parameters, adipose tissue distribution and prognosis prediction in chronic kidney Disease patients.

BACKGROUND: Lipid management in clinic is critical to the prevention and treatment of Chronic kidney disease (CKD), while the manifestations of lipid indicators vary in types and have flexible association with CKD prognosis. PURPOSE: Explore the associations between the widely used indicators of lipid metabolism and their distribution in clinic and CKD prognosis; provide a reference for lipid management and inform treatment decisions for patients with non-dialysis CKD stage 3-5. METHODS: This is a retrospective cohort study utilizing the Self-Management Program for Patients with Chronic Kidney Disease Cohort (SMP-CKD) database of 794 individuals with CKD stages 3-5. It covers demographic data, clinical diagnosis and medical history collection, laboratory results, circulating lipid profiles and lipid distribution assessments. Primary endpoint was defined as a composite outcome(the initiation of chronic dialysis or renal transplantation, sustained decline of 40% or more in estimated glomerular filtration rate (eGFR), doubled of serum creatinine (SCr) from the baseline, eGFR less than 5 mL/min/1.73m2, or all-cause mortality). Exposure variables were circulating lipid profiles and lipid distribution measurements. Association were assessed using Relative risks (RRs) (95% confidence intervals (CIs)) computed by multivariate Poisson models combined with least absolute shrinkage and selection operator (LASSO) regression according to categories of lipid manifestations. The best model was selected via akaike information criterion (AIC), area under curve (AUC), receiver operating characteristic curve (ROC) and net reclassification index (NRI). Subgroup analysis and sensitivity analysis were performed to assess the interaction effects and robustness.. RESULTS: 255 individuals reached the composite outcome. Median follow-up duration was 2.03 [1.06, 3.19] years. Median age was 58.8 [48.7, 67.2] years with a median eGFR of 33.7 [17.6, 47.8] ml/min/1.73 m2. Five dataset were built after multiple imputation and five category-based Possion models were constructed for each dataset. Model 5 across five datasets had the best fitness with smallest AIC and largest AUC. The pooled results of Model 5 showed that total cholesterol (TC) (RR (95%CI) (per mmol/L) :1.143[1.023,1.278], P = 0.018) and percentage of body fat (PBF) (RR (95%CI) (per percentage):0.976[0.961,0.992], P = 0.003) were significant factors of composite outcome. The results indicated that comprehensive consideration of lipid metabolism and fat distribution is more critical in the prediction of CKD prognosis.. CONCLUSION: Comprehensive consideration of lipid manifestations is optimal in predicting the prognosis of individuals with non-dialysis CKD stages 3-5.

The impact of body mass index on clinicopathological features of nonalcoholic fatty liver disease in Taiwan.

BACKGROUND AND AIM: The aim of this study was to assess the impact of body mass index (BMI) on the clinical and histological characteristics of patients with nonalcoholic fatty liver disease (NAFLD). METHODS: Patients with clinically diagnosed NAFLD who received liver biopsy were retrospectively enrolled from 2007 to 2019. For comparison, all of the patients were divided into lean body mass (< 23 kg/m2 ), overweight (23-24.9 kg/m2 ), and obesity (BMI â‰§ 25 kg/m2 ). RESULTS: A total of 572 patients with histologically confirmed NAFLD, including 40 (6.99%) lean body mass, 54 (9.44%) overweight, and 478 (83.57%) obese patients, were recruited. Obese NAFLD patients had significantly higher grade of steatosis (grade 3: 29.92% vs 22.22% vs 12.5%, P < 0.0001) and hepatocyte ballooning (grade 2: 14.85% vs 12.96% vs 12.5%, P < 0.0001) than overweight and lean NAFLD patients. The prevalence of nonalcoholic steatohepatitis (NASH) was 22.5%, 25.93%, and 36.19% in lean, overweight, and obese NAFLD patients, respectively. Obesity was significantly associated with fibrosis severity (P = 0.03). The fibrosis index based on four factors (FIB-4) score can identify NAFLD patients without significant fibrosis or with cirrhosis. The areas under the receiver-operating characteristic curve of FIB-4 score to identify patients without significant fibrosis or with cirrhosis were 0.82 (95% confidence interval [CI]: 0.69-0.96) and 0.87 (95% CI: 0.76-0.99) in lean patients; 0.77 (95% CI: 0.61-0.93) and 0.81 (95% CI: 0.59-1.0) in overweight patients; and 0.77 (95% CI: 0.72-0.82) and 0.89 (95% CI: 0.85-0.92) in obese patients. CONCLUSIONS: The majority of NAFLD patients are obese, as defined by BMI. Obesity was significantly associated with NASH and hepatic fibrosis severity in patients with NAFLD.

Self-management program for patients with chronic kidney disease (SMP-CKD) in Southern China: protocol for an ambispective cohort study.

BACKGROUND: Chronic kidney disease (CKD) is a major global health problem. Short-term self-management has been considered to effect some renal and psychological endpoints. However, there are currently very few studies about self-management for CKD that a) have been scientifically designed by a theory-based framework and b) that evaluate the long-term effects and working mechanism. This study presents the rationale and design of a theory-based cohort study to explore how this self-management intervention works and its effectiveness on the Chinese CKD population. METHODS: In this ambispective intervention cohort study,1,200 patients with CKD stages 1-5 will be recruited from July 2015 to July 2024 in 3 branches of Guangdong Provincial Hospital of Chinese Medicine (GPHCM) in Guangdong province, China. The patients in the self-management cohort will choose to receive an intervention that consists of education, nutrition/diet modification, lifestyle change recommendation, medication review, and psychology support based on Social Cognition Theory (SCT). The patients in the control cohort will do regular follow-ups based on the clinic rules. All the patients will be followed up for 5 years, or until the occurrence of a primary outcome. Detailed clinical, laboratory markers, nutritional status, psychological exposures and outcome questionaries will be collected semiannually in CKD stage 1-2 and trimonthly in stage 3-5 patients. The primary outcome is the occurrence of composite clinical endpoints (doubling of serum creatinine level, ESKD, loss of renal function (≥ 40% decline in GFR from baseline), death, major cardiovascular or cerebrovascular events). The main secondary outcomes include the absolute change and slope of eGFR, absolute changes of urinary protein creatinine ratio, 24-h urine proteinuria, intact parathyroid hormone level, and self-management adherence rate and quality of life from baseline to end of the study. The effectiveness of self-management will be analyzed and the association between longitudinal trajectories of self-management and renal outcomes will be evaluated. DISCUSSION: This study aims to provide further evidence for the effectiveness of theory-based self-management in CKD patients and to improve the lives of patients with CKD by slowing progression, improving psychological well-being and overall quality of life. TRIAL REGISTRATION: Chinese Clinical Trial Register (ChiCTR1900024633). 19 July, 2019. http://www.chictr.org.cn/showproj.aspx?proj=38378.

Mannoside-Modified Branched Gold Nanoparticles for Photothermal Therapy to MDA-MB-231 Cells.

Recently, gold nanoparticles (Au NPs) have been used to study the treatment of malignant tumors due to their higher biocompatibility and lesser toxicity. In addition, they can be excited through a specific wavelength to produce oscillating plasmonic photothermal therapy (PPTT) on the basis of the localized surface plasma resonance (LSPR) effect. Au NPs can be heated to kill cancer cells in specific parts of the body in a noninvasive manner. In this study, branched gold nanoparticles (BAu NPs) were prepared by mixing HAuCl4 in a 4-(2-hydroxyethyl)-1-piperazineethanesulfonic acid (HEPES) buffer solution in a molar ratio of 1:2000. The UV-vis absorption peak was detected in the range of 700-1000 nm. Subsequently, BAu NPs were chemically linked to a thiol-modified mannoside molecule via a stable sulfur-Au covalent bond (Man@BAu NPs). Due to the presence of abundant mannose receptors on human-breast-cancer cells, MDA-MB-231, Man@BAu NPs were found to be abundant inside cancer cells. After irradiating the Man@BAu NP-laden MDA-MB231 switch with a near-infrared (NIR) laser at 808 nm wavelength, the photothermal-conversion effect raised the surface temperature of Man@BAu NPs, thus inducing cell death. Our experiment results demonstrated the advantages of applying Man@BAu NPs in inducing cell death in MDA-MB-231.

A computational study of the Fenton reaction in different pH ranges.

The reaction of iron(ii) and hydrogen peroxide, namely the Fenton reaction, is well-known for its strong oxidizing capability. While the Fenton reactions are ubiquitous and have wide applications in many areas, the detailed mechanism, especially the nature of the reactive intermediates responsible for oxidation, is not completely clear. In this work, the performances of various density functional theory (DFT) methods on the relative energies of key Fenton intermediates are evaluated. The DFT method selected from the benchmark study is then exploited to investigate the aqueous Fenton reactions in different pH conditions. The results show that at pH > 2.2, the major Fenton oxidants are high-valent oxoiron(iv) aquo complexes. However, depending on the pH conditions, these complexes can exist in three protonation states that display quite different oxidation reactivities. The oxidizing power of FeIV[double bond, length as m-dash]O is found to be principally determined by the total charge of the ligands and is less influenced by the axial ligand effect. Moreover, the calculations reveal that the presence of the hydronium ion can stabilize the intermediate of the hydroxyl radical and further inhibit oxoiron(iv) formation via proton transfer. The contribution of hydroxyl radicals could compete with the oxoiron(iv) species at pH below 2.2. In addition, high-level ab initio calculations question the existence of the iron(iv)-dihydroxo intermediate suggested in the literature. The implications of the computational results for the Fenton oxidation process, cytochrome P450, and catalyst design are discussed.

Time-resolved FTIR study of light-driven sodium pump rhodopsins.

Light-driven sodium ion pump rhodopsin (NaR) is a new functional class of microbial rhodopsin. A previous flash photolysis study of Krokinobacter eikastus rhodopsin 2 (KR2) revealed the presence of three kinetically distinct intermediates: K, L/M, and O. Previous low-temperature Fourier-transform infrared (FTIR) spectroscopy of KR2 showed that photoisomerization from the all-trans to the 13-cis form is the primary event of the Na+ pumping photocycle, but structural information on the subsequent intermediates is limited. Here, we applied step-scan time-resolved FTIR spectroscopy to KR2 and Nonlabens dokdonensis rhodopsin 2 (NdR2). Both low-temperature static and time-resolved FTIR spectra resolved a K-like intermediate, and the corresponding spectra showed few differences. Strong hydrogen-out-of-plane (HOOP) vibrations, which appeared in the K intermediate, are common among other rhodopsins. It is, however, unique for NaR that such HOOP bands are persistent in late intermediates, such as L and O intermediates. This observation strongly suggests similar chromophore structures for the K, L, and O intermediates. In fact, an isotope-labeled study that used 12,14-D2 retinal revealed that the chromophore configuration of the O intermediate in NaR is 13-cis. In contrast to the vibrations of the chromophore, those of the protein differ among intermediates, and this is related to the sodium-pumping function. The molecular mechanism of the light-driven sodium pump is discussed on the basis of the present time-resolved FTIR results.

A simple and efficient method for constructing azepino[4,5-b]indole derivatives via acid catalysis.

A new synthetic methodology has been developed to prepare the biologically important azepino[4,5-b]indole derivatives under Brønsted acid catalysis. The notable features of this protocol include its operational simplicity, high reaction yields and environmentally benign and mild reaction conditions.

Direct infrared observation of hydrogen chloride anions in solid argon.

To facilitate direct spectroscopic observation of hydrogen chloride anions (HCl-), electron bombardment of CH3Cl diluted in excess Ar during matrix deposition was used to generate this anion. Subsequent characterization were performed by IR spectroscopy and quantum chemical calculations. Moreover the band intensity of HCl- decays slowly when the matrix sample is maintained in the dark for a prolonged time. High-level ab inito calculation suggested that HCl- is only weakly bound. Atom-in-molecule charge analysis indicated that both atoms of HCl- are negatively charged and the Cl atom is hypervalent.

Photochemistry and infrared spectrum of single-bridged diborane(5) anion isolated in solid argon.

Three-center two-electron bonds are important for understanding electron-deficient molecules. To examine such a molecule, we produced a diborane(5) anion with a single-bridged structure upon electron bombardment during matrix deposition of Ar containing a small proportion of diborane(6). The diborane(5) anion was destroyed upon photolysis at 180, 220, 385, and 450 nm, but not at 532 nm. Moreover, the possible formation of neutral diborane(5) was observed upon photolysis at 385 and 450 nm, whereas neutral diborane(3) was observed upon photolysis at 180 and 220 nm. The observed line wavenumbers, relative intensities, and isotopic ratios of the diborane(5) anion agreed satisfactorily with those predicted by density functional theory calculations at the B3LYP/aug-cc-pVTZ level of theory. Thus, this method produced the boron hydride anion of interest with few other fragments, which enabled us to clearly identify the IR spectrum of the diborane(5) anion.

Alkaloids from Pandanus amaryllifolius: Isolation and Their Plausible Biosynthetic Formation.

Pandanus amaryllifolius Roxb. (Pandanaceae) is used as a flavor and in folk medicine in Southeast Asia. The ethanolic crude extract of the aerial parts of P. amaryllifolius exhibited antioxidant, antibiofilm, and anti-inflammatory activities in previous studies. In the current investigation, the purification of the ethanolic extract yielded nine new compounds, including N-acetylnorpandamarilactonines A (1) and B (2); pandalizines A (3) and B (4); pandanmenyamine (5); pandamarilactones 2 (6) and 3 (7), and 5(E)-pandamarilactonine-32 (8); and pandalactonine (9). The isolated alkaloids, with either a γ-alkylidene-α,ß-unsaturated-γ-lactone or γ-alkylidene-α,ß-unsaturated-γ-lactam system, can be classified into five skeletons including norpandamarilactonine, indolizinone, pandanamine, pandamarilactone, and pandamarilactonine. A plausible biosynthetic route toward 1-5, 7, and 9 is proposed.

Interaction of electrons with cisplatin and the subsequent effect on DNA damage: a density functional theory study.

Cisplatin, Pt(NH3)2Cl2, is a leading chemotherapeutic agent that has been widely used for various cancers. Recent experiments show that combining cisplatin and electron sources can dramatically enhance DNA damage and the cell-killing rate and, therefore, is a promising way to overcome the side effects and the resistance of cisplatin. However, the molecular mechanisms underlying this phenomenon are not clear yet. By using density functional theory calculations, we confirm that cisplatin can efficiently capture the prehydrated electrons and then undergo dissociation. The first electron attachment triggers a spontaneous departure of the chloride ion, forming a T-shaped [Pt(NH3)2Cl]˙ neutral radical, whereas the second electron attachment leads to a spontaneous departure of ammine, forming a linear [Pt(NH3)Cl](-) anion. We further recognize that the one-electron reduced product [Pt(NH3)2Cl]˙ is extremely harmful to DNA. It can abstract hydrogen atoms from the C-H bonds of the ribose moiety and the methyl group of thymine, which in turn leads to DNA strand breaks and cross-link lesions. The activation energies of these hydrogen abstraction reactions are relatively small compared to the hydrolysis of cisplatin, a prerequisite step in the normal mechanism of action of cisplatin. These results rationalize the improved cytotoxicity of cisplatin by supplying electrons. Although the biological effects of the two-electron reduced product [Pt(NH3)Cl](-) are not clear at this stage, our calculations indicate that it might be protonated by the surrounding water.

A Chinese patent medicine's long-term efficacy on non-dialysis patients with CKD stages 3-5: a retrospective cohort study.

Background: Chinese patent medicine is commonly used in China as an important treatment mechanism to thwart the progression of chronic kidney disease (CKD) stages 3-5, among which Niaoduqing granules are a representative Chinese patent medicine; however, its long-term efficacy on CKD prognosis remains unclear. Methods: Patients were grouped according to Niaoduqing granule prescription duration (non-Niaoduqing granule (non-NDQ) group vs Niaoduqing granule (NDQ) group). Serum creatinine (SCr) variation was compared using a generalized linear mixed model (GLMM). Multivariate Cox regression models were constructed, adjusting for confounding factors, to explore the risk of composite outcomes (receiving renal replacement therapy (RRT) or having an estimated glomerular filtration rate (eGFR)<5 mL/min/1.73 m2, ≥50% decline in the eGFR from the baseline, and doubling of SCr) in individuals consuming Niaoduqing granules. Results: A total of 1,271 patients were included, with a median follow-up duration of 29.71 (12.10, 56.07) months. The mean SCr Z-scores for the non-NDQ group and NDQ group were -0.175 and 0.153, respectively, at baseline (p = 0.015). The coefficients of the NDQ group from visit 1 to visit 5 were -0.207 (95% CI: -0.346, -0.068, p = 0.004), -0.214 (95% CI: 0.389, -0.039, p = 0.017), -0.324 (95% CI: 0.538, -0.109, p = 0.003), -0.502 (95% CI: 0.761, -0.243, p = 0.000), and -0.252 (95% CI: 0.569, 0.065, p = 0.119), respectively. The survival probability was significantly higher in the NDQ group (p = 0.0039). Taking Niaoduqing granules was a significant protective factor for thwarting disease progression (model 1: HR 0.654 (95% CI 0.489-0.875, p = 0.004); model 2: HR 0.646 (95% CI 0.476, 0.877, p = 0.005); and model 3: HR 0.602 (95% CI 0.442, 0.820, p = 0.001)). Conclusion: The long-term use of Niaoduqing granules improved SCr variation and lowered the risk of CKD progression by 39.8%.

Association between Anemia Severity and Ischemic Stroke Incidence: A Retrospective Cohort Study.

Stroke patients presenting with anemia at the time of stroke onset had a higher risk of mortality and development of other cardiovascular diseases and comorbidities. The association between the severity of anemia and the risk of developing a stroke is still uncertain. This retrospective study aimed to evaluate the association between stroke incidence and anemia severity (by WHO criteria). A total of 71,787 patients were included, of whom 16,708 (23.27%) were identified as anemic and 55,079 patients were anemia-free. Female patients (62.98%) were more likely to have anemia than males (37.02%). The likelihood of having a stroke within eight years after anemia diagnosis was calculated using Cox proportional hazard regression. Patients with moderate anemia had a significant increase in stroke risk compared to the non-anemia group in univariate analyses (hazard ratios [HR] = 2.31, 95% confidence interval [CI], 1.97-2.71, p < 0.001) and in adjusted HRs (adj-HR = 1.20, 95% CI, 1.02-1.43, p = 0.032). The data reveal that patients with severe anemia received more anemia treatment, such as blood transfusion and nutritional supplementation, and maintaining blood homeostasis may be important to preventing stroke. Anemia is an important risk factor, but other risk factors, including diabetes and hyperlipidemia, also affect stroke development. There is a heightened awareness of anemia's severity and the increasing risk of stroke development.

Generation of a whole-brain hemodynamic response function and sex-specific differences in cerebral processing of mechano-sensation in mice detected by BOLD fMRI.

BOLD fMRI has become a prevalent method to study cerebral sensory processing in rodent disease models, including pain and mechanical hypersensitivity. fMRI data analysis is frequently combined with a general-linear-model (GLM) -based analysis, which uses the convolution of a hemodynamic response function (HRF) with the stimulus paradigm. However, several studies indicated that the HRF differs across species, sexes, brain structures, and experimental factors, including stimulation modalities or anesthesia, and hence might strongly affect the outcome of BOLD analyzes. While considerable work has been done in humans and rats to understand the HRF, much less is known in mice. As a prerequisite to investigate mechano-sensory processing and BOLD fMRI data in male and female mice, we (1) designed a rotating stimulator that allows application of two different mechanical modalities, including innocuous von Frey and noxious pinprick stimuli and (2) determined and statistically compared HRFs across 30 brain structures and experimental conditions, including sex and, stimulus modalities. We found that mechanical stimulation lead to brain-wide BOLD signal changes thereby allowing extraction of HRFs from multiple brain structures. However, we did not find differences in HRFs across all brain structures and experimental conditions. Hence, we computed a whole-brain mouse HRF, which is based on 88 functional scans from 30 mice. A comparison of this mouse-specific HRF with our previously reported rat-derived HRF showed significantly slower kinetics in mice. Finally, we detected pronounced differences in cerebral BOLD activation between male and female mice with mechanical stimulation, thereby exposing divergent processing of noxious and innocuous stimuli in both sexes.

An investigation of low-protein diets' qualification rates and an analysis of their short-term effects for patients with CKD stages 3-5: a single-center retrospective cohort study from China.

BACKGROUND: The feasibility and efficacy of low-protein diets (LPD) treatment in chronic kidney disease (CKD) is controversial. Based on the characteristics of the Chinese diet, we observe the qualification rates and short-term clinical effects of LPD for CKD patients in our center. METHODS: This is a retrospective cohort study. CKD stages 3-5 patients who were regularly followed up 5 times (over 2 years) and treated with LPD were included. We collected clinical data to observe the changes in LPD qualification rates and divided patients into LPD and non-LPD group according to the average dietary protein intake (DPI) of 5 follow-up time points and compared the changes in primary and secondary outcome measures between the two groups. RESULTS: We analyzed data from 161 eligible CKD stages 3-5 patients. From baseline to the 5th follow-up time point, the LPD qualification rates of all patients were 11.80%, 35.40%, 47.82%, 53.43% and 54.04%, respectively. For primary outcome measures, the urine protein/creatinine ratio (UPCR) decreased more in the LPD group than in the non-LPD group [Median (interquartile range, IQR) of the difference between the 5th follow-up time point and baseline: 0.19 (- 0.01-0.73) vs. 0.10 (- 0.08-0.27), P < 0.001]. We constructed three classes of mixed linear models (model I, II, III). The UPCR slopes were all negative in the LPD group and positive in the non-LPD group (P < 0.001). Meanwhile, in model I, the estimate glomerular filtration rate(eGFR) decline slope in the LPD group was lower than that in the non-LPD group [slope (standard error): - 1.32 (0.37) vs. - 2.35 (0.33), P = 0.036]. For secondary outcome measures, body mass index (BMI) triglycerides (TG), body weight, and fat free mass (FFM) showed stable statistical differences in the comparison of LPD and non-LPD groups, with greater declines in the former. CONCLUSION: The results of this study suggest that LPD treatment can reduce UPCR in patients with CKD stages 3-5, and may also delay the decline in eGFR. Meanwhile, it also reduces BMI, TG, body weight, and FFM, thus the need to prevent malnutrition in clinical implementation.

Deciphering pathological behavior of pediatric medullary thyroid cancer from single-cell perspective.

Background: Pediatric medullary thyroid cancer (MTC) is one of the rare pediatric endocrine neoplasms. Derived from C cells of thyroid glands, MTC is more aggressive and more prompt to metastasis than other types of pediatric thyroid cancer. The mechanism remains unclear. Methods: We performed single-cell transcriptome sequencing on the samples of the primary tumor and metastases lymph nodes from one patient diagnosed with MTC, and it is the first single-cell transcriptome sequencing data of pediatric MTC. In addition, whole exome sequencing was performed and peripheral blood was regarded as a normal reference. All cells that passed quality control were merged and analyzed in R to discover the association between tumor cells and their microenvironment as well as tumor pathogenesis. Results: We first described the landscape of the single-cell atlas of MTC and studied the interaction between the tumor cell and its microenvironment. C cells, identified as tumor cells, and T cells, as the dominant participant in the tumor microenvironment, were particularly discussed in their development and interactions. In addition, the WES signature of tumor cells and their microenvironment were also described. Actively immune interactions were found, indicating B cells, T cells and myeloid cells were all actively participating in immune reaction in MTC. T cells, as the major components of the tumor microenvironment, proliferated in MTC and could be divided into clusters that expressed proliferation, immune effectiveness, and naive markers separately.

Applying Healthcare Failure Mode and Effect Analysis and the Development of a Real-Time Mobile Application for Modified Early Warning Score Notification to Improve Patient Safety During Hemodialysis.

OBJECTIVE: Patients undergoing hemodialysis are a high-risk population. This study identified possible errors by using a healthcare failure mode and effect analysis system to improve patient safety during hemodialysis. METHODS: A multidisciplinary collaborative team, including physicians, nurses, information technicians, and medical staff members, was assembled. A flow diagram was used to indicate each process of the hemodialysis procedure from evaluating patient condition to transporting the patient back to the ward from the hemodialysis center. We scored all possible failure modes using the hazard scoring method as a combination of the occurrence frequency and severity. These potential failure modes were used to identify and evaluate possible risks by using a risk scoring matrix. RESULTS: Thirty failure modes were identified across 6 processes, and their potential causes were explored. Four major strategies for addressing most of the failure modes were implemented: establishment of a mobile application that sends real-time automated alerts to the medical team based on the Modified Early Warning Score, design of a modified dialysis Identify-Situation-Background-Assessment-Recommendation checklist for dialysis, technician education and training, and internal auditing and monitoring of the implementation of the entire process. After the implementation of the strategies, the hazard scores of patients during dialysis dropped by 71.2% from 170 points to 49 points. CONCLUSIONS: The healthcare failure mode and effect analysis system was useful for evaluating potential risk during dialysis. Using the mobile application reduced the occurrence of emergency resuscitation during hemodialysis and significantly improved the communication between medical personnel.

Formation of Para-H2O by Vacuum-UV Photolysis of O2 in Solid Hydrogen: Implication for Astrochemistry.

The observation that the ortho to para ratio (OPR) of interstellar H2O is smaller than 3 is an important yet unresolved subject in astronomy. We irradiated O2 embedded in solid H2 at 3 K with vacuum-ultraviolet (VUV) light and observed IR lines associated with para-H2O (denoted as pH2O) and nonrotating H2O-(oH2)n (where oH2 denotes ortho-H2) but no lines associated with ortho-H2O (denoted as oH2O). After maintaining the matrix in darkness for ∼30 h, the amount of pH2O decreased, accompanied by an increase in H2O-(oH2)n via diffusion of oH2. After that, the continuous nuclear-spin conversion from oH2 to para-H2 (denoted as pH2) in solid H2 over time resulted in the conversion of nonrotating H2O-(oH2)n to rotating pH2O in solid pH2. The observation of the formation and conversion of pH2O in our experiment suggests a plausible route in which VUV irradiation of O2 and H2 adsorbed on grain surfaces might be responsible for the smaller OPR of interstellar H2O.

Developing and validating a prognostic prediction model for patients with chronic kidney disease stages 3-5 based on disease conditions and intervention methods: a retrospective cohort study in China.

OBJECTIVES: To develop and validate a nomogram model to predict chronic kidney disease (CKD) stages 3-5 prognosis. DESIGN: A retrospective cohort study. We used univariate and multivariate Cox regression analysis to select the relevant predictors. To select the best model, we evaluated the prediction models' accuracy by concordance index (C-index), calibration curve, net reclassification index (NRI) and integrated discrimination improvement (IDI). We evaluated the clinical utility by decision curve analysis. SETTING: Chronic Disease Management (CDM) Clinic in the Nephrology Department at the Guangdong Provincial Hospital of Chinese Medicine. PARTICIPANTS: Patients with CKD stages 3-5 in the derivation and validation cohorts were 459 and 326, respectively. PRIMARY OUTCOME MEASURE: Renal replacement therapy (haemodialysis, peritoneal dialysis, renal transplantation) or death. RESULTS: We built four models. Age, estimated glomerular filtration rate and urine protein constituted the most basic model A. Haemoglobin, serum uric acid, cardiovascular disease, primary disease, CDM adherence and predictors in model A constituted model B. Oral medications and predictors in model A constituted model C. All the predictors constituted model D. Model B performed well in both discrimination and calibration (C-index: derivation cohort: 0.881, validation cohort: 0.886). Compared with model A, model B showed significant improvement in the net reclassification and integrated discrimination (model A vs model B: NRI: 1 year: 0.339 (-0.011 to 0.672) and 2 years: 0.314 (0.079 to 0.574); IDI: 1 year: 0.066 (0.010 to 0.127), p<0.001 and 2 years: 0.063 (0.008 to 0.106), p<0.001). There was no significant improvement between NRI and IDI among models B, C and D. Therefore, we selected model B as the optimal model. CONCLUSIONS: We constructed a prediction model to predict the prognosis of patients with CKD stages 3-5 in the first and second year. Applying this model to clinical practice may guide clinical decision-making. Also, this model needs to be externally validated in the future. TRIAL REGISTRATION NUMBER: ChiCTR1900024633 (http://www.chictr.org.cn).

Quzhi Formula Alleviates Nonalcoholic Steatohepatitis by Impairing Hepatocyte Lipid Accumulation and Inflammation via Bip/eIF2α Signaling.

Background and Aims: The Quzhi formula, a Chinese medicine compound prescription, relieves nonalcoholic steatohepatitis (NASH) symptoms. This study aimed to explore the mechanism of the Quzhi formula against NASH. Methods: A choline-deficient, L-amino acid-defined, high-fat diet induced a NASH mouse model and a free fatty acid-induced mouse hepatocyte cell model were used to evaluate the function of Quzhi formula in vivo and in vitro. Network pharmacology and molecular docking technology were performed to uncover the possible protective mechanisms of the Quzhi formula against NASH. Key factors in liver lipid metabolism and endoplasmic reticulum (ER) stress pathway were evaluated to verify the mechanism. Results: The positive contribution of the Quzhi formula on NASH was confirmed in vivo and in vitro. Abnormal accumulation of lipid in the liver and inflammatory responses were significantly decreased by the Quzhi formula. Network pharmacological analysis and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis showed that the Quzhi formula protected against NASH by regulating ER stress and inflammatory responses, which was enhanced by further molecular docking analysis. In addition, mechanism exploration showed that Quzhi formula mainly reduced ER stress by downregulating Bip/eIF2α signaling. Conclusions: The Quzhi formula protected against NASH by inhibiting lipid accumulation, ER stress, and inflammatory responses, which supports the potential use of Quzhi formula as an alternative treatment for NASH.